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 being developed at PureTech as a potential new standard of care (SOC) for the treatment of idiopathic pulmonary fibrosis (IPF), a progressive and fatal lung disease estimated to affect over 230,000 people across the U.S. and EU5². Only about 25% of IPF patients have ever been treated with either FDA-approved therapeutic (pirfenidone and nintedanib)³, yet combined sales of these medications in 2022 were more than $4 billion⁴, representing a significant market opportunity in IPF and other fibrotic lung diseases.

Despite achieving blockbuster status, the current SOC treatments only modestly slow lung function decline, as their effectiveness is limited by poor tolerability at higher doses. This results in suboptimal efficacy, reduced patient uptake, and poor adherence—all due to a tolerability ceiling that prevents dosing levels that could significantly improve patient outcomes.

Our studies have shown that deupirfenidone may overcome these limitations and – to our knowledge – is the only investigational therapeutic for IPF that has demonstrated the potential to stabilize lung function decline over at least 26 weeks while maintaining safety and tolerability. Beyond IPF, deupirfenidone could also address multiple underserved fibrotic diseases, including progressive fibrosing interstitial lung diseases (ILDs) and other fibrotic conditions.

Program Discovery Process by the PureTech Team
- We acquired deupirfenidone in July 2019 based on insights gained internally and via unpublished findings through our network of collaborators. Deupirfenidone 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 deuteration technology and successfully developed deutetrabenazine (Austedo®), the first deuterated drug to ever receive FDA approval.⁵
- Deupirfenidone is a deuterated form of pirfenidone, one of the two FDA-approved SOC treatments. The strategic replacement of three hydrogen atoms with deuterium at the site of metabolism has been shown to enhance the beneficial pharmacology and clinically-validated efficacy of pirfenidone while maintaining a favorable tolerability profile. This enhancement allows greater levels of drug exposure to be achieved with deupirfenidone compared to the highest approved dose of pirfenidone, without sacrificing tolerability.
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. ¹ 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.⁶
- Despite only about 25% of IPF patients in the U.S. ever being treated with either standard-of-care drug,³ 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.
- Based on robust Phase 2b data, we believe that deupirfenidone has multi-billion-dollar revenue potential for several key reasons:
  - It has the potential to deliver best-in-class efficacy.
  - Its profile may expand the IPF market by increasing patient uptake and adherence.
  - With its highly differentiated efficacy and safety profile, deupirfenidone has blockbuster potential, with additional upside in other ILDs.
- 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.
  - ELEVATE IPF was a global, 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.
    - Deupirfenidone 825 mg TID demonstrated the potential to stabilize lung function decline. Patients treated with deupirfenidone 825 mg TID experienced an FVC decline of -21.5 mL over 26 weeks, which is comparable to the expected natural lung function decline in healthy adults aged 60 and older.
    - The deupirfenidone arms, 550mg TID and 825mg TID, exhibited dose-dependent efficacy with an FVC reduction from baseline of -80.7mL and -21.5mL, respectively. The placebo and pirfenidone arms responded as reported in previous studies with an FVC reduction from baseline of -112.5mL and -51.6mL, respectively. The performance of these control arms and the dose-dependent response of the deupirfenidone arms suggests that the efficacy of deupirfenidone was not likely a chance observation.
  - The deupirfenidone 825 mg TID arm had an effect size, compared to placebo, that was 50% greater than that seen with pirfenidone (80.9% vs. 54.1%, respectively). Additionally, preliminary pharmacokinetic results indicate that deupirfenidone 825 mg TID achieved ~50% higher exposure than pirfenidone 801 mg TID, corresponding with the greater efficacy results demonstrated with deupirfenidone 825 mg TID.
  - Deupirfenidone was generally well-tolerated with a favorable adverse event profile at both doses studied.
  - 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.
  - The Phase 2b open label extension (OLE) trial is ongoing. Patients administered deupirfenidone in the blinded portion of the study continued their treatment and dose in the open label extension. Patients administered pirfenidone or placebo in the blinded portion of the study were re-randomized to one of the deupirfenidone doses in the OLE. 170 patients (90% of those eligible) from the blinded portion of the study continued into the OLE. As of March 14, 2025, 140 patients have continued in the OLE, with 85 patients having received at least 52 weeks of treatment with deupirfenidone. Preliminary data from those receiving deupirfenidone 825 mg TID indicate that the significant slowing of lung function decline observed in Part A of the trial has been sustained through 52 weeks of treatment, supporting the durability of the treatment effect with this dose and its potential to stabilize lung function decline over time. Detailed OLE results will be presented at an upcoming scientific forum.
- 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
- We will present additional details from the Phase 2b trial at the American Thoracic Society International Conference in May 2025.
- We intend to discuss the results from the Phase 2b trial with the FDA and are targeting a meeting before the end of Q3 2025, with the goal of initiating a Phase 3 clinical trial in IPF by the end of 2025. We anticipate providing further guidance later this year following the finalization of the trial design and FDA interactions.
Intellectual Property
- As of December 31, 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 also have one US patent and one US patent application in-licensed from Auspex directed to formulations of deuterated pirfenidone, both of which expire in 2035. The deupirfenidone IP portfolio further comprises numerous US and foreign patent applications, which are solely owned by PureTech. This IP includes 13 pending US patent applications and 39 foreign 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 2045, exclusive of possible patent term adjustments or extensions.

Deupirfenidone is an investigational drug not approved by any regulatory authority.

² GlobalData Epidemiology and Market Size Search. EU5=United Kingdom, France, Germany, Italy and Spain.

³ 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

⁴ Roche 2022 Annual Report and Boehringer Ingelheim 2022 Financial Results.

⁵ Austedo was first approved by the FDA for the treatment of chorea associated with Huntington’s disease in adults in 2017.

⁶ 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.

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.