7 January 2022 - - US-based clinical-stage biotherapeutics company PureTech Health plc (NASDAQ: PRTC) (LSE: PRTC) has posted results from a randomized, double-blind crossover study in healthy older adults demonstrating that approximately 50% fewer subjects treated with PureTech's LYT-100 (deupirfenidone) experienced gastrointestinal -related adverse events compared to subjects treated with pirfenidone (17.4% vs. 34.0%), the company said.

Pirfenidone is approved by the US Food and Drug Administration for the treatment of idiopathic pulmonary fibrosis, an orphan disease that is chronic and progressive resulting in significant morbidity and mortality.

Based on these results, additional data generated from PureTech's robust LYT-100 clinical program and recent regulatory feedback, the company intends to advance LYT-100 into late-stage clinical development for the treatment of IPF, beginning with a dose-ranging study evaluating six months of treatment with LYT-100 initiating in the first half of 2022.

PureTech believes the results of this study, together with a Phase 3 study, could serve as the basis for registration in the US.

LYT-100 is a selectively deuterated form of pirfenidone that is designed to retain the potent and clinically-validated anti-fibrotic and anti-inflammatory activity of pirfenidone with a differentiated pharmacokinetic profile that has translated into favorable tolerability, as demonstrated by data from multiple human clinical studies.

Pirfenidone is one of the two standard of care treatments approved for IPF, along with nintedanib, both of which are efficacious but associated with significant GI-related tolerability issues.

Tolerability issues associated with pirfenidone result in treatment discontinuations and/or dose reductions below the FDA-approved dose of 801 mg three times a day, thereby limiting its effectiveness in patients with IPF.

Based on a recently published observational study and independent market research, only about 26% of IPF patients are treated with the current standard of care treatments despite their proven efficacy.

This suggests that a vast majority of IPF patients are not currently being treated, and further supports the significant need for new, tolerable treatment options.

A previous clinical study comparing a lower dose of pirfenidone than the FDA-approved dose noted a dose-efficacy response, but whether doses higher than the marketed dose can achieve increased efficacy has not been adequately explored in patients with IPF.

In the upcoming dose-ranging study, PureTech also plans to investigate LYT-100 in IPF patients at a dose with a higher total drug exposure than the currently approved dose of pirfenidone to see if higher exposure results in improved efficacy.

The double-blind, randomized, crossover study evaluated the tolerability of LYT-100 550 mg TID versus pirfenidone 801 mg TID in 49 healthy older adults aged 60-79, an age group consistent with that of the IPF patient population.

The dose of LYT-100 used in this study was selected based on pharmacokinetics and modeling data from prior studies, which together suggest that 550 mg TID results in similar exposure levels achieved with 801 mg TID of pirfenidone.

The study showed that 38% fewer subjects treated with LYT-100 experienced any AEs compared with those treated with pirfenidone (30.4% vs. 48.9%).

Additionally, approximately 50% fewer subjects experienced GI-related AEs with LYT-100 compared with pirfenidone (17.4% vs. 34.0%), most notably nausea (15.2% with LYT-100 vs. 29.8% with pirfenidone), which is the most common AE associated with pirfenidone.

No serious AEs were reported in the study, and there was one AE-related discontinuation in each arm, the company said.

Though not powered to show statistical significance, this study provides evidence that LYT-100 has the potential to offer an important tolerability advantage over pirfenidone and helps to inform PureTech's development plans with this therapeutic candidate in IPF.

Based on the data generated to date and discussions with the FDA, PureTech plans to pursue a streamlined development program for LYT-100 in IPF, capitalizing on efficiencies of the 505(b) (2) pathway.

The dose-ranging study, which is anticipated to begin in the first half of 2022, will enroll approximately 250 treatment naïve patients to evaluate LYT-100 efficacy relative to placebo and compare relative tolerability and efficacy for pirfenidone.

The planned study will evaluate TID dosing of LYT-100 taken with meals.

The TID regimen is designed to reduce the maximal drug concentration, known to correlate with GI-related AEs with pirfenidone, while maintaining the same or higher overall systemic exposure as pirfenidone.

Pending positive clinical and regulatory feedback, the program will advance into a Phase 3 study.

To oversee the LYT-100 development program in IPF, Paul Ford, M.D., Ph.D., has joined PureTech as SVP of Clinical Development.

Dr. Ford is an experienced clinical pulmonologist with more than 20 years of research and development expertise dedicated to IPF and other respiratory conditions.

To date, LYT-100 has been studied in more than 400 subjects and demonstrated a favorable safety profile as part of PureTech's ongoing development work and indication prioritization.

The company has conducted multiple Phase 1 studies to further evaluate the PK, dosing and tolerability of LYT-100 in healthy volunteers and healthy older adults, the results of which have helped inform PureTech's development plans in IPF.

These studies, as well as other ongoing studies, will also help to inform potential future development plans in other indications beyond IPF.

LYT-100 is PureTech's most advanced therapeutic candidate from within its Wholly Owned Pipeline.

A deuterated form of pirfenidone, an approved anti-inflammatory and anti-fibrotic drug, LYT-100 is being advanced for the potential treatment of conditions involving inflammation and fibrosis, including lung disease (IPF and Long COVID respiratory complications and related sequelae) and disorders of lymphatic flow, such as lymphedema.

PureTech is also exploring the potential evaluation of LYT-100 in other inflammatory and fibrotic conditions such as myocardial and other organ system fibrosis based on the strength of existing clinical data around the use of pirfenidone in these indications.