deupirfenidone (LYT-100) / Teva, PureTech - LARVOL DELTA

Deupirfenidone Compared to Placebo and Pirfenidone in Idiopathic Pulmonary Fibrosis: ELEVATE IPF Phase 2b Trial (ATS 2025) - No abstract available

Clinical • Late-breaking abstract • P2b data • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases

ELEVATE: LYT-100 in Patients With Idiopathic Pulmonary Fibrosis (IPF) (clinicaltrials.gov) - P2 | N=240 | Active, not recruiting | Sponsor: PureTech | Trial completion date: Aug 2025 ➔ Dec 2025

Trial completion date • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases

PureTech’s Deupirfenidone (LYT-100) Slowed Lung Function Decline in People with Idiopathic Pulmonary Fibrosis (IPF) as Measured by Forced Vital Capacity (FVC), Achieving the Primary and Key Secondary Endpoints in the ELEVATE IPF Phase 2b Trial (Businesswire) - P2b | N=240 | ELEVATE (NCT05321420) | Sponsor: PureTech | "PureTech Health plc...today announced positive results from ELEVATE IPF...The rate of FVC decline at week 26 with: deupirfenidone 825 mg TID compared to placebo was statistically significant (-21.5 mL vs. -112.5 mL, respectively; p=0.02)4 and represents a robust treatment effect of 80.9% as a monotherapy; for context, the level of six-month natural decline in lung function as measured by FVC expected in healthy adults over 60 years old is approximately -15.0 mL to -25.0 mL. pirfenidone 801 mg TID showed a treatment effect of 54.1% compared to placebo (-51.6 mL vs. -112.5 mL, respectively), which is consistent with previously reported pirfenidone clinical trial data. The trial also achieved its key secondary endpoint based on a prespecified Bayesian analysis, with a posterior probability of 99.6%."

P2b data • Idiopathic Pulmonary Fibrosis

PureTech’s Deupirfenidone (LYT-100) Slowed Lung Function Decline in People with Idiopathic Pulmonary Fibrosis (IPF) as Measured by Forced Vital Capacity (FVC), Achieving the Primary and Key Secondary Endpoints in the ELEVATE IPF Phase 2b Trial (Yahoo Finance) - P2b | N=NA | ELEVATE (NCT05321420) | Sponsor: | Puretech | "'The ELEVATE IPF trial broke new ground in Phase 2 trial design in IPF; this was the first time that a new therapy (deupirfenidone) has been evaluated alongside one of the two existing standard-of-care treatments (pirfenidone),' said Toby Maher, MD, PhD...'Deupirfenidone 825 mg TID reduced lung function decline to near-physiologic levels over 26 weeks and had an effect size, compared with placebo, that was approximately 50% greater than that seen with pirfenidone. Deupirfenidone has the potential to offer patients a highly effective and tolerable treatment option. These are extremely exciting results from a Phase 2b trial, and I am very enthusiastic about the continued development of deupirfenidone.'"

Media quote • P2b data • Idiopathic Pulmonary Fibrosis • Pulmonary Disease

Study to Determine Potential for Drug-drug Interactions When Co-administering Deupirfenidone (LYT-100) and Nintedanib (clinicaltrials.gov) - P1 | N=30 | Not yet recruiting | Sponsor: PureTech

New P1 trial

BAYESIAN APPROACH FOR ELEVATE IPF: RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL TO EVALUATE EFFICACY, SAFETY, AND DOSE RESPONSE OF DEUPIRFENIDONE (LYT-100) IN IPF (CHEST 2024) - "There is precedent for leveraging Bayesian methodology in IPF studies (i.e., phase 2 programs for BI 1015550 and BMS-986278) to minimize the number of patients exposed to placebo while still generating data sufficient for decision making in drug development...The study will evaluate approximately 240 treatment-naïve adult participants, or those with less than 6 months exposure to nintedanib, at least 40 years of age at approximately 120 study centers globally... The Bayesian dynamic borrowing approach leverages the plethora of placebo data available from prior IPF studies. This approach has the potential to significantly enhance the statistical power of this study while limiting the number of patients required to be treated with placebo. CLINICAL IMPLICATIONS: Bayesian dynamic borrowing allows for historic IPF controls to complement clinical trial data to maximize the number of patients exposed to active treatment arms and minimize the number exposed to placebo."

Clinical • Idiopathic Pulmonary Fibrosis • Immunology • Oncology • Rare Diseases

PureTech Presents Research Highlighting Burden of Idiopathic Pulmonary Fibrosis (IPF) and Use of a Bayesian Statistical Analysis for LYT-100 (Deupirfenidone) at CHEST 2024 Annual Meeting (PRNewswire) - "PureTech presented qualitative and quantitative research that highlights both the burden of IPF as well as gaps in disease management that exacerbate the quality of life for people with IPF. The 90-person survey found that the majority of participants experience a high burden of disease that interferes with their normal activities, including shortness of breath (86%), fatigue (78%) and cough (77%)...Beyond this, PureTech’s research revealed commonalities and differences in the patient experience for those receiving care at interstitial lung disease (ILD) centers (n=45) versus community pulmonary practices (CPP) (n=45)...Antifibrotic treatment rates at ILD centers and CPPs were similar, but differences existed in perceived communication around antifibrotic treatment options."

Clinical data • Idiopathic Pulmonary Fibrosis • Immunology

PureTech Presents Research Highlighting Burden of Idiopathic Pulmonary Fibrosis (IPF) and Use of a Bayesian Statistical Analysis for LYT-100 (Deupirfenidone) at CHEST 2024 Annual Meeting (Businesswire) - "PureTech also presented a clinical abstract reviewing its plan to evaluate the primary outcome of the Phase 2b ELEVATE IPF clinical trial using a prespecified Bayesian approach...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 Bayesian linear mixed effects model including dynamic borrowing. This approach augments the placebo arm sample size with external placebo data from historical IPF trials. A Bayesian approach has the advantage of enhancing overall statistical power and improving decision-making while limiting the number of patients required to be treated with placebo in a fatal disease."

Clinical protocol • Idiopathic Pulmonary Fibrosis • Immunology

PureTech to Present at CHEST 2024 Annual Meeting (Businesswire) - "PureTech Health plc...announced its onsite presence at the CHEST 2024 Annual Meeting in Boston, Massachusetts, from October 6-9. The Company will deliver two oral presentations and one poster relating to LYT-100 (deupirfenidone) for the treatment of idiopathic pulmonary fibrosis (IPF) as well as the Company’s research surrounding the experiences of patients with IPF. The data to be presented have informed the clinical and commercial strategies supporting LYT-100 as well as advocacy and patient engagement work around the management and treatment of people with IPF. Topline results from the Phase 2b ELEVATE IPF trial are expected by the end of 2024."

Clinical • P2b data • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease

PureTech Health plc – Half-Year Report (Businesswire) - "PureTech expects topline results from the Phase 2b ELEVATE IPF dose-ranging trial of LYT-100 in patients with IPF by the end of 2024. The trial is designed to evaluate the efficacy, tolerability, safety and dosing regimen of LYT-100 in patients with IPF compared to placebo and will also assess the relative efficacy of two doses of LYT-100....It also expects topline data from its Phase 2 COLLECTiVE202 clinical trial of VE202 for the treatment of ulcerative colitis ('UC')in 2025."

P2 data • P2b data • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology

ELEVATE: LYT-100 in Patients With Idiopathic Pulmonary Fibrosis (IPF) (clinicaltrials.gov) - P2 | N=240 | Active, not recruiting | Sponsor: PureTech | Recruiting ➔ Active, not recruiting

Enrollment closed • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases

LYT-100 in Patients With BCRL (clinicaltrials.gov) - P2 | N=50 | Terminated | Sponsor: PureTech | Phase classification: P1/2 ➔ P2

Phase classification • Breast Cancer • HER2 Breast Cancer • Oncology • Solid Tumor

Enrollment complete for Phase 2b trial testing LYT-100 in IPF patients (Pulmonary Fibrosis News) - P2 | N=240 | ELEVATE (NCT05321420) | Sponsor: PureTech | "'LYT-100 has the potential to have a profound impact on the way IPF is managed by allowing patients to start, continue and fully benefit from treatment, both as monother...and investigator in the trial, said in a company press release. 'This milestone in the ELEVATE IPF trial is very exciting, and I look forward to the full results as a potential step forward for the large, underserved IPF patient community,' Maher said."

Media quote • P2b data • Idiopathic Pulmonary Fibrosis

PureTech Announces Completion of Enrollment in Phase 2b ELEVATE IPF Trial of LYT-100 (Deupirfenidone) in Idiopathic Pulmonary Fibrosis (Businesswire) - "PureTech Health plc...announced that enrollment has been completed in the ELEVATE IPF Phase 2b clinical trial evaluating LYT-100 (deupirfenidone) in patients with idiopathic pulmonary fibrosis (IPF)....Topline results are expected in the fourth quarter of 2024."

Enrollment closed • P2b data • Fibrosis • Idiopathic Pulmonary Fibrosis • Respiratory Diseases

Pulmonary Function at Minimum 10 Years After Segmental Pedicle Screw Instrumentation for Thoracic Adolescent Idiopathic Scoliosis. (PubMed, Spine (Phila Pa 1976)) - "FVC improved by a mean of 510 ml from preoperative to 10-year follow-up in patients undergoing pedicle screw instrumentation for thoracic AIS. Despite 76% scoliosis correction and significant improvement of absolute lung volume values, more than one-third of these surgically treated otherwise healthy young adults fulfilled the criteria for pulmonary function impairment at 10-year follow-up."

Journal

ELEVATE: LYT-100 in Patients With Idiopathic Pulmonary Fibrosis (IPF) (clinicaltrials.gov) - P2 | N=240 | Recruiting | Sponsor: PureTech | Trial completion date: Mar 2024 ➔ Aug 2025 | Trial primary completion date: Dec 2023 ➔ Oct 2024

Trial completion date • Trial primary completion date • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases

LYT-100 in Post-acute COVID-19 Respiratory Disease (clinicaltrials.gov) - P2 | N=185 | Terminated | Sponsor: PureTech | Completed ➔ Terminated; Part A of the study was completed; Part B of the study was terminated

Trial termination • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

LYT-100 in Healthy Volunteers and BCRL (clinicaltrials.gov) - P1/2 | N=50 | Terminated | Sponsor: PureTech | Phase classification: P2a ➔ P1/2 | Completed ➔ Terminated; Primary objective/endpoint has been established, will not pursue development of the disease indication further

Phase classification • Trial termination • Breast Cancer • HER2 Breast Cancer • Oncology • Solid Tumor

PureTech Year End Update and Outlook for 2024 (Businesswire) - "PureTech continues to build and will further expand its Wholly Owned Pipeline focus in pulmonary and rare diseases. Certain Glyph intellectual property will remain at PureTech. Key catalysts expected in 2024 include results from idiopathic pulmonary fibrosis (IPF) late-stage trial of LYT-100 in Q4 2024."

P2b data • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology

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

Media quote

PureTech Presents Data from LYT-100 (Deupirfenidone) Trial in Healthy Older Adults at CHEST Annual Meeting (Businesswire) - P1 | N=NA | "Results informed dose selection for ongoing, global Phase 2b ELEVATE IPF trial, with topline data expected in 2024...PureTech Health plc...presented clinical data supporting the differentiated profile of LYT-100 (deupirfenidone) at the CHEST Annual Meeting in Honolulu, Hawaii....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....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."

P1 data • P2b data • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease

DEUPIRFENIDONE (LYT-100) DOSE-SELECTION RATIONALE FOR A PHASE 2B IDIOPATHIC PULMONARY FIBROSIS (IPF) STUDY-ELEVATE (CHEST 2023) - P2 | "AE incidence rates were generally associated with Cmax of parent and/or 5CP metabolite for LYT-100 and PIRF. LYT-100 550mg TID fed had a similar AUC to PIRF 801mg TID with a lower Cmax and lower AE rates. However, PK differences did not fully explain the lower AE rates seen with 824mg TID LYT-100."

P2b data • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Infectious Disease • Novel Coronavirus Disease • Pulmonary Disease • Respiratory Diseases

PureTech Health plc – Half-Year Report (Businesswire) - "We expect topline results from the Phase 2b dose-ranging trial of LYT-100 in patients with IPF in 2024. We plan to pursue a streamlined development program for LYT-100 in IPF and are using the same endpoints that have supported past approvals. Pending positive clinical and regulatory feedback, we intend to advance the program into a Phase 3 trial."

P2b data • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease

Safety and Tolerability of LYT-100 (Deupirfenidone) in Post-Acute Sequelae of SARS-CoV-2 (PASC) "Long COVID" Patients Presenting With Respiratory Complications (ATS 2023) - "In contrast to the hypothesized role of pulmonary fibrosis in PASC, we did not observe significant baseline fibrosis or progression. The minimal fibrosis at baseline improved in most patients irrespective of treatment arm. These data suggest antifibrotics would not be beneficial in these patients and not surprisingly, LYT-100 did not improve PASC."

Clinical • Cough • Dyspepsia • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Infectious Disease • Novel Coronavirus Disease • Pain • Pulmonary Disease • Respiratory Diseases

PureTech Announces Annual Results for Year Ended December 31, 2022 (Businesswire) - "PureTech is currently evaluating two doses of LYT-100, one with comparable exposure to the approved dose of pirfenidone and one with a higher level of exposure, in a global, randomized double blind, placebo-controlled trial in patients with IPF, which is expected to serve as the first of two registration enabling trials. Topline results are expected in 2024."

Clinical data • Idiopathic Pulmonary Fibrosis • Immunology