LYT-100

For the potential treatment of idiopathic pulmonary fibrosis (IPF)

Positive topline Phase 2b results announced in December 2024.
See the press release HERE.

For the potential treatment of idiopathic pulmonary fibrosis (IPF)

Positive topline Phase 2b results announced in December 2024.
See the press release HERE.

< PROGRAMS

Our programs ¹

Discovery

Preclinical

Phase 1

Phase 2

Phase 3

Deupirfenidone

LYT-100

Idiopathic pulmonary fibrosis (IPF)

Phase:
2

Initial Indications:
IPF

Patient Population:

~120K in US

~110K in EU5

Key Differentiations:

Therapeutic candidate being advanced for the potential treatment of conditions involving inflammation and fibrosis, including idiopathic pulmonary fibrosis (IPF). Also being advanced under the Animal Rule for medical countermeasures; plans underway to study LYT-100 in progressive fibrosing interstitial lung disease (PF-ILDs) as well as other fibrotic conditions where there is human data with pirfenidone suggestive of clinical benefit.

More about LYT-100

Phase completed

Phase in progress

¹ We have an active IND on file with the FDA for LYT-100. The FDA and corresponding regulatory authorities will ultimately review our clinical results and determine whether our wholly-owned therapeutic candidates are safe and effective. No regulatory agency has made any such determination that LYT-100 is safe or effective for use by the general public for any indication.

Conditions involving inflammation and fibrosis, including idiopathic pulmonary fibrosis

Deupirfenidone (LYT-100) is currently in development for the treatment of idiopathic pulmonary fibrosis (IPF), which is a rare, progressive and fatal lung disease. Deupirfenidone is a deuterated form of pirfenidone and is designed to retain the beneficial pharmacology and clinically-validated efficacy of pirfenidone but with a differentiated pharmacokinetic and tolerability profile. Deupirfenidone has demonstrated strong, consistent, and durable efficacy and a favorable tolerability profile in PureTech’s Phase 2b ELEVATE IPF clinical trial.

Deupirfenidone also has the potential to address multiple underserved diseases, including progressive fibrosing interstitial lung diseases, a group of lung diseases closely related to IPF, as well as other fibrotic conditions where there is human data with pirfenidone suggestive of clinical benefit.

Key Points of Innovation & Differentiation
- Deupirfenidone slowed lung function decline in patients with IPF as measured by forced vital capacity (FVC) in the Phase 2b ELEVATE IPF trial. It also demonstrated favorable tolerability at both doses studied. The strength of the data to date suggests that deupirfenidone has the potential to serve as a new standard of care.
- Pirfenidone (Esbriet®) is approved for the treatment of IPF in the US and other countries. Pirfenidone has been shown to slow the decline of lung function and research suggests it extends life by approximately 2.5 years in patients with IPF.¹ It is one of two standard-of-care treatments for IPF, with nintedanib (OFEV®) being the other.
Program Discovery Process by the PureTech Team
- We acquired LYT-100 in July 2019 based on insights gained internally and via unpublished findings through our network of collaborators. LYT-100 was originally developed by Auspex Pharmaceuticals, Inc. (Auspex), where our Chief Executive Officer, Bharatt Chowrira, Ph.D., J.D., served as Chief Operating Officer. Auspex (now a wholly owned subsidiary of Teva Pharmaceuticals), pioneered the deuteration technology and successfully developed deutetrabenazine (Austedo®), the first deuterated drug that received FDA approval.
Patient Need & Market Potential
- There are over 232,000 people in the US and the EU5 countries (Italy, Spain, France, Germany and the United Kingdom) living with IPF. ^2,3 IPF is a progressive condition characterized by irreversible scarring of the lungs that makes it difficult to breathe. The prognosis of IPF is poor, with the median survival after diagnosis generally estimated at two to five years.¹
- Despite only about 25% of IPF patients in the U.S. currently being treated with either standard-of-care drug,⁴ Esbriet (pirfenidone) and Ofev (nintedanib) have achieved blockbuster status. Deupirfenidone has the potential to serve as a new standard-of-care and/or expand the treated patient population, representing a significant market opportunity in IPF and other fibrotic lung diseases.
- Pirfenidone has also shown activity in patients with non-IPF PF-ILDs, and other organ system fibrosis.
Milestones Achieved & Development Status
- In December 2024, we announced positive topline results from the ELEVATE IPF Phase 2b clinical trial evaluating deupirfenidone in patients with IPF. The randomized, double-blind, active- and placebo-controlled, dose-ranging trial evaluated deupirfenidone at two dose levels (550 mg and 825 mg) three times a day (TID) over 26 weeks in patients with IPF. The trial achieved its primary endpoint based on the prespecified Bayesian analysis, with a 98.5% posterior probability. This means there is a 98.5% probability that the pooled deupirfenidone arms were superior to placebo in slowing the rate of lung function decline in people with IPF, as measured by FVC at 26 weeks. The trial also successfully demonstrated a dose-dependent response. The deupirfenidone 825 mg TID arm reduced lung function decline to near-physiologic levels over 26 weeks and had an effect size, compared to placebo, that was approximately 50% greater than that seen with pirfenidone. Deupirfenidone was generally well-tolerated with a favorable adverse event profile at both doses studied.
- In October 2023, we presented expanded data at the CHEST Annual Meeting 2023 from a completed trial of deupirfenidone in healthy older adults, which informed the two doses selected for the ongoing Phase 2b trial (ELEVATE IPF). In addition to supporting the improved tolerability of LYT-100 versus the FDA-approved dose of pirfenidone, the new data presented supported the selection of a higher dose of deupirfenidone with the potential for improved efficacy that is now being evaluated in ELEVATE IPF.
- In January 2022, we announced results from a randomized, double-blind crossover trial in healthy older adults demonstrating that approximately 50% fewer subjects treated with deupirfenidone GI-related AEs compared to subjects treated with pirfenidone (17.4% vs. 34.0%). In an additional clinical trial, deupirfenidone also demonstrated that it 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.
Expected Milestones
- Initiation of Phase 3 by the end of 2025.
Intellectual Property
- As of June 2024, the deupirfenidone patent portfolio includes 32 active patents acquired from Auspex, which provide broad coverage of compositions of matter, formulations and methods of use for deuterated pirfenidone, including the deupirfenidone compound. This IP estate comprises six issued US patents and 26 patents issued in 23 foreign jurisdictions, which are expected to expire in 2028 and may be extended by up to five years. In addition, we have in-licensed one US patent and one US patent application from Auspex directed to formulations of deuterated pirfenidone, both of which expire in 2035, and also filed additional patent applications on deupirfenidone, including five (5) pending US patent applications, 31 foreign applications and three (3) international PCT applications directed to the use of deuterated pirfenidone, including deupirfenidone, for the treatment of a range of conditions. Any issued patents claiming priority to these applications are expected to expire in 2039 through 2044, exclusive of possible patent term adjustments or extensions.

¹ Fisher, M., Nathan, S. D., Hill, C., Marshall, J., Dejonckheere, F., Thuresson, P., & Maher, T. M. (2017). Predicting Life Expectancy for Pirfenidone in Idiopathic Pulmonary Fibrosis. Journal of Managed Care & Specialty Pharmacy, 23(3-b Suppl), S17 -S24. https://doi.org/10.18553/jmcp.2017.23.3-b.s17.

² United Kingdom, France, Germany, Italy and Spain.

³ GlobalData Epidemiology and Market Size Search.

⁴ Dempsey, T., Payne, S. C., Sangaralingham, L. R., Yao, X., Shah, N., & Limper, A. H. (2021). Adoption of the Antifibrotic Medications Pirfenidone and Nintedanib for Patients with Idiopathic Pulmonary Fibrosis. Annals of the American Thoracic Society, 18(7), 1121–1128. https://doi.org/10.1513/annalsats.202007-901oc

Deupirfenidone is currently in development for the treatment of idiopathic pulmonary fibrosis (IPF). It is a deuterated form of pirfenidone, which is one of the two standard-of-care treatments approved to treat IPF, in addition to nintedanib. Deuteration is intended to make deupirfenidone break down more slowly in the body than pirfenidone. In PureTech’s Phase2b trial, deupirfenidone demonstrated the beneficial pharmacology and clinically-validated efficacy of pirfenidone and the high dose of deupirfenidone demonstrated strong, consistent and durable efficacy with a favorable tolerability profile.