Idiopathic pulmonary fibrosis (IPF) drug development is gaining momentum as companies explore novel therapeutic targets and report encouraging clinical trial results. With current treatments offering limited efficacy, the pursuit of therapies that can halt or reverse disease progression remains a critical unmet need.
FOXO3 Activation as a Novel Approach
Refoxy Pharma recently secured $9.58 million in funding to accelerate preclinical development of RP-01, a therapy targeting FOXO3. According to Victor Bustos, COO and co-founder of Refoxy Pharma, FOXO3 is a "pivotal master regulator of healthy aging." The company's F.act Finder platform identifies pharmacological activators of FOXO3, which plays a key role in fibrogenesis, the mechanism that aids wound healing and repair. Unlike existing treatments like nintedanib and pirfenidone, which address specific molecular pathways, RP-01 aims to modulate the master switch of tissue repair.
Boehringer Ingelheim's Nerandomilast Nears Regulatory Submission
Boehringer Ingelheim is preparing to submit a New Drug Application (NDA) for nerandomilast, an oral inhibitor of phosphodiesterase 4B (PDE4B). In a Phase 3 trial, nerandomilast met its primary endpoint, demonstrating a significant change from baseline in Forced Vital Capacity (FVC) at week 52 compared to placebo. FVC is a measure of lung function. If approved, nerandomilast will compete with Boehringer's own nintedanib (Ofev) and Roche's pirfenidone (Esbriet).
Promising Phase 2 Results for ISM001-055 and ENV-101
Insilico Medicine is advancing its AI-designed IPF drug, ISM001-055, after positive Phase 2a results. The trial, conducted in China with 71 patients, showed a dose-dependent improvement in FVC after 12 weeks of treatment. ISM001-055 targets TNIK, an anti-fibrotic target. Endeavor BioMedicines' ENV-101, a hedgehog inhibitor, also demonstrated encouraging results in a Phase 2a trial, showing a 1.9% mean improvement in FVC from baseline compared to a 1.3% decline in the placebo group. ENV-101 also reversed key measures of lung disease, such as quantitative lung fibrosis (QLF) and quantitative interstitial lung disease (QILD).
BMS's LPA1 Antagonist Gains Breakthrough Therapy Designation
Bristol Myers Squibb's LPA1 antagonist, BMS-986278, received FDA Breakthrough Therapy Designation following positive Phase 2 results. The study showed that 60 mg of BMS-986278 given twice daily reduced the rate of decline in FVC by 69% compared to placebo over 26 weeks. High levels of LPA and activation of LPA1 are linked to the pathogenesis of IPF and progressive pulmonary fibrosis. A Phase 3 study is currently underway.
Other Notable Developments
Vicore Pharma's buloxibutid, targeting the renin-angiotensin system, hit both primary and secondary endpoints in a Phase 2a trial, demonstrating improved lung function. Pliant Therapeutics' bexotegrast, a dual inhibitor targeting αvβ6 and αvβ1 integrins, decreased total lung collagen and alleviated chronic cough symptoms in a Phase 2a trial. Surrozen and TCGFB are collaborating to discover antibodies targeting TGF-β, while Arda Therapeutics is exploring antibody-drug conjugates for IPF treatment. Contineum Therapeutics, which recently went public, is advancing its LPA1R antagonist into a Phase 1b study.
With approximately 3 million people worldwide affected by IPF, the development of new treatments beyond nintedanib and pirfenidone is crucial. Biopharmaceutical companies are actively pursuing diverse drug types and targets to address the unmet needs of IPF patients.
