A new therapeutic agent discovered and developed at The Ohio State University will soon be used for cancer treatment at the patient's bedside as part of a clinical trial. The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC – James)-led trial represents the first human testing of a new, best-in-class DHODH inhibitor discovered then fully developed and moved toward commercialization at Ohio State.
Jabez Biosciences is the industrial development partner for the single-center clinical trial to test this new drug, known only as HOSU-53 while in testing. The oral drug targets cancer by stopping a key enzyme, dihydroorotate dehydrogenase (DHODH), which is involved in important cellular metabolic processes that enable cancer to grow and spread. This includes the development of precursors for new DNA and RNA molecules, which cancer cells depend on heavily.
Asrar Alahmadi, MBBS, will serve as principal investigator of the OSUCCC – James clinical trial, which will first enroll patients with solid tumors, including small cell lung cancer, and Non-Hodgkin's lymphoma. The OSUCCC - James is home to one of just nine National Cancer Institute (NCI)-funded phase I/II experimental clinical trial units in the United States.
Chad Bennett, PhD, senior director of chemistry for the Drug Development Institute (DDI) at the OSUCCC – James, is co-lead investigator of the drug development research team behind the development of this new drug. "We are introducing a best-in-class drug that we believe holds tremendous potential to help patients who have limited effective treatment options. It is such an incredibly exciting development."
New class of cancer inhibitor drugs
The challenge is to starve the cancer cells, while not disturbing healthy cells. Stressing the cancer cells by depriving them of essential building blocks (called pyrimidines) both directly kills the cancer cells and makes them more susceptible to other therapies, including immune therapies. The investigational drug to be tested has been shown in preclinical and cell models to strike this careful balance."
Chad Bennett, PhD, senior director of chemistry, Drug Development Institute (DDI), OSUCCC – James
Sebastian Biglione, PhD, PharmD, director of clinical and regulatory strategy for the DDI notes that the DHODH inhibitor discovery story started at Ohio State several years ago as a collaboration between former OSUCCC – James scientist and clinician John C. Byrd, MD, an internationally known specialist in hematologic malignancies, and his former mentor at Hendrix College in Arkansas, Thomas E. Goodwin, PhD, and undergraduate students working under him who generated the prototype compound (HOSU-3). Byrd's team screened the molecules for pre-clinical activity. This partnership initiated a project that was accelerated by OSU's DDI to discover and develop HOSU-53 and grew to include the University of Cincinnati when Byrd and his team relocated there.
"Researchers at Ohio State, led by (former faculty) Erin Hertlein, PhD, and Ola Elgamal, PhD, partnered with (current faculty) Sandip Vibhute, PhD, Jerry Hilinski, PhD, Chris Coss, PhD, Sebastian Biglione, PhD, PharmD, and myself – preclinical drug discovery and development experts in Ohio State's DDI and the Drug Discovery Shared Resource – to develop a DHODH inhibitor clinical candidate with potency and pharmacologic properties suitable for testing in a clinical trial at the OSUCCC – James," said Bennett.
The trial is expected to open at the OSUCCC - James in the winter of 2024.
Ohio State's unique internal tech incubator model drives research innovation
The launch of this trial is the culmination of a robust collaboration drawing on expertise from across the university, including the OSUCCC – James, Drug Development Institute, College of Pharmacy, College of Medicine, Ohio State Office of Innovation and Economic Development and Enterprise for Research, Innovation and Knowledge.
"It is really unique to not only identify a promising drug discovery in the lab but also have the in-house expertise and capabilities to then take that drug through the Food and Drug Administration Investigational New Drug application process, build a business plan, secure a commercial clinical partner – and then open that trial at our institution to benefit the patients of central Ohio and beyond," said Jeff Patrick, PharmD, senior director of the DDI and clinical pharmacist. "This is a true testament to the investment in team, knowledge and infrastructure Ohio State has made to ensure we can propel these promising discoveries from the lab to ultimately benefit patients."
This work was supported by the Harry T. Mangurian Jr. Foundation, the Paula and Rodger Riney Foundation and Pelotonia. Additional collaborators in this work include Ohio State's Tyler Wilson, PhD, Mitch Phelps, PhD, Min Hai, Joo Young Na, PhD, Celeste Alverez, PhD, Alice Mims, MD, Uma Borate, MBBS, David P. Carbone, MD, PhD, Don Benson, MD, PhD, Robert Wesolowski, MD. Mouad Abdulrahim, MD, formerly with Hendrix College, also contributed to this study.
Industrial development partner Jabez Biosciences, Inc. is a clinical-stage biopharmaceutical oncology company founded by industry veterans in 2023, focuses on targeting key mechanistic drivers of cancer and tumor biology. Jabez is dedicated to bringing best-in-class treatment modalities to patients, aiming to improve and extend lives by combining potential targets for monotherapies with established standards of care.
New method accelerates drug discovery from years to months