A year to the day after the Trump administration slashed $500 million in funding from mRNA-based programs, the FDA approved Moderna’s flu vaccine based on the technology. Weeks later, Moderna and Merck revealed positive Phase 3 results for their personalized mRNA-based cancer vaccine. In the words of one mRNA specialist, “science won.”
One of the 21st century’s most controversial therapeutic modalities, mRNA appears to have turned a corner this summer, first with the FDA approval of Moderna’s flu vaccine and then the surprise Phase 3 win for the company’s Merck-partnered personalized cancer vaccine.
“It really underscores the promise of the technology and reinvigorates the space,” Jeff Coller, professor of RNA Biology and Therapeutics at Johns Hopkins University, told BioSpace.
The newfound momentum follows a hard year for mRNA companies. In August 2025, the Department of Health and Human Services (HHS) terminated around $500 million in BARDA contracts associated with mRNA vaccine development, affecting companies like Moderna, Pfizer and AstraZeneca. Five months earlier, National Institutes of Health officials reportedly encouraged scientists to remove all references to mRNA vaccine technology from their grant applications.
“Last year was a really challenging year. It was quite disappointing for the progress in this space,” Amy Walker, CEO of 4basebio, a CDMO offering mRNA services, told BioSpace.
Walker agreed that sentiment is now changing. “It absolutely is thawing,” she said. “If we look at our client base . . . there’s a huge amount of mRNA research going on.”
Andrew Tsai, managing director at Jefferies, also sees a shift in the perception of mRNA, and he pinpoints Merck and Moderna’s Phase 3 readout last month as the cause. Before that, most people believed mRNA was a viable technology but “not necessarily something that was a game changer,” he told BioSpace. But then the INTerpath-001 trial showed that intismeran autogene in combination with Keytruda improved outcomes in patients with melanoma.
“The market reaction suggests it is something game changing,” Tsai said.
mRNA nuances
For Roberta Duncan, founder and principal of strategic consulting firm The Modeste Duncan Group, the current chapter in mRNA’s epic tale can be looked at from two angles: therapeutics and public health.
“If you start to kind of pull it apart, there is this whole therapeutic and public health from the same platform mRNA story,” Duncan, who also serves as on the executive board of the Alliance for mRNA Medicines, told BioSpace. mRNA exploded onto the scene during the COVID-19 pandemic—and was quickly inserted into the U.S. political debate over vaccines.
Moderna’s Spikevax and Pfizer-BioNTech’s Comirnaty—both developed and authorized to protect against COVID in less than a year—are mRNA-based. COVID vaccines based on this technology are estimated to have saved around 3 million lives in the U.S., Paul Offit, director of the Vaccine Education Center at Children’s Hospital of Philadelphia, told BioSpace last year. Then, “It became political,” Offit said. “Highly political.”
But while vaccines are politically charged, with the population divided, “everybody’s afraid of cancer,” Coller said.
“Nobody wants to get cancer, and you’ll take poison if you have cancer, right?” he continued. “That’s what chemotherapy is, and mRNA is a natural product.”
Oncology could also be a smoother regulatory road. With its COVID-19 vaccine Spikevax, Moderna had to deal with the CDC’s Advisory Committee on Immunization Practices (ACIP) and “vaccine mandate politics,” Duncan said. In immuno-oncology, these are not factors.
“It’s such a very interesting story with so many nuances and dimensions to it, all sitting in one house,’ she mused.
For Coller, the August 5 approval of Moderna’s mFLUVISA—which came exactly a year after the HHS funding cuts—and the positive intismeran data, are a “vindication” of mRNA in preventing and treating disease. The FDA’s greenlight and the positive trial results showed “that this is a safe platform that has the power to really alter the way we treat both infectious disease as well as some of the most recalcitrant cancers that humans face.”
Beyond melanoma and pancreatic cancer—where BioNTech and Roche’s cancer vaccine autogene cevumeran has shown potential in a small Phase 1 trial—Coller pointed to mRNA’s potential to treat glioblastoma, the most aggressive primary brain tumor. Like pancreatic cancer, the glioblastoma prognosis is frightening, with just 5–7% of patients surviving five years after a diagnosis.
Coller also sees wide-ranging potential for the application of mRNA beyond cancer. There are around 300 haploinsufficiencies—genetic situations in which a single functional copy of a gene cannot produce the necessary protein—that could potentially lead to disease, he said. Coller offered the example of gene therapy for rare genetic disorders where a base editor is being transiently expressed.
“This is a perfect combination of technologies, where you have CRISPR base editor combinations being married with mRNA, and then of course LNPs [lipid nanoparticles], or delivery mechanisms,” Coller said. This enables the very transient expression of a group of proteins that could edit the genome and correct a mutation, he explained. “That’s powerful.”
mRNA’s full story still unwritten
It’s not all upside in the mRNA space. On Aug. 28, BioNTech discontinued a Phase 2 trial of a personalized mRNA-based therapy in colorectal cancer after an independent data safety monitoring board recommended discontinuing the trial due to futility.
“We expect the termination to reduce confidence in autogene cevumeran and raise questions about whether vaccine-induced immune responses can prevent recurrence without concurrent checkpoint inhibition or chemotherapy,” BMO Capital Markets wrote the same day.
Coller acknowledged that the mRNA story is far from finished.
“There’s still lots of barriers,” he said. “With most modern kind of interventions like this, delivery is always a challenge. We’re really good at getting to the liver . . . but getting mRNA to other cell types is something we have to really seriously invest in now.”
Coller offered the brain as a prime example. “The technology to deliver an mRNA to the brain would be useful for rare genetic disease as well as brain cancer,” he said.
Tsai, for his part, wants to see more data. “Investors are still not entirely certain whether [intismeran] is broadly applicable to other tougher solid tumors,” such as renal, lung and bladder cancers, he said.
Solid tumors “tend to be immune privileged, so it can be difficult,” Coller added. However, he continued, “there may be ways to train tumors to be more immunogenic, to make them more hot rather than cold, using mRNA technologies.”
Walker is similarly optimistic about the use of mRNA to treat tumors. She cited the early results for BioNTech and Roche’s autogene cevumeran in pancreatic cancer as a hopeful sign that personalized cancer vaccines “will be much better at targeting solid tumors, perhaps, than others [modalities].” Follow-up results reported in April show that nearly 90% of participants in a Phase 1 trial whose immune systems responded to the vaccine were still alive up to six years after receiving the last treatment, according to Memorial Sloan Kettering Cancer Center.
The industry could soon have another solid tumor dataset to reference. Tsai is expecting a readout for a Phase 2 trial of Merck and Moderna’s intismeran autogene in renal cell carcinoma later this year or in early 2027.
The partners are demonstrating that it’s possible to scale up manufacturing to support a potential launch.
“They’re developing commercial manufacturing validation for individualized products,” Duncan said. There were 1,137 participants in the INTerpath-001 trial, randomized to 2:1 to receive the combination or single-agent Keytruda for approximately a year after having cutaneous melanoma removed surgically. “Each one goes from tumor sequencing to new antigen selection to contract formulation, treatment administration, for over 1,100 people globally. . . . It’s like the manufacturing scale that we’ve been talking about with individualized medicine, that it’s coming, it’s coming. It’s here.”
As for those “political headwinds,” Coller said, they still exist, but they’re failing to hold back innovation. He recalled an August 2 interview with CNN anchor Dana Bash where Kennedy said that “mRNA was not useful, or dangerous in treatment of infectious disease in treatment of respiratory diseases.” Three days later, the FDA approved Moderna’s mRNA-based flu vaccine.
“Science won,” Coller said. “Science trumped the political movement.”
