Next-Generation ADCs: Bispecific ADCs, Dual Payloads, and ADC-IO Combinations | Oncology Modality Intelligence

Description

List of Tables

Daiichi Sankyo's DXd franchise made Japan the center of the antibody-drug conjugate world; the question this report addresses is what comes after the franchise's first act. Enhertu and Datroway established the topoisomerase-inhibitor payload era, but the next generation is already visible in Japanese pipelines and in the deals Japanese and Western companies are signing with Chinese inventors. Three design directions define it. Bispecific ADCs - molecules binding two tumor antigens at once, led by SystImmune's izalontamab brengitecan, partnered to Bristol Myers Squibb in December 2023 - promise to widen the treatable population where single-antigen expression is heterogeneous. New payload and linker chemistry - Eisai's eribulin-payload strategy with Bliss Biopharm's BB-1701, dual-payload constructs, and novel topo1 variants - aims to escape the resistance patterns emerging against first-generation payloads. And ADC-immunotherapy combinations, pairing conjugates with PD-(L)1 backbones in trials enrolling Japanese sites, are testing whether the modality belongs in first-line regimens rather than after them. Daiichi Sankyo's own next wave - patritumab deruxtecan, ifinatamab deruxtecan, raludotatug deruxtecan, and earlier-stage constructs - sits alongside AstraZeneca's AZD9592 and the Kelun, RemeGen, Hengrui, and DualityBio programs flowing toward Western partners. The contested ground is scientific and commercial at once: whether bispecific binding translates into clinical advantage, whether payload diversification solves resistance or merely displaces it, and whether Japan's regulatory and trial infrastructure keeps the country at the modality's frontier as invention shifts partly toward China. None of these questions is academic for Japan: the country supplies the modality's defining chemistry, its leading commercial franchise, and a clinical-trial network that global sponsors still court. The report maps each design direction with named programs and deals, the Japanese pipeline footprint, combination-trial activity, manufacturing implications, and the partnering geometry. It serves oncology business-development teams, competitors benchmarking against the DXd standard, investors in ADC-platform companies, and Japanese stakeholders assessing the country's next position in the modality it helped define.

Scope and Coverage

The report covers bispecific ADCs, next-generation payloads and linkers, dual-payload constructs, ADC-IO combinations, and the Japanese and Chinese pipelines behind them, with deal structures and Japan trial participation mapped program by program.

Report Highlights

Daiichi Sankyo's next-wave DXd programs: patritumab, ifinatamab, raludotatug deruxtecan, and DS-3939
Bispecific ADC frontier: izalontamab brengitecan, AZD9592, and SKB571
Payload diversification: eribulin (BB-1701), dual payloads, and topo1 variants
ADC-PD-(L)1 combination programs enrolling Japanese sites
The China-to-West ADC deal flow: SystImmune/BMS, DualityBio, Kelun/Merck structures
Japan's position as ADC invention shifts: regulatory, trial, and manufacturing factors

Product Code: JPH-104

Table of Content

1. Executive Summary

2. Next-Generation ADCs: 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

Daiichi Sankyo (JP) - DXd franchise and next wave: patritumab deruxtecan, ifinatamab deruxtecan, raludotatug deruxtecan, and DS-3939
AstraZeneca (UK) - DXd co-development partner; AZD9592 EGFRXc-MET bispecific ADC; ADC-IO combinations
Merck & Co (US) - partner for three DXd ADCs (Oct 2023) and global partner for Kelun's sacituzumab tirumotecan
Gilead Sciences (US) - Trodelvy franchise and ADC-IO combination programs
Kelun-Biotech (CN) - sacituzumab tirumotecan China approvals 2024-2025; SKB571 bispecific ADC; Merck alliance
RemeGen (CN) - disitamab vedotin franchise and RC88 next-wave assets
Bliss Biopharm (CN) - BB-1701 eribulin-payload HER2 ADC partnered with Eisai
Eisai (JP) - global partner for BB-1701 and its eribulin-payload ADC strategy
Hengrui (CN) - SHR-A1811 (HER2), SHR-A1904 (CLDN18.2), and SHR-A1921 (TROP2) ADC pipeline
SystImmune (CN) - izalontamab brengitecan (BL-B01D1) EGFRXHER3 bispecific ADC partnered with BMS (Dec 2023)
Bristol Myers Squibb (US) - ex-China partner for izalontamab brengitecan
DualityBio (CN) - DB-1303 (HER3) and DB-1311/BNT324 (B7-H3) with BioNTech, GSK, and Avenzo deals

Product Code: JPH-104

List of Tables

Table 1. DXd franchise recap: Enhertu and Datroway approval history in Japan
Table 2. Merck & Co partnership for three DXd ADCs (2023): structure and scope
Table 3. Patritumab deruxtecan: HER3-directed program status and Japan filings
Table 4. Ifinatamab deruxtecan: B7-H3 program in small-cell lung cancer and beyond
Table 5. Raludotatug deruxtecan: CDH6 program design and development plan
Table 6. DS-3939 and Daiichi Sankyo earlier-stage ADC constructs
Table 7. AZD9592: AstraZeneca's EGFRXc-MET bispecific ADC program
Table 8. Izalontamab brengitecan (BL-B01D1): SystImmune's EGFRXHER3 bispecific ADC
Table 9. SystImmune-Bristol Myers Squibb partnership (2023): terms and governance
Table 10. Kelun-Biotech sacituzumab tirumotecan: China approvals (2024-2025) and Merck alliance
Table 11. SKB571 and Kelun's bispecific ADC follow-ons
Table 12. RemeGen disitamab vedotin franchise and RC88 next-wave assets
Table 13. Bliss Biopharm BB-1701: eribulin-payload HER2 ADC partnered with Eisai
Table 14. Eisai ADC strategy built on eribulin payload chemistry
Table 15. Hengrui ADC pipeline: SHR-A1811 (HER2), SHR-A1904 (CLDN18.2), and SHR-A1921 (TROP2)
Table 16. DualityBio DB-1303 (HER3) and DB-1311/BNT324 (B7-H3) partnering history
Table 17. Dual-payload ADC constructs in preclinical and early clinical development
Table 18. Linker chemistry evolution: stability, bystander control, and cleavage design
Table 19. Topoisomerase-1 payload variants and resistance-escape rationale
Table 20. Resistance mechanisms to first-generation ADC payloads
Table 21. Antigen-heterogeneity rationale for bispecific ADC design
Table 22. ADC-IO mechanistic rationale: immunogenic cell death and combination logic
Table 23. ADC-pembrolizumab combination programs enrolling Japanese sites
Table 24. ADC combinations with PD-(L)1XVEGF bispecific backbones
Table 25. Gilead Trodelvy franchise and its ADC-IO combination programs
Table 26. First-line development logic for ADC-based regimens
Table 27. Japan trial participation across next-generation ADC programs
Table 28. PMDA experience with novel ADC constructs: review considerations
Table 29. CLDN18.2 ADC competition relevant to Japan: Astellas and Hengrui programs
Table 30. B7-H3 target competition across ADC and radioligand modalities
Table 31. Manufacturing considerations for bispecific and dual-payload ADCs
Table 32. CDMO capacity for ADC production serving Japan supply
Table 33. Biomarker and testing requirements for next-generation ADC targets
Table 34. Deal-term benchmarks across China-to-West ADC transactions, 2023-2025
Table 35. Japanese companies' ADC partnering options in the current market
Table 36. Competitive-position matrix of next-generation ADC programs
Table 37. Scenario grid for bispecific ADC clinical validation
Table 38. Scenario grid for payload-diversification strategies
Table 39. Scenario grid for ADC-IO first-line adoption in Japan
Table 40. NHI pricing considerations for successive ADC generations
Table 41. Safety-management frameworks for novel ADC payloads
Table 42. Risk register for ADC-platform investors
Table 43. Risk register for incumbents defending first-generation franchises
Table 44. Key opinion leader landscape in Japanese ADC development
Table 45. Watchlist of next-generation ADC readouts and filings, 2026-2028
Table 46. Stakeholder map: originators, partners, CDMOs, regulators, and societies
Table 47. Technology-assessment framework for evaluating ADC platforms
Table 48. Historical lessons from the first DXd wave for next-generation strategy
Table 49. Implications of next-generation ADCs for Japanese trial-infrastructure planning
Table 50. Timeline of next-generation ADC programs and deals, 2023-2026

List of Figures

Figure 1. ADC modality anatomy: antibody, linker, payload, and target
Figure 2. DXd franchise map: approved products and next-wave programs
Figure 3. Merck-Daiichi Sankyo three-ADC partnership structure (2023)
Figure 4. Patritumab deruxtecan program arc toward Japan filings
Figure 5. Ifinatamab deruxtecan development footprint in SCLC
Figure 6. Raludotatug deruxtecan and DS-3939 pipeline positions
Figure 7. AZD9592 bispecific ADC design schematic
Figure 8. Izalontamab brengitecan EGFRXHER3 binding logic
Figure 9. SystImmune-BMS partnership map (2023)
Figure 10. Sacituzumab tirumotecan China-to-global pathway with Merck
Figure 11. Kelun next-wave constructs including SKB571
Figure 12. RemeGen RC88 and the disitamab vedotin franchise arc
Figure 13. BB-1701 eribulin-payload design and the Eisai partnership
Figure 14. Eisai payload-driven ADC strategy map
Figure 15. Hengrui ADC pipeline across HER2, CLDN18.2, and TROP2
Figure 16. DualityBio partnering web: BioNTech, GSK, and Avenzo
Figure 17. Dual-payload construct design concepts
Figure 18. Linker-chemistry evolution map
Figure 19. Topo1 payload variants and resistance-escape hypotheses
Figure 20. First-generation payload resistance-mechanism map
Figure 21. Antigen heterogeneity and the bispecific ADC rationale
Figure 22. ADC-IO mechanistic rationale diagram
Figure 23. ADC-pembrolizumab combination trial footprint in Japan
Figure 24. ADC combinations with PD-(L)1XVEGF backbones
Figure 25. Trodelvy franchise and Gilead combination programs
Figure 26. First-line development logic for ADC regimens
Figure 27. Japan site participation map across next-generation ADC programs
Figure 28. PMDA review considerations for novel ADC constructs
Figure 29. CLDN18.2 ADC competition map relevant to Japan
Figure 30. B7-H3 target competition across modalities
Figure 31. Manufacturing critical path for bispecific and dual-payload ADCs
Figure 32. CDMO network map for Japan ADC supply
Figure 33. Biomarker-testing requirements for next-generation ADC targets
Figure 34. China-to-West ADC deal timeline, 2023-2025
Figure 35. Deal-term benchmark map across ADC transactions
Figure 36. Japanese companies' ADC partnering option map
Figure 37. Competitive-position matrix of next-generation ADC programs
Figure 38. Bispecific ADC validation scenario tree
Figure 39. Payload-diversification scenario tree
Figure 40. ADC-IO first-line adoption scenario tree for Japan
Figure 41. NHI pricing frame for successive ADC generations
Figure 42. Safety-management framework for novel payloads
Figure 43. Risk map for ADC-platform investors
Figure 44. Risk map for first-generation franchise incumbents
Figure 45. Japanese ADC KOL landscape
Figure 46. Next-generation ADC readout and filing calendar, 2026-2028
Figure 47. Stakeholder map across originators, partners, CDMOs, and regulators
Figure 48. ADC platform technology-assessment framework
Figure 49. Lessons map from the first DXd wave
Figure 50. Next-generation ADC program and deal timeline, 2023-2026

Next-Generation ADCs: Bispecific ADCs, Dual Payloads, and ADC-IO Combinations | Oncology Modality Intelligence | US, EU5, Japan & China

Description

Table of Contents

List of Tables

Table of Content

1. Executive Summary

2. Next-Generation ADCs: 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