Nerviano Medical Sciences S.r.l., a member of NMS Group and a clinical stage company discovering and developing innovative therapies for the treatment of cancer, recently announced that the first patient has been dosed in its Phase 1 clinical trial of NMS-812 in adult patients with relapsed refractory Multiple Myeloma (MM).
NMS-812 is a novel potent oral inhibitor of PERK (PKR-like endoplasmic reticulum kinase) that also inhibits GCN2 (General Control Nonderepressible 2). PERK and GCN2 are effectors of the Integrated Stress Response (ISR), a pro-survival pathway exploited by cancer cells to survive stress. PERK is a key effector of the unfolded protein response (UPR) and GCN2 is a sensor of amino acid deficiency. Both proteins modulate the eIF2α/ATF4 axis promoting tumor survival and drug resistance as well as, via direct and indirect mechanisms, the immune response.
“PERK/GCN2 targeting has strong potential as an anti-cancer mechanism. NMS is pleased to mark this first patient milestone for the PERKA-812-001 program which, the company plans to develop in various malignancies hoping to address many important clinical questions in patients where there is an unmet need,” said NMS Chief Medical Officer Lisa Mahnke, M.D., PhD.
About the PERKA-812-001 Clinical Program
This is a Phase 1, first-in-human (FIH), open-label, non-randomized, multi-center study to explore the safety, tolerability, pharmacokinetics and preliminary antitumor activity of NMS-812 in adult patients with relapsed refractory Multiple Myeloma (MM) who have exhausted standard treatment options or for whom standard therapy is considered unsuitable.
The study includes a dose escalation and expansion phase and will enroll up to a total of 65 participants. Once the dose is identified, the dose expansion will include two arms, one arm with NMS-812 as single agent and the other one with NMS-812 in combination with dexamethasone. Visit clinicaltrials.gov (NCT05027594) for more details.
About NMS-812 in Multiple Myeloma
NMS-812 is an extremely potent, orally available inhibitor of PERK and GCN2, key regulators of the ISR, with potential for first-in-class. Cancer cells are subjected to extrinsic and intrinsic stress conditions, which result in UPR/ISR activation as a survival mechanism. Notably, tumors arising from professional secretory cells, such as MM, have a constitutively activated UPR, therefore PERK inhibition leads to MM cancer cell death due to proteotoxicity. Based on preclinical data, PERK inhibition may represent a novel effective strategy to inhibit the growth of these tumors as well as other types of tumors, with potential synergism with current SOC such as proteasome inhibitors in MM.