Clinical programs

Clinical Programs

We are exploiting our core Discovery engine to constantly develop new molecular entities with potential for “first in class “ and “best in class”. Our projects target a broad number of solid tumors and haematological indications, with a focus on biomarker selected patient populations. We are developing projects in house into clinical development in order to accelerate the clinical benefit for our patients.

NMS-153

Primary liver cancer is the sixth most common neoplasm and among the leading cause of cancer-related death worldwide. Hepatocellular carcinoma (HCC) constitutes 80-90% of all primary liver cancers. Its incidence is increasing and will soon surpass one million annual cases worldwide. Most HCC cases are diagnosed at advanced stages where, despite the recent approval of TKIs as well as checkpoint inhibitors, there is a high unmet medical need.

NMS-153 is a highly potent and selective inhibitor of the MPS1 kinase, which is a mitotic regulator frequently overexpressed and activated in cancer, with broad preclinical activity in different tumor settings, including HCC.

MPSA-153-001 is a Phase I/II study of NMS-153 as single agent in HCC open for recruitment.

NMS-293

PARP is an enzyme implicated in the regulation of DNA repair. PARP inhibition has already been proven a successful therapeutic strategy for treatment of patients carrying deleterious germline and/or somatic BRCA mutations, present in a relevant percentage of breast, ovarian, prostate and pancreatic cancers.
NMS-293 is a potent and selective inhibitor of PARP-1 with unique features compared with other PARP inhibitors, such as its selectivity for PARP-1 vs. PARP-2 and lack of DNA trapping effects, which may result in higher tolerability in terms of undesired hematopoietic effects. Due to its high brain penetration it has potential for efficacy against primary brain tumors and CNS metastases.

PARPA-293-001, a Phase I study of NMS-293 as single agent, is ongoing in solid tumors enriched for BRCA mutant tumors
(ClinicalTrials.gov Identifier: NCT04182516).

NMS-812

NMS-812 is a novel, potent and orally bioavailable dual inhibitor of PERK (PKR-like endoplasmic reticulum kinase) and GCN2 (General Control Nonderepressible 2), with potential for first-in-class in several potential oncology indications. PERK and GCN2 are effectors of the Integrated Stress Response (ISR), a pro-survival pathway exploited by cancer cells to survive stress. The dual inhibition of the ISR, the pathway involved in survival of cancer cells to standard therapy may potentially overcome drug resistance and offer superior anti-proliferative activity. In addition, NMS-812 also modulates the immune response via direct and indirect mechanisms which may contribute to anti-cancer activity. The first in human (FIH) study showed excellent pharmacokinetic profile allowing daily oral dosing and likely permissive safety for further development. Based on preclinical data and its unique, dual inhibition of the two key components of the Integrated Stress Response mechanism, NMS-812 may represent a novel strategy for Acute Myeloid Leukemia (AML), with potential for synergies with other drugs and potential to overcome drug resistance.