PD-1 x TIGIT Bispecifics After the TIGIT Phase 3 Setbacks | Oncology Modality Intelligence

Description

List of Tables

TIGIT was immuno-oncology's favorite next checkpoint, and then the pivotal readouts turned against it. Roche's tiragolumab carried the field on the strength of early lung-cancer data, and when the SKYSCRAPER Phase 3 program read out in 2024-2025, the mechanism's flagship collapsed; Merck & Co discontinued its vibostolimab program after its own Phase 3 readouts, GSK walked away from the iTeos belrestotug collaboration after the GALAXIES-Lung-201 readout in May 2025, iTeos itself wound down, and BeiGene terminated the AdvanTIG-302 study of ociperlimab. What remains is a rump of programs and a genuinely interesting question: was the target wrong, or were the constructs? The survivors argue the latter. AstraZeneca's rilvegostomig, a purpose-built PD-1XTIGIT bispecific now in Phase 3, embodies the case that bispecific avidity and Fc engineering - the features the earlier antibodies lacked or handled differently - are where the mechanism's value lives. Arcus and Gilead's domvanalimab, an Fc-silent antibody, continued through the STAR-221 and STAR-121 readouts, keeping the Fc-function debate open rather than settled. Junshi's JS006 persists on the toripalimab backbone, and Bristol Myers Squibb retains a residual program. For Japan the question lands close to home: Japanese sites enrolled in the global TIGIT programs, so Japanese data are inside the readouts that reset the class; and Ono Pharmaceutical, co-originator of the PD-1 franchise that defines modern IO, faces the follow-on question every IO incumbent now faces - if not TIGIT, then what? This report reconstructs the class's rise and reset with named programs and readout sequences, dissects the construct-design hypotheses that separate the survivors from the discontinued, profiles the remaining pipeline and its owners, maps Japan's participation in the evidence base, and builds the valuation framework for distressed TIGIT assets: what the mechanism might still be worth, to whom, and on what evidence. It serves oncology investors pricing the reset, business-development teams assessing distressed or stranded assets, and IO incumbents - in Japan and elsewhere - deciding where the next backbone comes from.

Scope and Coverage

The report covers TIGIT biology and the anti-TIGIT development history, the Phase 3 readout sequence and program dispositions, surviving bispecific and Fc-engineered programs, construct-design hypotheses, Japanese trial participation, and the domestic IO follow-on question including Ono's position.

Report Highlights

The SKYSCRAPER, KeyVibe, and GALAXIES readout sequence and what each program concluded
Program dispositions: Roche, Merck, GSK/iTeos, and BeiGene decisions mapped
Rilvegostomig (AZD2936) as the lead surviving bispecific hypothesis
Domvanalimab and the Fc-function debate through the STAR-221 and STAR-121 readouts
Japan's position: site participation in global programs and the Ono follow-on question
Valuation framework for distressed TIGIT assets and stranded combination programs

Product Code: JPH-111

Table of Content

1. Executive Summary

2. PD-1 x TIGIT Bispecifics After the TIGIT Phase 3 Setbacks: Modality Overview and Mechanism Landscape

3. Global Pipeline and Deal Activity

4. Key Programs, Clinical Readouts, and Evidence Status

5. Japan Relevance: Trials, Approvals, and Partnerships

6. Regulatory and Pricing Considerations in Japan

7. Competitive Positioning and Valuation Considerations

8. Watch Items and Upcoming Catalysts

9. Appendix: Methodology and Sources

Companies Mentioned

Roche (CH) - tiragolumab: SKYSCRAPER Phase 3 readouts and program termination (2024-2025)
Merck & Co (US) - vibostolimab KeyVibe program discontinued after Phase 3 readouts
GSK (UK) - belrestotug partner; GALAXIES-Lung-201 readout (May 2025); ended the iTeos collaboration
iTeos Therapeutics (BE) - belrestotug originator; company wind-down following the program outcome
AstraZeneca (UK) - rilvegostomig (AZD2936) PD-1XTIGIT bispecific, the lead remaining program, in Phase 3
BeiGene (CN) - ociperlimab with AdvanTIG-302 terminated; Tevimbra franchise context
Junshi (CN) - JS006 anti-TIGIT on the toripalimab backbone
Arcus Biosciences (US) - domvanalimab (Fc-silent); STAR-221 (Dec 2025) and STAR-121 (Apr 2026) readouts
Gilead (US) - Arcus partner; TIGIT retreat and capital reallocation
Bristol Myers Squibb (US) - BMS-986207 residual anti-TIGIT program
Compugen (IL) - TIGIT target-biology pioneer; COM902 lineage to rilvegostomig
Ono Pharmaceutical (JP) - Opdivo co-originator facing the domestic IO follow-on question after the global TIGIT reset

Product Code: JPH-111

List of Tables

Table 1. TIGIT biology primer: the DNAM-1 axis and checkpoint rationale
Table 2. Anti-TIGIT development history from first agents to Phase 3
Table 3. Roche tiragolumab program structure across the SKYSCRAPER series
Table 4. SKYSCRAPER Phase 3 readout sequence and program disposition, 2024-2025
Table 5. Merck & Co vibostolimab KeyVibe program and its discontinuation
Table 6. GSK-iTeos belrestotug collaboration structure and the GALAXIES-Lung-201 readout (2025)
Table 7. iTeos Therapeutics wind-down following the program outcome
Table 8. BeiGene ociperlimab and the AdvanTIG-302 termination decision
Table 9. AstraZeneca rilvegostomig (AZD2936): bispecific design and Phase 3 program
Table 10. Compugen COM902 lineage and target-biology contributions to the class
Table 11. Arcus domvanalimab Fc-silent design and the Gilead partnership
Table 12. STAR-221 readout (2025) and STAR-121 readout (2026): designs and contexts
Table 13. Gilead capital reallocation following the TIGIT retreat
Table 14. Junshi JS006 on the toripalimab backbone: program status
Table 15. Bristol Myers Squibb BMS-986207 residual program
Table 16. Residual global anti-TIGIT pipeline by construct and sponsor
Table 17. Construct-design hypotheses: Fc function, avidity, and bispecific geometry
Table 18. Fc-competent versus Fc-silent antibody debate and its evidence
Table 19. Biomarker hypotheses for TIGIT activity: PD-L1, TIGIT expression, and beyond
Table 20. Combination-backbone dependencies across discontinued and surviving programs
Table 21. Indication-by-indication record of TIGIT development in NSCLC, GI, and other tumors
Table 22. Japanese-site participation across the global TIGIT programs
Table 23. Japanese patient data within the pivotal readouts: availability and interpretation
Table 24. PMDA implications of the global TIGIT reset for pending and planned filings
Table 25. Ono Pharmaceutical's IO franchise position after the TIGIT reset
Table 26. Domestic IO follow-on options for Japanese incumbents
Table 27. Alternative checkpoint targets absorbing post-TIGIT attention
Table 28. PD-(L)1XVEGF bispecifics as the class that absorbed TIGIT's strategic role
Table 29. Deal and partnership history in the TIGIT class
Table 30. Distressed-asset inventory: stranded TIGIT programs and their owners
Table 31. Valuation framework for post-setback checkpoint assets
Table 32. Precedent set: prior checkpoint mechanisms following Phase 3 setbacks
Table 33. Scenario grid for rilvegostomig and the bispecific hypothesis
Table 34. Scenario grid for domvanalimab and the Fc-silent hypothesis
Table 35. Scenario grid for Japanese IO follow-on strategy at Ono and peers
Table 36. Competitive-position matrix of surviving TIGIT programs
Table 37. Risk register for investors holding TIGIT-exposed assets
Table 38. Risk register for companies acquiring distressed TIGIT programs
Table 39. Key opinion leader reassessment of the DNAM-1 axis after the readouts
Table 40. Trial-design lessons from the TIGIT Phase 3 generation
Table 41. Biomarker-development requirements for any class revival
Table 42. Watchlist of surviving-program readouts and decisions, 2026-2028
Table 43. Stakeholder map: sponsors, partners, investigators, and acquirers
Table 44. Due-diligence checklist for distressed TIGIT asset transactions
Table 45. Portfolio-reallocation patterns among companies exiting the class
Table 46. Implications of the TIGIT reset for IO combination strategy globally
Table 47. Implications of the TIGIT reset for Japanese trial-portfolio planning
Table 48. Key-question tree for oncology investors after the reset
Table 49. Key-question tree for BD teams assessing distressed assets
Table 50. Timeline of the TIGIT class from mechanism to reset, 2016-2026

List of Figures

Figure 1. DNAM-1 axis biology and the TIGIT checkpoint rationale
Figure 2. Anti-TIGIT development arc from early promise to Phase 3
Figure 3. Roche SKYSCRAPER program map
Figure 4. SKYSCRAPER readout sequence and disposition timeline, 2024-2025
Figure 5. Merck KeyVibe program arc and discontinuation
Figure 6. GSK-iTeos collaboration structure and the GALAXIES readout (2025)
Figure 7. iTeos wind-down pathway
Figure 8. BeiGene ociperlimab program and the AdvanTIG-302 decision
Figure 9. Rilvegostomig bispecific design schematic
Figure 10. Rilvegostomig Phase 3 program structure
Figure 11. Compugen lineage in TIGIT target biology
Figure 12. Domvanalimab Fc-silent design and the Gilead partnership map
Figure 13. STAR-221 and STAR-121 readout contexts
Figure 14. Gilead capital-reallocation map after the TIGIT retreat
Figure 15. Junshi JS006 position on the toripalimab backbone
Figure 16. Residual global TIGIT pipeline map
Figure 17. Construct-design hypothesis map: Fc, avidity, and geometry
Figure 18. Fc-competent versus Fc-silent evidence map
Figure 19. Biomarker hypothesis map for TIGIT activity
Figure 20. Backbone-dependency map across class programs
Figure 21. Indication-by-indication record of TIGIT development
Figure 22. Japanese-site participation map across global TIGIT programs
Figure 23. Japanese-patient data availability within pivotal readouts
Figure 24. PMDA implications of the global reset
Figure 25. Ono IO franchise position after the reset
Figure 26. Domestic IO follow-on option map for Japanese incumbents
Figure 27. Alternative checkpoint targets absorbing post-TIGIT attention
Figure 28. PD-(L)1XVEGF as the strategic successor class
Figure 29. TIGIT class deal and partnership history map
Figure 30. Distressed-asset inventory map
Figure 31. Post-setback checkpoint valuation framework
Figure 32. Precedent map: checkpoint mechanisms after Phase 3 setbacks
Figure 33. Bispecific-hypothesis scenario tree
Figure 34. Fc-silent-hypothesis scenario tree
Figure 35. Japanese IO follow-on scenario tree
Figure 36. Competitive-position matrix of surviving programs
Figure 37. Risk map for TIGIT-exposed investors
Figure 38. Risk map for distressed-asset acquirers
Figure 39. KOL reassessment map for the DNAM-1 axis
Figure 40. Trial-design lessons from the TIGIT Phase 3 generation
Figure 41. Biomarker-development requirements for a class revival
Figure 42. Surviving-program readout and decision calendar, 2026-2028
Figure 43. Stakeholder map across the post-reset class
Figure 44. Distressed-asset due-diligence checklist
Figure 45. Portfolio-reallocation patterns among class exits
Figure 46. IO combination-strategy implications of the reset
Figure 47. Japanese trial-portfolio implications of the reset
Figure 48. Key-question tree for investors
Figure 49. Key-question tree for distressed-asset BD teams
Figure 50. TIGIT class timeline from mechanism to reset, 2016-2026

PD-1 x TIGIT Bispecifics After the TIGIT Phase 3 Setbacks | Oncology Modality Intelligence | US, EU5, Japan & China

Description

Table of Contents

List of Tables

Table of Content

1. Executive Summary

2. PD-1 x TIGIT Bispecifics After the TIGIT Phase 3 Setbacks: Modality Overview and Mechanism Landscape

3. Global Pipeline and Deal Activity

4. Key Programs, Clinical Readouts, and Evidence Status

5. Japan Relevance: Trials, Approvals, and Partnerships

6. Regulatory and Pricing Considerations in Japan

7. Competitive Positioning and Valuation Considerations

8. Watch Items and Upcoming Catalysts

9. Appendix: Methodology and Sources

Companies Mentioned

List of Tables

List of Figures