basimglurant (NOE-101) / Roche, Noema Pharma - LARVOL DELTA

The Mechanism of Metabotropic Glutamate Receptor 5 in the Tumorigenesis, Progression and Angiogenesis of Hepatocellular Carcinoma (APASL 2025) - "For research in vitro, after changing the expression of mGluR5 by agonist (DHPG) or antagonist (RG7090), CCK8 proliferation assay, colony formation assay, wound healing assay, Transwell migration and invasion assays and flow cytometry were performed for assessing the abilities of proliferation, migration, invasion and apoptosis...MPEP inhibited the capillarization and angiogenesis from inhibiting CD31, CD34, LECT2, Tie1, VEGFA and VEGFR2, which was similar to the antiangiogenic effect of Lenvatinib. 1. The expression of mGluR5 was higher in HCC cells and tissues, suggesting that mGluR5 may play a carcinogenic role in the tumorigenesis and progression of HCC. 2."

Hepatocellular Cancer • Hepatology • Oncology • Solid Tumor • CD31 • CD34 • LECT2 • PECAM1 • TIE1

Basimglurant (NOE-101) in Children, Adolescents, and Young Adults With TSC (clinicaltrials.gov) - P2 | N=61 | Active, not recruiting | Sponsor: Noema Pharma AG | Trial primary completion date: Nov 2024 ➔ Mar 2025

Trial primary completion date • CNS Disorders • Epilepsy

Basimglurant (NOE-101) in Children, Adolescents, and Young Adults With TSC (clinicaltrials.gov) - P2 | N=61 | Active, not recruiting | Sponsor: Noema Pharma AG | Recruiting ➔ Active, not recruiting

Enrollment closed • CNS Disorders • Epilepsy

Targeting mGluR5 in Fibroblasts Provides a Promising Avenue in Idiopathic Pulmonary Fibrosis: Prospective of Repositioning Basimglurant, A Negative Allosteric Modulator of mGluR5 (ATS 2024) - "mGluR5 is a rational therapeutic target for treating IPF, and the repositioning of basimglurant for treating IPF may provide an expedited treatment option for patients afflicted with this disease."

Clinical • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases • ACTA2 • COL1A1 • CTGF • PYCR1 • SERPINE1 • SLC7A11 • TGFB1

Repositioning of Basimglurant (mGluR5 Antagonist) for the Treatment of Idiopathic Pulmonary Fibrosis (ATS 2024) - " First for target validation, PF was induced by oropharyngeal administration of bleomycin (1 U/kg b. w. ) in both mGlur5 wildtype (Grm5+/+, WT) and mGluR5 knockout (Grm5-/-, KO) mice. mGluR5 antagonists are already proven to be safe and well tolerated in patients. Thus, the current preclinical validation could rapidly expedite the translation of the existing mGluR5 antagonists for IPF and other indications of interstitial lung diseases."

Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases • ACTA2 • COL1A1 • SERPINE1 • TGFB1

An Efficacy and Safety Study of Basimglurant in Patients With Trigeminal Neuralgia. (clinicaltrials.gov) - P2/3 | N=200 | Recruiting | Sponsor: Noema Pharma AG | Trial completion date: Aug 2024 ➔ Jan 2026 | Trial primary completion date: Apr 2024 ➔ Jan 2025

Trial completion date • Trial primary completion date • Neuralgia • Pain

Basimglurant in Children, Adolescents, and Young Adults With TSC (clinicaltrials.gov) - P2 | N=54 | Recruiting | Sponsor: Noema Pharma AG | Trial completion date: Aug 2025 ➔ Jan 2026 | Trial primary completion date: Mar 2024 ➔ Nov 2024

Trial completion date • Trial primary completion date • CNS Disorders • Epilepsy

Basimglurant in Children, Adolescents, and Young Adults With TSC (clinicaltrials.gov) - P2 | N=54 | Recruiting | Sponsor: Noema Pharma AG | Phase classification: P2b ➔ P2

Phase classification • CNS Disorders • Epilepsy

Rationale for the Use of Basimglurant, a Novel mGluR5 Negative Allosteric Modulator, as a Treatment for Seizures Associated with Tuberous Sclerosis Complex (AES 2023) - "Taken together, these data suggest a significant role for mGluR5 in pathophysiological mechanisms of TSC. The results from exploratory studies in mouse models of TSC demonstrates proof-of-principle that selective mGluR5 NAMs such as basimglurant could have therapeutic utility on TSC through two parallel mechanisms: 1) normalization of the excitatory neuronal imbalance thereby reducing seizure phenotypes and 2) reduction of protein synthesis in brain cells which may have an impact on tumour growth."

Brain Cancer • CNS Disorders • Epilepsy • Oncology • Solid Tumor • TSC1

Basimglurant in Children, Adolescents, and Young Adults With TSC (clinicaltrials.gov) - P2b | N=54 | Recruiting | Sponsor: Noema Pharma AG | Trial primary completion date: Nov 2023 ➔ Mar 2024

Trial primary completion date • CNS Disorders • Epilepsy

Noema Pharma, Founded by Sofinnova Partners, Raises CHF 103 Million (USD 112 Million) in Series B Financing (Businesswire) - "Sofinnova Partners...today announced that Noema Pharma ('Noema'), has raised an oversubscribed CHF 103 million (approx. USD 112 million) Series B financing round. Sofinnova co-founded and seed financed Noema in 2019 with Dr. George Garibaldi and Luigi Costa. The company was established to advance clinical stage assets in-licensed from Roche....The proceeds of the Series B financing will be used to advance Noema Pharma's clinical-stage assets, including its lead compound basimglurant (NOE-101), an mGluR5 inhibitor that is being evaluated in Phase 2b clinical trials for severe pain in Trigeminal Neuralgia (TN)..."

Financing • CNS Disorders • Neuralgia • Pain

An Efficacy and Safety Study of Basimglurant in Patients With Trigeminal Neuralgia. (clinicaltrials.gov) - P2/3 | N=200 | Recruiting | Sponsor: Noema Pharma AG | Trial completion date: May 2024 ➔ Aug 2024

Trial completion date • Neuralgia • Pain

Basimglurant in Children, Adolescents, and Young Adults With TSC (clinicaltrials.gov) - P2b | N=54 | Recruiting | Sponsor: Noema Pharma AG | Trial completion date: Jul 2024 ➔ Aug 2025 | Trial primary completion date: Jun 2024 ➔ Nov 2023

Trial completion date • Trial primary completion date • CNS Disorders • Epilepsy

Noema Pharma Receives FDA Fast Track Designation for basimglurant (NOE-101) in Trigeminal Neuralgia (GlobeNewswire) - "Noema Pharma...announces that the US Food and Drug Administration (FDA) has granted Fast Track designation to its mGluR5 inhibitor basimglurant (NOE-101) for the treatment of trigeminal neuralgia (TN)."

Fast track designation • CNS Disorders • Neuralgia • Pain

Clinical investigations of compounds targeting metabotropic glutamate receptors. (PubMed, Pharmacol Biochem Behav) - "PET ligands for mGlu5Rs have been studied in a range of patient populations and several mGlu5R antagonists have been tested for potential efficacy in patients including mavoglurant, diploglurant, basimglurant, GET 73, and ADX10059...Fenobam was approved for use as an anxiolytic prior to its recognition as an mGlu5R antagonist. mGlu2/3R agonists (pomaglumated methionil) and mGlu2R agonists (JNJ-40411813, AZD 8529, and LY2979165) have been studied in patients with schizophrenia with promising but mixed results. Antagonists of mGlu2/3Rs (decoglurant and TS-161) have been studied in depression where TS-161 has advanced into a planned Phase 2 study in treatment-resistant depression...The mGlu4R potentiator, foliglurax, did not meet its primary endpoint in patients with Parkinson's disease. Ongoing efforts to develop mGluR-targeted compounds continue to promise these glutamate modulators as medicines for psychiatric and neurological disorders."

Journal • CNS Disorders • Depression • Developmental Disorders • Epilepsy • Fragile X Syndrome • Gastroenterology • Gastroesophageal Reflux Disease • Genetic Disorders • Mental Retardation • Mood Disorders • Movement Disorders • Pain • Parkinson's Disease • Psychiatry • Schizophrenia

Basimglurant in Children and Adolescents With TSC (clinicaltrials.gov) - P2b | N=55 | Recruiting | Sponsor: Noema Pharma AG | Trial completion date: Apr 2024 ➔ Jul 2024 | Initiation date: May 2022 ➔ Mar 2021

Trial completion date • Trial initiation date • CNS Disorders • Epilepsy

Basimglurant in Children and Adolescents With TSC (clinicaltrials.gov) - P2b | N=55 | Recruiting | Sponsor: Noema Pharma AG | Not yet recruiting ➔ Recruiting | Trial completion date: May 2023 ➔ Apr 2024 | Trial primary completion date: May 2023 ➔ Apr 2024

Enrollment open • Trial completion date • Trial primary completion date • CNS Disorders • Epilepsy

Noema Pharma announces first patient dosed in Phase 2b LibraTN study of mGluR5 inhibitor NOE-101 in trigeminal neuralgia (GlobeNewswire) - "Noema Pharma...today announces the dosing of its first patient in its Phase 2b clinical trial of the mGluR5 inhibitor NOE-101 in trigeminal neuralgia (TN)."

Trial status • CNS Disorders • Neuralgia • Pain

Noema Pharma Announces FDA Investigational New Drug Authorization for Phase 2b LibraTN Study of mGluR5 Inhibitor NOE-101 in Trigeminal Neuralgia (GlobeNewswire) - "Noema Pharma...today announces the U.S. Food and Drug Administration (FDA) has authorized an Investigational New Drug (IND) application to initiate a Phase 2b clincial trial of the mGluR5 inhibitor NOE-101 in trigeminal neuralgia (TN). The LibraTN trial is a multi-center, 24-week, prospective, double-blind, randomized-withdrawal, placebo-controlled study to evaluate the efficacy and safety of NOE-101 in adults with pain associated with TN. NOE-101 has previously been found to be safe and well-tolerated in adult subjects. The LibraTN trial is expected to report in H1 2024."

IND • New P2b trial • P2b data • CNS Disorders • Neuralgia • Pain

Noema Pharma to Host Key Opinion Leader Webinar on Trigeminal Neuralgia “Trigeminal Neuralgia? You are not alone” (GlobeNewswire) - "Noema Pharma...today announced that it will host a key opinion leader (KOL) webinar...on Friday, February 11, 2022, at 12 pm Eastern Time / 6 pm Central European Time....The potential treatment options for the management of pain associated with trigeminal neuralgia, including NOE-101 mGluR5 NAM (basimglurant), will also be discussed. The Noema Pharma management team will provide a company overview and update on its clinical efforts to bring NOE-101 to patients and physicians."

Clinical • CNS Disorders • Neuralgia • Pain

An Efficacy and Safety Study of Basimglurant in Patients With Trigeminal Neuralgia. (clinicaltrials.gov) - P2/3 | N=200 | Recruiting | Sponsor: Noema Pharma AG

New P2/3 trial • Neuralgia • Pain

Basimglurant in Children and Adolescents With TSC (clinicaltrials.gov) - P2b; N=55; Not yet recruiting; Sponsor: Noema Pharma AG

Clinical • New P2b trial • CNS Disorders • Epilepsy

Ketamine and other glutamate receptor modulators for depression in adults with unipolar major depressive disorder. (PubMed, Cochrane Database Syst Rev) - "Our findings show that ketamine and esketamine may be more efficacious than placebo at 24 hours. How these findings translate into clinical practice, however, is not entirely clear. The evidence for use of the remaining glutamate receptor modulators is limited as very few trials were included in the meta-analyses for each comparison and the majority of comparisons included only one study. Long term non-inferiority RCTs comparing repeated ketamine and esketamine, and rigorous real-world monitoring are needed to establish comprehensive data on safety and efficacy."

Clinical • Journal • Review • CNS Disorders • Depression • Epilepsy • Major Depressive Disorder • Mood Disorders • Psychiatry

Novel Glutamatergic Modulators for the Treatment of Mood Disorders: Current Status. (PubMed, CNS Drugs) - "This manuscript gives a brief overview of the glutamate system and its relevance to rapid antidepressant response and discusses the existing clinical evidence for glutamate receptor-modulating agents, including (1) broad glutamatergic modulators ((R,S)-ketamine, esketamine, (R)-ketamine, (2R,6R)-hydroxynorketamine [HNK], dextromethorphan, Nuedexta [a combination of dextromethorphan and quinidine], deudextromethorphan [AVP-786], axsome [AXS-05], dextromethadone [REL-1017], nitrous oxide, AZD6765, CLE100, AGN-241751); (2) glycine site modulators (D-cycloserine [DCS], NRX-101, rapastinel [GLYX-13], apimostinel [NRX-1074], sarcosine, 4-chlorokynurenine [4-Cl-KYN/AV-101]); (3) subunit (NR2B)-specific N-methyl-D-aspartate (NMDA) receptor antagonists (eliprodil [EVT-101], traxoprodil [CP-101,606], rislenemdaz [MK-0657/CERC-301]); (4) metabotropic glutamate receptor (mGluR) modulators (basimglurant, AZD2066, RG1578, TS-161); and (5) mammalian target of rapamycin complex 1..."

Journal • Review • Bipolar Disorder • CNS Disorders • Depression • Gastrointestinal Disorder • Major Depressive Disorder • Mood Disorders • Psychiatry

Understanding exposure-receptor occupancy relationships for metabotropic glutamate receptor 5 (mGlu) negative allosteric modulators across a range of pre-clinical and clinical studies. (PubMed, J Pharmacol Exp Ther) - "The aim of this study was to measure the RO of the mGlu NAM, HTL0014242, in rodents and cynomolgus monkey and to compare its plasma, and brain, exposure-RO relationships with those of clinically tested mGlu NAMs dipraglurant, mavoglurant and basimglurant. Significance Statement Despite the long history of mGlu as a therapeutic target and progression of multiple compounds to the clinic, no formal comparison of exposure-receptor occupancy relationships has been conducted. Our data indicate for the first time that a consistent, unified relationship can be observed between exposure and mGlu receptor occupancy when unbound brain concentration and receptor affinity are taken into account across a range of species for a diverse set of mGlu NAMs, including a new drug candidate, HTL0014242."

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