SMURF1

Insilico Medicine is offering up a closer look at mid-stage results for its AI-developed idiopathic pulmonary fibrosis (IPF) drug candidate, ISM001-055, which demonstrated improved lung capacity in patients — positioning it as a potential competitor in the challenging IPF space.The small molecule targeting TNIK achieved the primary safety endpoint as well as key secondary efficacy goals, according to a barebones topline readout in September.On Tuesday, Insilico said patients in a Phase IIa trial who received the highest dose of 60 mg daily showed a mean 98.4 mL improvement from baseline in forced vital capacity (FVC) at 12 weeks, while the placebo group experienced a 62.3 mL decline. The treatment group also saw a 3.05% improvement in percent predicted FVC from baseline, compared to a 1.84% decline in the placebo arm."We aim to set industry benchmarks for drug discovery and development using generative AI and commit to pioneering innovative solutions for complex medical challenges," said CEO Alex Zhavoronkov.The 71-patient trial, conducted in China, also revealed improvements in quality of life, with patients on the highest dose experiencing a meaningful 2-point improvement on the Leicester Cough Questionnaire.Safety data showed the drug was well-tolerated across all dosing groups. The most common side effects were diarrhoea and abnormal liver function, each occurring in 14.8% of treated patients, with all adverse events rated as mild or moderate.Eyeing pivotal trialInsilico says talks with regulatory bodies are up next, as well as the possible pursuit of a pivotal trial of ISM001-055 in IPF patients.Bearing in mind the shortcomings of cross-trial comparisons, the Phase IIa results appear competitive with existing IPF treatments. Roche's approved drug Esbriet (pirfenidone) showed treatment differences of 157-193 mL in FVC decline over 52-72 weeks in two Phase III trials, while a third study showed no significant difference. Boehringer Ingelheim's Ofev (nintedanib) demonstrated differences of 94-131 mL versus placebo in annual FVC decline across three clinical trials.Slow IPF progressThe IPF space has been riddled by setbacks. Companies like FibroGen and Galecto have terminated key IPF programmes and proceeded to trim their respective workforces due to study failures. Novartis also recently shut down mid-stage lung disease trials involving its SMURF1 inhibitor LTP001, including for IPF, although it hasn't yet shared detailed clinical results.However, the field received a boost when Boehringer announced its oral PDE4B inhibitor nerandomilast succeeded in Phase III testing—the first IPF drug trial to meet its primary endpoint in over a decade. The company said in September that it planned to submit regulatory applications in the US and other markets.Insilico plans to present detailed results from its Phase IIa study at an upcoming medical conference.

Novartis has terminated a mid-stage trial of an oral treatment candidate for idiopathic pulmonary fibrosis, the company confirmed to Endpoints News . The Swiss pharma giant axed a Phase 2 study of LTP001 last Thursday, according to the federal trials registry. The study cull was cited as a “sponsor decision.” A spokesperson added the company will “continue to evaluate future potential for IPF.” Investigators were testing the experimental medicine against placebo as a once-daily medicine for patients with IPF, in which lung scarring disrupts breathing and can lead to death within a few years of diagnosis. Some patients in the trial also received one of the two standard-of-care medicines, Roche’s Esbriet and Boehringer Ingelheim’s Ofev, both of which were FDA-approved in 2014. Generic versions of Esbriet are available and Roche confirmed in February it was looking at “potential options for Esbriet,” including a potential sale. Multiple other biotechs are working on potential treatments for IPF, including Pliant , PureTech and Avalyn Pharma . Boehringer is planning to send another IPF medicine, the oral drug nerandomilast, to the FDA for regulatory approval based on Phase 3 results last month. LTP001 is also being studied in pulmonary arterial hypertension, or PAH, a rare lung condition that recently received a key approval with Merck’s Winrevair. PAH impacts about 40,000 people in the US and causes high blood pressure in the lungs and heart. In Novartis’ July earnings presentation, PAH was listed as the lead indication for LTP001. Shortly thereafter, the company ended a placebo-controlled Phase 2 and an extension study of the candidate in PAH. On Monday, the spokesperson reiterated the company continues to advance LTP001 in PAH. “There have been no concerning or new safety signals observed to date,” the spokesperson added. LTP001 is an inhibitor of SMURF1, which has been found to be elevated in pulmonary arteries in animal models. Johnson & Johnson received an FDA green light for a single-tablet combination treatment for PAH earlier this year. Aerovate’s treatment candidate recently flunked a mid-stage test, which led to lay offs . Gossamer Bio and Diagonal Therapeutics are among other biotechs exploring this space.