30 June 2022 - - US-based clinical-stage biotherapeutics company PureTech Health plc (NASDAQ: PRTC) (LSE: PRTC) has initiated a clinical study of LYT-100 (deupirfenidone), PureTech's wholly-owned therapeutic candidate for the potential treatment of idiopathic pulmonary fibrosis, to support its registration-enabling package, the company said.

LYT-100 is a selectively deuterated form of pirfenidone. Pirfenidone is a proven therapy for IPF, a devastating condition where the favorable tolerability, safety and potentially higher exposure of LYT-100 could have an important impact on patient adherence and outcomes.

IPF is a chronic orphan condition that causes progressive scarring of the lungs, and approximately 130,000 people in the US are living with the disease.

The prognosis of IPF is poor, with the median survival after diagnosis generally estimated at two to five years.

Pirfenidone is approved by the US Food and Drug Administration for IPF, yet there are serious limitations to pirfenidone's clinical use, primarily due to severe gastrointestinal -related tolerability issues.

LYT-100 is designed to retain the potent and clinically validated anti-fibrotic and anti-inflammatory activity of pirfenidone but has demonstrated a highly differentiated pharmacokinetic profile that has translated into improved tolerability in PureTech's ongoing clinical development program.

To date, LYT-100 has been studied in more than 400 subjects and demonstrated a favorable safety and tolerability profile.

In a crossover study in healthy older adults with similar median age to patients with IPF, PureTech showed that approximately 50% fewer subjects experienced GI-related adverse events with LYT-100 compared with pirfenidone (17.4% vs. 34.0%) and substantially fewer subjects experienced AEs with LYT-100 vs. pirfenidone.

PureTech also recently showed that LYT-100 can be safely dosed with a higher total drug exposure than the currently approved dose of pirfenidone, which could translate into improved efficacy over pirfenidone.

The global, randomized, placebo-controlled registration-enabling study is designed to evaluate the efficacy, tolerability, safety and dosing regimen of LYT-100 to help inform the study design for a potential pivotal study and to assess the relative efficacy of LYT-100 compared to pirfenidone.

A total of approximately 240 patients will be randomized 1: 1: 1: 1 to receive either one of two dose levels of LYT-100, the FDA-approved dose of pirfenidone, or a placebo.

One of the LYT-100 arms will evaluate 550 mg three times a day of LYT-100, which has previously demonstrated the comparable exposure as the currently approved dose of pirfenidone (801 mg TID), and the other arm will evaluate an 825 mg TID dose of LYT-100, which has demonstrated higher exposure than the currently approved dose of pirfenidone with the potential for improved efficacy.

The primary objective of the study is to demonstrate a statistically significant and clinically meaningful difference in the slope of decline in a measure of lung function, Forced Vital Capacity, in the LYT-100 treatment arms compared to placebo over six months.

The study will also evaluate safety, tolerability and the slope of FVC decline in the LYT-100 treatment arms compared to pirfenidone, though this analysis is not powered to demonstrate strict non-inferiority.

FVC is an established measure of pulmonary function in IPF and has served as the basis for FDA approval of the currently marketed treatments for IPF.

Topline results from the study are expected by the end of 2023.