In a twist, preclinical research in metabolic disease is peaking more investor interest at the American Diabetes Association’s annual meeting than in past years.
As the GLP-1 and weight loss market becomes increasingly crowded, more companies have turned to earlier-stage candidates that use different mechanisms of action than GLP-1s. They’re also pivoting away from focusing on weight loss percentages and toward other markers of success, like preservation of lean mass, impact on the liver and cardiovascular benefits.
William Blair analyst Andy Hsieh told Endpoints News that investor interest in preclinical candidates is twofold: the commercial opportunity in the obesity space is “vast,” and potentially worth up to $150 billion, and companies are already working on the next generation of therapies, creating a “trickling down” effect.
“I think that’s what people are interested in in preclinical assets, which is: what’s next?” Hsieh said. “What’s beyond the GLP-1s?”
Gilead moves into obesity
Gilead’s oral GLP-1 candidate might be still at an early stage, but it’s already attracting attention from analysts.
At ADA this weekend, the company presented data from a preclinical study of GS-4571, which found that the drug improved glucose tolerance in mice and led to a 5% to 6% weight loss over five days. Obese monkeys saw an 8% weight loss over a month.
In a note on Friday, Jefferies analysts said their thesis has been that the preclinical program is not an important area of focus for Gilead. However, they also noted that Gilead “is presenting the data and wouldn’t present the data” if it didn’t care about the program.
The company is currently conducting the Phase 2 WAYFIND trial, which is trying out different combinations of the fixed-dose combination of cilofexor and firsocostat (both liver drugs) with Novo Nordisk’s semaglutide in non-alcoholic steatohepatitis (NASH), which is now sometimes referred to as MASH. According to ClinicalTrials.gov, it’s set to wrap in November.
Viking shows 10% fat loss in rats with dual agonism
Viking is developing a “series” of dual amylin and calcitonin receptor agonists (DACRAs) to test out their effect on body weight and other metabolic biomarkers in rats.
In an abstract published June 14, researchers determined that the dual agonism “represents a promising therapeutic approach to metabolic disorders such as obesity and diabetes.”
The drug also reduced the amount of food the rats would eat in the first three days after one dose. After three days following the dose, the rats saw up to an 8% reduction in body weight compared to the rats who were dosed with Novo’s CagriSema.
William Blair analysts agreed that the agonism is promising, writing in a Saturday note that they “view the new program as a positive surprise and are encouraged that management continues to expand its internal obesity care pipeline.”
Biohaven targets loss of lean muscle mass
Investors may have been disappointed in Biohaven’s autoimmune disease treatment earlier this year, but its preclinical myostatin inhibitor is showing progress in obese mouse models, according to data presented at ADA this weekend.
In line with efforts to help patients lose weight without losing lean mass, taldefgrobep alfa showed a “significant” reduction in body weight while also increasing lean mass. According to Biohaven, which is owned by Pfizer, these results showed promise as both a monotherapy and in combination with a GLP-1.
In the 4-week trial, taldefgrobep alfa as a monotherapy reduced fat by 26% and increased lean mass by nearly 15%, while semaglutide alone reduced lean mass by 6.5% at the highest dose. As a combo, weight loss was 7.6%, while lean mass increased by 15% at the lowest dose with semaglutide and 13% at the higher dose.
“These anti-myostatin medications have the potential to be an important partner with GLP-1s and optimize the overall health of individuals and prevent that lean mass loss that I think is really concerning,” Peter Ackerman, Biohaven’s VP of clinical development, told Endpoints News.