GLP-1/Amylin/GIP/Glucagon GPCR Unimolecular/Multi-Receptor Ago-PAMs
Targeting multiple metabolic GPCRs with a single molecule offers the promise of developing therapeutics with superior efficacy and reduced side effects for the treatment of obesity and diabetes by simultaneously activating complementary pathways to better regulate appetite, energy balance, and metabolism.
Oban has identified a highly conserved allosteric pocket present across all the major metabolic GPCRs, including GLP-1, GIP, glucagon and amylin receptors. We are targeting this site for the development of a novel class of small molecules: pan-metabolic multimodal agonists that possess intrinsic agonism (direct activation) combined with positive allosteric modulator (PAM) activity across multiple receptors.
Next Development Milestone: Identification of clinical lead compound
Peptide GPCR (Ago-biased)
Oban is targeting development of therapeutics for obesity and diabetes at a unique peptide GPCR which can simultaneously regulate both sides of energy balance: suppression of appetite and increase in energy expenditure.
Small molecule drugs targeting this GPCR offer the potential of a complete metabolic intervention as a monotherapy or in combination with GLP-1, GIP, or amylin agonists, providing a non-overlapping mechanism to increase energy expenditure and enhance fat-specific weight loss.
Next Development Milestone: Identification of clinical lead compound
GLP-1 Neuronal Activator (Ago-biased)
Oban is targeting a GPCR that selectively stimulates brainstem GLP-1 neurons projecting to the hypothalamus satiety centers but is not present on the nausea-producing brainstem neurons of the chemoreceptor trigger zone (CTZ).
Small molecule drugs which can activate this receptor have the potential to produce a robust and sustained reduction in food intake while bypassing the mechanism underlying nausea and vomiting, the most limiting side effect of current GLP-1 Receptor Agonists (GLP-1 RAs). Biased small molecule GLP-1 NA agonists have the potential to be used as monotherapy or in combination with GLP-1, GIP, or amylin agonists.
Next Development Milestone: Identification of clinical lead compound
Muscarinic M4 (Ago-PAM)
OBN-06 is a proprietary, orally active, muscarinic M4 receptor ago-PAM for neuropsychiatric and neurological indications. The compound exhibits best-in-class selectivity for the M4 receptor with essentially no activity at the highly related muscarinic M2 receptor, associated with cardiovascular effects. OBN-06 exhibits dose-dependent activity in commonly used animal models of schizophrenia/psychosis, including reversal of amphetamine- and PCP-induced hyperlocomotion, as well as amphetamine-induced impairments in prepulse inhibition, a measure of sensory gating function. Notably, these effects occur in the absence of cardiovascular side effects that have been reported for other less-selective compounds in this class.
Current Status: IND-enabling studies
Next Development Milestone: Filing IND for Schizophrenia