The race to develop new obesity drugs is playing out with measures of how much and how quickly patients shed weight. Raj Kannan, CEO of startup Alveus Therapeutics, sees the field shaping up as a crowded market with me-too drugs offering incremental differences. He also sees this field focusing on the quantity rather than the quality of weight loss.
Some of the weight patients lose is lean mass, which is basically everything else besides fat. Gastrointestinal side effects continue to be a problem for these drugs. These complications lead many patients to discontinue treatment, and when that happens, the weight that returns is fat, not lean mass.
“We wanted to solve the biggest unmet need in the marketplace, which is not losing weight,” Kannan said. “You have drugs today that you can lose weight on, so we want to certainly offer that. But where we thought that we need to build a portfolio is around maintaining that weight loss, providing better tolerability and meaningfully better body composition benefits.”
Enhanced Direct Enrollment: Georgia Access and the Power of Partnership
Across the nation, state-based health insurance exchanges are searching for ways to better serve their communities while making enrollment easier, more personal, and more accessible for everyone.
Alveus has been quietly researching new obesity medications for the past two years. On Thursday, the Philadelphia- and Copenhagen-based startup revealed $159.8 million in financing to support a pipeline led by a drug that could rival an obesity product in late-stage development by Amgen.
Alveus’s lead program, ALV-100, targets two receptors, GLP-1 and GIP. Those receptors are already addressed in a single drug by an FDA-approved product, the blockbuster drug Zepbound from Eli Lilly. The pharmaceutical giant engineered this weekly injectable peptide drug to activate both targets. By contrast, the Alveus drug activates GLP-1 but blocks GIP.
Whether to agonize or antagonize GIP as a way to treat metabolic disease continues to be a matter of debate in the drug R&D community, but there’s growing momentum in the GIP-blocking camp. Amgen is in late-stage clinical development with MariTide, an antibody-peptide conjugate designed to activate the GLP-1 receptor and block the GIP receptor. Helicore Biopharma addresses only the GIP receptor. After emerging from stealth nearly a year ago backed by $65 million in financing, the startup began Phase 1 testing of its antibody GIP antagonist, HCR-188, as a potential treatment for obesity.
Alveus’s preclinical research indicates drugging GLP-1 and GIP together are complementary, protecting against weight gain while also enhancing the effect on GLP-1, said Alveus Chief Scientific Officer and Head of R&D Jacob Jeppesen. He also pointed to the clinical trial data to date for Amgen’s obesity drug as further validation of this approach.
The Power of One: Redefining Healthcare with an AI-Driven Unified Platform
In a landscape where complexity has long been the norm, the power of one lies not just in unification, but in intelligence and automation.
“The combination here is really important,” Jeppesen said. “And then we have the clinical data from MariTide suggesting or showing that there is really great synergies between those mechanisms.”
The long-acting antibody component of Amgen’s drug is intended to support a dosing interval of a month, perhaps even longer. Alveus chose a fusion protein rather than a peptide to hit GLP-1 and GIP for durability of effect that enables less frequent dosing, Jeppesen said. An investor presentation states Alveus is aiming for quarterly dosing. Kannan said the goal is to offer dosing advantages over other obesity drugs and the planned Phase 2 study will evaluate a range of dosing intervals.
Alveus was founded and incubated by New Rhein Healthcare Investors, which provided seed financing for the startup. Jeppesen was Alveus’s first employee, bringing his experience in diabetes and cardiovascular drug research at Novo Nordisk. He was soon joined by Chief Business & Strategy Officer Brian Bloomquist, an 18-year veteran of Eli Lilly. Kannan, who was most recently CEO of I-Mab, said that rather than building Alveus around a technology platform or even a molecule, the startup was tasked with building a portfolio that reflected where the market for obesity drugs would be in the future.
Like many new obesity drugs moving forward in clinical development, Alveus’s lead asset came from China. ALV-100 advanced as far as Phase 1 testing in Australia under China-based Gmax Biopharm. Alveus licensed ex-China rights to the drug.
The startup’s internally developed pipeline stems from Jeppesen’s research on another target, the amylin receptor. Novo Nordisk and Roche are among the companies developing amylin-targeting drugs, but there are multiple amylin receptors. Jeppesen said research in recent years has yielded greater understanding of what happens when each amylin receptor is activated. Alveus’s ALV-200 is a peptide engineered to selectively activate amylin receptor 3, leading to desired metabolic outcomes such as satiety and lean mass preservation, he said. The Alveus pipeline also includes a non-selective oral small molecule designed to target amylin and calcitonin receptors.
Alveus’s Series A financing was led by New Rhein, Andera Partners, and Omega Funds. The other disclosed participants in the round were Sanofi Capital, Kurma Partners, and Avego BioScience Capital. Kannan said the capital will support plans for Phase 2 testing of ALV-100. By the second half of 2027, Alveus expects to have data that characterizes the molecule and enables the company to select the Phase 3 dose. The capital will also support the rest of the pipeline, including plans to advance ALV-200 to the clinic in mid-2027.
“We built a portfolio really to offer diversity and flexibility, which we believe will really be the future of the obesity market, focusing in on these unmet needs,” Jeppesen said. “And that’s really what has been the focus from day one, to build that portfolio.”
Photo by Alveus Therapeutics