Inside Moderna’s Biggest mRNA Test Since COVID

Video summary

Moderna and Merck’s personalized mRNA vaccine beat Keytruda alone in a Phase 3 melanoma trial, after 1,000 cancer-vaccine trials failed.

Moderna CEO Stéphane Bancel told a16z’s Jorge Conde that Moderna and Merck’s individualized mRNA treatment met its Phase 3 primary endpoint of recurrence-free survival in melanoma and, unexpectedly, its secondary endpoint of distant metastasis-free survival. The result follows more than 10 years of work and a field history of over 1,000 failed cancer-vaccine trials. The treatment compares tumor and healthy-cell DNA, uses an algorithm to select up to 34 mutations, and encodes them in a patient-specific mRNA vaccine to train T cells to recognize cancer; about 90% of selected antigens differ between patients. Bancel said the current process takes about 42 days from biopsy to hospital delivery, with a Massachusetts facility capable of producing tens of thousands of doses. Moderna hopes to file for approval and make the treatment available in 2027. The company is also testing the approach in lung, kidney, bladder, pancreatic and gastric cancers, while exploring rare liver diseases and autoimmune treatments.

Chapters

1. 0:00How Moderna Went From COVID to Cancer: DNA-Matched Vaccines and Phase 3 Melanoma Results
2. 2:48Phase 3 Melanoma News: Moderna–Merck Vaccine Meets Two Survival Endpoints
3. 5:46Keytruda’s 60% Five-Year Disease-Free Rate and Moderna’s Targeted T-Cell Training
4. 9:23Cancer Vaccine Means Retraining Immunity to Prevent Melanoma’s Return
5. 11:16Why mRNA and Patient-Specific Selection Changed Cancer Vaccines After 1,000 Failed Trials
6. 15:09Moderna’s 34-Neoantigen Algorithm: A Ten-Year Model Set for FDA-Guided Improvement
7. 18:48The Operational Challenge: Sequencing Each Tumor to Make a Patient-Specific Vaccine
8. 20:1642-Day Needle-to-Needle Delivery: Synthetic Production and Smaller Vaccine-Making Machines
9. 24:33Marlborough Capacity: Tens of Thousands of Doses, With Pricing Still Undisclosed
10. 27:08Regulating Personalized mRNA: Process BLA and Consistent Outputs for the FDA
11. 29:37Beyond Melanoma: Moderna Tests mRNA in Lung, Kidney, Bladder, Pancreatic, and Gastric Cancers
12. 35:58From COVID and Cancer to Rare Liver Disease Studies and Personalized Autoimmune Treatments