EMP-01: Our MDMA derivative for Social Anxiety Disorder (SAD), a potentially better tolerated alternative to MDMA

With my weekly blog series, I will do a deep dive into each of our clinical compounds and illustrate why we are excited about their potential in mental health indications. You can read earlier blogs here: RL-007, GRX-917 and VLS-01.

Social Anxiety Disorder (SAD) is a mental health condition characterized by an intense, persistent fear of social situations. Unfortunately, the condition is common, with approximately 7.1% of U.S. adults, or about 18 million individuals, suffering from SAD in the past year[1]. Current front-line treatment for SAD includes psychotherapy and antidepressants, but accessibility, tolerability, and overall therapeutic response to these approaches is often poor. Only 35% of patients with SAD recover after 10 years of prospective follow-up[2].

This treatment gap is why we are developing EMP-01, an oral formulation of the R-enantiomer of MDMA for the treatment of SAD. MDMA (commonly referred to by its street name 'ecstasy') is a pharmacologically complex compound that, when consumed, creates unique prosocial and empathogenic effects. However, several challenges associated with the use of MDMA have emerged, including its impact on body temperature, blood pressure, heart rate and its propensity to cause anxiety and bruxism (jaw clenching).

Based on our research to date, what sets EMP-01 apart from MDMA is its more selective pharmacology, which has shown to improve tolerability on several key measures compared to racemic MDMA. Notably, EMP-01 also induces a distinct experiential profile that differentiates it from MDMA. We explore our Phase 1 data in more detail below.

Overview of Social Anxiety Disorder (SAD)

SAD is an area of high unmet medical need, with approximately 18 million people in the U.S. diagnosed in the past year and no novel molecules approved in over two decades. Of adults with SAD in the past year, 30% had serious impairment, 39% had moderate impairment, and 31% had mild impairment.

Currently, the first-line treatment for SAD includes psychotherapy and antidepressants, particularly selective serotonin reuptake inhibitors (SSRIs). However, these treatments often have limitations:

• Low recovery rate: Only 35% of patients with SAD recovered after 10 years of prospective follow-up[3].
• Slow onset of action: Front-line SSRI treatments for anxiety disorders typically have a slow onset (4-12 weeks).
• Side effects: Many patients experience side effects from SSRIs, including sexual dysfunction, weight gain, and sleep disturbances.

EMP-01 (R-MDMA)

Our candidate EMP-01 is an oral formulation of the R-enantiomer of MDMA being developed for the treatment of SAD. EMP-01's pharmacology is more targeted than that of MDMA, preferentially targeting the serotonergic system with much less effect upon dopamine and norepinephrine-mediated neurotransmission.

Phase 1 Results of EMP-01

We’ve completed a Phase 1 single ascending dose trial to assess the safety and tolerability of orally administered EMP-01 in healthy volunteers. The study enrolled 32 participants who received 75mg, 125mg, 175mg, or 225mg of EMP-01 or placebo in a 6+2 design.

Key findings from the Phase 1 study include:

1. Safety and Tolerability:

• EMP-01 was generally well-tolerated, with all adverse events classified as either mild or moderate.
• Only 1 out of 24 participants (4%) experienced bruxism, which is a common side effect of racemic MDMA.
• Body temperature remained in the normal range across all cohorts, unlike the hyperthermia sometimes observed with racemic MDMA.

2. Pharmacodynamics:

• EMP-01 demonstrated a unique, dose-dependent subjective effect profile.
• The 225mg dose showed statistically significant increases in emotional breakthroughs, which have been associated with efficacy in anxiety studies involving classical psychedelics.
• Some measures of self-compassion significantly increased with the 225mg dose at the 1-week follow-up visit. This is particularly relevant as SAD patients report lower levels of self-compassion than healthy controls.

3. Subjective Experience:

• The qualitative profile of the effects was generally found to be more like classical psychedelics (e.g., psilocybin or LSD) than MDMA.
• Study facilitators reported that EMP-01 appeared to produce a more inward-focused and "peaceful" experience compared to their experience facilitating MDMA therapies.

These results are encouraging and support the continued development of EMP-01 for SAD. The unique profile of EMP-01, combining elements of both MDMA and classical psychedelics, may offer a novel approach to treating this challenging disorder.

Next Steps

Based on these positive Phase 1 results, we plan to initiate a Phase 2 study of EMP-01 in patients with SAD. The trial is expected to begin around year-end 2024, with topline data anticipated around year-end 2025.

Given the significant unmet need in SAD treatment and the promising early results of EMP-01, we are optimistic about its potential to provide a new therapeutic option for individuals struggling with this debilitating condition.

Learn more about our programs here.

Forward-Looking Statements

Please note that the information provided above contains forward-looking statements. We have based these forward-looking statements largely on our current expectations and projections about future events and trends that we believe may affect our financial condition, results of operations, business strategy, short-term and long-term business operations and objectives, and financial needs. These forward-looking statements are subject to a number of important factors that could cause actual results to differ materially from those in the forward-looking statements, including the risks, uncertainties, and assumptions described under "Summary Risk Factors" below, “Risk Factors” in Item 1A of Part I, “Management’s Discussion and Analysis of Financial Condition and Results of Operations” in Item 7 of Part II and elsewhere in our Form 10-K for the year ended December 31, 2022, filed with the Securities and Exchange Commission.

Any forward-looking statements made herein speak only as of the date of this communication, and you should not rely on forward-looking statements as predictions of future events. Although we believe that the expectations reflected in the forward-looking statements are reasonable, we cannot guarantee that the future results, performance, or achievements reflected in the forward-looking statements will be achieved or will occur. Except as required by applicable law, we undertake no obligation to update any of these forward-looking statements for any reason after the date hereof or to conform these statements to actual results or revised expectations.

[1] National Institutes of Health

[2] Keller MB. Social anxiety disorder clinical course and outcome: review of Harvard/Brown Anxiety Research Project (HARP) findings. J Clin Psychiatry. 2006

[3] National Institutes of Health