RAS, SOS1 & SHP2 inhibitors, global pipeline

Last Update: Aug 7, 2022

Approved therapies

Company Product MoA Indication Approval
Amgen Lumakras (sotorasib) KRAS G12C inhibitor KRAS G12C-mutated locally advanced or metastatic NSCLC, after at least one systemic therapy May 2021 (US), Sep 2021 (UK, CA), Jan 2022 (EU, JPN)
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Global pipeline

Company Candidate MoA Indication Phase
Amgen (Carmot) Sotorasib (AMG 510)1 KRAS G12C NSCLC, advanced CRC, other tumors III
Mirati Adagrasib (MRTX849)2 KRAS G12C NSCLC, CRC, pancreatic III
Novartis JDQ4433 KRAS G12C KRAS G12C mutant solid tumors (┬▒TNO155 & spartalizumab) Ib/II
Roche (Genentech) GDC-60364 KRAS G12C NSCLC, CRC, advanced solid tumors I
BridgeBio BBP-454 pan-KRAS inhibitor KRAS mutant cancers I
Moderna/Merck mRNA-5671 (Merck V941) KRAS vaccine NSCLC, CRC, advanced solid tumors I
Boehringer (Lupin) BI 1701963 SOS1 inhibitor:pan-KRAS w/ MEKi (trametinib) or KRAS G12Ci, KRAS-mutant NSCLC/CRC I
JNJ JNJ-74699157 (ARS-3248) KRAS G12C KRAS G12C mutant solid tumors I
Revolution Medicines RMC-62365 Multi-RAS(ON) (H-,K-,N-) inhibitor RAS-addicted cancers I/Ib
Jacobio Pharma JAB-21822 KRAS G12C NSCLC with KRAS G12C mutation I
Innovent Biologics IBI351 KRAS G12C KRAS G12C mutant advanced tumors I
Araxes Pharma/JNJ ARS-1620 KRAS G12C Solid tumors IND cleared
Mirati MRTX1133 KRAS G12D Pancreatic, CRC, NSCLC IND
Eli Lilly LY3537982 KRAS G12C Solid tumors IND
Revolution Medicines RMC-5845 SOS1 inhibitor - IND
Erasca ERAS-3490 KRAS G12C KRASm G12C solid tumors IND
Immuneering IMM-1-104 Dual MEK inhibitor/pan-KRAS/NRAS RAS mutant solid tumors IND
Affinity-T Therapeutics - TCR targeting KRAS G12V - IND
Revolution Medicines RMC-6291 K/NRAS G12C (ON) RAS-addicted cancers Preclin
Mirati MRTX1257 KRAS G12C - Preclin
Mirati - SOS1 inhibitor - Preclin
Sanofi/X-Chem Compound B KRAS G12C - Preclin
Biotheryx - KRAS targeted protein degrader - Disc
Anchiano Therapeutics MCI-062 Pan-RAS inhibitor (H, K, N-RAS) - Preclin
Erasca ERAS-4 KRAS G12D - Disc
Erasca ERAS-2/3 RAS-GTP - Disc
Erasca ERAS-10 RAS/MAPK protein degrader - Disc
Affinity-T Therapeutics - TCR targeting KRAS G12D - Disc
SQZ Biotech SQZ-AAC-KRAS RBCs carrying mut. KRAS antigens KRAS mut. solid tumors Preclin
Schrodinger/BMS - SOS1/KRAS KRAS driven cancers Disc
Immuneering - KRAS4b - Disc
Bayer BAY-293 SOS1 inhibitor - Disc
Erasca ERAS-9 SOS1 inhibitor - Disc
Company Candidate MoA Indication Phase
Revolution Medicines RMC-4630 SHP2 inhibitor w/ MEK inhibitor (cobimetinib) solid tumors Ib/II
BridgeBio BBP-398 SHP2 inhibitor RTK/MAPK-driven cancers I+
Novartis TNO155 SHP2 inhibitor RAS mutant tumors I
Relay Therapeutics RLY-1971 SHP2 inhibitor Advanced solid tumors I
Erasca ERAS-601 SHP2 inhibitor RAS/MAPK altered tumors I
HUYA bioscience HBI-2376 SHP2 inhibitor - Pre-IND
Discontinued Candidate MoA Indication Phase
Eli Lilly LY3499446 KRAS G12C Advanced solid tumors I
AstraZeneca (Ionis) AZD4785 Anti-KRAS ASO Solid tumors I
Gilead (Kite/NCI) KRAS TCR Anti-KRAS G12D TCR GI, pancreatic, CRC I
1. Lumakras (sotorasib): Ongoing Ph3 confirmatory study vs docetaxel (CodeBreaK201). Ongoing combination trials with: Anti-EGFR (panitumumab), Anti-PD-1, SHP2 (ERAS-601, RMC-4630), ERK 1/2 (ERAS-007) , MEK/RAF (VS-6766).
2. Adagrasib: multiple Phase 2/3 studies underway. Filing NDA in 2H21 for 2L+ NSCLC. Phase 1/2 KRYSTAL study - 51 patients with advanced/metastatic NSCLC with mutant KRAS G12C, 23 PRs (45%), 26 SD. Combination trial with BI 1701963 in lung and CRC patients announced Sep. 18 2020. Phase 2 topline results reported 20 Sep 2021, 43% ORR, 80% DCR in advanced NSCLC with KRAS G12C mutation following prior systemic therapy. Press release.
3. JDQ443: initial clinical data reported at AACR2022, 57% cORR (4/7) at R2PD 200 mg BID in NSCLC. 35% cORR (7/20) across doses. Ongoing multiple combinations (including with SHP2 inhibitor TNO155). Press release.
4. GDC-6036: trial ongoing, monotherapy multiple combinations, including with Relay's RLY-1971. FIH data reported at WCLC22, 46% cORR (26/57), most AEs low grade. No DLTs reported. RP2D dose: 400 mg QD.
5. RMC-6236: first patient dosed June 28 2022. Press release.

NSCLC = Non-small cell lung cancer. CRC = Colorectal cancer. RTK = Receptor tyrosine kinase. GI = Gastrointestinal.

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