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Addex Therapeutics Publishes Preclinical Research on ADX71743
Addex Therapeutics announced publication of new preclinical research demonstrating that ADX71743, a selective negative allosteric modulator of metabotropic glutamate receptor 7, significantly modulates sleep-wake regulation and stress-related neurochemistry in animal models. The data, published in the International Journal of Neuropsychopharmacology, expands the growing body of evidence supporting mGlu7 as an important mechanism regulating key brain functions and a promising therapeutic target across a range of central nervous system disorders, including mood disorders, anxiety disorders, post-traumatic stress disorder, and other conditions associated with dysregulated stress responses. In the study, ADX71743 increased wakefulness while reducing both REM and non-REM sleep in rats. The compound also altered stress-induced changes in key neurotransmitters, including glutamate, GABA and monoamines, across multiple brain regions in awake animals, producing neurochemical effects consistent with modulation of stress-responsive neural circuits. Together, these findings further validate the pharmacological profile of selective mGlu7 inhibition in vivo and provide additional support for the therapeutic potential of this novel mechanism. Previous studies have demonstrated that selective mGlu7 inhibition can modulate anxiety-related behaviors, disrupt maladaptive fear memory reconsolidation and influence glutamatergic signaling in both rodent and human brain tissue.
Addex Therapeutics Reports Antitussive Activity of GABAB Modulator
Addex Therapeutics announced preclinical data demonstrating antitussive activity of its GABAB positive allosteric modulator candidate in a bleomycin-induced idiopathic pulmonary fibrosis exacerbated chronic cough model. In studies evaluating chronic once-daily administration of a lead GABAB PAM candidate in BLM-exposed animals, robust and sustained antitussive efficacy was observed, with significant reductions in cough frequency and increased cough latency over the treatment period. Improved lung pathology outcomes, including lower Ashcroft scores and reduced percentage of affected lung tissue suggesting an impact on fibrosis, were demonstrated compared to untreated BLM-exposed animals at both Day 7 and Day 28. The safety profile remained favorable, with no meaningful changes in respiratory rate, or body temperature. The compound was well tolerated throughout the study, supporting its potential for chronic administration.
Addex Therapeutics' Spin-Out Neurosterix to Complete NTX-253 Clinical Study in Q2
Addex Therapeutics announced that its spin-out company, Neurosterix, is on track to complete its Phase 1 clinical study evaluating NTX-253 in Q2. NTX-253 is an investigational potent, selective, orally available positive allosteric modulator of the muscarinic M4 receptor being developed for the treatment of schizophrenia. The study is designed to generate an early-stage clinical data package assessing safety, tolerability, and pharmacokinetics across both healthy adult participants and those with stable schizophrenia. The clinical study includes a multi-part, ascending-dose design intended to efficiently characterize NTX-253's clinical profile and support subsequent patient-focused development. The study includes both single ascending dose and multiple ascending dose components, incorporating key translational elements such as food-effect and cerebrospinal fluid assessments. Healthy adult participants will receive a single oral dose of NTX-253 or placebo across sequentially escalating dose cohorts. This phase includes a dedicated food-effect cohort to assess the impact of food on NTX-253 pharmacokinetics. A separate SAD cohort in healthy volunteers will evaluate NTX-253 concentrations in cerebrospinal fluid, providing early insight into central nervous system exposure and brain penetration. In the MAD phase, participants will receive once-daily oral dosing of NTX-253 or placebo for 10 consecutive days, with sequential dose escalation. This phase is designed to evaluate safety, tolerability, and steady-state pharmacokinetics following repeated dosing. The MAD phase includes two dedicated cohorts of adults with stable schizophrenia, representing early clinical evaluation in the target patient population. Participants in these cohorts will have their antipsychotic medications withdrawn for up to eight days prior to dosing with NTX-253, enabling assessment of safety and PK in patients while maintaining clinical stability. Neurosterix was spun-out of Addex in April 2024, raising $65M in a Series A financing led by funds affiliated with Perceptive Advisors. Addex retains a 20% equity interest in Neurosterix.
Addex Therapeutics Ltd - ADR Trading Halted Due to Volatility Trading Pause
Addex Therapeutics Ltd - ADR trading halted, volatility trading pause
Addex Therapeutics Publishes New Data on Anxiety Treatment
Addex Therapeutics announced publication of data in Molecular Psychiatry demonstrating that targeting metabotropic glutamate receptor 7 with negative allosteric modulators could be transformative in the treatment of anxiety and fear-related disorders, such as post-traumatic stress disorder. In the study, scientists from the Center for Psychiatric Neurosciences in Lausanne, Switzerland, evaluated the effects of ADX71743, a highly selective mGlu7 NAM, in established models of fear learning and memory. The results demonstrated that mGlu7 modulation can selectively interfere with the reconsolidation of fear memories, the process in the brain that re-stabilizes a fear memory after it is recalled. This process is increasingly being recognized as a potential therapeutic intervention point in anxiety and trauma-related conditions. Electrophysiological analyses provided mechanistic support for mGlu7 target engagement. ADX71743 modulated glutamatergic transmission at thalamus-to-amygdala synapses. Under baseline conditions, the compound increased spontaneous excitatory signaling, while under high-stimulation conditions it prevented long-term potentiation, a cellular process associated with memory formation. Notably, similar synaptic effects were observed in human brain tissue, mirroring findings in rodent models.
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