Advancing the Fight Against Cancer through mRNA & AI
Last week, we, along with our partner, Merck, announced follow up-data from the Phase 2b study evaluating mRNA-4157, our investigational individualized neoantigen therapy (INT), in combination with pembrolizumab, Merck’s anti-PD-1 therapy, in patients with high-risk melanoma (stage III/IV) following complete resection. As we continue to follow participants in the mRNA-4157-P201 study, this planned supplemental analysis showed a continued clinical benefit of this combination compared to pembrolizumab alone after three years, building on previous positive analyses and increasing our confidence in the potential of INT.
How Does an INT Work?
It’s no secret that cancer can be an extremely difficult disease to treat, largely because every person’s cancer is different - arising from a unique set of evolving tumor mutations. Individualized treatments, created out of the DNA sequence of the tumor, aim to help solve this challenge through a customized approach. mRNA-4157 is developed using both DNA and mRNA sequencing data and may provide a targeted immune response by inducing t-cell recognition of cancer cells based on their neoantigens, or pieces of protein, that are presented on the surface of the cancer cell and result from the DNA mutations.
Learn more about how INT works in patients with cancer:
Individualizing Cancer Care
For the last seven years, Moderna and Merck have collaborated in a shared commitment to drive research forward for innovative modalities in earlier stages of cancer, where we can make the most meaningful impact for patients. As of today, there are no currently approved INTs. By building on developments in immunologic understanding, cancer biology, and the role of mRNA, we hope to further advance the field and help individualize cancer care.
A Testament to the Power of AI
While the combination of mRNA-4157 and pembrolizumab may be a medical breakthrough, it is also a technological one. Our vision is to build the best individualized medicine platform in the world, from the patient and site experience to manufacturing execution and delivery. However, there are complexities that come with creating one therapy for one patient, in terms of the intricacies of drug design as well as optimizing manufacturing schedules and resources to ensure timely delivery of doses.
AI plays an important role in simplifying these processes and helping us move with speed and precision, especially when confronted with thousands of patient batches. On the design end, a series of fully integrated AI algorithms takes next-generation sequencing data from tumor and blood samples, reviews their genetic mutations, and predicts up to 34 of those neoantigens that are most likely to elicit an immune response. This algorithm has the potential to learn over time, through pairing clinical and immunogenicity data, and will hopefully become better at selecting the most clinically active neoantigens.
On the manufacturing end, we created Maestro, an end-to-end digital solution that offers cross functional views of all manufacturing activities for every patient in the INT clinical trial program. This holistic view allows Moderna to tightly coordinate tasks across clinical operations, manufacturing, quality assurance, shipment logistics and more, and automatically adjust downstream planning in light of any changes to ensure INT is delivered in time for every patient’s target dose date. Our AI scheduling algorithm helps automatically place a patient’s batch schedule onto a timeline, taking into account a real-time snapshot of our manufacturing capability in all constraints. As the volume of patient batches we execute on in parallel increases, this solution is critical to ensuring supply chain planners have a comprehensive view of each patient batch and is in sync with any clinical site scheduling updates to ensure we deliver every INT dose on time.
The Road Ahead
We have bold ambitions regarding the potential of individualized neoantigen therapy, looking across many different tumor types and settings to build a comprehensive strategy. In July, we and Merck, announced the initiation of a pivotal Phase 3 randomized INTerpath-001 clinical trial evaluating mRNA-4157 in combination with pembrolizumab, as an adjuvant treatment in patients with resected high-risk (Stage IIB-IV) melanoma. Global recruitment in INTerpath-001 has begun (NCT05933577). We have also initiated a Phase 3 trial in non-small cell lung cancer that is actively enrolling globally (INTerpath-002, NCT06077760) and plan to expand the development program to many additional tumor types. To supply product to these trials and in preparation for the future, Moderna announced that we are building a manufacturing site in Marlborough, MA as a commercial INT manufacturing facility.
None of these studies would be possible, however, without the hard work of our investigators and research staff at all the clinical sites. Thank you! And we also would like to applaud all our clinical trial participants who selflessly sacrificed their time and donated their efforts by agreeing to be part of our clinical research program. We extend to all our promise to vigorously interrogate the potential of mRNA therapy in oncology and hope to bring this therapy to the patients who need it as quickly as possible.
Please note, mRNA-4157 is an investigational asset and has not been determined safe or effective by the FDA.
Moderna Forward-Looking Statements
This post contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including statements regarding: the ability for mRNA-4157/V940 and Merck’s pembrolizumab to show a significant benefit over KEYTRUDA (pembrolizumab) alone in adjuvant melanoma; the tolerability and safety profile for mRNA-4157; the ability of an individualized neoantigen therapy to provide a robust and targeted immune response by specific to a patient’s tumor mutation signature; plans for studying individualized neoantigen therapy in additional types of cancer; and Moderna’s use of AI to build the best individualized medicine platform in the world. The forward-looking statements in this post are neither promises nor guarantees, and you should not place undue reliance on these forward-looking statements because they involve known and unknown risks, uncertainties, and other factors, many of which are beyond Moderna's control, and which could cause actual results to differ materially from those expressed or implied by these forward-looking statements. These risks, uncertainties, and other factors include, among others, those risks and uncertainties described under the heading "Risk Factors" in Moderna’s Annual Report on Form 10-K for the fiscal year ended December 31, 2022, filed with the U.S. Securities and Exchange Commission (SEC), and in subsequent filings made by Moderna with the SEC, which are available on the SEC’s website at www.sec.gov. Except as required by law, Moderna disclaims any intention or responsibility for updating or revising any forward-looking statements contained in this press release in the event of new information, future developments or otherwise. These forward-looking statements are based on Moderna's current expectations and speak only as of the date of this post.