Bristol-Myers Squibb Company / Agenus Inc.

Solid tumors including non-small cell lung cancer (anti-TIGIT bispecific)

236K US cases/yr · $25.0B Global NSCLC drug market 2021 (USD MM) · 131880 US lung cancer deaths annually

Disease Overview

The AGEN1777 program targets TIGIT-driven immune evasion across PD-(L)1-experienced and PD-(L)1-naïve solid tumors, with non-small cell lung cancer (NSCLC) as the lead indication priority. NSCLC is the largest oncology commercial opportunity globally, with approximately 235,760 new US lung cancer cases and 131,880 deaths projected in 2021 (American Cancer Society) of which ~85% are non-small cell. Approximately 60-70% of NSCLC patients present with advanced/metastatic disease at diagnosis, and despite checkpoint inhibitors transforming the front-line setting (Keytruda monotherapy in PD-L1≥50%, Keytruda+chemo, Tecentriq+bevacizumab+chemo, Opdivo+Yervoy+chemo, Imfinzi+tremelimumab+chemo), 5-year survival remains roughly 25-30% for stage IV PD-L1-high and below 10% for PD-L1-low/negative. Mechanisms of resistance include T-cell exhaustion, regulatory T-cell infiltration, MHC downregulation, and alternative checkpoint upregulation including TIGIT, LAG-3, and TIM-3. TIGIT is co-expressed with PD-1 on tumor-infiltrating lymphocytes and Tregs, making dual blockade an attractive strategy. The total NSCLC drug market exceeded $25B globally in 2021 (Keytruda alone delivered $17.2B in 2021 across indications, with NSCLC contributing the majority).

Competitive Landscape

At deal date (May 2021) the anti-TIGIT space was the most contested next-generation immuno-oncology checkpoint after PD-(L)1, with five Phase 3 programs and >20 Phase 1/2 candidates. Roche/Genentech tiragolumab (TIGIT IgG1) had reported positive Phase 2 CITYSCAPE data in 1L PD-L1-high NSCLC at ASCO 2020 and was running Phase 3 SKYSCRAPER-01 (1L NSCLC PD-L1≥50% combo with atezolizumab). Merck vibostolimab (MK-7684, IgG1) was in Phase 3 KEYVIBE program with pembrolizumab across NSCLC, melanoma, and SCLC. Bristol Myers Squibb's existing IO-bet was BMS-986207 (Fc-active TIGIT) plus a non-Fc-active variant from Compugen — and AGEN1777 was BMS's third TIGIT bet, an Fc-enhanced bispecific against a second undisclosed checkpoint to differentiate via stronger Treg depletion and broader checkpoint coverage. Other competitors: GlaxoSmithKline GSK4428859A/EOS-448 (iTeos partnership $625M+, Jun 2021), Arcus Biosciences/Gilead domvanalimab (TIGIT) and AB154 (PVRIG, Phase 2/3 ARC-7/PACIFIC-8), Beigene ociperlimab (Phase 3 AdvanTIG NSCLC, $2.2B Novartis option Dec 2021 then returned 2023), Innovent IBI-939, Astellas ASP8374 (anti-TIGIT, partnered with Potenza and Keytruda combo), Eli Lilly LY3415244 (TIGIT/PD-L1 bispecific). The space has been substantially de-risked downward since 2021: Roche tiragolumab missed key endpoints in SKYSCRAPER-01 (Mar 2022), SKYSCRAPER-02 SCLC (May 2022), Merck vibostolimab missed in KEYVIBE-008 SCLC (Nov 2023), and BMS-986207 was deprioritized in 2024. AGEN1777 itself was returned to Agenus by BMS in Aug 2024.