Kirsten Rat Sarcoma Viral (KRAS) Inhibitors Market: Competitive Landscape, Pipeline, and Market Analysis, 2022

Kirsten Rat Sarcoma Viral (KRAS) oncogene is the mutated isoform of RAS, having the most common mutations in cancer, accounting for 85% of RAS-driven human cancers. KRAS basically acts as an on/off switch for cell growth with a normal function of regulating cell growth, but when mutated, results in uncontrollable cell growth. KRAS inhibitors bind to the cysteine residue in KRAS G12C mutations and lock the protein in its inactive form, thereby arresting cell proliferation and suppressing tumor growth. The KRAS inhibitors can be used for the treatment of non-small cell lung cancer, pancreatic cancer, colorectal cancer, and endometrial cancer. In the USA and Europe, the mutation of KRAS (G12C) mutation is estimated to affect more than 70,000 patients with occurrence in 14% of non-small cell lung cancer patients (approximately 44,000 patients), in 3-4% of colorectal cancer patients (approximately 20,000 patients), and in 2% of pancreatic cancer patients (approximately 4,000 patients.) Similarly, for KRAS (G12D), it is estimated to affect 1,80,000 patients in the USA and Europe with occurrence in 36% of pancreatic patients, 12% of colorectal cancer patients, 6% of endometrial cancer patients, 4% of NSCLC adenocarcinoma patients. Amgen, Mirati Therapeutics, Taiho Oncology, and Bayer are currently providing KRAS inhibitors for the treatment of cancer patients in the market. Apart from these molecules, KRAS-Ioder, developed by Silenseed is currently in phase-II clinical trial.

Approved Drug Molecules for KRAS Inhibitors

LUMAKRAS (Sotorasib)

KRAZATI (Adagrasib)

LONSURF (Trifluridine and Tipiracil)

STIVARGA (Regorafenib)

Drugs under the Pipeline for KRAS Inhibitors

KRAS-Ioder (siG12D-LODER) - Phase-II

Library TCR - T-cell therapy - Phase-II

anti-KRAS G12D mTCR PBL - Phase-I/II

JAB-3312 - Phase-I/II

ELI-002 - Phase-I/II

KRAS peptide vaccine - Phase-I

SLATE-KRAS - Phase-I/II

MSC -derived Exosomes with KrasG12D siRNA - Phase-I

GEC-225 - Phase-I

HS-10370 - Phase-I/II

Mdc3/8-KRAS vaccine - Phase-I

Clinical Activity and Development of KRAS Inhibitors

Currently, KRAS inhibitor is being developed by 22 companies, with 20 products in the pipeline, while most of them are in the initial phase of clinical trial. KRAS-Ioder is the only molecule in the Phse-II clinical trial.

• In June 2023, Biomea Fusion Inc. Patented GTPase KRAS (G12C mutant) and (G12D mutant) inhibitors have shown to be potential for the treatment of cancer, autoimmune diseases and inflammatory disorders.
• In June 2023, Research at the University of California Oakland and 1200 Pharma LLC developed GTPase KRAS (G12C mutant) inhibitors reported to be useful for the treatment of cancer.
• In June 2020, Jacobio Pharmaceuticals collaborated with AbbVie to develop and commercialize the KRAS G12C inhibitor in combination with the SHP2 inhibitor.

Key Developments

• In June 2023, Amgen, Inc. announced new data for efficacy of Lumakras (Sotorasib), a small molecule inhibitor in advanced non-small cell lung cancer (NSCLC) and metastatic colorectal cancer (mCRC) among patients with KRAS G12C-mutation.
• In June 2023, Innovent presented Phase 1 clinical data for IBI351 (KRASG12C Inhibitor) as monotherapy for metastatic colorectal cancer.