Alcohol use disorder (AUD) is a major global health issue. In the US, AUD affects over 14 million people over theage of 18. While there are three approved drugs for AUD, less than 4% of patients eligible for pharmacotherapyare prescribed a medication - likely due to limited efficacy of currently approved agents. Also, the relapse ratefor AUD continues to be exceedingly high. Thus, new therapies are urgently needed for AUD. Both preclinicaland clinical evidence suggest that antagonism of the type 1 cannabinoid (CB1) receptor is a promising strategyfor AUD. However, first generation CB1 blockers produced adverse psychiatric effects in ~6% of patients makingthem unsuitable for chronic use. Artiam Bio is developing second generation CB1 blockers that are designed tobe efficacious without producing adverse psychiatric effects. Artiam Bio's approach takes into consideration thatintrinsic activity of the CB1 receptor is required for emotional welfare, and that first-generation full inverseagonists/antagonists like SR141716A (rimonabant) completely abrogated this necessary beneficial process. Thecompounds developed by Artiam, including its lead molecule and backup, are high affinity but low intrinsicefficacy partial inverse agonists that preserve basal activity of the CB1 receptor - thereby reducing thepotential of adverse neuropsychiatric events. Supportive evidence comes from rodent studies presented in thisapplication. For this Phase 1 STTR application, Artiam's team will partner with investigators from University ofNorth Carolina's Bowles Alcohol Research Center to perform efficacy studies with its lead compound in a ratmodel of alcohol consumption and relapse. Further, additional behavioral studies are proposed in anxiety-pronemice using a chronic dosing regimen to further de-risk Artiam's lead compound for clinical development.Successful completion of these studies will pose Artiam's lead compound, which has good drug-like properties,for clinical development to treat AUD.
Public Health Relevance Statement: PROJECT NARRATIVE
We have developed specialized blockers of the type 1 cannabinoid receptor. We will test one such compound for
alcoholism, which is a major problem. In addition, we will do studies to de-risk this compound for eventual
clinical development.
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