Moderna Says Intismeran Needs No PD-1 Backbone and Plans to Move Into Stage I Disease, as Phase III Data Near at ESMO
CEO Stéphane Bancel and new Chief Development Officer David Berman outline the Intismeran expansion plan, Lynch syndrome vaccine ambitions and rare disease timing at the Bernstein Healthcare Forum, September 23, 2026
Moderna used its appearance at Bernstein's 3rd Annual Healthcare Forum to argue that the market still undervalues the breadth of its platform. The more important message for investors was strategic. Management believes Intismeran, its individualized neoantigen therapy partnered 50-50 with Merck, can work without a PD-1 inhibitor. If that holds in the clinic, the addressable market extends well beyond the post-surgical, add-on-to-KEYTRUDA setting where the drug is currently being tested. Neither executive gave Phase III numbers ahead of the ESMO presentation. Berman did lay out why he believes the dataset is unusually robust.
Intismeran: Why Management Believes the Phase III Is a Strong Approval Case
Berman, who joined from Immunocore in March and previously worked on ipilimumab at Bristol-Myers Squibb and on Imfinzi at AstraZeneca, framed the adjuvant melanoma trial as a high bar. The control arm is KEYTRUDA, not placebo. "This trial adds on to KEYTRUDA versus KEYTRUDA. So it's not a very easy control arm to beat," he said. He noted that the study hit its primary endpoint at the first interim analysis and also hit distant metastasis-free survival, a secondary endpoint, at that same look. In his words, it is the first adjuvant Phase III to achieve both at an interim, and the first to beat PD-1 monotherapy as an add-on.
Berman also pointed out that the trial pooled Stage II and Stage III patients into a single population. Stage II is harder to beat, so a statistically significant result across the combined group says more about the strength of the effect. With roughly 1,100 patients in a blinded, controlled design, he said, "I'm very confident that we have a strong case for approval." Bernstein's Courtney Breen noted the earlier Phase II data did not yield a filing path. That history explains why management is emphasizing the size and rigor of the Phase III. Bancel said the focus now is filing the BLA "as fast as we can." Pricing was deferred until the data are public.
A Bigger Claim: Intismeran Without a Checkpoint Inhibitor
The most consequential new framing was Berman's assertion that Intismeran does not depend on a PD-1. He asked Bancel to hold the point for emphasis. "Intismeran does not need a PD-1 to be active," he said, adding that the industry's assumption that everything must be layered onto a checkpoint inhibitor "is not the case." His reasoning is that the therapy acts upstream, alerting the immune system, whereas checkpoint inhibitors release a brake downstream.
That belief underpins an earlier-stage strategy. Moderna has a Phase III in Stage I lung cancer and a randomized Phase II in non-muscle invasive bladder cancer with BCG. Bancel argued that checkpoint inhibitors are not used in Stage I disease because of their long-term autoimmune side effects, and that diagnostics are moving earlier. He described a possible future in which a patient receives Intismeran as a monotherapy, "at your local CVS," as an intramuscular injection of 9 doses every 3 weeks. That is aspirational. It rests on a clinical hypothesis not yet tested in a registrational setting, and the Phase III population is melanoma patients receiving KEYTRUDA.
The broader program is large. There are 3 Phase III lung trials, including one that has stopped screening and should complete randomization later this year. Renal cell and bladder cancer readouts are expected over roughly the next 12 months. Berman drew on Phase II subset analysis showing similar efficacy in high and low tumor mutational burden patients to argue that tumors at or above the TMB level of cutaneous melanoma should be responsive. Management also flagged metastatic disease as higher risk, because a biopsy from one lesion may not represent all lesions. Pancreatic and gastric cancers are being studied as well. Phase I pancreatic data are expected later this year. Bancel said Moderna and Merck are looking at ways to accelerate the program, which already has 9 studies ongoing, because "the plan cannot be the same from when you believe something to when you know something."
Manufacturing Is Not the Constraint; Hospitals Are
Bancel was direct about where he sees scaling risk. He said the bottleneck will be hospital logistics, not manufacturing or payers. Moderna and Merck are building teams to onboard sites one by one, ranking hospitals by importance, and using a digital tracking platform for biopsies, data and patient workflow, tools he said were not available in the Phase II or even the Phase III. Merck, he said, "is an amazing commercial machine" and will handle payer relationships.
On manufacturing, he described a cell-free, enzyme-based liquid process that scales out rather than up. "Our biggest cost is depreciation of the clean room," he said, so the goal is smaller machines with a smaller footprint and shorter cycle times. He said compressing production from 5 weeks to 1 week materially changes output economics. He was emphatic: "Do I worry about manufacturing? Not a minute." Investors should treat that as confidence, not evidence. No cost-per-dose or throughput figures were provided.
Bancel also pointed to a moat that he thinks investors underappreciate. Moderna receives only raw sequencing data of healthy and tumor DNA from partners, while the selection of the 34 neoantigens is proprietary. Because each product is individualized, he argued, a generic copy would be difficult to define, let alone get approved. That claim has not been tested with regulators.
The commercial structure with Merck is a virtual joint venture. Costs for sales, clinical studies, manufacturing capital and operating expenses are split 50-50, and profits are shared equally.
Lynch Syndrome and the Next Oncology Wave
Management gave more color on what comes after Intismeran, and the lead item is an off-the-shelf vaccine for Lynch syndrome, a genetic condition Bancel said affects about 1 in 300 people and can raise the risk of some cancers by up to 10x. Patients share frameshift neoantigens, which makes the condition suitable for a standardized product. A Phase I/II is ongoing in the U.K. with Oxford. The long-term goal is cancer interception: giving a periodic vaccine to high-risk, otherwise healthy people. Berman called it a high-probability program, with the thymus unlikely to have eliminated reactive T cells to these neoantigens. Bancel described it as "the most derisked application based on Intismeran as a read-across" and noted Moderna owns it 100%. He suggested a retail pharmacy channel could also support the vaccine business. Dosing frequency is unknown, and the study has to show clinical benefit.
Beyond Lynch, Moderna has Phase I off-the-shelf vaccines against shared tumor antigens. Berman acknowledged "a higher scientific risk," since the thymus may delete T cells reactive to these self-proteins, though T-cell activation has been observed. In multiple myeloma, the company is testing what Berman said is the first multiplexed mRNA drug encoding 3 T-cell engagers in a single product, in heavily pretreated patients. Data are due later this year. He called it a sentinel program whose success would support further investment in solid tumor applications. Autoimmune efforts include an in vivo CAR-T program heading to the clinic, with further updates expected over the next 12 to 18 months.
Rare Disease: Propionic Acidemia Data Due in Q4
Pivotal data in propionic acidemia (PA) are expected in the fourth quarter. Bancel set a high expectation, saying that for children at the dose used in the pivotal study, "the data is wow," and that it is a time-bound Phase III in a genetic disease with no target biology risk. He pitched PA as the first of a liver franchise, citing more than 12 published preclinical models of rare liver diseases using the same lipid and manufacturing process, and said the pace of clinical entry is a matter of financial discipline.
He also tied rare disease to a margin argument. Moderna's cost of goods "don't look great" because the plants sit largely idle for half the year given vaccine seasonality. Filling that capacity with rare disease product would spread fixed costs. That is a reasonable operating logic, but it depends on approvals and launches that have not occurred.
Platform Positioning, Balance Sheet and Candid Admissions
Bancel argued that Moderna is now the only mRNA platform company left. He cited CureVac's Phase III failure and exit, BioNTech's plan to split into two companies, and Sanofi's decision to stop its mRNA vaccine programs. The company has 5 approved vaccines, with 2 launching this year. Breen acknowledged the setbacks of the past year, including late-stage disappointment in CMV, the push-out of norovirus, and FDA friction over filing strategies. Management did not address those directly. Bancel was candid about the past few years: "It's not fun when your sales go down 90%."
Breen noted that Moderna raised $2.6 billion in convertible notes a few weeks ago, but the executives did not give specifics on use of proceeds. Bancel said he does not manage to next-quarter EPS and aims to create a 10x return over 5 to 10 years. His message was that Intismeran is just the beginning. "This is not our best product," he told staff after the August data. "It's an amazing first oncology product."