Merck & Co. Inc. / LaNova Medicines Ltd.

Solid tumors (PD-1/VEGF bispecific, lung and other)

235K US cases/yr · $55.0B Global immuno-oncology market 2024 (PD-(L)1-based) · 29500 Keytruda 2024 global sales (USD MM) being defended

Disease Overview

The PD-1/VEGF bispecific antibody class emerged in 2024 as potentially the most disruptive next-generation immuno-oncology mechanism, driven by Akeso/Summit's ivonescimab besting Merck's Keytruda (pembrolizumab) head-to-head on progression-free survival in the Chinese Phase 3 HARMONi-2 trial in first-line PD-L1-positive non-small cell lung cancer. NSCLC alone accounts for approximately 234,580 new US cases annually (ACS 2024 Cancer Facts & Figures) and remains the leading cause of cancer mortality (125,070 deaths). PD-(L)1 monotherapy or in combination with chemotherapy is standard of care in first-line metastatic NSCLC, with Keytruda generating $29.5B in 2024 (Merck 10-K). The global IO market exceeds $55B across NSCLC, melanoma, renal cell, urothelial, head & neck, MSI-H, triple-negative breast and multiple other solid tumors. Merck faces the 2028 Keytruda composition-of-matter patent cliff (biosimilar entry 2028-2030 depending on formulation), and the company has pivoted aggressively toward subcutaneous Keytruda, novel combinations and next-generation IO bispecifics to preserve franchise value. LM-299 positions Merck against Summit/Akeso's ivonescimab and Pfizer/3SBio's PD-1/VEGF program as the three most credible global PD-1/VEGF challengers.

Competitive Landscape

The PD-1/VEGF bispecific category is the most contested near-term IO segment. Lead global competitor: ivonescimab (AK112, Akeso/Summit Therapeutics) — Phase 3 HARMONi-2 topline showed PFS superiority over Keytruda in 1L PD-L1+ NSCLC; approved in China May 2024 for EGFR-mutant NSCLC progressed on TKI. Challengers: LM-299 (LaNova/Merck, Phase 1 in China) — Merck's $588M upfront plus $2.7B milestone bet; SSGJ-707 (3SBio, licensed to Pfizer for $1.25B upfront plus milestones May 2025, deal announced post-LM-299). Established IO backbones being defended or displaced: pembrolizumab (Keytruda, Merck) — category dominator; nivolumab (Opdivo, BMS) — including Opdivo Qvantig subq; atezolizumab (Tecentriq, Roche); durvalumab (Imfinzi, AstraZeneca); cemiplimab (Libtayo, Regeneron). Adjacent next-gen IO: LAG-3 (relatlimab/Opdualag, BMS), TIGIT (tiragolumab, Roche — failed multiple Phase 3s), anti-PVRIG (surzebiclimab, Compugen/Gilead). Merck has signaled LM-299 could also be combined with its anti-TIGIT vibostolimab and LAG-3 favezelimab, yielding a three-platform post-Keytruda architecture.