Summary of Key Points
Recently, the mRNA cancer vaccine sector has experienced a stark contrast in success: The vaccine developed in collaboration between Moderna and Merck (intismeran), when used in combination with the PD-1 drug Keytruda, achieved positive results in a phase three trial for melanoma, causing Moderna's stock price to double. In contrast, the similar vaccine developed by BioNTech and Roche (cevumeran) was prematurely discontinued in a phase two trial for colorectal cancer due to higher mortality rates, resulting in a nearly 8% drop in BioNTech's stock price. Both vaccines are “customized” mRNA cancer vaccines, but the outcomes differ significantly. The key difference lies not in the mRNA technology itself, but in the choice of indications, research and development strategies, and partners.
One Success, One Failure: The Divergent Fates of the Two mRNA Vaccines
Let’s clarify the events:
- Moderna’s Approach: On August 19th, their vaccine intismeran, when used in combination with Merck’s Keytruda (a highly effective immunotherapy drug) for the treatment of malignant skin cancer (melanoma), showed positive results in a phase three trial, indicating a potential reduction in the risk of post-surgery recurrence. This news caused Moderna’s stock price to rise by 100%.
- BioNTech’s Approach: A week later (August 28th), their vaccine cevumeran, in a phase two trial for colorectal cancer, resulted in a higher death rate in the group using the vaccine, leading to the premature termination of the trial and a 8% drop in BioNTech’s stock price.
Both companies gained prominence with their COVID-19 vaccines, but they had been focusing on mRNA cancer vaccines long before the pandemic. The fundamental concept behind these vaccines is to “tailor the treatment to each patient” by identifying “new antigens” unique to cancer cells in the patient’s tumor and using mRNA to stimulate the immune system to attack these antigens.
Indications: The Critical Difference Between “Hot” and “Cold” Tumors
The reason for such different outcomes despite using mRNA vaccines is the type of cancer being targeted:
- Hot Tumors (Melanoma): Melanoma cells have many genetic mutations, making them easy to target for the vaccine. The tumors also contain a large number of immune cells (T cells) that can be activated by the vaccine. The combination of the vaccine with PD-1 drugs (like Keytruda) is particularly effective.
- Cold Tumors (Colorectal Cancer): Most colorectal cancers have fewer genetic mutations, making it difficult to identify target antigens. There are also fewer immune cells in the tumors, making it challenging for the vaccine to effectively attack cancer cells. PD-1 drugs are generally ineffective against this type of cancer. BioNTech chose to target this difficult case, effectively leaving the vaccine to fight a tough battle on its own.
Research and Development Strategies: Strong Partnerships vs. Risky Approaches
The trial designs also played a significant role:
- Moderna and Merck: Their combination of vaccine and Keytruda was designed to prevent recurrence after melanoma surgery, building on an already effective treatment approach, thus increasing the chances of success.
- BioNTech and Roche: BioNTech’s vaccine was either used alone or in combination with Roche’s PD-L1 drug, but for the more challenging colorectal cancer indication, increasing the likelihood of failure.
Moreover, Moderna’s current trials are focused on “hot tumors” such as lung and bladder cancer, where immunotherapy has already proven effective. In contrast, BioNTech is betting heavily on less promising areas like colorectal and pancreatic cancer, facing competition from other drugs (e.g., KRAS-targeted drugs already approved for pancreatic cancer).
The Importance of Partnerships
The quality of partners is crucial:
- Merck’s Role: Merck’s Keytruda is a cornerstone drug in the treatment of hot tumors, providing a solid foundation for Moderna’s vaccine, enhancing its effectiveness.
- Roche’s Support: Roche’s PD-L1 drug is less widely used compared to Keytruda, and Roche has had limited success in tumor immunology research (e.g., the failed TIGIT antibody drug). Additionally, Roche has reduced its investment in cevumeran, with no new clinical trials planned (while Moderna has three phase three trials in progress for lung cancer).
In summary, while mRNA cancer vaccines hold great potential, they are not a panacea. Success is more likely in “hot tumors,” where existing treatments are effective. For patients, being effective in hot tumors represents a significant breakthrough. For companies, strategic choices are more important than the technology itself.
(End of the analysis.)