The rewards of discovery: A PhD candidate’s journey to clinical trials

Min Hai, a PhD candidate in the Phelps-Coss Laboratory at The Ohio State University College of Pharmacy, is three years into her doctoral training and can already claim a role in guiding a drug candidate through discovery and into clinical trials. 

At the intersection of data science and biology, Hai has been cracking the code on safe and effective dosing strategies for patients. For the past two years, her research has focused on the pharmacometric development of HOSU-53 (JBZ-001) – spending countless hours in front of a computer monitor helping to drive this promising new cancer therapy molecule forward. 

In July 2024, HOSU-53 received Investigational New Drug (IND) approval from the U.S. Food and Drug Administration (FDA), a major milestone for the drug’s development team. This approval was supported largely by the efforts of Hai and her lab mates. 

With IND approval secured, clinical trials for the dihydroorotate dehydrogenase (DHODH) inhibitor are now underway at The Ohio State University Wexner Medical Center (OSUWMC). 

The successful translation of a drug candidate from discovery to clinical trials within an academic institution is an extraordinary event. It provides a unique and invaluable opportunity for trainee researchers like Hai to gain hands-on experience that mirrors the industry landscape. 

“Our trainees will be able to say that they supported the IND-enabling research for a molecule in clinical studies,” said Chris Coss, PhD ‘08, assistant professor and co-principal investigator of the Phelps-Coss Lab. “Many drug development professionals work an entire career without being able to make this claim. Our trainees will have very precious experience that will give them a competitive advantage in pursuing their next positions.” 

HOSU-53 was introduced to the College of Pharmacy by Dr. Coss in 2022, who had become involved when the molecule emerged from lead optimization efforts at the Drug Development Institute (DDI). While the DDI team had already begun characterizing the molecule’s preclinical pharmacology profile, additional expertise was needed to build a comprehensive picture in preparation for FDA submission.  

Enter the drug modelling team of the Phelps-Coss Lab. 

Drug development can’t move forward without the essential work of modelling wizards like Hai, who use mathematical equations to pinpoint how a drug is absorbed, distributed, metabolized and eliminated from the body.  

“Using modeling, we can characterize a drug’s pharmacokinetics (PK)—how it’s processed in the body—and integrate available pharmacodynamic (PD) data to understand the relationship between drug exposure and response,” Hai said. “Modeling serves as a powerful tool to translate preclinical findings into clinical applications. It helps guide dose selection and provides the evidence the FDA needs to greenlight clinical trials.” 

As a first-year graduate student, Hai was invited to join the HOSU-53 project under the mentorship of Dr. Mitch Phelps, Kimberly Professor of Pharmacy and co-principal investigator of the Phelps-Coss Lab. With support from Postdoctoral Scholar Jooyoung Na, PhD, and Fellow PhD Candidate Kyeongmin Kim, MS, Hai took on the challenge of analyzing preclinical datasets and constructing complex models to simulate the behavior of the drug in the human body. 

“The more data I have, the happier I am,” Hai said with a laugh. “When Dr. Phelps told me that the DDI had a massive preclinical dataset, I was immediately hooked.” 

From December 2022 to July 2024, Hai led the pharmacometric analysis of HOSU-53, conducting non-compartmental analysis (NCA) and PK/PD modeling with over 10 preclinical studies in three different species carried out by Charles River Laboratories, WuXi AppTec and Hera BioLabs. 

“Oftentimes, our modeling projects in the Phelps-Coss Lab are used to estimate and explain datasets that are more abstract,” Dr. Na said. “For HOSU-53, we actively influenced the guidance for future testing. It was exciting and very rapid fire. The DDI and partnering contact research organizations (CROs) would send us data, and we’d turn around results within a day to inform their next round of preclinical testing.” 

Throughout this intense period, Hai and colleagues met multiple times per week with Drs. Phelps and Coss, DDI leadership and folks from the consulting team at Bexon Clinical. 

“At each meeting, we discussed data analysis, model refinements and next steps based on new experimental findings,” Hai explained. “Eventually, we reached a point where we were ready to submit the IND application.” 

The collective efforts of Hai and her peers turned HOSU-53 from a promising molecule into a first-in-human clinical trial candidate. The experience underscored how crucial trainee contributions are to translational research. 

“Most experimental work at a university is carried out by trainees,” Dr. Coss emphasized. “Oftentimes, a concern is expressed that since a trainee is, by definition, learning on the job, they will not be as efficient or effective as a ‘professional.’ However, the open secret in science is that a talented and creative trainee can outperform a professional in many cases.” 

The Phelps-Coss Lab continues to serve as the primary data analysis center for HOSU-53's clinical trials being conducted at OSUWMC. Continuing this collaboration maintains a unique window into the drug discovery process for trainee researchers at the College of Pharmacy.  

“At the American Conference on Pharmacometrics, a lot of people from industry stopped by my poster presentation on HOSU-53,” Hai recalled. “They were surprised that an academic institution was able to produce this amount of data with adequate analysis that ultimately resulted in IND approval.” 

Still heavily involved in the pharmacometric work for HOSU-53, Hai is now focused on refining human simulation profiles in preparation for the first patient data. Her work will help update the model and support the identification of dosing strategies that balance safety with potential therapeutic benefit.  

Hai’s data-modelling turnaround continues to be tight, particularly as it will ensure non-toxic trial dosing of subjects, but the rapid pace doesn’t faze her all that much. She’s caught up in the satisfaction of ushering the project forward. 

“It’s incredible to know that my contribution to HOSU-53 has been acknowledged by the FDA,” Hai said. “I joined early enough to witness the key milestones – when we first identified the therapeutic window, when we designed the clinical protocol. It’s really become like my baby. Watching it grow and move forward has been one of the most rewarding parts of my PhD journey.”