Determination of Route of Administration and Cardiac Safety of a Novel Psychoplastogen for the treatment of SUDs

ABSTRACT Delix Therapeutics is developing psychoplastogens, compounds that promote rapid and sustained neuroplasticity. This new class of compounds was identified by Delix founder, Professor David Olson (UC Davis). DLX-007 is a novel, potent psychoplastogen designed and inspired by known psychoplastogens Ibogaine and 5-MeO-DMT. Similar to these clinically effective compounds, DLX-007 promotes structural and functional neural plasticity in circuits relevant for the treatment of substance use disorders (SUDs) with demonstrated efficacy for a variety of substances in preclinical models including opioid use disorder (OUD). In addition to reducing heroin- consumption and producing antidepressant-like effects in rodent, DLX-007 avoids many of the safety concerns abundant to ibogaine. DLX-007 has completed GLP IND-enabling studies, showing a good safety profile and desired effect in relevant preclinical models of OUD. In order to further advance the development of DLX-007 and position it for transition to human trials, Delix proposes to establish the ideal administration profile, while maintaining acceptable cardiotoxic safety, for the treatment of humans. In this proposal, we will first assess the ideal route of administration by establishing the pharmacokinetic (PK) parameters of intramuscular administration in three preclinical species, modelling the predicted human PK and comparing those results to previously obtained PK parameters for intravenous and oral administration. Secondly, we will use a state-of-the-art cardiovascular safety assay to validate and expand the comparative improvements our compound has in relation to ibogaine’s notorious cardio-safety profile. This proposal introduces a novel treatment paradigm for SUD, namely, leveraging structural plasticity. Delix’s DLX-007 is a high potential therapeutic for OUD, preserving its neuroplastic promoting characteristics and behavioral efficacy of ibogaine but without the hallucinogenic liabilities and reduced cardiotoxic liabilities. DLX- 007 treatment may reverse opioid-induced structural changes and its clinical development could enhance the therapeutic arsenal for treating OUD, in particular because it provides a non-opioid receptor-based therapeutic that might be capable of reversing the underlying disease neuropathology long-term. Due to DLX-007’s improved safety profile relative to its parent compound, we anticipate that DLX-007 may also have broad therapeutic potential for treating multiple SUDs in addition to other neuropsychiatric and neurodegenerative disorders characterized by dendritic spine and synapse loss in the PFC and its downstream targets.