MSP-1014 · program
MSP-1014 for Major depressive disorder
Lead program for MSP-1014: a single registered Phase IIa/IIb, two-part adaptive study (ISRCTN31103960) evaluating the safety, PK/PD, tolerability and preliminary efficacy of MSP-1014 (MSP-1014.OX) in patients with major depressive disorder who have a partial or inadequate response to an SSRI taken for at least 8 weeks, conducted at Clerkenwell Health (London, UK) and funded by Mindset Pharma. Part 1 (open-label, 10 evaluable patients) assesses three ascending single doses (30, 50, 70 mg) given ~4 weeks apart, each combined with Acceptance and Commitment Therapy (ACT); Part 2 (double-blind, randomized, placebo-controlled, ~60 patients up to ~82) compares the maximum tolerated dose to placebo, with change in MADRS at 4 weeks post-baseline as the primary efficacy endpoint. MHRA and Research Ethics Committee approval was granted in 2023 (REC ref 23/EE/0032; IRAS 1006861); the trial was announced to commence as early as Q4 2023 with a planned window of January 2023 to October 2024. The program transferred to Otsuka following its 2023 acquisition of Mindset Pharma; no topline results or program status updates have been publicly disclosed since, so the current status is unknown. Phase 2 reflects the highest stage reached.
Development timeline
- The planned study window for ISRCTN31103960 (January 2023 - October 2024; recruitment to July 2024) elapsed with no public topline results or program status update from Otsuka/Mindset. Program status set to unknown pending disclosure; no evidence of either continuation into a next phase or formal discontinuation has been published.↗
- Otsuka Pharmaceutical Co., Ltd. (via Otsuka America, Inc.) agreed to acquire Mindset Pharma in an all-cash plan-of-arrangement valued at ~CAD$80M (~US$59.2M), with MSP-1014 as the lead asset; transaction expected to close on/about 19 Oct 2023 subject to Supreme Court of British Columbia approval. The MSP-1014 MDD program transferred to Otsuka upon closing.↗
- Mindset Pharma announced MHRA and Research Ethics Committee approval to initiate a Phase II study of MSP-1014 for major depressive disorder in the UK (two-part adaptive design: Part 1 dose escalation with ACT; Part 2 randomized placebo-controlled), expected to commence as early as Q4 2023. (Registry: ISRCTN31103960; REC 23/EE/0032.)↗
- Mindset Pharma presented a poster at Neuroscience 2022 highlighting preclinical data on MSP-1014, its psilocin-prodrug lead candidate: head-twitch response (a 5-HT2A target-engagement correlate) was higher after subcutaneous MSP-1014 than psilocybin at the same dose, while MSP-1014 did not reduce locomotor activity or core body temperature at 3 and 10 mg/kg (psilocybin did), and it is rapidly/completely metabolized to psilocin. Findings suggested tolerability may be superior to psilocybin.↗
Clinical trials in Major depressive disorder
ISRCTN31103960MSP-1014.OX (ISRCTN31103960; REC 23/EE/0032; IRAS 1006861)Phase 2Completedn=70
A dose-finding and proof-of-concept study of the efficacy and safety of MSP-1014.OX in patients with major depressive disorder
Formulations
| Formulation | Route | Regimen | Pharmacokinetics |
|---|---|---|---|
| MSP-1014 oral Oral administration; Phase 2 evaluates a single dose (selected from up to three escalating doses in Part 1) alongside Acceptance and Commitment Therapy | Oral | Single dose | — |
Mechanism of action
MSP-1014 is a prodrug that is rapidly and completely metabolized to psilocin (4-hydroxy-DMT, the active metabolite of psilocybin), particularly via the oral route. Psilocin acts as an agonist at the serotonin 5-HT2A receptor (gene HTR2A), the canonical molecular target of classic serotonergic ('classic') psychedelics; cortical 5-HT2A agonism is hypothesized to drive rapid, durable antidepressant effects via enhanced neuroplasticity. Like other tryptamine psychedelics, psilocin is a non-selective serotonin receptor agonist that also engages 5-HT2C and 5-HT1A receptors, but 5-HT2A agonism is regarded as the primary therapeutically relevant action. In preclinical models MSP-1014 produced a higher head-twitch response (a behavioral correlate of 5-HT2A target engagement) than psilocybin at the same dose, consistent with effective central 5-HT2A activation.
| Target | Action | Affinity |
|---|---|---|
| 5-HT2AprimaryHTR2A | Agonist | —ⓘ |
← Full MSP-1014 compound page (identity, identifiers, all indications)
Sources
- 5-HT2A receptor (HTR2A), GtoPdb object 6 — IUPHAR/BPS Guide to Pharmacology
- ISRCTN31103960 - A dose-finding and proof-of-concept study of the efficacy and safety of MSP-1014.OX in patients with major depressive disorder — ISRCTN Registry (BMC)
- Mindset Pharma Presents Poster at Neuroscience 2022 Highlighting Preclinical Data on MSP-1014 - Tolerability May Be Superior to Psilocybin (14 Nov 2022) — Mindset Pharma Inc. / BioSpace
- Mindset Pharma Receives Approval for Phase II Clinical Trial Evaluating MSP-1014 for the Treatment of Major Depressive Disorder — Mindset Pharma Inc. / BioSpace
- MSP-1014 — Wikipedia
- Otsuka Pharmaceutical to Acquire Mindset Pharma (~CAD$80M all-cash; lead asset MSP-1014) — Otsuka Pharmaceutical / Mindset Pharma / BioSpace
- Safety and PK/PD profile of MSP-1014 in major depressive disorder (MDD) patients - research summary (REC 23/EE/0032; IRAS 1006861; ISRCTN31103960) — UK Health Research Authority (HRA)