Summary
- Moderna (MRNA) saw its stock price soar approximately 131% on Wednesday after the Phase 3 INTerpath-001 trial demonstrated success in its endpoints for intismeran autogene combined with Keytruda in melanoma patients.
- The innovative treatment, intismeran autogene, is a personalized mRNA therapy designed from the mutations found in a patient’s tumor, used alongside Merck's Keytruda immunotherapy.
- Investors who were shorting Moderna incurred around $4.8 billion in mark-to-market losses as the stock's value more than doubled, with short interest at 13.5% of the free float.
Moderna's personalized mRNA cancer vaccine achieved a significant milestone by passing its first Phase 3 trial, prompting a market reaction akin to a major victory.
On Wednesday, shares of Moderna surged roughly 131%, more than doubling to nearly $148, with an intraday high of $163, marking an unprecedented single-day increase. Merck (MRK), which markets Keytruda, also experienced a substantial rise following the announcement.
Myriad: What will the Fed do in September? Click to make your prediction.The two companies revealed that the Phase 3 INTerpath-001 trial met its goals for recurrence-free survival and distant metastasis-free survival in patients who had undergone surgery for stage IIB–IV melanoma.
This marks the first positive outcome for a personalized neoantigen therapy in a Phase 3 trial and the inaugural success for an mRNA-based cancer treatment.
Understanding the Therapy
Intismeran autogene, also known as V940 or mRNA-4157, is not a standard mass-produced medication. Instead, healthcare providers analyze a patient’s tumor to identify its specific mutations, and the mRNA instructs the body to generate neoantigens—protein fragments that the immune system can recognize and attack.
Keytruda, an anti-PD-1 agent, enhances the activity of immune cells. Together, these treatments aim to eliminate any remaining cancer cells following surgery.
The combined approach from Moderna and Merck outperformed Keytruda alone, which is the current standard treatment, on both clinical endpoints. This is the first instance where a personalized neoantigen therapy has demonstrated a significant clinical advantage over the widely used immunotherapy in adjuvant settings (post-surgery treatment to prevent recurrence). For Moderna, which has been struggling after a decline in its COVID-related business and has faced substantial short-selling pressure, this trial outcome represents a critical moment for the company.
This development also triggered a reaction in the market. When a heavily shorted stock surges, investors who have bet against it rush to buy back shares to minimize their losses—a phenomenon reminiscent of the 2021 GameStop trading frenzy. Recently, short sellers in crypto-related stocks incurred losses totaling $2.6 billion as the market swung, and Moderna's stock movement was even more pronounced.
"With each shorted share now down almost $100, this kind of pressure is precisely what can lead to a squeeze," stated Peter Hillerberg, co-founder of ORTEX.
The trial will continue to assess overall survival rates and other secondary endpoints that have yet to be reported.