Topline Findings
- MetaVia Expands DA-1241 Research: The collaboration with Syntekabio leverages AI-driven DeepMatcher technology to identify new therapeutic indications for DA-1241, an oral GPR119 agonist targeting cardiometabolic diseases.
- Promising Phase IIa Results in Metabolic Dysfunction-Associated Steatohepatitis (MASH): DA-1241 demonstrated significant reductions in liver enzyme alanine transaminase levels, biomarkers of inflammation and fibrosis, and improved glycemic control in patients with MASH.
- DeepMatcher AI Accelerates Drug Discovery: Syntekabio’s DeepMatcher platform enables large-scale virtual screening and lead optimization across diverse protein targets, enhancing the precision and speed of identifying novel drug candidates.
MetaVia announced a research collaboration with Syntekabio, an AI-driven drug discovery company, to explore additional indications for DA-1241, its oral GPR119 agonist currently in development for cardiometabolic diseases. According to MetaVia, the partnership builds on positive results from a Phase IIa trial (NCT06054815), a 16-week study involving 109 patients with presumed metabolic dysfunction-associated steatohepatitis (MASH), including those with pre-diabetes or type 2 diabetes.1,2
How Will MetaVia and Syntekabio Expand the Potential of DA-1241?
"The strong safety and tolerability profile shown in our Phase IIa data gives us confidence in DA-1241's broader therapeutic potential," stated Hyung Heon Kim, president, CEO, MetaVia, in a press release. "Building on this clinical foundation, we are collaborating with Syntekabio to strategically expand the potential value of DA-1241. Specifically, we will leverage their proprietary DeepMatcher compound-protein interaction (CPI) AI prediction platform to conduct large-scale virtual screening against more than 1,700 validated protein targets to uncover new, high-potential indications while ensuring specificity and minimizing the risk of off-target effects.”
Clinical Potential ofDA-1241
The novel oxyntomodulin (OXM) analogue has a similar function as GLP1R and GCGR dual agonists, according to MetaVia. OXM a natural gut hormone, activates GLP1R and GCGR to lower food intake and increase energy expenditure. This mechanism of action may produce favorable reductions in body weight vs. selective GLP1R agonists, the company stated in a press release.
Key Findings from the Phase IIa Trial
- Results from the trial, first published in May, showed that patients with baseline alanine transaminase (ALT) levels between 40 and 200 U/L experienced dose-dependent reductions in ALT, with the 100 mg dose achieving a statistically significant 22.8 U/L decrease after 16 weeks, regardless of diabetes status.
- The 100 mg dose also significantly lowered key biomarkers of systemic inflammation and fibrosis.
- Notably, cytokeratin 18, a marker of liver cell death, decreased by 30.5%.
- Beyond liver-related effects, DA-1241 demonstrated strong glycemic control, reducing hemoglobin A1c (HbA1c) by 0.37%, 0.41%, and 0.54% at weeks four, eight, and 16, respectively, from a baseline of 6.99%, even though nearly half of the participants were non-diabetic.
- Among patients with type 2 diabetes, HbA1c fell by 1.08%.3
What Is Syntekabio’s DeepMatcher Platform?
Syntekabio describes DeepMatcher as an AI-based platform designed to predict interactions between small molecules and target proteins, a critical step in drug discovery. Built on a biophysics-informed deep learning framework, the platform enables more precise identification of compounds across large chemical spaces, including those with novel structures.
