Mays Cancer Center researcher and SignalRx earn NCI business grants to develop drugs for first-in-human clinical trials

Daruka Mahadevan, MD, PhD

An internationally recognized physician-scientist of Mays Cancer Center at UT Health San Antonio, together with SignalRx Pharmaceuticals Inc., have secured two National Cancer Institute business grants to further develop drugs on a pathway to first-in-human cancer clinical trials.

The clinical translational researcher, Daruka Mahadevan, MD, PhD, division chief of hematology and medical oncology at UT Health San Antonio and Mays Cancer Center, says the drugs simultaneously disrupt two or three molecular targets that are involved in the growth, survival and progression of cancer. In contrast, most cancer drugs are developed to disrupt just one cancer target at a time.

The Small Business Technology Transfer (STTR) grants, which support cooperative research between small businesses and not-for-profit institutions with an eye toward commercialization, total approximately $300,000.

“With these two grants, we can unlock the potential of dual- or triple-targeted anti-cancer drugs that could significantly improve the lives of pediatric and adult cancer patients,” said Dr. Mahadevan, who also is the director of the Institute for Drug Development and associate director for clinical research at UT Health San Antonio and Mays Cancer Center.

The small-molecule inhibitor drugs will undergo pre-clinical trials for the treatment of lung, pancreatic and breast cancer, and lymphoma. The development aligns with UT Health San Antonio’s standing as the leading research university in South Texas.

“Our role in new cancer-drug development is important for both the history and future of this cancer center and our community,” said Ruben Mesa, MD, FACP, executive director of Mays Cancer Center.

Collaborating to make a difference

Dr. Mahadevan previously worked with SignalRx medicinal chemist Joseph Garlich, PhD, who then was with Semafore Therapeutics, on development of an inhibitor drug for cancer. Dr. Garlich and SignalRx structural biologist Guillermo A. Morales, PhD, MBA, chief scientific officer, used computer modeling to design the two new unique inhibitor drugs that equally bind and disrupt two or three known cancer targets at the same time.

Now, they are collaborating with Dr. Mahadevan to further develop these two novel drugs for testing in humans for the first time. First-in-human studies typically take place after a new drug has been tested in laboratory and animal studies prior to first-phase clinical trials, according to the NCI.

Once laboratory studies are completed for these two new drugs, an Investigational New Drug (IND) application will be submitted to the U.S. Food and Drug Administration to start the first-in-human clinical trials. The expected timeline to the first-phase clinical trials is one to two years from successfully completing the current studies.

The first drug, known as SF2523, is a small-molecule inhibitor drug that targets two cancer proteins at once, a “dual inhibitor.” Its targets are phosphoinosityl-3-kinase (PIK3CA), a protein that is key to cancer survival, and Bromodomain-containing protein 4 (BRD4) that controls the MYC gene that promotes abnormal cancer growth. The drug is being tested in EFGR- and KRAS-gene mutated non-small cell lung cancer and MYC/BCL2 double-hit, high grade diffuse large B-cell lymphoma, an aggressive form.

The second drug, SRX3177, is a triple inhibitor targeting the same two cancer proteins as SF2523, plus cyclin-dependent kinase 4/6 (CDK4/6), important in cancer cell division and growth. This drug is being tested in aggressive forms of B-cell lymphoma and ER/PR-positive, PIK3CA-mutated breast cancer, the most common.

“Targeting multiple cancer proteins in a tumor at once using just one small-molecule inhibitor drug, and without harming normal tissue, is an innovative approach to cancer therapeutics,” Dr. Mahadevan said. “I look forward to working with SignalRx to further develop these groundbreaking medications. It should really make a difference in patient outcomes.”

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