Moderna and BioNTech, both navigating their post-COVID future while reimagining cancer treatments, have encountered manufacturing hurdles along their respective journeys.
BioNTech took center stage at the European Society for Medical Oncology (EMSO) and unveiled data showcasing a revamped formula for their CAR-T therapy, BNT211. The modified therapy demonstrated clinical promise with an impressive overall response rate of 45% among 38 out of 44 evaluated patients.
Benjamin Rengstl, M.D., Director of Clinical Development and Immunoreceptor Therapy at BioNTech, revealed that this presentation marked the debut of an innovative manufacturing process. This new approach emphasizes automation, robustness, and scalability, resulting in a more potent product. However, the enhanced formula also led to an increase in toxicities, necessitating a reevaluation of dose escalation. Rengstl expressed the importance of developing protocols with swift turnaround times, underlining that this new protocol will pave the way for BioNTech’s next generation of products, transitioning from retroviral vectors to virus-free gene editing techniques. Rengstl emphasized that the only delay in the BNT211 program was related to optimizing the dose for the phase 1/2 trial to ensure patient safety.
BioNTech is also expanding its global manufacturing capabilities to support clinical trials for BNT211 worldwide. Rengstl mentioned the need for a minimum of 100 patients to demonstrate the therapy’s effectiveness, with 44 already enrolled in the early-stage phase 1/2 trial.
Concurrently, Moderna is collaborating with pharmaceutical giant Merck & Co., known as MSD in Spain, on a personalized cancer vaccine named mRNA-4157, slated to enter phase 3 trials. While no major revelations were made at ESMO, both companies made their presence felt.
Merck’s Jane Healy, M.D., Ph.D., Vice President of Early Clinical Development, emphasized the uniqueness of their approach: tailoring the treatment to each patient’s tumor. By sequencing the tumor and identifying distinctive mutations likely to be recognized by the immune system, they craft a vaccine customized to the patient’s specific needs. Healy explained that these neoantigens are absent in healthy tissue, making the approach highly targeted and promising.
While the concept appears straightforward, Healy acknowledges manufacturing complexities, akin to those faced in the CAR-T field. She anticipates logistical challenges in patient trials, primarily stemming from the need for personalized therapy for each patient. The current turnaround time stands at six to eight weeks, suitable for early-stage “micro-metastatic” cancers. For rapidly progressing diseases, the therapy’s delayed action might not be ideal.
The demand for such therapies remains uncertain, and Moderna and Merck must address logistical challenges to facilitate commercial adoption if phase 3 data proves successful. Healy envisions some aspects of the process can be automated and hopes that its relative simplicity compared to CAR-T therapies will be advantageous.
Healy acknowledges the challenges ahead but sees the potential for success in a therapy that boasts fewer complexities than CAR-T treatments. As they navigate these uncharted waters, both Moderna and BioNTech are positioning themselves at the forefront of innovation in the field of personalized cancer treatments.