Verge Genomics has nominated a second development candidate, VRG201, targeting long-term weight management and metabolic homeostasis. VRG201 is an oral, first-in-class therapy that aims to correct the underlying metabolic dysfunction leading to obesity and help patients sustain weight loss while freeing them from significant lifestyle modifications.
Although glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have revolutionised weight management by reducing caloric intake, the results are often not sustained. Up to 50% of patients discontinue GLP-1 RAs within the first year and face rapid weight regain. VRG201 addresses these gaps by targeting the underlying metabolic pathways leading to abnormal weight gain and the development or worsening of obesity.
VRG201 selectively inhibits CD38, a critical enzyme in regulating cellular NAD+ (nicotinamide adenine dinucleotide) levels and energy metabolism. By restoring NAD+ balance and CD38 upregulation, VRG201 prevents excess calories from turning into fat by improving metabolic function. This mechanism supports VRG201’s potential to complement GLP-1 RAs and offers a new approach to treating metabolic disease.
Verge is focused on developing therapeutics for complex diseases with high unmet need, using human genomics from patient disease tissues and machine learning. Verge has created a proprietary, all-in-human CONVERGE platform, featuring one of the field’s largest and most comprehensive databases of multi-omic patient data. The company is led by experienced computational biologists and drug developers who are successfully advancing clinical and preclinical therapeutic programs in various diseases, including ALS and Parkinson’s disease.
“Using human patient multi-omics data, the CONVERGE® target discovery platform identified CD38 as a key regulator of metabolic dysfunction,” said Dr Robert H Scannevin, Chief Scientific Officer at Verge Genomics. “Recognising CD38’s central role in metabolic disease, we developed VRG201, a novel small-molecule inhibitor targeting CD38 enzymatic activity. VRG201 reduced weight gain in a preclinical, diet-induced obesity model and improved phenotypes linked to metabolic syndrome, including nonalcoholic fatty liver disease. Our innovative approach differs from oncology strategies that target CD38 with antibodies to destroy cancerous immune cells. Instead, VRG201 focuses on restoring NAD⁺ balance and addressing CD38 dysregulation, enhancing energy metabolism, and reducing fat storage. This mechanism offers a groundbreaking alternative to current obesity treatments, which often rely on appetite suppression. We are excited to pioneer the first small-molecule inhibitor of CD38 enzymatic activity into clinical trials, marking a significant leap in treating metabolic diseases through a unique mechanism.”
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