A Diverse, Market-Driven Pipeline
The DDI works with world-renowned investigators who perform cutting-edge research in multidisciplinary teams.
The DDI advances research through its Pipeline and Pilot Funding Programs. Pilot projects receive funding to support early validation and guidance from DDI’s industry-trained scientists to determine if the project has commercial drug development potential. Promising pilot projects are considered for inclusion into the DDI Pipeline Portfolio.
Every pipeline program receives strategic guidance from DDI’s unique team and advisory board of scientists and business experts with deep experience in the private sector. DDI’s diverse cross-functional teams support robust discovery and development through lead optimization; Chemistry, Manufacturing, and Controls (CMC); Investigational New Drug (IND)-enabling studies; and into the clinic – a true bench to bedside effort – setting it apart from other university translational units.
A list of projects under development for 2024 includes:
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 antigen signature, is being developed for use in treating a variety of cancer types. Project collaborators include: Damien Gerald, PhD (DDI co-Lead); Reena Shakya, PhD (DDI co-Lead); Thomas Cherpes, MD; Rodolfo Miguel-Vicetti, PhD; David O’Malley, MD; James Rocco, MD, PhD; and the Cell Therapy Lab.
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 rate-limiting enzyme for de novo pyrimidine synthesis. The OSUCCC – James, in collaboration with Hendrix College, is developing a series of DHODH inhibitors for treating solid tumors and hematologic malignancies, including acute myeloid leukemia (AML). Preclinical studies have demonstrated best-in-class activity in multiple cancer models, and we are now positioning this molecule for an IND submission to the FDA. Project collaborators include: Chad Bennett, PhD (DDI Lead); Asrar Alahmadi, MD, MBBS; Don Benson, MD, PhD; John Byrd, MD (Univ. of Cincinnati); David Carbone, MD, PhD; Tom Goodwin, PhD (Hendrix College); Erin Hertlein, PhD (Univ. of Cincinnati); Alice Mims, MD; Mitch Phelps, PhD; Qi-en Wang, PhD; Robert Wesolowski, MD; Biostatistics Shared Resource, Clinical Treatment Unit and Clinical Trials Processing Laboratory; Clinical Trials Office; Drug Discovery Shared Resource (formerly Medicinal Chemistry); and Pharmaco-Analytical Shared Resource.
Selective Estrogen Receptor Modulator (ER-β Agonist) as a New Approach to Targeting Cancer – A novel series of selective, non-steroidal estrogen receptor beta agonists are in development 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 7 non-cancer disease indications. Data for several of these indications have shown promising potential and are being further pursued for drug development. Project collaborators include: Chad Bennett, PhD (DDI co-Lead); Chris Coss, PhD (DDI co-Lead); Shyam Bansal, PhD (Penn State); Mathew Cherian, PhD; Steven Clinton, MD, PhD; Thomas Mace, PhD; and Raju Raval, MD, DPhil.
Aryl Hydrocarbon Receptor as a Target for Glioblastoma and CNS-involved Solid Tumors – The aryl hydrocarbon receptor (AHR) has been implicated as a sensor of environmental chemicals and a critical regulator of immune cell development. This team is developing small molecule antagonists of AHR that strengthen the body’s anti-tumor immune response. Project collaborators include: Jerry Hilinski, PhD (DDI Lead); Don Benson, MD, PhD; Bethany Mundy-Bosse, PhD; and Drug Discovery Shared Resource (formerly Medicinal Chemistry).
Mps1/TTK Kinase Inhibitor as a Treatment for Cancer – Mps1 is a protein that regulates cell division, and its overexpression is associated with poor cancer outcomes across many indications. This team is developing selective inhibitors of Mps1 and utilizing bioinformatics to identify potential biomarkers for patient selection and combination with targeted therapies. Project collaborators include: Jerry Hilinski, PhD (DDI Lead); Don Benson, MD, PhD; Merve Hasanov, MD; Ning Jin, MD; Kari Kendra, MD, PhD; Anne Noonan, MBBCh; Matthew Summers, PhD; Monica Venere, PhD; and Anna Vilgelm, MD, PhD; Drug Discovery Shared Resource (formerly Medicinal Chemistry); and Target Validation Shared Resource.
Inhibition of MKLp2 (Kif20a) as a Therapeutic Strategy for Glioblastoma – MKLp2, also known as Kif20a, is a kinesin family member that participates in cell division and is highly expressed in many cancer types. The DDI is collaborating with kinesin expert Matthew Summers, PhD, and glioblastoma modeling expert Monica Venere, PhD, to develop selective inhibitors of MKLp2.
Targeting Ligand-Free GARP for the Treatment of Solid Tumors – Glycoprotein A repetitions predominant (GARP) is a non-signaling surface docking receptor for latent transforming growth factor beta (TGFβ). TGFβ activation via GARP suppresses the immune response in the tumor microenvironment, and GARP expression has been shown to correlate with poorer cancer outcomes. The DDI is collaborating with the Pelotonia Institute for Immuno-Oncology to develop a therapeutic antibody targeting uncomplexed, ligand-free GARP to enhance the body’s anti-tumor immune response. Project collaborators include: Damien Gerald, PhD (DDI Lead); David Carbone, MD, PhD; Zihai Li, MD, PhD; Mitch Phelps, PhD; and Pharmaco-Analytical Shared Resource.
Pilot Programs
Evaluating Sumolyation Inhibition as a Promising Approach to Treat Acute Myeloid Leukemia
Investigators: Bethany Mundy-Bosse, PhD, and Aharon Freud, MD, PhD
Evaluating Novel Papaverine Derivatives for Radio-Sensitization
Investigators: Nicholas Denko, MD, PhD, and Mark Mitton-Fry, PhD
Evaluating Novel, Next-generation Tubulin Destabilizers
Investigators: Karl Werbovetz, PhD, and Christopher Coss, PhD
Evaluating Bioabsorbable Magnesium-Alloy Implants for Oral Cancer Reconstruction
Investigators: David Dean, PhD, and Alan Luo, PhD
Building the DDI and Managing its Pipeline
The DDI pipeline is focused on the development of therapeutics and diagnostics for the treatment of cancer. Building and managing the pipeline is a dynamic process. New projects are routinely evaluated for probability of scientific and commercial success. Projects are continually assessed, with the reallocation of investments to the most promising drug development projects. Pipeline decisions are made early and rapidly using data-driven go/no-go decisions, tracking progress against planned development timelines, and evaluating changes to the commercial or intellectual property landscape. The DDI accelerates projects using parallel workstreams and supplementary funding resources that augment activity in the Principal Investigator’s lab. All new investments and go/no-go decisions are determined with input from our scientific advisory board.
Timeline
- November 2011: Creation of Ohio State’s Drug Development Institute
- 2013: First investments in DDI pipeline projects
- 2016: First licensing partnership – two Phase I trials completed at the OSUCCC –James
- 2018-2021: DDI builds its team to support its various functions
- 2021: DDI receives a $13.7 million gift from the Paula and Rodger Riney Foundation to establish the Riney Family Foundation Myeloma Center for Advanced Research Excellence (M-CARE)
- 2021: M-CARE enrolls its first clinical trial patient
- 2023: DDI submits its first pre-IND package and M-CARE opens its second clinical trial for myeloma patients
- 2024: DDI prepares Ohio State’s first commercial IND package for a wholly home-grown small molecule inhibitor and M-CARE opens its third clinical trial for myeloma patients
For more information, contact the DDI at ddi@osumc.edu.