TNIK

On the back of mid-stage data for its lead candidate, Insilico Medicine raised $110 million in a series E to progress its portfolio of AI-designed drugs, according to a LinkedIn post on Wednesday from CEO Alex Zhavoronkov. The round was led by Value Partners Group, which Zhavoronkov called one "of the largest publicly-traded asset management firms in Asia." Other existing investors, including Warburg Pincus, OrbiMed Advisors and Lilly Ventures, contributed to the round, which placed the private company's valuation at more than $1 billion, according to a report from Bloomberg. A January release from the government of Pudong — a district in Shanghai, China — said that Pudong Venture Capital, Puxing Synergy Fund and Xiyi Venture Capital also participated in the financing. The fresh capital adds to a $95-million series D total the biotech raised in 2022 across two tranches.AI assetsAccording to Insilico's website, it has 31 total programmes in development, with the most advanced being ISM001-055, a drug candidate for idiopathic pulmonary fibrosis (IPF). The company said in September that the small molecule targeting TNIK met the primary safety endpoint and key secondary efficacy endpoints in a Chinese Phase IIa study, and weeks later disclosed specific data from the trial. Patients with IPF who received the high, 60-mg daily dose of ISM001-055 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."However, the Phase IIa readout is not the only reason for this round," Zhavoronkov said in his post. "We have taken both the generative platforms and the reinforcement learning pipeline to a completely new level with over 700 different models. The funding will be used to progress the therapeutic pipeline and to advance and expand our end-to-end generative AI platform."In addition to ISM001-055, Insilico has nine other assets that have either begun clinical testing, or have received clearance from the FDA to do so. Three assets have been out-licensed to commercial partners, and a fourth is moving forward under a co-development deal with Fosun Pharma. The firm also has a discovery deal with Sanofi worth up to $1.2 billion in biobucks. The company's pipeline is supported by its Generative Biologics technology to design de novo peptides, nanobodies and antibodies; the PandaOmics target discovery engine platform; and its AI small molecule generation platform, Chemistry42, among others.

A clinical study testing a Pliant Therapeutics drug once considered a promising prospect for treating a fatal lung disorder is now on pause at the recommendation of independent outside observers. Pliant disclosed few details and said it is still reviewing data, but the clock is ticking for the company to figure out next steps for the drug and the patients in the clinical trial. The pause on the Phase 2b test is voluntary, Pliant said in its announcement after Friday’s market close. No new idiopathic pulmonary fibrosis (IPF) patients will be enrolled during this pause. Currently enrolled participants will remain in the study but will not be dosed with the experimental drug, bexotegrast. The study will remain blinded to preserve integrity of the data. Pliant said it has informed clinical trial investigators and is in the process of informing regulators. IPF is a progressive disorder in which scar tissue builds up in the lungs, leading to worsening lung function that eventually becomes fatal. The few available treatments slow IPF’s progression but do not modify the course of the disease. Bexotegrast is a small molecule designed to inhibit TGF-beta, a signaling protein that leads to the production of collagen that impairs lung function. presented by Artificial Intelligence What Keeps Healthcare CIOs Up at Night: Balancing Technology Investments with Consumer Expectations When it comes to managing inbound phone calls, underperformance has devastating cost implications. By Stephanie Baum Phase 2a results reported last year showed that after 12 weeks, the Pliant drug led to a reduction in collagen while the placebo group showed an increase in collagen. Pliant also said the reduction in collagen correlated with improvement in lung function. No safety signals were reported in this study. The trial that’s now paused is the Phase 2b portion of a Phase 2b/3 study designed to evaluate treatment with bexotegrast for 52 weeks. This placebo-controlled test was expected to post preliminary data in 2026. Over the course of a clinical trial, a data safety monitoring board, an independent body comprised of outside experts, evaluates safety and efficacy data at regular intervals. In Pliant’s announcement, the company said the board’s recommendation of a trial pause followed a prespecified data review. To Leerink Partners analyst Faisal Khurshid, the voluntary pause and the continued blinding of the trial could mean the trial did not trigger pre-specified stopping criteria for safety or efficacy. But it also means the board saw something concerning enough to recommend pausing all patient dosing, he said in a note sent to investors. Since the study did not meet pre-specified stopping criteria, Pliant may not be required to unblind the study, Khurshid said. Unblinding the study would mean all data integrity would be lost. Khurshid added that the board may be taking a conservative stance of not providing the exact reasoning to Pliant. That leaves the company to choose whether to unblind the data to learn the reason. Losing data integrity means Pliant would need to start over, assuming there is a path forward for the drug. The other choice is to maintain the blind and try to work with the board in a way that does not compromise data integrity. Sponsored Post The Funding Model for Cancer Innovation is Broken — We Can Fix It Closing cancer health equity gaps require medical breakthroughs made possible by new funding approaches. By Eve McDavid - CEO of Mission-Driven Tech “In theory we think the resolution could be something like stopping one of the dose levels, excluding certain patient types, or prohibiting certain background therapies,” Khurshid said. “Again, this is all speculation. It will be important this occurs quickly as many patients were midway through a 52-week dosing period and the handling of the dosing suspension may become an issue the longer this goes.” If the study is salvageable, moving forward would likely require a major amendment to the clinical trial protocol, Khurshid said. He added that even in an optimistic scenario, Pliant may need to restart a pivotal clinical trial program, which would mean a multi-year delay. Investors did not welcome any of these options. Shares of Pliant opened Monday at $3.02, down more than 61% from Friday’s closing price. Pliant is one of several companies working to develop new drugs for IPF. Boehringer Ingelheim is at the front with nerandomilast, a small molecule designed to inhibit phosphodiesterase 4B (PDE4B), an enzyme whose roles include regulating inflammation. After announcing this drug met the main goal of its pivotal IPF studies last September, the company said it planned to seek approvals from the FDA and other regulators around the world. Nerandomilast is also in development for a different respiratory condition, interstitial lung disease. On Monday, Boehringer reported the drug met the main goal of a Phase 3 study in this indication. Full safety and efficacy data will be released in the second quarter of this year. Meanwhile, PureTech Health is developing deupirfenidone (formerly LYT-100), which employs chemical modifications to improve the tolerability of the old IPF drug pirfenidone. In December, PureTech reported its drug met key goals of a Phase 2b study with results showing improvement in measures of lung function. Another company, Insilico Medicine, is in mid-stage clinical development with ISM001-055, a small molecule inhibitor of an enzyme called TNIK. This IPF drug candidate was discovered with Insilico’s artificial intelligence platform technology. Photo by Flickr user Dominick Guzzo via a Creative Commons license

iStock, jetcityimage Eli Lilly’s idiopathic pulmonary fibrosis deal with Mediar is centered around MTX-463, an anti-WISP1 antibody that early studies have found to be safe and capable of engaging its target. Eli Lilly on Friday entered into a global licensing deal with Mediar Therapeutics, aiming to develop a first-in-class therapy for idiopathic pulmonary fibrosis. The back-heavy deal will see Lilly hand over $99 million in upfront payment and near-term milestones, according to a Mediar news release, while the Boston biotech will be eligible to up to $687 million in downstream development and commercialization milestones. Mediar will also be able to receive high-single to low-double-digit royalties on future potential net sales. At the core of the deal is MTX-463, a potentially first-in-class human IgG1 antibody that targets and neutralizes the WNT1-inducible signaling pathway protein-1 (WISP1). Typically excreted into the extracellular environment, WISP1 plays a central role in the progression of fibrosis and is typically associated with the severity of fibrotic diseases. According to Mediar, early data from in vitro and mouse models suggest that inhibiting WISP-1 signaling could lower fibrosis. The biotech has recently completed a Phase I study of MTX-463 in healthy volunteers, demonstrating that the candidate could reliably engage WISP1—thereby interfering with its downstream signaling—while having an encouraging tolerability profile. Under Friday’s collaboration, Lilly and Mediar will push MTX-463 into Phase II development to test the antibody’s potential as a treatment for idiopathic pulmonary fibrosis (IPF), a respiratory illness characterized by scarring in the lungs, leading to breathing difficulties. The partners plan to launch the mid-stage study, led by Mediar, in the first half of 2025. After Phase II, Lilly will assume responsibility over all further clinical development and commercialization activities for MTX-463. Outside of MTX-463, Mediar will continue to independently develop its two other fibrosis programs, including the anti-EphrinB2 antibody MTX-474 and a SMOC2 program, for which it expects to nominate a candidate in the first half of this year. The Lilly-Mediar partnership is likely to shake up the competitive IPF space, which just months ago saw a pair of promising clinical readouts. In September 2024, Boehringer Ingelheim announced that its Phase III FIBRONEER-IPF study met its primary endpoint , showing that the investigational drug nerandomilast improves lung function in patients. At the time, the company announced that it planned to use FIBRONEER-IPF to support a drug application for nerandomilast. Days later, Insilico Medicine disclosed that its potential first-in-class small molecule drug ISM001-055 also cleared Phase IIa , with data showing that the anti-TNIK candidate elicited dose-dependent improvements in lung function.