Reunion Neuroscience: Psychedelic Prodrug RE104 For The Treatment of Post-Partum Depression Moves Into Phase 2 Clinical Trials.

1. RE104 is a psychedelic prodrug that was safe and well tolerated by healthy participants in a phase 1 clinical trial.
2. RE104 produced an effective response at 33 mg which will be the effective dose used in the phase 2 trial investigating its efficacy in the treatment of PPD.

The Latest

A first-in-human, double-blind phase 1 clinical trial funded by Reunion Neuroscience Inc. investigated the safety, tolerability, and pharmacological profile of RE104, a proprietary psychedelic prodrug the company hopes to investigate in the treatment of postpartum depression (PPD). In this study, 48 healthy participants were enrolled across 6 dose levels ranging from 5.5 mg to 44 mg. In general, RE104 was safe and well tolerated by all study participants. Nausea, asymptomatic sinus tachycardia, headache, and restlessness were the most commonly reported adverse effects (AE). Only two participants taking doses of 35 mg and 40 mg experienced a severe AE in the form of agitation which was treated appropriately with midazolam. Drug effect, and mystical experience questionnaires were used to determine the effective dose of RE104. These questionnaires asked patients questions like whether they felt the effect of the drug, whether they felt high, and whether they experienced psychedelic experiences (transcendence of time and space, ineffability, etc.). The study found a dose of 33 mg of RE104 was needed to produce an effective response.

Physician’s Perspective

Childbirth is generally considered a joyous occasion for families. However, 1 in 7 women can experience a major depressive episode (MDE) around this time. This is called PPD. The cause of PPD is not well understood, however, there may be some evidence for the role of rapid alterations in pregnancy-related hormones, and dysregulation in hormones involved in the stress response and lactation. The symptoms of PPD are the same as those seen in MDE: low mood, anhedonia, insomnia/hypersomnia, and suicidal ideation among others. The first line of treatment for mild to moderate PPD is psychotherapy or an antidepressant with a low risk of transfer via breast milk to the baby like sertraline. For women with severe PPD, the first-line treatment is zuranolone, a steroid-based antidepressant. Electroconvulsive therapy can also be offered to women who are breastfeeding. Untreated PPD can lead to the development of chronic depression in mothers, and due to the abuse the child may endure as a result of this, children are at risk of developing mental health and behavioral issues in the future. Psychedelics are becoming a hot topic of research in the treatment of multiple psychiatric illnesses. Reunion Neuroscience’s RE104 offers a unique approach to the treatment of PPD with a psychedelic compound which unlike other treatments will be given as a single dose.

Molecular Target of Therapy

In earlier research, the active form of psilocybin (colloquially known as magic mushrooms), 4-OH-DMT has shown therapeutic effect in the treatment of depression. These effects can last for months. 4-OH-DMT is, however, unfavorable for treatment as the psychoactive effect can last between 6-8 hours and requires monitoring by a healthcare provider. RE104 is a psychedelic prodrug that converts to the active form 4-OH-DiPT, a 4-OH-DMT analog. Like psilocybin much of the way 4-OH-DiPT works is not known. The current understanding is that 4-OH-DiPT acts on 5-HT2A serotonin receptors. This action is thought to cause changes to the brain which lead to a reduction in depressive symptoms. Unlike psilocybin, the psychoactive effect of 4-OH-DiPT only lasts 1-3 hours, and theoretically may offer comparable lasting therapeutic effects.

Company History

Reunion Neuroscience Inc. is a biopharmaceutical company currently specializing in the development of psychedelic-based therapeutics. Recently, Reunion Neuroscience secured $103M in series A funding as they move into phase 2 clinical trials for RE104. This phase 2 clinical trial will investigate the safety and efficacy of a single dose of 33 mg of RE104 given subcutaneously to patients with PPD. This trial is poised to begin in the first half of 2024. In addition to RE104, the company is in the preclinical phase of development of their RE200 series drugs which are to be highly selective against 5-HT2A receptors, with no off-target effects. Data on the RE200 series remains to be released.

Further reading: https://reunionneuro.com/wp-content/uploads/2023/06/23-RNR-3851_ASCP23_RE104_Poster_M1-3.pdf

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