u/SustainableStocks

Neutral rating remains, but PT raised to $120.

MRNA disclosed highly anticipated data from the Phase 3 INTerpath-001 study evaluating MRK-partnered individualized neoantigen therapy intismeran in combination with Keytruda in Stage II-IV adjuvant melanoma (n= 1,137) and we spoke with management. At a pre-specified interim analysis, the combination demonstrated statistically significant and clinically meaningful improvements in recurrence free survival (primary endpoint) and distant metastasis-free survival (key secondary) versus Keytruda and per protocol, the study will continue to evaluate other secondary endpoints, including overall survival. Importantly, intismeran's safety profile is benign with no new signals observed. While specific data was not provided, our prior analysis suggests a hazard ratio in the low-to-mid 0.70 range would support statistical significance, noting management has described the bar at the interim as high, and we expect more fulsome data at an upcoming international medical meeting (potentially the European Society for Medical Oncology, October 23-27, which we are attending). In our view, success in melanoma was priced in, with MRNA shares trading +100% now reflecting readthrough to other solid tumor indications (per nine ongoing intismeran studies, with Phase 2 data in renal cell carcinoma (RCC) in 2026/early-27 followed by muscle invasive bladder cancer and Phase 3 non-small cell lung cancer (NSCLC) data in 2027, where success in RCC would suggest likely efficacy in indications where Keytruda is effective). MRNA and MRK intend to discuss the data with regulators to potentially file for approval - we model for global peak sales of $4.3bn in melanoma, and $6.6bn in NSCLC, pre-adjustment for 50/50 economics with MRK. Overall, this data is the initial unlock for MRNA's cancer vertical, and the first positive pivotal data for MRNA outside of the respiratory vaccine franchise.

Phase 3 Intismeran study in adjuvant melanoma met the primary and a key secondary endpoint at interim
Fully enrolled as of September 2024, INTerpath-001 is a randomized, double-blind, placebo- and active comparator-controlled study assessing the safety and efficacy of intismeran plus Keytruda (versus placebo plus Keytruda) in preventing disease recurrence in patients (n=1,089) with resected melanoma who are at a high risk of recurrence. Today, MRNA announced positive topline results, noting the study met the primary endpoint of recurrence-free survival (RFS) and key secondary endpoint of distant metastatis-free survival (DMFS) at an interim analysis. On safety, the profile was consistent with that observed in prior studies of the combination, with no new safety signals observed. MRNA and partner MRK (covered by Asad Haider) plan to present the data at an upcoming international medical meeting (potentially at the European Society for Medical Oncology conference, October 23-27), and will engage with regulators on filing submissions for intismeran in combination with Keytruda.
Recall, the Phase 3 study design is consistent with the prior Ph2b trial, where patients in INTerpath-001 are randomized 2:1 to receive treatment with either intismeran + Keytruda (the combination treatment arm) or placebo + Keytruda (the control treatment arm), where intismeran is administered for up to 9 doses (Q3W) and Keytruda is administered until the earlier of 1) roughly one year of treatment, and 2) patients experience either disease recurrence or unacceptable toxicity. As in the Ph2b trial, the Ph3's primary endpoint is RFS, with distant metastasis-free survival (DMFS) and overall survival (OS) evaluated as secondary endpoints (though we note the latter, OS, was an exploratory endpoint rather than secondary in the Ph2b). Similarly, patient baseline characteristics in the Ph3 trial will include a diagnosis of resectable, cutaneous melanoma, complete surgical resection within 13 weeks prior to receipt of the first Keytruda dose, and patients' being disease free at study entry, all as in the Ph2b trial. Beyond melanoma, MRNA is evaluating intismeran across multiple tumor types and stages of disease, including non-small cell lung cancer (NSCLC), bladder cancer (data likely in 2027) and renal cell carcinoma (RCC; data potentially in 2026 or 2027). Additional clinical studies include the Phase 2b KEYNOTE-942/mRNA-4157-P201 trial in adjuvant melanoma and a Phase 1 study exploring adjuvant pancreatic ductal adenocarcinoma, perioperative gastric carcinoma and perioperative NSCLC.
We spoke with management, who noted that the study met the primary RFS and secondary DMFS endpoints, and that per the protocol, the study will continue in order to evaluate other key secondary endpoints, including overall survival (OS). MRNA additionally noted the higher statistical bar for an interim analysis. On readthrough to additional indications, MRNA expressed confidence per the translational data in melanoma presented earlier this year, noting the intismeran mechanism appears synergistic with Keytruda. In colder tumors, MRNA is taking a taking signal seeking (Phase 1) approach, including in pancreatic and gastric tumors - per management, data in these indications could be available in 2026/27.
In our view, the positive topline Phase 3 INTerpath-001 result is encouraging, and is the initial unlock for MRNA's cancer vertical. We next look to intismeran data in RCC, which is considered a colder tumor vs. melanoma - if intismeran can show benefit in RCC, then efficacy in additional indications where Keytruda has shown benefit is likely.

Model Changes: We 1) Increase our PoS for intismeran in melanoma to 100% (from 90% prior), given we now think approval is likely based on this morning's update. We also increase our peak sales in melanoma to $4.3bn from $2.8bn prior, given the success at the interim analysis supports a stronger clinical profile than our base assumption; 2) Increase our PoS for intismeran in non-small cell lung cancer (NSCLC) to 85% (from 70% prior), given we see readthrough from the supportive data from the Phase 3 study in melanoma. We also increase our peak sales in NSCLC to $6.6bn from $4bn prior given the readthrough and increased confidence on the commercial opportunity given the profile that was achieved in the large Phase 3 in melanoma; and 3) Increase our TGR to 5% (from 4%), given we see increased platform value per readthrough to other solid tumor indications. Our 12-month PT moves to $120 (from $67 prior).
MRNA (Neutral): We are Neutral rated on MRNA. Our 12-month PT of $120 is based on a 100% DCF value (11% WACC and 5% TGR, from 4% prior given the unlocking of the platform in oncology). Upside risks: Commercial risk - higher than anticipated sales and penetration into patient populations, earlier-than-expected approval timelines from the oncology programs, other pipeline success and competitive failures. Downside risks: Failure to demonstrate clinical proof of concept across additional modalities or across additional oncology indications, IP risk, manufacturing difficulties and financing/dilution, failure to achieve the projected commercial profile, physician/payor pushback on use and coverage, approval of competitor drugs.

From 7/20. Goldman Sachs raises PT for Moderna to $67 (from $49) and maintains neutral rating.

Here is the full research note:

MRNA is developing an individualized neoantiogen cancer therapy, intismeran, in collaboration with MRK, where interim Phase 3 data in adjuvant Stage II-IV melanoma in combination with Keytruda versus Keytruda alone is expected this year from the MRK-designed INTerpath-001 study. Intismeran could establish the commercial oncology vertical as MRNA's first approved product outside of respiratory vaccines, and carries expansion opportunities into other solid tumors per nine ongoing Phase 2 and 3 studies, with additional pipeline efforts (see our Science Day note). We are constructive on the data following impressive 5-year Phase 2 results (hazard ratio (HR)=0.510 on recurrence free survival (RFS)), noting INTerpath-001 leverages the same primary endpoint. Translation of this signal to a larger Phase 3 (1,089 vs. 157 patients in Phase 2) is the largest risk given the potential for efficacy attenuation historically seen in oncology studies; however the Phase 2 was randomized, which increases our confidence. With regard to the probability-of-success of the first interim, we performed an analysis informed by MRK’s prior studies that suggests a high likelihood of success given: 1) our estimate that ~310-320 RFS events have accrued to-date, implying the interim could be performed at a high information fraction (given ~85% of total events are accrued), and 2) a hazard ratio in the low-to-mid 0.70 range would support statistical significance and thus early success. At current levels ($62/share), adjuvant melanoma and some readthrough to other solid tumor indications (we next expect Phase 2 data in renal cell carcinoma this year/early 2027 followed by muscle invasive bladder cancer, with non-small cell lung cancer data likely in 2027) are largely priced in (details within) - however, options markets imply +49% by mid-January on success. In the downside scenario, shares will move towards the base business (~$25/share), and there is a possibility that the study proceeds beyond the first interim. We raise our 12-month price target to $67 (from $49).

May 21 (Reuters) - Moderna and Merck's combination therapy for skin cancer helped reduce risk of cancer spreading to another part of the body by 59% after five years of follow-up, data from ‌a mid-stage trial showed Thursday.

The study tested Moderna's experimental personalized cancer vaccine intismeran autogene, in combination with Merck's blockbuster immunotherapy Keytruda, in melanoma patients after surgery to assess whether the combination prevented their cancer from returning. The trial enrolled 157 patients from 2019 ⁠to 2021.

Link: https://www.reuters.com/business/healthcare-pharmaceuticals/moderna-merck-cancer-combo-cuts-melanoma-spread-risk-five-years-2026-05-21/