Otsuka Pharma and Merck collaborate to develop Kras inhibitor

Release date: 2020-01-07 Views: 0

Source: US Traditional Chinese Medicine

Today, Merck announced that it will cooperate with Taiho and Astex of Otsuka Pharmaceuticals to develop small molecule anti-cancer drugs, including Kras inhibitors. Merck will pay a $ 50 million down payment for a total of $ 2.5 billion in mileage. The three will merge pre-clinical related projects and share technology secrets. Merck will acquire exclusive global rights to these products in research and will be responsible for the development and marketing of these projects, while Taiho retains some rights in Japan and the Asia-Pacific region.

Astex was originally a British company and was acquired by Otsuka in 2013. At present, Taiho, another subsidiary of Otsuka, has two cooperation projects. Among them, the combination of cedazuridine and decitabine ASTX727 succeeded in a phase III clinical trial called ASCERTAIN, but the main asset SGI-110 (guadecitabine) was in a phase III AML clinical trial in 2018 failure. Astex's core competitiveness is a technology platform called Pyramid ™ Fragment-Based Drug Design (FBDD), which is sometimes more efficient than difficult HTS targets for difficult drug targets. The BCL inhibitor Venatoclax is discovered through this technology. The industry generally believes that traditional HTS technology is difficult to find this drug. However, FBDD rarely finds such a difficult drug and it is a technology that needs to be improved, but at least it provides a new means of entry.

Speaking of difficult-to-drug targets Kras is definitely a horn. Kras is the most frequently mutated tumor-driving gene. About 30% of all tumors have Kras mutations, but because of its high difficulty in drug-making, this target has not been developed for many years. In the past 7 or 8 years, a subtype called G12C mutation was first captured, using FBDD technology. Now Amgen and Mirati's G12C variant Kras inhibitors have produced a good response rate in early clinical, especially lung cancer. Therefore, the interest of all pharmaceutical Kras variant subtypes in the pharmaceutical industry has further increased, and many large pharmaceutical companies have recently entered this field. In addition to today's small-molecule collaboration, Merck previously worked with Moderna to develop mRNA-5671, a tumor vaccine drug targeting four major Kras variants.

Kras mutations can cause profound changes in tumor cells, and there are a large number of downstream signaling pathway activities that affect different functions of the cells. Inhibiting Kras itself will not only produce a certain level of response, but even tumors in unilateral non-responders may become more fragile and more sensitive to the compound. Merck's R & D boss said that it would continue to expand the population of highly selective therapy. Broad-spectrum anticancer drugs now rely on precision combination therapies rather than sweep-type chemotherapy. G12C mutations are more common in lung cancer. Merck already has Keytruda, the largest product in the largest tumor market for lung cancer, so it is logical to expand the site with Kras inhibitors with the help of existing sales and marketing systems. A recent subgroup analysis of KN042 showed that Kras mutants are more sensitive to K drugs, which reduces 58% of the risk of death in Kras mutants and 72% of the risk of death in G12C mutants.

Amgen's AMG510 is now the leading product of G12C mutation, BI has a pan-Kras inhibitor, but Merck's competitiveness in confirming targets will make these temporary leaders feel a lot of pressure. From ACE inhibitors in the 1980s, DPP4 inhibitors 15 years ago, and recently Keytruda's cornering overtaking, Merck has shown me-too masters to follow the final execution of super overtaking. Me-too is more than just extending the half-life of the first product. It is the essence of me-too that runs the second half faster and finds a mechanism more efficiently. The failure of SGI-110 made the industry question the judgment of Otsuka Pharmaceutical's 800 million acquisition of Astex. Today this cooperation gave Astex a chance to commit crimes and Merchant ’s participation greatly increased the chance of success.

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