Zhī tōng cǎi jīng APP learned that on July 10, the National Medical Products Administration (NMPA) drug evaluation center website showed that the application of JAB-23E73 (previously named as JAB-23400, JAB-23425), a new drug of pan-KRAS inhibitor developed by Arcus Biosciences (01167), has been approved for clinical trials. The product is currently the world's first oral broad-spectrum KRAS inhibitor with significant progress.
KRAS is a popular target that domestic and foreign companies are competing for, with 2.7 million new patients with KRAS mutations worldwide each year. With the cancer entering the era of targeted therapy, the subdivision degree of new anti-tumor drugs for indication is gradually deepening, and the industry has difficulty seeing similar super products like PD-1. As a broad-spectrum KRAS inhibitor targeting a wide range of patients, pan-KRAS inhibitor has rare value for the development of anti-tumor drugs. With the second fastest clinical progress in the world, this product has the potential to enter the global market.
16.6% of Chinese cancer patients have KRAS mutations. (Data source: KRAS G12C mutations in Asia: a landscape analysis of 11,951 Chinese tumor samples, Translational Lung Cancer Research, 2020)
In terms of development speed, it is highly likely that JAB-23E73 will complete a Phase I and a single-arm registrational Phase II trial, and submit a new drug application for the market within 2-3 years. The cycle of a clinical trial is closely related to the speed of patient enrollment. From the number of patients, patients with KRAS-related mutations are 8-10 times the number of patients with only KRAS G12C, and the recruitable patient population is larger. In China, there are about 0.67 million cancer patients with KRAS mutations each year. Looking back at the clinical development experience of Arcus Biosciences' KRAS G12C inhibitor glecirasib for the treatment of non-small cell lung cancer, the interval between clinical approval and completion of registrational trials was less than 2 and a half years. Therefore, the expected development cycle of the broad-spectrum KRAS inhibitor for more potential patients will be shorter, the clinical advancement efficiency will be higher, and the product value can be realized in a short period of time.
In terms of market competition, Arcus Biosciences' pan-KRAS inhibitor is currently the world's first oral broad-spectrum KRAS inhibitor with only two MNCs, Pfizer and Boehringer Ingelheim, laying out. Currently, the only similar product in the world in the clinical stage is Revolution Medicines' pan-RAS inhibitor RMC-6236, but there is a mechanism difference between pan-KRAS and pan-RAS (pan-RAS simultaneously inhibits HRAS and NRAS, which is more likely to cause toxicity). As a product with differentiation and few entrants, Arcus Biosciences' pan-KRAS has expectations of licensing out to overseas markets. The management of Arcus Biosciences said on a conference call earlier that multiple companies are interested in this product, and obtaining some clinical data will help facilitate business development negotiations, and give the product value further room to grow.
Due to the drag of the Hong Kong stock market and the pharmaceutical sector, Arcus Biosciences is undervalued in the capital market, with a market cap of less than HKD 1.2 billion, which is equal to the cash held by the company. This forms a great contrast to the company's potential pipeline layout.
In terms of core pipeline, Arcus Biosciences has submitted a new drug application for glecirasib, a KRAS G12C inhibitor, for second-line non-small cell lung cancer indications in May, which will soon bring commercial revenue to the company for the first time. Arcus Biosciences also has JAB-3312, the world's only SHP2 inhibitor in the registrational clinical stage, which plans to become a first-line therapy globally through combination therapy. According to data released by Arcus Biosciences at the ASCO conference in June, the objective response rate (cORR) of first-line non-small cell lung cancer (NSCLC) patients was 64.7% (66/102), and the median progression-free survival (mPFS) was 12.2 months. The cORR of the best dose group was as high as 77.4% (24/31).
Revolution Medicines has gained a market value of 6.1 billion USD only with pan-RAS, and the soon-to-be approved pan-KRAS inhibitor JAB-23E73 is expected to become another super product for Arcus Biosciences, opening up a new space for its valuation.