LYT-100

Conditions involving inflammation and fibrosis, including idiopathic pulmonary fibrosis

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Our programs ¹

Discovery

Preclinical

Phase 1

Phase 2

Phase 3

LYT-100

Deupirfenidone

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

LYT-100 (deupirfenidone) is currently in development for idiopathic pulmonary fibrosis (IPF), which is a rare, progressive and fatal disease. LYT-100 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. LYT-100 is a deuterated form of pirfenidone and is designed to retain the beneficial pharmacology and clinically-validated efficacy of pirfenidone with a highly differentiated pharmacokinetic (PK) profile. In multiple clinical trials, LYT-100 has demonstrated a favorable tolerability profile, which may keep patients on treatment longer to enable more optimal disease management.

Key Points of Innovation & Differentiation
- LYT-100 has shown a 50% reduction in gastro-intestinal (GI) related adverse events (AEs) in a crossover trial versus pirfenidone in healthy older adults. We believe the differentiated tolerability profile of LYT-100 will address one of the key reasons that patients on current standard of care dose reduce, discontinue or switch from otherwise efficacious treatments.^1,2 We have also been able to dose LYT-100 at a higher exposure level, potentially enabling improved efficacy. Given this, we believe LYT-100 has the potential to become standard of care and to become a backbone therapy in the treatment for IPF.
- 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.³ 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
Fibrosis and Inflammation-Related Lung Diseases
- There are over 232,000 people in the US and EU5 living with IPF.^4,5 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.³
- Only about 25% of IPF patients are currently being treated with either standard of care drug,² yet Esbriet and Ofev achived blockbuster status, representing a significant market opportunity for LYT-100 in IPF and other fibrotic lung diseases.
- We engaged an independent third-party market research firm to survey pulmonologists who actively treat IPF patients to assess the commercial opportunity for LYT-100 in IPF. The surveyed pulmonologists noted an unmet need for treatments with improved tolerability profiles, and 80-90% highlighted GI AEs as the primary reason their patients discontinue or dose reduce on current treatments. Pulmonologists said they would prescribe a new product with an improved tolerability profile and comparable efficacy to nearly 44% of their new IPF patients, and nearly 80% indicated they would prescribe it more than pirfenidone. Based on this survey, if approved by the FDA, LYT-100 would be expected to have a significant impact on the IPF market if the improved tolerability profile seen in the Phase 1 crossover study is reproduced in later stage trials and demonstrates the same or enhanced efficacy compared to standard of care.
- Pirfenidone has also shown activity in patients with non-IPF PF-ILDs, and other organ system fibrosis.
Milestones Achieved & Development Status
IPF
- In April 2024, we announced completion of enrollment in the ELEVATE IPF Phase 2b clinical trial evaluating LYT-100 in patients with IPF. ELEVATE IPF is a global, randomized, double-blind, placebo-controlled Phase 2b clinical trial designed to evaluate the efficacy, tolerability, safety and dosing regimen of LYT-100 in patients with IPF compared to placebo. The trial has four arms: placebo, pirfenidone, a dose of LYT-100 with comparable exposure to the FDA-approved dose of pirfenidone and a dose of LYT-100 with a higher level of exposure than the FDA-approved dose of pirfenidone. The primary endpoint is the rate of decline in Forced Vital Capacity (FVC) for the combined LYT-100 arms versus placebo over the 26-week treatment period using a prespecified Bayesian approach. Other key endpoints include tolerability measures, biomarkers and patientreported outcomes. Both doses of LYT-100 will be compared to pirfenidone, though the trial is not powered to show a statistical difference in efficacy between LYT-100 and pirfenidone.
- In October 2023, we presented expanded data at the CHEST Annual Meeting 2023 from a completed trial of LYT-100 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 LYT-100 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 LYT-100 GI-related AE compared to subjects treated with pirfenidone (17.4% vs. 34.0%). In an additional clinical trial, LYT-100 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
- Topline results from ELEVATE IPF are expected by the end of 2024. A streamlined development program is planned using the same endpoints that have supported past approvals. Pending positive clinical and regulatory feedback, the program will advance into a Phase 3 trial. We believe the results of the Phase 2b trial, together with a Phase 3 trial, could serve as the basis for registration in the U.S. and other geographies.
Intellectual Property
- As of June, 2024, the LYT-100 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 LYT-100 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 LYT-100, 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 Cottin, V., Koschel, D., Günther, A., Albera, C., Azuma, A., Sköld, C. M., Tomassetti, S., Hormel, P., Stauffer, J., Kirchgaessler, K., & Maher, T. M. (2018). Long-term safety of pirfenidone: results of the prospective, observational PASSPORT study. ERJ Open Research, 4(4), 00084–02018. https://doi.org/10.1183/23120541.00084-2018

² 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

³ 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.

⁴ United Kingdom, France, Germany, Italy and Spain.

⁵ GlobalData Epidemiology and Market Size Search.

LYT-100 maintains the pharmacology of pirfenidone but has a highly differentiated PK profile as well as favorable tolerability, as demonstrated by data from multiple human clinical studies. Based on prior work with pirfenidone, a substantial amount of preclinical and clinical data support LYT-100’s broader potential in inflammatory and fibrotic conditions, including IPF.