NMS-812 / Nerviano Medical Sciences - LARVOL DELTA

NMS-812, a clinical stage dual PERK and GCN2 modulator, is effective in AML as monotherapy and in combination with venetoclax/azacitidine in venetoclax resistant setting (EORTC-NCI-AACR 2026) - "Abstract will be available as of 4 November (with consent of the author)"

Clinical • Combination therapy • Monotherapy • Acute Myelogenous Leukemia • Oncology

NMS-812, a clinical stage dual PERK and GCN2 modulator, with activity in Multiple Myeloma, AML and solid tumors (EACR 2026) - "PERK and GCN2 are involved in tumor growth and resistance to chemotherapies. NMS-812, a dual PERK/GCN2 inhibitor, is endowed with antitumor activity as single agent and in combination with SOC, suggesting that PERK/GCN2 modulation by NMS-812 can thwart resistance to chemotherapies. NMS-812 has also immune-modulatory properties with ICD induction and anti-tumor activity relying on the immune system."

Clinical • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Multiple Myeloma • Oncology • Ovarian Cancer • Ovarian Clear Cell Cancer • Solid Tumor • ATF4 • CALR • EIF2A • EIF2S1

Ph I Study in Adult Patients With Relapsed or Refractory Multiple Myeloma (clinicaltrials.gov) - P1 | N=5 | Terminated | Sponsor: Nerviano Medical Sciences | N=65 ➔ 5 | Trial completion date: Apr 2025 ➔ Jan 2024 | Recruiting ➔ Terminated; The decision is not based on emerging safety or efficacy concerns but on strategic reasons related to the changing and competitive treatment options in Multiple Myeloma

Enrollment change • Trial completion date • Trial termination • Hematological Malignancies • Multiple Myeloma • Oncology

Study of NMS-03597812 in Adult Patients With Relapsed/Refractory Acute Myeloid Leukemia (clinicaltrials.gov) - P1 | N=124 | Recruiting | Sponsor: Nerviano Medical Sciences | Not yet recruiting ➔ Recruiting

Enrollment open • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

Study of NMS-03597812 in Adult Patients With Relapsed/Refractory Acute Myeloid Leukemia (clinicaltrials.gov) - P1 | N=124 | Not yet recruiting | Sponsor: Nerviano Medical Sciences

New P1 trial • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

Nerviano Medical Sciences announces FDA protocol clearance of new IND application for NMS-812, a first-in-class dual inhibitor of PERK/GCN2. Brian Sherer, PhD. appointed to lead and accelerate the development. (NMS Group Press Release) - "Nerviano Medical Sciences...today announced that the United States Food and Drug Administration (FDA) has cleared the protocol for investigational new drug (IND) application for NMS812, a first-in-class orally bioavailable and highly potent small molecule dual inhibitor of PERK/GCN2...NMS expects to initiate enrollment of patients with relapsed/refractory AML including patients with TP53 mutations in the Phase I PERKA-812-003 trial in the second half of 2024."

Clinical • IND • New P1 trial • Acute Myelogenous Leukemia • Hematological Malignancies • Oncology

Nerviano Medical Sciences announces FDA protocol clearance of new IND application for NMS-812, a first-in-class dual inhibitor of PERK/GCN2. Brian Sherer, PhD. appointed to lead and accelerate the development. (NMS Group Press Release) - P1 | N=65 | NCT05027594 | Sponsor: Nerviano Medical Sciences | "NMS-812 has very strong scientific rational in the multiple myeloma indication by modulating the unfolded protein response via PERK in the integrated stress response (ISR) pathway since this is a high protein production setting...The first in human (FIH) study showed excellent pharmacokinetic profile allowing daily oral dosing and likely permissive safety for further development. The multiple myeloma indication was deprioritized because it would require significant resources due to multiple treatment lines, but NMS is fully committed to continuing in partnership with other companies interested in the multiple myeloma space....NMS today also announces the discontinuation of the FIH clinical trial with NMS-812 in the setting of relapsed/refractory multiple myeloma (NCT05027594) due to strategic reasons."

P1 data • Trial termination • Hematological Malignancies • Multiple Myeloma • Oncology

Ph I Study in Adult Patients With Relapsed or Refractory Multiple Myeloma (clinicaltrials.gov) - P1 | N=65 | Recruiting | Sponsor: Nerviano Medical Sciences | Trial primary completion date: Nov 2023 ➔ Jun 2024

Trial primary completion date • Hematological Malignancies • Multiple Myeloma • Oncology

NMS-812, a novel potent PERK inhibitor that also inhibits GCN2, exhibits strong anti-tumor activity as single agent and in combination in preclinical models (AACR 2023) - "NMS-812 is a novel dual, PERK/GCN2 inhibitor with potential for first-in-class, that validates dual PERK and GCN2 inhibition as a therapeutic approach for MM and other PERK/GCN2-dependent settings. Based on these promising results, a Ph1 study has been started in Multiple Myeloma with plans to expand to other malignancies in the near future."

Preclinical • Hematological Malignancies • Lymphoma • Multiple Myeloma • Oncology • Solid Tumor