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Merck partners with Hengrui for next-generation selective PARP1 inhibitor and antibody-drug conjugate

Merck has announced a strategic collaboration with Jiangsu Hengrui Pharmaceuticals (Hengrui). The partnership includes an exclusive license worldwide (ex-China) to develop, manufacture and commercialize Hengrui’s next-generation potent and selective PARP1 (poly (ADP-ribose) polymerase 1) trapping inhibitor HRS-1167.

The agreement also includes an option to an exclusive license worldwide (ex-China) to develop, manufacture and commercialize Hengrui’s Claudin-18.2 antibody-drug conjugate (ADC) SHR-A1904. In addition, Merck has the option to co-promote both assets in China.

“This partnership with Hengrui fully aligns with both our external innovation ambition and our oncology research and development strategy by diversifying our robust internal pipeline in our focus areas of DNA damage response inhibition and antibody-drug conjugates,” said Danny Bar-Zohar, Global Head of Research & Development and Chief Medical Officer for the Healthcare business of Merck.

“The synergies of these assets with our portfolio offer broad potential for development and the opportunity to advance more therapeutic options for patients with difficult-to-treat cancers. We look forward to leveraging the significant expertise of Hengrui and our strong collaboration ahead.”

Compared with first-generation PARP inhibitors, the selectivity and differentiated safety profile of PARP1-specific inhibitors could offer the opportunity to expand their therapeutic impact in established and new indications.

HRS-1167 has shown encouraging signs of clinical activity and patient benefit in Phase I trials as a monotherapy and has higher potential to combine with chemotherapy as well as novel agents, compared with previous attempts with first-generation PARP inhibitors. This aligns with the company’s overarching development approach of DNA damage response (DDR) inhibitors, exploring their synergistic activity and maximizing their potential impact in combination with other anticancer therapies and approaches. Merck is researching the potential to treat cancer through inhibition of multiple targets in the DDR cascade, including ATR, ATM, DNA-PK, and PARP.

Additionally, should the company exercise its option, SHR-A1904 would complement Merck’s internal preclinical and clinical ADC portfolio applying different linker payload technologies. The first ADC developed using Merck’s own technology, M9140, a CEACAM5-targeting ADC, is being evaluated in an ongoing Phase Ia/b study in patients with metastatic colorectal cancer.

“Given the high unmet need in oncology, we are excited to work closely with Merck to bring Hengrui’s innovations to cancer patients worldwide,” said Frank Jiang, board member and Chief Strategy Officer of Hengrui Pharma. “Partnering with Merck on our PARP franchise is an important milestone on Hengrui’s globalization journey. We look forward to advancing our molecules rapidly through development and reaching patients in need.”

Under the terms of the agreement, Merck will provide Hengrui with an upfront payment of €160 million. Hengrui will receive payments for the achievement of certain development, regulatory and commercial milestones and tiered royalties on net sales by Merck. Potential payments may total up to €1.4 billion.

 

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