From 1.25 Billion to Zero: The Ups and Downs of SHP2 Inhibitor Development and China's Surge in Pharmaceutical industry

On December 14, 2020, two giants in the biotech space, Relay Therapeutics and Genentech, announced a major collaboration. Gentec has acquired the development and commercialization rights for Relay Therapeutics' drug candidate, LY-1971, with a view to achieving a breakthrough in the field of cancer therapy. Relay Therapeutics has thus secured $125 million in initial funding, including a $100 million down payment and $25 million in near-term payments, as well as up to $695 million in potential milestone payments. Ly-1971, a SHP2 inhibitor, was then in Phase I clinical trials for solid tumors such as non-small cell lung cancer, colorectal cancer, and head and neck squamous cell carcinoma, showing great promise.

However, this cooperation did not go as smoothly as expected. Genentech's decision to terminate its agreement with Relay Therapeutics without disclosing a specific reason has made the future of RLY-1971 uncertain. The decision sent Relay Therapeutics' shares down 1.78 percent, while also depriving the company of the opportunity to receive an additional $675 million milestone payment.

The development of SHP2 inhibitors has been fraught with setbacks. Revolution Medicines and Sanofi ended their collaboration on the SHP2 inhibitor RC-4630 in December 2022. Despite the positive data performance of RC-4630 at the 2022 World Lung Cancer Congress, the two companies chose to part ways. Revolution Medicines received a $50 million upfront payment and more than $5 billion in milestone payments in its 2018 partnership with Sanofi, but the end of that partnership is certainly a blow to the SHP2 inhibitor space.

In July 2023, AbbVie also announced that it was giving up its exclusive rights to SHP2 inhibitors acquired from Cax, a decision based on its asset portfolio and strategic adjustments. As a non-receptor protein tyrosine phosphatase, the role of SHP2 in a variety of carcinogenic signaling pathways makes it an important target for cancer therapy.

In spite of this, Chinese pharmaceutical companies have not given up the exploration of SHP2 inhibitors. Gax's JAB-3312 performed well in Phase II data presented at the ASCO meeting and is currently in Phase III clinical trials. In addition, Qinhao Pharmaceutical's HBI-2376 and Beida Pharmaceutical's BPI-442096 have also shown promising efficacy, adding confidence for Chinese pharmaceutical companies to compete in this field.

In the future, SHP2 inhibitors may accelerate the market process by combining with KRAS G12C inhibitors, but the complexity and challenge of new drug development cannot be ignored. Whether Chinese pharmaceutical companies can surpass in the development of SHP2 inhibitors and break the monopoly of the international market, we will wait and see.