Target Pair ◆ egfr-lgr5
EGFR × LGR5DRAFT
1 · Executive Snapshot
Active Assets: 5 ｜ Companies: 5 ｜ Events: 4
60
Opportunity ScoreHold
≥80 Golden / 65–79 Watch / <65 Hold（dim 1–5 × weighted, gp-master methodology）
2 · Why This Pair
Emerging pair combining EGFR (mature, validated) with LGR5 (Wnt/stemness, tumor-initiating cell marker) to target resistance populations in EGFR-driven tumors; lead asset petosemtamab (Merus) is the only clinical EGFR×LGR5 bispecific.
3 · Asset Landscape
- 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 · Companies
- 01Merus (originator/clinical lead)
- 02Carina Biotech
- 03Surrozen
- 04Boehringer Ingelheim (SZN-413 licensee)
- 05Academic groups (ADC)
5 · Clinical & Deal Events
| Date | Event | Company |
|---|---|---|
| 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 · Risks & Failures
- 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 · Discovery Questions
- 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 · Research Tools
- 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 · Assay Workflow
Binding → Dual Binding → Functional (per PRD §20 §9).
10 · Services
11 · Evidence
Last reviewed: 2026-08-19 ｜ Confidence: medium ｜ Evidence: Score 60/100 = Hold (PRD §7); only Grade A/B facts; full ledger in gp-master (Grade C/D excluded)
Full evidence ledger: gp-master/GP-04_egfr-lgr5.md（本仓库 docs/artifacts/gp-master/，未托管外链）
Next steps