Meet Dr. Jack Bleesing, MD, PhD, Medical Director, Medpace
Medpace is proud to welcome Dr. Jack Bleesing, an accomplished immunologist and board-certified physician-scientist, with 20+ years of experience to our medical leadership team.
In this brief interview, we explore Dr. Bleesing’s extensive background and his unparalleled insight into early-phase programs and cutting-edge therapies that he brings to Medpace.
You’ve spent over two decades in immunology and rare disorders for pediatrics. What led you to apply that experience within a CRO setting at Medpace?
Although I was trained as an immunologist, I have spent most of my professional career in the cancer and blood disease setting. The rigor and scientific structure of treatment approaches, protocols from carefully conducted clinical trials, and the unique partnerships between patients/families and treatment teams have always resonated with me. These partnerships extend into the clinical research space, whether for observational studies in immunodeficiency and immunodys regulatory conditions or new therapeutic approaches in cellular and gene therapy (CGT).
Since having been exposed to and immersed in clinical research with far-reaching (and fast-moving) advances being translated into innovative new treatments, it seemed the perfect time to leverage my own expertise and experience in clinical immunology, CGT, and rare diseases in pediatrics, and make the transition to clinical development.
What stood out to me about Medpace is the focus on science and the collaborative physician-led model, where they are embedded in all cross-functional teams. This approach is especially important in areas where biology, trial design, trial execution, and particularly risk mitigation is congruently complex.
How does your background in immune deficiency, immune dysregulation, and transplant inform your approach to cell and gene therapies?
Suppressing the normal function of the immune system has been standard treatment for many disorders. More recently, new therapeutic interventions exploit our immune system in the fight against cancer, and increasingly, for other diseases.
In my approach, I pay particular attention to this immune balance between suppression/interference and augmentation as it applies to the process of guiding therapeutics successfully through the pipeline. Importantly, lessons learned in hematology and oncology can be translated to other therapeutic areas (e.g., autoimmune diseases or cellular therapy in rare diseases), but also from one therapeutic approach to another. My background in CGT, the immunology-of-CGT, and a sharp focus on the immune balance, enables me to look at concepts such as trial design, safety assessment, and biomarker development to help define the best strategy to bring new advanced therapeutics to a wide repertoire of (rare) diseases.
What are the biggest scientific or safety challenges you see in early-phase cell and gene therapy trials?
I think an important starting point is the fact that scientific challenges surrounding CGT stem from fundamental biological obstacles at the crossroads of molecular and cell biology and immunology.
Dose-finding presents a unique challenge, given that the dose is represented by the vector particles, but the therapeutic agents are the cells that are to be transduced. As such, the dose-response relationship is complex and potentially consisting of two phases: inflammatory reactions that share features with AAV-gene therapy, and CAR cell expansion toxicity emerging later, depending on transduction efficiency.
Focusing a bit more on safety challenges, the pharmacovigilance infrastructure is largely built for conventional drugs and not completely adapted yet for CGT. While these therapies offer curative potential there are significant safety issues related to prolonged biological activity, systemic immune system derailment that include acute inflammation, and immunogenicity towards vectors, molecules and cells and lasting genomic alterations that may last beyond typical observation periods and/or have a delayed presentation.
CRISPR-based approaches come with a new category of genotoxicity risk, in the form of off-target modifications, deletions or chromosomal rearrangements. These may disrupt normal gene function or confer a proliferative advantage to cells that lead to clonal expansion years later. The FDA recently issued draft guidance regarding safety assessments in genome editing products, using sensitive next-generation sequencing methods. However, the scientific challenge is not only detecting these off-target edits but also figuring out the potential clinical consequences for the patients.
How does your rare immune disorders experience translate to cell and gene therapy in today’s landscape?
We have known for a long time that rare immune disorders, such as inborn errors of immunity (IEIs) and primary immune regulatory disorders (PIRD, a subset of IEIs), are in essence“experiments of nature” that highlight critical components and functions of our immune system. Taking care of patients with these disorders has instilled a deep-seated respect for the human immune system and what can happen if the balance is disturbed (in either direction). At the same time, today’s landscape of CGT has benefited greatly from the foundational knowledge and experience derived from those “experiments” and their treatment (and treatment complications).
As my focus widened beyond these rare immune disorders, the foundational knowledge and experience can be used to strengthen the scientific basis of CGT trials, as well as align this with specific protocol considerations that focus on safety, particularly in early-phase trials. Looking at safety from the perspective of the Immune Balance, one can appreciate that advanced therapies require anticipation of application-specific toxicity patterns with the added challenge that it may not always be straightforward to separate product-related toxicities from background disease and prior treatments.
An early, and consistent, lesson in taking care of patients with rare immune disorders has been that patients are unique and require an individualized approach. Similarly, in the design and execution of trials of advanced therapeutics, there rarely is a one-size-fits-all path.
Looking ahead, where do you see the greatest opportunity for innovation in cell and gene therapy, especially in hematology and oncology?
Many of the greatest opportunities in CGT development stem directly from today’s challenges. In hematology and oncology several areas stand out as particularly promising:
- Advancing allogeneic (“off-the-shelf”) CAR therapies: Current approved CAR therapies are largely autologous, requiring individualized manufacturing that can be time-intensive, costly, and operationally complex. The field is increasingly moving toward allogenic and in vivo approaches that may improve scalability and broaden access.
- Reducing or eliminating lymphodepletion: In non-malignant disorders especially, eliminating the need for lymphodepletion could reduce toxicities such as CRS, neurotoxicity, and immunodeficiency while enabling treatment of patients with comorbidities or poor bone marrow reserve. It may also reduce hospitalization requirements and overall treatment burden.
- Improving CAR cell durability and persistence: Continued innovation is needed to address host-versus-graft rejection and optimize long-term activity and functionality of allogenic CAR therapies.
- Expanding combination treatment strategies: There is a growing opportunity to combine CGT approaches with other therapeutic modalities to enhance efficacy and potentially improve durability of response.
- Leveraging biomarkers more effectively: Biomarkers in CGT are increasingly important not only as endpoints, but as tools to better understand how living, evolving therapies interact with the immune system and patient-specific biology over time.
- Balancing efficacy with long-term immune health: As CGT applications expand into non-malignant and rare disease, there will be increasing focus on safeguarding immune balance while maintaining therapeutic benefit, particularly in settings where efficacy and toxicity are closely linked.
Overall, the field is rapidly evolving beyond oncology alone, with significant future opportunities expected across rare and non-malignant disease innovation continuing to address current development and treatment limitations.
WHY BIOPHARMA CHOOSES MEDPACE
Medpace brings unmatched therapeutic focus, regulatory insight, and operational agility to oncology trials. Our global, cross-functional model empowers Sponsors to navigate stringent regulatory pathways, complex enrollment logistics, and evolving protocol demands, without compromising speed or data integrity.
From dose escalation through global expansion, Medpace partners with Sponsors to adapt dynamically, overcome operational barriers, and ensure timely trial progress, delivering excellence where it matters most: the lives of vulnerable patients.