28 May 2020 - - US-based biotherapeutics company PureTech Health plc (LSE: PRTC) plans to advance its wholly-owned clinical-stage product candidate LYT-100 (deupirfenidone) as a potential treatment for serious respiratory complications, including inflammation and fibrosis, that persist following the resolution of SARS-CoV-2 (COVID-19) infection, the company said.

LYT-100 employs a multimodal mechanism of action to potentially reduce, delay or prevent the lung dysfunction that has recently been documented in COVID-19 patients, including those who have recovered from the infection.

The global, randomised, placebo-controlled trial is expected to begin in 3Q20 and will evaluate LYT-100 in non-critical COVID-19 patients with respiratory complications. Patients will continue treatment for up to three months.

LYT-100 is an oral anti-fibrotic and anti-inflammatory small molecule. It is a deuterated analogue of pirfenidone.

Oral pirfenidone is approved for the treatment of idiopathic pulmonary fibrosis in the United States, European Union, Japan and a number of other countries and has received Breakthrough Therapy designation from the FDA for unclassifiable interstitial lung disease.

In prior Phase 1, healthy volunteer studies, LYT-100 has shown a differentiated and superior pharmacokinetic profile compared to pirfenidone, suggesting improved efficacy, tolerability and safety, while retaining the same intrinsic pharmacology of pirfenidone.

Preclinical research also shows that LYT-100 potently inhibits a range of pro-inflammatory cytokines including IL6, TNF alpha and TGF-beta.

PureTech expects to initiate a global, multi-centre, randomized, double-blinded, placebo-controlled trial in 3Q20 to evaluate the efficacy, safety and tolerability of LYT-100 in non-critical COVID-19 patients with respiratory complications. Patients will continue treatment for up to three months.

The trial is expected to enroll approximately 150 patients, with a primary endpoint measuring pulmonary function testing.

The trial will also assess exploratory endpoints including pharmacokinetics, acute inflammatory biomarkers, hospitalization events, imaging and patient-reported outcomes. PureTech expects to announce topline results in mid-2021.

As previously announced, in March 2020 PureTech initiated a Phase 1 trial of LYT-100 evaluating its safety, tolerability and the pharmacokinetic profile of multiple doses in healthy participants.

Results from this trial are anticipated later this year, and a subsequent proof-of-concept trial in people with breast cancer-related, upper limb secondary lymphedema is expected to begin in 2020, with topline results expected in 2021.

PureTech is also evaluating additional inflammatory and fibrotic conditions that could potentially be addressed with LYT-100.

LYT-100 is PureTech's most advanced wholly-owned product candidate. A deuterated form of pirfenidone, an approved anti-inflammatory and anti-fibrotic drug, LYT-100 is being developed for the potential treatment of a range of conditions involving fibrosis, inflammation and impaired lymphatic flow, including lymphedema, idiopathic pulmonary fibrosis, interstitial pneumonias, unclassifiable interstitial lung disease and other interstitial lung disease, radiation-induced fibrosis and focal segmental glomerulosclerosis.

LYT-100 is currently being evaluated in a Phase 1 multiple ascending dose and food effect trial in healthy volunteers with a subsequent assessment in patients with breast cancer-related, upper limb secondary lymphedema expected to begin in 2020.

PureTech also plans to initiate a trial in 3Q20 evaluating LYT-100 as a potential treatment for serious respiratory complications, including inflammation and fibrosis, that persist following the resolution of SARS-CoV-2 (COVID-19).

PureTech is a clinical-stage biotherapeutics company dedicated to discovering, developing and commercialising highly differentiated medicines for devastating diseases, including intractable cancers, lymphatic and gastrointestinal diseases, central nervous system disorders and inflammatory and immunological diseases, among others.

The company has created a broad and deep pipeline through the expertise of its experienced research and development team and its extensive network of scientists, clinicians and industry leaders.

This pipeline, which is being advanced both internally and through PureTech's Founded Entities, is comprised of 23 product candidates and one product that has been cleared by the US Food and Drug Administration.

All of the underlying programs and platforms that resulted in this pipeline of product candidates were initially identified or discovered and then advanced by the PureTech team through key validation points based on the company's unique insights into the biology of the brain, immune and gut, or BIG, systems and the interface between those systems, referred to as the BIG Axis.