ENX-101 / Engrail Therap - LARVOL DELTA

ENX-101, a GABAA receptor α2,3,5-selective positive allosteric modulator, displays antiseizure effects in rodent seizure and epilepsy models. (PubMed, Epilepsia) - "ENX-101 is an α2,α3,α5-selective GABAA receptor PAM that has high potency and partial efficacy. The drug is highly effective in rodent seizure and epilepsy models. ENX-101 is most potent in the GAERS model of absence epilepsy, and active in the 6 Hz model and amygdala kindled rats. These results demonstrate that a partial, subtype-selective GABAA receptor PAM has activity in translationally validated preclinical epilepsy screening models. Clinical evaluation of ENX-101 as a treatment for focal and generalized epilepsies is warranted."

Journal • Preclinical • Absence Seizure Disorder • CNS Disorders • Epilepsy

New GABA-Targeting Therapies for the Treatment of Seizures and Epilepsy: II. Treatments in Clinical Development. (PubMed, CNS Drugs) - "The first group consists of positive allosteric modulators of GABA receptors and includes Staccato alprazolam (an already marketed benzodiazepine being repurposed in epilepsy as a potential rescue inhalation treatment for prolonged and repetitive seizures), the α2/3/5 subtype-selective agents darigabat and ENX-101, and the orally active neurosteroids ETX155 and LPCN 2101...These include bumetanide, a diuretic agent that has undergone clinical trials in phenobarbital-resistant neonatal seizures and for which the rationale for further development in this indication is under debate, and ivermectin, an antiparasitic drug currently investigated in a randomised double-blind trial in focal epilepsy. The last group comprises a series of highly innovative therapies, namely GABAergic interneurons (NRTX-001) delivered via stereotactic cerebral implantation as a treatment for mesial temporal lobe epilepsy, an antisense oligonucleotide (STK-001) aimed at upregulating NaV1.1 currents..."

Journal • Review • CNS Disorders • Epilepsy • Gene Therapies

ENACT: A Study of ENX-101 as Adjunctive Treatment in Patients With Focal Seizures (clinicaltrials.gov) - P2 | N=0 | Withdrawn | Sponsor: Engrail Therapeutics INC | N=180 ➔ 0 | Not yet recruiting ➔ Withdrawn

Enrollment change • Trial withdrawal • CNS Disorders • Epilepsy

ENACT: A Study of ENX-101 as Adjunctive Treatment in Patients With Focal Seizures (clinicaltrials.gov) - P2 | N=180 | Not yet recruiting | Sponsor: Engrail Therapeutics INC

New P2 trial • CNS Disorders • Epilepsy

Engrail Therapeutics Announces Positive Results of ENX-101 Phase 1b Clinical Study and Prepares for Initiation of ENACT Phase 2 Trial in Focal Epilepsy (Businesswire) - P1b | N=9 | "Engrail Therapeutics...has announced positive results from a phase 1b clinical trial of ENX-101, a subtype-selective GABA-A positive allosteric modulator (PAM). The phase 1b clinical trial data were presented on June 6, 2022, at the 2022 Epilepsy Pipeline Conference in Santa Clara, California. Following these results and recent interaction with the US FDA that included alignment on the phase 2 development program, Engrail plans to initiate the ENACT Trial, an international multi-center phase 2 clinical trial to evaluate the efficacy and safety of ENX-101 in patients with focal epilepsy....There were no dose-related, clinically meaningful changes in vital signs, electrocardiograms, physical exams, or clinical laboratory values. Treatment-emergent adverse events (TEAEs) were generally mild and transient."

P1 data • CNS Disorders • Epilepsy