Eliem Therapeutics, Inc. provided an update on its pipeline programs, including the announcement of interim results from its ongoing Phase 1 clinical trial of ETX-155. ETX-155 program: ETX-155 is a novel GABAA receptor positive allosteric modulator (GABAA PAM) that is being developed for the treatment of major depressive disorder (MDD) and epilepsy. Following the observation of lower-than-expected drug exposure levels in the three subjects evaluated in a Phase 1b photosensitive epilepsy (PSE) trial, the Company initiated a Phase 1, single and repeat dose, clinical trial in healthy subjects to confirm the pharmacokinetic profile of ETX-155 in advance of a planned Phase 2a clinical trial in subjects with MDD.

The drug exposure levels from the recently executed single dose part of the Phase 1 pharmacokinetic trial (N=42) were compared with the population pharmacokinetic model built with data from healthy subjects evaluated in the original, previously disclosed Phase 1 trials (N=70). Results demonstrated that at the 60-milligram dose, there was no meaningful difference between exposures obtained with different batches, and that the low exposures observed in the Phase 1b PSE trial are within the range of previously reported moderate variability. In addition, and upon extensive investigation, no irregularities or differences were observed with chemistry, manufacturing, and controls (CMC) associated with the drug product and the drug substance batches used in the PSE trial or with other newly produced drug substance and product.

Given the encouraging safety, tolerability, and pharmacokinetic profile of the 60-milligram dose in the prior two Phase 1 repeat dose trials and well-tolerated single dose data with a 75-milligram dose in the ongoing Phase 1 pharmacokinetic trial, the Company plans to evaluate a 75-milligram dose of ETX-155 in the repeat dose part of the ongoing Phase 1 pharmacokinetic trial in healthy subjects prior to making a decision on the dose for the planned Phase 2a MDD trial. Final results from the Phase 1 pharmacokinetic trial, including the repeat dose cohort, are expected in the fourth quarter of 2022. The Company is positioned to initiate the Phase 2a MDD trial in the first quarter of 2023 using either the 60-milligram or 75-milligram dose of ETX-155, depending on the final exposure, safety and tolerability results from the ongoing Phase 1 pharmacokinetic trial.

Assuming initiation in the first quarter of 2023, the topline data for the Phase 2a MDD trial would be expected in mid-2024. Kv7.2/3 channel opener program: The Company's preclinical program targets the Kv7.2/3 potassium channel (Kv7), a target that has clinical validation in pain and epilepsy. The Company has filed foundational intellectual property claims on its novel Kv7 compounds.

In addition, while pursuing further lead evaluation, the Company has initiated the scaling up of two pre-candidates to enable the initiation of IND-enabling safety studies, expected in the first quarter of 2023, with Phase 1 studies planned to initiate in the first half of 2024. The Company's novel Kv7 compounds have demonstrated high potency and differentiated selectivity in electrophysiology assays, and in vivo anticonvulsant activity in the maximal electroshock seizure (MES) rat model. Preclinical data on the Kv7 compounds are planned to be reported later in the fourth quarter of 2022.

Anxiolytic for generalized anxiety disorder (GAD): The Company has discontinued early preclinical development of a novel, non-sedating anxiolytic for the potential treatment of GAD because none of the compounds investigated achieved the required profile.