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While a couple of frontrunners have taken the early lead in the race to capture the market for obesity drugs, major pharmaceutical firms still see a lot of room for innovation and growth in this area, experts from companies working in the space told the BIO CEO and Investor Conference.
“This is not a field like oncology, where we’ve had 55 years of a war on cancer, understanding the molecular pathogenesis of disease. I think that we’re really just at the tip of the iceberg. So we’re seeing a lot of engagement with pharma,” said Elaine Cheung, Chief Business Officer at Moonwalk Biosciences, during a Jan. 10 panel at the New York conference entitled “Obesity: Next Medicines with Impact.”
Panelists’ descriptions of their company’s innovations, and the value they can contribute, show the field has evolved in a number of fascinating ways, as the next generation of weight loss drugs—as well as combination/sister drugs—gain maturity and are poised to enter the market.
Moderator Michael Yee, Managing Director at Jefferies, said obesity drugs are set to be a $100-150 billion class of medications. “There is no bigger topic in healthcare than the GLP-1 revolution—short of AI,” he added.
The variety of the field was exemplified by panelists’ description of their firm’s clinical-phase drug candidates, some with results coming soon.
“Five different companies, five different exciting products,” Yee said. “Only two of the companies have GLP-1 based products.” The other three panelists represented companies that are actively researching and making headway on different aspects of weight loss science to help solve the industry’s most pressing issues, as well as expand the landscape for what these metabolic drugs can do.
Improving tolerability
One key improvement researchers are investigating is the gastrointestinal (GI) tolerability of GLP-1 drugs.
“An area that we really see some limitations in the current class of GLP-1s is around adherence and retention. The discontinue rate is pretty high,” explained Kent Hawryluk, President & CEO at MBX Biosciences. “Almost 65% of obese patients in a JAMA study discontinued, less than half of them reinitiated. And we know that that’s largely the GI side effect that’s driving that.”
This is one reason that drugs outside of GLP-1s are getting so much attention—and why further research into how to improve GLP-1 drugs continues.
For example, CB1 drugs, which target cannabinoid receptors, are making a surprise comeback in the weight loss space—a development no one saw coming even a year ago, Yee said.
“The goal of weight loss and treating obesity is to do it in a manner that’s healthy and sustainable,” said Puneet Arora, Chief Medical Officer at Skye Bioscience, which is in Phase 2 of its clinical trial for a CB1 drug. “The GLP-1s are great drugs. They have taken us to a point where we’ve demonstrated that you can get great weight loss and you can target biological pathways.” But, he added, there is more to be done.
“What we want to do at this point is to treat obesity in a way that’s not just a suppression of appetite,” Arora continued. “We want to do it in a way that’s sustainable, where you can preserve lean mass, preserve energy expenditure, preserve people’s ability to keep weight off over the long term, and to target the core of the disease—not just decrease appetite.” CB1 drugs, he argued, are solving a number of those issues—as well as addressing past stumbling blocks.
Protecting against psychiatric effect
The resurgence of CB1 drugs highlights another issue: preventing these drugs from passing through the blood-brain barrier.
As Yee explained, early CB1 drugs, despite their effectiveness for weight loss, had some notable psychiatric effects, including suicidality—a contributor to the previous “bearishness” around their use.
Early CB1 drugs, which were small molecule drugs, were only effective if they got high enough doses inside the central nervous system, past the blood brain barrier—but that was also when the psychiatric effects, which included everything from foggy headedness to even feeling “high,” began.
Arora said researchers at his firm, Skye Biosciences, are working to develop peripherally restricted small molecules. The monoclonal antibody Skye Biosciences is developing is engineered to go to the periphery of the blood brain barrier, achieving impressive efficiency in weight loss without crossing the blood brain barrier.
Improving retention
Patient retention is also an issue when it comes to weight loss drugs, Hawryluk said,
Patients are more likely to stick with a drug that doesn’t require increased amounts of dosing, which is why a number of researchers are looking into ways to develop drugs that patients may only have to take once a week, or even once a month. The bonus element to this research is that these drugs are simultaneously addressing GI tolerability, Hawryluk noted.
The use of oral drugs instead of injectable ones is another potential means of improving long-term retention, said Xiayang Qiu, Founder and CEO of Regor Therapeutics, whose firm is working on a small molecule, oral drug.
The research into small molecule weight loss drugs also addresses the issue of scalability, Qui noted “It’s proven that you can take a small molecule drug once daily, for example, and many chronic diseases can be treated,” he said.
Muscle’s role in weight loss
Another interesting aspect of the panel’s discussion was the role that lean muscle mass has in weight loss.
Jay Backstrom, President & CEO of Scholar Rock, explained his company is addressing muscle mass retention for those taking weight-loss drugs by targeting latent myostatin. “Our approach to cardio metabolic research is really founded on our understanding of muscle and the regulation and how, in fact, muscle plays such a role in metabolism, insulin sensitivity, glucose uptake, when you look at the effect of loss of lean muscle mass with the existing therapies, we thought we could enhance the profile by preserving lean muscle,” he said.
Scholar Rock’s work in the role of lean muscle mass and weight loss, is also addressing the issue of the quality of weight lost by patients. Patients using early weight loss drugs were reporting unideal levels of decreased muscle mass. As such, it is interesting that research into how drug developers can address this takes an almost fighting-fire-with-fire approach.
Epigenetics in weight loss
Cheung from Moonwalk Biosciences, discussed her company’s research into the role of epigenetics when it comes to weight loss.
“I think the role of gene expression regulation, which is fundamentally controlled at the epigenomic level, plays a huge role in these weight conditions,” she said. “And so being able to interrogate, discover and then validate those targets and pathways is very central to our approach.”
The concept is enticing: If epigenetics plays a role in things like mental health along the familial genetic line, why not weight?
The introduction of the epigenetical aspect of the conversation was reflective of just how complex the weight loss conversation has become. If the rapid expansion of research between 2024 and 2025 is any indicator, the sky’s the limit for weight management in the coming years.
