Delix Therapeutics is planning to initiate two studies to evaluate patients with major depression investigating its lead neuroplastogen candidate, DLX-001, Delix CMO Dr. Aaron Koenig told Pharmaceutical Technology.

Upon the completion of an ongoing Phase I study, the Bedford, Massachusetts-based biotech will take the small molecule into two planned trials—a Phase Ib study and a Phase II study, Koenig said.

DLX-001 is a neuroplastogen designed to promote neuroplasticity without giving rise to the deleterious attributes of first- and second-generation psychedelics. “With many psychoactive drugs, you’re talking about the concentrations that you’re able to maintain, continuously engaging the receptor for some period of time. We think that this [DLX-001] has a Cmax-driven effect, meaning that it’s about flipping the switch on the receptor so that downstream effects can then occur,” said Koenig.

In May, the company released Phase I data, which demonstrated that treatment with DLX-001 does not produce any psychedelic type experiences such as hallucination or dissociation at any of the evaluated doses. DLX-001 was also seen to have a favourable safety and tolerability profile.

The purpose of the upcoming Phase Ib study is to conduct an in depth exploration of the safety, tolerability, pharmacokinetics, and the preliminary efficacy of DLX-001 in patients with major depression, said Koenig. The single-site study will take place in an inpatient unit and begin dosing patients later this year, he said.

As per Koenig, the maximum tolerated dose for DLX-001 has not yet been reached in Phase I, which confirmed that DLX-001 dosed daily over a week is well tolerated. The Phase Ib study will be a blinded comparison of daily dosing and intermittent dosing that will provide some directional data around the dosing frequency of the drug, and the Phase II design. 

The Phase II study, which should begin in April 2025, is designed to dose patients in an outpatient setting for up to four weeks, at which point the patients will enter a follow up period when the sub-acute effects of the drug on mood will be characterised, Koenig explained. Additionally, the study will also give clues on whether the drug’s effects can be maintained after treatment discontinuation.

Presently, the plan is to evaluate one month of daily dosing in three arms with either active drug, placebo, or a pulsatile combination of the two, said Koenig. Each experimental arm will be comprised of 30 – 40 patients, and Delix is aiming to achieve a benchmark effect size for DLX-001 comparable to what is observed with dosing with racemic ketamine or psilocybin, he added.