AVL-3288 / Anvyl - LARVOL DELTA

Chronic administration of caffeine, modafinil, AVL-3288 and CX516 induces time-dependent complex effects on cognition and mood in an animal model of sleep deprivation. (PubMed, Pharmacol Biochem Behav) - "Caffeine has anxiolytic effect in acute administration. The improvement of memory in chronic period may be associated with the neuroprotective effects of caffeine. AVL-3288 had a short-term positive effect on memory, but tolerance to these effects developed over time. Furthermore, no anhedonia was observed in AVL-3288 and CX516 groups in contrast to vehicle, caffeine and modafinil groups. This indicates that AVL-3288 and CX516 may show protective effect against depression."

Journal • Preclinical • CNS Disorders • Depression • Mood Disorders • Psychiatry

Enhancing cognitive function in chronic TBI: The Role of α7 nicotinic acetylcholine receptor modulation. (PubMed, Exp Neurol) - "Parietal cortex and hippocampal atrophy were not improved with AVL-3288 treatment in either wild-type or Chrna7 mice. Our results indicate that AVL-3288 improves cognition during the chronic recovery phase of TBI through modulation of the α7 nAChR."

Journal • CNS Disorders • Vascular Neurology • CHAT • CHRNA7

The nicotinic acetylcholine receptor modulator AVL-3288 attenuates hippocampal-based cognitive deficits following repeated mild traumatic brain injury in adolescent rats (Neuroscience 2021) - "Therefore, male and female rats underwent repeated mild injury or sham surgery in adolescence and then were injected with AVL-3288 at 30 minutes prior to testing the animals in either the MWM or NOL tasks at 4 weeks post-injury (female n=6/drug group, n=5/vehicle group; male n=6/group). Treatment with AVL-3288 attenuated injury-induced cognitive deficits in both tasks (treatment p=0.004 MWM, p=0.001 NOL) suggesting that reduced activity of the nAChR may underlie post-traumatic cognitive deficits.; Grant Support: NS1108098"

Preclinical • CNS Disorders • Cognitive Disorders • Vascular Neurology

Newly added product (Anvyl Press Release) - P1, Schizophrenia

Pipeline update • CNS Disorders • Schizophrenia

Positive allosteric modulation of the α7 nicotinic acetylcholine receptor as a treatment for cognitive deficits after traumatic brain injury. (PubMed, PLoS One) - "Our results demonstrate that AVL-3288 improves hippocampal synaptic plasticity, and learning and memory performance after TBI in the chronic recovery period. Enhancing cholinergic transmission through positive allosteric modulation of the α7 nAChR may be a novel therapeutic to improve cognition after TBI."

Journal

Double blind, two dose, randomized, placebo-controlled, cross-over clinical trial of the positive allosteric modulator at the alpha7 nicotinic cholinergic receptor AVL-3288 in schizophrenia patients. (PubMed, Neuropsychopharmacology) - "Primary outcomes were negative, with non-significant worsening for both active groups vs. placebo in the P50 and minimal between group changes on the RBANS. In conclusion, the results did not indicate efficacy of the compound, consistent with most prior results for the nα target."

Clinical • Journal

Double Blind, Two Dose, Cross-Over Clinical Trial of the Positive Allosteric Modulator at the Alpha7 Nicotinic Cholinergic Receptor AVL-3288 in Schizophrenia Patients (ACNP 2019) - "The lack of target engagement changes are consistent with a lack of clinical effect, and are consistent both with failing the AVL-3288 compound. We are unaware of active studies using this mechanism, and when viewed with the totality of negative meta-analysis and failed Phase III studies, these results raise questions about the utility of further study of the n-alpha7 receptor as a viable target in schizophrenia. Although our results are negative, this study is a successful example of the NIMH Fast-Fail approach ."

Clinical

Clinical Trial of AVL-3288 in Schizophrenia Patients (clinicaltrials.gov) - P1; N=24; Completed; Sponsor: New York State Psychiatric Institute; Recruiting ➔ Completed

Clinical • Trial completion