Merck KGaA is reaffirming its commitment to the burgeoning field of PARP inhibitors, making a substantial investment of $169M to secure exclusive rights to a PARP1 inhibitor known as HRS-1167 outside of China. This strategic move is further supported by the potential for an additional 1.4 billion euros in milestone payments, strengthening Merck’s position in the competitive landscape of cancer therapeutics. Notably, this arena has seen significant activity from pharmaceutical giants like AstraZeneca and Gilead Sciences.
The drug in question, HRS-1167, is currently in development by China’s Jiangsu Hengrui Pharmaceuticals. It recently initiated a phase 1 clinical trial for this candidate, focusing on patients with advanced solid tumors. Although this development puts HRS-1167 behind the leading PARP inhibitors in terms of development timeline, both Hengrui, and Merck have identified a unique opportunity to enhance the first-generation treatments available.
Merck’s interest in HRS-1167 is based on compelling evidence suggesting that PARP1-specific inhibitors could potentially address some of the limitations associated with existing therapies. Notably, these limitations include hematologic toxicity, which restricts dosing and the feasibility of combining these drugs with other treatment modalities. Lynparza and Zejula, which inhibit both PARP1 and PARP2, are marred by these challenges. If the primary efficacy of these treatments is attributed to their impact on PARP1 and their toxicity primarily stems from PARP2 inhibition, a PARP1-specific inhibitor could offer the positive aspects of Lynparza and Zejula while bypassing the associated drawbacks. Several pharmaceutical companies have recognized the potential of this approach.
AstraZeneca has been at the forefront of this trend, initiating a series of phase 1 and 2 clinical trials for their selective PARP1 inhibitor, AZD5305. Additionally, they are investigating AZD9574, a PARP1 inhibitor with the ability to penetrate the blood-brain barrier. Meanwhile, Gilead expanded its portfolio with the acquisition of XinThera, a move that added a preclinical-stage PARP1 drug candidate to their pipeline.
Merck KGaA’s interest in PARP1-selective inhibitors goes hand in hand with their ongoing efforts in the field of DNA damage response (DDR) targets. Their research encompasses ATR, ATM, and DNA-PK, presenting opportunities for combining therapies with diverse approaches to combat cancer. A PARP inhibitor with improved safety profiles could open up possibilities for combination therapies.
In addition to the HRS-1167 agreement, Merck’s collaboration with Hengrui encompasses an option related to SHR-A1904, an antibody-drug conjugate (ADC) aimed at Claudin18.2. This protein has attracted significant attention from companies like Amgen, Astellas, AstraZeneca, BioNTech, and Legend Biotech, who recognize its potential as an oncology target. These firms are researching ADCs, bispecific antibodies, and cell-based therapies targeting Claudin18.2.
Hengrui is concurrently conducting three phase 1 and phase 1/2 trials for SHR-A1904.