Supercede Therapeutics, a startup biotech company focused on small molecule drug development, announced promising preclinical efficacy data for its lead obesity treatment program. The company's oral small molecule inhibitor, SPCD-4-79, demonstrated significant weight reduction effects both as monotherapy and in combination with existing GLP-1 therapies in diet-induced obesity mouse models.
Novel Oral Approach to Validated Target
SPCD-4-79 represents the first orally bioavailable, low molecular weight compound designed to block the signaling activity of both isoforms of the Activin receptor Type II (ACTRIIA and ACTRIIB). The ACTRII pathway responds to ligands in the TGFβ superfamily, including Activin, Myostatin, and Inhibin E, inducing gene expression changes across multiple tissues including adipose, liver, and muscle.
Previous clinical validation of ACTRII inhibition came from Phase II studies using bimagrumab, a monoclonal antibody requiring intravenous administration. These studies, including work by Heymsfield et al. published in JAMA Network Open and the BELIEVE Study presented at the American Diabetes Association's 85th Scientific Sessions, demonstrated significant fat reduction while stimulating lean body mass increases. Eli Lilly acquired the bimagrumab program through its 2023 acquisition of Versanis Bio.
Compelling Preclinical Efficacy Data
In diet-induced obesity mice studies, SPCD-4-79 demonstrated dose-dependent efficacy across multiple metabolic parameters. As monotherapy, the compound achieved reductions of up to 34% in fat mass, 48% in total liver mass, 80% in liver fat, and 17% in overall body weight compared to vehicle controls.
Comparative studies with semaglutide showed the GLP-1 agonist reduced fat mass by up to 39%, liver mass by up to 61%, liver fat by up to 97%, and body weight by up to 21%. However, the combination of SPCD-4-79 and semaglutide produced superior results, reducing fat mass by up to 74% and overall body weight by up to 36%.
Preserved Lean Mass Profile
A critical finding was the preservation of lean body mass with the combination therapy. Both semaglutide alone and the SPCD-4-79 combination showed similar lean mass reduction of 8% and 9% respectively, primarily attributed to liver mass reduction rather than muscle loss. This suggests the combination maintains the lean mass preservation benefits associated with ACTRII inhibition.
Development Timeline and Next Steps
"We are excited about the preclinical demonstration of efficacy in DIO mice with our lead compound, both as monotherapy and especially in combination with GLP-1 agonists," said Ilan Zipkin, founder and CEO of Supercede Therapeutics. "These data provide additional motivation to advance the program through formal nomination of a development candidate and towards an IND and eventual clinical studies."
The company completed a seed financing round in 2024 and has generated novel intellectual property relating to ACTRII inhibition in obesity. Additional IP covering the lead compounds was licensed from Fudan University and East China Normal University in Shanghai, China, with representation by bioSeedin.
Supercede plans to advance SPCD-4-79 through formal development candidate nomination toward Investigational New Drug (IND) filing and clinical studies, potentially offering the first oral option for targeting the clinically validated ACTRII pathway in obesity treatment.
