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Bristol Myers Squibb is sharing its phase 2 results at the European Respiratory Society 2023 international congress this week. After scoring in a more common form of pulmonary fibrosis in May, Bristol Myers Squibb’s lysophosphatidic acid receptor 1 (LPA1) antagonist has turned out positive results in a rarer incarnation of the disease. The clinical win ups the pressure on a pair of entrenched blockbusters in interstitial lung disease—Roche’s Esbriet and Boehringer Ingelheim’s Ofev. Angling for the first-in-class title, BMS’ investigational LPA1 antagonist BMS-986278 triumphed in a phase 2 study in patients with progressive pulmonary fibrosis (PPF). At 26 weeks, two daily 60-mg doses of BMS' candidate reduced the rate of decline in percent predicted forced vital capacity (ppFVC)—a key measure of lung function in patients with PPF—by 69% versus placebo.  BMS is sharing the results at the European Respiratory Society 2023 international congress this week. Notably, 38% of patients in the study received a background antifibrotic therapy like Roche’s pirfenidone, also known as Esbriet, or Boehringer’s nintedanib, which goes by the commercial moniker Ofev. BMS-986278’s success on top of existing pulmonary fibrosis treatments suggests the drug could have potential as an add-on to established therapies. Pulmonary fibrosis occurs when the lung tissue becomes damaged and scarred. The disease is characterized by shortness of breath, coughing and fatigue. PPF is less common than its sibling idiopathic pulmonary fibrosis (IPF), though PPF has shown a similar prognosis to IPF. Both diseases are fatal, with a median survival time of three to five years and a five-year survival rate of roughly 45%, BMS said in a press release. In BMS’ phase 2 study, parallel cohorts of IPF and PPF patients received 30 mg or 60 mg of the company’s LPA1 prospect twice daily over 26 weeks. Things didn’t go as smoothly for the lower dose of the drug, which only charted a 42% relative reduction in forced vital capacity versus placebo. However, BMS noted that across doses, treatment was consistent with or without background antifibrotics like Esbriet and Ofev. BMS-986278’s safety profile was generally well tolerated in both treatment arms, BMS said. Side effect rates were on par with the dummy drug, and discontinuation rates were low, the company added. Across placebo and both doses of the drug, the most common side effects reported were diarrhea, COVID-19, cough and difficult or labored breathing. The PPF win comes several months after BMS posted positive phase 2 results on its drug candidate in IPF. In May, the company reported that a 60-mg dose of BMS-986278 reduced the rate of decline 62% on a measure of ppFVC. The company found that the 30-mg dose was not effective on the same measure. Given that phase 2 success, BMS plans to begin work on a phase 3 program, the company’s chief medical officer Samit Hirawat, M.D., said earlier this year. On top of Monday’s PPF win, BMS said its drug will now be assessed in the phase 3 ALOFT (An LPA1 antagonist for pulmonary Fibrosis Trial) program. Both Roche’s and Boehringer’s entrenched antifibrotics have ginned up blockbuster sales over the years. In 2022, Ofev brought home full-year sales of 3.2 billion euros (about $3.4 billion). Esbriet, for its part, started to suffer from the entry of generics in last year’s second quarter, Roche said in a recent earnings release. The drug posted (PDF) full-year 2022 sales of 718 million Swiss francs (roughly $805 million). Ofev is patent protected until 2029.

-Company on track to begin enrolling healthy volunteers in the second half of 2023- SAN DIEGO--(BUSINESS WIRE)-- Pipeline Therapeutics a clinical-stage biopharmaceutical company pioneering precision neuroregeneration, today announced that the U.S. Food and Drug Administration (FDA) cleared the company to initiate its Phase 1 clinical trial of PIPE-791 in healthy volunteers. The Company’s wholly owned program, PIPE-791, is a potent, selective and brain-penetrant small molecule antagonist of the lysophosphatidic acid 1 receptor (LPA1). LPA1 is a critical element in bioactive phospholipid signaling, and is a powerful mediator of both nervous system and systemic inflammatory conditions. Specifically, LPA1 inhibition has important therapeutic potential through augmentation of remyelination and mitigation of neuro-inflammation. Multiple sclerosis (MS) is a leading indication for PIPE-791, as there are no currently approved medicines designed to prevent neuronal loss and mitigate clinical disability in MS patients. “The FDA clearance of PIPE-791’s IND marks another significant milestone for Pipeline and demonstrates our team’s continued focus and commitment to bringing precision therapies to patients with neurological diseases,” said Carmine Stengone, President and CEO of Pipeline. “PIPE-791 is our second clinical program and our first to address both remyelination and neuro-inflammation. We look forward to evaluating our first-in-class approach to LPA1 inhibition with PIPE-791, with the goal to deliver meaningful benefit to individuals with MS, as well as other neurological and systemic diseases.” Stephen Huhn, M.D., Chief Medical Officer and Senior Vice President of Clinical Development of Pipeline, added, “We are excited to initiate the Phase 1 study of PIPE-791, which is designed to assess the safety and tolerability of PIPE-791 compared to placebo in healthy volunteers. We expect to commence dosing in the second half of 2023.” The Phase 1 clinical trial of PIPE-791 will be conducted as a randomized, double-blind, placebo-controlled dose-ranging study, and enroll approximately 80 healthy volunteer subjects. About PIPE-791 The Company’s wholly owned program, PIPE-791, is advancing toward clinical development for remyelination and neuro-inflammation. PIPE-791 is a potent, selective, brain-penetrant small molecule antagonist of the LPA1 receptor that has demonstrated activity in in vitro and in vivo models and was tolerated in IND-enabling studies. Lysophosphatidic acid (LPA) is a pro-inflammatory lipid, upregulated in the plasma, peripheral blood mononuclear cells and cerebrospinal fluid of MS patients. LPA activates the G-protein coupled LPA1 receptor on both oligodendrocyte precursor cells (OPCs) and microglia resulting in a local neuroinflammatory response limiting remyelination. PIPE-791 has demonstrated in vitro evidence of oligodendrocyte differentiation, myelination, and protection from cytokine-induced oligodendrocyte cell death. In pre-clinical in vivo models, PIPE-791 has demonstrated evidence of central nervous system LPA1 receptor occupancy, increased remyelination, and inhibition of neuro-inflammation. About Pipeline Therapeutics Pipeline Therapeutics is a clinical-stage biopharmaceutical company pioneering the development and commercialization of first-in-class therapies for precision neuroregeneration including myelin restoration, synaptogenesis and axonal repair. The Company has a broad pipeline of programs to address multiple CNS disorders. In April 2023, Pipeline announced that it entered into a global license and development agreement with Janssen Pharmaceutica NV (Janssen) for its lead program, PIPE-307, a highly selective M1 antagonist, in central nervous system disorders. The Company’s second program, PIPE-791, an LPA1 receptor antagonist, has received FDA clearance of its IND and is advancing into Phase 1 testing. For more information, please visit and engage with us on LinkedIn.