PureTech Regulatory News (PRTC)

October 11, 2023

PureTech Health plc

PureTech Presents Data from LYT-100 (Deupirfenidone) Trial in Healthy Older Adults at CHEST Annual Meeting

LYT-100 demonstrated ~50% improvement versus pirfenidone in key adverse events at a comparable exposure level, which may lead to better patient compliance and improved treatment outcomes in IPF

LYT-100 also demonstrated favorable tolerability at a 43% higher exposure level, supporting the exploration of a higher dose for potentially enhanced efficacy in IPF

Results informed dose selection for ongoing, global Phase 2b ELEVATE IPF trial, with topline data expected in 2024

PureTech Health plc (Nasdaq: PRTC, LSE: PRTC) ("PureTech" or the "Company"), a clinical-stage biotherapeutics company dedicated to changing the lives of patients with devastating diseases, presented clinical data supporting the differentiated profile of LYT-100 (deupirfenidone) at the CHEST Annual Meeting in Honolulu, Hawaii.

The presentation expands on data from a completed trial of LYT-100 in healthy older adults, which informed the two doses selected for the ongoing, global Phase 2b dose-ranging trial of LYT-100 (ELEVATE IPF) in patients with idiopathic pulmonary fibrosis (IPF). In addition to supporting the improved tolerability of LYT-100 versus the FDA-approved dose of pirfenidone, the data provide insights into the selection of the higher dose of LYT-100 that is also being evaluated in ELEVATE IPF.

The trial showed that a 550 mg dose of LYT-100 given three times daily (TID) provided bioequivalent drug exposure to the FDA-approved dose of pirfenidone, 801 mg TID. LYT-100 also demonstrated a 24% lower peak drug concentration than pirfenidone, which is a key factor generally associated with tolerability. As previously announced, this dose also achieved an approximately 50% reduction in participants experiencing gastro-intestinal (GI) and central nervous system (CNS)-related adverse events (AEs) compared to those taking pirfenidone.

Additionally, the data showed that a higher dose of LYT-100 (824 mg TID), which achieved a 43% higher exposure level, was well-tolerated with no additional incidence of GI or CNS AEs when titrated up from LYT-100 550 mg TID in this trial, supporting the potential to provide enhanced efficacy with favorable tolerability in IPF. This hypothesis is supported by Phase 3 data with pirfenidone that showed a dose-response effect on forced vital capacity and survival in people with IPF.[1] PureTech is therefore investigating the efficacy and tolerability of LYT-100 at 550 mg TID and 825 mg TID in the Phase 2b ELEVATE IPF trial.

"These data highlight the potential for LYT-100 to improve both the treatment experience for people with IPF and - most importantly - enable them to stay on treatment longer and at an efficacious dose, which should improve their clinical outcomes," said Julie Krop, M.D., Chief Medical Officer of PureTech Health. "Our goal with the ELEVATE IPF trial is to validate the ability of LYT-100 to deliver a more tolerable treatment with equivalent efficacy to pirfenidone at one dose while also exploring the potential for enhanced efficacy at a higher dose." 

"Tolerability is a major challenge with the currently available IPF treatments, and it often results in both temporary and permanent dose reductions, premature discontinuation and a reluctance for patients to even begin treatment," said Dr. Toby Maher, M.D., Ph.D., Professor of Medicine and Director of Interstitial Lung Disease at Keck School of Medicine, University of Southern California, Los Angeles, who is presenting the poster at CHEST and is an investigator in the ELEVATE IPF trial. "The unique profile of deupirfenidone may offer not only improved tolerability, but it also provides us with the opportunity to assess whether a higher dose is associated with improved efficacy - a strategy that has not been possible to test with pirfenidone due to its poor tolerability. This may benefit both patients currently taking standard-of-care antifibrotic drugs as well as the 75% of people with IPF in the US who are not on treatment. The IPF treatment landscape is in desperate need of new therapeutic approaches that can be used either as monotherapies or as the backbone for combination therapy, and I look forward to the results of the ELEVATE IPF trial."

About Idiopathic Pulmonary Fibrosis (IPF)

Idiopathic pulmonary fibrosis (IPF) is a rare, progressive and fatal lung disease with a median survival of 2-5 years.[2] Pirfenidone is one of only two drugs approved to treat IPF, and it has been shown to improve survival by approximately three years compared to supportive care alone.2 However, tolerability issues with both of the standard-of-care drugs result in patients discontinuing treatment or reducing their dose. As a result, nearly three out of every four people with IPF forego treatment with these otherwise efficacious medicines.[3]

About LYT-100 (Deupirfenidone)

LYT-100 (deupirfenidone) is being advanced for the treatment of conditions involving inflammation and fibrosis, including idiopathic pulmonary fibrosis (IPF). It is a deuterated form of pirfenidone that is designed to retain the beneficial pharmacology and clinically-validated efficacy of pirfenidone with a highly differentiated pharmacokinetic (PK) profile. This PK profile has translated into favorable tolerability as demonstrated across multiple clinical studies in more than 400 individuals.

Pirfenidone is one of the two standard-of-care treatments approved for IPF, along with nintedanib, both of which are efficacious but associated with significant tolerability issues. These tolerability issues result in treatment discontinuations and/or dose reductions below the FDA-approved dose, thereby limiting the effectiveness of these otherwise efficacious medicines. With LYT-100, PureTech aims to deliver better outcomes for patients by enabling individuals to maintain the same or higher doses for longer. PureTech believes LYT-100 has the potential both to supplant the current standard-of-care treatments and to serve a larger market of patients who are unable to tolerate current therapies.

For more information on the global, Phase 2b ELEVATE IPF trial, visit clinicaltrials.gov (NCT05321420). Those in the United States may also visit ELEVATEIPF.com.

About PureTech Health

PureTech is a clinical-stage biotherapeutics company dedicated to giving life to new classes of medicine to change the lives of patients with devastating diseases. The Company has created a broad and deep pipeline through its experienced research and development team and its extensive network of scientists, clinicians and industry leaders that is being advanced both internally and through its Founded Entities. PureTech's R&D engine has resulted in the development of 27 therapeutics and therapeutic candidates, including two (Plenity® and EndeavorRx®) that have received both US FDA clearance and European marketing authorization and a third (KarXT) that has been filed for FDA approval. A number of these programs are being advanced by PureTech or its Founded Entities in various indications and stages of clinical development, including registration enabling studies. All of the underlying programs and platforms that resulted in this pipeline of therapeutic candidates were initially identified or discovered and then advanced by the PureTech team through key validation points.

For more information, visit www.puretechhealth.com or connect with us on X, formerly known as Twitter, @puretechh.

Cautionary Note Regarding Forward-Looking Statements

This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements contained in this press release that do not relate to matters of historical fact should be considered forward-looking statements, including without limitation those statements that relate to our hypotheses and expectations around the treatment potential associated with LYT-100, including potential tolerability and efficacy benefits as compared to the current standard of care for IPF patients, our product candidates and approach towards addressing major diseases, and our future prospects, developments, and strategies. The forward-looking statements are based on current expectations and are subject to known and unknown risks, uncertainties and other important factors that could cause actual results, performance and achievements to differ materially from current expectations, including, but not limited to, those risks, uncertainties and other important factors described under the caption "Risk Factors" in our Annual Report on Form 20-F for the year ended December 31, 2022 filed with the SEC and in our other regulatory filings. These forward-looking statements are based on assumptions regarding the present and future business strategies of the Company and the environment in which it will operate in the future. Each forward-looking statement speaks only as at the date of this press release. Except as required by law and regulatory requirements, we disclaim any obligation to update or revise these forward-looking statements, whether as a result of new information, future events or otherwise.