With GLP-1 receptor agonists expected to dominate the weight loss market in the near term, several young companies are building on this mechanism, while others are taking a completely different approach.
The 2021 and 2023 approvals of Novo Nordisk’s Wegovy and Eli Lilly’s Zepbound, respectively, ignited a GLP-1 market that is expected to exceed $100 billion in the next decade. GLP-1 receptor agonists are expected to remain the main class of anti-obesity drugs and dominate the space for at least the next several years, and several startups with GLP-1 assets have debuted over the past few years. In addition, some new companies are taking different approaches.
Costanza Alciati, a pharma analyst at GlobalData, told BioSpace in an email that GLP-1s will definitely dominate the market in the near future, but “new entrants into the space are already looking for the next drug class that could revolutionize the space.”
Companies taking an alternative approach are forecast to capture only a very small portion of the obesity market—roughly 6.3%—across the seven major markets (U.S., France, Germany, Italy, Spain, UK and Japan) by the end of 2031, according to Sara Reci, a senior analyst at GlobalData.
The weight-loss focus is of course not limited to startups but applies to many other companies—including Novo and Lilly. In addition to investigating products with novel molecular targets, the industry is looking toward alternate routes of GLP-1 administration and extended intervals between treatment, among other strategies.
“The first generation is the GLP-1 [agonist] injection; the next will be combinations and different dosing,” Damien Conover, director of equity strategy at Morningstar, told BioSpace.
Smaller players are far behind leaders like Novo and Lilly, said Evan Seigerman, managing director and senior research analyst at BMO Capital Markets. “If they are not in Phase II right now, it will be very hard to get something approved by 2028 or 2029,” he told BioSpace. “They need to run large Phase III trials to evaluate efficacy and safety. Smaller companies are figuring out what to do next, and the good ones will get acquired.”
Here are five startups that have launched into the obesity space within the past six years and the approaches they’re pursuing.
Metsera
Founded in 2022 by Population Health Partners and ARCH Venture Partners, Metsera is focused on developing next-generation medicines to treat obesity and metabolic diseases. The clinical-stage company emerged from stealth in April with $290 million in financing, led by ARCH Venture Partners. Metsera’s pipeline of injectable and oral products is sourced from the company’s proprietary library of over 20,000 gut hormone peptides and peptide/antibody conjugates. Products currently in development include an injectable GLP-1 receptor agonist in Phase I trials with what the company claims is a potentially class-leading duration of effect; a dual amylin/calcitonin receptor agonist (DACRA) that is engineered for duration of effect and will be used in combination with the GLP-1 receptor agonist; and a unimolecular GLP-1, GIP, glucagon (GGG) asset designed to be combined with the DACRA.
35Pharma
Founded in 2021, 35Pharma is a private, clinical-stage biopharmaceutical company with a focus on designing and developing transforming growth factor-beta (TGF-beta) superfamily ligand traps to treat pulmonary hypertension, obesity and cardiometabolic diseases.
35Pharma is currently developing HS135, a multi-specific receptor ectodomain ligand trap designed to neutralize activins & GDFs, which according to the company are clinically validated drivers of cardiopulmonary and metabolic disease. After encouraging preclinical study results, Health Canada cleared the way for a Phase I clinical trial in January. The single-center, double-blind, randomized, placebo-controlled trial in healthy postmenopausal women will study the safety, pharmacokinetics and change in biomarkers related to activin and GDF biology following subcutaneous administration of HS135.
ProFound Therapeutics
ProFound Therapeutics is leveraging previously undiscovered human proteins to develop treatments for a wide range of diseases. Flagship initially committed $75 million to found the company in 2022, enabling the continued expansion of its ProFoundry platform for the discovery of new targets and supporting the company’s efforts to build a robust R&D pipeline.
Last month, ProFound and Pfizer announced that they will conduct research on potential first-in-class therapies for obesity. This collaboration is part of potential $7 billion partnership struck between Flagship and Pfizer in 2023.
Metaphore Biotechnologies
Like Profound, Metaphore was also launched by Flagship, in its case just last year with an initial commitment of $50 million. Metaphore’s MIMiC platform uses biomimicry and machine learning in a bid to harness what it calls transformative therapeutic potential of functional molecular mimics.
In 2024, Metaphore and Novo Nordisk announced a collaboration to create a portfolio of novel research programs to develop transformational medicines, including new therapies for obesity management. The terms of the agreement will see Novo paying up to $600 million in upfront, development and commercial milestone payments, as well as tiered royalties on annual net sales of licensed products, to be shared between Metaphore and Flagship. Novo will also reimburse R&D costs and participate in a future financing round for Metaphore, according to the announcement.
EraCal Therapeutics
EraCal Therapeutics, spun off from the University of Zurich and Harvard in September 2018, is another company focused on developing novel strategies to treat obesity. In January 2022 it formed a research collaboration with Novo Nordisk aimed at identifying new drug targets that could regulate food intake and other metabolic phenotypes.
Then, earlier this year, the startup signed a partnership and license agreement with Novo focused on developing and marketing an oral, small-molecule treatment for obesity. Under the agreement, Novo obtained all exclusive rights to develop and commercialize EraCal’s oral small molecule asset. In return, EraCal will receive upfront, development and commercial milestones of potentially $255 million, and royalties on sales if the drug reaches the market.
The small molecule was discovered using EraCal’s platform technology and uses a new mechanism of action to regulate appetite and body weight. It is an appetite inhibitor that targets an undisclosed protein that controls peripheral liver-brain signaling. The candidate also works with GLP-1-targeting agents but doesn’t bind to any of the currently known anti-obesity drug targets such as serotonin 5HT2C or GLP-1 receptors.
