• We acquired LYT-100 in July 2019 based on insights gained internally and via unpublished findings through our network of collaborators.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 President and Chief Business, Finance and Operating 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.

• There are approximately 120,000 people in the US and 110,000 people in the EU5 living with IPF.⁶ 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.⁴
• Only about 25% of IPF patients are currently being treated with either standard of care drug,³ yet combined sales of Esbriet and Ofev in 2022 were more than $4 billion, representing a significant market opportunity in IPF and other fibrotic lung diseases.⁷
• In 2022, 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.

• In June 2022, we announced the initiation of ELEVATE IPF, a Phase 2b clinical trial of LYT-100 for the potential treatment of IPF. The global, randomized, placebo-controlled registration-enabling trial is designed to evaluate the efficacy, tolerability, safety and dosing regimen of LYT-100. The primary objective of the trial is to demonstrate a clinically meaningful difference versus placebo in a measure of lung function, Forced Vital Capacity (FVC), over 6 months. The trial will also assess the relative efficacy of two doses of LYT-100, one with comparable exposure to the approved dose of pirfenidone and one with a higher level of exposure that has the potential for improved efficacy. Both doses will be compared to pirfenidone.
• 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 (deupirfenidone) experienced gastrointestinal (GI)-related adverse events (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.
• In May 2022, we presented additional data from the healthy older adults study at the American Thoracic Society 2022 International Conference. Notably, LYT-100 at 550 mg TID (fed state) met the criteria for bioequivalence for exposure compared to the FDA-approved dosage of pirfenidone – 801 mg TID – but with a lower Cmax. Higher dosages of LYT-100 may provide enhanced antifibrotic and anti-inflammatory activity.

Medical Countermeasures

• LYT-100 is also being developed for medical countermeasures under FDA Animal Rule,¹which allows for the approval of drugs based on well-controlled animal models when human efficacy studies are not ethical or feasible. PureTech may be eligible to receive a priority review voucher from the FDA for a medical countermeasure application upon approval.

• Topline results from the Phase 2b dose-ranging trial of LYT-100 in patients with IPF are expected in 2024. We also plan to pursue a streamlined development program for LYT-100 in IPF, capitalizing on efficiencies of the 505(b)(2) pathway. Pending positive clinical and regulatory feedback, the program will advance into a Phase 3 study. We believe the results of the Phase 2b study, together with a Phase 3 study, could serve as the basis for registration in the US and other geographies.

• As of December 31, 2022, 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 which expires in 2035, and also filed additional patent applications on deupirfenidone, including 19 pending US patent applications, 17 foreign applications and one international PCT application directed to the use of deuterated pirfenidone, including LYT-100, for the treatment of a range of conditions. As of July 2023, any issued patents claiming priority to these applications are expected to expire in 2039 through 2044, exclusive of possible patent term adjustments or extensions or other exclusivities.