mavoglurant (STP7) / Novartis, STALICLA - LARVOL DELTA

Efficacy and Safety of Twelve Anti-Dyskinetic Drugs in Parkinson's Disease: A Bayesian Network Meta-Analysis of Randomized Controlled Trials. (PubMed, Eur J Neurol) - "Amantadine ER improved dyskinesia significantly versus amantadine IR. Both formulations of amantadine were superior as OFF time-reducing agents compared to other anti-dyskinetic drugs, whereas amantadine IR non-significantly reduced OFF time versus amantadine ER."

Journal • Retrospective data • Review • CNS Disorders • Movement Disorders • Parkinson's Disease

Influence of Mavoglurant on Alcohol Craving and Drinking in Heavy Drinkers (clinicaltrials.gov) - P1 | N=63 | Recruiting | Sponsor: Yale University | Phase classification: P2 ➔ P1

Phase classification • Addiction (Opioid and Alcohol)

Stalicla Secures CHF 2 Million Financing Led by Addex Therapeutics to Advance Precision Medicine Neurodevelopmental Disorder Programs (GlobeNewswire) - "STALICLA SA...announced the successful closing of a CHF 2 million financing led by Addex Therapeutics. This financing will sustain operations and program development in neurodevelopmental disorders as Stalicla prepares for its upcoming Series C and the partnering of key programs. This financing underscores investor confidence in Stalicla’s innovative DEPI precision neuro platform and its portfolio of precision autism assets, STP1 and STP2. The company is also progressing its STP7 (mavoglurant) program, the most clinically advanced mGluR5 negative allosteric modulator, having concluded a Phase 3 enabling drug-drug interaction study in October 2024."

Financing • Autism Spectrum Disorder • CNS Disorders

Functional Neuroimaging of Alcoholism Vulnerability: Probing Glutamate and Reward, Using the mGluR5 Inhibitor Mavoglurant (clinicaltrials.gov) - P1 | N=80 | Recruiting | Sponsor: Yale University | Trial completion date: Jun 2025 ➔ Jul 2026 | Trial primary completion date: Jun 2025 ➔ Jul 2026

Trial completion date • Trial primary completion date • Addiction (Opioid and Alcohol)

Mavoglurant reduces cocaine use in patients with cocaine use disorder in a phase 2 clinical trial. (PubMed, Sci Transl Med) - "Adverse events in the treatment group were headache, dizziness, and nausea. In this small and short trial, mavoglurant reduced cocaine and alcohol use in patients with chronic cocaine use disorder."

Clinical • Journal • P2 data • Addiction (Opioid and Alcohol) • CNS Disorders • Pain • Psychiatry

Treatment for Dyskinesia in Parkinson's Disease: A Network Meta-analysis of Randomized Controlled Trials. (PubMed, Mov Disord) - "This RCT-based NMA identifies and ranks nine efficacious interventions for dyskinesia in PD. GPi-DBS may be the most effective therapy for treating dyskinesia, with IR amantadine ranking highest among oral medications. Novel anti-dyskinetic medications are associated with less-favorable tolerance profiles."

Journal • Retrospective data • CNS Disorders • Movement Disorders • Parkinson's Disease

STA-P7-C001: Phase1, STP7 Cocaine Drug-Drug Interaction Study (clinicaltrials.gov) - P1 | N=21 | Completed | Sponsor: Stalicla SA | Recruiting ➔ Completed

Trial completion

Negative effect of treatment with mGluR5 negative allosteric modulator AFQ056 on blood biomarkers in young individuals with Fragile X syndrome. (PubMed, SAGE Open Med) - P2 | "These findings indicate that AFQ056 does not provide benefits as assessed by primary or secondary endpoints. ClincalTrials.gov NCT02920892."

Biomarker • Journal • Autism Spectrum Disorder • Developmental Disorders • Fragile X Syndrome • Genetic Disorders • Mental Retardation • MMP9

Influence of Mavoglurant on Alcohol Craving and Drinking in Heavy Drinkers (clinicaltrials.gov) - P2 | N=63 | Recruiting | Sponsor: Yale University | Not yet recruiting ➔ Recruiting

Enrollment open • Addiction (Opioid and Alcohol)

The mGlu5 receptor negative allosteric modulator mavoglurant reduces escalated cocaine self-administration in male and female rats. (PubMed, Psychopharmacology (Berl)) - "These findings suggest that the mGlu5 receptor is involved in escalated cocaine self-administration. These findings support the development of clinical trials of mavoglurant to evaluate its potential therapeutic benefits for CUD."

Journal • Preclinical • CNS Disorders • Mental Retardation • Psychiatry • Substance Abuse

STA-P7-C001: Phase1, STP7 Cocaine Drug-Drug Interaction Study (clinicaltrials.gov) - P1 | N=20 | Recruiting | Sponsor: Stalicla SA | Not yet recruiting ➔ Recruiting

Enrollment open

Functional Neuroimaging of Alcoholism Vulnerability: Probing Glutamate and Reward, Using the mGluR5 Inhibitor Mavoglurant (clinicaltrials.gov) - P1 | N=80 | Recruiting | Sponsor: Yale University | Trial completion date: Jul 2026 ➔ Jun 2025 | Trial primary completion date: Jul 2026 ➔ Jun 2025

Trial completion date • Trial primary completion date • Addiction (Opioid and Alcohol)

Influence of Mavoglurant on Alcohol Craving and Drinking in Heavy Drinkers (clinicaltrials.gov) - P2 | N=80 | Not yet recruiting | Sponsor: Yale University | Initiation date: Jan 2024 ➔ Apr 2024

Trial initiation date • Addiction (Opioid and Alcohol)

Functional Neuroimaging of Alcoholism Vulnerability: Probing Glutamate and Reward, Using the mGluR5 Inhibitor Mavoglurant (clinicaltrials.gov) - P1 | N=80 | Recruiting | Sponsor: Yale University | Trial completion date: Jul 2024 ➔ Jul 2026 | Trial primary completion date: Jul 2024 ➔ Jul 2026

Trial completion date • Trial primary completion date • Addiction (Opioid and Alcohol)

Phase1, STP7 Cocaine Drug-Drug Interaction Study (clinicaltrials.gov) - P1 | N=20 | Not yet recruiting | Sponsor: Stalicla SA

New P1 trial

Constrained numerical deconvolution using orthogonal polynomials. (PubMed, Heliyon) - "We demonstrate the effectiveness of the proposed method through two practical applications: the estimation of COVID-19 curves and the study of mavoglurant, an experimental drug. Our results show that the extended method presents a sum of squared residuals in the same order of magnitude of that of the original Cutler's method and other widely known unconstrained deconvolution techniques, but obtains instead physically plausible solutions, correcting the errors introduced by the alternative methods considered, as illustrated in our case studies."

Journal • Infectious Disease • Novel Coronavirus Disease

Influence of Mavoglurant on Alcohol Craving and Drinking in Heavy Drinkers (clinicaltrials.gov) - P2 | N=80 | Not yet recruiting | Sponsor: Yale University

Trial completion date • Trial primary completion date • Addiction (Opioid and Alcohol)

Influence of Mavoglurant on Alcohol Craving and Drinking in Heavy Drinkers (clinicaltrials.gov) - P2 | N=80 | Not yet recruiting | Sponsor: Yale University

New P2 trial • Addiction (Opioid and Alcohol)

Mavoglurant in Alcohol Drinking (clinicaltrials.gov) - P1 | N=34 | Completed | Sponsor: Yale University | Recruiting ➔ Completed

Trial completion

Inhibiting metabotropic glutamate receptor 5 after stroke restores brain function and connectivity. (PubMed, Brain) - "Using multiple behavioral tests we observed that treatment with negative allosteric modulators (NAMs) of mGluR5 (MTEP, fenobam, and AFQ056) for 12 days, starting 2 or 10 days after stroke, restored lost sensorimotor functions, without diminishing infarct size...Recovery was prevented by activation of mGluR5 with the positive allosteric modulator VU0360172, and accelerated in mGluR5 KO mice compared to wild-type mice...We conclude that neuronal circuitry subserving sensorimotor function after stroke is depressed by a mGluR5-dependent maladaptive plasticity mechanism that can be restored by mGluR5 inhibition. Post-acute stroke treatment with mGluR5 NAMs combined with rehabilitative training may represent a novel post-acute stroke therapy."

Journal • Cardiovascular • CNS Disorders • Depression • Ischemic stroke • Psychiatry

Effects of AFQ056 on language learning in fragile X syndrome. (PubMed, J Clin Invest) - P2 | "Despite the large body of evidence supporting use of mGluR5 NAMs in animal models of FXS, this study suggests that this mechanism of action does not translate into benefit for the human FXS population and that better strategies are needed to determine which mechanisms will translate from pre-clinical models to humans in genetic neurodevelopmental disorders."

Journal • CNS Disorders • Developmental Disorders • Fragile X Syndrome • Genetic Disorders • Psychiatry

Functional Neuroimaging of Alcoholism Vulnerability: Probing Glutamate and Reward, Using the mGluR5 Inhibitor Mavoglurant (clinicaltrials.gov) - P1 | N=80 | Recruiting | Sponsor: Yale University | Trial completion date: Apr 2024 ➔ Jul 2024 | Trial primary completion date: Jul 2023 ➔ Jul 2024

Trial completion date • Trial primary completion date • Addiction (Opioid and Alcohol)

Targeted Treatments for Fragile X Syndrome. (PubMed, Adv Neurobiol) - "Current treatment trials including the use of cannabidiol (CBD) topically and metformin orally have positive preliminary data, and both of these medications are available clinically. The use of the phosphodiesterase inhibitor (PDE4D), BPN1440, which raised the level of cAMP that is low in FXS has very promising results for improving cognition in adult males who underwent a controlled trial. There are many more targeted treatments that will undergo trials in FXS, so the future looks bright for new treatments."

Journal • Fragile X Syndrome • Genetic Disorders

". @Novartis offloads mGlur5 drug mavoglurant to Swiss #biotech Stalicla, as it nears phase 3 programme in #cocaineusedisorder https://t.co/mHBqrMotd2" (@pharmaphorum)

Mavoglurant in Alcohol Drinking (clinicaltrials.gov) - P1 | N=40 | Recruiting | Sponsor: Yale University | Trial completion date: May 2023 ➔ Aug 2023

Trial completion date