PureTech Health plc, a clinical-stage biotherapeutics company dedicated to discovering, developing and commercializing highly differentiated medicines for devastating diseases, recently announced the initiation of its global, Phase 2 trial of LYT-100 (deupirfenidone) in Long COVID respiratory complications and related sequelae. LYT-100 is PureTech’s wholly-owned product candidate that is being advanced for the potential treatment of conditions involving inflammation and fibrosis and disorders of lymphatic flow. The initiation follows the completion of a Phase 1 multiple ascending dose and food effect study for LYT-100, which demonstrated favorable proof-of-concept for LYT-100’s tolerability and pharmacokinetic (PK) profile.

Fibrosis and inflammation are common mechanisms across several lung diseases, and there is increasing data that respiratory complications of SARS-CoV-2 (COVID-19), including shortness of breath, begin during the acute phase of illness and may persist as lung fibrosis develops. Similar respiratory complications caused by Severe Acute Respiratory Syndrome (SARS) lasted for years in many survivors. According to a research letter published in the Journal of the American Medical Association (JAMA), more than 40 per cent of COVID-19 survivors assessed in an Italian study still reported shortness of breath an average of 60 days following symptom onset. These data suggest that a significant percentage of COVID-19 survivors may be at risk for respiratory complications and other sequelae, which is a condition that is now colloquially referred to as “Long COVID.”

“COVID-19 is a global public health crisis with severe and long-lasting effects. Patients around the world have reported persistent suffering, including serious respiratory complications that can last for months after the acute infection resolves, and – even with vaccines – there is great a need for treatment options for Long COVID,” said Toby Maher, M.D., Ph.D., professor of clinical medicine and director of interstitial lung disease at Keck School of Medicine of the University of Southern California and the principal investigator on PureTech’s Long COVID Phase 2 trial. “The anti-fibrotic and anti-inflammatory properties of LYT-100 hold potential for treating a range of respiratory conditions, including the long-lasting health burden associated with post-acute COVID-19. I am encouraged by the data generated with LYT-100 to date, and I am excited to be involved in this trial addressing a critically important public health need in the current COVID-19 pandemic.”

LYT-100 is a deuterated, oral small molecule designed to overcome the challenges associated with pirfenidone, an approved and marketed anti-inflammatory and anti-fibrotic drug. Pirfenidone is currently approved for the treatment of idiopathic pulmonary fibrosis (IPF), but it is associated with significant tolerability issues and dose-limiting toxicities. LYT-100, a new chemical entity, retains the pharmacology of pirfenidone but has a differentiated PK profile, which is designed to enable improved tolerability, less frequent dosing and potentially increased efficacy.

PureTech’s global, randomized, double-blind, placebo-controlled Phase 2 trial is designed to evaluate the efficacy, safety and tolerability of LYT-100 in adults with post-acute COVID-19 respiratory complications. The primary endpoint of the trial will be the six-minute walk test distance. Secondary endpoints, including pharmacokinetics, inflammatory biomarkers, imaging and patient-reported outcomes including dyspnea and the 36-Item Short Form Health Survey, will also be evaluated. The study has initiated in both the United States and Europe, and results are expected in the second half of 2021.