Merck pays $169M for selective PARP1 drug, stepping up challenge to AstraZeneca and Gilead

Merck KGaA is doubling down on its bet that PARPs are just getting started, paying 160 million euros ($169 million) for ex-China rights to a rival to Lynparza and Zejula. The outlay, which is backed by up to 1.4 billion euros in milestones, strengthens the German drugmaker’s hand in a cancer field targeted by AstraZeneca and Gilead Sciences. 

The PARP1 inhibitor, HRS-1167, is in development at China’s Jiangsu Hengrui Pharmaceuticals. Hengrui began a phase 1 clinical trial of the candidate in patients with advanced solid tumors last year, putting it a long way behind the leading PARP inhibitors. AstraZeneca’s Lynparza won FDA approval in 2014 and was joined on the U.S. market by Zejula, now owned by GSK, in 2017. However, Hengrui and Merck have identified an opportunity to improve on the first-generation treatments. 

Merck’s bet on HRS-1167 is underpinned by evidence that PARP1-specific inhibitors can overcome some of the limitations of existing treatments, notably the hematologic toxicity that constrains their dosing and suitability for use in combinations. Lynparza and Zejula inhibit PARP1 and PARP2, a protein that is implicated in the survival of intermediate cells that develop into blood cells. 

If the efficacy of the treatments is primarily driven by their effect on PARP1, and their toxicity mainly linked to the inhibition of PARP2, a PARP1-specific could provide the benefits of Lynparza and Zejula without the downsides. Multiple drugmakers have bought into that idea.

AstraZeneca is leading the way, launching a series of phase 1 and 2 clinical trials for selective PARP1 inhibitor AZD5305 and a study of its brain-penetrating sibling AZD9574. Gilead bought XinThera to add a preclinical-stage PARP1 drug candidate to its pipeline earlier this year.

Merck KGaA secured a chance to license Nerviano Medical Sciences’ candidate NMS-293 for up to $65 million in upfront and option fees 11 months ago. A spokesperson for Merck told Fierce Biotech that it still has the option on NMS-293.

Merck is buying PARP1-selective inhibitors to complement its own work on other DNA damage response (DDR) targets. The German drugmaker is working on DDR targets including ATR, ATM and DNA-PK and sees opportunities to combine the therapies with different approaches to treating cancer. A safer PARP inhibitor could unlock combination opportunities. 

The agreement between Merck and Hengrui also covers an option on SHR-A1904, an antibody-drug conjugate (ADC) aimed at Claudin18.2. Companies including Amgen, Astellas, AstraZeneca, BioNTech and Legend Biotech have identified Claudin18.2 as a promising oncology target, leading them to study ADCs, bispecific antibodies and cell therapies aimed at the protein.

Hengrui is running three phase 1 and phase 1/2 trials of its candidate. Merck sees the solid tumor drug candidate as complementary to its own preclinical and clinical ADC portfolio, which uses different linker payload technologies.