On September 2, Innovent announced that it had reached a global exclusive licensing agreement with Genfleet. Innovent, as an exclusive partner of Genfleet, will obtain the right to develop and commercialize GFH925 (KRAS G12C inhibitor), a candidate drug targeting KRAS G12C that is commonly found in lung cancer and other solid tumors, in China (including Chinese Mainland, Hong Kong, S.A.R., China, Macau, S.A.R., China and Taiwan, China). At the same time, Innovent will also have the option of global development and commercialization rights.
According to the agreement, Innovent will pay Genfleet a down payment of USD22 million and a cumulative amount of less than USD50 million to support the global development. If Innovent exercises the option of global rights and interests, Genfleet will be eligible for milestone payment of no more than USD240 million from Innovent and gradient royalties based on the annual net sales of GFH925 in China and worldwide. This cooperation of authorization involves an amount of more than USD300 million.
GFH925 is an efficient oral new molecular entity compound independently developed by Genfleet with complete intellectual property rights. By covalently and irreversibly modifying the cysteine residue of KRAS G12C protein mutant, it effectively inhibits GTP/GDP exchange mediated by this protein, thus down-regulating the activation level of KRAS protein. Preclinical selective test for cysteine also shows high selective inhibitory effect of GFH925 on this mutation site. In addition, GFH925 can inhibit the downstream signal transduction pathway after inhibiting KRAS protein and effectively induce apoptosis and cell cycle arrest of tumor cells, thus achieving anti-tumor effect.
According to the preclinical experimental data, GFH925 has the potential best-in-class activity. It can effectively inhibit the growth of various tumor cell lines carrying KRAS G12C mutation, which will accelerate the clinical validation. Other preclinical trials also show the potential of combination with other therapies.
The Marketing of Amgen AMG510 breaks the "curse" that it's impossible to create effective medicine for KRAS G12C.
As one of the three major types of RAS genes, KRAS is the most common oncogene, accounting for 85% of RAS mutations. According to the basic research, KRAS has mutations in various cancers, among which the mutation rate of pancreatic cancer is as high as 90%, and this mutation also occurs in colon cancer and lung cancer (mostly NSCLC), as well as cholangiocarcinoma, carcinoma of small intestine, skin cancer, bladder cancer and breast cancer. Unfortunately, because KRAS is a featureless and nearly spherical structure and has no obvious binding site, it is difficult to synthesize a compound that can target binding and inhibit its activity. Therefore, it is almost impossible to be overcome for a long time, and was once considered as a non-pharmaceutical target.
In May this year, Lumakras (AMG510), an inhibitor of KRAS G12C developed by Amgen, was approved for marketing by FDA and became the world's first anticancer drug targeting specific KRAS gene mutation. The listing of Lumakras (AMG510) seemed as an official announcement dispelling the saying that it's impossible to create effective medicine for KRAS oncogene and caused a sensation in academia and industry. More and more healthcare supply companies at home and abroad were attracted to join this subdivision track.
At present, no drugs with the same target have been approved in China. Besides GFH925, there are drugs under research such as D-1553 of Inventisbio, JAB-21822 of Jacobio, BPI-421286 of Betta.
D-1553 of Inventisbio
D-1553 is an oral inhibitor of KRAS G12C mutation independently developed by Inventisbio, which is aimed at advanced solid tumors such as non-small cell lung cancer and colorectal cancer with KRAS G12C mutation. D-1553 has shown excellent selectivity and tumor inhibition effect in preclinical studies.
D-1553 was approved for Phase I/II clinical trials by the Center for Drug Evaluation, NMPA (National Medical Products Administrat...
(All Rights Reserved)