Eliem Therapeutics, Inc. provided an update on its plans to advance its ETX-155 clinical program. ETX-155 is a novel, neuroactive steroid GABAA receptor positive allosteric modulator (PAM) that the Company plans to evaluate in subjects with major depressive disorder (MDD), perimenopausal depression (PMD), and epilepsy. In April 2022, the Company elected to delay advancing ETX-155 into Phase 2a depression trials to determine the root cause of a lower-than-expected exposure observed in a Phase 1b proof-of-concept trial of ETX-155 in photosensitive epilepsy (PSE).

Based on an initial review of ongoing analyses, the Company believes that the reduced exposure levels were most likely related to certain aspects of the chemistry, manufacturing, and controls (CMC) for the different batches of drug product used in the Phase 1 healthy volunteer trials and the Phase 1b PSE trial. Evaluation and implementation of CMC process modifications to ensure consistency of drug product manufacturing are currently underway. In parallel, the Company plans to initiate a Phase 1 pharmacokinetic trial in healthy subjects using the drug batches that were used in the Phase 1b PSE trial.

The objective of this Phase 1 trial is to identify the dose required to provide a similar exposure to that of the 60-milligram dose used in the previous 14-day repeat dose Phase 1 healthy volunteer trial. Once a dose level with appropriate exposure and safety is confirmed, the Company intends to initiate its previously planned Phase 2a trial of ETX-155 in MDD patients. Results from the Phase 1 pharmacokinetic trial are expected in the fourth quarter of 2022, and the subsequent randomized, placebo-controlled Phase 2a trial in MDD patients is expected to initiate in the first quarter of 2023.

This Phase 2a trial is anticipated be a proof-of-concept study with 4-week treatment, with subjects randomized 1:1 to either ETX-155 or placebo, evaluating efficacy endpoints from day 3 through day 42. Assuming Phase 2a MDD trial initiation in the first quarter of 2023, topline data from this trial would be expected in mid-2024. The Company is postponing the initiation of the planned Phase 2a trial in PMD, which will provide additional investment flexibility for the progression of Eliem's pipeline.

The Company will consider resuming the PSE trial after the expected readout of the Phase 1 pharmacokinetic trial in the fourth quarter of 2022. In addition to ETX-155, the Company expects to report topline data for its clinical candidate, ETX-810, in lumbosacral radicular pain (LSRP) in the third quarter of 2022 and is progressing a novel Kv7 channel opener program that is expected to begin IND-enabling studies in the second half of 2022.