Cellenkos and the Future of T-Regulatory Cell Therapy: A Conversation with Simrit Parmar

We recently spoke with Simrit Parmar, MD, founder of Cellenkos, Inc. about their pioneering work in T-regulatory cell therapies. Our discussion covered the intricate mechanisms of these therapies, the promising results from their clinical trials, and the strategic direction of Cellenkos’ development programs. We focused particularly on CK0804, a product showing significant potential in treating myelofibrosis and other inflammatory disorders. This dialogue highlighted the scientific innovations at Cellenkos and provided insights into the future of cell therapy in addressing complex medical conditions.

What roles do T-regulatory cells play in our immune system, especially in inflammation and autoimmune diseases?

Simrit Parmar: T-regulatory cells are crucial regulators within the immune system, acting as a subtype of T cells that help resolve unwanted inflammation. These cells target cytotoxic T cells responsible for driving uncontrolled inflammation, functioning as the body’s policemen to maintain checks and balances. In autoimmune diseases, where inflammation can persist and cause damage, T-regulatory cells suppress such a prolonged inflammatory response, ensuring the immune system does not mistakenly attack the body’s tissues. This regulatory function prevents excessive immune responses from leading to chronic conditions.

The body constantly encounters foreign antigens as well as internal threats, where inflammation is a natural mechanism to expel such threats. However, when inflammation overstays its welcome, T-regulatory cells intervene to resolve it, preventing potential damage from chronic inflammation. This ability to modulate the immune response makes T-regulatory cells a key focus in developing therapies for inflammatory and autoimmune diseases, as we offer a targeted approach to restoring immune balance without broadly suppressing the immune system.

Your recent Phase 1B trial data for CK0804 in myelofibrosis patients showed promising results. Could you elaborate on the specific mechanisms through which this product exerts its effects?

Upon reaching the site of inflammation, T-regulatory cells deplete IL-2, act as cytokine sinks, secrete suppressor cytokines like interleukin-10, and can kill cytotoxic T cells and other harmful players. This comprehensive approach allows CK0804 to resolve inflammation and effectively improve myelofibrosis patients’ symptoms. The trial’s encouraging results, with six out of nine patients experiencing more than a 50% reduction in symptom burden, highlight the potential of CK0804 as a transformative therapy for this challenging condition.

How are you aligning your clinical development strategies to meet regulatory expectations, especially with the FDA’s clearance of your IND application for CK0804 as an add-on therapy?

Simrit Parmar: As more drugs have been approved for treatment of myelofibrosis, the company is expanding its trials to include patients resistant to these newer treatments. This strategic alignment not only meets regulatory expectations but also addresses a broader patient population, enhancing the potential impact of our therapy. The ability to administer our CK0804 cells outpatient with no major side effects and their complementary nature to existing therapies allows for potential combination treatments, further broadening the scope of our clinical development.

The cells can be given without hospitalization and have shown no major side effects. This outpatient administration is a significant advantage, making the therapy more accessible and less burdensome for patients. Additionally, the complementary mechanisms of action of the cells with existing approved products create opportunities for synergy, allowing for combination treatments that could enhance efficacy and address unmet medical needs. This strategic approach positions Cellenkos to effectively navigate regulatory pathways and bring our innovative therapies to market.

What preliminary safety and efficacy data have you observed in your second cohort, and how do these outcomes influence your approach to dosing and patient selection?

Simrit Parmar: Cellenkos has been cautious with patient monitoring, initially requiring a four-hour observation period post-infusion, now reduced to two hours based on safety data. This reduction reflects the therapy’s favorable safety profile, allowing for a more streamlined patient experience. Efficacy observations have led the company to adjust dosing schedules to address immune escape between doses, ensuring a more consistent reduction in the inflammatory response. For instance, in the trial, certain patients experienced immune escape between the first and second doses, prompting a modification to weekly doses initially, followed by monthly doses.

The importance of adapting our approach based on observed data has informed patient selection and dosing strategies. By interweaving insights from different programs, Cellenkos can create intelligent solutions for subsequent trials, optimizing the effectiveness of our therapies. This adaptive strategy enhances the potential for successful outcomes and demonstrates the company’s commitment to evidence-based decision-making in clinical development.

How do you prioritize resource allocation among your various clinical programs, and what criteria guide your decisions to advance a candidate into clinical development?

Simrit Parmar: Cellenkos prioritizes resource allocation based on unmet medical needs, such as aplastic anemia, where our lead asset, CK0801, has shown promising results in inducing transfusion independence. The durability of response, akin to a transplant, drives our decision to prioritize resources for a pivotal trial. For instance, patients who responded to CK0801 experienced durable independence from blood and platelet transfusions for almost 3.5 years, highlighting the transformative potential of this therapy and justifying its prioritization. This focus on high-impact areas ensures that our resources are directed toward programs with the greatest potential to improve patient outcomes.

Cellenkos considers its candidates’ scalability and commercial viability when advancing them into clinical development. The company’s ability to manufacture large quantities of cells from a single manufacturing campaign and its innovative cryopreservation techniques support the scalability of its therapies. By ensuring consistent product quality and scalability, Cellenkos can effectively market its therapies, addressing clinical and commercial considerations. This strategic approach allows the company to balance scientific innovation with practical implementation, ensuring that our therapies can reach the patients who need them most.

What innovations have you implemented to ensure consistent product quality and scalability for allogenic T-regulatory cell therapies?

Simrit Parmar: Cellenkos has implemented several innovations to ensure consistent product quality and scalability for our allogeneic T-regulatory cell therapies. One key innovation is using umbilical cord blood as the cell source, which provides hardwired, naive cells that can be infused across HLA barriers without preconditioning with chemotherapy and/or lymphodepletion. This approach enhances the safety and efficacy of our therapies and simplifies the manufacturing process. Additionally, our cryopreservation techniques allow for long-term storage and rapid deployment, which is crucial for timely treatment access. During the COVID-19 pandemic, Cellenkos was able to create drug depots across different clinical trial sites, ensuring that patients could receive treatment quickly despite logistical challenges.

Cellenkos has addressed two main items: the source of the cells and commercial scale-up. By deriving cells from umbilical cord blood, we have harnessed the natural protective mechanisms present in the umbilical cord, which connects the baby to the mother’s placenta. These cells are hardwired to be protective, reducing the risk of transforming into effector T cells, a major issue that plagues autologous Treg cell therapy. The company has also developed innovative programs and new IP to cryopreserve these cells using control rate freezers, storing them in liquid nitrogen for up to three years. This capability ensures that when a patient needs the therapy, it can be administered almost immediately, overcoming a significant point of failure in cell therapy.

How do collaborations, such as your study with Mount Sinai, enhance your research capabilities, and what outcomes do you anticipate from these partnerships?

Simrit Parmar: By partnering with experts like Dr. Ron Hoffman at Mount Sinai, Cellenkos can validate and expand our research through third-party evaluation. These partnerships allow the company to explore new questions and validate our findings, enhancing our scientific credibility and understanding of our therapies’ potential. For instance, collaborating with Mount Sinai enables Cellenkos to examine its cells in various models and conditions, providing deeper insights into our mechanisms and potential applications. This collaborative approach strengthens our research and fosters innovation and discovery.

Collaborations with scientific laboratories that pursue deep science allow Cellenkos to examine and interrogate its cells in different systems, providing valuable insights that may not have been considered internally. Third-party validation adds credibility to our company and scientific acumen, helping us learn about our CK0804 cells in different conditions. Specifically, the collaboration with Mount Sinai involves examining the interaction of the cells with other approved agents in the field and exploring specific PDX models to understand how these cells can interact with newly diagnosed myelofibrosis. These layers of examination are crucial for advancing our research and development efforts.