Bexotegrast

An Insilico Medicine drug candidate spawned by the company’s artificial intelligence technology now has clinical data showing breathing improvement in patients who have a debilitating lung disorder. While these preliminary results are encouraging for the company and for an AI drug discovery field that has weathered setbacks, there’s little detail to evaluate the Insilico drug on its own merits, let alone see how it matches up to competitors that includes one molecule some industry observers view as potentially best in class. The disease is idiopathic pulmonary fibrosis (IPF), a chronic disorder that causes scarring in the lungs and an irreversible decline in the organ’s function. IPF is a prevalent disease, affecting an estimated 5 million people worldwide, mainly older adults. Once diagnosed, patients survive a median of three to four years. The cause of IPF is unknown; standard therapies are older drugs that slow its progression but do not alter the course of the disease. Insilico’s drug, ISM001-055, targets and inhibits Traf2- and Nck-interacting kinase (TNIK), an enzyme that plays a role in signaling pathways associated with disease. While TNIK inhibition has been studied as a way to treat cancer, Insilico’s technology identified this target as a promising one for fibrosis, the formation of scar tissue characteristic of IPF. The company then used generative AI to design the small molecule that is now its IPF drug candidate. Details about this development process were published in March in Nature Biotechnology. Included in the paper were preclinical data and results from Phase 0 (small doses of drug tested in low numbers of people) and Phase 1 studies. presented by Health IT Accelerating Claim Processing: Strategies to Shorten the Life of a Claim These strategies and practices can significantly shorten the life cycle of claims, leading to quicker resolutions and improved financial outcomes. By Greenway Health The results announced last week are from a placebo-controlled Phase 2a study that enrolled 71 IPF patients in China. Patients were randomly assigned to receive a 30 mg dose of the drug once daily, a 30 mg dose twice daily, a 60 mg dose once daily, or a placebo. The main goal of the 12-week study is assessing the ISM001-055’s safety and tolerability across all dose levels. Measuring improvement in forced vital capacity (FVC), which is how much air a person can exhale, is a secondary endpoint. Without disclosing any figures, Insilico said ISM001-055 met the primary endpoint of safety and posted positive results on the secondary efficacy endpoint. The company added that these results show a dose-dependent improvement in FVC, with the largest improvement observed in the cohort that received the 60 mg dose once daily. Insilico said more details about the preliminary data will be released at an upcoming medical conference and the trial results will be submitted for publication in a peer-reviewed journal. A parallel Phase 2 study in the U.S. is actively enrolling patients. Following the positive results from this mid-stage study, Insilico said it will discuss with regulatory authorities the design of a Phase 2b study that will explore extended treatment durations and larger groups of patients. Meanwhile, the clinical trial results so far keep Insilico in the mix of drug developers pursuing IPF, though it still trails those rivals. On Sept. 16, Boehringer Ingelheim announced its IPF drug candidate hit the main goal of its pivotal studies, paving the way for regulatory submissions to the FDA and other health authorities around the world. The Boehringer drug, nerandomilast, is a small molecule designed to inhibit phosphodiesterase 4B (PDE4B), an enzyme whose roles include regulating inflammation. Sponsored Post Get Ready for HLTH 2024: A Preview Guide HLTH 2024, scheduled for October 20-23 at the Venetian Expo Center in Las Vegas, will highlight new programming, a physicians roundtable, generative AI, the shifting landscapes of telemedicine, retail health, women's health, and lots more. By Stephanie Baum Boehringer studied its twice-daily pill in two placebo-controlled Phase 3 studies, one in IPF and the other in progressive pulmonary fibrosis (PPF), a progressive and fibrotic disease that shares characteristics with IPF. The main goal of both studies was to show the absolute change in FVC measured at 52 weeks. Without releasing details, Boehringer said preliminary results show nerandomilast met this goal. The company added that full efficacy and safety data will be presented in the first half of next year. The company did not specify a timeline for the expected regulatory submissions for the drug. Pliant Therapeutics’ contender is bexotegrast, a small molecule inhibitor of TGF-beta. This signaling protein contributes to IPF by sparking high levels of collagen, which in turn leads to a progressive loss of elasticity and function in the lungs. During the recent European Respiratory Society (ERS) meeting, Pliant presented Phase 2 results showing its drug led to a reduction in collagen after 12 weeks of treatment. Study participants who received a placebo experienced an increase in collagen. The reduction in treated patients correlates with improvement in lung function, specifically FVC and cough severity, Pliant said. In a note sent to investors this after the ERS meeting, Leerink Partners analyst Faisal Khurshid said bexotegrast’s collagen data provide “compelling proof of disease modification.” He added that the safety analyses continue to suggest the Pliant drug has a clean profile. Khurshid said bexotegrast has potential to become a best-in-class treatment option in IPF and the collagen data give incremental confidence ahead of Phase 2b data expected in mid-2026. PureTech Health’s approach to IPF is to improve on pirfenidone, brand name Esbriet, an old IPF drug whose gastrointestinal and skin side effects lead many patients to stop taking the medication. Despite those limitations, Leerink Partners’ Khurshid noted in a research note that branded Esbriet generated $1.3 billion in peak sales before going generic. PureTech’s IPF drug, LYT-100, is pirfenidone with chemical modifications to improve its tolerability. “We have a favorable view on LYT-100 as it improves on a known anti-fibrotic drug in a manner that should diminish well-recognized safety liabilities,” Khurshid said. “While this is an improvement on an existing molecule, we see it as a real opportunity in an area of high unmet need.” A Phase 2b test of LYT-100 is currently evaluating two doses of the drug compared to pirfenidone and a placebo. With the lower dose, the study aims to show whether the PureTech drug improves on the safety profile of pirfenidone. Evaluating the higher dose is meant to assess whether higher exposure of the drug offers even better efficacy while still retaining acceptable safety. Khurshid said there is less evidence to support the latter hypothesis, but Leerink sees it as an intriguing upside opportunity.

SOUTH SAN FRANCISCO, Calif., Sept. 10, 2024 (GLOBE NEWSWIRE) -- Pliant Therapeutics, Inc. (Nasdaq: PLRX), a late-stage biotechnology company and leader in the discovery and development of novel therapeutics for the treatment of fibrotic diseases, announced its presentations at the European Respiratory Society (ERS) International Congress 2024 taking place in Vienna, Austria September 7 - 11, 2024. “Presentations made by Pliant colleagues and investigators at the 2024 ERS Congress include additional clinical data from our recently announced type 1 collagen PET imaging study, an integrated safety summary from our INTEGRIS clinical programs and non-clinical data from our bexotegrast development program. Taken together, these data provide further support for the late-stage development of this novel therapeutic as part of our ongoing BEACON-IPF trial,” said Éric Lefebvre, M.D., Chief Medical Officer at Pliant Therapeutics. Bexotegrast reduces type 1 collagen deposition in participants with idiopathic pulmonary fibrosis (IPF) after 12 weeks of therapy In a late-breaker oral presentation, Sydney B. Montesi, M.D., Assistant Professor of Medicine at Massachusetts General Hospital, Havard Medical School presented results from the first interventional Phase 2, single-center, randomized, double-blind, placebo-controlled trial (NCT05621252) evaluating type 1 collagen deposition by positron emission tomography (PET) imaging in the lungs of participants with IPF. Following 12 weeks of treatment, bexotegrast demonstrated a reduction in type 1 collagen in contrast to an increase on placebo, supporting bexotegrast’s antifibrotic effects and suggesting favorable lung remodeling. In addition, treatment with bexotegrast showed numerical improvements in forced vital capacity, cough severity, and prognostic biomarkers, suggesting its potential for disease modification in idiopathic pulmonary fibrosis (IPF). Lastly, measurements by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), bexotegrast demonstrated an increased peak enhancement and a faster contrast washout rate, suggesting improvements in lung microvasculature and decreased extravascular extracellular volume, further supporting the PET imaging findings. Safety and tolerability of bexotegrast in Phase 2 trials of idiopathic pulmonary fibrosis (IPF) and primary sclerosing cholangitis (PSC) In an oral presentation, Gregory Cosgrove, M.D. FCCP, Vice President of Clinical Development at Pliant Therapeutics presented an integrated safety summary of bexotegrast from the INTEGRIS Phase 2a trials in IPF and primary sclerosing cholangitis (PSC). Results showed that, at 12 weeks of treatment, bexotegrast was well tolerated with no related serious adverse events with most adverse events being mild to moderate with low discontinuation rates across both trials. Bexotegrast is antifibrotic in precision cut-lung slices prepared from fibrotic interstitial lung disease explants In a late-breaker oral presentation, Johanna Schaub, Ph.D., Principal Scientist II, Translational Sciences at Pliant Therapeutics, presented a study assessing the antifibrotic effects of bexotegrast, a dual αvβ6/αvβ1 integrin inhibitor, in precision cut-lung slices from patients with progressive fibrosing interstitial lung diseases (ILD) other than IPF. Results showed that integrin αvβ6 levels were increased in lungs from patients with a diverse set of fibrotic ILDs and that bexotegrast decreased profibrogenic gene expression in lung slices generated from a wide range of ILD lung explants. In addition, the antifibrotic activity of bexotegrast was found to be similar in slices from IPF and non-IPF explants. These data support the further investigation into the antifibrotic activity of bexotegrast in ILD-associated progressive pulmonary fibrosis (PFF). Post-hoc biomarker analysis in participants with IPF receiving bexotegrast over 12-weeks in INTEGRIS-IPF In a poster presentation, Martin Decaris, Ph.D., Senior Director, Translational Sciences at Pliant Therapeutics, presented results from a post-hoc proteomic analysis of plasma samples from the INTEGRIS-IPF Phase 2a clinical trial of bexotegrast in patients with IPF. Results showed that plasma levels of several previously identified biomarkers of ILD progression, including integrin beta-6, were reduced in participants receiving bexotegrast at the 320 mg dose versus placebo. Plasma integrin beta-6 levels were also found to negatively correlate with changes in lung function as determined by percent predicted forced vital capacity (FVCpp). Further analyses of plasma biomarkers are included as part of the ongoing global Phase 2b/3 BEACON-IPF trial. Posters presented at the ERS International Congress 2024 are available on Pliant’s website under the Publications section at https://pliantrx.com/publications. About Pliant Therapeutics, Inc. Pliant Therapeutics is a late-stage biopharmaceutical company and leader in the discovery and development of novel therapeutics for the treatment of fibrotic diseases. Pliant's lead product candidate, bexotegrast (PLN-74809), is an oral, small molecule, dual selective inhibitor of αvß6 and αvß1 integrins that is in development in the lead indications for the treatment of idiopathic pulmonary fibrosis, or IPF, and primary sclerosing cholangitis, or PSC. Bexotegrast has received Fast Track Designation and Orphan Drug Designation from the U.S. Food and Drug Administration (FDA) in IPF and PSC and Orphan Drug Designation from the European Medicines Agency in IPF and PSC. Pliant has initiated BEACON-IPF, an adaptive Phase 2b/3 trial of bexotegrast in IPF. Pliant is conducting a Phase 1 study for its third clinical program, PLN-101095, a small molecule, dual-selective inhibitor of αvß8 and αvß1 integrins, that is being developed for the treatment of solid tumors. In addition, Pliant has received regulatory clearance for the conduct of a Phase 1 study of PLN-101325, a monoclonal antibody agonist of integrin α7β1 targeting muscular dystrophies. For additional information, please visit: www.PliantRx.com. Follow us on social media: X, LinkedIn, and Facebook. Forward-Looking Statements Statements contained in this press release regarding matters that are not historical facts are "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995. Words such as "may," "will," "expect," "anticipate," "estimate," "intend," and similar expressions (as well as other words or expressions referencing future events, conditions, or circumstances) are intended to identify forward-looking statements. These statements include those regarding the potential for the future development of bexotegrast. Because such statements deal with future events and are based on our current expectations, they are subject to various risks and uncertainties and actual results, performance or achievements of Pliant Therapeutics could differ materially from those described in or implied by the statements in this press release. These forward-looking statements are subject to risks and uncertainties, including those related to the development and commercialization of our product candidates, including any delays in our ongoing or planned preclinical or clinical trials, the impact of current macroeconomic and marketplace conditions, including the effects of COVID-19, on our business, operations, clinical supply and plans, our reliance on third parties for critical aspects of our development operations, the risks inherent in the drug development process, the risks regarding the accuracy of our estimates of expenses and timing of development, our capital requirements and the need for additional financing, including the availability of additional term loans under our loan facility, and our ability to obtain and maintain intellectual property protection for our product candidates. These and additional risks are discussed in the sections titled "Risk Factors" and "Management's Discussion and Analysis of Financial Condition and Results of Operations" in our Quarterly Report on Form 10-Q for the period ended June 30, 2024 which we filed with the SEC on August 7, 2024, and is available on the SEC's website at www.sec.gov. Unless otherwise noted, Pliant is providing this information as of the date of this news release and does not undertake any obligation to update any forward-looking statements contained in this document as a result of new information, future events or otherwise. Investor and Media Contact:Christopher KeenanVice President, Investor Relations and Corporate CommunicationsPliant Therapeutics, Inc.ir@pliantrx.com