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.
June 24, 2024

  • NMS-812: A clinical phase potent and selective PERK/GCN2 inhibitor, a potential first-in-class targeting the integrated stress response (ISR)
  • The United States Food and Drug Administration (FDA) has cleared the protocol for new investigational new drug (IND) application for NMS-812, 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 acute myeloid leukemia (AML) in the Phase Ia/Ib PERKA-812-003 trial in the second half of 2024.
  • NMS discontinues the FIH clinical trial with NMS-812 in the setting of relapsed/refractory multiple myeloma (NCT05027594) due to strategic reasons, however dosing established initial reasonable pharmacokinetics and safety
  • Brian Sherer, PhD., a pharmaceutical leader with over 25 years of experience in discovery and development joins NMS to lead development of PERK/GCN2 and assist the portfolio


NERVIANO, IT and BOSTON, MA, USA, June 24, 2024 – Nerviano Medical Sciences S.r.l. (“NMS” and “the Company”), a part of NMS Group S.p.A. (NMS Group) and Nerviano Medical Sciences, Inc., a wholly owned subsidiary of NMS Group, focused on the discovery and development of oncology drugs and the largest oncological R&D company in Italy, today announced that the United States Food and Drug Administration (FDA) has cleared the protocol for investigational new drug (IND) application for NMS-812, a first-in-class orally bioavailable and highly potent small molecule dual inhibitor of PERK/GCN2.

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.  In addition, NMS-812 inhibits GCN2, another ISR component, affecting mainly amino acid deprivation stress, to augment cell death.  Together the double inhibition likely overcomes resistance.  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-812’s ability to inhibit two key components, PERK and GCN2, of the ISR, may offer superiorapoptosis in other cancer settings such as AML.  In addition, NMS-812 modulates the immune response via direct and indirect mechanisms which may contribute to anti-cancer activity.

Acute Myeloid Leukemia (AML) is an aggressive hematological malignancy. According to American Cancer Society, in 2024, an estimated 20,800 new cases of leukemia will be diagnosed in the US and 11,220 people will die from the disease.

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.

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.

“Acute Myeloid Leukemia (AML) remains an aggressive hematological malignancy with tremendous unmet medical need especially in the p53 mutant patient population. Based on preclinical data and unique dual Integrated Stress Response mechanism, NMS-812 may represent a novel strategy for AML through the unfolded protein response and amino acid deprivation stressors , with potential for synergies with other drugs and potential to overcome drug resistance.” said Lisa Mahnke, MD, Ph.D., Chief Medical Officer at NMS. “We are thrilled to have Brian to join the NMS team to lead the development.”

Brian has had leadership roles with Exelixis, EMD Serono, and AstraZeneca over a 25 year career.  He has been instrumental in the discovery and early development of more than 10 small molecule clinical candidates.

In addition to PERK/GCN2, Brian will also lead NMS’  MPS1 asset, leveraging his extensive expertise.

“Both PERK/GCN2 and MPS1 assets hold potential as first-in-class drugs for subsets of cancers with high unmet medical needs. Our teams have made remarkable progress in developing these novel assets, and we are excited about the future under Brian’s leadership.” said Lisa Mahnke.

Link PR: 20240624-NMS-PERK-Study May Proceed-Brian Sherer as AL-Final

from NMSGroup

 

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