Led by DDI Senior Director and Clinical Pharmacist Jeff Patrick, PharmD, the institute is staffed by industry-trained scientists and employs a collaborative management process to ensure efficient advancement for all projects. Project activities are divided between the DDI and investigators and are executed in parallel to achieve this process. The desired outcome is to advance projects to the point of partnership with industry to ensure that translational research at the OSUCCC – James can benefit patients.
Thanks to a $10 million gift received in 2020 from the Paula and Rodger Riney Foundation to establish the Riney Family Foundation Myeloma Center for Advanced Research Excellence (Myeloma CARE), the DDI and the OSUCCC – James continued to advance multiple myeloma research in 2021. The Myeloma CARE program is led by Don Benson, MD, PhD, along with the DDI’s Senior Director of Biochemistry, Jerry Hilinski, PhD, who leads DDI efforts to guide new therapies from bench to bedside.
The DDI advances research through its Pipeline and Pilot Funding Programs. Pilot funding provides up to $50,000 of early validation support to determine if a project has drug-development potential and should be considered for inclusion in the DDI Pipeline Portfolio. For select projects that require unique support, the DDI may provide Ohio State investigators with funding for regulatory filing needs or to initiate a Request for Proposals (RFP) Program to explore additional disease indications. A list of projects under development for 2022 includes:
DDI Pipeline Portfolio
Activated B cells as a therapeutic cancer vaccine platform – A novel B cell-based therapeutic cancer vaccine, with the potential to be personalized to an individual’s tumor signature, is being developed for use in treating a variety of cancers.
DHODH inhibitors for treatment of hematologic malignancies – Recent proof-of-concept research has rekindled interest in targeting cancers through inhibition of dihydroorotate dehydrogenase (DHODH). The Ohio State University, in collaboration with Hendrix College, is developing a series of DHODH inhibitors for treating hematologic malignancies, including acute myeloid leukemia. Over the past year, preclinical studies have demonstrated that the lead molecule has best-in-class activity in cancer models. DDI scientists are positioning this molecule for Investigational New Drug (IND) submission to the FDA.
Selective estrogen receptor modulator (ER-B agonist) as a new approach to targeting cancer – A novel series of selective non-steroidal estrogen receptor beta agonists is being developed for treating cancer, precancerous conditions and potentially non-cancer indications. This project initiated the DDI’s first RFP program to harness the power of the Ohio State network to explore additional applications in 11 cancer and seven non-cancer disease indications. Several of these indications, including prostate cancer, glioblastoma, non-alcoholic steatohepatitis (NASH) and ischemic heart failure, have shown promising potential and are being pursued for drug development.
Myeloma CARE Program pipeline
The aryl hydrocarbon receptor as a target for multiple myeloma – The aryl hydrocarbon receptor (AHR) has been implicated as a sensor of environmental chemicals and has been demonstrated by researchers at Ohio State to functionally contribute to multiple myeloma survival. This team is developing small molecule inhibitors of AHR intended to modify the immunophenotype of multiple myeloma cells and strengthen the body’s anti-myeloma immune response to address this significant unmet need in myeloma.
TTK kinase inhibitor as a treatment for cancer – TTK is a protein that regulates cell division, and its overexpression is associated with poor outcomes in multiple myeloma as well as other hematologic malignancies and solid tumor types. This team is optimizing a homegrown Ohio State TTK inhibitor and testing therapeutic combination strategies to inform future clinical trials.
DHODH inhibitors for treatment of hematologic malignancies – As stated earlier, recent proof-of-concept research has rekindled interest in targeting cancers by inhibiting dihydroorotate dehydrogenase (DHODH). Ohio State’s lead DHODH inhibitor has been evaluated in numerous preclinical AML and multiple myeloma studies, and it demonstrates significant antitumor efficacy both as a single agent and in combination with other multiple myeloma therapeutics. Based on this data, this DHODH inhibitor has been selected as a preclinical candidate. Independent New Drug (IND)-enabling studies are scheduled for later this year to facilitate phase I clinical trials.
Analysis of primary multiple myeloma samples – Since 2011, the OSUCCC – James’ multiple myeloma program has banked over 400 patient samples. This portion of the Myeloma CARE program, led by Francesca Cottini, MD, involves analyzing subsets of those samples to make discoveries about the impact of certain genetic changes on myeloma outcomes and disease characteristics. Additionally, samples are being analyzed to help understand factors influencing progression in patients who have undergone autologous stem cell transplant.
Pilot programs
- Testing the Ability of Fasnall to Block Coronavirus Replication (Principal investigator (PI): Jesse Kwiek, PhD)
- Evaluating the Inhibition of Mitotic Proteins TTK and MKLp2 as a Therapeutic Strategy for Glioblastoma (PIs: Matthew Summers, PhD, and Monica Venere, PhD)
- The Role of SUMOylation on NK Cell Development and Function (PIs: Bethany Mundy-Bosse, PhD, and AharonFreud, MD, PhD)
- Evaluating Glycoprotein-A Repetitions Predominant Protein (GARP) Blockade to Overcome Immune Checkpoint Inhibitor Resistance (PI: Zihai Li, MD, PhD)
- Evaluating Papavarine Derivatives as Modulators of Cancer Metabolism (PI: Nicholas Denko, MD, PhD)
- Biomedical Device Initiative: 3D Printed Cranial Implants for the Treatment of Oral Cancer (PI: David Dean, PhD, Alan Luo, PhD, Ed Herderick, PhD)