First-in-Human Trial Launched for Novel DHODH Inhibitor HOSU-53 in Solid Tumors and Lymphomas
Key Insights
A Phase I/II clinical trial is set to begin at Ohio State University, evaluating the novel DHODH (search) inhibitor HOSU-53 in patients with advanced solid tumors (search) and Non-Hodgkin's lymphoma (search).
HOSU-53, developed at Ohio State, targets dihydroorotate dehydrogenase (DHODH (search)), a key enzyme in cancer cell metabolism, aiming to disrupt DNA and RNA synthesis.
Preclinical studies suggest HOSU-53 can selectively starve cancer cells by depriving them of pyrimidines, potentially enhancing the efficacy of other cancer therapies.
A first-in-human clinical trial is slated to commence at The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC – James), evaluating HOSU-53, a novel dihydroorotate dehydrogenase (DHODH (search)) inhibitor, in patients with advanced solid tumors (search) and Non-Hodgkin's lymphoma (search). This Phase I/II trial marks a significant step in translating Ohio State University-led research into potential cancer therapeutics.
The trial will assess the safety and efficacy of HOSU-53, an orally administered drug designed to inhibit DHODH (search), a crucial enzyme involved in cellular metabolic processes that fuel cancer growth and spread. DHODH plays a key role in the synthesis of pyrimidines, essential building blocks for DNA and RNA. By blocking this enzyme, HOSU-53 aims to disrupt cancer cell proliferation and survival.
Targeting DHODH for Cancer Therapy
Chad Bennett, PhD, senior director of chemistry for the Drug Development Institute (DDI) at the OSUCCC – James, emphasized the potential of HOSU-53, stating, "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."
The rationale behind targeting DHODH (search) lies in the selective vulnerability of cancer cells to disruptions in pyrimidine synthesis. Cancer cells rely heavily on rapid DNA and RNA production to sustain their uncontrolled growth. By inhibiting DHODH, HOSU-53 aims to selectively starve cancer cells of these essential building blocks, potentially leading to cell death and tumor regression.
Preclinical Evidence Supports Clinical Translation
Preclinical studies have demonstrated that HOSU-53 can effectively inhibit DHODH (search) activity and suppress cancer cell growth in vitro and in vivo. These studies suggest that HOSU-53 can strike a careful balance by 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.
Trial Design and Patient Population
The clinical trial, led by Asrar Alahmadi, MBBS, will initially enroll patients with solid tumors (search), including small cell lung cancer (search), and Non-Hodgkin's lymphoma (search). The OSUCCC - James is one of a select few National Cancer Institute (NCI)-funded phase I/II experimental clinical trial units in the United States.
The trial is expected to open at the OSUCCC - James in the winter of 2024. Jabez Biosciences (search) is the industrial development partner for the single-center clinical trial to test this new drug, known only as HOSU-53 while in testing.
Collaborative Effort Drives Innovation
The development of HOSU-53 and the launch of this clinical trial represent a collaborative effort involving researchers and resources from across Ohio State 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.
Jeff Patrick, PharmD, senior director of the DDI and clinical pharmacist, highlighted the unique capabilities at Ohio State, stating, "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."