Target Pair ◆ egfr-lgr5
EGFR × LGR5DRAFT
数据列表以英文版为准（Grade A/B 证据，见 gp-master）。
1 · 概览
活跃资产: 5 ｜ 公司: 5 ｜ 事件: 4
60
机会评分持有
≥80 黄金 / 65–79 观察 / <65 持有（五维加权，方法论见 gp-master）
2 · 为什么值得做
新兴配对：EGFR（成熟已验证）+ LGR5（Wnt/干性、肿瘤起始细胞标志物），针对 EGFR 驱动肿瘤的耐药群体；先导资产 petosemtamab（Merus）为唯一临床 EGFR×LGR5 双抗。
3 · 资产格局
- 01Petosemtamab (MCLA-158) — Merus, EGFR×LGR5 BsAb, Phase 1/2 → Phase 2 (mCRC), Grade A/B
- 02CNA3103 — Carina Biotech, LGR5 CAR-T, Phase 1/2a (adjacent, single-target)
- 03EGFR×LGR5 BsAb-ADC — academic, preclinical (bioRxiv 2026, Grade B)
- 04SZN-043 — Surrozen, ASGR1×RSPO BsAb (adjacent), discontinued (tox)
- 05SZN-413 — Surrozen → Boehringer Ingelheim license (adjacent, ~$600M reported)
4 · 公司
- 01Merus (originator/clinical lead)
- 02Carina Biotech
- 03Surrozen
- 04Boehringer Ingelheim (SZN-413 licensee)
- 05Academic groups (ADC)
5 · 临床与交易事件
| 日期 | 事件 | 公司 |
|---|---|---|
| 2016 | EGFR×LGR5 BsAb patent priority (PB10651 lead) | Merus |
| 2024-07-08 | petosemtamab Phase 2 (2L mCRC) first patient dosed | Merus |
| 2025-10 | mCRC interim data — AACR-NCI-EORTC 2025 plenary | Merus |
| 2025 | Randomized NCT07702032 (vs cetuximab, RAS/BRAF WT left-sided mCRC) registered | Merus |
6 · 风险与失败
- 01Emerging: only one clinical asset (petosemtamab); no peer-reviewed efficacy/safety full-text
- 02LGR5 loss → MET-STAT3 resistance pathway (Grade A)
- 03Normal-tissue stem-cell on-target toxicity risk (LGR5 is an intestinal stem-cell marker)
- 04Zero EGFR×LGR5 deals to date; anti-LGR5 reagent gap (Genentech patent WO2010016766A2: no known anti-Lgr5 antibody recognizes endogenous Lgr5)
7 · 研发问题
- 01LGR5 expression threshold / patient selection (biomarker data not public)
- 02KRAS/BRAF interplay for EGFR×LGR5 vs anti-EGFR monotherapy
- 03Can validated anti-LGR5 reagents / PDO screening be supplied (tool gap)?
- 04Upgrade triggers: Phase 2 full data, NCT07702032 start, first EGFR×LGR5 deal, second clinical asset
8 · 研究工具
- 01EGFR ECD (mature formats: His/Avi/biotin)
- 02LGR5 reagents — gap (validated anti-LGR5 detection), PDO screening support
- 03Dual-binding SPR/BLI panel
- 04Reference: cetuximab-class anti-EGFR
9 · 实验工作流
结合 → 双结合 → 功能（PRD §20 §9）。
10 · 服务
11 · 证据
最近审校: 2026-08-19 ｜ 置信度: medium ｜ 证据: Score 60/100 = Hold (PRD §7); only Grade A/B facts; full ledger in gp-master (Grade C/D excluded)
完整证据台账: gp-master/GP-04_egfr-lgr5.md（本仓库 docs/artifacts/gp-master/，未托管外链）
下一步