Immunome's Undervalued Gamma Secretase Inhibitor Pipeline in Light of SpringWorks' Merck Acquisition

The acquisition of SpringWorks Therapeutics by Merck KGaA for $3.9 billion in April 2025 has sent shockwaves through the rare disease oncology sector. This blockbuster deal, driven by SpringWorks' two FDA-approved gamma secretase inhibitors—OGSIVEO (nirogacestat) for desmoid tumors and GOMEKLI (mirdametinib) for neurofibromatosis type 1—underscores the premium investors are willing to pay for therapies targeting unmet medical needs in niche markets. Yet, as SpringWorks' valuation soars, Immunome's varegacestat pipeline remains conspicuously undervalued, despite its direct alignment with the same high-margin, high-growth therapeutic niche.

The SpringWorks Premium: A Benchmark for Rare Disease Innovation

SpringWorks' nirogacestat (OGSIVEO) generated $172 million in U.S. net product revenue in 2024, up from just $5.4 million in 2023, while its mirdametinib (GOMEKLI) launched in early 2025 as the first and only therapy for NF1-associated plexiform neurofibromas. Merck's $3.9 billion acquisition price implies a valuation multiple of approximately 23x 2024 revenue for OGSIVEO alone, assuming conservative revenue projections for GOMEKLI. This premium reflects not only the drugs' clinical differentiation but also the strategic value of entering a market where orphan drug exclusivity and high pricing power are table stakes.

Merck's rationale was clear: SpringWorks' portfolio filled a critical gap in its rare disease strategy, offering first-in-class therapies for desmoid tumors and NF1—conditions with patient populations too small for Big Pharma but lucrative enough to justify blockbuster pricing. The acquisition also aligned with broader industry trends, as global orphan drug spending is projected to exceed $200 billion by 2030.

Immunome's Varegacestat: A Parallel Path, A Dislocated Valuation

Immunome's varegacestat, a gamma secretase inhibitor in Phase 3 trials for desmoid tumors, mirrors SpringWorks' OGSIVEO in mechanism, indication, and unmet need. Yet, despite identical clinical positioning and Orphan Drug Designations from both the FDA (2023) and EMA (2025), Immunome trades at a fraction of SpringWorks' valuation. As of June 2025, Immunome holds $268 million in cash and is on track to report topline data from its RINGSIDE Part B trial by year-end—a pivotal event that could catalyze a re-rating.

The dislocation is stark. SpringWorks was acquired at a 23x revenue multiple for a drug already generating $172 million in 2024 revenue. Immunome's varegacestat, if approved, could replicate this success. Desmoid tumors affect fewer than 1,500 patients annually in the U.S., yet current therapies are suboptimal. Varegacestat's Phase 2 data, presented at ASCO 2025, showed robust tumor volume reductions and manageable safety, positioning it as a best-in-class candidate. With a potential $200,000–$300,000 annual price tag (similar to OGSIVEO), varegacestat could generate $300 million+ in peak sales—a figure that would justify a valuation far exceeding Immunome's current market cap of ~$1.2 billion.

The Broader Pipeline: A Multi-Modal Catalyst Engine

While varegacestat is Immunome's crown jewel, its pipeline extends beyond single-asset speculation. The company's ADC platform, anchored by the proprietary HC74 payload, is advancing IM-1021 (ROR1-targeted) in Phase 1 trials and three preclinical ADCs. IM-3050, a FAP-targeted radioligand, is set to enter Phase 1 in late 2025, adding another layer of diversification. These programs, though earlier-stage, leverage Immunome's expertise in targeted therapies for rare cancers—a strategy that mirrors SpringWorks' focus but with a broader modalities toolkit.

Critically, Immunome's cash runway extends through 2027, eliminating the need for near-term dilution. This financial discipline, combined with its pipeline's alignment with orphan drug incentives, positions it to capitalize on the same market dynamics that drove Merck's acquisition.

Market Underappreciation and Catalyst-Driven Re-Rating

The market's underappreciation of Immunome stems from its smaller scale and lack of commercial infrastructure compared to SpringWorks. However, this is a false distinction. Merck's acquisition of SpringWorks wasn't about commercial execution—it was about acquiring a differentiated asset in a high-margin niche. Immunome's varegacestat, if successful, could attract similar interest from Big Pharma, particularly as Merck and others seek to bolster their rare disease portfolios.

Key catalysts in 2025 include:
1. RINGSIDE Part B topline data (Q4 2025): A positive readout could trigger a 50%+ re-rating.
2. IM-3050 Phase 1 initiation (Q4 2025): Validates Immunome's expansion into radioligand therapy.
3. EMA Orphan Drug Designation for varegacestat (already secured): Opens the European market, where Immunome could partner with larger players.

Investment Thesis: Buy on the Dislocation

Immunome's valuation is a classic case of strategic dislocation. While SpringWorks commanded a $3.9 billion premium for its rare disease assets, Immunome offers a similar risk/reward profile at a 10x discount. The company's varegacestat pipeline, combined with its diversified ADC and radioligand programs, represents a compelling opportunity for investors seeking exposure to the high-growth orphan drug sector.

For those who missed the SpringWorks/Merck deal, Immunome is the next best bet. With a clear path to regulatory milestones, a strong cash position, and a market that has yet to price in its full potential, Immunome is a buy for the long-term and a must-watch for catalyst-driven traders.