AI-Created Insilico Drug Shows Promise in Lung Disease, But Competitors Lead - MedCity News

An Insilico Medicine drug candidate, developed through the company's artificial intelligence technology, has yielded clinical data indicating breathing improvements in patients with a severe lung disorder. This preliminary data is promising for both Insilico and the AI-driven drug discovery field, although specific details are scarce. This makes it challenging to thoroughly assess the drug’s efficacy and compare it to rival treatments, including a molecule some industry experts consider potentially superior.

The targeted disease is idiopathic pulmonary fibrosis (IPF), a chronic condition that leads to lung scarring and a decline in lung function. IPF impacts around 5 million people globally, primarily affecting older adults, and has a median survival rate of three to four years post-diagnosis. The cause of IPF remains unknown, and current treatments only slow its progression without altering the disease's course.

Insilico's drug, ISM001-055, inhibits Traf2- and Nck-interacting kinase (TNIK), an enzyme involved in disease-related signaling pathways. While TNIK inhibition has been explored for cancer treatment, Insilico's technology identified it as a promising target for fibrosis, which is a hallmark of IPF. Utilizing generative AI, the company designed the small molecule now in clinical trials for IPF. This development process, including preclinical data and results from initial Phase 0 and Phase 1 studies, was published in Nature Biotechnology in March.

The recently announced results stem from a placebo-controlled Phase 2a study involving 71 IPF patients in China. Participants were randomly assigned to receive either a 30 mg dose once daily, a 30 mg dose twice daily, a 60 mg dose once daily, or a placebo. The 12-week study aimed to evaluate the safety and tolerability of ISM001-055 at various doses, with improvements in forced vital capacity (FVC)—the amount of air a person can exhale—serving as a secondary endpoint.

Insilico disclosed that ISM001-055 met its primary safety endpoint and showed positive results in the secondary efficacy endpoint, indicating a dose-dependent improvement in FVC, with the most significant improvement seen in the group receiving the 60 mg dose once daily. More detailed data will be presented at an upcoming medical conference and submitted for publication in a peer-reviewed journal. A parallel Phase 2 study is currently enrolling patients in the U.S.

Following these positive mid-stage results, Insilico plans to discuss the design of a Phase 2b study with regulatory authorities. This future study will explore extended treatment durations and larger patient groups. Meanwhile, Insilico remains competitive in the IPF drug development field but still lags behind other contenders.

On September 16, Boehringer Ingelheim reported that its IPF drug candidate achieved the main goal in pivotal studies, setting the stage for regulatory submissions to the FDA and global health authorities. Boehringer’s drug, nerandomilast, inhibits phosphodiesterase 4B (PDE4B), an enzyme involved in inflammation regulation. Boehringer conducted two placebo-controlled Phase 3 studies, one for IPF and the other for progressive pulmonary fibrosis (PPF), both aiming to measure the absolute change in FVC at 52 weeks. Preliminary results indicated that nerandomilast met this primary goal, with full data to be presented early next year.

Pliant Therapeutics is also in the race with its drug, bexotegrast, a small molecule inhibitor of TGF-beta, a signaling protein that contributes to IPF by increasing collagen production, which leads to lung stiffness and functional loss. Pliant’s Phase 2 results showed that bexotegrast led to a reduction in collagen and corresponding improvements in lung function and cough severity.

PureTech Health is looking to improve on pirfenidone, an older IPF drug, with its candidate LYT-100, which has chemical modifications to enhance tolerability. A Phase 2b study is evaluating LYT-100 against pirfenidone and placebo, aiming to show improved safety and potentially better efficacy at higher doses.

Insilico's progress, along with ongoing advancements from competitors like Boehringer Ingelheim, Pliant Therapeutics, and PureTech Health, underscores the active and evolving landscape of IPF drug development, with each company striving to offer the next breakthrough treatment for this debilitating disease.