Will Moderna report positive Phase 3 results for intismeran (mRNA-4157) in adjuvant melanoma by December 31, 2026?

Base rate for oncology Phase 3 success is 50-60% (inverse of 40-50% failure per Black Swan Beacon). However, the resolution also requires data readout by Dec 31, 2026. The trial is 'fully enrolled' but described as 'potentially' reading out in 2026 -- adjuvant melanoma endpoints are event-driven and timeline is uncertain. I estimate ~65-70% probability of data readout in 2026 and ~55-60% conditional success given the strong 49% recurrence reduction at 5 years in Phase 2b. Combined: approximately 0.42. The new CMO with oncology background and full enrollment are positive signals, but CMV Phase 3 failure introduces a negative platform signal.

Timing is the dominant risk factor. 'Fully enrolled' does not mean imminent readout -- adjuvant melanoma trials are event-driven, requiring sufficient recurrence events to power the analysis. The resolution requires positive results BY December 31, 2026, and Moderna's own language ('potentially in 2026') hedges significantly. I estimate only 60-65% probability of data availability by year-end. Conditional on readout, the 49% recurrence reduction at 5 years is strong Phase 2 data, but the committee-established 40-50% failure base rate must be respected. The CMV failure and 'accumulating setbacks' per Stress Scanner suggest Moderna's non-COVID R&D track record is unproven. Combined probability: ~0.35.

The 49% melanoma recurrence reduction at 5 years is one of the stronger Phase 2 oncology datasets and meaningfully improves on the generic 50-60% Phase 3 success base rate -- perhaps to 55-60% conditional success. Full enrollment is a necessary precondition met, and the new CMO with oncology background signals institutional commitment. However, the unresolved debate about whether R&D spend is justified or reckless creates real uncertainty about execution capability. Timing risk is material: fully enrolled trials still require sufficient events for interim or final analysis. I estimate 65-70% readout probability by year-end. The competitive landscape gap (oncology not benchmarked vs. CAR-T, bispecifics, ADCs) introduces unknown competitive risk. Combined: 0.40.

Two independent risks compound here. First, does the Phase 3 read out by December 2026? The trial is fully enrolled but 'potentially' reading out in 2026 is a hedge -- adjuvant melanoma event-driven endpoints can take years after enrollment completes. I give 60-70% odds of data by year-end. Second, does it succeed? The committee-established 40-50% failure rate is the anchor. The 49% Phase 2b reduction is genuinely strong, but Phase 2 to Phase 3 attrition in oncology is well-documented, and Moderna's CMV vaccine just failed Phase 3. Combined: 0.55 success * 0.65 timing = 0.36, rounded to 0.37.

The CMV Phase 3 failure is a material negative signal for Moderna's ability to translate promising earlier-stage data into Phase 3 success. While oncology and infectious disease are different therapeutic areas, the common platform is mRNA and the company has zero non-COVID Phase 3 successes. The pipeline has 'accumulating setbacks' per Stress Scanner, R&D is $3.3-3.4B against $1.6-2.0B revenue, and the CDER regulatory independence is untested (E0 -- the most dangerous gap). Timing risk is significant: 'potentially in 2026' is deliberately vague. I weight success lower than the generic base rate given platform-specific concerns. 0.48 success * 0.66 timing = 0.32.

The 49% reduction at 5 years in Phase 2b KEYNOTE-942 is not speculative -- it is confirmed committee-verified clinical data representing one of the stronger oncology Phase 2 datasets. Intismeran in combination with Keytruda (the standard of care) adds meaningful incremental benefit. This suggests the Phase 3 has a better-than-average success probability within oncology, perhaps 55-60%. Moderna has strong institutional incentive to report quickly given that the stock trades near cash value and this is the highest-information-gain catalyst. Timing: I estimate 65-70% chance of data in 2026 given full enrollment and corporate urgency. Combined: 0.57 * 0.67 = 0.38.

Two key factors: base rate Phase 3 success ~50-60% and timing risk (readout by Dec 2026) ~65%. The 49% recurrence reduction at 5 years is strong Phase 2 data that slightly improves base rate. Combined: ~0.38. New CMO with oncology background is modestly positive.

Dominant risk is timing -- 'potentially in 2026' is vague for a question requiring results BY Dec 31, 2026. Event-driven endpoints in adjuvant melanoma can take years post-enrollment. CMV Phase 3 failure and 'accumulating setbacks' weigh against platform confidence. Conservative estimate.

Fully enrolled Phase 3 with strong Phase 2 data (49% reduction). Timing is the main risk -- ~62-65% chance of readout by year-end. Base rate success ~55% given strong Phase 2. Combined: 0.55 * 0.65 = 0.36. The market assigning zero option value means significant upside if positive, but does not change the probability of the event itself.