What if Type 2 diabetes could be treated by addressing insulin resistance before its damaging effects take hold? Temple researchers may have found a way. Now, their novel approach is moving beyond the lab and toward potential clinical development.

Developed by researchers at Temple’s School of Pharmacy, VTX-31 is designed to protect GLUT4, a protein that plays a critical role in moving glucose from the bloodstream into muscle and fat cells and restoring insulin responsiveness. To advance the technology toward further development and, ultimately, clinical testing, Temple has entered into an agreement with Valhalla Therapeutics.  

VTX-31 grew out of research led by biochemist Salim Merali, professor emeritus in Temple University’s School of Pharmacy, and School of Pharmacy collaborators Carlos Barrero, associate professor; George Morton, research scientist; and Wayne Childers, associate director of the Moulder Center for Drug Discovery Research. Their research identified damage to GLUT4 as an important factor in the development of insulin resistance.  

“What is significant about this work is that we are targeting the root cause of insulin resistance,” Merali said. “By protecting GLUT4, we may be able to restore how the system is supposed to function and ultimately change how metabolic disease is treated.”

Tracing insulin resistance to its source

When the body is working properly, insulin signals GLUT4 to move to the surface of the cell, where it helps bring glucose inside. When that process breaks down, glucose begins to accumulate in the bloodstream, contributing to insulin resistance and eventually Type 2 diabetes.  

Merali found that this breakdown begins earlier than previously understood. Excess nutrients and high-fat diets can trigger oxidative stress, a kind of chemical imbalance inside cells. That stress can damage proteins, including GLUT4, interfering with the body’s ability to process glucose.  

“When we eat that much, our cells work overtime, especially the mitochondria,” Merali said. “As it is working overtime, the mitochondria produces oxidative stress. One of the proteins that we found got damaged was GLUT4.”

The finding helped shift how insulin resistance is understood. Instead of viewing it only as a condition that emerges after broader metabolic dysfunction, the research pointed to a more precise molecular trigger.

“These findings challenged the prevailing views of insulin resistance,” Merali said. “It links overnutrition to impaired glucose metabolism.”

That insight led to the development of VTX-31. Unlike GLP-1 therapies, which primarily affect appetite and hormone signaling, VTX-31 is designed to protect GLUT4 and preserve the process that allows insulin to help cells take in glucose.

From discovery to spinout

Valhalla Therapeutics gives the Temple technology a pathway forward. Temple entered into an exclusive startup agreement with the company, led by pharmaceutical and biotechnology executive and entrepreneur Ihor Terleckyj, to advance VTX-31.  

For Terleckyj, who has spent much of his career developing and commercializing diabetes therapies, the potential of the approach stood out because it targets a different point in the disease process.

“Within minutes of reviewing the data, I saw the potential for VTX-31 to slow the progression of Type 2 diabetes and transform how the disease is managed over the long term,” Terleckyj said.  

Supporting the path from science to market

One of the earliest champions of Merali’s research was the late Peter Doukas, who served as dean of the School of Pharmacy for more than 30 years. Doukas encouraged Merali and his team to pursue not only what the research could reveal about insulin resistance, but also what that discovery might one day make possible for patients.

That reflected a philosophy Doukas championed throughout his tenure: that discoveries in pharmacy should have a path beyond the laboratory, including the potential to become new medicines and technologies. His early support helped the team continue exploring both the scientific significance of the GLUT4 findings and their therapeutic possibilities.

As the research progressed, Temple provided additional support to help move it closer to commercialization. Merali’s work was selected for the first cohort of Temple’s Innovation Flight Fund, which provides funding to help high-potential research reach key commercialization milestones.

“Temple is a strong research enterprise producing discoveries that have reached the market,” said Josh Gladden, vice president for research. “But getting those discoveries to the point where they can be licensed takes years of development and significant university investment to answer the right questions along the way.”

Temple’s technology commercialization team also helped establish Valhalla and continues to support the company through the Innovation Nest, or iNest, connecting it with industry experts, investors and other resources. These efforts have included opportunities at the 2026 BIO International Convention and a Mid-Atlantic Diamond Ventures.

“Spinning out a company based on a Temple discovery is not the end of our work with an entrepreneur,” explained Stephen Nappi, associate vice president of technology commercialization and business development. “Our team continues to support companies as they move forward, helping them build industry relationships, connect with investors and identify resources needed to advance the technology and build a successful company.”

Moving closer to patients

The technology already has a foundation in human disease: The damage to GLUT4 that inspired the therapeutic approach was first identified in a human study. Subsequent disease models showed that VTX-31 improved insulin responsiveness and measures of organ function.  

The next step is to build on that evidence through further development and, ultimately, clinical testing to determine whether the therapy is safe and effective in patients.

“Together, those findings provide a strong rationale for advancing VTX-31 into further development,” Terleckyj said. “We believe it could be especially valuable for patients with difficult-to-treat Type 2 diabetes who face the greatest risk of complications, including kidney failure, heart attack, vision loss and stroke.”

Because disrupted glucose metabolism is involved in multiple metabolic diseases, VTX-31 could also have applications beyond Type 2 diabetes, including metabolic dysfunction-associated steatohepatitis, or MASH, a serious liver disease previously known as NASH, and the prevention of diabetic complications.

For Merali, commercialization is the next step in fulfilling the purpose of his research. “The goal is not just to understand insulin resistance in the lab, but to turn that understanding into something that can help patients,” he said.