PD-1 × VEGF-ADRAFT
1 · Executive Snapshot
Active Assets: 5 ｜ Companies: 5 ｜ Events: 6
≥80 Golden / 65–79 Watch / <65 Hold（dim 1–5 × weighted, gp-master methodology）
2 · Why This Pair
Combines PD-1 checkpoint blockade with VEGF-A anti-angiogenesis in one molecule; flagship pair with ivonescimab/AK112 (Akeso→Summit) approved ×3 in China and US BLA under FDA review (PDUFA 2026-11-14) — the highest-gravity BsAb pair in the pool.
3 · Asset Landscape
- 01Ivonescimab/AK112 — Akeso→Summit, PD-1×VEGF, approved China ×3, US BLA under review (PDUFA 2026-11-14)
- 02CTX-10726 — Compass, preclinical
- 03CR-001 — Crescent, Phase 1/2
- 04SIM0689 — Simcere, IND 2026-06
- 05(adjacent red sea: pumitamig/BNT327, IMM2510 — PD-L1×VEGF, not this pair)
4 · Companies
- 01Akeso (origin)
- 02Summit Therapeutics (US partner, up to $5B deal 2022)
- 03Compass
- 04Crescent
- 05Simcere
5 · Clinical & Deal Events
| Date | Event | Company |
|---|---|---|
| 2022 | Summit–Akeso license (up to US$5B) | Summit/Akeso |
| 2024 | ivonescimab approvals in China (×2); BioNTech–Biotheus $800M upfront (adjacent PD-L1×VEGF) | Akeso/BioNTech |
| 2025-04 | HARMONi-2 OS (HR≈0.777) weaker than PFS implied — stock drop | Akeso/Summit |
| 2025-10 | HARMONi-3 interim OS miss + protocol amendment + canceled $500M share sale | Summit |
| 2026-08 | HARMONi-6 survival-benefit-narrowing reports at 3rd China approval | Akeso |
| 2026-11-14 | US BLA PDUFA date (ivonescimab) | FDA/Summit |
5b · Auto-tracked (clinicaltrials.gov)
| Date | Event | Asset |
|---|---|---|
| 2026-08-19 | A Study of Chidamide Combined With Ivonescimab in the Treatment of Advanced Non-Small Cell HIGH | ivonescimab/AK112 |
| 2026-08-19 | A Study of AK117/AK112 in Metastatic Triple-Negative Breast Cancer HIGH | ivonescimab/AK112 |
| 2026-08-19 | Ivonescimab Plus Chemotherapy in Patients With Initially Unresectable Colorectal Cancer Li HIGH | ivonescimab/AK112 |
Auto-ingested via intel_ingest.py (Grade A, clinicaltrials.gov); refreshed weekly, human-confirmed.
6 · Risks & Failures
- 01HARMONi-2 OS (HR≈0.777) weaker than PFS implied; HARMONi-3 interim OS miss + protocol amendment
- 02Western-patient PFS weaker than China data
- 03HARMONi-6 survival-benefit-narrowing reports (Aug 2026)
- 04Class precedent failure: bintrafusp alfa (PD-L1×TGF-β) Phase 3 failure; ImmuneOnco–Axion >$2B license termination (PD-L1×VEGF)
- 05Single-asset concentration; exhaustive asset count incomplete (China undisclosed)
7 · Discovery Questions
- 01Pivotal OS numbers for HARMONi-3/-6 (paywalled/granularity)
- 02Western-patient efficacy vs China data (ethnicity/biology questions)
- 03Exhaustive preclinical PD-1×VEGF asset count (China undisclosed)
- 04Differentiation vs PD-L1×VEGF (pumitamig) in the clinic
8 · Research Tools
- 01PD-1 (PDCD1) ECD — mature formats
- 02VEGF-A ECD (VEGFA) — mature formats
- 03Human/Cyno cross-species
- 04Dual-binding SPR/BLI panel
- 05Reference: bevacizumab-class anti-VEGF, pembrolizumab-class anti-PD-1
9 · Assay Workflow
Binding → Dual Binding → Functional (per PRD §20 §9).
10 · Services
11 · Evidence
Last reviewed: 2026-08-19 ｜ Confidence: medium ｜ Evidence: Score 77/100 草案：PRD §7 阈值=Watch，旗舰样板建议 Golden——待创始人校准；Grade A/B only（AZ $15B 传闻=Grade D 不入公开）
Full evidence ledger: gp-master/GP-01_pd1-vegf-a.md（本仓库 docs/artifacts/gp-master/，未托管外链）
Next steps