February 2025: Obesity & Weight Loss - Antibody Drugs
Biointron2025-02-03Read time: 5 mins
Antibody therapeutics are emerging as a promising avenue in the fight against obesity, a condition that significantly elevates the risk of cardiovascular disease, type 2 diabetes, and certain cancers. Anti-obesity medications often target appetite suppression or metabolic enhancement, but antibody-based treatments can also modulate specific biological pathways involved in fat storage and energy balance. As the prevalence of obesity continues to rise globally, the development of antibody-based therapies could provide a targeted and effective treatment option, complementing existing strategies and addressing the complex mechanisms underlying obesity.
On January 28, Helicore Biopharma emerged from stealth to continue advancing its portfolio of first-in-class GIP antagonists for obesity and related conditions. HCR-188, a clinic-ready monoclonal antibody, is entering first-in-human clinical studies with top-line data anticipated in the second half of 2025. They are building on existing validation of GIP pathway antagonism with differentiated antibody format and a novel focus on binding to GIP, rather than to GIP receptor. They successfully raised $65M in Series A funding, with a portfolio including GIP antibody conjugates.
DOI:10.1126/sciadv.abf1948
On January 2, iBio, Inc. offered a potential $29M deal with AstralBio for a preclinical anti-myostatin antibody (IBIO-600) that it hopes can induce weight loss while retaining muscle mass. By binding to the FcRn receptor with over 10-fold higher affinity than normal IgG, the subcutaneously administered antibody holds potential for reduced dosing frequency. In vivo studies in rodents and nonhuman primates have begun, with first results expected in early 2025 and clinical trials not expected until 2026. iBio itself has initiated a bispecific antibody program targeting myostatin/activin A to treat obesity and cardiometabolic disorders.
Image credit: iBio
Further down the pipeline, Laekna and Eli Lilly and Company have agreed on a clinical collaboration for LAE102, a monoclonal antibody targeting Activin Receptor Type 2A (ActRIIA) for the treatment of obesity. ActRIIA is a receptor that has been shown to play a critical role in muscle regeneration and lipid metabolism. This collaboration aims to accelerate development of LAE102 through phase 1 study, with the potential to offer muscle-preserving weight loss in patients with obesity. LAE102 has shown preclinical promise by increasing lean mass and decreasing fat mass, and may become a complementary treatment to GLP1R agonists.
Myostatin/activin signaling in muscle. DOI: 10.1016/j.biocel.2013.05.019
Excitingly, there are two novel antibody-based drugs in Phase 2 trials towards the treatment of obesity! Skye Bioscience Inc.’s nimacimab is a humanized monoclonal antibody that blocks CB1 signaling, which can have anti-fibrotic, anti-inflammatory and metabolic actions. CB1 is expressed throughout the body, especially in tissues important to metabolism and metabolic disorders such as adipose (fat), muscle, stomach, liver, and kidneys. CB1 inhibition in fat tissue directly promotes the expenditure of energy stored in fat, and therefore the breakdown of fat. They began a phase 2 trial last August as a weight loss therapy in obese patients while assessing lean mass retention and gastrointestinal side effects. The injection is being studied on its own and in combination with Wegovy, Novo Nordisk’s GLP-1 weight loss blockbuster. Phase 2 obesity data is expected by Q2 2025.
Meanwhile, Amgen’s maridebart cafraglutide (MariTide) is a bispecific glucagon-like peptide 1 (GLP-1) receptor agonist and glucose-dependent insulinotropic polypeptide receptor (GIPR) antagonist. This antibody-peptide conjugate molecule is being investigated for the treatment of obesity and Type 2 diabetes mellitus. Pre-clinical studies have demonstrated that simultaneously activating GLP-1 and inhibiting GIP pathways had a stronger effect on weight loss than targeting either GLP-1 or GIP receptors alone. As of now, MariTide is under ongoing Phase 2 trials, and has demonstrated up to ~20% average weight loss at 52 weeks without a weight loss plateau in people living with obesity or overweight.
Image credit: Amgen
All in all, antibody-based therapies represent a promising frontier in obesity treatment, offering targeted interventions that address specific biological mechanisms underlying weight gain. Recent developments have demonstrated the potential of monoclonal antibodies, bispecific antibodies, and antibody conjugates! As research progresses, these therapies may complement existing treatments, providing more personalized and effective options for individuals struggling with obesity.
