LYT-100

Dedicated to advancing transformative treatments for people with serious respiratory diseases

Positive topline Phase 2b results for deupirfenidone announced in December 2024. Read the press release HERE.

New publication in BMC Pulmonary Medicine highlighting untold experiences of people living with IPF. Read 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.

< PORTFOLIOS

Conditions involving inflammation and fibrosis, including idiopathic pulmonary fibrosis

100% Equity

Phase 2b completed

Description

Conditions involving inflammation and fibrosis, including idiopathic pulmonary fibrosis

ECONOMIC INTEREST¹

100% Equity

Stage of Development

Phase 2b completed

¹ We have an active IND on file with the FDA for deupirfenidone. The FDA and corresponding regulatory authorities will ultimately review our clinical results and determine whether deupirfenidone is safe and effective. No regulatory agency has made any such determination that deupirfenidone 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). 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 May 2025, we delivered a late-breaking, oral presentation at the 2025 American Thoracic Society (ATS) International Conference in San Francisco. The presentation provided further insights into the successful Phase 2b ELEVATE IPF trial of deupirfenidone (LYT-100), highlighting the strength and durability of deupirfenidone’s treatment effect through at least 52 weeks while maintaining favorable tolerability in patients living with IPF.
  - Preliminary data from the ongoing open-label extension (OLE) study suggest that this treatment effect is durable out to at least 52 weeks. As of May 9, 2025, a total of 101 patients had received at least 52 weeks of treatment with deupirfenidone. Those in the deupirfenidone 825 mg TID arm experienced a decline in FVC of -32.8 mL over the 52-week period,⁷ which is similar to the expected natural decline in lung function in healthy older adults over one year (approximately -30.0 mL to -50.0 mL).⁸ These new data provide additional support for the durability of the treatment effect observed with this dose and reinforce its potential to stabilize lung function decline over time, while maintaining favorable safety and tolerability.
- In May 2025, we announced the publication of new research in BMC Pulmonary Medicine that provides a comprehensive view into the lived experiences of people with IPF. The study identifies critical barriers to treatment, opportunities for improved community engagement, and the need for patient-centered approaches in the development of new therapeutics.
  Read the press release HERE for the summary of key research highlights.
  The full paper, titled "Perspectives of People Living with Idiopathic Pulmonary Fibrosis: A Qualitative and Quantitative Study," is available on the journal's website HERE.
- 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
- Expects to meet with the FDA by the end of the third quarter of 2025
- Additional findings from the OLE to be shared at the European Respiratory Society (ERS) International Congress in September 2025, including “switch data” from participants who transitioned to deupirfenidone in OLE after initially receiving placebo or pirfenidone during the 26-week blinded portion of the Phase 2b trial
- Pending FDA alignment, aims to initiate Phase 3 trial in IPF in the first half of 2026
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.

⁷ Analysis conducted using the same methodology to assess rate of decline in FVC at 26 weeks from the double-blind portion of the trial. In the double-blind portion of the trial, efficacy analysis used a random coefficient regression model with absolute FVC including baseline as response variable and week, treatment and interaction between week and treatment as fixed effect. The analysis was performed based on the predefined Full Analysis Set.

⁸ Valenzuela, C., Bonella, F., Moor, C., Weimann, G., Miede, C., Stowasser, S., Maher, T. (2024). Decline in forced vital capacity (FVC) in subjects with idiopathic pulmonary fibrosis (IPF) and progressive pulmonary fibrosis (PPF) compared with healthy references; Poster presented at the European Respiratory Society International Congress, Vienna, Austria; and Luoto, J., Pihlsgård, M., Wollmer, P., & Elmståhl, S. (2019). Relative and absolute lung function change in a general population aged 60-102 years. The European Respiratory Journal, 53(3), 1701812. https://doi.org/10.1183/13993003.01812-2017

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.

Program Supplemental Slides