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Novo Nordisk is pairing up with another Flagship-founded biotech to create new obesity medications, and GLP-1 remains in the frame. The Danish pharma giant, which leads the GLP-1 field alongside Eli Lilly, will tap into the “molecular mimicry” work at Metaphore Biotechnologies to make one or two obesity management therapeutics, the companies said Thursday morning. Novo will deliver up to $600 million in upfront payments and biobucks to Metaphore and Flagship’s Pioneering Medicines. Novo and Pioneering Medicines have a broad relationship that also includes an obesity pact with Omega Therapeutics . You’ll get access to free articles each month, plus you can customize what newsletters get delivered to your inbox each week, including breaking news.

Novo Nordisk is doubling down on its quest for novel obesity medicines, inking a potentially lucrative deal with Flagship Pioneering start-up Metaphore Biotechnologies to develop up to two multitarget therapeutics using the biotech's MIMIC platform.The Danish drugmaker could shell out up to $600 million in upfront and milestone payments, plus royalties, spurring hopes that Metaphore's machine learning-powered molecular mimicry approach could unlock a new class of longer-acting, more potent medicines aimed at the GLP-1 receptor and related obesity pathways.'Molecular mimics'"Metaphore's platform aims to mimic the interactions between molecules with impressive accuracy by capturing their natural dynamics at the point of interface, potentially leading to therapeutics that require infrequent dosing," noted Uli Stilz, head of Novo Nordisk's Bio Innovation Hub. The approach systematically isolates pharmacophores – the essential features where a drug binds its target – and designs "molecular mimics" that are then enhanced with fine-tuned therapeutic properties like function, selectivity, and multi-targeting.The collaboration stems from Novo Nordisk's strategic partnership with Flagship Pioneering from 2022. It also marks the third tie-up under the alliance following deals with Cellarity and Omega Therapeutics announced earlier the year to develop new treatments for obesity and metabolic dysfunction-associated steatohepatitis (MASH).As part of the latest deal, the partners will work toward advancing the programmes through to preclinical development, after which Novo Nordisk could decide to move them into clinical testing.Future financing roundIn addition to the up to $600 million in upfront, development and commercial milestones, and potential royalties to be split with Pioneering Medicines, Flagship's in-house drug development unit, Novo Nordisk will also cover research costs and participate in a future financing round for Metaphore. The biotech, which launched in 2023 with $50 million from Flagship, told FirstWord it had no additional details about the financing round "to share at this time."With over 800 million adults globally living with obesity, the pharmaceutical industry has been actively seeking to develop new treatments that could challenge Novo Nordisk's pole position with Wegovy (semaglutide). For its part, the Danish drugmaker continues to innovate in the space as well, with an obesity pipeline that includes a once daily oral version of Wegovy, as well as CagriSema, a fixed-dose, once-weekly injection combining semaglutide with amylin analogue cagrilintide. Both those programmes are currently in Phase III.The company is also working on once-daily oral and once-weekly subcutaneous forms of amycretin, a long-acting co-agonist of GLP-1 and amylin.

Pictured: Novo Nordisk's corporate headquarters in Denmark/iStock, Ole Schwander Novo Nordisk on Thursday entered into a research collaboration agreement with the Flagship-founded Metaphore Biotechnologies to develop up to two next-generation GLP-1 receptor agonists for the treatment of obesity. As per the terms of the deal, Novo will hand over up to $600 million in upfront, development and commercial milestone payments, and will reimburse R&D costs. In addition, Metaphore will be eligible for tiered royalties on annual sales of approved products that come out of the collaboration. The Danish pharma has also agreed to participate in a future financing round that Metaphore holds. In return, Novo will gain access to Metaphore’s proprietary MIMIC platform, which can copy the interactions between molecules, to develop multitarget investigational therapeutics that can activate the GLP-1 receptor and affect related pathways, according to Thursday’s news release. These candidates will be designed to have scalable, long-acting effects. Metaphore’s MIMIC platform will support the development of these next-generation GLP-1 candidates by creating high-resolution maps of what the biotech calls the “pharmacophore,” or the essential features of a molecule that can kick off a specific cascade. MIMIC then uses these pharmacophores as bases for novel therapeutic candidates, whose characteristics can in turn be fine-tuned. For instance, MIMIC-designed compounds can have better specificity and selectivity for their target or have multiple affinities, longer half-lives and other similar functionalities, according to Metaphore. Uli Stilz, head of the Novo Nordisk Bio Innovation Hub, said in a statement that Metaphore’s MIMIC technology has “impressive accuracy” at capturing the natural dynamics between molecules at their point of interface, “potentially leading to therapeutics that require infrequent dosing.” Thursday’s deal will allow Novo to also apply a machine learning approach to obesity management, Stilz added. Leveraging the power of AI might also help Novo retain its dominance in the lucrative obesity market, particularly as its main competitor Eli Lilly closes in. In March 2024, Reuters reported that Lilly’s weight-loss drug Zepbound—which is also a GLP-1 agonist but additionally targets the GIP receptor—surpassed Novo’s Wegovy in new prescriptions in the U.S. Aside from the growing market share of Wegovy, Lilly is also leading the industry in terms of oral GLP-1 treatments, with its small molecule drug candidate orforglipron currently in Phase III. Mid-stage data released in June 2023 underscored orforglipron’s strong potential, reducing body weight by between 9.4% and 14.7% at 36 weeks versus placebo’s 2.3%.In its full-year 2023 business report, the pharma announced that it was already ramping up manufacturing capacity for the oral candidate. Tristan Manalac is an independent science writer based in Metro Manila, Philippines. Reach out to him on LinkedIn or email him at tristan@tristanmanalac.com or tristan.manalac@biospace.com.