Researcher turns startup founder to pursue promising oral diabetes drug

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rep shalev tiximed v 353x500pxAnath Shalev, M.D., director of the UAB Comprehensive Diabetes Center, launched TIXiMED in 2021 to translate her lab's discoveries into an oral medication that limits the need for insulin and improves quality of life for patients with diabetes. Human trials could begin in late summer 2023.For many people who have Type 1 diabetes, life can become a seven-letter word: insulin.

“One of the repeatedly expressed challenges of those with diabetes is to be completely dependent on daily injections of insulin or insulin pumps,” said Anath Shalev, M.D., director of UAB’s Comprehensive Diabetes Center (UCDC) and professor in the Department of Medicine. Shalev has spent the past two decades pursuing a new treatment option — one that can actually reverse the effects of diabetes. She has found something so promising that it convinced her to do something she had always resisted: start a company.

At TIXiMED, which launched in 2021, “our team is ultimately aiming to provide an additional oral medication to limit the need for insulin and help manage glucose control and improve quality of life,” Shalev said. That medication could enter human trials as early as late summer 2023.

“We tried to find other ways of doing it”

Twenty years ago, Shalev identified a protein involved in the beta cell death behind diabetes: TXNIP. At that point, Shalev was a researcher at the NIH’s National Institute of Diabetes, Digestive and Kidney Diseases. She knew that long years of careful experiments lay between this discovery and a drug that could treat patients.

A decade later, at UAB, Shalev and her team identified a common blood pressure drug that could cut TXNIP production in half. They received funding from a foundation, JDRF, to conduct a clinical trial of the blood pressure drug verapamil. The success of that trial paved the way for more studies, including one published in March 2022 that followed patients with Type 1 diabetes for two years after they started taking verapamil. Trial participants taking verapamil required less insulin than those who did not, and other Type 1 diabetes-induced changes were reversed as well.

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But it was always clear that verapamil was a proof-of-concept, rather than the end goal. In parallel with its verapamil studies, Shalev’s lab identified a small molecule, TIX100, that targets TXNIP more effectively, without the side effects that verapamil can bring. (In addition to protecting against models of Type 1 and Type 2 diabetes, TIX100 has shown protective effects for nonalcoholic fatty liver disease.)

Shalev’s work with TIX100 garnered significant attention from the scientific and diabetes community, and she was encouraged by many to spin off the intellectual property into a startup.

About the UAB Comprehensive Diabetes Center

The UAB Comprehensive Diabetes Center is a University-Wide Interdisciplinary Research Center with more than 200 faculty members from 10 different schools and many departments.

“My response was ‘I’m a researcher, not a businessperson,’” Shalev said. “I was very reluctant. It was really only when we exhausted everything we can do in academia that I began to consider it. We tried to find other ways of doing it, but this was the best way to reach our goal of getting it to patients.”

“We have to have partners”

In July 2021, TIXiMED officially incorporated, with Shalev and Michael Goodrich, principal of Birmingham-based private-business incubator First Avenue Ventures, as co-founders. Shalev also is chief scientific officer for TIXiMED. “We have to have partners in moving this forward,” she said. “I took my sweet time in finding a person I could truly trust, and I found that in Mike Goodrich. We also got to work with great investors for our seed round and now are looking at expanding these partnerships.” In fall 2022, Shalev received the EntrepreHER award from the Bill L. Harbert Institute for Innovation and Entrepreneurship at UAB as part of its annual Innovation Awards.

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In 2021, First Avenue Ventures launched a multimillion-dollar life sciences fund with a focus on research developed at UAB.

No one understands the science behind TXNIP and TIX100 better than Shalev, but now the work required revolves around questions of manufacturing and navigating regulations: safety and toxicology studies, applying for an investigational new drug (IND) designation from the Food and Drug Administration, and so on. “That is something that needs to be done with professionals,” Shalev said. “It is a massive amount of work, and we are glad to be supported by our scientific advisory board, development team and several expert contractors. I think it’s a good model for a small company — stay lean while employing top expertise.”

The final studies required for FDA approval of a first-in-human clinical trial were completed in December 2022, and “we should be on track to apply early this year,” Shalev said. “If everything goes well, TIX100 could be in patients by late summer. That is exciting.”

Shalev says her experience is setting a precedent for other researchers in the Comprehensive Diabetes Center hoping to accelerate their discoveries to the clinic. “Each entity is very different,” Shalev said. “Is it a small molecule? A biologic? At what stage will it need external support? That affects whether you need lab space outside the university, for example. There are many different variables, but what we are trying to do in the Comprehensive Diabetes Center is create a pipeline, so that when the next person may need to start this process, they don’t have to reinvent the wheel.”

“Major headaches, but it can be a lot of fun”

A new founder offers advice for other researchers considering launching a startup:

Go in with eyes wide open. Launching your own company “is a lengthy process,” Shalev said. “I don’t recommend that anyone jump in without thinking long and hard beforehand. It is a challenge and a steep learning curve. If you do it, you have to do it right. When I was considering it, I had a lot of people tell me to run …. But luckily, I also got a lot of encouragement and support.”

Build strong teams. “By entering this new arena, the amount of expertise required, especially if you are at a later stage as we are with TIXiMED, is hard to overestimate,” Shalev said. “You have to have partners who are true professionals in multiple distinct areas; having good, knowledgeable people to work with is key. This is why TIXiMED has contracted several top research and manufacturing organizations to cover all the expertise needed. Now we have these team meetings with each of them, and there are between five and 10 highly qualified people on the call: chemists, toxicologists, regulatory specialists — everyone who needs to be involved to move this forward.”

There are rewards, too. “It’s not all a piece of cake, but it can be a lot of fun,” Shalev said. “It has been a year and a half of very heavy work to get this far. It has caused me some major headaches, but I have enjoyed it. As a physician-scientist, to see it coming all the way to getting ready to go into patients is very rewarding.”