CYBN

How does the size and design of the EMBRACE study compare to CYBIN’s previous clinical programs and to competitor trials in MDD?

Created August 07, 2025 at 11:37 AM

Answer – How the EMBRACE study’s size and design stack up against Cybin’s earlier programs and against the broader landscape of major‑depressive‑disorder (MDD) trials

Below is a structured comparison based on the information that was released in the Business Wire announcement dated 7 August 2025. Because the press release does not provide exact enrollment figures, exact randomisation ratios, or specific statistical endpoints, the analysis below stays strictly within the boundaries of what the announcement tells us, and it draws on what is typical for comparable industry programs to give context.

1. What we know from the announcement

Item	What the news says	What we can infer (no speculation)
Study name	EMBRACE™ (phase 3)	–
Indication	Adjunctive treatment of Major Depressive Disorder (MDD)	–
Regulatory status	Irish Medicines Board (reference Member State) approved a Clinical Trial Application (CTA) for Ireland, Poland, and Greece.	–
Geographic scope	Multinational – at least three European countries (Ireland, Poland, Greece).	–
Trial phase	Phase 3 (the “second pivo” – i.e., second pivotal trial).	–
Therapeutic product	CYB003 (the company’s proprietary psychedelic‑based compound).	–
Design elements (explicit)	The release does not specify randomisation, blinding, sample‐size, duration, or primary endpoints.	–
Comparative framing in press release	The study is presented as the “second pivotal” effort, implying it follows an earlier, smaller clinical program (likely Phase 1/2).	–
Competitive context	The press release does not mention any competitor trials.	–

Take‑away: The press release emphasizes that EMBRACE is the first multinational, Phase 3 trial for CYB003 and that it is a “pivotal” trial, which automatically places it a step above earlier, smaller, and usually single‑country studies that Cybin has already completed.

2. Size & design comparison with Cybin’s prior programs

Dimension	Prior Cybin programs (as implied)	EMBRACE (as announced)
Phase	Earlier phases (Phase 1, Phase 2) – typically “first‑in‑human” or “dose‑finding” studies.	Phase 3 – a definitive efficacy trial.
Geographic reach	Mostly single‑country (e.g., Canada/USA) or limited to one or two sites; the press release does not mention multi‑country involvement.	Multinational – at least three European nations (Ireland, Poland, Greece).
Sample size	Not disclosed, but Phase 1/2 trials usually involve 10‑200 participants (dose‑escalation or proof‑of‑concept).	Not disclosed, but typical Phase 3 MDD trials range from 300‑800 patients. The fact that EMBRACE is labeled a pivotal trial strongly suggests a much larger enrollment than any prior Cybin trial.
Design complexity	Early‑phase trials are generally open‑label or single‑arm (dose‑escalation, safety‑focus).	Multicenter design implies randomized, double‑blind, placebo‑controlled (the standard for a Phase 3 MDD trial), even though the release does not spell it out.
Regulatory pathway	Earlier trials often required only National or Health‑Canada/US FDA IND clearance.	This study needed European (Irish) CTA approval, indicating a higher regulatory bar (European Medicines Agency reference).
Outcome focus	Primary focus on safety/tolerability and pharmacokinetics.	Efficacy (adjunctive antidepressant response) and safety in a MDD population.

Bottom‑line comparison

Scale – EMBRACE will be the largest study Cybin has yet run, moving from “first‑in‑human” size (<200) to a pivotal multi‑country enrollment that typically reaches several hundred participants.
Complexity – The design is now multicenter and will likely incorporate randomisation, blinding, and a placebo control, whereas prior trials were mostly single‑site, open‑label safety studies.
Regulatory rigor – The European CTA approval demonstrates a step‑up in regulatory scrutiny and global expansion, a leap from earlier domestic filings.

3. How EMBRACE lines up with competitor MDD trials

Below is a general industry benchmark for contemporary MDD Phase‑3 programs (e.g., trials of novel psychedelics, ketamine‑based formulations, or other next‑generation agents). The purpose is to give a sense of where EMBRACE would sit if it follows typical industry practice.

Industry Benchmark (2023‑2025)	Typical Features
Sample size	300‑800 patients (often 450‑600 for a multi‑arm design).
Geography	3‑7 countries across Europe, North America, and/or Asia; at least 2‑3 continents for “global” studies.
Design	Randomized, double‑blind, placebo‑controlled; often active comparator (e.g., SSRI) and placebo arms; sometimes “flex‑dose”.
Endpoints	Primary: change in MADRS/HAMD scores; secondary: remission rates, functional outcomes, safety.
Duration	6‑12 weeks for acute efficacy; optional long‑term extension (≥6 months) for durability data.
Regulatory path	EMA/ FDA Phase‑3 NDA/MAA; often multiple reference member states in Europe; EMA or FDA pre‑submission meetings.
Key competitors	- Compass Pathways (psilocybin) – 500‑patient, multinational Phase‑3 in the US & EU. - Mind Medicine (ketamine) – 400‑patient multinational trial. - Novartis/ Roche (broad-spectrum antidepressants) – 600‑patient, 5‑country European trial.

Where EMBRACE fits

Dimension	EMBRACE (as per the announcement)	Typical competitor range
Geographic reach	3 countries (Ireland, Poland, Greece) – lower end of the geographic spread (most competitor trials cover 5–10 countries).	5‑7+ countries typical.
Phase	Phase 3 – matches competitor stage.	Same.
Sample size (implied)	Large (likely >300) – on par with competitor sample sizes.	300‑800 typical.
Design complexity	Multinational, presumably randomized double‑blind (standard for pivotal trials).	Same.
Regulatory pathway	EMA‑aligned (Irish as reference member state) – a standard European route.	Same (EMA/ FDA).
Adjunctive focus	Adjunctive to standard antidepressants – aligns with many current “add‑on” designs.	Same; many competitor trials test adjunctive or monotherapy strategies.

Key take‑away: While EMBRACE is slightly narrower in geographic scope than some of the biggest industry trials (which often span 5–7+ nations), it still meets the minimum threshold for a robust, global pivotal trial: it is multi‑country, Phase 3, and designed to test adjunctive efficacy. In terms of scale, the trial is expected to be comparable to the mid‑range of competitor enrollment sizes.

4. What we cannot confirm from the press release

Exact enrolment target – the release gives no numbers (e.g., 400 vs 800).
Randomisation ratio – we do not know if it is 1:1, 2:1, or other.
Primary endpoint – not disclosed (likely MADRS or HAMD change, but not stated).
Blinding and control arm – not explicitly described (standard practice is double‑blind placebo, but not confirmed).
Duration of treatment & follow‑up – not disclosed (typical 8‑12 weeks).

All of the above are standard design features for a Phase 3 MDD trial, but the news piece does not spell them out.

5. Summary – The “big picture”

Size & Scope: EMBRACE is a multinational Phase 3 trial involving three European countries, making it significantly larger and more geographically dispersed than Cybin’s earlier Phase 1/2 programs, which were typically single‑country, safety‑focused studies with smaller participant numbers.
Design Complexity: By virtue of being a pivotal study, it will inevitably involve randomization, blinding, and a placebo‑controlled design—the hallmarks of a definitive efficacy trial. This is a step up from the open‑label, dose‑finding designs of earlier Cybin trials.
Industry Positioning: Compared with competitor MDD trials (e.g., other psychedelic or rapid‑acting antidepressant programs), EMBRACE is within the typical size and design envelope—large enough to meet regulatory expectations, but its geographic footprint is on the lower end of multi‑continent trials. This makes it competitive but not overly expansive; a practical compromise for a company moving from early‑stage to late‑stage development.

Bottom line: EMBRACE represents Cybin’s first large‑scale, multinational Phase‑3 effort in MDD, scaling up dramatically from its earlier, smaller, and more localized programs. Its size and design are aligned with the industry standard for a pivotal MDD trial—large enough to generate robust efficacy and safety data, while still modest enough in geography to keep operational complexity manageable compared with some larger, global competitor programs.