The obesity drugs taking the market by storm are great—leading to substantial weight loss for patients and potentially changing the course of future disease. But Regeneron’s Chief Scientific Officer George Yancopoulos, M.D., Ph.D., sees plenty of room for improvement.
“Despite all the enthusiasm surrounding GLP-1 agonists for obesity, it has been increasingly recognized that the profound weight loss is accompanied by substantial muscle loss, accounting for up to as much as 40% of the weight loss,” Yancopoulos said during a fourth-quarter earnings call Friday morning. “This potentially irretrievable muscle loss can be catastrophic for patients. It may even lead to major public health concerns in the future.”
Regeneron wants to fill the gaps in care with a combo approach from its pipeline, adding trevogrumab or garetosmab to semaglutide (Wegovy) to improve the quality of weight loss that patients experience.
The obesity market is currently owned by Novo and Eli Lilly, which have Wegovy and Zepbound, respectively, approved for the indication.
Regeneron is also testing a solution for what happens after treatment with Novo Nordisk’s semaglutide ends. Once a patient has lost the weight, how can they keep it off without continuing with the weekly injections forever?
A phase 2 study is expected to get underway in May, according to Yancopoulos. The trial will test the addition of the anti-myostatin trevogrumab to semaglutide with and without the anti-activin A medicine garetosmab to improve the quality of weight loss, as well as maintenance post-semaglutide. Enrollment is set to start midway through the year once results from an early safety study are available in healthy volunteers.
“We believe that inhibiting new pathways on top of GLP-1 receptor agonism has the potential to achieve comparable overall reductions in body weight, but with improved quality of a weight loss, resulting in more fat loss while preserving or actually increasing muscle mass,” Yancopoulos said.
Yancopoulos acknowledged that there are other companies out there trying to provide a similar supporting role with muscle preservation via myostatins, but said Regeneron is taking a unique approach thanks to the in-house discovery of two ligand growth factors that control muscle size. Regeneron’s meds aim to block the antibodies for both.
“It's going to be a combination of both efficacy and safety that matters here,” Yancopoulos said. He believes that Regeneron’s more targeted approach will avoid some of the safety issues that will crop up with other myostatin efforts.
Roche is one of the companies working with myostatins. The Swiss pharma bought out Carmot Therapeutics late last year, with hopes of combining the anti-myostatin antibody RO7204239 with the biotech's incretin treatments. RO7204239 was originally being tested to strengthen the muscles of people with spinal muscular atrophy but CEO Thomas Schinecker similarly sees a role in patching up problems with GLP-1s.
On 2seventy
Earlier this week, Regeneron announced the acquisition of 2seventy bio’s cell therapy pipeline, which will be tucked into a new unit called Regeneron Cell Medicines. A handful of staffers from the oncology-focused company will come over to Regeneron as well.
Yancopoulos said the goal of the deal is to combine Regeneron’s antibody capabilities with 2seventy’s cell therapy approach. The two companies have worked together since 2018.
“Thus far, even in the setting of this collaboration, the CAR-T space has been separate from the biologic space,” he said. “And even though we were working together as separate companies, it was a little harder to really move forward in an expedited fashion the incredible opportunities that I believe that we have to combine what we think is the largest and most exciting portfolio of biologics in immunotherapy together with cell therapy approaches.”
Now, with the assets in house, Regeneron can try something different.
“Nobody else has really tried that. Nobody else has really led that,” Yancopoulos said. “Now that we're really together all in with our new selected colleagues from 2seventy and their capabilities, we believe that we will now have the first opportunity to really try this new set of combination approaches against cancer.”
He continued: “We believe we will be alone in that capability until somebody else tries to copy us and do what we're doing here.”