Merck signs €1.4bn cancer alliance with China’s Hengrui

Merck KGaA's Danny Bar-Zohar
Merck KGaA

Merck’s chief medical officer Danny Bar-Zohar

Germany’s Merck KGaA has reached a deal with Chinese pharma company Jiangsu Hengrui that covers a pair of cancer drugs, including a ‘next-generation’ PARP inhibitor and an antibody-drug conjugate.

The deal includes an upfront fee of €160 million ($169 million) and could swell to €1.4 billion if development, regulatory, and commercial objectives are met, making it one of the largest pipeline-boosting in-licensing deals for the German company in recent years.

Merck gets exclusive rights to Hengrui’s PARP1 drug HRS-1167 outside China under the terms of the agreement, and also picks up an option for an ex-China license to SHR-A1904, an ADC directed at Claudin-18.2 – currently a hot target in biopharma. Merck also gets an option to co-promote both drugs in China.

In a statement, the German company said that selective PARP1 inhibitors have the potential for a “differentiated” safety profile compared to the first generation of PARP drugs, currently led by $3.7 billion blockbuster Lynparza (olaparib) from AstraZeneca and MSD (known as Merck & Co in the US and Canada), which bind to PARP1 and PARP2.

“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,” it added.

The drug will slot in alongside other R&D programmes at Merck, investigating inhibitors of DNA damage response that, along with PARP, include drugs targeting ATR, ATM, and DNA-PK.

AZ is also working on a selective PARP1 inhibitor called AZD5305 and has generated results showing improved safety and tolerability, as well as greater tumour control in patients with ovarian, HER2-negative breast, pancreatic, and prostate cancers with BRCA1/2, PALB2, or RAD51C mutations, in the phase 1/2 PETRA study.

Meanwhile, SHR-A1904 will complement Merck’s own ADC portfolio, currently led by M9140, a CEACAM5-targeting ADC being tested in a phase Ia/b study in patients with metastatic colorectal cancer.

Claudin-18.2 emerged in the last few years as a compelling target in oncology drug development, with a number of companies - including Astellas, Innovent, I-Mab, BioNTech, and Legend Biotech - having drugs in clinical testing.

Astellas looks to be slightly in front in this category with its zolbetuximab candidate, having reported clinical data in gastric or gastroesophageal junction (GEJ) adenocarcinoma earlier this year that it said should support regulatory filings.

“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,” commented Merck’s chief medical officer, Danny Bar-Zohar.

Prior to the Hengrui deal, Merck’s biggest in-licensing transaction in recent years was an €898 million deal with Debiopharm, including €188 million upfront, which gave it rights to IAP inhibitor xevinapant for head and neck cancer.