MORGANTOWN – A groundbreaking new drug that could revolutionize the treatment of opioid use disorder was developed here in Morgantown. Human clinical trials are on the horizon. And the findings from the first successful testing have been published in the Proceedings of the National Academy of Sciences.
The drug is called GATC-1021, developed by California-based GATC Health at its Morgantown lab in the WVU Innovation Corp., using the company’s Operon AI platform.
We talked with five people about the creation and development of GATC-1021, and you’ll see some common themes among them – about addressing the stigma of opioid use disorder (OUD), about the importance of this advancement taking shape here in West Virginia, and more.
First, a quick bit of background: GATC’s Operon AI platform simulates human physiology and biochemistry, to help predict what is a safe drug, what is an efficacious drug, what drug doesn’t have off-target side effects even before it gets into the clinic. This reduces the risk, time, and cost of traditional drug discovery while simulating clinical trial outcomes before laboratory work begins.
Alexa Martin, a WVU alumna and senior scientist at GATC, led the drug development. Other forms of treatment, such as buprenorphine and methadone work via harm risk reduction – they use one opioid to wean the person off another. GATC didn’t want to take that route, she said.
They also didn’t want to go the route – now making some use – of using psychedelics. Instead, GATC-1021 treats the underlying condition.
Through the Operon platform, she said, they identified a biomarker signature [the FDA explains that a biomarker is a defined characteristic that is measured as an indicator of normal biological or disease processes, or responses to an exposure or intervention] from human brain tissues – in this case the the brain tissues of 20,000 deceased fentanyl addicts who donated their brains to science.
Identifying that biomarker led GATC to develop the GATC-1021 compound that targets serotonin pathways implicated in addiction. [The Cleveland Clinic explains that serotonin is a chemical that carries messages between nerve cells in the brain and throughout your body. influencing learning, memory, happiness as well as regulating body temperature, sleep, sexual behavior and hunger. Lack of enough serotonin is thought to play a role in depression, anxiety, mania and other health conditions.]
Testing of the GATC-1021 compound in fentanyl-addicted rats, Martin said, showed reduced fentanyl use without any noticeable behavioral issues or physical side effects.
The compound also increased markers of “neuroplasticity,” defined as the brain’s capacity to change and adapt in response to experiences, learning, and environmental changes.
In long term addiction, Martin said, the things that used to provide that happiness don’t work, only the drug provides that serotonin pleasure. The brain gets rewired to say it needs fentanyl to survive. GATC-1021 helps leverage the brain the other direction, so it doesn’t need fentanyl.
When Martin came to the Morgantown lab in 2023, she said, GATC had already sketched out the concept of what they wanted. She was their first chemist and began doing computational work. It took about 2 ½ years to reach the stage of the rat studies – instead of the 12 years to prepare for FDA filing in typical pharmaceutical development.
Martin emphasized the hometown angle of GATC’s work. They’re investing money in their lab and, in consequence, in the community. The staff is growing. They have collaborators in WVU’s chemistry department, pharmacy school, medical school. “We’re really trying to utilize the fact that we’re just across the street from WVU.”
And they’re bringing people back to West Virginia – as they did with her, she said.
The rats
Christie Fowler, professor at University of California Irvine, conducted the rat testing and published the article in PNAS. GATC approached her to do the pre-clinical studies in her lab, she said.
Operon, she said, had targeted two receptors in the brain – the serotonin 2A and 6 receptors. Historically in drug development, they try to target just one.
“This is a more kind of nuanced approach, with different levels of activation of two receptors to see if we could get a better outcome, and that’s what we were able to show.”
They tested two compounds and the one called GATC-1021 proved more effective. They used a self-administration procedure with an implanted catheter that allowed the rats to get fentanyl through IV infusions. They were trained to press a lever to get the infusion.
Through the testing, “We did see a decrease in the number of fentanyl infusions, so they took less fentanyl over time.” And testing their behavior, they saw no negative side effects.
Fowler said she is not involved with the next steps of GATC-1021 but offered some perspectives.
“I think it will be really interesting to see with this drug molecule if it can be used with other substances of abuse.” Other opioids, cocaine, nicotine act on similar mechanistic pathways in the brain – so it could have broader application. And drug use often comes with comorbid mental health disorders, so perhaps it could be effective there.
Drug use carries a stigma, she said. Seeking help can also carry a stigma. And companies veer away from therapeutic development because it’s not profitable – because people don’t obtain treatment because of the stigma.
“Giving people the grace and hope and understanding – that people who are dependent on drugs, they can have a really productive future in our society, and so being able to develop therapeutics to help them is really essential.”
The vision
Tyrone Lam is chief business officer of GATC Health.
With the rat trials complete and the PNAS article published, he said, they are pursuing an Investigational New Drug enabling application with the FDA, in hopes of beginning human trials next year.
“From a company standpoint, it’s really validating,” he said. They took on one of the most difficult therapeutic areas – the neurological disease of addiction. This validates their AI platform and opens the door to other possibilities of treating all sorts of central nervous system and neurological diseases – PTSD, anxiety, depression.
Personally, he said, “I’m very hopeful. … The opportunity to help remove the stigma associated with addiction is big.”
Patients are reluctant to take medications that are addictive. “To have a medication that actually treats the source of the disease, actually makes it more reputable that it [addiction] is a disease. … Let’s keep our fingers crossed that this drug is going to get into the market sooner than later.
“I think it’s going to remove a lot of the stigma associated with opioid use disorder and addiction in general,” he said. “I think law enforcement and the judicial system are going to be elated.” A GATC-1021 pill can’t be diverted, repackaged and sold on the black market – because it won’t deliver the thrill of an addictive drug.
Looking ahead at GATC here in West Virginia, they are pursuing treatments for diabetes and ALS. They have 11 full-time employees and a state-of-the-art lab.
For GATC-1021, “I’m hopeful that at least some of the early clinical trial is going to happen in West Virginia and the surrounding region.” West Virginia has been at the forefront of the opioid epidemic and through local trials patients could get access to treatment before the final FDA approval.
“We want it happen in West Virginia, because it’s the right place.”
The addiction expert
Dr. Stephen Loyd is chief medical officer of Cedar Recovery – a chain of treatment facilities in Tennessee and Virginia – and director of the West Virginia Office of Drug Control Policy.
He met Lam, he said, in Washington, D.C., during the pandemic. Lam’s planned development of an OUD medication stirred his interest.
The two most effective OUD medications are opioids [methadone, buprenorphine], Loyd said, and Lam was looking at drug development for treatments that aren’t controlled substances.
On top of that was the AI approach – being able to predict the body’s physiological response without putting it in a body, shortening the timeframe of drug development.
And GATC-1021 offers faster healing of the connection between the reward system and decision-making parts of the brain. “For me, that’s a game changer in what I do every day,” he said.
About 1 in 10 people get help for OUD, Loyd said. Many don’t get help because of the stigma. On top of that, methadone is one of the most effective treatments for fentanyl use disorder but West Virginia has a moratorium on methadone clinics. “The reality is that puts a hamper on people reaching out for help.”
And some refuse treatment because they don’t want to use opioids.
So GATC-1021 offers hope, he said. So does another avenue of research going on at WVU’s Rockefeller Neuroscience Institute: focused ultrasound, led by RNI Executive Director Ali Rezai.
“This is a paradigm shifting possibility, along with what’s going on there at RNI,” Loyd said. “They’re going to open up access to treatment that does not involve controlled substances, and I think that’s a massive deal.”
The state advocate
Dr. Tom Takubo wears several hats: state senator, physician specializing in pulmonary critical care, and executive vice president at WVU Medicine. He has been a key advocate for bringing GATC to Morgantown.
Takubo talked about first meeting Lam and learning about GATC Health. “What was so fascinating for me is the synergies of what we’re trying to do here in West Virginia.”
The state has the nation’s oldest, sickest, most poorly educated population. When he won election to the Legislature in 2014, the opioid death rate was already the nation’s highest, at 32 per 100,000. But that number soared to 110 per 100,000. It’s trending down a bit now, but still a major issue.
“The advantage of what GATC’s been able to do, is they can treat thousands at a time. That’s what’s really going to move the needle,” Takubo said. “Part of what GATC is doing is kind of letting the world know, hey, there is a new way of doing things. For West Virginia, being a part of that, that’s all a plus.”
Lam also joined in this conversation, and both delved into the West Virginia aspect.
“We could have moved to any state,” Lam said. “We chose West Virginia.” With the emphasis on “speed of business,” GATC can get fast decisions. And there are two major research universities working on addiction and chronic health conditions.
He has a vision of pharmaceutical research, development and manufacturing companies coming here that might want to use the Operon platform to accomplish their work more efficiently.
And, Takubo said, he is encouraging the universities to look ahead and develop a platform to assist GATC in doing drug development. That will benefit the nation and world, but West Virginia first.
“That’s what we’re working on. We keep working every day toward it.”
