The weight loss drug space is booming, and drugmakers can’t make enough GLP-1s like Ozempic, Wegovy, Mounjaro and Zepbound to meet the soaring demand. But the market, which could be worth upwards of $200 billion in the next decade, is also crowded with pharmas and biotechs clamoring to add their own blockbuster hopefuls to the mix.
One of the potential new drug classes comes from biopharma Rivus Pharmaceuticals — these controlled metabolic accelerators are once-daily oral doses that stand out in clinical trials by being as effective as GLP-1s without some of the negative side effects, the company claims. Despite a marked reduction in body mass, however, Rivus isn’t targeting the “weight loss market” and instead aiming to treat cardiovascular conditions, according to CEO Dr. Jayson Dallas, who was appointed to the top job last year.
“I think so much of the attention has pivoted to the cosmetic component of this,” he said. “And we come at this from a more therapeutic perspective.”
The company has two CMA candidates in the pipeline — the lead candidate HU6, currently in phase 2 trials, and RV-002 ANT-Activator, which is in preclinical studies. While Dallas doesn’t kowtow to the label of weight loss, both drugs are indeed targeting obesity among their indications. But HU6 is also targeting patients with the fatty liver disease MASH, heart failure with preserved ejection fraction and Type 2 diabetes, with interim trial results expected within the year.
With the ongoing studies using an untapped therapeutic target, Rivus aims to open the door to treating obesity, cardiovascular disease and liver conditions without resorting to a me-too GLP-1.
“I don't want to downplay the impact of the GLP-1s. As a clinician, I think it’s fantastic we actually have a viable therapeutic option today. But it's not the perfect solution for everybody.”
Dr. Jayson Dallas
CEO, Rivus Pharmaceuticals
A metabolic approach
Two of the biggest differences between the effects of CMAs and GLP-1s can be seen in muscle mass and metabolic rate, according to Dallas. GLP-1 agonists work by mimicking the action of glucagon-like peptide 1 hormones, stimulating the production of insulin when blood sugar levels start to rise. These effects help control diabetes directly, but also lead to weight loss by impacting hunger levels.
But the weight loss resulting from GLP-1s is not just fat loss and has been shown to cause muscle loss and a slower metabolic rate. The muscle loss associated with GLP-1 medications for some users has even led virtual care provider Omada Health to expand their GLP-1 program with a focus on regaining lost muscle mass. Last year, Eli Lilly began looking at combining its GLP-1 blockbuster Mounjaro, which exceeded $5 billion in 2023 sales, with experimental drug azelaprag, which has been shown to preserve muscle mass, from California biotech BioAge Labs.
CMAs, on the other hand, target metabolic rate, according to Dallas.
“Instead of working the energy intake side of the equation, our biology works on the energy consumption side of the equation,” Dallas said. “What if, independent of how much intake there is, we simply turned up your metabolism a little bit? What if in the background, our body was burning more calories and burning more energy as we went about our day-to-day business?”
CMAs break down sugars and fats to speed up the metabolic rate, reducing fat and treating a range of cardiometabolic diseases. The difference of a higher metabolic rate is “imperceptible,” he said, and the pill keeps muscle loss and inflammation to a minimum.
“At the cellular level, you're switching off the production of reactive oxygen species, or free radicals, and therefore shutting down inflammation,” Dallas said. “And if we look at our inflammatory response compared to others, we see about four times the reduction in a measure of inflammation … for the same amount of weight loss that you would expect given any other mechanism of losing weight.”
Dallas also claims CMAs have fewer of the tough side effects that come with GLP-1s, such as nausea, vomiting and diarrhea.
“I don't want to downplay the impact of the GLP-1s,” he said. “As a clinician, I think it’s fantastic we actually have a viable therapeutic option today. But it's not the perfect solution for everybody.”
Path to commercialization
Going forward, Dallas is focused on building the company’s discovery group. Since taking the helm, he has pushed to bring the group from its base in Charlottesville, Virginia, to San Francisco for access to a hub of biotech talent. The move is also part of the long-term thinking for future commercialization.
“As we think about scaling the organization toward an IPO and going public, and building up the organization, we needed to make certain that we had a footprint that also had a presence in what was a more traditional pharma/biotech talent pool geography that we could dig into,” said Dallas, who is already based in the Bay Area.
The company has raised $167 million in two fundraising rounds, including most recently a $132 million series B in 2022.
Dallas is bullish on the drug’s approval pathway after Madrigal Pharmaceuticals recently gained FDA approval for Rezdiffra, the first MASH drug on the market.
“We've now got line of sight to a regulatory pathway, but also line of sight to actually doing something that we can measure for this population,” he said.
