Merck KGaA takes another shot at PARP1
But today’s deal with Jiangsu Hengrui doesn’t mean that the group is turning away from an earlier tie-up with Nerviano.
But today’s deal with Jiangsu Hengrui doesn’t mean that the group is turning away from an earlier tie-up with Nerviano.
Merck KGaA is doubling down on selective PARP1 inhibition, announcing a collaboration with Jiangsu Hengrui today over HRS-1167 for €160m up front. AstraZeneca currently leads this field, while another big player, Gilead, has also signalled its interest here with the takeout of the preclinical player Xinthera in May.
Merck also already has a presence in PARP1, through a smaller collaboration with Nerviano Medical Sciences signed last year. Today’s tie-up might suggest that the group is no longer interested in Nerviano – but the earlier deal is still in play, a spokesperson for the company told ApexOnco.
A clue about why German Merck might want two distinct PARP1 inhibitors could come from Astra’s approach: the UK company is developing saruparib and AZD9574, with the latter said to be brain penetrant.
Similarly, Nerviano’s NMS-293 is also thought to penetrate the CNS, while there is no mention of this property in today’s press release. The Merck spokesperson declined to comment on the brain-penetrant properties of either agent.
Apart from Merck and Astra, the only other clinical-stage selective PARP1 comes from Jiangsu Hansoh, according to an analysis of OncologyPipeline, although there are various assets at the preclinical stage.
Merck, which now has an exclusive ex-China licence to develop HRS-1167, highlighted the favourable toxicity profile of PARP1-selective inhibitors, a property it says could expand the PARPs into new indications. Merck cited signs of clinical activity with HRS-1167 as monotherapy in phase 1, although data have not been publicly presented.
Crowding into Claudin
Merck’s deal today also included an option over an exclusive licence, outside China, covering Jiangsu Hengrui’s Claudin18.2-targeting ADC SHR-A1904. In addition, the German group has the option to co-promote both projects in China.
Claudin18.2 has emerged as a very popular target so, if Merck does opt in, competition will be fierce.
PARP1-selective inhibitors in clinical development
| Project | Company | Key trial(s) | Note |
|---|---|---|---|
| Saruparib | AstraZeneca | Ph1/2 Petra in solid tumours & Petranha in prostate cancer | First Petra data at AACR 2022: 28% ORR (7/25) |
| NMS-293* | Nerviano Medical/ Merck KGaA | Ph1 PARPA-293-001 in solid tumours; ph1/2 PARPA-293-002 in glioblastoma | Early data presented at AACR-NCI-EORTC; Merck signed collaboration Sep 2022 |
| AZD9574* | AstraZeneca | Ph1/2 Certis1 in solid tumours | Preclinical data at AACR 2022 |
| HRS-1167 | Jiangsu Hengrui/ Merck KGaA | Ph1 in solid tumours | Merck signed collaboration Oct 2023 |
| HS-10502 | Jiangsu Hansoh | Ph1 in solid tumours |
Note: *said to be brain penetrant. Source: OncologyPipeline.
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