METHODS OF TREATING FIBROTIC- AND COLLAGEN-MEDIATED DISEASES AND DISORDERS WITH DEUPIRFENIDONE CROSS-REFERENCE TO RELATED APPLICATIONS [0001] This application claims the benefit of U.S. Provisional Application No.^63/432,208, filed December 13, 2022, and claims the benefit of U.S. Provisional Application No. 63/431,530, filed December 9, 2022, and claims the benefit of U.S. Provisional Application No. 63/403,481, filed September 2, 2022, and claims the benefit of U.S. Provisional Application No. 63/374,362, filed September 1, 2022, and claims the benefit of U.S. Provisional Application No. 63/356,653, filed June 29, 2022, and claims the benefit of U.S. Provisional Application No.63/352,107, filed June 14, 2022, and claims the benefit of U.S. Provisional Application No. 63/341,828, filed May 13, 2022, and claims the benefit of U.S. Provisional Application No.63/341,269, filed May 12, 2022, and claims the benefit of U.S. Provisional Application No. 63/341,279, filed May 12, 2022, and claims the benefit of U.S. Provisional Application No.63/341,281, filed May 12, 2022, and claims the benefit of U.S. Provisional Application No.63/326,132, filed March 31, 2022, and claims the benefit of U.S. Provisional Application No. 63/326,129, filed March 31, 2022, all of which are herein incorporated by reference in their entirety and for all purposes. BACKGROUND [0002] There exists a need for a therapy that can slow disease progression in patients with a variety of disorders of a fibrotic nature, including but not limited to interstitial lung diseases (ILDs), lymphedema, certain infectious diseases and their sequelae, certain inflammatory diseases and their sequelae, and other fibrotic- or collagen-mediated diseases and disorders. Poor drug tolerability, including dose-limiting side effects and toxicity associated with gastrointestinal intolerability (e.g., nausea, diarrhea, and other GI events), headache, and photosensitivity, as well as other adverse side effects, are limitations of current treatments for fibrotic- or collagen-mediated diseases and disorders. The dose-limiting side effects and/or toxicity typically require, and are therefore managed by, one or more of the following treatment options: administration of lower, less efficacious doses, periodic reduction(s) of efficacious dose, periodic or permanent cessation of drug (treatment interruption or discontinuation), and/or inability to maintain patients on a sustained treatment program or long-term maintenance dose (e.g., without treatment interruption). Particularly, tolerability issues significantly limit the usage of pirfenidone, resulting in dose reduction, switch of drug, and/or interruption or discontinuation of antifibrotic therapy. Pirfenidone, one of only two drugs currently approved in the US by the FDA for treatment of idiopathic pulmonary fibrosis (IPF), suffers from these poor tolerability issues. Studies (see, e.g., Dempsey, 2021) have indicated that only 21% of patients who initiated therapy with pirfenidone remained on pirfenidone at the recommended dose after 2 years. Poor tolerability and the aforementioned management thereof, including a significant incidence of permanent dose reduction and treatment discontinuation, is associated with reduced clinical efficacy and a lost opportunity for full clinical benefit. [0003] Accordingly, there exists a need for a therapy having a superior tolerability profile compared to current antifibrotics for the treatment of fibrotic- and collagen-mediated diseases and disorders, and other disorders of a fibrotic nature. Particularly, there exists a need for a treatment option that allows for dosing which can achieve higher drug exposure than the current treatment options which are limited due to dose-limiting side effects and/or toxicity, which possess a superior tolerability profile compared to current antifibrotics, or both, such that continuous (e.g., uninterrupted) treatment can be maintained. SUMMARY [0004] In one aspect is provided a method of treating a fibrotic- or collagen-mediated disease or disorder, the method comprising administering to a subject in need thereof total daily dose from about 825 to about 2475 mg of a deuterium-enriched pirfenidone having the structure: , wherein the fibrotic- or treated in the subject. [0005] In some embodiments, the total daily dose is 1650 mg. [0006] In some embodiments, the total daily dose is 2475 mg. [0007] In some embodiments, the total daily dose is administered in three equal administrations. [0008] In some embodiments, the total daily dose is administered in three equal administrations of 825 mg each (825 mg TID). [0009] In some embodiments, the total daily dose is administered in three equal administrations of 550 mg each (550 mg TID). [0010] In some embodiments, the LYT-100 is administered without regard to food. [0011] In some embodiments, the LYT-100 is administered without food. [0012] In some embodiments, the LYT-100 is administered with food. [0013] In some embodiments, the LYT-100 is administered without dose escalation. [0014] In some embodiments, administering comprises titrating up to the total daily dose from an initial total daily dose which is below the total daily dose. [0015] In some embodiments, administering comprises titrating up to the total daily dose from an initial total daily dose which is below the total daily dose, and wherein titrating comprises administering the LYT-100 in three daily doses of 550 mg each for three days, followed by administering the LYT-100 in three daily doses of 825 mg each. [0016] In some embodiments, the fibrotic- or collagen-mediated disease or disorder is acute interstitial pneumonia (AIP), alcoholic liver disease, allograft injury after organ transplantation, medical device or implant rejection, anthracosis, asbestosis, atrial fibrilation, cardiac fibrosis, chalicosis, chronic hypersensitivity pneumonitis (CHP, HP), chronic kidney disease, chronic sarcoidosis, cirrhosis, CREST syndrome, cryptogenic organizing pneumonia (COP), cystic fibrosis, a dermatopolymyositis (PM/DM, including polymyositis and dermatomyositis), desquamative interstitial pneumonia (DIP), diffuse parenchymal lung disease, edema, endotoxin- induced liver injury after partial hepatectomy or hepatic ischemia, fibrotic non-specific interstitial pneumonitis (fNSIP), fibrotic hypersensitivity pneumonitis (fHP), fibrotic sarcoidosis, focal segmental glomerulosclerosis (FSGS), hepatitis-C fibrosis, Hermansky-Pudlak syndrome, hypertrophic cardiomyopathy (HCM), idiopathic interstitial pneumonias (IIPs), idiopathic non- specific interstitial pneumonia (iNSIP, NSIP), intercapillary or intracapillary glomerulosclerosis, interstitial pneumonia with autoimmune features (IPAF), juvenile dermatomyositis polymyositis, juvenile systemic sclerosis (J-SSC), keloid scarring, lupus nephritis, lymphedema, mediastinal fibrosis, medical device or implant rejection, membranous nephropathy, minimal change disease, mixed connective tissue disease, multiple sclerosis, neurofibromatosis, neutropenia-associated fibrosis. non-alcoholic steatohepatitis (NASH), non-idiopathic pulmonary fibrosis, pneumoconioses, polycystic kidney disease, polymyositis/dermatomyositis (PM/DM), primary lymphedema, pulmonary fibrosis caused by a respiratory infection. pulmonary sarcoidosis, renal fibrosis, rheumatoid arthritis, sarcoidosis, scleroderma, secondary lymphedema, silicosis, spleen fibrosis caused by sickle-cell anemia, systemic sclerosis, tuberculosis, uterine fibroids, or any disorder ameliorated by modulating fibrosis. [0017] In some embodiments, the fibrotic- or collagen-mediated disease or disorder is an interstitial lung disease (ILD). In some embodiments, the ILD is an exposure-related ILD, a drug- induced ILD, an autoimmune interstitial lung disease, unclassifiable interstitial lung disease (uILD), progressive fibrotic interstitial lung disease (pfILD), respiratory bronchiolitis-ILD (RB- ILD), a connective tissue disease-related ILD (CTD-ILD), rheumatoid arthritis (RA-ILD), systemic sclerosis (SSc-ILD), mixed connective tissue disease-ILD, scleroderma related ILD, or ILD related to chronic sarcoidosis. In some embodiments, the ILD is a progressive fibrosing ILD (PF-ILD). [0018] In some embodiments, the fibrotic- or collagen-mediated disease or disorder is a respiratory disease stemming from a viral respiratory infection. [0019] In some embodiments, the fibrotic- or collagen-mediated disease or disorder is a result of infection with the corona virus disease, COVID-19. [0020] In some embodiments, the fibrotic- or collagen-mediated disease or disorder is breast cancer-related lymphedema. [0021] In some embodiments, the fibrotic- or collagen-mediated disease or disorder is not idiopathic pulmonary fibrosis (IPF). [0022] In some embodiments, the fibrotic- or collagen-mediated disease or disorder is alleviated. [0023] In some embodiments, progression of the fibrotic- or collagen-mediated disease or disorder is delayed, slowed, or arrested. [0024] In another aspect is provided a method of treating a fibrotic- or collagen-mediated disease or disorder, the method comprising administering to a subject in need thereof a deuterium-enriched pirfenidone having the structure: wherein the administering is exposure of LYT-100 in the subject which is the same or about the same as the systemic exposure of pirfenidone achieved when pirfenidone is administered at a total daily dose of 2403 mg. [0025] In some embodiments, the dose of LYT-100 is a total daily dose of 1650 mg. [0026] In some embodiments, the total daily dose is administered in three equal administrations. [0027] In some embodiments, the total daily dose is administered in three equal administrations of 550 mg each (550 mg TID). [0028] In some embodiments, the LYT-100 is administered without regard to food. [0029] In some embodiments, the LYT-100 is administered without food. [0030] In some embodiments, the LYT-100 is administered with food. [0031] In some embodiments, the LYT-100 is administered without dose escalation. [0032] In some embodiments, the fibrotic- or collagen-mediated disease or disorder is acute interstitial pneumonia (AIP), alcoholic liver disease, allograft injury after organ transplantation, medical device or implant rejection, anthracosis, asbestosis, atrial fibrilation, cardiac fibrosis, chalicosis, chronic hypersensitivity pneumonitis (CHP, HP), chronic kidney disease, chronic sarcoidosis, cirrhosis, CREST syndrome, cryptogenic organizing pneumonia (COP), cystic fibrosis, a dermatopolymyositis (PM/DM, including polymyositis and dermatomyositis), desquamative interstitial pneumonia (DIP), diffuse parenchymal lung disease, edema, endotoxin- induced liver injury after partial hepatectomy or hepatic ischemia, fibrotic non-specific interstitial pneumonitis (fNSIP), fibrotic hypersensitivity pneumonitis (fHP), fibrotic sarcoidosis, focal segmental glomerulosclerosis (FSGS), hepatitis-C fibrosis, Hermansky-Pudlak syndrome, hypertrophic cardiomyopathy (HCM), idiopathic interstitial pneumonias (IIPs), idiopathic non- specific interstitial pneumonia (iNSIP, NSIP), intercapillary or intracapillary glomerulosclerosis, interstitial pneumonia with autoimmune features (IPAF), juvenile dermatomyositis polymyositis, juvenile systemic sclerosis (J-SSC), keloid scarring, lupus nephritis, lymphedema, mediastinal fibrosis, medical device or implant rejection, membranous nephropathy, minimal change disease, mixed connective tissue disease, multiple sclerosis, neurofibromatosis, neutropenia-associated fibrosis. non-alcoholic steatohepatitis (NASH), non-idiopathic pulmonary fibrosis, pneumoconioses, polycystic kidney disease, polymyositis/dermatomyositis (PM/DM), primary lymphedema, pulmonary fibrosis caused by a respiratory infection. pulmonary sarcoidosis, renal fibrosis, rheumatoid arthritis, sarcoidosis, scleroderma, secondary lymphedema, silicosis, spleen fibrosis caused by sickle-cell anemia, systemic sclerosis, tuberculosis, uterine fibroids, or any disorder ameliorated by modulating fibrosis. [0033] In some embodiments, the fibrotic- or collagen-mediated disease or disorder is an interstitial lung disease (ILD). In some embodiments, the ILD is an exposure-related ILD, a drug- induced ILD, an autoimmune interstitial lung disease, unclassifiable interstitial lung disease (uILD), progressive fibrotic interstitial lung disease (pfILD), respiratory bronchiolitis-ILD (RB- ILD), a connective tissue disease-related ILD (CTD-ILD), rheumatoid arthritis (RA-ILD), systemic sclerosis (SSc-ILD), mixed connective tissue disease-ILD, scleroderma related ILD, or ILD related to chronic sarcoidosis. In some embodiments, the ILD is a progressive fibrosing ILD (PF-ILD). [0034] In some embodiments, the fibrotic- or collagen-mediated disease or disorder is a respiratory disease stemming from a viral respiratory infection. [0035] In some embodiments, the fibrotic- or collagen-mediated disease or disorder is a result of infection with the corona virus disease, COVID-19. [0036] In some embodiments, the fibrotic- or collagen-mediated disease or disorder is breast cancer-related lymphedema. [0037] In some embodiments, the fibrotic- or collagen-mediated disease or disorder is not idiopathic pulmonary fibrosis (IPF). [0038] In some embodiments, the fibrotic- or collagen-mediated disease or disorder is alleviated. [0039] In some embodiments, progression of the fibrotic- or collagen-mediated disease or disorder is delayed, slowed, or arrested. [0040] In yet another aspect is provided a method of treating a fibrotic- or collagen-mediated disease or disorder, the method comprising administering to a subject in need thereof a deuterium- enriched pirfenidone having the structure: wherein the administering is exposure of LYT-100 in the subject which is greater than the exposure achieved when pirfenidone is administered at a total daily dose of 2403 mg. [0041] In some emobdiments, the administering is at a dose that achieves a systemic exposure of LYT-100 in the subject which is greater than the systemic exposure of pirfenidone achieved when pirfenidone is administered at a total daily dose of 2403 mg, wherein the total daily dose of pirfenidone is administered in three doses of 801 mg each (801 mg TID). [0042] In some emobdiments, the administering is at a dose that achieves a systemic exposure of LYT-100 in the subject which is about 1.1x to about 1.9x the systemic exposure of pirfenidone achieved when pirfenidone is administered at a total daily dose of 2403 mg, optionally wherein the total daily dose of pirfenidone is administered in three doses of 801 mg each (801 mg TID). [0043] In some embodiments, the administering is at a dose that achieves a systemic exposure of LYT-100 in the subject which is about 1.25x to about 1.75x the systemic exposure of pirfenidone achieved when pirfenidone is administered at a total daily dose of 2403 mg, optionally wherein the total daily dose of pirfenidone is administered in three doses of 801 mg each (801 mg TID). [0044] In some embodiments, the dose of LYT-100 administered achieves a systemic exposure that is 1.25x to 1.75x the systemic exposure of pirfenidone achieved when pirfenidone is administered at a total daily dose of 2403 mg. [0045] In some embodiments, the administering is at a dose that achieves a systemic exposure of LYT-100 in the subject which is about 1.4x to 1.6x the systemic exposure of pirfenidone achieved when pirfenidone is administered at a total daily dose of 2403 mg, optionally wherein the total daily dose of pirfenidone is administered in three doses of 801 mg each (801 mg TID). [0046] In some embodiments, the administering is at a dose that achieves a systemic exposure of LYT-100 in the subject which is 1.4x to 1.5x the systemic exposure of pirfenidone achieved when pirfenidone is administered at a total daily dose of 2403 mg, optionally wherein the total daily dose of pirfenidone is administered in three doses of 801 mg each (801 mg TID). [0047] In some embodiments, the administering is at a dose that achieves a systemic exposure of LYT-100 in the subject which is about 1.5x the systemic exposure of pirfenidone achieved when pirfenidone is administered at a total daily dose of 2403 mg, optionally wherein the total daily dose of pirfenidone is administered in three doses of 801 mg each (801 mg TID). [0048] In some emobdiments, the administering is at a dose that achieves a systemic exposure of LYT-100 in the subject which is about 85% to about 125% the systemic exposure of pirfenidone achieved when pirfenidone is administered at a total daily dose of 2403 mg, optionally wherein the total daily dose of pirfenidone is administered in three doses of 801 mg each (801 mg TID). [0049] In some emobdiments, the administering is at a dose that achieves a systemic exposure of LYT-100 in the subject which is 125% to 175% the systemic exposure of pirfenidone achieved when pirfenidone is administered at a total daily dose of 2403 mg, optionally wherein the total daily dose of pirfenidone is administered in three doses of 801 mg each (801 mg TID). [0050] In some embodiments, the administering is at a dose that achieves a systemic exposure of LYT-100 in the subject which is 140% to 160% greater than the systemic exposure of pirfenidone achieved when pirfenidone is administered at a total daily dose of 2403 mg, optionally wherein the total daily dose of pirfenidone is administered in three doses of 801 mg each (801 mg TID). [0051] In some embodiments, the administering is at a dose that achieves a systemic exposure of LYT-100 in the subject which is 140% to 150% greater than the systemic exposure of pirfenidone achieved when pirfenidone is administered at a total daily dose of 2403 mg, optionally wherein the total daily dose of pirfenidone is administered in three doses of 801 mg each (801 mg TID). [0052] In some embodiments, the administering is at a dose that achieves a systemic exposure of LYT-100 in the subject which is about 150% of the systemic exposure of pirfenidone achieved when pirfenidone is administered at a total daily dose of 2403 mg, optionally wherein the total daily dose of pirfenidone is administered in three doses of 801 mg each (801 mg TID). [0053] In some emobdiments, the administering is at a dose that achieves a systemic exposure of LYT-100 in the subject which is about 10% to about 90% greater than the systemic exposure of pirfenidone achieved when pirfenidone is administered at a total daily dose of 2403 mg, optionally wherein the total daily dose of pirfenidone is administered in three doses of 801 mg each (801 mg TID). [0054] In some emobdiments, the administering is at a dose that achieves a systemic exposure of LYT-100 in the subject which is about 25% to about 75% greater than the systemic exposure of pirfenidone achieved when pirfenidone is administered at a total daily dose of 2403 mg, optionally wherein the total daily dose of pirfenidone is administered in three doses of 801 mg each (801 mg TID). [0055] In some embodiments, the administering is at a dose that achieves a systemic exposure of LYT-100 in the subject which is 25% to 75% greater than the systemic exposure of pirfenidone achieved when pirfenidone is administered at a total daily dose of 2403 mg, optionally wherein the total daily dose of pirfenidone is administered in three doses of 801 mg each (801 mg TID). In some embodiments, the administering is at a dose that achieves a systemic exposure of LYT-100 in the subject which is 40% to 60% greater than the systemic exposure of pirfenidone achieved when pirfenidone is administered at a total daily dose of 2403 mg, optionally wherein the total daily dose of pirfenidone is administered in three doses of 801 mg each (801 mg TID). [0056] In some embodiments, the administering is at a dose that achieves a systemic exposure of LYT-100 in the subject which is 40% to 50% greater than the systemic exposure of pirfenidone achieved when pirfenidone is administered at a total daily dose of 2403 mg, optionally wherein the total daily dose of pirfenidone is administered in three doses of 801 mg each (801 mg TID). [0057] In some embodiments, the administering is at a dose that achieves a systemic exposure of LYT-100 in the subject which is about 50% greater than the systemic exposure of pirfenidone achieved when pirfenidone is administered at a total daily dose of 2403 mg, optionally wherein the total daily dose of pirfenidone is administered in three doses of 801 mg each (801 mg TID). [0058] In some embodiments, the dose of LYT-100 that achieves a systemic exposure of LYT- 100 in the subject which is greater than the systemic exposure of pirfenidone achieved when pirfenidone is administered at a total daily dose of 2403 mg is a total daily dose of 2475 mg. [0059] In some embodiments, the total daily dose is administered in three equal administrations. [0060] In some embodiments, the total daily dose is administered in three equal administrations of 825 mg each (825 mg TID). [0061] In some embodiments, the LYT-100 is administered without regard to food. [0062] In some embodiments, the LYT-100 is administered without food. [0063] In some embodiments, the LYT-100 is administered with food. [0064] In some embodiments, the LYT-100 is administered without dose escalation. [0065] In some embodiments, administering comprises titrating up to the total daily dose from an initial total daily dose which is below the total daily dose. [0066] In some embodiments, administering comprises titrating up to the total daily dose from an initial total daily dose which is below the total daily dose, and wherein titrating comprises administering the LYT-100 in three daily doses of 550 mg each for three days, followed by administering the LYT-100 in three daily doses of 825 mg each. [0067] In some embodiments, the fibrotic- or collagen-mediated disease or disorder is acute interstitial pneumonia (AIP), alcoholic liver disease, allograft injury after organ transplantation, medical device or implant rejection, anthracosis, asbestosis, atrial fibrilation, cardiac fibrosis, chalicosis, chronic hypersensitivity pneumonitis (CHP, HP), chronic kidney disease, chronic sarcoidosis, cirrhosis, CREST syndrome, cryptogenic organizing pneumonia (COP), cystic fibrosis, a dermatopolymyositis (PM/DM, including polymyositis and dermatomyositis), desquamative interstitial pneumonia (DIP), diffuse parenchymal lung disease, edema, endotoxin- induced liver injury after partial hepatectomy or hepatic ischemia, fibrotic non-specific interstitial pneumonitis (fNSIP), fibrotic hypersensitivity pneumonitis (fHP), fibrotic sarcoidosis, focal segmental glomerulosclerosis (FSGS), hepatitis-C fibrosis, Hermansky-Pudlak syndrome, hypertrophic cardiomyopathy (HCM), idiopathic interstitial pneumonias (IIPs), idiopathic non- specific interstitial pneumonia (iNSIP, NSIP), intercapillary or intracapillary glomerulosclerosis, interstitial pneumonia with autoimmune features (IPAF), juvenile dermatomyositis polymyositis, juvenile systemic sclerosis (J-SSC), keloid scarring, lupus nephritis, lymphedema, mediastinal fibrosis, medical device or implant rejection, membranous nephropathy, minimal change disease, mixed connective tissue disease, multiple sclerosis, neurofibromatosis, neutropenia-associated fibrosis. non-alcoholic steatohepatitis (NASH), non-idiopathic pulmonary fibrosis, pneumoconioses, polycystic kidney disease, polymyositis/dermatomyositis (PM/DM), primary lymphedema, pulmonary fibrosis caused by a respiratory infection. pulmonary sarcoidosis, renal fibrosis, rheumatoid arthritis, sarcoidosis, scleroderma, secondary lymphedema, silicosis, spleen fibrosis caused by sickle-cell anemia, systemic sclerosis, tuberculosis, uterine fibroids, or any disorder ameliorated by modulating fibrosis. [0068] In some embodiments, the fibrotic- or collagen-mediated disease or disorder is an interstitial lung disease (ILD). In some embodiments, the ILD is an exposure-related ILD, a drug- induced ILD, an autoimmune interstitial lung disease, unclassifiable interstitial lung disease (uILD), progressive fibrotic interstitial lung disease (pfILD), respiratory bronchiolitis-ILD (RB- ILD), a connective tissue disease-related ILD (CTD-ILD), rheumatoid arthritis (RA-ILD), systemic sclerosis (SSc-ILD), mixed connective tissue disease-ILD, scleroderma related ILD, or ILD related to chronic sarcoidosis. In some embodiments, the ILD is a progressive fibrosing ILD (PF-ILD). [0069] In some embodiments, the fibrotic- or collagen-mediated disease or disorder is a respiratory disease stemming from a viral respiratory infection. [0070] In some embodiments, the fibrotic- or collagen-mediated disease or disorder is a result of infection with the corona virus disease, COVID-19. [0071] In some embodiments, the fibrotic- or collagen-mediated disease or disorder is breast cancer-related lymphedema. [0072] In some embodiments, the fibrotic- or collagen-mediated disease or disorder is not idiopathic pulmonary fibrosis (IPF). [0073] In some embodiments, the fibrotic- or collagen-mediated disease or disorder is alleviated. [0074] In some embodiments, progression of the fibrotic- or collagen-mediated disease or disorder is delayed, slowed, or arrested. BRIEF DESCRIPTION OF THE DRAWINGS [0075] FIG. 1 is a graphical illustration of a crossover clinical trial study design according to a non-limiting embodiment of the disclosure. [0076] FIG. 2 is a graphical illustration of another crossover clinical trial study design according to a non-limiting embodiment of the disclosure. [0077] FIG.3 is a table showing the extrapolated steady-state exposures (AUC _24ss ) and steady- state C _max values of LYT-100 for 450 mg – 550 mg TID dosing based on PK data from two separate cohorts (12A and 12B) and a pooled dataset. The pharmacokinetic parameters were calculated using steady state AUC _0-24 after administration of LYT-100 dosed at 1000 mg BID or pifenidone dosed at 801 mg TID. The data demonstrates that a dose of 550 mg TID LYT- 100 has a steady-state exposure (AUC) that is calculated to be equivalent to 98.5% of the steady- state exposure (AUC) of pirfenidone dosed at 801 mg TID, and a C _max that is calculated to be equivalent to 67.4% of the C _max of pirfenidone dosed at 801 mg TID. [0078] FIG.4 is a table showing the extrapolated steady-state exposures (AUC _24ss ) and steady- state C _max values of LYT-100 for 700 mg – 1000 mg BID dosing (1400 mg – 2000 mg daily dose) versus 450 mg – 850 mg TID dosing (1350 mg – 2550 mg daily dose). The data demonstrates that a dose of 825 mg BID LYT-100 (1650 mg daily dose) has a steady-state exposure (AUC) that is calculated to be equivalent to 98.5% of the steady-state exposure (AUC) and 101.1% of the steady-state Cmax of pirfenidone dosed at 801 mg TID. In contrast, a dose of 550 mg TID LYT-100 (1650 mg daily dose) has a steady-state exposure (AUC) that is calculated to be equivalent to 98.5% of the steady-state exposure (AUC) and 67.4% of the steady-state Cmax of pirfenidone dosed at 801 mg TID. [0079] FIG. 5A is a summary of the pharmacokinetic and tolerability results of a Phase 1 cross-over study conducted in healthy adults dosed with 850 mg BID LYT-100. [0080] FIG. 5B is a table showing the incidence of treatment-emergent adverse events (TEAEs) in a cross-over study of healthy older adults comparing LYT-100850 mg BID versus pirfenidone 801 mg TID. The data shows that the incidence of gastrointestinal AEs with LYT- 100 was 37.1% with LYT-100 versus 29.7% with pirfenidone; the incidence of nervous system AEs was 45.7% with LYT-100 versus 35.1% with pirfenidone; and the incidence of nausea was increased with both LYT-100 and pirfenidone when dosed after fasting. [0081] FIG. 6 is a graphical depiction of side effects encountered in a healthy older patient population for LYT-100 at 550 mg TID and pirfenidone at 801 mg TID. [0082] FIG. 7A is a graphical depiction of time versus exposure for LYT-100 for a dose of 550 mg TID. [0083] FIG. 7B is a graphical depiction of time versus exposure for LYT-100 for a dose of 824 mg TID. [0084] FIG. 7C is a graphical depiction of time versus exposure for the major metabolite for a dose of 550 mg TID. [0085] FIG. 7D is a graphical depiction of time versus exposure for the major metabolite for a dose of 824 mg TID. [0086] FIG. 8 is a table showing the pharmacokinetic parameters for LYT-100 and the major metabolite for doses of 550 mg TID and 824 mg TID. [0087] FIG.9A is a graphical depiction of time versus exposure for LYT-100 for doses of 550 mg TID and 824 mg TID in the crossover study of Example 1 and two prior dosing studies. [0088] FIG.9B is a graphical depiction of time versus exposure for the major metabolite for doses of 550 mg TID and 824 mg TID in the crossover study of Example 1 and two prior dosing studies. [0089] FIG. 10 is a graphical illustration of the mean plasma concentrations over time for pirfenidone dosed at 801 mg TID, and for LYT-100 dosed at 550 mg TID and 824 mg TID. [0090] FIG. 11 is a graphical illustration of the mean plasma concentrations of the major metabolite over time for pirfenidone dosed at 801 mg TID, and for LYT-100 dosed at 550 mg TID and 824 mg TID. [0091] FIG.12 is a graphical depiction of plasma concentration versus time for pirfenidone at 550 mg TID and LYT-100 at 824 mg TID following day 3 in the crossover study of Example 1. [0092] FIG.13A is a graphical depiction of subject weight versus exposure for LYT-100 for 550 mg TID and 824 mg TID doses in the crossover study of Example 1 and in three prior dosing studies. [0093] FIG. 13B is a graphical depiction of subject weight versus exposure for the major metabolite for 550 mg TID and 824 mg TID doses in the crossover study of Example 1 and in three prior dosing studies. [0094] FIG.14A is a graphical depiction of subject age versus exposure for LYT-100 normalized to 550 mg TID in the crossover study of Example 1 and in three prior dosing studies. [0095] FIG.14B is a graphical depiction of subject age versus exposure for the major metabolite of LYT-100 normalized to 550 mg TID in the crossover study of Example 1 and in three prior dosing studies. [0096] FIG. 15A is a graphical summary of exposure versus dose in the crossover study of Example 1 and a prior dosing study demonstrating the achievement of bioequivalence to 801 mg TID pirfenidone for 550 mg TID LYT-100. [0097] FIG. 15B is a graphical summary of exposure versus dose in the crossover study of Example 1 and a prior dosing study demonstrating the achievement of bioequivalence to 801 mg TID pirfenidone for 550 mg TID LYT-100. [0098] FIG. 15C is a graphical summary of exposure versus dose in the crossover study of Example 1 and a prior dosing study demonstrating the achievement of bioequivalence to 801 mg TID pirfenidone for 550 mg TID LYT-100. [0099] FIG. 15D is a graphical summary of exposure versus dose in the crossover study of Example 1 and pooled data from a prior dosing study demonstrating the achievement of bioequivalence to 801 mg TID pirfenidone for 550 mg TID LYT-100. [0100] FIG.16 is a graphical summary of exposure versus dose for pooled data from the crossover study of Example 1 and three prior dosing studies and demonstrating the achievement of bioequivalence to 801 mg TID pirfenidone for 550 mg TID and 687 mg TID LYT-100. [0101] FIG. 17 is a table showing the predicted bioequivalence for various LYT-100 TID doses using data from the crossover study of Example 1 and three prior dosing studies. [0102] FIG. 18A is a graphical cartoon illustration of predicted plasma concentrations over time for pirfenidone at 801 mg TID, LYT-100 at 550 mg TID, and LYT-100 at 825 mg TID. [0103] FIG.18B is a table showing the ratio of predicted plasma concentrations for pirfenidone at 801 mg TID versus LYT-100 dosed at 550 mg TID and 825 mg TID. [0104] FIG.19 is a table showing a summary of baseline demographic characteristics with respect to age and sex for subjects in the COVID-19 clinical study of Example 3. [0105] FIG.20 is a table showing a summary of baseline demographic characteristics with respect to ethnicity, race, and time from COVID diagnosis for subjects in the COVID-19 clinical study of Example 3. [0106] FIG.21 is a table showing a summary of subject disposition for the enrolled population in the COVID-19 clinical study of Example 3. [0107] FIG. 22 is a table showing a summary of treatment emergent adverse events judged to be at least possibly related to LYT-100 in the COVID-19 clinical study of Example 3. [0108] FIG.23 is a table showing the metabolism of pirfenidone and LYT-100 in the presence of individual CYP isozymes in the assay of Example 4. [0109] FIG. 24 is a graphical depiction of activity results for LYT-100 and pirfenidone in the BioMap Fibrosis Panel of Example 5. [0110] FIG. 25A is a graphical illustration showing that TNF-α response to LPS was reduced by pretreatment with both pirfenidone and LYT-100. [0111] FIG. 25B is a graphical illustration showing that IL-6 response to LPS was reduced by pretreatment with both pirfenidone and LYT-100. [0112] FIG. 26 depicts representative photomicrographs of Sirius-red stained liver sections demonstrating that LYT-100 significantly reduced the area of fibrosis. [0113] FIG. 27 is a graphical illustration showing the percent fibrosis area for LYT-100 versus vehicle and control. [0114] FIG. 28A is a graphical illustration showing that LYT-100 does not induce survival of Primary Mouse Lung Fibroblasts (PMFL). [0115] FIG. 28B and FIG. 28C are graphical illustrations showing that LYT-100 reduced TGF- β-induced total collagen level in PMFLs in a 6-well and 96-well format, respectively. [0116] FIG. 28D and FIG. 28E are graphical illustrations showing that LYT-100 reduced TGF- β-induced soluble fibronectin levels and soluble collagen levels. [0117] FIG.29A is a graphical illustration showing that LYT-100 does not affect survival of L929 cells. [0118] FIG.29B is a graphical illustration showing that LYT-100 inhibits TGF-induced collagen synthesis. [0119] FIG. 29C is a graphical illustration showing that LYT-100 significantly inhibits TGF-β- induced total collagen levels. [0120] FIG. 29D is a graphical illustration showing that LYT-100 significantly inhibits TGF-β- induced soluble collagen levels. [0121] FIG. 29E is a graphical illustration showing that LYT-100 signficantly reduces soluble fibronectin levels in the absence and presence of TGF-β-induction. [0122] FIGs.30A-30D depict results of once daily administration of LYT-100 to reduce swelling in a mouse lymphedema model. [0123] FIG. 31 is a graphical depiction of percent change in body weight over time for rats in Phase I of the bleomycin induced lung fibrosis model of Example 11. [0124] FIG.32A is a graphical depiction of lung weight to body weight percentage over time for rats in Phase I of the bleomycin induced lung fibrosis model of Example 11. [0125] FIG. 32B is a graphical depiction of lung weight to body weight percentage over time for rats in Phase I of the bleomycin induced lung fibrosis model of Example 11. [0126] FIG. 33A is a graphical depiction of body weight over time for rats in Phase II of the bleomycin induced lung fibrosis model of Example 11. [0127] FIG. 33B is a graphical depiction of percent change in body weight over time for rats in Phase II of the bleomycin induced lung fibrosis model of Example 11. [0128] FIG. 34A is a graphical depiction of lung weight over time for rats in Phase II of the bleomycin induced lung fibrosis model of Example 11. [0129] FIG. 34B is a graphical depiction of lung weight over time for rats in Phase II of the bleomycin induced lung fibrosis model of Example 11. [0130] FIG.35A is a graphical depiction of lung weight to body weight percentage over time for rats in Phase II of the bleomycin induced lung fibrosis model of Example 11. [0131] FIG. 35B is a graphical depiction of lung weight to body weight percentage over time for rats in Phase II of the bleomycin induced lung fibrosis model of Example 11. [0132] FIG. 36A is a graphical depiction of hydroxyproline content in left lung tissue for rats in Phase II of the bleomycin induced lung fibrosis model of Example 11. [0133] FIG. 36B is a graphical depiction of hydroxyproline content in left lung tissue for rats in Phase II of the bleomycin induced lung fibrosis model of Example 11. [0134] FIG.37 is a table showing the hydroxyproline content in left lung tissue across the various treatment groups in Phase II of the bleomycin induced lung fibrosis model of Example 11. [0135] FIG. 38A is a graphical depiction of hydroxyproline content in lung tissue across the various treatment groups in Phase II of the bleomycin induced lung fibrosis model of Example 11. [0136] FIG. 38B is a graphical depiction of hydroxyproline content in lung tissue across the various treatment groups in Phase II of the bleomycin induced lung fibrosis model of Example 11. [0137] FIG. 39 is a table showing the hydroxyproline content in lung tissue across the various treatment groups in Phase II of the bleomycin induced lung fibrosis model of Example 11. [0138] FIG.40A is a graphical depiction of mean lung fibrosis score across the various treatment groups in Phase II of the bleomycin induced lung fibrosis model of Example 11. [0139] FIG.40B is a graphical depiction of mean lung fibrosis score across the various treatment groups in Phase II of the bleomycin induced lung fibrosis model of Example 11. [0140] FIG.40C is a graphical depiction of median lung fibrosis score across the various treatment groups in Phase II of the bleomycin induced lung fibrosis model of Example 11. [0141] FIG.40D is a graphical depiction of median lung fibrosis score across the various treatment groups in Phase II of the bleomycin induced lung fibrosis model of Example 11. [0142] FIG. 41 is a graphical depiction of frequency of lung fibrosis scores across the various treatment groups in Phase II of the bleomycin induced lung fibrosis model of Example 11. DETAILED DESCRIPTION [0143] Disclosed herein is a method of treating fibrotic- or collagen-mediated disease or disorders, the method comprising administering to a subject in need thereof LYT-100. In some embodiments, the method comprises administering a total daily dose of LYT-100 that achieves a systemic exposure comparable to (e.g., the same or about the same as) the systemic exposure of 2403 mg daily dosing of pirfenidone (including, e.g., 801 mg TID dosing). In some embodiments, the method comprises administering a total daily dose of LYT-100 that achieves a systemic exposure greater than the systemic exposure of pirfenidone dosed at 2403 mg daily dose, e.g., 801 mg TID dosing. The method may in some embodiments engender increased patient compliance, provide a higher exposure of LYT-100 than that of pirfenidone achieved with the currently approved dose (801 mg TID) of pirfenidone, or both, and can ultimately result in a more effective therapeutic agent to address the underlying mechanisms of fibrotic- or collagen-mediated diseases and disorders. [0144] Overall, the results disclosed herein indicate that LYT-100 has the potential for use in treating indications where pirfenidone is shown to have benefit but where tolerability concerns limit its dose, and potentially its efficacy. Accordingly, the disclosed method may be beneficial in treating a range of fibrotic- or collagen-mediated diseases and disorders. The features, benefits, and utility of the method are each described further herein below. Definitions [0145] While the terms used herein are believed to be well understood by one of ordinary skill in the art, definitions are set forth herein to facilitate explanation of the presently disclosed subject matter. [0146] The articles "a" and "an" are used herein to refer to one or to more than one (i.e., to at least one) of the grammatical object of the article. [0147] The term "about" used throughout this specification is used to describe and account for small fluctuations. For example, the term "about" can refer to greater than, less than or equal to ±10%, such as greater than, less than or equal to ±5%, greater than, less than or equal to ±2%, greater than, less than or equal to ±1%, greater than, less than or equal to ±0.5%, greater than, less than or equal to ±0.2%, greater than, less than or equal to ±0.1% or greater than, ess than or equal to ±0.05%. All numeric values herein are modified by the term "about," whether or not explicitly indicated. A value modified by the term "about" of course includes the specific value. For instance, "about 5.0" must include 5.0. [0148] The term "Adverse Event" refers to any event, side-effect, or other untoward medical occurrence that occurs in conjunction with the use of a medicinal product in humans, whether or not considered to have a causal relationship to this treatment. An AE can, therefore, be any unfavourable and unintended sign (that could include a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Events meeting the definition of an AE include: Exacerbation of a chronic or intermittent pre-existing condition including either an increase in frequency and/or intensity of the condition; New conditions detected or diagnosed after study drug administration that occur during the reporting periods, even though it may have been present prior to the start of the study; Signs, symptoms, or the clinical sequelae of a suspected interaction; Signs, symptoms, or the clinical sequelae of a suspected overdose of either study drug or concomitant medications (overdose per se will not be reported as an AE/SAE). AE's may have a causal relationship with the treatment, may be possibly related, or may be unrelated. Severity of AEs may be graded as one of: Mild (Grade 1): A type of AE that is usually transient and may require only minimal treatment or therapeutic intervention. The event does not generally interfere with usual activities of daily living; Moderate (Grade 2): A type of AE that is usually alleviated with additional specific therapeutic intervention. The event interferes with usual activities of daily living, causing discomfort but poses no significant or permanent risk of harm to the research participant; Severe (Grade 3): A type of AE that interrupts usual activities of daily living, or significantly affects clinical status, or may require intensive therapeutic intervention; Life-threatening (Grade 4): A type of AE that places the participant at immediate risk of death; Death (Grade 5): Events that result in death. [0149] As used herein, the term "clinically effective amount," "clinically proven effective amount," and the like, refer to an effective amount of an API as shown through a clinical trial, e.g., a U.S. Food and Drug Administration (FDA) clinical trial. [0150] The term "is/are deuterium," when used to describe a given variable position in a molecule or formula, or the symbol "D," when used to represent a given position in a drawing of a molecular structure, means that the specified position is enriched with deuterium above the naturally occurring distribution of deuterium. In some embodiments, deuterium enrichment is of no less than about 1%, no less than about 5%, no less than about 10%, no less than about 20%, no less than about 50%, no less than about 70%, no less than about 80%, no less than about 90%, no less than about 98%, or in some embodiments no less than about 99% of deuterium at the specified position. In some embodiments, the deuterium enrichment is above 90% at each specified position. In some embodiments, the deuterium enrichment is above 95% at each specified position. In some embodiments, the deuterium enrichment is about 99% at each specified position. [0151] The term "deuterium enrichment" refers to the percentage of incorporation of deuterium at a given position in a molecule in the place of hydrogen. For example, deuterium enrichment of 1% at a given position means that 1% of molecules in a given sample contain deuterium at the specified position. Because the naturally occurring distribution of deuterium is about 0.0156%, deuterium enrichment at any position in a compound synthesized using non-enriched starting materials is about 0.0156%. The deuterium enrichment can be determined using conventional analytical methods, such as mass spectrometry and nuclear magnetic resonance spectroscopy. [0152] The term "fibrosis" refers to the deposition of extracellular matrix components, excessive fibrous connective tissue, or scarring within an organ or tissue. [0153] The term "idiopathic pulmonary fibrosis (IPF)" refers to a type of lung disease that results in scarring of the lungs (pulmonary fibrosis) for which the origin of the disease state may be unknown. [0154] Terms such as "treating" or "treatment" or "to treat" or "alleviating" or "to alleviate" refer to therapeutic measures that cure, slow down, ameliorate or lessen one or more symptoms of, halt progression of, and/or ameliorate or lessen a diagnosed pathologic condition or disorder. Thus, those in need of treatment include those already with the disorder. In some embodiments, treatment may be administered after one or more symptoms have developed. In other embodiments, treatment may be administered in the absence of symptoms. For example, treatment may be administered to a susceptible individual prior to the onset of symptoms (e.g., in light of a history of symptoms and/or in light of genetic or other susceptibility factors). Treatment may also be continued after symptoms have resolved, for example to prevent or delay their recurrence. In some embodiments, a subject is successfully "treated" for a disease or disorder according to the methods provided herein if the patient shows, e.g., total, partial, or transient alleviation or elimination of symptoms associated with the disease or disorder. For example, "treating edema" can include, but is not limited to, decreasing swelling, decreasing inflammation, decreasing fibrosis, decreasing pain, increasing range of motion, decreasing heaviness, decreasing tightness, decreasing skin thickening, and/or improving lymphatic function. "treating a fibrotic-mediated disease or disorder" can include, but is not limited to, decreasing or alleviating one or more symptoms of the fibrotic- mediated disease or disorder; delaying, slow downing, halting, ameliorating, lessening, and/or decreasing fibrosis in a tissue, e.g., lung tissue, cardiac tissue, skin tissue or other tissue affected by fibrosis; delaying, slow downing, halting, ameliorating or lessening the progression of the fibrotic-mediated disease or disorder; delaying, slow downing, halting, ameliorating or lessening the onset of the fibrotic-mediated disease or disorder; decreasing swelling, inflammation, fibrosis and/or pain in a tissue, e.g., lung tissue, cardiac tissue, skin tissue or other tissue; improving pulmonary or respiratory function; and/or improving function in a fibrotic tissue or a tissue susceptible to fibrosis. [0155] Used in comparison with LYT-100, the term "pirfenidone administered at a dose or dosing that achieves the same or about the same systemic exposure" refers to the dose, dosing, or administration of pirfenidone at which the AUC of pirfenidone in a subject is the same or about the same as the AUC achieved with LYT-100 in a subject at the specified dosing of LYT-100. In some instances, "pirfenidone administered at a dose or dosing that achieves the same or about the same systemic exposure" may refer to pirfenidone administered to a subject at a total daily dose of 2403 mg. In some instances, "pirfenidone administered at a dose or dosing that achieves the same or about the same systemic exposure" may refer to pirfenidone administered to a subject at 801 mg TID. [0156] The term "pharmaceutical composition" refers to a preparation that is in such form as to permit the biological activity of the active ingredient to be effective, and which contains no additional components that are unacceptably toxic to a subject to which the composition would be administered. Pharmaceutical compositions can be in numerous dosage forms, for example, tablet, capsule, liquid, solution, soft gel, suspension, emulsion, syrup, elixir, tincture, film, powder, hydrogel, ointment, paste, cream, lotion, gel, mousse, foam, lacquer, spray, aerosol, inhaler, nebulizer, ophthalmic drops, patch, suppository, and/or enema. Pharmaceutical compositions typically comprise a pharmaceutically acceptable carrier, and can comprise one or more of a buffer (e.g. acetate, phosphate or citrate buffer), a surfactant (e.g. polysorbate), a stabilizing agent (e.g. human albumin), a preservative (e.g. benzyl alcohol), a penetration enhancer, an absorption promoter to enhance bioavailability and/or other conventional solubilizing or dispersing agents. Choice of dosage form and excipients depends upon the active agent to be delivered and the disease or disorder to be treated or prevented, and is routine to one of ordinary skill in the art. [0157] The terms "subject" and "patient" refers to a mammalian subject, including a human subject. In some embodiments, the patient is human subject. [0158] The term "LYT-100" refers to a selectively deuterium-enriched form of pirfenidone. Specifically, LYT-100 is 5-(methyl-d ₃ )-1-phenylpyridin-2-(1H)-one (CAS# 1093951-85-9) which may alternatively be referred to as deupirfenidone or 2(1H)-Pyridinone, 5-(methyl-d3)-1-phenyl. LYT-100 has the following structure: Reference to "LYT-100" herein any hydrate, solvate, crystalline polymorph, amorphous form, or the like, of 5-(methyl-d ₃ )-1-phenylpyridin-2-(1H)-one. LYT-100 can be prepared by methods known to one of skill in the art and routine modifications thereof, and/or procedures found in Esaki et al., Tetrahedron 2006, 62, 10954-10961, Smith et al., Organic Syntheses 2002, 78, 51-56, U.S. Pat. No. 3,974,281, U.S. Pat. No. 8,680,123, WO2003/014087, WO 2008/157786, WO 2009/035598, WO 2012/122165, or WO 2015/112701; the entirety of each of which is hereby incorporated by reference; and references cited therein and routine modifications thereof. Methods for Treating Fibrotic- or Collagen-Mediated Diseases and Disorders Pirfenidone [0159] Pirfenidone (Deskar ^® ), CAS# 53179-13-8, Pirespa, AMR-69, Pirfenidona, Pirfenidonum, Esbriet, Pirfenex, 5-methyl-1-phenyl-1H-pyridin-2-one, 5-Methyl-1-phenyl-2-(1H)-pyridone, 5- methyl-1-phenylpyridin-2(1H)-one, is an orally administered small molecule with anti-fibrotic effects which has been approved in the United States and elsewhere for treatment of idiopathic pulmonary fibrosis (IPF). (pirfenidone). [0160] Pirfenidone has and antifibrotic properties. It is likely that multiple mechanisms contribute to the unique profile of pirfenidone. Pirfenidone attenuates fibroblast proliferation, production of fibrosis-associated proteins and cytokines, and biosynthesis and accumulation of extracellular matrix in response to cytokine growth factors such as TGF-β and platelet-derived growth factor, or PDGF (Schaefer et al., Eur Respir Rev. 2011; 20:85-97; InterMune UK, Ltd. Esbriet ^® Summary of Product Characteristics, 2011). Specifically, pirfenidone blocks the production and activity of TGF-β, a key growth factor that increases collagen production while decreasing its degradation. Moreover, administration of pirfenidone reduces the production of other fibrogenic factors that are induced by TGF-β, such as fibronectin and connective tissue growth factor (Schaefer et al., 2011). Pirfenidone is capable of blocking bleomycin-induced PDGF production as well as fibroblast and hepatic stellate cell proliferation in response to PDGF (DiSario et al., J. Hepatol. 2002 Nov. 37.5.584-591). Pirfenidone inhibits the expression of TNF-α, IL-6, IL-1, and intercellular adhesion molecule 1 (ICAM-1) (Schaefer et al., 2011). In a murine macrophage-like cell line, pirfenidone suppressed TNF-α production or secretion through mitogen- activated protein kinase and c-Jun N-terminal kinase-independent mechanisms and increased the levels of IL-10, an anti-inflammatory cytokine (Schaefer et al., 2011). [0161] In IPF clinical trials, many of the most common adverse reactions were GI (nausea, abdominal pain, diarrhea, dyspepsia, vomiting, and gastroesophageal reflux disease), in addition to fatigue, rash, and photosensitivity reactions. The frequency of these adverse reactions led to discontinuation of 14.6% of patients participating in those clinical trials. In a prospective, real-world observational study of 1009 patients with IPF initiating pirfenidone, 35% of patients had an adverse reaction and dose adjustment, 28% discontinued, and 11% had dose adjustments and discontinued. (Cottin, ERJ Open Res, 2018, 4(4)). Consequently, the overall adoption of anti-fibrotic medications, including pirfenidone, has been low. A study used the US OptumLabs Data Warehouse to identify 10,996 patients with IPF with medical and pharmacy claims between October 1, 2014, to July 31, 2019. The study showed that 73.6% of patients with IPF never received an antifibrotic (pirfenidone or nintedanib) during the observation period (Dempsey et al. Ann Am Thorac Soc.2021;18(7):1121-1128). In a large post- marketing analysis of 10996 patients diagnosed with IPF, only 13.2% received treatment with pirfenidone during a 5-year follow-up period, the same percentage that received treatment with the other marketed antifibrotic drug nintedanib. (Dempsey, 2021). AEs were noted as a barrier to both adoption and persistence of pirfenidone and nintedanib in IPF patients. [0162] Nintedanib (Ofev; Boehringer Ingelheim) received FDA approval in 2014 for the treatment of patients with idiopathic pulmonary fibrosis. Subsequently, it has been approved for slowing the progression of lung fibrosis in patients with systemic sclerosis (scleroderma), as well as those with other rheumatologic disease who have progressive lung fibrosis (progressive fibrosing interstitial lung disease). Nintedanib is a small molecule that inhibits multiple receptor tyrosine kinases and nonreceptor tyrosine kinases. Specifically, nintedanib inhibits platelet-derived growth factor (PDGF) receptor-alpha and -beta, fibroblast growth factor (FGF) receptor 1–3, vascular endothelial growth factor (VEGF) receptor 1–3, and fms-like tyrosine kinase-3. Of these tyrosine kinase receptors, FGF, PDGF, and VEGF have been implicated in the pathogenesis of idiopathic pulmonary fibrosis. Nintedanib binds competitively to the adenosine triphosphate binding pocket of these receptors and blocks the intracellular signaling, which is crucial for the proliferation, migration, and transformation of fibroblasts, representing essential mechanisms of the idiopathic pulmonary fibrosis pathology. [0163] As reported in Prescribing Information for Ofev, in the study leading to FDA approval, nintedanib was associated with numerous side effects. The most common adverse reactions (≥5%) with nintedanib therapy included diarrhea (62%), nausea (24%), abdominal pain (15%), vomiting (12%), liver enzyme elevation (14%), decreased appetite (11%), headache (8%), weight loss (10%), and hypertension (5%). Overall, 21% of patients who received nintedanib and 15% of patients who received placebo discontinued treatment because of an adverse event. The most frequent adverse reactions leading to the discontinuation of nintedanib were diarrhea, nausea, and decreased appetite. In a 2019 retrospective study, nausea, vomiting or thrombocytopenia was reported to have led to permanent discontinuation of nintedanib, and temporary discontinuation due to adverse effects was common (Nakamura et al. Ann Transl Med.2019 Jun; 7(12): 262). Nintedanib may have adverse effects on the liver, and blood tests for liver enzymes are recommended at the start of medication and regular intervals during the first 3 months of treatment. [0164] Pirfenidone has not been tested for clinical efficacy above doses of 801 mg TID due to poor tolerability, including gastrointestinal adverse effects, nausea, weight loss, and photosensitive skin rash (among other AEs). Although some studies have been performed using higher doses of pirfenidone, well-controlled efficacy studies have not yet been done with pirfenidone doses higher than 2403 mg daily dose. Thus, while high doses of pirfenidone - up to 801 mg TID pirfenidone - are associated with improved efficacy in IPF (compared with doses less than 2403 mg daily), an upper threshold to improved clinical efficacy has not been achieved to date because doses higher than 801 mg TID have not been tested in well-controlled clinical efficacy studies due to the poor tolerability. Thus, there is a clear need for novel therapies that improve on the AE profile of pirfenidone while maintaining the anti-inflammatory and antifibrotic activity of pirfenidone for treatment of fibrotic- or collagen-mediated diseases and disorders. LYT-100 Pharmacology [0165] As disclosed herein, LYT-100 retains the pharmacology of pirfenidone. Particularly, LYT- 100 possesses anti-inflammatory and antifibrotic properties consistent with pirfenidone. Preclinical data disclosed herein demonstrate the antifibrotic and anti-inflammatory activity of LYT-100 (see, e.g., Examples 6-11). For instance, pretreatment with oral doses of 100 and 300 mg/kg LYT-100 inhibited TNFα and IL-6 in a rat lipopolysaccharide (LPS) model of systemic inflammation (Example 6), and LYT-100 at a dose of 60 mg/kg/day significantly reduced the area of liver fibrosis in a streptozocin-induced non-alcoholic steatohepatitis (NASH) mouse model (Example 7). [0166] LYT-100 also reduced pro-inflammatory cytokines and suppressed TGF-β and downstream signaling to inhibit fibrosis in Primary Mouse Lung Fibroblasts (Example 8). Particularly, LYT- 100 was found to: (i) reduce TGF-β-induced cell proliferation, (ii) reduce both background and TGF-β-induced levels of insoluble (structural) collagen; (iii) reduce both background and TGF-β- induced levels of soluble collagen; and (iv) reduce both background and TGF-β-induced levels of soluble fibronectin in primary mouse lung fibroblast (Example 8). [0167] With reference to Example 9, LYT-100 (i) inhibits collagen synthesis, in the absence or presence TGF-β induction; (ii) inhibits total collagen levels in the absence or presence TGF-β induction; (iii) inhibits soluble collagen levels in the absence or presence TGF-β induction; and (iv) reduces soluble fibronectin levels in the absence and presence of TGF-β-induction. [0168] Further, a DiscoverX BioMAP Fibrosis Panel was used to evaluate LYT-100 and pirfenidone as described in Example 5. Similar results were observed with both compounds in the three systems, indicating that the antifibrotic profile of pirfenidone is retained in LYT-100. [0169] LYT-100 demonstrated activity in a mouse model of lymphedema (Example 10) and in a rat bleomycin-induced pulmonary fibrosis model (Example 11). [0170] LYT-100 maintains the pharmacological profile of pirfenidone, and by virtue of the deuterium kinetic isotope effect on enzyme kinetics, has a differentiated pharmacokinetic profile relative to pirfenidone. Further, LYT-100 has an unexpectedly high tolerability, including a higher GI tolerability. The deuteration of pirfenidone to create LYT-100 slows its metabolism (Chen et al., Clinical Phar, in Drug Dev. 2021, 11(2), 220-234), and the altered metabolism may be associated with the reduced adverse effects and improved tolerability observed with LYT-100. allowing for higher dosing for greater effectiveness without the adverse effects seen at equivalent doses for pirfenidone. This discovery also allows for dosing without titration to immediately, and potentially more effectively, treat patients [0171] Accordingly, in one aspect is provided a method of treating a fibrotic- or collagen-mediated disease or disorder, the method comprising administering to a subject in need thereof a total daily dose from about 825 mg to about 2550 mg of a deuterium-enriched pirfenidone having the structure: , wherein the fibrotic- or collagen-mediated disease or disorder is treated in the subject. [0172] To arrive at the method disclosed herein (i.e., the dose range), numerous dose-ranging PK studies of LYT-100 were performed (e.g., several dose-ranging MAD studies ranging from total daily doses of 1000 mg to 4000 mg of LYT-100). PK modeling data incorporated the results of various MAD PK studies to reduce variability inherent in multiple studies of small sample size. The results of the pooled data from these various dose-ranging studies is shown below in Table 18 and indicated that 1) a dose of 550 mg TID LYT-100 had a systemic exposure (AUC) of about 90- 98% (average about 95%) of the AUC achieved with pirfenidone (2403 mg dose, 801mg TID) and a Cmax of about 73-80% (average about 77%) of the Cmax achieved with pirfenidone (2403 mg dose, 801mg TID); and 2) a dose of 825 mg TID had a systemic exposure (AUC) of about 139- 148% (average about 143%) of the AUC achieved with pirfenidone (2403 mg dose, 801mg TID) and a Cmax of about 109 - 121% (average about 115%) of the Cmax achieved with pirfenidone (2403 mg dose, 801 mg TID). Notably, pirfenidone has not previously been tested for clinical efficacy above doses of 801 mg TID due to poor tolerability. [0173] Table 1 summarizes the pharmacokinetic results of a cross-over study administering a dose of LYT-100550 mg TID versus pirfenidone 801 mg TID. The results are expressed as Mean (SD), and shows that at the 550 mg TID dose, the AUC of LYT-100 is similar to that of pirfenidone dosed at the 801 mg TID dose while the C _max is lower. The AUC _0-24 of LYT-100 meets the criterion for bioequivalence (geometric mean ratio = 0.875; 90% Confidence Interval = 0.842 to 0.910) with pirfenidone 801 mg TID, while the Cmax does not). The major metabolite of both pirfenidone and LYT-100, 5-carboxypirfenidone, showed lower C _max and AUC _0-24 after LYT-100 dosing at 550 mg TID compared to pirfenidone 801 mg TID. The reduced C _max of the parent and the 5- carboxypirfenidone with LYT-100 may be responsible for lowering the gastric side effects of pirfenidone while the similar level of total exposure (AUC) is expected to provide efficacy in fibrotic- or collagen-mediated diseases and disorders. Similar results were also seen on Day 4 or 14 after a single 550 mg dose of LYT-100 or 801 mg of pirfenidone was administered in the fasted state (Table 2). The C _max of the parent and the 5-carboxy metabolite were increased to a smaller extent after LYT-100 dosing than after pirfenidone dosing. Table 1: Pharmacokinetic Parameters of LYT-100, Pirfenidone, and 5-Carboxypirfenidone after the 3 Days of Dosing in the Fed State LYT-100 550 mg TID PK Pirfenidone 801 mg TID PK ^Analyte _Cmax AUC _0-24 C _max AUC _0-24 one after the 3 Days of Dosing in the Fed State Followed by a Single Dose in the Fasted State on Day 4/14 LYT-100 550 mg TID PK Pirfenidone 801 mg TID PK Parameters on Day 4/14 (Fasted) Parameters on Day 4/14 (Fasted) and dose amounts that were associated with improved tolerability (compared to the currently approved treatment of IPF, e.g., pirfenidone 801 mg TID). The dose that minimized AEs with a similar overall exposure level (AUC) to pirfenidone 801 mg TID was LYT-100550 mg TID. [0175] As shown in Table 3, LYT-100550 mg TID and pirfenidone 801 mg TID PK and AE data were compared in the fed and fasted states (LYT-100-2021-103, Part 2). At the 550 mg TID (e.g., similar drug exposure level to approved 801 TID pirfenidone), lower AEs were observed with LYT-100 in both the fed and fasted states compared with pirfenidone. Specifically, administering a daily dose of 1650 mg LYT-100 demonstrated that LYT-100550 mg TID was associated with improved tolerability compared to pirfenidone, including a 50% reduction in gastrointestinal- related AEs and a 45% reduction in CNS-related AEs (see Example 1 and Results for LYT-100- 2021-103 Part 2, shown in Table 3). [0176] Although the AEs observed with the administration of 550 mg TID LYT-100 in the fasted state were higher than the AEs seen in the fed state, the AEs with LYT-100550 mg TID in the fasted state were still much lower than those seen with pirfenidone 801 mg TID in the fasted state. These results demonstrate that, at the same/similar drug exposure level of 801 TID pirfenidone, LYT-100 administered 550 TID has improved tolerability (less AEs) and the option of being given in the fasted state if needed, such as with individual variation in timing of meals. These data provide the rationale for selecting the 550 mg TID dose of LYT-100 in the treatment of fibrotic- or collagen-mediated diseases and disorders. When rates of AEs were ordered from lowest to highest, Cmax values for parent compound for each of these conditions similarly sorted from lowest to highest: Lowest AE rates and Cmax to highest AEs and Cmax = LYT-100550 mg (fed) to LYT- 100550 mg (fasted) to pirfenidone 801 mg (fed) to pirfenidone 801 mg (fasted) - Table 3 (LYT- 100-2021-103 Part 2). Levels of the 5-carboxy metabolite also sorted from lowest to highest in the above order (Table 3) (LYT-100-2021-103 Part 2).

_{e i e} ^f _r ⁱ ₁ - _{e i e} ^f _r ^{i m} _{( 1 7} ) ^{) 4} _{L 2} - m ₉ ^. _{4 7} ^. ₆ C ₀ ^/ _r ^{h 4 1} ) _{( ( 0} D ⁰ ₁ ^I - _{T d} ^K U _{* P} A ^g _c D ₄ ^{. S} _{1 9} ¹ _{. (} ^{3 7} _{6 ) )} ⁵ _{. )} ³ _{. )} ³ _{. )} ² _{. )} ⁷ ₎ ⁷ _{T g} ^e ₆ m ^{Y m} _F ⁴ _{n 1 6} ⁴ ₌ ^% ₍ ^{6 4 4} _{0 0} ² _. ⁸ _. ⁸ _{0 =} ^{) a} N _{n ( 3 ( 2 ( 2 ( ( ( L 0} ⁵ ₅ N ^x _{L e ) a} M ⁰ _{. )} m ^m _/ ^{3 0} _{1 4 4 . (} ¹ ₍ C ^g _c ⁶ ₆ ^{2 m} ₍ ^. _{8 0} ^. _{4 s} ^c _i ^{t * /} e ⁿ _t ^y _{x i} ^{n o e} _s k _{e b t} ^t i _{n s} e ^r _{n e} ^{i g a a} _{i a} ^/ m Pt _{r n} ^{e o} _t ^s _s ^r _e ^s _{s o} ^{r c} _a ^{r l} _v ^d _{a a o} ^E _{r a} ^{P c} - ^b _a ^{o e} _{s n} ⁱ t _{e i} ^{h s} r _p ^{l o e} _{a f} ⁱ _{s y} ^S _e ^{h d} _c ^{a e} _n m ^{t e} _{s si} ^u _a ^m _{r o} ^a _{i p} ^{s n} _i ^{m m} _o ^{n c} _e ^t _s ^s _{u r} ^o _{s d} ^{a i} e _z ^z _i r ^{K 5} _e ^r _e ^D a _P ^K m ^v _I N V D _y D _o ^d _{si i} ^o D D _v ^r _i D H D h _{P d} G _{b e P} A A N [0177] Table 4 summarizes the pharmacokinetic results and shows that at the 550 mg TID dose, the PK parameters of LYT-100 and the metabolite, 5-carboxypirfenidone were similar to those seen in Part 2 of the study at the 550 mg TID dose of LYT-100. At the higher dose of 824 mg TID, the AUC _0-24 and C _max were higher than those seen with pirfenidone; however, the corresponding parameters of the metabolite 5-carboxypirfenidone were similar/slightly lower. The adverse event data (Table 6) shows that even at the 824 mg TID dose, the frequency of the most common adverse events was very low. The higher exposures combined with low frequency of adverse events provide the rationale for using the 825 mg TID dose of LYT-100 in the treatment of fibrotic- or collagen-mediated diseases and disorders. Table 4: Pharmacokinetic Parameters of LYT-100, Pirfenidone, and 5-Carboxypirfenidone after the 3 Days of Dosing in the Fed State LYT-100550 mg TID LYT-100824 mg TID ) [0178] The dose of LYT-100 was optimized to achieve similar systemic exposure (AUC) to pirfenidone 801 mg TID. The dose of LYT-100 was also optimized to achieve similar Cmax to pirfenidone 801 mg TID while maximizing exposure (AUC). The Cmax and AUC values obtained using the pooled LYT-100 PK data in comparison with 801 mg TID pirfenidone were confirmed in subsequent individual studies of 550 mg TID LYT-100 and 824 mg TID LYT-100, thus confirming our confidence in the modeling data and the use of 550 mg TID and 825 mg TID LYT- 100 doses. [0179] The dose of LYT-100 was optimized to achieve similar Cmax to pirfenidone 801 mg TID while maximizing drug exposure (AUC). Study LYT-100-2021-103 Part 3 was a randomized, double-blinded, parallel arm, placebo-controlled study conducted in healthy older adults to evaluate the safety and tolerability of titrated high dose LYT-100 compared to placebo under fed conditions. Based on the observations of improved tolerability (but comparable total exposure) for a lower TID dose of LYT-100 compared to pirfenidone in Part 2 (550 TID LYT-100), the decision was made to test the safety and tolerability of a higher TID dose of LYT-100, to achieve a higher overall predicted AUC or total exposure than the approved dose of pirfenidone (801 mg TID). Subjects between the ages of 60 and 80 were randomized to receive LYT-100 or placebo. Subjects were administered up to 550 mg LYT-100 TID for 3 days (to steady state [Day 1 to Day 3]) compared to placebo administered TID for 3 days to steady state. On Day 4 to Day 6, subjects were administered 824 mg LYT-100 TID for 3 days compared to placebo TID for 3 days to steady state. A summary of the dosing scheme is provided below in the Example section (Example 2). [0180] Table 5 summarizes the pharmacokinetic results and shows that at the 550 mg TID dose, the PK parameters of LYT-100 and the metabolite, 5-carboxypirfenidone were similar to those seen in Part 2 of the study at the 550 mg TID dose of LYT-100. At the higher dose of 824 mg TID, the AUC _0-24 and C _max were higher than those seen with pirfenidone 801 mg TID; however, the corresponding parameters of the metabolite 5-carboxypirfenidone were similar or slightly lower. The adverse event data (Table 6) shows that even at the 824 mg TID dose, the frequency of the most common adverse events was very low. The higher exposures combined with low frequency of adverse events provide the rationale for using the 825 mg TID dose of LYT-100 in treating fibrotic- or collagen-mediated diseases and disorders. Table 5: Pharmacokinetic Parameters of LYT-100, Pirfenidone, and 5-Carboxypirfenidone after the 3 Days of Dosing in the Fed State LYT-100550 mg TID LYT-100824 mg TID ) [0181] LYT-100824 mg TID achieved approximately 25% higher AUC with a modestly higher Cmax compared to historic pirfenidone PK values. Surpisingly, as shown in Table 6, this high dose of LYT-100 (825 mg TID) was well-tolerated. Prior to completing the tolerability study shown in Table 6, it was not known such high dose – 825 mg TID LYT-100 which is the equivalent of about 120-150 % exposure of 801 TID prifenidone) – could be sufficienty tolerated to be included in a clinical efficacy study. Table 6. Pharmacokinetic parameters and adverse events for LYT-100 and 5-carboxypirfenidone metabolite Healthy Older Part 3 LYT 100 LYT 100 L 6) 3) dies [0182] Table 7 summarizes the pharmacokinetic results for the 550 mg TID doses and the 825 mg TID, along with the observed adverse events and frequency, and further provides comparative data for pirfenidone in a related study.

^{r et} _i ^{f l} - _o ^b _{r a} ^t _e ^. _f ^{m r} _i ^e _{n (} ^o _d ^{i t} _{r n} ^e f _r ⁱ _{tl p} ^y _x ^o _b ^{r r} _l ^d _n t ^a _l ^, _e ⁿ _o ^d _i ⁿ _e ^f _ri ^p, ₀ ⁰ ₁ - _T Y ^Lr _o ^f _s ^t _n ^e _v ^e e ^{d v} _{l 4 d} O ² _L ^{) )} - ^m ₂ ^. ₉ ^{. a} _y ^{0 /} _{r 1} ³ _{2 (} ² ₍ ⁿ _o ^{d ht} C ^h l D U _{* ) 0} ^. ₂ m _n ^{a a} _{e 0} ^{0 I} T ^r ₃ A ^g _c D ₂ ^{3 1} _. ⁹ _{3 ) ) ) )} ⁾ ₅ ⁾ _{5 )} ^m _{o s e} H ₁ - _{g d} ^{e 1} m ^S _{( 1 6} ^{1 % 3} _. ^t _T ^{8 2} _. ² _. ^. ₂ ^. ₂ ² _. ^c _{t e} ^Y m _{F =} N _n ^a _{= ( 0 0} ^{4 4} ₀ N _{n ( ( (} ¹ ₍ ¹ ₍ ⁴ ₍ ^s _{o L 0} ⁾ _{e ) ) 2 1 1 3 3 1} ^{m m} _a ^{5 r} _{5 a} ^x _L M a ⁴ _. ^{2 0} _. ^{2 e} _r ^{p c} C ^{m m} _/ ^g ( ( ^a c ^{4 4 t} _{a i 3} ^. ₇ ^{. h t m} _{e ( 9 4 t e} ^{n s} _{i o} ^{k h} _{t o} ^c _{s a} ^c _i ^{t * /} _{e e} ^y _s ^t _{s n} ^{i /} m ^{e r} _a ^m _r ⁿ _t ^a _i ⁿ _x ^{o et} _h ^k _{e o} ^r _{b i a} ^{r l} _n ^{e r} v _e ^d a _o ^{b E} _{r a} ^{g o e} _{s n} ^{i a} _e ^a _{i a} s ^u t _i ^hr _p ^{P t l} _r ^o _{n t f} ^oi _s ^s _{y s} ^r _{e e} ^{h s} c _{s d} e ^et _{r r} ^e _a ^{n mn S s d} _r ^a _n ^{i o P} _. ^c _a ^{P c} _{- a} ^{t e} _{s si a} ^{m a 7} m ^{K 5} _e ^r _e ^D N _{o i p} ^s _{i o} ^c _e ^t _u ^o _d ^a _z ^z _p ^e _e V D _y ^m _{o si si} ^o _{v si e} H _{i r} D ^{s l r} _{a P} ^K m ^v _I D ^d D D ^r D _{E b} ^h _{P d} G _{b e} A ^a _P A A N * _T [0183] The 550 mg TID and 825 mg TID doses of LYT-100 were optimized to key PK parameters and demonstrated to improve tolerability as compared with 2304 mg daily dose (801 mg TID) pirfenidone, surpisingly even at a higher systemic drug exposure. This improved tolerability of LYT-100 relative to pirfenidone was unexpected and may significantly improve compliance with a sustained high efficacious dose (e.g., by reducing the frequency of dose reductions, treatment interruptions, and/or temporary or permanent discontinuations experienced with the use of pirfenidone). [0184] Overall, as described in Examples 1 and 2 of the present disclosure, in Parts 1 and 2 of the clinical study, 850 mg BID of LYT-100 closely matched the AUC with slightly higher Cmax with pirfenidone 801 mg TID; and 550 mg TID LYT-100 dose matched the AUC (within BE) with lower Cmax compared to pirfenidone 801 mg TID. With continued reference to the Examples, in the first study, on day 3, LYT-100550 mg TID dosed in the fed state, had a 24% lower C _max with a similar AUC versus fed pirfenidone 801 mg TID; on day 4, both pirfenidone and 550 mg TID LYT-100, dosed in the fasted state, resulted in higher drug exposures, with a larger C _max increase for pirfenidone; on day 3, in the fed state, the metabolite C _max was 46% lower for LYT-100 vs pirfenidone; and AE rates trended with C _max of parent and metabolite (for fasted pirfenidone, fed pirfenidone, fasted LYT-100, and fed LYT-100, the AE rates respectively, were: GI 28.3%, 10.6%, 11.1%, 6.5%; CNS 21.7%, 14.9%, 8.9%, 8.7%). With continued reference to the Examples, in the second study, on day 3, LYT-100 dosed at 824 mg TID had a C _max 57% higher and an AUC _0-24 43% higher than those for LYT-100 dosed at 550 mg. The AEs were low and comparable between LYT-100824 mg TID and placebo (GI 0%, CNS 0%, 16.7% infection (COVID-19) for both arms). [0185] With further reference to the Examples, results of Part 3 of the Study were unexpected given the predictions based on Study Parts 1 and 2). Specifically, 1) LYT-100550 mg TID had much lower AUC but similar Cmax compared to Part 2; 2) LYT-100824 mg TID had lower AUC than predicted; Cmax was 17% higher than with pirfenidone; 3) although higher variability was seen in PK parameters of LYT-100 in Part 3, the Metabolite/Parent Ratio was consistently lower with LYT-100 compared to pirfenidone (i.e., the 5-carboxy metabolite exposures are lower when comparing the same doses of LYT-100 and pirfenidone); 4) the GI AE’s and nausea are much lower with LYT-100 (550 mg TID) compared to pirfenidone 801 mg TID; 5) dosing in the fed state lowered the GI-related AE’s, especially for pirfenidone, but had less of an impact on AEs with LYT-100; 6) the GI AE’s appear early during treatment; and 7) better tolerability of LYT-100 at the 550 mg TID dose allows subjects to have better adherence with the full dose, which may result in a better clinical outcome in various fibrotic- or collagen-mediated diseases and disorders. [0186] In the disclosed method, the dose and frequency of dosing may vary based on the diseases or disorder and the severity thereof, as well as on the desired pharmacokinetic parameters and tolerability profile. Particularly, the improved tolerability of LYT-100 (e.g., less adverse side effects) can allow dosing at therapeutic (efficacious) levels, e.g., including dosing at the current approved therapeutic dose for pirfenidone, with less or no treatment interruption, less or no treatment discontinuation, less or no dose-lowering in treating fibrotic- or collagen-mediated diseases or disorders. This greater tolerability of deuterium-enriched pirfenidone LYT-100 can allow for sustained or long-term treatment at therapeutic dosing resulting in effective treatment of patients afflicted with a variety of fibrotic- or collagen-mediated diseases and disorders. The improved tolerability also provides the potential for dosing without titration or with a reduced duration of titration, to more rapidly and effectively treat patients with a variety of fibrotic- or collagen-mediated diseases and disorders. The improved tolerability also provides the potential for higher dosing (systemic exposure) for greater effectiveness without the adverse effects seen at equivalent doses (systemic exposure) for pirfenidone. [0187] As described above, the method generally comprises administering LYT-100 at a total daily dose from about 825 mg to about 2550 mg of LYT-100. In some embodiments, LYT-100 is administered at a daily dose that achieves the same or about the same systemic exposure as pirfenidone administered at a dose of 2403 mg/day. In some embodiments, the method comprises administering a total daily dose of LYT-100 that achieves a systemic exposure greater than the systemic exposure of pirfenidone dosed at 2403 mg daily dose, e.g., 801 mg TID dosing. [0188] In some embodiments, the total daily dose is from about 825 to about 1650 mg, such as about 825, about 1100, about 1375, or about 1650 mg. In some embodiments, the total daily dose in 825 mg. [0189] In some embodiments, the total daily dose is from about 1650 to about 2550 mg of LYT- 100, such as about 1650, about 1700, about 1750, about 1800, about 1850, about 1900, about 1950, about 2000, about 2050, about 2100, about 2150, about 2200, about 2250, about 2300, about 2350, about 2400, about 2450, about 2475, about 2500, or about 2550 mg. In some embodiments, the total daily dose is from about 1650 mg to about 2475 mg. In some embodiments, the total daily dose is 1650 mg. In some embodiments, the total daily dose is 2475 mg. [0190] In some embodiments, the total daily dose is administered in three equal administrations. In some embodiments, the LYT-100 is administered in three equal doses of 550 mg each (550 mg TID). In some embodiments, the LYT-100 is administered in three equal doses of 825 mg each (825 mg TID). In some embodiments, the LYT-100 is administered in three equal doses of 275 mg each (275 mg TID). [0191] In some embodiments, the LYT-100 is administered without regard to food. In some embodiments, the LYT-100 is administered without food. In some embodiments, the LYT-100 is administered with food. [0192] In some embodiments, the LYT-100 is administered orally without food in three daily doses of 550 mg each. In some embodiments, the LYT-100 is administered orally with food in three daily doses of 550 mg each. [0193] In some embodiments, the LYT-100 is administered orally without food in three daily doses of 825 mg each. In some embodiments, the LYT-100 is administered orally with food in three daily doses of 825 mg each. [0194] In some embodiments, the LYT-100 is administered orally without food in three daily doses of 275 mg each. In some embodiments, the LYT-100 is administered orally with food in three daily doses of 275 mg each. [0195] In some embodiments, the LYT-100 is administered without dose escalation. In some embodiments, the LYT-100 is administered in three equal administrations of 825 mg each, without dose escalation. [0196] In some embodiments, the LYT-100 is administered with dose escalation. In some embodiments, three daily doses of 550 mg each are administered for three days, followed by administering LYT-100 at a dosage of 825 mg TID. Referring to the crossover study described in Example 2, initial data for the occurrence of adverse events in healthy elderly subjects taking doses of 550 mg TID (1650 mg/day) followed by 824 TID (2472 mg/day) indicates that adverse events (particularly gastrointestinal (GI) disorders and nervous system disorders) do not increase and may decrease or even disappear with this dose titration scheme. [0197] In comparison, as reported in regulatory summaries leading to approval of Esbriet (pirfenidone), escalating daily doses (801, 1602, 2403, 3204, and 4005 mg/day, provided in three equal doses) of pirfenidone were tested in a cohort of healthy older subjects (PIPF-005). The number of AEs (headache, dyspepsia, nausea, back pain) reported increased with increasing total daily dose. The higher C _ma x values at higher dosages increased the odds of experiencing a gastrointestinal (GI) AE, and it was noted that this was consistent with previous studies for pirfenidone. As reported for study PIPF-005, for the three times daily dose of 801 mg (2403 mg/day), the C _max was 11.85 μg/mL, which falls between the C _max values reported for 550 mg TID and 824 mg TID in Example 2. [0198] In some embodiments, the method comprises administering LYT-100 at a first total daily dose of 825 mg for a first period and a second total daily maintenance dose of 1650 mg. In some embodiments, the method comprises administering LYT-100 at a first total daily dose of 1650 mg for a first period and a second total daily maintenance dose of 2475 mg. In some embodiments, the method comprises administering LYT-100 at a first total daily dose of 825 mg for a first period, a second total daily dose of 1650 mg for a second period, and then a total maintenance dose of 2475 mg. In some embodiments, the method comprises administering LYT-100 at a first total daily dose of 825 mg for a first period of about 7 days and a second total daily maintenance dose of 1650 mg. In some embodiments, the method comprises administering LYT-100 at a first total daily dose of 1650 mg for a first period of about 7 days and a second total daily maintenance dose of 2475 mg. In some embodiments, the method comprises administering LYT-100 at a first total daily dose of 825 mg for a first period of about 7 days, a second total daily dose of 1650 mg for a second period of about 7 days, and then a total maintenance dose of 2475 mg. In some embodiments, the method comprises administering LYT-100 at a first total daily dose of 825 mg for a first period of about 14 days and a second total daily maintenance dose of 1650 mg. In some embodiments, the method comprises administering LYT-100 at a first total daily dose of 1650 mg for a first period of about 14 days and a second total daily maintenance dose of 2475 mg. In some embodiments, the method comprises administering LYT-100 at a first total daily dose of 825 mg for a first period of about 14 days, a second total daily dose of 1650 mg for a second period of about 14 days, and then a total maintenance dose of 2475 mg. In some embodiments, the method comprises administering LYT- 100 at a first total daily dose of 825 mg for a first period of 7-14 days and a second total daily maintenance dose of 1650 mg. In some embodiments, the method comprises administering LYT- 100 at a first total daily dose of 1650 mg for a first period of 7-14 days and a second total daily maintenance dose of 2475 mg. In some embodiments, the method comprises administering LYT- 100 at a first total daily dose of 825 mg for a first period of 7-14 days, a second total daily dose of 1650 mg for a second period of 7-14 days, and then a total maintenance dose of 2475 mg. [0199] In some embodiments, the method comprises administering LYT-100 in three daily doses of 275 mg each for a first period and in three daily doses of 550 mg each for a second maintenance dose. In some embodiments, the method comprises administering LYT-100 in three daily doses of 550 mg each for a first period and in three daily doses of 825 mg each for a second maintenance dose. In some embodiments, the method comprises administering LYT-100 in three daily doses of 275 mg each for a first period, in three daily doses of 550 mg each for a second period, and then in three daily doses of 825 mg each for a maintenance dose. In some embodiments, the method comprises administering LYT-100 in three daily doses of 275 mg each for a first period of about 7 days and in three daily doses of 550 mg each for a second maintenance dose. In some embodiments, the method comprises administering LYT-100 in three daily doses of 550 mg each for a first period of about 7 days and in three daily doses of 825 mg each for a second maintenance dose. In some embodiments, the method comprises administering LYT-100 in three daily doses of 275 mg each for a first period of about 7 days, in three daily doses of 550 mg each for a second period of about 7 days, and then in three daily doses of 825 mg each for a maintenance dose. In some embodiments, the method comprises administering LYT-100 in three daily doses of 275 mg each for a first period of about 14 days and in three daily doses of 550 mg each for a second maintenance dose. In some embodiments, the method comprises administering LYT-100 in three daily doses of 550 mg each for a first period of about 14 days and in three daily doses of 825 mg each for a second maintenance dose. In some embodiments, the method comprises administering LYT-100 in three daily doses of 275 mg each for a first period of about 14 days, in three daily doses of 550 mg each for a second period of about 14 days, and then in three daily doses of 825 mg each for a maintenance dose. In some embodiments, the method comprises administering LYT-100 in three daily doses of 275 mg each for a first period of 7-14 days and in three daily doses of 550 mg each for a second maintenance dose. In some embodiments, the method comprises administering LYT-100 in three daily doses of 550 mg each for a first period of 7-14 days and in three daily doses of 825 mg each for a second maintenance dose. In some embodiments, the method comprises administering LYT-100 in three daily doses of 275 mg each for a first period of 7-14 days, in three daily doses of 550 mg each for a second period of 7-14 days, and then in three daily doses of 825 mg each for a maintenance dose. [0200] In any of the above embodiments, the LYT-100 is administered orally without food. In any of the above embodiments, the LYT-100 is administered orally with food. In any of the above embodiments, the LYT-100 is administered orally without regard to food. In any of the above embodiments, the total daily dose, e.g., 825 mg, 1650 mg or 2475 mg may be adjusted to lower daily dose, for example, as described elsewhere in the specification. [0201] In some embodiments, LYT-100 administered in a total daily dose of 1650-2475, in three daily doses, results in increased tolerability as compared with pirfenidone administered at 801 mg TID. In some embodiments, the increased tolerability is due to a reduction in one or more adverse events or side effects. In some embodiments, the one or more adverse events are nervous system side effects. In some embodiments, the one or more adverse events are gastrointestinal events. In some embodiments, the LYT-100 is administered in three daily doses of 550 mg each. [0202] In some embodiments, LYT-100 administered in a total daily dose of 1650-2475, in three daily doses, results in a lower steady-state C _max as compared with pirfenidone administered at 801 mg TID. In some embodiments, the LYT-100 is administered in three daily doses of 550 mg each. [0203] In some embodiments, LYT-100 administered in a total daily dose of 1650-2475, in three daily doses, results in a steady-state exposure (AUC) of LYT-100 which is the same or about the same as the steady-state exposure (AUC) of pirfenidone achieved when pirfenidone is administered at 801 mg TID. In some embodiments, LYT-100 administered in a total daily dose of 1650-2475, in three daily doses, results in a steady-state exposure (AUC) of LYT-100 which is bioequivalent to the steady-state exposure (AUC) of pirfenidone when pirfenidone is administered at 801 mg TID. In some embodiments, the LYT-100 is administered in three daily doses of 550 mg each. [0204] In some embodiments, LYT-100 administered in a total daily dose of 1650-2475, in three daily doses, results in the same or about the same steady-state exposure (AUC) of LYT-100 achieved for pirfenidone when pirfenidone is administered at 801 mg TID, and results in a lower steady-state C _max of LYT-100 achieved for pirfenidone when pirfenidone is adminsitered at 801 mg TID. In some embodiments, the steady-state exposure of LYT-100 is about 90% of the AUC of pirfenidone achieved when pirfenidone is administered at a total daily dose of 2403 mg, and wherein the total daily dose of pirfenidone is administered in three doses of 801 mg each (801 mg TID). In some embodiments, the lower steady-state C _max of LYT-100 is about 75-80% of the C _max of pirfenidone achieved when pirfenidone is administered at a total daily dose of 2403 mg, and wherein the total daily dose of pirfenidone is administered in three doses of 801 mg each (801 mg TID). In some embodiments, at this dosing, the LYT-100 has an increased or improved tolerability that is due to a reduction in one or more adverse events or side effects as compared with pirfenidone administered at 801 mg TID. In some embodiments, the LYT-100 is administered in three daily doses of 550 mg each. [0205] In some embodiments, LYT-100 administered in a total daily dose of 1650-2475, in three daily doses, results in the same or about the same steady-state exposure (AUC) as compared with pirfenidone administered at 801 mg TID and increased or improved tolerability as compared with pirfenidone adminsitered at 801 mg TID. In some embodiments, the increased or improved tolerability is due to a reduction in one or more adverse events or side effects. In some embodiments, LYT-100 is administered in three daily doses of 550 mg each. [0206] In some embodiments, LYT-100 administered in a total daily dose of 1650-2475, in three daily doses, results in a higher steady-state exposure (AUC) as compared with pirfenidone administered at 801 mg TID. In some embodiments, the LYT-100 is administered in three daily doses of 825 mg each. [0207] In some embodiments, LYT-100 administered in a total daily dose of 1650-2475, in three daily doses, results in the same or about the same steady-state Cmax as compared with pirfenidone administered at 801 mg TID. In some embodiments, the LYT-100 is administered in three daily doses of 825 mg each. [0208] In some embodiments, LYT-100 administered in a total daily dose of 1650-2475, in three daily doses, results in a higher steady-state exposure (AUC) as compared with pirfenidone administered at 801 mg TID and the same or about the same steady-state Cmax as compared with pirfenidone administered at 801 mg TID. In some embodiments, the LYT-100 is administered in three daily doses of 825 mg each. [0209] In some embodiments, LYT-100 administered in a total daily dose of 1650-2475, in three daily doses, results in a higher steady-state exposure (AUC) as compared with pirfenidone administered at 801 mg TID and has the same or about the same tolerability (e.g., the incidence of adverse events is not significantly different) as compared with pirfenidone administered at 801 mg TID. In some embodiments, LYT-100 administered in a total daily dose of 1650-2475, in three daily doses, results in a higher steady-state exposure (AUC) as compared with pirfenidone administered at 801 mg TID and has an increased or improved tolerability that is due to a reduction in one or more adverse events or side effects. In some embodiments, the LYT-100 is administered in three daily doses of 825 mg each. [0210] In some embodiments, LYT-100 administered in a total daily dose of 1650-2475, in three daily doses, results in the same or about the same steady-state Cmax as compared with pirfenidone administered at 801 mg TID and has the same or about the same tolerability (e.g., the incidence of adverse events is not significantly different) as compared with pirfenidone administered at 801 mg TID. In some embodiments, LYT-100 administered in a total daily dose of 1650-2475, in three daily doses, results in the same or about the same steady-state Cmax as compared with pirfenidone administered at 801 mg TID and has an increased or improved tolerability that is due to a reduction in one or more adverse events or side effects. In some embodiments, the LYT-100 is administered in three daily doses of 825 mg each. [0211] In some embodiments, the LYT-100 is administered at a dose that achieves a systemic exposure of LYT-100 in the subject which is about 85-125% of the systemic exposure of pirfenidone achieved when pirfenidone is administered at a total daily dose of 2403 mg, and wherein the total daily dose of pirfenidone is administered in three doses of 801 mg each (801 mg TID). [0212] In some embodiments, the dose of LYT-100 that achieves the systemic exposure of LYT- 100 in the subject which is about 85-125% of the systemic exposure of pirfenidone is 825 mg TID. [0213] In some embodiments, the dose of LYT-100 that achieves the systemic exposure of LYT- 100 in the subject which is about 85-125%of the systemic exposure of pirfenidone also achieves a C _max of LYT-100 in the subject which is about 115 – 125% of the C _max of pirfenidone achieved when is administered at a total daily dose of 2403 mg, and wherein the total daily dose of pirfenidone is administered in three doses of 801 mg each (801 mg TID). In some embodiments, at this dosing, the LYT-100 has the same or about the same tolerability (e.g., the incidence of adverse events is not significantly different) as compared with pirfenidone administered at 801 mg TID. In some embodiments, at this dosing, the LYT-100 has an increased or improved tolerability that is due to a reduction in one or more adverse events or side effects as compared with pirfenidone administered at 801 mg TID. In some embodiments, the LYT-100 is administered in three daily doses of 825 mg each. [0214] As described above, in some embodiments, administration of LYT-100 according to the disclosed method results in increased or improved tolerability that is due to a reduction in one or more adverse events or side effects in a subject as compared with pirfenidone administered at a dose or dosing that achieves the same or about the same systemic exposure. [0215] In any of these embodiments wherein one or more side effects is reduced, the incidence, the severity, ot both may be reduced. In some embodiments, the incidence (i.e., the frequency with which side effects occur) of side effects in an individual patient or in a patient popoluation, is reduced by at least 30% as compared with pirfenidone administered at a dose or dosing that achieves the same or about the same systemic exposure. For example, in some emboidments, the incidence of side effects is reduced by at least 35%, at least 40%, or at least about 50% as compared with pirfenidone administered at a dose or dosing that achieves the same or about the same systemic exposure. In some embodiments, the incidence of side effects is reduced by at least 30% as compared with pirfenidone administered at a total daily dose of 2403 mg, including e.g., at 801 mg TID. [0216] In some embodiments, the incidence of side effects is reduced when the subject is dosed in a fed state as compared with pirfenidone administered at a dose or dosing that achieves the same or about the same systemic exposure in a fed state. In some embodiments, the incidence of side effects is reduced when the subject is dosed in a fasted state as compared with pirfenidone administered at a dose or dosing that achieves the same or about the same systemic exposure in a fasted state. [0217] In some embodiments, the one or more side effects is a gastrointestinal side effect(s). In some embodients, the one or more side effects is a nervous system side effect(s). In some embodiments, the one or more side effects is a combination of gastrointestinal side effect(s) and nervous system side effect(s). Examples of gastrointestinal side effects include nausea, vomiting, and abdominal pain or distension. [0218] In some embodiments, the nervous system and/or gastrointestinal side effects in a subject are reduced with administration of LYT-100 at a total daily dose of 1650 mg, optionally wherein the LYT-100 is administered TID. In some embodiments, the nervous system and/or gastrointestinal side effects in a subject are reduced with administration of LYT-100 at a total daily dose of 2475 mg, optionally wherein the LYT-100 is administered TID. Fibrotic-and collagen-mediated diseases and disorders [0219] The disclosed method generally treats fibrotic-and collagen-mediated diseases and disorders. Accordingly, the method may treat a variety of diseases and disorders of a fibrotic and/or inflammatory nature. In some embodiments, the fibrotic- or collagen-mediated disease or disorder, or a symptom thereof, is alleviated. In some embodiments, the onset of the fibrotic- or collagen- mediated disease or disorder is delayed, slowed, or arrested. In some embodiments, the progression of the fibrotic- or collagen-mediated disease or disorder is delayed, slowed, or arrested. Edema and Lymphedema [0220] In some embodiments, the method treats edema. Edema is an abnormal accumulation of fluid beneath the skin and in body cavities including, but not limited to, limbs, hands/feet, upper body (breast/chest wall, shoulder, back), lower body (buttocks, abdomen), genital (scrotum, penis, vulva), head, neck, or face. The abnormal accumulation of fluid can occur when capillary filtration exceeds lymphatic drainage. In this way, all edema has a lymphatic component. Edema includes lymphedema, lymphatic dysfunction, lymphatic tissue fibrosis, idiopathic edema, peripheral edema, and eye edema. Edema includes acute edema, chronic edema, post-operative edema, gradual-onset edema, primary edema and secondary edema. Chronic edema is edema that has been present for more than three months and can include lymphedema (primary-failure of the lymphatic development and secondary-following damage to the lymphatics), venous edema, chronic swelling due to immobility, edema related to advanced cancer, chronic swelling associated with lymphedema, chronic swelling related to obesity, and chronic swelling associated with rare vascular malformations such as Klippel-Trenaunay syndrome. Symptoms of edema can include accumulation of fluid beneath the skin and in body cavities, swelling, fullness, or puffiness of tissues, inflammation, fibrosis, heaviness, pain, decreased range of motion, aching, recurring infections, skin thickening, or discomfort. In some embodiments, "edema" does not include pulmonary edema or cerebral edema. In some embodiments, the edema is lymphedema, including primary and secondary lymphedema. [0221] Accordingly, in some embodiments, the method treats lymphedema. In some embodiments, the lymphedema is primary lymphedema. In some embodiments, the lymphedema is secondary lymphedema. In some embodiments, the lymphedema is breast cancer-related lymphedema. In some embodiments, the lymphedema is mild to moderate breast cancer-related lymphedema. [0222] Lymphedema is a chronic debilitating disease of fibrotic and inflammatory origin that afflicts millions of people and is characterized by severe swelling in parts of the body, typically the arms or legs, due to the build-up of lymph fluid and inflammation, fibrosis and adipose deposition. Lymph is a clear fluid collected from body tissues that transports fats and proteins from the small intestine, removes bacteria, viruses, toxins, and certain proteins from tissues and supplies white blood cells, specifically lymphocytes, to the bloodstream to help fight infections and other diseases. Drainage of lymphatic fluid from tissues is important because the accumulation of lymphatic fluid can be pro- inflammatory. When there is injury to the lymphatics—for example surgery or radiation damage— this can block lymphatic flow and cause pro-inflammatory fluid to accumulate in tissue. This can kick off a vicious feedback loop of inflammation and fibrosis that can cause lymphatic pumping to fail and lymphedema to occur. In lymphedema, the healthy lymphatic fluid homeostasis fails, creating an environment where immune cells begin infiltrating into the tissue and releasing pro- inflammatory and pro-fibrotic cytokines, such as TGF-β. This can create fibrosis of, e.g., arm tissue and the lymphatics themselves. This can further impair lymphatic flow. While the lymphatic system is naturally regenerative, trying to regrow and repair after injury, the feedback loop of fibrosis and inflammation impairs that regeneration. Lymphedema is a serious disease with significant health consequences, including disfigurement and debilitation. Patients have chronic swelling of the affected extremity, a sense of heaviness, pain, discomfort, skin damage, fibrosis, recurrent infections, limited mobility, and decreased quality of life. [0223] In developed countries such as the United States, lymphedema occurs most often as a complication of cancer treatment. Thus, secondary lymphedema is the most prevalent form of lymphedema, and can develop after surgery, infection or trauma, and is frequently caused by cancer, cancer treatments such as radiation and chemotherapy, trauma or infections resulting in damage to or the removal of lymph nodes. As a complication of cancer treatment, lymphedema occurs as a result of iatrogenic injury to the lymphatic system, usually as a result of lymph node dissection. According to estimates, as many as 1 in 3 patients who undergo lymph node dissection later develop lymphedema. Large skin excisions and adjuvant therapy with radiation may also cause lymphedema. In addition, obesity and radiation are known risk factors for the development of lymphedema. [0224] Lymphedema of the leg and its advanced form, known as elephantiasis, are significant causes of disability and morbidity in areas endemic for lymphatic filariasis, with an estimated 14 million persons affected worldwide (Stocks et al., PLoS Negl Trop Dis.2015 Oct 23;9(10):e0004171). Over 1.1 billion people worldwide are at risk for lymphatic filariasis (Walsh et al, PLoS Negl Trop Dis. 2016 Aug 22;10(8):e0004917). Lymphatic filariasis is distributed from Latin America, across central Africa, southern Asia and into the Pacific Islands. Filarial infection is mosquito-transmitted, but efforts to control transmission that are based exclusively on mosquito control have had limited success (Lammie et al., Ann N Y Acad Sci. 2002 Dec;979:131-42; discussion 188-96). Wuchereria bancrofti (Wb) is the most widely distributed of the three nematodes known to cause lymphatic filariasis (LF), the other two being Brugia malayi and Brugia timori. Wuchereria bancrofti is the species responsible for 90% of lymphatic filariasis in humans. Filarial infection can cause a variety of clinical manifestations, including lymphoedema of the limbs, genital disease (hydrocele, chylocele, and swelling of the scrotum and penis) and recurrent acute attacks. These acute attacks are caused by secondary infections, to which the lower limbs with lymphatic damage are predisposed, and which are extremely painful and are accompanied by fever. Most infected people do not have symptoms, but virtually all of them have subclinical lymphatic damage and as many as 40% have kidney damage, with proteinuria and hematuria. [0225] In lymphedema, the accumulation of protein-rich interstitial fluid leads to inflammation and an accumulation of fibroblasts, adipocytes, and keratinocytes that transform the initially soft swollen tissue into a hard fibrotic tissue with stiff, thickened skin. Fibrosis is a scarring process, which is characterized by excess deposition of collageneous and non-collagenous extracellular matrix (ECM) due to the accumulation, proliferation, and activation of fibroblasts and myofibroblasts. Fibroblasts are the main cells that produce, maintain, and reabsorb extracellular matrix (ECM) (reviewed in Kendall and Feghali-Bostwick, Front. Pharmacol., 27 May 2014). Fibroblasts produce the structural proteins of the ECM, expressing different ECMs in different tissues requiring differing degrees of rigidity and flexibility; e.g., fibril rigidity is provided by collagen type I, while expansive stretching ability is provided by elastin proteins. As the major producers of ECM, fibroblasts are also the central mediators of the pathological fibrotic accumulation of ECM and of the cellular proliferation and differentiation that occurs in response to prolonged tissue injury and chronic inflammation in multiple fibrotic diseases including lymphedema. [0226] Dysfunctions of the lymphatic system have remained largely untreated or poorly addressed by current therapeutics. There are currently no approved drug therapies for the treatment of lymphedema. Furthermore, at present, there is no known pharmacologic therapy that can halt progression or promote resolution of lymphedema. The current standard of care for lymphedema is management, primarily with compression and physical therapy to control swelling. [0227] LYT-100 is believed to be ideally suited to address lymphedema by virtue of its anti- inflammatory and anti-fibrotic properties, which target the exact mechanisms of the feedback loop that contributes to lymphedema. [0228] Efficacy of the treatment may be determined by improvements in one or more of limb volume, visual-analogue scales (VAS) related to signs and symptoms of lymphedema, or scores in assessment tools such as the Lymphedema Symptom Intensity and Distress Survey-Arm (L- SIDS-A) and Lymphedema Quality of Life Tool-Arm (LYMQOL). [0229] Limb volume and/or extent of fibrosis may be evaluated by bioimpedance, perometry, tissue firmness, and the like. Bioimpedance, or water content, can be measured via Bioelectrical impedance spectroscopy (BIS). Multiple frequency bioelectrical impedance spectroscopy (BIS) provides accurate relative measures of protein-rich fluid in the upper limb of patients. BIS is a noninvasive technique that involves passing an extremely small electrical current through the body and measuring the impedance (or resistance) to the flow of this current. The electrical current is primarily conducted by the water containing fluids in the body. BIS quantifies the amount of protein-rich fluid in lymphedema by comparison of the affected and non-affected limbs. Relative limb volume can be measured by the truncated cone method of circumferential tape measurement. Perometry is a noninvasive technique involving a Perometer (Pero-System), which uses infrared light to scan a limb and obtain measurements of the limb's circumference. The tissue dielectric constant measures the local tissue water content under the skin at various depths ranging from skin to subcutis. The results are converted into a 0-100% scale to reflect subcutaneous fluid deposition that can occur in early- stage lymphedema. To measure tissue firmness, a tonometer device is pressed into the skin to measure the amount of force required to make an indent in the tissue. The resulting measurement gauges the degree of firmness or fibrosis (tissue scarring) under the skin to assess the severity of lymphedema. [0230] The VAS for pain, swelling, discomfort, and function is a graphic scale having a straight line with endpoints from 0 to 10 that is marked by the patient to correlate to their extreme limits of pain, swelling, discomfort and function, ranging from "not at all" to "as bad as it could be." The higher marks on the line indicates the worse condition. [0231] The Lymphedema Symptom Intensity and Distress Survey-Arm (L-SIDS-A) is a self- report tool consisting of 36 items to evaluate arm lymphoedema and associated symptoms in breast cancer survivors. Symptoms are rated on a ten-point scale (5 points for intensity of the symptom and 5-point for how distressed the patient felt) for heaviness, tightness, pain, stabbing pain, cramping, numbness, achiness, swelling, hardness, tingling, pins and needles, difficulty moving, raising the arm and sadness. Lower scores indicate a higher quality of life. [0232] The Lymphedema Quality of Life Tool-Arm (LYMQOL) is a patient completed questionnaire that assesses upper limb lymphoedema and symptoms and ability to perform common functional activities in patients with BCRL. It covers four domains: symptoms, body image/appearance, function, and mood. It also includes an overall quality of life rating. The overall QOL item ranges from 1-10. Subjects with more severe limb dysfunction have higher scores corresponding to lower quality of life. [0233] In some embodiments, the subjectwith lymphedema has or has had cancer, for example, a cancer comprising a solid tumor. In some embodiments, the subject has or has had breast cancer or a cancer affecting female reproductive organs, cutaneous system, musculoskeletal system, soft tissues of the extremities or trunk, male reproductive system, urinary system, or the head and neck. In some embodiments, the subject has undergone axillary lymph node dissection. In some embodiments, the subject has received treatment for cancer, and the edema, lymphedema, or lymphatic injury is associated with the cancer treatment or diagnosis. For example, the subject may be receiving or may have received chemotherapy or radiation therapy for cancer treatment or other indications, or may have had one or more lymph nodes surgically removed in the course of cancer treatment or diagnosis. [0234] In some embodiments, the subject has sustained a lymphatic injury (for example as the result of removal, ligation or obstruction of lymph nodes or lymph vessels, or fibrosis of lymph tissue), or the subject is obese or has or has had an infection that leads to edema, such as lymphedema. In some embodiments, the infection is a skin infection or a history of skin infection related to lymphedema or lymphatic injury. In some embodiments, the infection is a parasitic infection that obstructs lymphatic flow or injures the lymphatic system. In some embodiments, the subject has sustained lymphatic injury from joint replacement, trauma, burns, radiation, or chemotherapy. [0235] In some embodiments, the lymphedema occurs in one or both arms, such as in the hand, wrist, forearm, elbow, upper arm, shoulder, armpit, or combination of arm areas or the entire arm. In some embodiments, the lymphedema occurs in one or both legs, such as in the foot, ankle, leg, knee, upper leg or thigh, groin, hip, or combination of leg areas or the entire leg. In some embodiments, the lymphedema occurs in the head, neck, jaw, chest, breast, thorax, abdomen, pelvis, genitals, or other areas of the body cavity. In some embodiments, the lymphedema occurs in one or more limbs, or in one or more limbs and another area of the body. [0236] In some embodiments, the subject has Stage I lymphedema. In some embodiments, the subject or patient has Stage II lymphedema. In some embodiments, the subject or patient has Stage III lymphedema. In some embodiments, the subject or patient is reduced in stage from Stage III to Stage II or Stage I, or from Stage II to Stage I. [0237] LYT-100 can be used to treat the underlying mechanisms of other forms of secondary or primary lymphedema, for example, lymphatic filariasis. In some embodiments the lymphedema results from a vascular defect, including venous insufficiency, venous malformation, arterial malformation, capillary malformation, lymphovascular malformation, or cardiovascular disease. [0238] In some embodiments, the disclosed method effects one or more of the following: a) reduce tissue swelling, b) reduce lymphatic fluid stasis or "pooling," c) reduce tissue fibrosis, d) reduce tissue inflammation, e) reduce infiltration of leukocytes, f) reduce infiltration of macrophages, g) reduce infiltration of naive and differentiated T-cells, h) reduce TGF-β1 expression and reduce expression and/or activation of downstream mediators (e.g., pSmad3), i) reduce levels of angiotensins and/or ACE, j) reduce collagen deposition and/or scar formation, k) improve or increase lymphatic function, l) improve or increase lymph fluid transport (e.g., lymphatic flow), m) improve or increase lymphangiogenesis, and/or n) improve or increase lymph pulsation frequency. Interstitial Lung Diseases [0239] In some embodiments, the method treats an interstitial lung disease (ILD). ILDs encompasses a large and heterogeneous group of parenchymal lung disorders which overlap in their clinical presentations and patterns of lung injury. ILDs include several diseases of unknown cause, as well as ILDs known to be related to other diseases or to environmental exposures. Common characteristics of ILD are scarring (pulmonary fibrosis) and/or inflammation of the lungs. The interstitium is an interconnected fine mesh of tissue that extends through each lung, supporting the alveoli (air sacs) of the lung. Under normal conditions, the interstitium is so thin that it doesn’t show up on X-rays or CT scans. All forms of ILD result in thickening of the interstitium, e.g., through inflammation, scarring, or a buildup of fluid. ILD can either be transient (acute) or long-term (chronic). A plethora of substances and conditions can lead to ILD. Even so, in some cases, the causes are never found. Such disorders without a known cause are grouped together under the label of idiopathic interstitial pneumonias, the most common and deadly of which is idiopathic pulmonary fibrosis (IPF). [0240] During the progression of ILDs such as IPF, an accumulation of extra cellular matrix components such as collagen and an increase in the fibroblast population is observed. Persistent proliferation of fibroblasts is considered an important contributor to the lung architecture in IPF, including the diminished interstitial spaces of the alveoli. Thus, reducing TGF-β-induced proliferation of fibroblasts and structural collagen with LYT-100 has the potential to prolong lung function in IPF. In addition to inhibiting TGF-β-induced insoluble collagen level, LYT-100 also inhibits TGF-β-induced secreted collagen and fibronectin β. Secreted collagen and fibronectin not only increase the rate of formation of fibrotic foci in the lung, these proteins can also act as ligands for integrin receptors. When integrin receptors are activated, they induce not only the proliferation of epithelial cells and fibroblasts of the lungs, but they also, along with TGF-β, induce epithelial mesenchymal transition (EMT) of the epithelial cells of the lungs. EMT causes these cells to migrate to different regions of the lungs. This migration is considered to be a very important contributor for the generation of new fibrotic foci in the lungs and progression of IPF. LYT-100 has the ability to inhibit TGF-β-induced pro-fibrotic processes and to reduce basal factors, which have the potential to exacerbate ongoing fibrosis. [0241] Non-limiting examples of ILDs include non-idiopathic pulmonary fibrosis, idiopathic non- specific interstitial pneumonia (iNSIP), autoimmune or connective tissue disease (CTD)-ILDs, unclassifiable ILDs (uILD), chronic hypersensitivity pneumonitis (HP), interstitial pneumonia with autoimmune features (IPAF), genetic and/or familial idiopathic pulmonary fibrosis (g/f IPF), chronic sarcoidosis, exposure-related ILDs, and drug-induced ILDs. [0242] In some embodiments, the ILD is iNSIP or interstitial pneumonia with autoimmune features (IPAF). In some embodiments, the ILD is chronic HP. Chronic HP is a complex syndrome caused by sensitization to an inhaled antigen that leads to an aberrant immune response in the small airways and lung parenchyma. Susceptibility is believed to be affected by genetics, antigen concentration and frequency of exposure, and immune tolerance. [0243] In some embodiments, the ILD is autoimmune or CTD-ILD. Autoimmune diseases are commonly associated with pulmonary complications including ILD. Patients across the spectrum of CTDs are at risk of developing ILD. In some embodiments, the autoimmune or CTD-ILD is systemic sclerosis ILD (SSc-ILD). In some embodiments, the ILD is rheumatoid arthritis ILD (RA-ILD). In some embodiments, the ILD is lupus-induced pulmonary fibrosis. In some embodiments, the ILD is scleroderma interstitial lung disease. In some embodiments, the ILD is mixed CTD-associated ILD. [0244] In some embodiments, the ILD is a childhood interstitial lung disease (chILD), which is a broad term for a group of rare lung diseases that can affect babies, children, and teens. These diseases have some similar symptoms, such as chronic cough, rapid breathing, and shortness of breath. These diseases also harm the lungs in similar ways. For example, they damage the tissues that surround the lungs' alveoli and bronchial tubes, and sometimes directly damage the air sacs and airways. The various types of chILD can decrease lung function, reduce blood oxygen levels, and disturb the breathing process. In some embodiments, the chILD is selected from a surfactant dysfunction mutation, a childhood lung developmental disorder such as alveolar capillary dysplasia, a lung growth abnormality, neuroendocrine cell hyperplasia of infancy (NEHI), pulmonary interstitial glycogenosis (PIG), idiopathic interstitial pneumonia (such as nonspecific interstitial pneumonia, cryptogenic organizing pneumonia, acute interstitial pneumonia, desquamative interstitial pneumonia, lymphocytic interstitial pneumonia), an alveolar hemorrhage syndrome, an aspiration syndrome, a hypersensitivity pneumonitis, an infectious or post infectious disease (bronchiolitis obliterans), eosinophilic pneumonia, pulmonary alveolar proteinosis, pulmonary infiltrates with eosinophilia, pulmonary lymphatic disorders (lymphangiomatosis, lymphangiectasis), pulmonary vascular disorders (haemangiomatosis), an interstitial lung disease associated with systemic disease process (such as connective tissue diseases, histiocytosis, malignancy-related lung disease, sarcoidosis, storage diseases), or a disorder of the compromised immune system (such as opportunistic infection, disorders related to therapeutic intervention, lung and bone marrow transplant-associated lung diseases, diffuse alveolar damage of unknown cause). [0245] In some embodiments, the ILD is chronic sarcoidosis or sarcoidosis-related pulmonary fibrosis. Sarcoidosis is an inflammatory disease characterized by the formation of granulomas in one or more organs of the body. When left unchecked, this chronic inflammation can lead to fibrosis. Sarcoidosis affects the lungs in approximately 90% of cases, but can affect almost any organ in the body. [0246] In some embodiments, the method treats an ILD which is an exposure-related ILD, or a drug- induced ILD. In some embodiments, the exposure-related ILD is pneumoconiosis. Pneumoconiosis is one of a group of ILDs caused by breathing in certain kinds of dust particles, such as asbestos, coal, or silica. In some embodiments, the exposure-related ILD is asbestos-induced pulmonary fibrosis, silica-induced pulmonary fibrosis, coal-induced pulmonary fibrosis, or other environmentally induced pulmonary fibroses. [0247] In some embodiments, the ILD is acute interstitial pneumonia (AIP, also known as Hamman- Rich syndrome). AIP is an acute, rapidly progressive idiopathic pulmonary disease that often leads to fulminant respiratory failure and acute respiratory distress syndrome (ARDS). In some embodiments, the ILD is alveolitis, including, chronic fibrosing alveolitis and fibrosing alveolitis. [0248] In some embodiments, the ILD is an unclassifiable ILD (uILD). The term “unclassifiable interstitial lung disease” was introduced in the American Thoracic Society/European Respiratory Society Consensus Classification of the Idiopathic Interstitial Pneumonias (IIP) in 2002 to encompass a subset of ILDs that cannot be classified within the confines of the current diagnostic framework. The paradoxical classification as “unclassifiable” results from either 1) inadequate or 2) discordant clinical, radiologic, and pathologic data, such that a specific ILD diagnosis is not possible. [0249] Many ILDs are characterized by inflammation and chronic fibrosis. Patients with certain types of chronic fibrosing ILD are at risk of developing a progressive phenotype. These include, but are not limited to, iNSIP, uILD, autoimmune ILDs, chronic sarcoidosis, HP, g/f IPF, and exposure- related diseases, such as asbestosis and silicosis. Because these various conditions share similarities regarding pathogenesis and clinical behavior, they are increasingly described under the umbrella terminology of “progressive fibrosing ILDs” (PF-ILDs) or “fibrosing ILD with a progressive phenotype.” A progressive phenotype is characterized histologically by self-sustaining fibrosis, a process common to a variety of conditions, and which leads to worsening quality of life, decline in lung function and, eventually, early mortality. The term “progressive phenotype” implies that progression of disease has occurred despite state-of-the-art management, including, for example, the use of corticosteroids and/or immunosuppressive therapy. One of the most common types of progressive fibrosing ILD is idiopathic pulmonary fibrosis (IPF). IPF is, by definition, a progressive fibrosing ILD of unknown cause, characterized by a decline in lung function and early mortality. The prognosis of IPF is poor, with the median survival after diagnosis generally estimated at 2 to 5 years. [0250] Estimates based on a survey and insurance claims in the USA indicate that 18–32% of patients diagnosed with non-IPF ILDs would develop progressive fibrosis (Wijsenbeek et al. "Progressive fibrosing interstitial lung diseases: current practice in diagnosis and management" Curr Med Res Opin 2019: 1–10). In the same study, time from symptom onset to death was estimated to be 61–80 months, a poor survival rate, yet better than that for IPF. The incidence and prevalence of PF-ILDs are not well defined, partly due to the heterogeneous nature of this group. It is estimated that there are on the order of 140,000-250,000 people in the United States living with PF-ILDs, including IPF. Currently, no drugs are approved for the treatment of progressive fibrotic ILDs other than nintedanib and pirfenidone for the treatment of IPF. Accordingly, LYT-100, having the potential for higher dosing than pirfenidone by virtue of its enhanced tolerability, may be particularly advantageous in treating PF-ILDs. [0251] In some embodiments, the ILD is a PF-ILD. In some embodiments, the PF-ILD is iNSIP, a CTD-ILD, a uILD, chronic fibrotic HP, a g/f IPF, sarcoidosis, an exposure-related ILD, or a drug-induced ILD. [0252] In some embodiments, the fibrotic- or collagen-mediated disease or disorder is not idiopathic pulonary fibrosis (IPF). Infection [0253] In some embodiments, the method treats an infection. In some embodiments, the infection is an inflammation-inducing infection. In some embodiments, the infection is a fibrosis-inducing infection. Inflammatory processes, such as those experienced by a viral infection can result in lung injury that leads to pulmonary fibrosis (Qiao et al., Pulmonary fibrosis induced by H5N1 viral infection in mice, Respir Res 10(1): 107 (2009)). In some embodiments, the infection is viral. In some embodiments, the infection is bacterial. [0254] In some embodiments, the method treats an infection-related tissue and/or organ change, damage, remodeling or inflammation in a subject. In some embodiments, the infection-related tissue and/or organ changes, damage, remodeling or inflammation is caused by or related to the triggering of an immune response or the contribution from an immune response. In some embodiments, the infection-related tissue and/or organ changes, damage, remodeling or inflammation is caused by or related to the triggering of an inflammatory response or the contribution from an inflammatory response. In some embodiments, tissue and/or organ damage is treated or prevented in the subject. In some embodiments, inflammation is treated or prevented in the subject. In some embodiments, tissue remodeling or insult is treated or prevented in the subject. In some embodiments, fibrosis is treated or prevented in the subject. [0255] In some embodiments, the fibrotic- or collagen-mediated disease or disorder is a respiratory disease or disorder stemming from a viral respiratory infection. In some embodiments, the respiratory infection is a viral respiratory infection. In some embodiments, the viral respiratory infection is caused by infection with human influenza virus H1N1, human influenza virus H7N9, SARS-CoV, SARS-CoV-2, MERS-CoV, HCoV-HKU1, or HCoV-OC43. In one embodiment, the viral respiratory infection is caused by a human influenza virus. In one embodiment, the human influenza virus is an H1N1 or H7N9 strain. [0256] In some embodiments, the viral respiratory infection is caused by a beta coronavirus. In some embodiments, the beta coronavirus is SARS-CoV, SARS-CoV-2, MERS-CoV, HCoV- HKU1, or HCoV-OC43. In some embodiments, the viral respiratory infection is Coronavirus Disease 2019 (COVID-19), previously designated 2019-nCoV. COVID-19 is an acute respiratory illness caused by the coronavirus, SARS-CoV-2. SARS-CoV-2 is a novel member of the beta coronavirus genus, which further includes four additional human virus species: HCoV-HKU1, HCoV-OC43, Middle East respiratory syndrome coronavirus (MERS-CoV), and the severe acute respiratory syndrome coronavirus (SARS-CoV). COVID-19 was identified as the cause of a cluster of pneumonia cases in Wuhan, a city in the Hubei Province of China, at the end of 2019. It subsequently spread throughout China and elsewhere, becoming a global health emergency. On the 11th of March 2020, the World Health Organization (WHO) declared COVID-19 as a pandemic. As of May 6, 2020, nearly 3.7 million people have been infected and around 260,000 people have died from COVID-19 worldwide. (Spagnolo et al., Lancet Respiratory Medicine, published online May 15, 2020 https://doi.org/10.1016/S2213-2600(20)30222-8). There are currently no drugs or other therapeutic agents approved to treat acute COVID-19. Current clinical management of COVID-19 includes infection prevention and control measures and supportive care of acute infection, including supplemental oxygen and mechanical ventilator support when indicated. The COVID-19 clinical course can progress from viral infection through mild, moderate, severe disease, and acute respiratory distress syndrome (ARDS). In some embodiments, the method treats the respiratory aftermath or complication(s) of a viral respiratory disease, e.g., a COVID-19 related infection. [0257] There is increasing evidence of complications that persist in survivors after the acute infection has resolved. These post-acute sequelae of COVID-19 are collectively being referred to as “Long Covid.” Long Covid is a complex pathophysiology that can involve tissue damage, residual inflammation, and fibrosis in the lung. These mechanisms can lead to lasting respiratory complications, including shortness of breath and other problems that could potentially last for years. There is presently a shadow pandemic of these Long Covid complications that may contribute to the enormous health, social, and economic cost of the pandemic. There are virtually no treatment options being developed that focus on treating or preventing these post-acute sequelae of COVID-19, including respiratory complications. Accordingly, there is an unprecedented medical need for such Long Covid treatments. [0258] In some embodiments, the treating is effective in preventing the development of pulmonary fibrosis, pulmonary dysfunction, or both in the subject, in the acute and/or post-acute COVID-19 infection timeframe. In some embodiments, the treating is effective in preventing the development of pulmonary fibrosis in the subject. In some embodiments, the treating is effective in preventing the development of pulmonary dysfunction in the subject. [0259] In some embodiments, the treating is effective in halting the progression of pulmonary fibrosis, pulmonary dysfunction, or both in the subject. In some embodiments, the treating is effective in halting the progression of pulmonary fibrosis in the subject. In some embodiments, the treating is effective in halting the progression of pulmonary dysfunction in the subject. [0260] In some embodiments, the treating is effective in slowing the progression of pulmonary fibrosis, pulmonary dysfunction, or both in the subject. In some embodiments, the treating is effective in slowing the progression of pulmonary fibrosis in the subject. In some embodiments, the treating is effective in slowing the progression of pulmonary dysfunction in the subject. [0261] In some embodiments, the treating is effective in ameliorating respiratory symptoms of the viral respiratory disease or viral respiratory infection. In some embodiments, the treating is effective in preventing respiratory symptoms of the viral respiratory disease or infection. In some embodiments, the respiratory symptoms are cough, dyspnea, or both. In some embodiments, the subject exhibits reduced cough, dyspnea, or both, relative to a subject that has not been treated with LYT-100. [0262] In some embodiments, the treatment is initiated within 90 days from a confirmed viral respiratory disease diagnosis. In some embodiments, the treatment is initiated within 60 days from a confirmed viral respiratory disease diagnosis. In some embodiments, the treatment is initiated within about 90, about 80, about 70, about 60, about 50, about 45, about 40, about 35, about 30, about 28, about 21, about 14, about 7, or about 1 day from a confirmed viral respiratory disease diagnosis. In some embodiments, the treatment is initiated between 90 and 42 days from a confirmed viral respiratory disease diagnosis. In some embodiments, the treatment is initiated within 42 days from a confirmed viral respiratory disease diagnosis. In some embodiments, the treatment is initiated within 30 days, within 14 days, within 10 days, or within 7 days from a confirmed viral respiratory disease diagnosis. In some embodiments, the treatment is initiated within 14 days from a confirmed viral respiratory disease diagnosis. In some embodiments, the treatment is initiated within from 1 day to 14 days from a confirmed viral respiratory disease diagnosis. In some embodiments, the treatment is initiated within 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 7 days, 10 days, or 14 days from a confirmed viral respiratory disease diagnosis. In some embodiments, the treatment is initiated between 14 and 28 days from a confirmed viral respiratory disease diagnosis. [0263] In some embodiments, the treatment is initiated during the acute phase of the viral respiratory disease. In some embodiments, the treatment is initiated during the post-acute phase of the viral respiratory disease. In some embodiments, the treatment is initiated during the acute phase of the viral respiratory disease and continued during the post-acute phase of the viral respiratory disease. [0264] In some embodiments, treating comprises administering an effective amount of LYT-100 daily for up to 3 months or 91 days. In some embodiments, treating comprises administering an effective amount of LYT-100 daily for up to 12 months. [0265] In some embodiments, the method treats one or more symptom(s) of a respiratory disease including impaired respiratory function. In one embodiment, the impaired respiratory function comprises reduced blood oxygen saturation. In some embodiments, the impaired respiratory function is determined by oximetry, reduced forced expiratory volume in one second (FEV1), reduced forced vital capacity (FVC), and reduced FEV1/FVC ratio. Consequently, in some embodiments, the disclosure provides methods for preventing or reducing the occurrence of, preventing or reducing the progression of, or reducing the time to resolution of impaired respiratory function in a subject, including a human subject. [0266] In some embodiments, the subject exhibits reduced evidence of lung fibrosis, respiratory complications, or pulmonary dysfunction relative to a subject who has not been treated with LYT- 100, as measured by a chest X-ray or a CT scan, or as evidenced by a pulmonary function test result. [0267] In some embodiments, the subject exhibits reduced evidence of lung fibrosis, respiratory complications, or pulmonary dysfunction relative to a subject who has not been treated with LYT- 100, as measured by a pulmonary function test result, wherein the pulmonary function test result is a statistically significant improvement in the distance walked on the six-minute walk test (6MWT) compared to a baseline 6MWT result in the treated subject. [0268] In some embodiments, at least a 25% reduction in one or more of the following biomarkers is achieved: C-Reactive Protein (CRP); d-dimer; cardiac troponin; ferritin; lactate dehydrogenase (LDH); interleukin-6 (IL-6); TGF-β1; TNF-α; IL-1β; PDGF- β; GCSF; VEGF. [0269] In some embodiments, the subject exhibits reduced evidence of lung fibrosis, respiratory complications, or pulmonary dysfunction relative to a subject who has not been treated with LYT- 100, as measured by a chest X-ray or a CT scan, or as evidenced by a pulmonary function test result. [0270] In some embodiments, one or more of the following is achieved in the subject: an improvement in blood oxygenation level in the human subject over 91 days of treatment, as determined by pulse oximetry; a 10 unit drop in an overall score in the Short Form Health Survey (SF-36 v2) over 91 days of treatment; an increase of ≥2 units in the overall St. George's Respiratory Questionnaire-Idiopathic Pulmonary Fibrosis (SGRQ-I) score over 91 days of treatment; an improvement in pulmonary inflammation; an improvement in fibrosis; an improvement in other radiographic abnormalities, as measured by determining at least a 2-point score improvement over 91 days of treatment on high resolution computed tomography (HRCT) scans, from the level of the upper thoracic inlet to the inferior level of the costophrenic angle over 28, 56, and 91 days of treatment utilizing the following scoring system: a) number of involved segments; and b) lung lobe involvement for each of five lobes via the semi- Quantitative Lung Fibrosis (QLF) added and Computer-Aided Diagnosis (CAD) QLF Scores. [0271] In some embodiments, a reduction in fibrosis or fibrotic lesions on high resolution computed tomography (HRCT) is achieved in the subject. In some embodiments, the fibrotic lesion reduced in the subject is one or more of ground glass opacity, reticular patterning, honeycombing, traction bronchiectasis, bronchiolectasis, interlobular septal thickening, ill-defined margins, air bronchogram, "crazy-paving" pattern, thickening of the adjacent pleura, nodules, cystic changes, pleural effusion, or lymphadenopathy. Cardiac diseases and disorders [0272] In some embodiments, the method treats cardiac diseases and disorders, including but not limited to heart failure, such as myocardial fibrosis-associated heart failure. eart failure (HF) is a chronic, progressive condition in which the heart muscle is unable to pump enough blood to meet the body’s needs for blood and oxygen, or to do so only at the cost of high filling pressures. HF presents clinically as a syndrome of exertional breathlessness, peripheral oedema and fatigue. HF is a major public health problem with an estimated worldwide prevalence of over 23 million (Bui et al. "Epidemiology and risk profile of heart failure." Nat Rev Cardiol 2011, 8: 30–41; Ponikowski et al. "Heart failure: preventing disease and death worldwide." ESC Heart Fail 2014, 1: 4–25)—a figure projected to rise as populations age. The incidence of HF has been reported as about 1–2% in developed countries and increases to 10% among people over 70 years of age. [0273] Despite advances in the treatment of HF over the last decades, morbidity and mortality remain high, and HF is a major contributor to the global health economic burden. HF is ultimately fatal, with only 35% of patients surviving 5 years after initial diagnosis. Accordingly, there is an umet need in the art for therapeutics which can modify the course of this disease. [0274] In some embodiments, the method treats myocardial fibrosis-associated heart failure (HF). The particular type of HF may vary. According to the newest European Society of Cardiology guidelines regarding HF, the categories of HF include HF with reduced ejection fraction (HFrEF; left ventricular ejection fraction [LVEF] < 40%); HF with preserved ejection fraction (HFpEF; LVEF ≥50%); and HF with mid-range ejection fraction (HFmrEF; LVEF in the range of 40–49%). In HFrEF, the systolic force generation of the heart is impaired, and consequently, the proportion of blood expelled with each contraction—the ejection fraction—is reduced. In HFpEF, routine parameters of systolic function are largely maintained but diastolic filling and relaxation are impaired (Ponikowski et al. Eur Heart J 2016, 37: 2129–2200). HFpEF is common—estimated to be responsible for >50% of HF cases. It is increasingly clear that myocardial fibrosis plays a role in the etiology of all forms of HF, and in particular, the pathophysiology of HFpEF (Moreo et al. "Influence of myocardial fibrosis on left ventricular diastolic function." Circ Cardiovasc Imaging 2009, 2: 437–443; González et al. "Myocardial interstitial fibrosis in heart failure: biological and translational perspectives." J Am Coll Cardiol 2018, 71: 1696–1706). [0275] Myocardial fibrosis is a complicated process resulting in the accumulation of extracellular matrix (ECM), leading to structural changes of the heart tissue and cardiac insufficiency. Myocardial fibrosis manifests with QRS prolongation, frequent ventricular premature beats, and ventricular tachycardia (VT) on electrocardiogram. Diffuse myocardial fibrosis may lead to impaired movement of the entire ventricular wall. An ultrasonic cardiogram can detect increased left ventricular end diastolic diameter, decreased ejection fractions, systolic dyssynchrony, and elevated filling pressures in myocardial fibrosis. [0276] In some embodiments, the method treats myocardial fibrosis-associated HF with reduced ejection fraction (HFrEF). In some embodiments, the method treats myocardial fibrosis-associated HF i with preserved ejection fraction (HFpEF). In some embodiments, the method treats myocardial fibrosis-associated HF with mid-range ejection fraction (HFmrEF). [0277] The presence and extent of myocardial fibrosis may be determined by any acceptable technique. In some embodiments, the presence and extent of myocardial fibrosis in the subject is determined using one or more of cardiovascular magnetic resonance, measurement of myocardial extracellular volume (e.g., via MRI), load-independent intrinsic left ventricular myocardial stiffness, histological analysis of endomyocardial biopsy samples stained for collagen (e.g., using picrosirius red under polarized light), quantitative analysis of collagent formation biomarkers in serum, and late gadolinium contrast enhancement (LGE) imaging. [0278] The myocardial fibrosis-associated HF may manifest as a number of symptoms or effects, such as abnormal heartbeat patterns (conduction block, atrial arrhythmia or ventricular arrhythmia). In some embodiments, the subject exhibits one or more of elevated levels of natriuretic peptides, increased left ventricular end diastolic diameter, systolic dyssynchrony, and elevated filling pressures. [0279] In some embodiments, the method disclosed herein reduces or prevents the progression of the myocardial fibrosis-associated HF, relative to a subject who has not been treated with LYT- 100. [0280] The method disclosed herein may reduce the progression of myocardial fibrosis. The method disclosed herein may reverse to varying extents the degree of myocardial fibrosis. In some embodiments, the method disclosed herein at least partially reverses myocardial fibrosis in the subject. In some embodiments, the method disclosed herein at least partially reverses myocardial fibrosis-associated HF. [0281] In some embodiments, the method disclosed herein ameliorates one or more symptoms or manifestations of myocardial fibrosis-associated HF. For example, in some embodiments, the method provides one or more of: a reduction in myocardial extracellular volume (ECV); an increase in 6 minute walk test (6MWT); an improved KCCQ score (0–100); an improved KCCQ clinical summary score (0–100); an improved KCCQ total symptom score (0–100); an improved Left ventricular EDVi, ml m ⁻² ; an improved Left ventricular ESVi, ml m ⁻² ; an improved Left ventricular EF, %; an improved Left ventricular mass index, g m ⁻² ; improved Native T1, ms; an improved absolute myocardial ECM volume, ml; an improved absolute myocardial cell volume, ml; an improved E/A ratio; an improved Lateral e′, cm s ⁻¹ ; an improved Septal e′, cm s ⁻¹ , an improved Average E/e′, cm s ⁻¹ ; an improved GLS, %; an improved PCr:ATP ratio (BCPSC); an improved Right ventricular EDVi, ml m ⁻² ; an improved Right ventricular EF (%) ;an improved Right ventricular PAP, mm Hg; an improved Left atrium volume, ml; an improved Left atrium volume index, ml m ⁻² ; an improved Left atrium strain (reservoir), %; an improved Left atrium strain (booster), %; an improved Left atrium strain (conduit), %. [0282] In some embodiments, the method disclosed herein an improvement in the distance walked in a 6-minute walk test (6MWT), relative to to a subject who has not been treated with LYT-100. [0283] In some embodiments, the method treats pulmonary hypertension, including Group 2 pulmonary hypertension and pulmonary arterial hypertension. [0284] In some embodiments, the method treats cardiomyopathy. In some embodiments, the cardiomyopathy is obstructive hypertrophic cardiomyopathy or non-obstructive hypertrophic cardiomyopathy. In some embodiments, the cardiomyopathy is cancer or cancer chemotherapy- related cardiomyopathy. In some embodiments, the cardiomyopathy is arrhythmogenic right ventricular cardiomyopathy. In some embodiments, the cardiomyopathy is associated with Alström Syndrome, Barth Syndrome, Danon disease, Friedreich's ataxia, Thalassemia or a transfusion- dependent anemia. [0285] In some embodiments, the method treats a cardiac disorder associated with or a manifestation of Chagas disease, Duchenne's muscular dystrophy, Fabry Disease, Meckel Syndrome, Mucopolysaccharidosis type I (MPS 1), Pompe disease, or Shwachman Diamond Syndrome. [0286] In some embodiments, the method treats carcinoid heart disease, endocardial fibroelastosis, endomyocardial fibrosis, or Löffler endocarditis. Hepatopulmonary syndrome [0287] In some embodiments, the method treats hepatopulmonary syndrome (HPS). HPS is a reduced arterial oxygen saturation due to dilated pulmonary vasculature in the presence of advanced liver disease or portal hypertension. It is a serious condition and can develop in any patient with chronic or acute liver disease, and is associated with high morbidity and mortality. Diagnostic criteria for HPS include: 1) Partial pressure of oxygen (PaO2) <80 mm Hg while breathing room air, or alveolar-arterial oxygen gradient (A-aO2) ≥ 15 mm while breathing room air (in patients over 64 years of age, A-aO2 >20 mm Hg is considered diagnostic); 2) Pulmonary vascular dilatation as shown by positive contrast-enhanced echocardiography or by radioactive lung-perfusion scanning (showing brain shunt fraction >6%); 3) Portal hypertension (with or without cirrhosis). The severity of HPS is based on PaO2 levels. Other fibrotic- and collagen-mediated diseases and disorders [0288] In some embodiments, the method treats acute interstitial pneumonia (AIP), alcoholic liver disease, allograft injury after organ transplantation, anthracosis, asbestosis, atrial fibrilation, chalicosis, chronic hypersensitivity pneumonitis, chronic kidney disease, cirrhosis, CREST syndrome, cryptogenic organizing pneumonia (COP), cystic fibrosis, dermatomyositis, dermatopolymyositis, desquamative interstitial pneumonia (DIP), diabetic rheumatoid arthritis, diffuse parenchymal lung disease, endotoxin-induced liver injury after partial hepatectomy or hepatic ischemia, fibrotic sarcoidosis, hepatitis-C fibrosis, hepatopulmonary syndrome, Hermansky-Pudlak syndrome, hypertrophic cardiomyopathy (HCM), keloid scarring, lupus nephritis, mediastinal fibrosis, medical device or implant rejection, membranous nephropathy, mixed connective tissue disease, neurofibromatosis, neutropenia-associated fibrosis, non-alcoholic steatohepatitis (NASH), pneumoconioses, polycystic kidney disease, polymyositis/dermatomyositis (PM/DM), pulmonary sarcoidosis, renal fibrosis, sarcoidosis, scleroderma, silicosis, spleen fibrosis caused by sickle-cell anemia, tuberculosis, uterine fibroids, or any disorder ameliorated by modulating fibrosis and/or collagen deposition. [0289] In treating any of the fibrotic- or collagen-mediated diseases or disorders disclosed herein, the LYT-100 is administered as disclosed herein above. In some embodiments, the LYT-100 is administered in a total daily dose from about 825 to about 2475 mg, such as 825 mg, 1650 mg or 2475 mg. In some embodiments, the administration is in three equal admninistrations. In some embodiments, the LYT-100 is administered in three equal doses of 550 mg each. In some embodiments, the LYT-100 is administered in three equal doses of 825 mg each. Clinical Endpoints and Biomarkers [0290] In some embodiments, treatment efficacy may be evaluated by reference to various clinical endpoints or biomarkers indicative of fibrotic and inflammatory processes. Many of these clinical endpoints are described above with respect to the specific disease or disorder. [0291] Suitable types of biomarkers include, but are not limited to, markers of alveolar epithelial cell injury and epithelial cell dysfunction, markers of alveolar macrophage activation, markers of TGF-β activation, markers of fibroblast proliferation and extracellular matrix production or turnover, markers of immune dysregulation, an markers of ECM production and turnover. In some embodiments, the biomarker is Krebs von den Lungen-6 antigen (KL-6), a surfactant protein (e.g., SP-A or SP-D), a matrix metalloprotease (e.g., MMP-1, MMP-7, MMP-8), PP1, YKL-40, IGFBP- 1, TNFRSA1F, ICAM-1, IL-6, IL-8, a CC chemokine ligand (e.g., CCL 16 and CCL 18), Insulin- like growth factor (IGF), an IGF-binding protein (IGFBP), Vascular endothelial growth factor (VEGF), periostin, or a combination thereof. Pharmaceutical Compositions [0292] In another aspect, pharmaceutical compositions are provided for administration in the methods described herein. Pharmaceutical compositions include the active compound, e.g., LYT- 100, and one or more pharmaceutically acceptable excipients or carriers. Solid dosage forms for oral administration include capsules, tablets, pills, powders, and granules. In such solid dosage forms, the active compound is mixed with at least one inert, pharmaceutically acceptable excipient or carrier such as sodium citrate or dicalcium phosphate and/or a) fillers or extenders such as starches, lactose, sucrose, glucose, mannitol, and silicic acid, b) binders such as, for example, carboxymethylcellulose, alginates, gelatin, polyvinylpyrrolidinone, sucrose, and acacia, c) humectants such as glycerol, d) disintegrating agents such as agar-agar, calcium carbonate, potato or tapioca starch, alginic acid, certain silicates, and sodium carbonate, e) solution retarding agents such as paraffin, f) absorption accelerators such as quaternary ammonium compounds, g) wetting agents such as, for example, cetyl alcohol and glycerol monostearate, h) absorbents such as kaolin and bentonite clay, and i) lubricants such as talc, calcium stearate, magnesium stearate, solid polyethylene glycols, sodium lauryl sulfate, and mixtures thereof. In the case of capsules, tablets and pills, the dosage form may also comprise buffering agents. [0293] Solid compositions of a similar type may also be employed as fillers in soft and hard-filled gelatin capsules using such excipients as lactose or milk sugar as well as high molecular weight polyethylene glycols and the like. The solid dosage forms of tablets, dragees, capsules, pills, and granules can be prepared with coatings and shells such as enteric coatings and other coatings well known in the pharmaceutical formulating art. They may optionally contain opacifying agents and can also be of a composition that they release the active ingredient(s) only, or preferentially, in a certain part of the intestinal tract, optionally, in a delayed manner. Examples of embedding compositions that can be used include polymeric substances and waxes. Solid compositions of a similar type may also be employed as fillers in soft and hard-filled gelatin capsules using such excipients as lactose or milk sugar as well as high molecular weight polyethylene glycols and the like. [0294] Embodiments of the present disclosure can be further defined by reference to the following non-limiting examples. It will be apparent to those skilled in the art that many modifications, both to materials and methods, can be practiced without departing from the scope of the present disclosure. EXEMPLIFICATION [0295] Examples 1 and 2 provide crossover studies comparing the safety, tolerability, and pharmacokinetics of deupirfenidone (LYT-100) and pirfenidone. Example 3 provides a study exploring tolerability of the deuterated pirfenidone LYT-100 in patients with COVID-19 Respiratory Illness. Example 4 provides the CYP isozyme profile of pirfenidone and LYT-100. Example 5 provides a BioMAP Fibrosis Panel screening study for LYT-100 and pirfenidone across a series of fibrosis biomarkers. Example 6 provides a rat lipopolysaccharide (LPS) model of systemic inflammation. Example 7 provides a streptozocin-induced non-alcoholic steatohepatitis (NASH) mouse model. Example 8 provides a study of inhibition of fibrosis with LYT-100 in Primary Mouse Lung Fibroblasts. Example 9 provides a study of inhibition of collagen synthesis with LYT-100. Example 10 provides a mouse model of lymphedema. Example 11 provides a rat bleomycin-induced pulmonary fibrosis model. Example 1: Crossover Dosing Study [0296] This study was a double-blind, randomized, two-period crossover study in older, healthy subjects to compare the safety, tolerability, and pharmacokinetics of deupirfenidone (LYT-100) and pirfenidone. The crossover study was performed at a single Study Center per Part in the United States. Study Description [0297] This study was conducted in two Parts: 1 and 2. [0298] Part 1 was a randomized, double-blinded, two period crossover study conducted in healthy older adults to compare the safety, tolerability, and pharmacokinetics of deupirfenidone (LYT- 100) with twice daily (BID) dosing of LYT-100 to pirfenidone. [0299] Part 2 was a randomized, double-blinded, two period crossover study conducted in healthy older adults to compare the safety, tolerability, and pharmacokinetics of deupirfenidone (LYT- 100) with three times daily (TID) dosing of LYT-100 to pirfenidone. Study Endpoints x Safety: - Treatment-emergent adverse events (TEAEs), including severity, and relatedness to study drug) - Physical examination - Vital signs - Electrocardiograms (ECGs) - Clinical laboratory parameters, including hematology, serum chemistry, coagulation, and urinalysis - New-onset concomitant medications x Pharmacokinetics: - Comparison of the key PK parameters (C _max,ss , C _min,ss , and AUC _0-24,ss ) between the parent compound (LYT-100 and pirfenidone) and primary metabolite (5- carboxypirfenidone). Other PK parameters were derived and compared. - Comparison of the key urine PK parameters (Ae _t1-t2 , CL _R , Fe _t1-t2 ) between the parent compound (LYT-100 and pirfenidone) and primary metabolite (5-carboxypirfenidone). Other urine PK parameters were derived and compared. - Food effect evaluation of LYT-100 and pirfenidone (C _max,ss , and AUC _0-6,ss ) for fed versus fasted. Study Design Part 1: [0300] Part 1 was a double-blind, randomized, two-period crossover study conducted in older, healthy subjects to determine the safety, tolerability, and PK of LYT-100 administered twice daily (BID) for 3 days (to steady state [Day 1 to Day 3 and Day 11 to Day 13]) compared to pirfenidone administered 3 times daily (TID) for 3 days (to steady state) under fed conditions. A final single dose of study drug (LYT 100 or pirfenidone) was administered on the morning of the fourth day in each treatment period (Day 4/Day 14) following an overnight fast of at least 8 hours to determine the effect of food on steady state PK parameters. [0301] Over encapsulation was utilized to match TID dosing for pirfenidone and to match the number of LYT-100 capsules administered for each dose. Thus, during LYT-100 treatment, the mid-day dose was placebo. Pirfenidone was administered at the current marketed dose of 801 mg TID (2403 mg daily dose). [0302] Approximately forty older healthy female and male adult subjects (1:1 target ratio) were randomized into 1 of 2 cohorts: Cohort 1 or Cohort 2, N = 20 subjects per cohort; minimum of 8 per sex per cohort. Subjects in each cohort were randomized to treatment sequence as follows: Sequence A: Pirfenidone to LYT-100; Sequence B: LYT-100 to pirfenidone. Dosing is outlined in Table 8. A graphical illustration of the study design for Part 1 is provided as FIG.1.

Table 8: Dosing Regimens by Cohort and Treatment Sequence (Part 1) Cohort Treatment Treatment Period 1 Treatment Period 2 Sequent Days 1 to 3 Day 4 Days 11 to 13 Day 14 M g 0 to pirfenidone in healthy adults was 850 mg BID LYT-100 (1700 mg daily dose) vs. 801 mg TID pirfenidone (2403 mg daily dose). The 850 mg BID LYT-100 (1700 mg daily dose) was selected based on the PK results from earlier studies. PK modelling work using data from the multiple ascending dose study and a single-dose crossover study of LYT-100 and pirfenidone indicated that a dose of LYT-100 of approximately 800-850 mg BID (1600-1700 mg daily dose) results in a similar systemic exposure to the marketed dose of pirfenidone (2403 mg daily dose). Based on these data, a randomized blinded cross-over study in older healthy adults was conducted (N=37) administering LYT-100850 mg BID 3 days fed dosing versus pirfenidone 801 mg TID 3 days fed dosing. The study is blinded with a placebo mid-day dose for LYT-100 to match TID pirfenidone dosing. There was a single AM fasting dose on Day 4 for both drugs. There was a 6-day wash-out period between drug cross-over. The 850 mg BID dose was selected as a match to the exposure for pirfenidone based on the outcome of the earlier PK crossover study, which indicated that an 850 mg BID daily dose of LYT-100 has about 102% of the steady-state systemic exposure of pirfenidone dosed daily at 801 mg TID. Part 2: [0304] Part 2 was a double-blind, randomized, two-period crossover study conducted in older healthy subjects to determine the safety, tolerability, and PK of LYT-100 administered three times daily (TID) for 3 days (to steady state [Day 1 to Day 3 and Day 11 to Day 13]) compared to pirfenidone administered TID for 3 days (to steady state) under fed conditions. A final single dose of study drug (LYT-100 or pirfenidone) was administered on the morning of the fourth day in each treatment period (Day 4 / Day 14) following an overnight fast of at least 8 hours to determine the effect of food on steady state PK parameters. Over-encapsulation was utilized to maintain study blind. Screening was performed up to 28 days prior to administration of the first dose of LYT- 100/pirfenidone. Only subjects who met all the applicable inclusion and none of the applicable exclusion criteria were randomized. Approximately 50 older healthy female and male adult subjects (1:1 ratio) were randomized into 1 of 2 cohorts: Cohort 1 or Cohort 2, N = ~25 subjects per cohort. Subjects in each cohort were randomized to treatment sequence as follows: • Sequence A: Pirfenidone to LYT-100 • Sequence B: LYT-100 to pirfenidone [0305] A graphical illustration of the study design for Part 2 is provided as FIG. 2. Dosing is outlined in Table 9.

Table 9: Dosing Regimens by Cohort and Treatment Sequence (Part 2) Cohort Treatment Treatment Period 1 Treatment Period 2 Sequent Days 1 to 3 Day 4 Days 11 to 13 Day 14 mg M d mg M d AM, tered as needed to match the number of LYT-100 capsules in order to maintain the blind. Each cohort starting concurrently or closely staggered. [0306] The LYT-100 dose for this crossover study directly comparing LYT-100 to pirfenidone in healthy adults was 550 mg TID LYT-100 (1650 mg daily dose) vs.801 mg TID pirfenidone (2403 mg daily dose). The 550 mg TID LYT-100 (1650 mg daily dose) was selected based on the PK results from earlier studies and the PK results obtained in Part 1 of this study. PK modelling work using data from the multiple ascending dose study, the single-dose crossover study of LYT-100 and pirfenidone and Part 1 of this study indicated that a dose of LYT-100550 mg TID (1650 mg daily dose) results in a similar systemic exposure to the marketed dose of pirfenidone (2403 mg daily dose). Particularly, it was predicted that a dose of 550 TID LYT-100 (1650 mg total daily dose) would achieve a steady-state systemic exposure that is about 99% of the steady-state systemic exposure observed for pirfenidone dosed at 801 mg TID. [0307] Based on these data, a randomized blinded cross-over study in older healthy adults was conducted (N=49) administering LYT-100550 mg TID 3 days fed dosing versus pirfenidone 801 mg TID 3 days fed dosing. There was a single AM fasting dose on Day 4 for both drugs. There was a 6-day wash-out period between drug cross-over. The 550 mg TID dose was selected as a match to the exposure for pirfenidone based on the outcome of the earlier PK crossover studies. [0308] See FIG. 3 and FIG. 4, which show that the predicted steady-state systemic exposure (AUC24ss) for LYT-100 dosed at 550 TID is 98.5% of the steady-state systemic exposure (AUC24ss) of pirfenidone dosed at 801 mg TID. Surprisingly, however, the C _max for LYT-100 dosed at 550 mg TID is predicted to be lower than the pirfenidone C _max resulting from pirfenidone administered at 801 mg TID. FIG.4 shows that the predicted steady-state C _max for LYT-100 dosed at 550 mg TID is 67.4% of the steady-state C _max for pirfenidone dosed at 801 mg TID. Without wishing to be bound by any particular theory, it is believed that the lower C _max of LYT-100 may contribute to the enhanced tolerability of LYT-100 relative to pirfenidone. Treatment Period 1 (Day -1 to Day 4) Parts 1 and 2 [0309] Subjects were admitted to the Clinical Research Unit (CRU) on Day -1 of Treatment Period 1 and were administered their assigned study drug (pirfenidone or LYT-100, with or without matching placebo) every 6 hours for 3 days until steady state (Day 1 to Day 3) under fed conditions. Subjects were then administered a single dose of their randomized treatment (pirfenidone or LYT- 100, with or without matching placebo) on the morning of Day 4 following an overnight fast of at least 8 hours. Subjects were discharged on Day 4 following successful completion of all assessments and at the Investigator’s discretion. Treatment Period 2 (Day 11 to Day 14) Parts 1 and 2 [0310] Following a minimum washout period of at least 7 days, subjects returned to the CRU and were admitted on the evening of Day 10 and were crossed over and administered the alternate study drug (pirfenidone or LYT-100, with or without matching placebo) every 6 hours for 3 days (Day 11 to Day 13) under fed conditions. Subjects were then administered a single dose of their randomized treatment on the morning of Day 14 following an overnight fast of at least 8 hours. Subjects were discharged on Day 14 following successful completion of all assessments and at the Investigator’s discretion. [0311] On Days 1 to 3 (Treatment Period 1) and Days 11 to 13 (Treatment Period 2) subjects were administered their assigned study drug TID, every 6 hours ± 0.25 hours (with approximately 240 mL of non-carbonated water), 30 minutes after the start of consumption of their standardized breakfast, lunch, or dinner (6 hours apart). An evening snack was served ≥ 3 hours following evening study medication administration. On Day 4 (Treatment Period 1) and Day 14 (Treatment Period 2), subjects were administered their assigned study drug once in the morning following an overnight fast of at least 8 hours (with approximately 240 mL of non-carbonated water). No additional fluids were allowed during the 1 hour pre- and post-dose [0312] On Fed Days, meals were provided as follows: x Breakfast: meal served 30 mins prior to AM dosing. Breakfast was completed within 30 mins of start time. x Lunch: meal served at least 4 h post-AM study drug dose, and 30 minutes prior to the mid-day dose in Part 5 (only). x Dinner: meal served at least 11.5 h post-AM dose and served 30 minutes prior to PM study drug dose. x Evening snack: Snack served at least 15 h post-AM dose (at least 3 h post-PM dose). [0313] On Fasted Days, meals were provided as follows: x On Day 4 (Period 1) and Day 14 (Period 2), breakfast was provided ≥ 4 hours post-study drug administration. Number of Subjects: Part 1 [0314] The objective was to recruit approximately 40 healthy older female and male adult subjects (target ratio 1:1 of males: females with a minimum of 8 per sex per cohort), unless additional subjects were required to support the statistical analysis. Part 1 was conducted with N=37 subjects who completed the study. Part 2 [0315] The objective was to recruit approximately 50 healthy older female and male adult subjects (target ratio 1:1 of males: females with a minimum of 15 per sex per cohort), unless additional subjects were required to support the statistical analysis. Part 1 was conducted with N=49 subjects who completed the study. Main Criteria for Inclusion and Exclusion Inclusion Criteria: 1. Male or female between 60 and 80 years old (inclusive) at the time of screening. 2. Subjects have a body mass index (BMI) between ≥ 18.0 and ≤ 35.0 kg/m ² at screening. 3. Willing and able to abstain from direct whole body sun exposure from 2 days prior to dosing and until final study procedures have been conducted. Subjects were instructed to avoid or minimize exposure to sunlight (including sunlamps), use an SPF 50 sun block, or higher, wear clothing that protects against sun exposure and avoid concomitant medications known to cause photosensitivity (including but not limited to tetracycline, doxycycline, nalidixic acid, voriconazole, amiodarone, hydrochlorothiazide, naproxen, piroxicam, chlorpromazine and thioridazine). Exclusion Criteria: 1. Pregnant or lactating at screening or baseline or planning to become pregnant (self or partner) at any time during the study, including the specified follow-up period. 2. History or presence of malignancy at screening or baseline, with the exception of adequately treated localised skin cancer (basal cell or squamous cell carcinoma) or carcinoma in-situ of the cervix. 3. Clinically significant infection within 28 days of the start of dosing, or infections requiring parenteral antibiotics within the 3 months prior to screening. Known exposure to another person with COVID-19 within the last 14 days is also an exclusion criterion, or a positive COVID test within five days prior to dosing. 4. Had major surgery, (e.g., requiring general anesthesia) within 3 months before Screening, based on Investigator’s discretion or has surgery planned during the time the participant is expected to participate in the study. 5. Suffering from clinically significant systemic allergic disease at screening or baseline or has a history of significant drug allergies including a history of anaphylactic reaction (particularly reactions to general anaesthetic agents); allergic reaction due to any drug which led to significant morbidity; prior allergic reaction to pirfenidone. 6. Chronic administration (defined as more than 14 consecutive days) of immunosuppressants or other immune-modifying drugs within 3 months prior to study drug administration. Corticosteroids are permitted at the discretion of the Investigator. History or presence at screening or baseline of a condition associated with significant immunosuppression. Positive test for hepatitis C antibody (HCV), hepatitis B surface antigen (HBsAg), or human immunodeficiency virus (HIV) antibody at screening. Symptoms of dysphagia at screening or baseline or known difficulty in swallowing capsules. Any condition at screening or baseline (e.g., chronic diarrhoea, inflammatory bowel disease or prior surgery of the gastrointestinal tract) that would interfere with drug absorption or any disease or condition that is likely to affect drug metabolism or excretion, at the discretion of the Investigator. History or presence at screening or baseline of cardiac arrhythmia or congenital long QT syndrome. QT interval corrected using Fridericia’s formula (QTcF) > 450 msec. ECG may be repeated30 to 60 minutes apart from the first one collected at screening. If repeat ECG is ≤450 msec, the second ECG may be used to determine patient eligibility. However, if repeat ECG confirms QTcF remains >450msec, the subject is not eligible. Use of tobacco or nicotine containing products in the previous 3 months prior to dosing or a positive urine cotinine test at Screening or Baseline. Lack of willingness to abstain from the consumption of tobacco or nicotine-containing products throughout the duration of the study and until completion of the final Follow-up visit. Regular alcohol consumption defined as > 21 alcohol units per week (where 1 unit = 284 mL of beer, 25 mL of 40% spirit or a 125 mL glass of wine) or the Participant is unwilling to abstain from alcohol for 48 h prior to admission and 48 h prior to study visits. Use of any of the following drugs within 30 days or 5 half-lives of that drug, whichever is longer, prior to study drug administration: a. Fluvoxamine, enoxacin, ciprofloxacin; b. Other inhibitors of CYP1A2 (including but not limited to methoxsalen or mexiletine); c. Contraceptives containing oestradiol, ethinyloestradiol or gestodene; d. Inducers of CYP1A2 (such as phenytoin), CYP2C9 or 2C19 (including but not limited to carbamazepine or rifampin); e. Any drug associated with prolongation of the QTc interval (including but not limited to moxifloxacin, quinidine, procainamide, amiodarone, sotalol). 17. Vaccination with a live vaccine within the 4 weeks prior to screening or that is planned within 4 weeks of dosing, and any non-live vaccination within the 2 weeks prior to screening or that is planned within 2 weeks of dosing (including those for COVID). 18. Use of any investigational drug or device within the longer of 30 days or five half-lives prior to screening. 19. Consumption of grapefruit, grapefruit juice, Seville oranges, Seville orange juice, or any foods containing these ingredients, within 7 days prior to dosing or unwilling to abstain from these throughout the duration of the study. Dosage and Mode of Administration: [0316] This was a crossover study in which subjects received both the test treatment (LYT-100) and the reference (pirfenidone). All subjects received LYT-100 (BID or TID) or pirfenidone (TID) for 3 days in each respective treatment period, with placebo over-encapsulation to maintain the blind. Part 1 subjects received LYT-100850 mg BID. Part 2 subjects received LYT-100550 mg TID. In Parts 1 and 2, all subjects also received a single dose of either LYT-100 or pirfenidone on the morning of the fourth day in each respective treatment period with placebo over-encapsulation to maintain the blind. x LYT-100 (Deupirfenidone) was provided as hard gelatin capsules. LYT-100 was stored at a controlled room temperature of 15°C to 25°C. x Pirfenidone (Esbriet) was provided as white to off-white hard gelatin capsules contain 267 mg of pirfenidone. x Both LYT-100 and pirfenidone were over-encapsulated to maintain study blind. Duration of Treatment: Parts 1 and 2 [0317] This study included a 28-day Screening period, two treatment periods (each 4 days in duration) with a minimum 7-day washout period between treatment periods, and a 3-day (± 1 day) post-last-dose safety follow-up visit. Thus, total duration of study participation for each subject was approximately 50 days. Treatment with double-blind study medication was 4 days for each of the two treatment periods, 8 days in total. Criteria for Evaluation Safety: [0318] Safety and tolerability was assessed by monitoring AEs, physical examination, vital signs, 12-lead ECGs, clinical laboratory values (hematology panel, multiphasic chemistry panel and urinalysis), and review of concomitant treatments/medication use. Pharmacokinetics: Parts 1 and 2 [0319] Subjects provided blood samples prior to treatment, i.e., Day -1 or Day 1 in Treatment Period 1, for the determination of CYP1A2, CYP2C9, CYP2C19, and CYP2D6 genotype to support exploratory PK analyses. Subjects were required to provide consent for genotyping. [0320] Blood samples for PK were collected for Cohorts 1 and 2 at specified times during both periods, as follows: x Days 1 & 11: 0 (pre-morning dose) x Days 2 & 12: no sampling x Days 3 & 13: 0 (pre-morning dose), and 1, 2, 3, 4, 6 (pre-mid-day dose), 7, 8, 9, 10, 12 (pre-evening dose), 13, 14, 15, 16, and 17 hours post-morning dose x Days 4 & 14: 0 (pre-morning dose), and 1, 2, 3, 4, 6 (post-dose), [0321] Plasma PK parameters for steady state dosing (Days 1 to 3 and Days 11 to 13) included, but are not limited to: x AUC _0-tau,ss (area under the time concentration curve from time zero to tau at steady state) x AUC _0-24,ss (area under the time concentration curve from time zero to 24 hours at steady state) x λz (terminal disposition rate constant/terminal rate constant) x t½ (elimination half-life) x C _max,ss (maximum concentration in a dosing interval) x T _max (time to maximum concentration, as reported relative to the beginning of a dosing interval in which maximum concentration occurred) x C _min,ss (lowest concentration in a dosing interval) x C _av,ss (average concentration during a dosing interval) x C _max,ss -C _min,ss /C _av,ss (degree of fluctuation) x C _max,ss -C _min,ss /C _min,ss (swing) x PTF% (peak-trough fluctuation) [0322] Plasma PK parameters for food effect analysis (Days 4 and 14) included, but are not limited to: x AUC _0-tau,ss (area under the time concentration curve from time zero to tau at steady state) x AUC _0-6,ss (area under the time concentration curve from time zero to 6 hours at steady state) x AUC _0-∞ (area under the time concentration curve from time zero to infinity) + AUC _0-∞/D x %AUC _ext (area under the time concentration curve extrapolated from time t to infinity as a percentage of total AUC) x λz (terminal disposition rate constant/terminal rate constant) x CL/F (apparent total clearance) x Vz/F (apparent volume of distribution) x Tmax (time to maximum concentration) x t _lag (lag time) Part 1 only [0323] Urine samples for PK were collected for Cohorts 1 and 2 at specified intervals during both treatment periods, as follows: x Days 1 and 11: pre-dose (subjects instructed to empty their bladders approximately 30 minutes prior to dosing) x Days 2 and 12: no urine sampling x Days 3 and 13: pre-dose (subjects instructed to empty their bladders approximately 30 minutes prior to dosing), 0 to 4, 4 to 8, 8 to 12, 12 to 16, and 16 to 24 hours post-AM dose x Days 4 and 14: 0 to 3 and 3 to 6 hours post-AM dose [0324] Urine samples for analysis of excretion in urine were collected, separated by specified time interval, and analyzed. The total volume of urine collected in each interval (t1 to t2) was noted. The urine PK parameters included, but are not limited to: x Ae _t1/2 (Amount excreted in urine over time) x CLR (Renal clearance) x Fraction of systemic clearance (CL/F) represented by the renal clearance (CLR/[CL/F]) x Fet1-t2 (Fraction of administered dose excreted in urine over the dosing intervals) Study endpoints were defined as follows: x Safety ^ AEs (type, severity, and relatedness to study drug) ^ Physical examination ^ Vital signs ^ Electrocardiograms (ECGs) ^ Clinical laboratory parameters (hematology, serum chemistry, coagulation, and urinalysis) ^ New-onset concomitant medications x Pharmacokinetics: ^ Comparison of the key plasma PK parameters (C _max,ss , C _min,ss , and AUC _0-24,ss ) between the parent compound (LYT-100 and pirfenidone) and primary metabolite (5-carboxypirfenidone). Other plasma PK parameters will also be derived and compared. ^ Comparison of the key urine PK parameters (Ae _t1-t2 , CL _R , Fe _t1-t2 ) between the parent compound (LYT-100 and pirfenidone) and primary metabolite (5-carboxypirfenidone). Other urine PK parameters may be derived and compared. ^ Food effect evaluation of LYT-100 and pirfenidone (C _max,ss , and AUC _0-6,ss ) for fed vs fasted. Results Part 1 [0325] It was determined that 1000 mg BID of LYT-100 provided an exposure (AUC) of LYT- 100 which was greater than the exposure of pirfenidone resulting from administration of the approved dose of pirfenidone (801 mg TID). It was further determined based on dose projections that doses of LYT-100 in the range of 800 to 850 mg BID would provide exposure (AUC) and maximal concentration (C _max ) values of LYT-100 which are comparable to those of pirfenidone when administered at 801 mg TID (2403 mg daily). [0326] The Part 1 study was conducted in healthy older adults as relevant age group for IPF. Overall, the head-to-head crossover study of Part 1 was designed at least in part to evaluate the tolerability impact of reducing exposure to the major metabolite. To this end, thirty-seven subjects were randomized in the blinded crossover study to receive 850 mg BID LYT-100 or 801 mg TID pirfenidone with three days of fed dosing and a 4 ^th day morning fasted dose. With reference to FIG. 5A, the C _max and AUC of parent drug for 850 mg BID LYT-100 were very similar to that of parent drug for 801 mg TID pirfenidone. Specifrically, the steady-state AUC and with 850 mg BID dosing was 102% AUC compared with the steady-state AUC for pirfenidone dosed at 801 mg TID and the steady-state C _max achieved was 104% of the C _max of the steady-state C _max for pirfenidone dosed at 801 mg TID. Fasting increased the C _max . The major metabolite (5-carboxypirfenidone) exposure was reduced for 850 mg BID LYT-100 relative to that when pirfenidone was dosed at 801 mg TID. [0327] The adverse events encountered in each treatment group are provided in FIG. 5B, which shows that no serious adverse events occurred in either group, and similar types of AEs were observed across both groups. No clinically meaningful differences between LYT-100 and pirfenidone in overall AE rates. [0328] With reference to FIG. 5B, the adverse events in both groups were primarily GI and nervous system, with nervous system AEs including headache and dizziness. As noted above, fasting increased C _max and was hypothesized to increase overall GI AE rates. Consistent with this hypothesis, there was an increase in nausea in both groups when dosed after fasting, and the timing and duration of the AEs was consistent with a C _max -related effect. As illustrated in FIG. 5B, and with reference to FIG. 5A, the results of this study show that reducing exposure to the major metabolite did not improve tolerability. Part 2 [0329] Part 2 was a double-blind, randomized, two-period crossover study conducted in older healthy subjects to determine the safety, tolerability, and PK of 550 mg of LYT-100 administered three times daily (TID) for 3 days (to steady state [Day 1 to Day 3 and Day 11 to Day 13]) compared to pirfenidone administered 801 mg TID for 3 days (to steady state) under fed conditions. A final single dose of study drug (LYT-100 or pirfenidone) was administered on the morning of the fourth day in each treatment period (Day 4 / Day 14) following an overnight fast of at least 8 hours to determine the effect of food on steady state PK parameters. [0330] Overall, 49 subjects were enrolled and included in the Safety Population, 24 subjects to Sequence A and 25 subjects to Sequence B. Five subjects (10.2%) did not complete the study. Two subjects in Cohort 2 discontinued due to a TEAE (1 subject in Sequence A (LYT-100) and 1 subject in Sequence B (pirfenidone)). Two subjects in Cohort 2 discontinued due to physician decision (1 subject in Sequence A (LYT-100) and 1 subject in Sequence B (pirfenidone)). One subject in Cohort 1, randomized to Sequence A, withdrew consent while taking LYT-100. [0331] The mean age of the overall population was 67.7; the mean age was similar in Cohorts 1 and 2 (68.5 and 66.9 years, respectively). The majority of subjects were female (53.1%; 52.2% in Cohort 1, 53.8% in Cohort 2), predominately white (81.6%), and the average BMI was 27.9 kg/m ² . The overall mean number of days of dosing with LYT-100 was 4.0 days (4.0 days in Cohort 1, 3.9 days in Cohort 2). The mean number of days of dosing with pirfenidone was 3.9 days (4.0 days in Cohort 1 and 3.9 days in Cohort 2). [0332] Preliminary PK analyses have been conducted to assess the comparability of the exposure to parent (pirfenidone or deupirfenidone) and metabolite (5-carboxy pirfenidone, regardless of treatment) after administration of LYT-100 relative to after the administration of pirfenidone. Summary statistics of the key PK parameters, shown by analyte, fed status, and treatment, are shown in Table 10. Overall, exposure in terms of parent drug (AUC _0-24 and C _max ) was slightly lower after administration of LYT-100 compared to pirfenidone and the time to C _max was slightly longer (median of 3 hours for LYT-100 and 2 hours for pirfenidone). Specifically, the C _max was about 20% lower for LYT-100 and did not meet criteria for bioequivalence. As expected, the major metabolite concentration was substantially lower after administration of LYT-100. Table 10. Pharmacokinetic Parameters After Administration of Pirfenidone or LYT-100 in Subjects Enrolled in Part 2 F ^{ed Status Analyte Treatment Cmax} T _max AUC _{0-24 (μg/mL)} (hr) (μg*hr/mL) ) ^{) ) ) )} q ered in the fed state (Days 3 or 13) are provided in Table 11. Despite the slightly lower exposure seen after administration of LYT-100 in the fed state, LYT-100 at a dose of 550 mg TID met the criteria for bioequivalence based on AUC _0-24 as the lower and upper limits of the 90% confidence interval for the geometric mean ratio fall within the required interval of 0.8 to 1.25.

Table 11. Bioequivalence Assessment using Data from Subjects Enrolled in Part 2 Parameter Geometric Mean Ratio (Lower 5 ^th , Upper 95 ^th ) nce [033 ] Us ng t e orego ng crossover data, a urt er s mu at on was per ormed. e s mu ation involved dose normalizing the observed AUC0-24 after administration of LYT-100 in each subject to calculate the expected AUC _0-24 after administration of a hypothetical dose of 550 mg TID. The resultant AUC _0-24 was then compared to the observed AUC _0-24 after administration of pirfenidone 801 mg TID to calculate an individual ratio of LYT-100 to pirfenidone. These ratios were then assessed using the same process described in Chow (Design and Analysis of Bioavailability and Bioequivalence Studies; Chapman & Hall/CRC Biostatistics Series, Chapman; Hall/CRC 2008) and the CDER (Guidance for Industry Statistical Approaches to Establishing Bioequivalence Center for Drug Evaluation and Research [CDER], FDA, 2001). The results of the simulation are provided in Table 12. Based upon these assessments, an LYT-100 dose regimen of 550 mg TID is predicted to provide comparable parent drug exposure to pirfenidone dosed at 801 mg TID. Table 12. Predicted Ratio of AUC0-24 and Cmax (LYT-100:Pirfenidone 801 mg TID) after the Administration of Hypothetical LYT-100 Dose using Pooled Data. 90% Confidence Interval dverse vent Summary [0335] Overall, 28 subjects (57.1%) experienced at least one TEAE; 14 (30.4%) while taking LYT-100 and 23 (48.9%) while taking pirfenidone. The most common TEAEs (>5% overall) were nausea, headache, dizziness, vomiting, and somnolence. A summary of these TEAEs, overall and by study medication, is provided in Table 13. Table 13. Summary of the Most Common (>5% Overall) TEAEs (Safety Population) LYT-100 Pirfenidone N=46 N=47 [0336] Ove %; 19 events) and moderate for 4 subjects (8.7%; 10 events). Overall TEAEs during pirfenidone dosing were mild in 17 subjects (36.2%; 42 events) and moderate in 6 subjects (12.8%; 8 events). Overall, TEAEs leading to study discontinuation were reported by 2 (4.1%) subjects in Cohort 2, one while receiving LYT-100 (nausea) and one while receiving pirfenidone (headache and dizziness). No deaths or serious AEs were reported. [0337] In this group of older adults (mean age=68) across the two treatment groups (LYT-100 at 550 mg TID vs pirfenidone at 801 mg TID, fed and fasted), the incidence of TEAE’s was notably reduced in the LYT-100 treatment arm compared to the pirfenidone arm for nausea and dizziness. Overall, in subjects experiencing at least one TEAE, the incidence was substantially lower in the LYT-100 group than in the pirfenidone group. Specifically, there was a 38% reduction in the overall incidence of TEAEs with LYT-100 vs. pirfenidone (30.4% versus 48.9%, respectively). [0338] FIG. 6 provides a graphical illustration of the reduction in GI and nervous system symptoms for LYT-100 at 550 mg TID versus pirfenidone at 801 mg TID in this patient population. With reference to FIG.6, fifty percent fewer subjects experienced GI-related AEs with LYT-100 compared to pirfenidone (17.4% versus 34.0%, respectively), including 50% fewer with nausea (15.2% versus 29.8%). Fewer subjects experienced nervous system AEs with LYT-100 compared to pirfenidone (17.4% vs.31.9%), notably dizziness (2.2% with LYT-100 versus 14.9% versus pirfenidone). These study results show that substantially fewer subjects taking LYT-100 experienced AEs compared with pirfenidone and approximately 50% fewer subjects experienced GI-related AEs with LYT-100 compared with pirfenidone. There were no differences in the incidence of study discontinuation between the treatment groups. The results suggest that LYT- 100 may be better tolerated at 550 mg TID than pirfenidone 801 mg TID in this subject population. [0339] With respect to fed versus fasted condition prevalence of TEAEs, there were 8 (17.4%) LYT-100-treated subjects who experienced at least 1 TEAE under fed conditions and 8 (17.8%) subjects under fasted conditions. There were 10 (21.3%) pirfenidone-treated subjects under fed conditions and 17 (37.0%) subjects under fasted conditions who experienced at least one TEAE. A summary of the most common TEAEs (≥10%) under fed and fasted conditions is provided in Table 14 for each study medication. Table 14. Summary of the Most Common TEAEs (≥5%) under Fed and Fasted Conditions (Safety Population) LYT-100 550 mg TID Pirfenidone 801 mg TID n (%) n (%) .9) [0340] In this study, fed conditions reduced the incidence of TEAEs in both treatment arms. In addition, LYT-100 was better tolerated in both the fed and fasted conditions than pirfenidone within these two dose groups. This improved tolerability of LYT-100 also seems to be amplified in the fasted state. Without wishing to be bound by any particular theory, it is believed that the greater incidence of TEAEs experienced by fasting subjects in both treatment groups may be causally related to the higher peak plasma concentrations (C _max ) of the parent molecules (pirfenidone or deupirfenidone) that result from their more rapid and extensive absorption during fasting than when taken with food. A causal role for higher C _max in tolerability is suggested by the observations that on the days of fasting, C _max was higher in both treatment groups, and the incidence of TEAEs was substantially greater for both treatment groups than on fed days. In addition, it is notable that the fasting increase in C _max in the pirfenidone group was associated with the greatest incidence of TEAEs in the study. Overall, the head-to-head crossover study of Part 2 was designed at least in part to evaluate the tolerability impact of reducing the parent C _max . As described herein above, the results of this study show that reducing the parent drug C _max improves tolerability. Example 2: LYT-100 Crossover Study- 550 and 824 mg TID [0341] This study was a double-blind, randomized, two-period crossover study in older, healthy subjects to compare the safety, tolerability, and pharmacokinetics of deupirfenidone (LYT-100) and pirfenidone. The crossover study was performed at a single Study Center per Part in the United States. Study Description [0342] This study was a randomized, double-blinded, parallel arm, placebo-controlled study conducted in healthy older adults to evaluate the safety and tolerability compared to placebo of a dose of LYT-100 that provides an exposure of LYT-100 which is approximately 150% of the exposure of pirfenidone when dosed at 801 mg TID and did not exceed 850 mg TID LYT-100. Study Endpoints x Safety: - Treatment-emergent adverse events (TEAEs), including severity, and relatedness to study drug) - Physical examination - Vital signs - Electrocardiograms (ECGs) - Clinical laboratory parameters, including hematology, serum chemistry, coagulation, and urinalysis - New-onset concomitant medications x Pharmacokinetics: - Comparison of the key PK parameters (C _max,ss , C _min,ss , and AUC _0-24,ss ) between the parent compound (LYT-100 and pirfenidone) and primary metabolite (5- carboxypirfenidone). Other PK parameters will also be derived and compared. - Comparison of the key urine PK parameters (Ae _t1-t2 , CL _R , Fe _t1-t2 ) between the parent compound (LYT-100 and pirfenidone) and primary metabolite (5-carboxypirfenidone). Other urine PK parameters may be derived and compared. - Food effect evaluation of LYT-100 and pirfenidone (C _max,ss , and AUC _0-6,ss ) for fed versus fasted. Study Design [0343] This was a randomized, double-blinded, parallel arm, placebo-controlled study conducted in healthy older adults to evaluate the safety and tolerability of titrated high dose LYT-100 compared to placebo under fed conditions. Thirty older healthy adults between the ages of 60 and 80 were randomized to receive LYT-100 or placebo. Subjects were administered 550 mg LYT- 100 three times daily (TID) for 3 days (to steady state [Day 1 to Day 3]) compared to 550 mg placebo administered TID for 3 days to steady state. Day 4 to Day 6, subjects were administered 824 mg LYT-100 TID for 3 days compared to 824 mg placebo TID for 3 days to steady state. Informed consent was obtained prior to the commencement of the study. Screening was performed up to 28 days prior to administration of the first dose of LYT-100/placebo. Only subjects who met all the applicable inclusion and none of the applicable exclusion criteria were randomized. The dosing schedule is outlined in Table 15.

Table 15: Dosing Regimen and Treatment Sequence N Dose, Days 1 to 3 Daily total dose Dose, Days 4 to 6 Daily total dose g Number of Subjects: [0344] Thirty healthy older female and male adult subjects (target ratio 1:1 of males: females with a minimum of 10 per sex per cohort) Main Criteria for Inclusion and Exclusion Inclusion Criteria: 1. Male or female between 60 and 80 years old (inclusive) at the time of screening. 2. Subjects have a body mass index (BMI) between ≥ 18.0 and ≤ 35.0 kg/m ² at screening. 3. Willing and able to abstain from direct whole body sun exposure from 2 days prior to dosing and until final study procedures have been conducted. Subjects should be instructed to avoid or minimize exposure to sunlight (including sunlamps), use an SPF 50 sun block, or higher, wear clothing that protects against sun exposure and avoid concomitant medications known to cause photosensitivity (including but not limited to tetracycline, doxycycline, nalidixic acid, voriconazole, amiodarone, hydrochlorothiazide, naproxen, piroxicam, chlorpromazine and thioridazine). Exclusion Criteria: 1. Pregnant or lactating at screening or baseline or planning to become pregnant (self or partner) at any time during the study, including the specified follow-up period. 2. History or presence of malignancy at screening or baseline, with the exception of adequately treated localised skin cancer (basal cell or squamous cell carcinoma) or carcinoma in-situ of the cervix. 3. Clinically significant infection within 28 days of the start of dosing, or infections requiring parenteral antibiotics within the 3 months prior to screening. Known exposure to another person with COVID-19 within the last 14 days is also an exclusion criterion, or a positive COVID test within five days prior to dosing. Had major surgery, (e.g., requiring general anesthesia) within 3 months before Screening, based on Investigator’s discretion or has surgery planned during the time the participant is expected to participate in the study. Currently suffering from clinically significant systemic allergic disease at screening or baseline or has a history of significant drug allergies including a history of anaphylactic reaction (particularly reactions to general anaesthetic agents); allergic reaction due to any drug which led to significant morbidity; prior allergic reaction to pirfenidone. Chronic administration (defined as more than 14 consecutive days) of immunosuppressants or other immune-modifying drugs within 3 months prior to study drug administration. Corticosteroids are permitted at the discretion of the Investigator. History or presence at screening or baseline of a condition associated with significant immunosuppression. Positive test for hepatitis C antibody (HCV), hepatitis B surface antigen (HBsAg), or human immunodeficiency virus (HIV) antibody at screening. Symptoms of dysphagia at screening or baseline or known difficulty in swallowing capsules. Any condition at screening or baseline (e.g., chronic diarrhoea, inflammatory bowel disease or prior surgery of the gastrointestinal tract) that would interfere with drug absorption or any disease or condition that is likely to affect drug metabolism or excretion, at the discretion of the Investigator. History or presence at screening or baseline of cardiac arrhythmia or congenital long QT syndrome. QT interval corrected using Fridericia’s formula (QTcF) > 450 msec. ECG may be repeated30 to 60 minutes apart from the first one collected at screening. If repeat ECG is ≤450 msec, the second ECG may be used to determine patient eligibility. However, if repeat ECG confirms QTcF remains >450msec, the subject is not eligible. 13. Use of tobacco or nicotine containing products in the previous 3 months prior to dosing or a positive urine cotinine test at Screening or Baseline. 14. Lack of willingness to abstain from the consumption of tobacco or nicotine-containing products throughout the duration of the study and until completion of the final Follow-up visit. 15. Regular alcohol consumption defined as > 21 alcohol units per week (where 1 unit = 284 mL of beer, 25 mL of 40% spirit or a 125 mL glass of wine) or the Participant is unwilling to abstain from alcohol for 48 h prior to admission and 48 h prior to study visits. 16. Use of any of the following drugs within 30 days or 5 half-lives of that drug, whichever is longer, prior to study drug administration: a. Fluvoxamine, enoxacin, ciprofloxacin; b. Other inhibitors of CYP1A2 (including but not limited to methoxsalen or mexiletine); c. Contraceptives containing oestradiol, ethinyloestradiol or gestodene; d. Inducers of CYP1A2 (such as phenytoin), CYP2C9 or 2C19 (including but not limited to carbamazepine or rifampin); e. Any drug associated with prolongation of the QTc interval (including but not limited to moxifloxacin, quinidine, procainamide, amiodarone, sotalol). 17. Vaccination with a live vaccine within the 4 weeks prior to screening or that is planned within 4 weeks of dosing, and any non-live vaccination within the 2 weeks prior to screening or that is planned within 2 weeks of dosing (including those for COVID). 18. Use of any investigational drug or device within the longer of 30 days or five half-lives prior to screening. 19. Consumption of grapefruit, grapefruit juice, Seville oranges, Seville orange juice, or any foods containing these ingredients, within 7 days prior to dosing or unwilling to abstain from these throughout the duration of the study. Dosage and Mode of Administration: [0345] This was a crossover study in which subjects received both the test treatment (LYT-100) and the reference (pirfenidone). x LYT-100 (Deupirfenidone) was provided as hard gelatin capsules. LYT-100 should be stored at a controlled room temperature of 15°C to 25°C. x Pirfenidone (Esbriet) was provided as white to off-white hard gelatin capsules contain 267 mg of pirfenidone. The cap of the capsule is printed with "PFD 267 mg" in brown ink. Pirfenidone should be stored at 15°C to 25°C. x Both LYT-100 and pirfenidone were over-encapsulated to maintain study blind. Duration of Treatment: [0346] This study included a 28-day Screening period, a 6-day treatment period consisting of: 3 days of up to 550 mg TID LYT-100 followed directly by 3 days of 824 mg TID LYT-100, or placebo. A 3-day (± 1 day) post-last-dose safety follow-up visit occured. Thus, total duration of study participation for each subject was up to 40 days. Criteria for Evaluation Safety: [0347] Safety and tolerability were assessed by monitoring AEs, physical examination, vital signs, 12-lead ECGs, clinical laboratory values (hematology panel, multiphasic chemistry panel and urinalysis), and review of concomitant treatments/medication use. Pharmacokinetics: [0348] Subjects provided blood samples prior to treatment, i.e., Day -1 or Day 1, for the determination of CYP1A2, CYP2C9, CYP2C19, and CYP2D6 genotype to support exploratory PK analyses. Subjects were required to provide consent for genotyping. Blood samples for PK were collected at specified times, as follows: • Day 1: 0 (pre-AM dose) • Day 2: no sampling • Day 3: 0 (pre-AM dose), and 1, 2, 3, 4, 6 (pre-mid-day dose), 7, 8, 9, 10, 12 (pre-PM dose), 13, 14, 15, 16, and 17 hours post-AM dose • Day 4: 0 (pre-AM dose) • Day 5: no sampling • Day 6: 0 (pre-AM dose), and 1, 2, 3, 4, 6 (pre-mid-day dose), 7, 8, 9, 10, 12 (pre-PM dose), 13, 14, 15, 16, and 17 hours post-AM dose • Day 7: 0 (same time as Day 6 pre-AM dose, discharge) [0349] Plasma concentration-time data for LYT-100, and its metabolite(s) were analyzed using noncompartmental methods. Plasma PK parameters for steady state dosing (Days 1 to 3 and Days 4 to 7) included, but were not limited to: • AUC _0-tau,ss (area under the time concentration curve from time zero to tau at steady state) • AUC _0-24,ss (area under the time concentration curve from time zero to 24 hours at steady state) • λ _z (terminal disposition rate constant/terminal rate constant) • t _½ (elimination half-life) • C _max,ss (maximum concentration in a dosing interval) • T _max (time to maximum concentration, as reported relative to the beginning of a dosing interval in which maximum concentration occurred) • C _min,ss (lowest concentration in a dosing interval) • C _av,ss (average concentration during a dosing interval) • C _max,ss -C _min,ss /C _av,s s (degree of fluctuation) • C _max,s s-C _min,ss /C _min,ss (swing) • PTF% (peak-trough fluctuation) [0350] Urine samples for PK were collected at specified intervals, as follows: • Days 1 and 4: pre-dose (subjects to be instructed to empty their bladders approximately 30 minutes prior to dosing) • Days 2 and 5: no urine sampling • Days 3 and 6: pre-dose (subjects to be instructed to empty their bladders approximately 30 minutes prior to dosing), 0 to 4, 4 to 8, 8 to 12, 12 to 16, and 16 to 24 hours post-AM dose [0351] Urine samples for analysis of excretion in urine will be collected, separated by specified time interval, and analyzed. The total volume of urine collected in each interval (t1 to t2) will be noted. The urine PK parameters included, but were not limited to: • Ae _t1-t2 (Amount excreted in urine over time) • CLR (Renal clearance) • Fraction of systemic clearance (CL/F) represented by the renal clearance (CLR/[CL/F]) • Fe _t1-t2 (Fraction of administered dose excreted in urine over the dosing intervals) Study endpoints are defined as follows: x Safety ^ AEs (type, severity, and relatedness to study drug) ^ Physical examination ^ Vital signs ^ Electrocardiograms (ECGs) ^ Clinical laboratory parameters (hematology, serum chemistry, coagulation, and urinalysis) ^ New-onset concomitant medications x Pharmacokinetics: ^ Comparison of the key plasma PK parameters (C _max,ss , C _min,ss , and AUC _0-24,ss ) between the parent compound (LYT-100 and pirfenidone) and primary metabolite (5-carboxypirfenidone). Other plasma PK parameters were also derived and compared. ^ Comparison of the key urine PK parameters (Ae _t1-t2 , CL _R , Fe _t1-t2 ) between the parent compound (LYT-100 and pirfenidone) and primary metabolite (5-carboxypirfenidone). Other urine PK parameters may have bene derived and compared. ^ Food effect evaluation of LYT-100 and pirfenidone (C _max,ss , and AUC _0-6,ss ) for fed vs fasted. Results- Pharmacokinetics [0352] Based on the observations of improved tolerability (but comparable total exposure) for a lower TID dose of LYT-100 compared to pirfenidone in Example 1, the safety and tolerability of a higher TID dose of LYT-100 (to achieve a higher overall predicted AUC or total exposure than the approved dose of pirfenidone (801 mg TID), and to explore the possibility of evaluating that dose in future efficacy studies), was evaluated in this study. [0353] Subjects between the ages of 60 and 80 were randomized to receive LYT-100 or placebo. Subjects were administered up to 550 mg LYT-100 TID for 3 days (to steady state [Day 1 to Day 3]) compared to placebo administered TID for 3 days to steady state. On Day 4 to Day 6, subjects were administered 824 mg LYT-100 TID for 3 days compared to placebo TID for 3 days to steady state. A summary of the dosing scheme is provided in Table 16. Table 16. Dosing Scheme Number of Dose, Total Dose, Total Subjects Days 1 to 3 Daily Dose Days 4 to 6 Daily Dose g ts to LYT-100 and 6 subjects to placebo. Seven subjects (23.3%) did not complete the study. The mean age of the overall population was 64.9; the mean age was similar in the LYT-100 and placebo groups, 65.0 and 64.5 years, respectively. The majority of subjects were male (56.7%; 66.7% in the LYT-100 group, 16.7% in the placebo group). The overall mean number of days of dosing with LYT-100 was 5.5 days. The mean number of days of dosing with placebo was 5.8 days. [0355] Data was obtained for thirty subjects. Eight subjects had all values reported as below level of quantitation (BLQ; assumed to be 6 placebo subjects plus 2 active subjects with Day 1 pre-dose samples only). One additional subject was excluded due to a large number of BLQ samples on both Days 3-4 and 6-7. Accordingly, twenty-one subjects had sufficient PK data available to calculate PK parameters at the lower dose (550 mg TID on Days 3-4). Three subjects only had data for Days 3-4, and therefore had missing PK parameters for the higher dose (824 mg TID on Days 6-7). [0356] The results for the pharmacokinetic assessments are provide in FIG.7A to FIG.18B. With reference to FIGS.7A-7D, the plasma concentrations for both the parent drug (LYT-100; SD-560) and major metabolite (5-carboxypirfenidone; SD-789) were higher for the 824 mg TID dose cohort (FIGS. 7B and 7D) relative to the 550 mg TID dose cohort (FIGS. 7A and 7C). The C _max , AUC, and T _max values in the fed state for LYT-100 and the major metabolite at the 550 mg and 824 mg TID doses are provided in FIG. 89. With reference to FIG. 8, for LYT-100, the C _max ratio for the 824 mg TID to the 550 mg TID dose was 1.45, and the AUC ratio was 1.44, demonstrating an approximately linear dose-exposure relationship. The C _max and AUC ratios for the metabolite were slightly reduced at 1.32 and 1.42, respectively. [0357] The results for this study were compared to the results obtained in a prior 850 mg BID study and a prior 550 mg TID study (described herein in Example 1). As shown in FIGS.10A and 10B (LYT-100 and major metabolite, respectively), although slightly lower, the AUC for the present 550 mg TID (days 1-3) study roughly matches up with the AUC of 550 mg TID from the prior 550 mg TID study (part 2; solid blue and solid green lines respectively; see also Example 1, Table 13), and the AUC and C _max for the 824 mg TID dose shows a pronounced/linear increase over that for the 550 mg TID dose. [0358] FIG. 10 provides a comparison of plasma concentrations of LYT-100 (dosed at 550 mg and 824 mg TID) and pirfenidone (dosed at 801 mg TID) versus time following the day 3 doses. With reference to FIG. 10, the concentration peaks for pirfenidone are higher than those for 550 mg LYT-100. FIG.11 provides a comparison of plasma concentrations of the major metabolite of LYT-100 (dosed at 550 mg and 824 mg TID) and pirfenidone (dosed at 801 mg TID) versus time following the day 3 doses. FIG. 12 provides a comparison of plasma concentrations versus time for pirfenidone at 801 mg TID and LYT-100 at 550 mg TID following the day 3 doses. [0359] FIG. 13A provides a comparison of AUC _0-24 versus body weight for LYT-100 administration across this and previous studies. FIG. 13B provides a comparison of AUC _0-24 versus body weight for the major metabolite of LYT-100 across this and previous studies. With reference to FIGS. 13A and 13B, a similar trend for impact of body weight was observed across all three groups, with an apparent exposure difference above and below a threshold of 70-75 kg. [0360] FIGS.14A and 14B provide a comparison of AUC _0-24 versus subject age for LYT-100 and the major metabolite, respectively, across this and previous studies. With reference to FIGS. 14A and 14B, age appears to impact AUC, with exposure increasing with age. [0361] Bioequivalence simulations were performed for AUC _24ss across this dosing study and three prior dosing studies. Results are provided in FIGS. 15A-15D and FIG. 16, which show that bioequivalence to 801 mg TID pirfenidone was achieved for 550 mg TID LYT-100 when pooled data from the studies was used, and bioequivalence was observed for a theoretical 687 mg TID dose (FIG.16). The results of the simulations across this study and three prior studies is provided in tabular form in FIG. 17. An illustrative prediction of plasma concentration over time for theoretical 550 mg TID and 825 mg TID dosing of LYT-100 and 801 mg TID dosing of pirfenidone is provided in FIG. 18A. With reference to FIG. 18A, it is predicted that for the 550 mg TID dosing, the maximal plasma concentration (Cmax) of LYT-100 achieved is less than the maximal plasma concentration of pirfenidone achieved with 801 mg TID dosing, but with a similar exposure (AUC). In contrast, it is predicted that with the 825 mg TID dosing, the Cmax of LYT- 100 achieved is only slightly more than the maximal plasma concentration of pirfenidone achieved with 801 mg TID dosing, but with a higher AUC. The estimated Cmax and AUC ratios of LYT- 100 to pirfenidone are provided in FIG. 18B. Results- Tolerability [0362] Four subjects discontinued due to an TEAE (3 (12.5%) subjects in the LYT-100 group and 1 (16.7%) subject in the placebo group). Three (12.5%) subjects withdrew consent; all were in the LYT-100 group. Overall, 9 subjects (30.0%) experienced at least one TEAE; 8 (33.3%) while taking LYT-100 and 1 (16.7%) while taking placebo. The most common TEAEs (>5% overall) were COVID-19 and headache. A summary of these TEAEs, overall and by study medication, is provided in Table 17. Table 17. Summary of the Most Common (>5% Overall) TEAEs (Safety Population) LYT-100 Placebo Overall N 24 N 6 N 30 y y y y onset of the COVID-19 events occurred within days 4 to 6; the onset of the headache events occurred within days 1 to 3. Overall, the majority of TEAEs were considered to be mild. There were 13 mild events reported by 8 (26.7%) subjects, 7 (29.2%) in the LYT-100 group and 1 (16.7%) in the placebo group. Two moderate TEAEs were reported by one (3.3%) subject; this subject was in the LYT-100 group. No TEAEs were severe. TEAEs were unrelated for 5 (16.7%) events and possibly related for 6 (13.3%) events. No events were probably related. Overall, TEAEs leading to study discontinuation were reported by 4 (13.3%) subjects; all were Covid-19. Of these 4 TEAEs, 3 (12.5%) occurred in the LYT-100 group and 1 (16.7%) occurred in the placebo group. No deaths or SAEs were reported during the study. [0364] Based on prior PK modeling studies, the AUC of LYT-100 at 824 mg TID is expected to be approximately 150% of the AUC for the approved pirfenidone dose of 801 mg TID. Within the 824 mg TID LYT-100 group (mean age=65), the dose was well tolerated over the 3 treatment days. In this dosage group, the most common TEAE was headache, and the majority of the events were mild. [0365] Using the foregoing crossover data, a further simulation was performed. The simulation involved dose normalizing the observed AUC _0-24 after administration of LYT-100 in each subject to calculate the expected AUC _0-24 after administration of various hypothetical TID doses. The resultant AUC _0-24 was then compared to the observed AUC _0-24 after administration of pirfenidone 801 mg TID to calculate an individual ratio of LYT-100 to pirfenidone. These ratios were then assessed using the same process described in Chow (Design and Analysis of Bioavailability and Bioequivalence Studies; Chapman & Hall/CRC Biostatistics Series, Chapman; Hall/CRC 2008) and the CDER (Guidance for Industry Statistical Approaches to Establishing Bioequivalence Center for Drug Evaluation and Research [CDER], FDA, 2001). The results of the simulation are provided in Table 18. Based upon these assessments, an LYT-100 dose regimen of 550 mg TID is predicted to provide comparable parent drug exposure to pirfenidone dosed at 801 mg TID. An LYT-100 dose regimen of 825 mg TID is predicted to provide parent drug exposure that is approximately 150% of that following administration of pirfenidone given 801 mg TID. Of note, the slower absorption of LYT-100 relative to pirfenidone results in a predicted C _max for LYT-100 at a dose of 825 mg TID that is only 15% higher than the corresponding C _max for pirfenidone at a dose of 801 mg TID. [0366] The actual and extrapolated exposure and C _max values for LYT-100 dosed at 550 and 824/825 mg TID, along with the tolerability data, support these two doses for studying the efficacy, safety, and dose response in idiopathic pulmonary fibrosis, as described below in Example 3.

Table 18. Predicted ratio of AUC _0-24 and C _max x (LYT-100:pirfenidone 801 mg TID) after the administration of various actual and hypothetical LYT-100 doses using pooled data LYT-100 Dose (mg TID) 90% Confidence AUC 24 C xamp e : - o era ty n at ents w t - esp ratory ness [0367] A Phase 2 multi-center randomized, double-blind, parallel arm, placebo-controlled trial was performed to evaluate the safety and efficacy of deupirfenidone (LYT-100) compared to placebo in post-acute adult patients with COVID-19 respiratory disease who were treated with supplemental oxygen (including MV, ECMO or any other means of oxygen administration) in the hospital for at least 1 day and have required only low flow nasal oxygen or no oxygen supplementation for at least 72 hours prior to screening. Patients received LYT-100 (deupirfenidone) formulated as powder in 250 mg capsules or matching placebo. Dosing was as provided in Table 19. An initial dosage of 500 mg BID was given the first 3 days of dosing, followed by 750 mg BID thereafter. Patients took LYT-100 study medication, or placebo (in Part A), orally and preferably with food, (solid or nutritional supplements, whenever possible), with approximately 10 to 12 hours between the two daily doses. Table 19: Dosing Regimens Day 1 to Day 3 Day 4 through Day 91 ebo [036 contnued respiratory complications following hospitalizaton for acute COVID-19 infection that required treatment with supplemental oxygen were randomized to receive LYT-100 or placebo in a ratio of 1:1, respectively. The baseline demographic characteristics of enrolled subjects and subject disposition are provided in FIG. 19 to FIG. 21. Tolerability Results [0369] LYT-100 was well-tolerated in this relatively sick patient population with multiple comorbidities and concomitant medications. There were no drug-related serious adverse events (SAEs) or deaths. The treatment emergent AE's occurring in the LYT-100 arm at a frequency greater than or equal to 5% are summarized in Table 20. With reference to Table 20, nausea was the only AE judged to be at least possibly related to LYT-100 with an incidence ≥5% (8.7% vs 2.4% with placebo). With further reference to Table 20, other AEs that have been commonly associated with pirfenidone and which were considered to be at least possibly related to LYT-100 treatment in this study included headache (4.3% vs.1.2% with placebo), dizziness (3.3% vs.1.2% with placebo), fatigue (2.2% vs. 0% with placebo), and rash (3.3% vs. 1.2% with placebo). Discontinuation rates due to AEs that were considered at least possibly related to LYT-100 were low in both arms (8.6% with LYT-100 vs.2.4% with placebo) and the majority of discontinuations in the LYT-100 arm were due to idiosyncratic events and not AEs commonly associated with pirfenidone. A summary of all treatment emergent adverse events judged to at least possibly be related to LYT-100 are provided as FIG. 22. Table 20: Treatment Emergent AEs occurring in LYT-100 (≥ 5%) Adverse Event Placebo: N LYT-100 750 mg ts [0370] Ov ffirm the profile of strong safety and tolerability profile of LYT-100 observed in previous studies, including those described in Examples 1 and 2 herein. The safety and tolerability of the 750 mg BID dosage in this relatively sick patient population suggest it may be equally well tolerated in other patient populations, such as those with fibrotic- or collagen-mediated diseases. Example 4: In Vitro Stability of Pirfenidone and LYT-100 in the Presence of Recombinant Human CYP Isozymes [0371] The metabolism of LYT-100 by isolated CYP isozyme preparations was evaluated and compared with the metabolism of pirfenidone (FIG. 27). Pirfenidone and LYT 100 were each incubated with recombinant human CYP1A2, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP3A4, and CYP3A5 expressed in heterologous cell systems. The half-life (t1/2) of each test article was determined. [0372] With reference to FIG. 23, pirfenidone and LYT-100 concentrations decreased by at least 15% during incubation with recombinantly expressed human CYP1A2, CYP2D6 and CYP2C19 isozymes. The t _1/2 of pirfenidone following incubation with CYP1A2, CYP2C19 and CYP2D6 was 3.18, 2.13 and 2.30 hours, respectively. The t _1/2 of LYT-100 following incubation with CYP1A2, CYP2C19 and CYP2D6 was 9.08, 3.67 and 2.72 hours, respectively. There was no significant metabolism by CYP2C8, CYP2C9, CYP3A4 or CYP3A5 isozymes, with more than 92% of the compounds remaining at the end of incubation. Therefore, no t _1/2 was calculated for those isozymes. These results confirm the stabilization against metabolism of LYT-100 vs. pirfenidone. Metabolism by CYP1A2 was the most affected by deuteration (~3-fold longer t _1/2 compared to pirfenidone). This result demonstrates the effect of deuteration of LYT-100 on the overall metabolism of pirfenidone as the CYP1A2 isozyme plays a key role in the metabolism of pirfenidone. Example 5: Activity Screen [0373] The DiscoverX BioMAP Fibrosis Panel was used to evaluate LYT-100 and pirfenidone. The panel contains 54 biomarker (cell surface receptors, cytokines, chemokines, matrix molecules and enzymes) readouts that capture biological changes that occur within the physiological context of the particular BioMAP system. LYT-100 and pirfenidone were tested in the BioMAP Fibrosis Panel at various dilutions starting at highest dose of 1700 μM in three cell/stimulus systems (myofibroblast [MyoF] composed of lung fibroblasts treated with TNF-D and TGF-β, renal proximal tubule epithelial cell (RE)MyoF including renal tubule epithelial cells and lung fibroblasts treated with TNF-D, and TGF-β, and small airway epithelial cell (SAE)MyoF comprising small airway epithelial cells and lung fibroblasts treated with TNF-a, and TGF- β). Similar results were observed with both compounds in the three systems (FIG. 24). Example 6: Inhibition of lipopolysaccharide (LPS)-induced plasma TNF-α and IL-6 Concentrations Following Oral Dose of LYT-100 in Male Sprague-Dawley Rats [0374] LYT-100 and pirfenidone dosing solutions were prepared by dissolving each in a vehicle of 1% carboxymethyl cellulose and 0.2% Tween-80 in water. LPS was diluted with sterile saline to 2 mg/mL and sonicated at 40°C for 20 minutes to generate a stock solution and stored at 4°C. Each day of use, the stock solution was further diluted to 0.03 mg/mL in sterile saline. [0375] Male Sprague-Dawley rats with indwelling femoral and jugular venous catheters (n=6-8 per dose and test article group) were used in this study. Rats were administered either vehicle (the dosing solution, 10 mL/kg), LYT-100 or pirfenidone at a concentration of 30, 100 or 300 mg/kg via syringe attached to an oral gavage needle. Sixty minutes after the oral dose, 0.03 mg/kg of LPS in 1 mL/kg saline was infused into the jugular vein. [0376] Blood samples were collected from the femoral vein into heparin-coated syringes 15 minutes prior to the LPS infusion (45 minutes after oral doses of test article), 90 minutes after the LPS infusion and 4 hours after the LPS infusion. Plasma was prepared by centrifugation of the blood samples at 14,000 rpm for 10 minutes. Plasma samples were stored at -70 ºC until analysis. [0377] LPS stimulated a strong inflammatory response, including the cytokines TNF-α and IL-6 (FIGS. 25A and 25B, respectively). With reference to FIG. 25A, in vehicle-pretreated rats, LPS increased plasma TNF-α concentrations from non-detectable concentrations to approximately 75,000 pg/mL 90 minutes after injection). This TNF-α response to LPS was reduced by pretreatment with both pirfenidone and LYT-100. Ninety minutes after LPS injection, pretreatment with oral doses of 100 and 300 mg/kg LYT-100 inhibited TNFα. At 100 mg/kg, TNF-α levels were 70 percent lower than those obtained using equivalent oral volumes of the vehicle control, and there was greater reduction in TNF-α response in rats pretreated with LYT-100 compared to pirfenidone (Table 21, Table 22, and FIG. 25A). Pretreatment with oral doses of 100 and 300 mg/kg LYT-100 also inhibited IL-6 similarly to pirfenidone (Table 23, Table 24, and FIG. 25B). Thus, LYT-100 retains pirfenidone’s activity to attenuate LPS-induced TNF-α and shows additional potency at an equivalent dose, likely due to the pharmacokinetic effect of deuteration. Table 21. Plasma TNFα concentrations (pg/ml) after oral pretreatment with vehicle, pirfenidone or LYT-100 and intravenous injection of LPS (1.5 hrs post-LPS) Dose, Vehicle pre- Pirfenidone pre-treatment ^a LYT-100 pre-treatment ^a mg/kg treatment ^a Table 22. Plasma TNFα concentrations (pg/ml) after oral pretreatment with vehicle, pirfenidone or LYT-100 and intravenous injection of LPS (4 hrs post-LPS) Dose, Vehicle pre- Pirfenidone pre-treatment ^a LYT-100 pre-treatment ^a mg/kg treatment ^a Table 23. Plasma IL-6 concentrations after oral pretreatment with vehicle, pirfenidone or LYT- 100 and intravenous injection of LPS (1.5 hrs post-LPS) Dose, Vehicle pre- Pirfenidone pre-treatment ^a LYT-100 pre-treatment ^a mg/kg treatment ^a

Table 24. Plasma IL-6 concentrations after oral pretreatment with vehicle, pirfenidone or LYT- 100 and intravenous injection of LPS (4 hrs post-LPS) Dose, Vehicle pre- Pirfenidone pre-treatment ^a LYT-100 pre-treatment ^a mg/kg treatment ^a 1 12 Example 7: LYT-100 Significantly Reduced Area of Fibrosis in Mouse Model [0378] Non-alcoholic steatohepatitis (NASH) is characterized by lobular inflammation, hepatocyte ballooning and degeneration progressing to liver fibrosis. LYT-100 was orally administered at 0 mL/kg (Vehicle only: 0.5% carboxymethylcellulose) or 10 mL/kg twice daily from 6-9 weeks of age in 18 male mice in which NASH mice was induced by a single subcutaneous injection of 200 μg streptozotocin solution 2 days after birth and feet with a high fat diet after 4 weeks of age. LYT-100 was administered at an oral dose of 30 mg/kg twice daily (60 mg/kg/day). In addition, nine non-NASH mice were fed with a normal diet and monitored. [0379] FIG. 26 depicts representative micrographs of Sirius-red stained liver sections illustrating that LYT-100 significantly reduced the area of fibrosis. Specifically, liver sections from the vehicle group exhibited collagen deposition in the pericentral region of the liver lobule. Further, the LYT-100 group showed a significant reduction in the fibrosis area compared to the vehicle group. These results demonstrate that LYT-100 has a potential to inhibit the progression of fibrosis. FIG. 27 illustrates the percent fibrosis area for LYT-100 versus vehicle and control. The results are also summarized Table 25 below. Table 25: Fibrosis Area Parameter Normal Vehicle LYT-100 [0380] Liver sections from the Vehicle group exhibited severe micro- and macro vesicular fat deposition, hepatocellular ballooning and inflammatory cell infiltration. While LYT-100 hepatocyte ballooning was similar to Vehicle, scores were lower for lobular inflammation and steatosis (Table 26). The components of the NAS Score are provided in Table 27. Table 26: NAFLD Activity Score S ^core Steatosis Lobular Inflammati _NAS Group n on Hepatocyte (mean D) Table 27. Definitions of NAS Components Item Score Extent sis, reduced inflammation, and reduced accumulation of fat (steatosis), as compared to the untreated NASH mice. Example 8: LYT-100 Reduction of TGF-β-induced proliferation and collagen levels in Primary Mouse Lung Fibroblasts [0382] LYT-100 was evaluated for an ability to reduce the TGF-β-induced proliferation of, and collagen levels in, Primary Mouse Lung Fibroblasts (PMLF). [0383] Inhibition of p38 members by LYT-100 is important as p38 members are activated by the TGF-β^ signaling pathway. TGF-β^ activation in turn plays a significant role in transcriptional induction of the collagen type IA2. The collagen type IA2 makes up the majority of extracellular matrix, which accumulates during progression of, e.g., fibrotic lung disease. Deposition of collagen is one of the most important components of fibrotic lung tissue, a process primarily induced by TGF-β. Since accumulation of insoluble collagen encroaches on the alveolar space, it plays pivotal role in distortion of lung architecture and progression of fibrotic lung disease. In addition to insoluble (structural) collagen, fibrotic lungs of IPF patients also show high levels of non-structural (soluble) collagen. Although this type of collagen may eventually become insoluble collagen, until then, soluble collagen can serve as a ligand for integrin receptors of lung fibroblasts and epithelial cells. Binding of soluble collagen to these receptors induces proliferation and migration of these cells. Fibronectin is another important component of fibrotic lungs as it is induced by TGF-β and functions both as a structural component of extra cellular matrix (ECM), as well as a ligand for integrin receptors. Just like soluble collagen, binding of fibronectin to integrin receptors induces the proliferation of fibroblast and epithelial cells of the lungs and plays a significant role in progression of IPF. Therefore, inhibition of TGF-β -induced collagen synthesis is an important target for fibrotic lung disease. Preparation of Primary Mouse Lung Fibroblast [0384] Primary Mouse lung fibroblast were prepared as follows. One lung was removed from 2 months old male BalbC Mouse, perfused with sterile PBS, minced and incubated in 2 ml of serum free Dulbecco's Modified Eagle's Medium (DMEM) containing 100 μg/ml of collagenase I for one hour at 37 ^o C. Each sample was centrifuged at 1500 r.p.m (revolution per minute) for 5 minutes, washed three times with PBS and the final cellular pellet was resuspended in DMEM supplemented with 10% serum and Pen/Strep, and incubated in 150 mm plates at 37ºC with 80% humidity and %% CO2. The growth medium was removed and fresh medium was added every day for 10 days. Testing the effect of LYT-100 on Survival of Primary Mouse Lung Fibroblast [0385] LYT-100 was evaluated for an ability to alter TGF-β-induced proliferation of PMLF. At Before testing the effect of LYT-100 on survival of these cells, fibroblasts were tripsinized and five thousand cells were plated into 96 well plate in 200 μL complete DMEM, and incubated until cells reached to 95-100% confluency, then the medium was removed and complete DMEM containing proline (10 μM) and ascorbic acid (20 μg/ml) was added. LYT-100, dissolved in pure ethanol, was added to the plates at a final concentration of 500 μM 1 h prior to addition of TGF-β^(5 ng/ml), and cells were further incubated for 72 hrs. One hundred μL of the growth medium was removed and 20 μL of MTT stock solution (prepared in PBS at 5.5 mg/ml concentration) was added and cells were incubated for 4 hours, then 100 μl of dimethyl sulfoxide was added, and absorbance of developed color was monitored at 540-690 nm. [0386] As shown in FIG. 28A, LYT-100 did not affect the survival of PMLFs alone. TGF-β^(5 ng/ml) significantly induced the proliferation of PMLFs by nearly 45% (p=0.001), and LYT-100 did appear to diminish TGF-β-induced proliferation of PMLFs by 10%, but this effect was not statistically significant (p=0.19). TGF-β-induced Insoluble Collagen Synthesis using 6-well plate format [0387] The effect of LYT-100 on inhibition of TGF-β-induced collagen synthesis was evaluated in PMLFs in a 6-well format. One hundred thousand Primary Mouse Lung Fibroblasts were plated in 6-well plates and incubated in complete DMEM until they reached confluency. The incubation medium was removed and complete DMEM containing proline (10 μM) and ascorbic acid (20 μg/ml) was added. LYT-100 was added to the plates at a final concentration of 500 μM 1 h prior addition of TGF-β (5 ng/ml), and cells were further incubated for 72 hrs. [0388] Supernatant was removed, cells were washed with cold PBS and 1 ml Sircol reagent was added. The Sircol reagent contains the collagen binding dye Sirius red. The cells were scraped off with Sircol reagent and samples were shaken for 5 h at room temperature (RT), centrifuged at 10,000 rpm for 5 min, supernatant was removed, the pellet was washed in 0.5 M acetic acid to remove unbound dye, and recentrifuged at 10,000 rpm for 5 min, supernatant was removed, and the final pellet was dissolved in 1 ml 0.5M NaOH and shaken at RT for 5 h. A sample of 100 μl of resultant solution was placed in 96-well. The color reaction was assessed by optical density at a wavelength of 600 nm. [0389] As shown in FIG. 28B, PMLFs responded to TGF-β^with increased total collagen levels, (increase of 21%; p=0.0087). LYT-100 inhibited this induction by 15% (p=0.026), as compared to the TGF-β alone, without reducing the background level of collagen. TGF-β-induced Insoluble Collagen Synthesis using 96-well plate format [0390] The effect of LYT-100 on TGF-β-induced collagen was confirmed in a high throughput collagen assay using 96-well plate format. Approximately 5,000 primary mouse fibroblasts were plated in complete DMEM in 96 well plates and incubated for 3 days at which time the cultures achieved confluency. After cells reached confluency, the medium was removed and fresh DMEM supplemented with ascorbic acid (20 μg /ml) and prolin (10 μMol) was added. LYT-100 was then added to the appropriate cultures at a final incubation concentration of 500 μM. One hour later, TGF-β^was added to the appropriate cultures at a final concentration of 5 ng/ml. After 72 hours, the media was replaced with a 0.5% glutaraldehyde solution. After 30 minutes, the adherent cells were washed and subsequently incubated with acetic acid at a final concentration of 0.5M. After a 30 min room temperature incubation, and subsequent washing steps, the wells were incubated with Sircol reagent. After 5 hours, the unbound dye was removed and the plates were washed and allowed to dry. To extract collagen-bound Sircol, 100 μL of alkaline solution (0.5M NaOH) was added and plates were shaken for 1 h on rotary shaker at room temperature. Absorbance at 600 nm was determined to detect bound collagen. [0391] As shown in FIG. 28C, in the 6-well format, TGF-β^induced insoluble collagen level by 40% (p=0.0002), LYT-100 diminished this TGF-β-stimulated collagen accumulation by 24% (p=0.0003) without reducing the background level of collagen. TGF-β-induced Soluble Fibronectin and Collagen Synthesis [0392] LYT-100 was evaluated for its ability to modify TGF-β-induced soluble fibronectin and soluble collagen synthesis using a selective ELISA. Approximately 5,000 primary mouse lung fibroblasts were plated in complete DMEM in 96 well plates and incubated for 3 days at which time the cultures achieved confluency. After cells reached to confluency, medium was removed and fresh DMEM supplemented with ascorbic acid (20 μg /ml) and prolin (10 μM) was added. LYT-100 was then added to the appropriate cultures at a final incubation concentration of 500 μM. One hour later, TGF-β^(5 ng/ml) was added to the appropriate cultures at a final concentration. After 72 hours, 200 μl samples of the supernatant were placed onto an ELISA plate and incubated overnight. After blocking with %1 BSA for 2 h, plates were incubated with either an anti-collagen type I antibody or an anti-fibronectin antibody. [0393] The plates were washed after 1 hour and incubated with secondary horseradish peroxidase- conjugated antibodies (anti-goat for the collagen antibody, anti-rabbit for the fibronectin antibody). After a series of washing steps the color reagent TMB (3,3’,5,5’-tetramethylbenzidine) was added and 15 minutes later the reactions were terminated with equal volumes of 2N H ₂ SO ₄ . The levels of soluble collagen and fibronectin were determined by evaluating absorbance at 450 nm. [0394] Referring to FIG.28D, TGF-β induced the level of soluble fibronectin by 16% (p=0.0021). LYT-100 inhibited TGF-β-dependent induction of fibronectin by 11% (p=0.0185). Moreover, LYT-100 also inhibited the background level of soluble fibronectin by 10% (p=0.03). [0395] As shown in FIG. 28E, TGF-β induced the level of soluble collagen by 20% (p=0.0185). LYT-100 inhibited this TGF-β-dependent increase by 36% (p=0.0001). Moreover, it also inhibited background level of soluble collagen by 23% (p=0.0115). [0396] In summary, LYT-100 was found to: (i) reduce TGF-β-induced cell proliferation, (ii) reduce both background and TGF-β-induced levels of insoluble (structural) collagen; (iii) reduce both background and TGF-β-induced levels of soluble collagen; and (iv) reduce both background and TGF-β-induced levels of soluble fibronectin. [0397] During the progression of fibrotic lung diseases such as IPF, an accumulation of extra cellular matrix components such as collagen and an increase in the fibroblast population is observed. Persistent proliferation of fibroblasts is considered an important contributor to the lung architecture in fibrotic lung disease, including the diminished interstitial spaces of the alveoli. Thus, reducing TGF-β-induced proliferation of fibroblasts and structural collagen with LYT-100 has the potential to prolong lung function in fibrotic lung disease. In addition to inhibiting TGF-β- induced insoluble collagen level, LYT-100 also inhibits TGF-β-induced secreted collagen and fibronectin β. Secreted collagen and fibronectin not only increase the rate of formation of fibrotic foci in the lung, but these proteins can also act as ligands for integrin receptors. When integrin receptors are activated, they induce not only the proliferation of epithelial cells and fibroblasts of the lungs, but they also, along with TGF-β, induce epithelial mesenchymal transition (EMT) of the epithelial cells of the lungs. EMT causes these cells to migrate to different regions of the lungs. This migration is considered to be a very important contributor for the generation of new fibrotic foci in the lungs and progression of fibrotic lung disease such as IPF. LYT-100 has the ability to inhibit TGF-β-induced pro-fibrotic processes and to reduce basal factors which have the potential to exacerbate ongoing fibrosis. Example 9: Effect of LYT-100 on L929 Cells [0398] The effect of LYT-100 on survival of L929 cells was determined. Five thousand L929 cells were plated in completed DMEN and incubated until confluency for 3 days. The medium was removed and complete DMEM containing proline (20 μg/ml) and ascorbic acid (10 uM) was added. LYT-100 was given at 500 μM 1 h prior addition of TGFE (5 ng/ml), and cells were further incubated for 72 hrs. An aliquot of 100 μL of medium was removed, 20 μL MTT solution was added for 4 hrs, then 100 μl of DMSO was added, and absorbance of the developed dark pink color was determined at 54-690 nM. FIG.29A illustrates that LYT-100 does not affect survival of L929 cells. [0399] The effect of LYT-100 on TGF-induced collagen synthesis in 6-wells was determined. 100,000 L929 cells were plated in complete DMEN and incubated until confluency for 3 days. Medium was removed and complete DMEM containing proline (20 μg/ml) and ascorbic acid (10 μM) was added. LYT-100 was added at 500 μM 1 hour prior addition of TGF-β (5 ng/ml). Cells were further incubated for 72 hrs. Supernatant was removed, cells were washed with cold PBS, 1 ml Sircol reagent was added onto the cells and cells were scraped off, samples were shaken for 5 h at RT, centrifuged at 10,000 rpm for 5 min, supernatant was removed, the pellet was dissolved in 0.5M acetic acid to remove unbound dye, and re-centrifuged at 10,000 rpm for 5 min, supernatant was removed and the final pellet was dissolved in 1 ml of 0.5M NaOH, shaken at RT for 5 h, 100 μl of resulted solution was placed in 96-well and absorbance was determined at 600 nM. The results are summarized in FIG. 29B, which illustrates that LYT-100 inhibits TGF- induced collagen synthesis. LYT-100 also significantly inhibits collagen synthesis in the absence of added TGF-β. [0400] Next, the effect of LYT-100 on TGF-induced collagen synthesis was confimed using a 96- well plate format. Five thousand L929 cells were plated in complete DMEN and incubated until confluency for 3 days. The medium was removed and complete DMEM containg proline (20 μg/ml) and ascorbic acid (10 μM) was added. LYT-100 was added at 500 μM 1 h prior addition of TGF-β (5 ng/ml). Cells were further incubated for 72 hrs. Supernatant was removed, 0.5% gluteraldehyde was added for 30 min at RT, removed, washed 3x with water, 0.5M acetic acid was added for 30 min at RT, removed, washed with water, air dried and 100 μl Sircol dye was added for 5 h at RT. The dye was removed, the plate was washed extensively under running water, air dried, and 200 μl of 0.5M NaOH was added, the plates were shaken at RT for 1 h, and absorbance was determined at 600 nm. The results summarized in FIG. 29C illustrate that LYT-100 significanly inhibited or reduced TGF-β-induced total collagen levels. LYT-100 also signficantly inhibited or reduced total collagen level in the absence of TGF-β induction. [0401] The effect of LYT-100 on TGF-induced soluble collagen synthesis was determined using a 96-well plate format. Five thousand L929 cells were plated in complete DMEN and incubated until confluency for 3 days. The medium was removed and complete DMEM containing proline (20 μg/ml) and ascorbic acid (10 μM) was added. LYT-100 was added at 500 μM 1 h prior addition of TGF-β (5 ng/ml). Cells were further incubated for 72 hrs. 200 μl supernatant of 96-well Sircol plate was placed onto ELISA plate and incubated overnight. The next day, supernatant was removed and 100 ul of 1% BSA in PBST was added and incubated for 2 h at RT, BSA was removed, plate was washed 3x with 200 μl of PBST, and anti-collagen type I a.b was added at 1:2000 dilution (prepared in %1 BSA in PBST), incubated at RT for 1 h, primary a.b was removed, plate was washed 3x with 200 μl PBST, and secondary anti-goat HRP was added at 1:2000 dilution, incubate at room temperature for 1 h, removed, the plate was washed 3x with 200 μl PBST, and 100 μl of TMB solution was added for color development for 15 min, then 100 μl of 2N H2SO4 was added to stop the reaction and absorbance of the developed yellow color was determined at 450 nm. [0402] As illustrated in FIG. 29D, LYT-100 significantly inhibits TGF-β-induced soluble collagen levels. LYT-100 also signficantly reduced soluble collagen levels in the absence of TGF- β-induction. [0403] Fibronectin is another important component of fibrotic lungs as it is induced by TGF-β and functions both as a structural component of extra cellular matrix as well as well as a ligand for integrin receptors. Just like soluble collagen, binding of fibronectin to integrin receptors induces the proliferation of fibroblast and epithelial cells of the lungs. The effect of LYT-100 on TGF- induced soluble fibronectin synthesis was determined using a process similar to that described in the above paragraph for soluble collagen synthesis, except that a fibronectin ELISA was used. As illustrated in FIG. 29E, LYT-100 signficantly reduced soluble fibronectin levels, in the absence and presence of TGF-β-induction. Example 10: LYT-100 Study in Mouse Model of Lymphedema [0404] This experiment tested the effect of LYT-100 in a mouse tail model of lymphedema. LYT- 100 or control (carboxymethylcellose) was delivered once daily by oral gavage, in mice with ablated tail lymphatics via circumferential excision and ablation of collecting lymphatic trunks. Tail volume was measured weekly for all animals, starting pre-surgery and continuing until the occurrence of COVID19 required termination of the study at 6 weeks. At sacrifice, tails were harvested for histology and immunofluorescent imaging to characterize tissue changes with surgery and LYT-100 or control treatment. Tail volume and markers of lymphatics, fibrosis, and inflammation were compared between LYT-100 and the control group. [0405] Animals: 14 adult (10–14 week old) C57BL/6 J mice.7 animals per group. [0406] Surgery: The superficial and deep collecting lymphatics of the mid portion of the tail were excised using a 2-mm full-thickness skin and subcutaneous excision performed at a distance of 15 mm from the base of the tail. Lymphatic trunks (collecting lymphatics) adjacent to the lateral veins were identified and ablated through controlled, limited cautery application under a surgical microscope. The dosing amounts, route and schedule are provided in Table 28. Table 28. Dosing regimens G T i l T i l i D i D i d ily ily ily Group 4 LYT-100 Crystals ground into fine 250mg/kg/day Oral powder and suspended in gavage, ily ily ily [0 . Table 29: Measurements Tail volume Calculated with truncated cone formula (Sitzia 1995) and confirmed es d d m l it it l s es, sis , Table 29: Measurements Metamorph software by calculating the ratio of red-orange:green- Table 30: Study Details Time Procedure Notes il ry [04 09] FIG.30A-D depicts results of once daily administration of LYT-100 to reduce swelling in a mouse lymphedema model over the six weeks. The mouse lymphedema model is graphically illustrated in FIG. 30A. As shown in FIG. 30B, daily administration of LYT-100 significantly reduced swelling as compared to carboxymethylcellulose control by 5 weeks. The images in FIG. 30C and FIG. 30D depict the differences in swelling at 6 weeks. Example 11: Evaluation of LYT-100 Efficacy in a Rodent Bleomycin-Induced Fibrosis Model [0410] The rodent bleomycin-induced fibrosis model (BLM) is commonly utilized in the preclinical setting as it appears to have clinical relevance as an animal model of human fibrosis (e.g., idiopathic pulmonary fibrosis) based on the observed pulmonary pathophysiology following the bleomycin challenge in rats. See, e.g., Corboz et al., Pumonary Pharm. & Ther. 49 (2018), 95- 103). Bleomycin is a metabolite of the bacterium Streptomyces verticillus first identified in 1962.

[0411] Specifically, bleomycin is a non-ribosomal hybrid peptide-polyketide natural product having the structure: [0412] While use as an antibiotic. Bleomycin is used as a chemotherapeutic agent in the treatment of various cancers, including Hodgkin's lymphoma, non-Hodgkin's lymphoma, testicular cancer, ovarian cancer, and cervical cancer among others. Bleomycin acts by induction of DNA strand breaks and may also inhibit incorporation of thymidine into DNA strands. DNA cleavage by bleomycin depends on oxygen and metal ions, at least in vitro, though the exact mechanism of DNA strand scission is unresolved. [0413] Common side effects associated with bleomycin chemotherapy include fever, weight loss, vomiting, rash, and a severe type of anaphylaxis. The most serious complication of bleomycin therapy, occurring with increasing dosage, is pulmonary fibrosis and impaired lung function. In high concentrations, bleomycin induces DNA strand rupture, generates free radicals, and causes oxidative stress tresulting in cell necrosis and/or apoptosis. Recent studies support the role of the proinflammatory cytokines IL-18 and IL-1beta in the mechanism of bleomycin-induced lung injury. Bleomycin is normally metabolized by the enzyme bleomycin hydrolase, but the lung is particularly susceptible to bleomycin toxicity by virtue of the scarcity of this enzyme in the lung. Lung inflammation, fibrosis, reductions in lung compliance, and impaired gas exchange are the consequences of a bleomycin challenge. [0414] In assessing anti-fibrotic potential of compounds of interest, evaluation is generally performed in the phase of established fibrosis, i.e., 10–15 days after the initiation, rather than in the early period of bleomycin-induced inflammation. Conversion of proline into hydroxyproline and incorporation into lung collagen occurs as early as 4 days after bleomycin administration. The switch between inflammation and fibrosis occurs in rats around day 9 after bleomycin administration. It was deemed desirable to evaluate activity of LYT-100 during both the inflammatory and fibrotic stages of the model. Accordingly, LYT-100 was administered starting at day 8 following bleomycin administration. Phase I Study [0415] Initially, a Phase I study was conducted to evaluate the effect of bleomycin and LYT-100 on body weight and lung weight in the rat BLM induced lung fibrosis model. The Phase I study design is provided in Table 31. Table 31. BLM Study Design- Phase I G _roup ^Intervention Test Article Test Article Dosing (Day 8- Number of Day 14 Necropsy en ol) [0416] For Groups 1, 2 and 3, bleomycin and vehicle dosing were conducted as indicated in Table 31 (0.45 mg/kg, at 1696 IU/mg of Bleomycin or saline on Day 1, 2, 3, 6 and 7). On days 8 to 13, LYT-100 was dosed via oral gavage once daily. Observations [0417] Animals were observed for a variety of clinical signs and symptoms following bleomycin and LYT-100 dosing. All animals dosed with bleomycin or saline had 100% incidence of abnormal sounds on Days 1, 2, 3, 6 and 7 which was alleviated by the next study day, confirming dosing to the lung. All animals dosed with bleomycin (Group 2 and 3) were observed with respiratory signs from Day 3, with 100% incidence of increased respiratory rate by Day 5. There was no observed increased respiratory rate for Group 1. Respiratory signs are an indication of acute inflammation secondary to bleomycin challenge. Some animals were observed with abnormal gait following initiation of LYT-100 administration on Day 8. The sign disappeared from the animals that showed it ~5 h after it was recorded, and it did not appear in the subsequent dosing occasions. Almost all the animals were noted to be subdued and with decreased activity following LYT-100 dosing on Days 8, 9 and 10, after which point the sign appeared only in Group 3 (Bleomycin / 400 mg/kg LYT-100) on Day 13. When this signa appeared, it disappeared ~5 h after it was recorded. All animals were observed with eyelids closed following initiation of LYT-100 administration on Day 8. The sign disappeared from the animals that showed it ~5 h after it was recorded, and it did not appear in the subsequent dosing occasions. Some animals in Groups 1 and 2 were observed with erected fur following initiation of LYT-100 administration on Day 8 and again on Day 11. The sign disappeared from the animals that showed it ~5 h after it was recorded, and it did not appear in the subsequent dosing occasions. Almost all of the animals were observed salivating following initiation of LYT-100 administration on Day. The sign disappeared from the animals that showed it ~5 h after it was recorded, and it did not appear in the subsequent dosing occasions. Results [0418] Body weight and lung weight were evaluated over the duration of the study to determine the effects of bleomycin and LYT-100 in the model. Body weight gain was impeded in Groups 2 and 3 that received Bleomycin between Days 1 to 9 (FIG. 31). With continued reference to FIG. 31, from Day 10 and until the end of Phase 1 on Day 14, body weight gain in Groups 2 and 3 resumed at a rate similar to Group 1 that received saline. Body weight gain (expressed as % of body weight compared with Day Minus 1 body weights) weight gain was impeded in Groups 2 and 3 that received Bleomycin between Days 1 to 9. From Day 10 and until the end of Phase 1 on Day 14, body weight gain in Groups 2 and 3 resumed at a rate similar to Group 1 that received saline. [0419] Lung weights were heavier in the bleomycin-treated animals (Group 1 vs Group 2 and Group 3 comparisons) as expected from this model. Lung weight ratios (expressed as % of body weight; FIGS. 32A and 32B) were heavier in the bleomycin-treated animals (Group 1 vs Group 2 and Group 3 comparisons) as expected from this model. [0420] Overall, Phase 1 was performed as per protocol and no deviations were considered to affect the integrity of the Phase’s outcome. During Phase 1 (Tolerability), LYT-100 was administered at high (400 mg/kg) and low (250 mg/kg) dose levels once daily (QD) from Day 8 until (including) Day 13 in healthy (high dose) and bleomycin-challenged (low and high dose) rats. LYT-100 was well tolerated by all animals and there was not an obvious correlation between dose level and presence of side effects. Any side effects observed were resolved within ~5 hours after they were noticed and they did not reappear before the following dosing occasions. Based on the animals' body weight developments, clinical signs, lung weights and lung weight to body weight ratios, the tolerability phase determined that LYT-100 administered QD at 400 mg/kg was well-tolerated by both healthy and bleomycin-challenged rats and that this dose levels will be used to examine LYT- 100's therapeutic potential during Phase 2 (Efficacy). Phase II Study [0421] Subsequently, a Phase II study was conducted to evaluate the efficacy of LYT-100 in the rat BLM induced lung fibrosis model. The Phase II study design is provided in Table 32. Table 32. BLM Study Design- Phase II G _roup ^Intervention Test Article Test Article Dosing (Day 8- Number of Day 28 Necropsy and n in Table 32 (0.45 mg/kg, at 1696 IU/mg of Bleomycin or saline on Day 1, 2, 3, 6 and 7). On days 8 to 27, LYT-100 was dosed via oral gavage once daily, and nintedanib was dosed twice daily via oral gavage. Observations [0423] Animals were observed for a variety of clinical signs and symptoms following bleomycin, saline, and LYT-100 dosing. All animals dosed with bleomycin or saline had 100% incidence of abnormal sounds on Days 1, 2, 3, 6 and 7 which was alleviated by the next study day, confirming dosing to the lung. All animals dosed with bleomycin (Groups 5 to 7) were observed with respiratory signs from Day 2, with 100% incidence of increased respiratory rate from Day 4 and until the end of the Study on Day 28. There was no observed increased respiratory rate for Group 4 that received saline. Respiratory signs are an indication of acute inflammation secondary to bleomycin challenge. Results [0424] Body weight and lung weight were evaluated over the duration of the study to determine the effects of bleomycin and LYT-100 in the model. Body weight gain was impeded between Days 1 to 9 in Groups 5, 6, and 7 that received Bleomycin (FIG. 33A). With continued reference to FIG. 33A, from Day 10 and until the end of the efficacy Phase on Day 28, body weight gain in Groups 5 (Bleomycin/Vehicle) and 6 (Bleomycin/LYT-100) resumed and at a rate similar to Group 4 that received Saline/Vehicle. Body weight gain in Group 7 (Blemoycin/Nintedanib) showed modest improvement after Day 8 and the rate of body weight gain remained slower compared with the other groups. Body weight gain (expressed as % of body weight compared with Day 1 body weights) was impeded between Days 1 to 9 in Groups 5, 6, and 7 that received bleomycin (FIG. 33B). With continued reference to FIG.33B, from Day 10 and until the end of the Efficacy Phase on Day 28, % of body weight gain in Groups 5 (Bleomycin/Vehicle) and 6 (Bleomycin/LYT-100) resumed and at a rate similar to Group 4 that received Saline/Vehicle. Percent of body weight gain in Group 7 (Bleomycin/Nintedanib) showed modest improvement after Day 8 and the rate of body weight gain remained slower compared with the other groups. [0425] Mean lung weight increased in the bleomycin-treated rats (Group 4, saline vs Group 5, Bleomycin; FIGS. 34A and 34B). With continued reference to FIGS. 34A and 34B, LYT-100 treatment did not affect mean lung weight in the bleomycin-treated rats (Group 5, Bleomycin/vehicle vs Group 6, Bleomycin LYT-100). Nintedanib-treated rats had reduced lung weight (Group 7 vs Group 5) similar to non-challenged rats (Group 7 vs Group 4). Lung weight ratios (expressed as % percentage of body weight; FIGS. 35A and 35B) increased in the bleomycin-treated rats (Group 4, saline vs Group 5, Bleomycin). LYT-100 treatment did not affect lung weight ratios in the bleomycin-treated rats (Group 5, Bleomycin / vehicle vs Group 6, Bleomycin / LYT-100). There was a trend for lower lung weight ratios in the Nintedanib-treated rats (Group 5 vs Group 7), however this lung ratio remained higher compared with non-challenged rats (Group 7 vs Group 4). [0426] Lung hydroxyproline content was measured for all groups (FIGS.36A, 36B, 37, 38A, 38B, 39). With reference to FIGS. 36A, 36B, 37, 38A, 38B, and 39, total left lung hydroxyproline (μg per left lung) was higher in the bleomycin-treated rats (Group 4, saline vs Group 5, Bleomycin). LYT-100 treatment did not affect total hydroxyproline levels in the bleomycin-treated rats (Group 5, Bleomycin/vehicle vs Group 6, Bleomycin/LYT-100). Lungs from animals treated with Nintedanib had lower levels of total hydroxyproline (Group 7 vs Group 5) but higher than non- challenged rats (Group 7 vs Group 4). Hydroxyproline content (μg per mg of wet lung) was higher in the bleomycin-treated rats (Group 4, saline vs Group 5, Bleomycin). LYT-100 treatment reduced the hydroxyproline content in the bleomycin-treated rats (Group 5, Bleomycin/vehicle vs Group 6, Bleomycin/LYT-100). Nintedanib treatment also reduced hydroxyproline content (Group 7 vs Group 5). [0427] Histopathology studies were performed to evaluate the extent of fibrosis in lung (FIGS. 40A-40D and FIG. 41). Mean and median fibrosis scores increased in the Bleomycin-treated rats (Group 4, saline vs Group 5, Bleomycin). LYT-100 or nintedanib treatment did not affect the fibrosis scores (Group 5, Bleomycin/vehicle vs Group 6, Bleomycin/LYT-100 or Group 7, Bleomycin/Nintedanib). LYT-100 and nintedanib treatments reduced median fibrosis scores (Groups 6 and 7 compared with Group 5). The majority of the fibrosis scores in Group 5 (Bleomycin/vehicle) distributed around Score 2 (39% of the lung sections and 3 (32% of the lung sections). In the LYT-100 and nintedanib treatments (Groups 6 and 7, respectively) the distribution of lung section fibrosis scores shifted towards Scores 1 (33% and 37% respectively) and 2 (36% and 33% respectively). [0428] Overall, Phase 2 was performed as per protocol and no deviations were considered to affect the integrity of the Phase’s outcome. Mirroring Phase 1, LYT-100 administered QD at 400 mg/kg from Day 8 until (including) Day 27 was well tolerated by all animals and any side-effects observed were resolved within ~5 hours after they were noticed and did not reappear before the following dosing occasions. Nintedanib administered twice daily (BID) at 60 mg/kg was used as a reference. LYT-100 did not negatively affect body weight developments, in contrast to nintedanib. LYT-100 reduced lung hydroxyproline content, suggesting reduced presence of connective tissue in the lungs. Consistent with the latter, lungs from LYT-100-treated rats also had reduced median fibrosis scores compared with vehicle controls. Example 12: Exploration of the Efficacy of LYT-100 in Treating Mycocardial Fibrosis and Heart Failure [0429] Patients with heart failure (HF) and evidence of myocardial fibrosis will be randomly assigned to receive LYT-100 or placebo for a period of time. [0430] Inclusion criteria may include one or more of the following: HF with preserved ejection fraction (HFpEF), HF with reduced ejection fraction, HF with mid-range ejection fraction, elevated levels of natriuretic peptides, increased left ventricular end diastolic diameter, systolic dyssynchrony, and elevated filling pressures. The extent of myocardial fibrosis may be measured using using one or more of cardiovascular magnetic resonance, myocardial extracellular volume, and load-independent intrinsic left ventricular myocardial stiffness. [0431] Endpoints for evaluation may include one or more of the following: reduction in myocardial extracellular volume (ECV); increase in 6 minute walk test (6MWT); improved KCCQ score (0–100); improved KCCQ clinical summary score (0–100); improved KCCQ total symptom score (0–100); improved Left ventricular EDVi, ml m ⁻² ; improved Left ventricular ESVi, ml m ⁻² ; improved Left ventricular EF, %; improved Left ventricular mass index, g m ⁻² ; improved Native T1, ms; improved absolute myocardial ECM volume, ml; improved absolute myocardial cell volume, ml; improved E/A ratio; improved Lateral e′, cm s ⁻¹ ; Septal e′, cm s ⁻¹ , improved Average E/e′, cm s ⁻¹ ; improved GLS, %; improved PCr:ATP ratio (BCPSC); improved Right ventricular EDVi, ml m ⁻² ; improved Right ventricular EF (%); improved Right ventricular PAP, mm Hg; improved Left atrium volume, ml; improved Left atrium volume index, ml m ⁻² ; improved Left atrium strain (reservoir), %; improved Left atrium strain (booster), %; improved Left atrium strain (conduit), %.