SyntheX, Inc.

VantAI believes artificial intelligence is the best tool to solve the geometric puzzle of glue discovery. Bristol Myers Squibb is offering Roivant-backed VantAI up to $674 million biobucks in a new partnership aimed at designing molecular glues as small-molecule therapeutics. The Big Pharma wants in on New York-based VantAI’s artificial intelligence platform in hopes of developing molecular glues, which are small molecules used to stabilize interaction between two proteins that don’t typically interact. The deal involves undisclosed targets of interest, but VantAI could receive up to $674 million in milestone payments plus royalties, and BMS also has the option to tack on additional therapeutic programs, according to a Feb. 13 news release. The independent generative AI company is a former Roivant Sciences that now receives financially backing from the Big Biotech after breaking off last spring. The AI company uses geometric learning to gain information about naturally occurring, evolved interfaces to mimic those interfaces during the design process. VantAI then applies a “protein-contact-first” approach to simplify chemical design challenges involved when bringing proteins together in the cell. The approach is designed to help optimize parameters for potency, selectivity and molecule size. "Molecular glues have proven extremely difficult to find but hold great promise as a treatment modality across a vast array of diseases,” VantAI CEO and founder Zachary Carpenter, Ph.D., said in the company release. “At VantAI, we view glue discovery as a challenging ‘geometric puzzle,’ and we believe that artificial intelligence is the best tool to find the missing piece.”  In 2022, the AI company inked a multiyear molecular glue and protein degrader partnership with Johnson & Johnson’s Janssen. Financial details for the deal were not disclosed. As for BMS, the pact is designed to accelerate the pharma’s discovery engine and address key unmet patient needs, Neil Bence, Ph.D., BMS vice president and head of oncology discovery, said in the release. It’s not BMS' first rodeo with molecular glues. The pharma partnered with San Francisco biotech SyntheX in October 2022 to develop and commercialize new small-molecule degraders. The $550 million biobucks deal takes aim at multiple unnamed targets using pre-specified E3 ligases and neosubstrates of interest. The molecular glue space has exploded in the past few years, with Big Pharma Roche inking several related collaborations last year, including a Monte Rosa Therapeutics deal centering around hard-to-drug targets and a deal with Orionis Biosciences through its Genentech unit.   Meanwhile, Merck & Co. has also gotten in on the action through a partnership with Proxygen—an Austrian biotech that already had molecular glue deals with Boehringer Ingelheim and Germany's Merck KGaA. Editor's note: This story was updated at 1:15 p.m. ET to clarify Roivant's involvement in VantAI.

Monte Rosa Therapeutics will lead on discovery and preclinical activities “to a defined point.” Roche has signed its second molecular glue deal in a month, this time paying $50 million upfront to Monte Rosa Therapeutics for the use of its QuEEN platform to target cancer and neurological diseases previously considered out of reach. Monte Rosa will employ the molecular glue degrader platform to work on therapies for targets “previously considered impossible to drug,” the Boston-based biotech said in a Oct. 17 release. Beyond the upfront payment, the company is eligible to receive milestone payments that could top $2 billion as well as royalties should any resulting therapies make it to market. Roche also has the option of expanding the collaboration to additional targets within the next two years, for which further payments would be piled on. Monte Rosa will lead on the discovery and preclinical activities “to a defined point,” it explained in the release, with Roche getting the exclusive rights to take the resulting candidates through further preclinical development and into the clinic. “Our QuEEN discovery engine, a highly validated and industry-leading molecular glue degrader platform, has been the cornerstone for Monte Rosa’s success, driving the discovery and development of our exquisitely selective MGDs successfully into the clinic,” CEO Markus Warmuth, M.D., said in the release. “This collaboration will enable and accelerate expansion of our platform into neuroscience and additional areas of oncology.” The deal comes less than a month after Roche entered the molecular glue space with a similarly structured deal. Back in September, it was Boston-based Orionis that received $47 million upfront—with the promise of $2 billion in milestones—from Roche’s Genentech unit as part of a multiyear pact revolving around its Allo-Glue platform. In today’s release, James Sabry, M.D., Ph.D., global head of pharma partnering at Roche, described molecular glue degraders as “a powerful new class of small molecules that target disease-related proteins that traditional approaches have been unable to address.” “Together with Monte Rosa, we look forward to tackling high-value targets in both oncology and neuroscience with the goal of unlocking new therapeutic possibilities," Sabry added. It was a day of double good news for Monte Rosa, as the biotech celebrated what it claimed was the first demonstration of a molecular glue degrader against a solid tumor. The GSPT1-directed candidate, dubbed MRT-2359, was shown to “significantly reduce GSPT1 protein levels in patient tumors and has shown evidence of tumor size reductions” in interim data from a phase 1 dose-escalation study, Monte Rosa said. “We’re highly encouraged by the safety profile, the depth of pharmacodynamic modulation of GSPT1 in tumors, and even more so by the early evidence of anti-tumor activity of MRT-2359 in patients with biomarker-positive cancers,” Warmuth said in a separate release. Roche isn’t the only Big Pharma that’s been looking to stick some molecular glue assets onto its pipeline. In October 2022, Bristol Myers Squibb joined up with San Francisco biotech SyntheX to develop and commercialize new small-molecule degraders. In April of this year, Merck & Co. got in on the action through a partnership with Proxygen—an Austrian biotech that already had molecular glue deals with Boehringer Ingelheim and Germany's Merck KGaA.

Roche is teaming up with a young biotechnology company to develop medicines that break down proteins tied to certain cancers and neurological diseases.Announced Tuesday, the partnership between Roche and Monte Rosa Therapeutics carries a $50 million upfront payment. The Boston-based Monte Rosa could receive $2 billion more, provided its drug programs hit specific research, commercial and sales milestones.Established in 2018, Monte Rosa specializes in molecular glue degraders a relatively new type of medicine that, in effect, grabs harmful proteins and forces them down a cells garbage chute. The company came out of stealth in mid-2020, announcing $32.5 million in funding from its original investors Versant Ventures and New Enterprise Associates. A year later, it raised $222 million through an initial public offering.Monte Rosas research programs target a range of illnesses, from genetic disorders to inflammatory diseases to cancer. The companys most advanced drug, named MRT-2359, entered human testing about a year ago. An early-stage clinical trial is currently evaluating its safety, tolerability and activity in a selection of cancers, including lung, neuroendocrine and diffuse large B cell lymphoma, that had been previously treated. (Early data from that trial were disclosed Tuesday, sending shares down by double digits.)Now, the partnership with Roche will enable and accelerate expansion of our platform into neuroscience and additional areas of oncology, said Markus Warmuth, Monte Rosas CEO, in a statement.We believe that molecular glue degraders are a powerful new class of small molecules that target disease-related proteins that traditional approaches have been unable to address, added James Sabry, Roches global head of pharma partnering.The deal has Monte Rosa leading discovery and preclinical activities against multiple cancer and neurological disease targets, up until a defined point. Roche then gains the right to exclusively pursue further development of the compounds.Additionally, both companies have agreed to a deal term that would allow them to expand their collaboration within its first two years. Should they choose to, Roche would owe Monte Rosa further payments. The biotech noted that it still retains full ownership of its pipeline programs.Tuesdays announcement comes about a month Roches Genentech subsidiary inked a similar deal, agreeing to pay Orionis Biosciences $47 million upfront in a research collaboration focused on developing molecule glue degraders for cancer and neurodegenerative conditions.Molecular glue research has attracted interest from other large pharmaceutical companies as well. Merck & Co., for instance, has twice in the past two years linked up with the Austrian biotech Proxygen. And last October, Bristol Myers Squibb said it was working with a San Francisco-based biotech called SyntheX to discover molecular glue degraders. SyntheX received cash and investment up front, and could take home more than half a billion dollars more if it achieves certain performance-based milestones.Sanofi, Astellas and Incyte have also bet on targeted protein degradation by partnering with a wave of smaller biotechs that have dedicated themselves to this research. '