GATC Health Corp and researchers from the University of California, Irvine (UCI) have published a joint study in the Proceedings of the National Academy of Sciences (PNAS). The peer-reviewed paper validates a novel drug candidate, GATC-1021, which was identified using GATC Health’s Operon AI platform to more precisely target the specific neurological dysregulations found in individuals with opioid use disorder (OUD).
The research was a collaboration led by Christie D. Fowler and her team at UCI’s Department of Neurobiology and Behavior, alongside GATC Health’s drug discovery team. By integrating GATC’s Operon platform with UCI’s preclinical expertise, the team successfully moved from identifying human brain biomarkers to discovering and validating a highly effective therapeutic in record time.
By leveraging AI to model complex human brain biology, GATC-1021 was designed to achieve a level of multi-target precision that would be difficult to identify through conventional methods, enabling simultaneous modulation of addiction-relevant pathways and delivering robust reductions in fentanyl intake without the safety and behavioural liabilities often associated with current therapies.
“This study provides compelling evidence for the power of AI-directed drug development to accelerate innovation,” said Fowler, lead author and professor & Chancellor’s Fellow, Neurobiology and Behavior at the Charlie Dunlop School of Biological Sciences at UCI.
“By using AI to analyse human postmortem brain tissue, we were able to design a compound that not only reduces opioid intake, but also directly addresses the underlying biological dysregulation driving addiction—something that has historically been difficult to achieve with conventional drug discovery approaches.”
The study, titled “AI-Derived Therapeutic Development of a Serotonin Receptor Targeting Drug for the Treatment of Opioid Use Disorder,” highlights several key milestones.
The GATC Operon platform identified a unique “biomarker signature” from human data that pointed to the dual modulation of the 5-HT2A and 5-HT6 serotonin receptors as a key treatment mechanism.
Preclinical trials conducted at UCI demonstrated that GATC-1021 significantly decreased fentanyl intake in both male and female subjects.
GATC-1021 treatment was shown to increase the percentage of thin dendritic spines, which are involved in learning and memory, and upregulated neuroplasticity genes like Bdnf in the prefrontal cortex.
Despite targeting serotonin receptors, the non-opioid GATC-1021 did not induce hallucinogenic-like behaviours (head-twitch responses), suggesting it can provide the neuroplastic benefits of psychedelics without the associated side effects.
“These findings provide a powerful prospective validation of our Operon platform’s ability to move from human tissue data to a highly efficacious drug candidate based on preclinical studies,” said Ian Jenkins, GATC’s chief science officer.
“By identifying markers of dysregulation directly from human brain tissue, GATC Health was able to bypass traditional ‘trial and error’ discovery, significantly accelerating the path to clinical potential.”
With more than 3m Americans suffering from OUD and a surge in synthetic opioid deaths, the need for innovative strategies is urgent. Current treatments like methadone and buprenorphine face challenges with long-term adherence and safety. GATC-1021 offers a promising new direction by focusing on a “polypharmacy” approach—targeting multiple biological pathways to restore balance to the brain’s reward system.
Rahul Gupta, president of GATC Health and former director of the White House Office of National Drug Control Policy – the first physician to serve in the role – said: “Having led the nation’s response to the opioid crisis, I’ve seen how important it is to expand the range of effective treatment options. GATC-1021 was designed from human data to target key neurological drivers of opioid dependence, with the goal of offering a non-opioid approach. Enabled by AI, this work points to a potentially complementary path that could broaden access to affordable care and support more people on their path to recovery.”