23 September 2022 - - Italy-based clinical stage company Nerviano Medical Sciences S.r.l. has signed a collaboration agreement with licensing option with German healthcare company Merck Healthcare KGaA for the next-generation highly selective and brain penetrant PARP1 inhibitor NMS-293, the company said.

PARP (poly (ADP-ribose) polymerase) is key in the repair of DNA damage and PARP inhibitors have been shown to be highly efficacious in the treatment of tumors deficient in homologous recombination repair, such as breast, ovarian, prostate and pancreatic cancers which are BRCA mutated.

NMS-293 is an orally available PARP1 inhibitor, designed to be more PARP1 selective and brain penetrant compared to first generation PARP inhibitors.

With its expected lower hematological side effect profile, it has the expected features for potential use not only as single agent but also in combination with DNA-damage accumulating agents in a wide range of tumors.

NMS-293 is currently in early clinical development for the treatment of patients with BRCA mutated tumors as single agent and with recurrent Glioblastoma, a brain tumor with very high medical need, in combination with temozolomide.

Under the current agreement, Merck will make early payments (up-front and option exercise fees) of up to USD 65m to NMS.

Furthermore, NMS will receive payments for the achievement of certain development, regulatory and commercial milestones and tiered royalties on net sales by Merck.

Upon exercise of the option, NMS will grant to Merck the exclusive rights to research, develop, manufacture, and commercialize NMS-293.

During the option period, NMS and Merck will collaborate on the clinical development of NMS-293 as monotherapy and in combination, with NMS designing, sponsoring, conducting, and funding global clinical trials.

NMS-293 is an orally available small molecule inhibitor of PARP1 and is currently in early clinical development for the treatment of patients with BRCA mutated tumors as single agent and with recurrent Glioblastoma, a brain tumor with very high medical need, in combination with temozolomide.

Nerviano Medical Sciences S.r.l. (NMS Srl) is focused on discovery and clinical development of small-molecule new chemical entities for oncology.

NMS Group is the largest oncological R and D company in Italy.

The NMS kinase inhibitor discovery platform as well as the antibody-conjugating payload platform are the driving forces of the group's innovation, securing global recognition of NMS in personalized therapy.

Recently entrectinib, originally discovered by NMS, is a targeted kinase inhibitor to treat NTRK1/2/3 and ROS1 dependent solid tumors that was licensed to Ignyta, now a member of the Roche Group, gained approvals for commercialization in all major markets.