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Item 1. Business

2025-02-27 compared with 2024-02-29 · 333 added, 456 removed, 834 unchanged (49% of the section changed)

We are a biotechnology company dedicated to accelerating patient access to evidence-based innovation in mental health.

We are motivated by the need to find better ways to help and empower people suffering with mental health challenges who are not helped by existing treatments, and are pioneering the development of a new model of psilocybin treatment, in which our investigational COMP360 psilocybin is administered in conjunction with psychological support, which we refer to as COMP360 psilocybin treatment.

We are motivated by the need to find better ways to help and empower people with serious mental health conditions who are not helped by existing treatments.

We are pioneering a new paradigm for treating mental health conditions focused on rapid and durable responses through the development of our investigational COMP360 psilocybin treatment, potentially a first in class treatment.

COMP360 is our proprietary psilocybin formulation that includes our pharmaceutical-grade polymorphic crystalline psilocybin, optimized for stability and purity.

We believe that our COMP360 psilocybin treatment - combining COMP360 psilocybin with psychological support from specially trained therapists - could offer a new approach to treatment of serious mental health conditions, including treatment-resistant depression, or TRD, a subset of major depressive disorder, or MDD, post-traumatic stress disorder, or PTSD, and anorexia nervosa .

Our initial focus is on TRD, comprising patients who are inadequately served by the current treatment paradigm.

We believe that our COMP360 psilocybin treatment could offer a new approach to treatment of serious mental health conditions, including treatment-resistant depression, or TRD, which is a subset of major depressive disorder, or MDD, post-traumatic stress disorder, or PTSD, and potentially many other serious mental health conditions .

Our initial focus is on TRD, comprising patients who are inadequately served by current treatment options.

In 2018, we received Breakthrough Therapy designation from the FDA for COMP360 for the treatment of TRD.

In November 2021, we announced positive top-line results from our Phase 2b clinical trial evaluating COMP360 in conjunction with psychological support for the treatment of TRD.

On November 3, 2022, The New England Journal of Medicine , the world’s leading peer-reviewed medical journal, published the positive results from our Phase 2b trial.

In November 2021, we announced positive top-line results from our Phase 2b clinical trial evaluating COMP360 for the treatment of TRD.

On November 3, 2022, The New England Journal of Medicine published the positive results from our Phase 2b trial.

This is the largest, randomized, controlled, double-blind psilocybin treatment clinical trial completed to date.

The objective of the Phase 2b study was to evaluate the efficacy and safety of a single dose of investigational COMP360 psilocybin (25mg or 10mg), compared to 1mg, in patients with TRD.

The results from the 233-participant trial showed a rapid and sustained response for patients receiving a single 25mg dose of COMP360 psilocybin administered with psychological support, with 29.1% of participants in remission by week 3 (p<0.002).

The trial achieved its primary endpoint for the 25mg dose, with a 25mg dose of COMP360 demonstrating a statistically significant (p<0.001) and clinically relevant treatment difference against the 1mg dose of COMP360 in reducing depressive symptom severity after three weeks.

The trial achieved its primary endpoint for the 25mg dose, with a 25mg dose of COMP360 demonstrating a statistically significant and clinically relevant treatment difference against the 1mg dose of COMP360 in reducing depressive symptom severity after three weeks.

At the beginning of 2023, we commenced our Phase 3 program evaluating our COMP360 psilocybin treatment in TRD.

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a single dose (25mg) monotherapy compared with placebo.

This trial is designed to replicate the treatment response seen in our Phase 2b trial (n=233).

We expect to report top-line data in the fourth quarter of 2024.

• Pivotal trial 2 (COMP006) (n= 568):

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25mg, 10mg and 1mg.

This trial is designed to investigate whether a second dose can increase treatment responders and whether a second dose can improve responses observed in our Phase 2b trial and to explore the potential for a meaningful treatment response from repeat administration of COMP360 10mg.

We expect to report top-line data by mid-2025.

This trial is designed to investigate whether a second dose can increase therapeutic response.

• The primary endpoint in both pivotal trials is the change from baseline in the MADRS (Montgomery-Åsberg Depression Rating Scale) total score at week 6.

Beyond TRD, we have ongoing Phase 2 trials in PTSD and anorexia nervosa.

We also provide support to research institutions conducting investigator-initiated studies, or IISs, with COMP360 psilocybin in areas of serious unmet need.

These are signal-generating studies that we believe may provide signals for new potential indications that we can explore further and may bring into our development pipeline.

For example , the University of California San Diego School of Medicine completed an IIS of COMP360 psilocybin in anorexia nervosa and presented positive data from this study at the Society of Biological Psychiatry Annual Meeting in May 2022.

Based on the data generated in this IIS, we decided to proceed with a Phase 2 clinical trial for anorexia nervosa.

Additional IIS studies are underway in a number of other indications including autism, suicidal ideation and severe TRD.

The need for innovation in mental health care is significant, given that the current treatment paradigm is ineffective for millions of people.

Our vision is a world of mental wellbeing – a world in which mental health isn’t simply the absence of

mental illness, but the ability to flourish.

We want to help reduce the stigma surrounding mental health, to acknowledge that “everyone has a story,” and to create a system of care for all who are not helped by the existing system and existing therapies.

Beyond TRD, we have been exploring other indications, including PTSD.

In May 2024, we completed and announced top-line results from our open label Phase 2 study to assess the safety and tolerability of COMP360 psilocybin treatment in participants with PTSD, as a result of trauma experienced as adults.

In line with the study design, the study enrolled 22 participants, who were monitored for a 12-week period post dosing.

The study met its primary safety endpoint and available secondary efficacy endpoints.

Study observations included meaningful and sustained symptom improvement from baseline in mean CAPS-5 total score, a measure of disease severity, and in Sheehan Disability Scale (SDS) score, a measure of functional impairment in daily life.

Administration of COMP360 was well-tolerated, with a safety profile consistent with previous studies of COMP360.

Based on the data from this trial, we are in the process of designing a late-stage PTSD program.

The need for innovation in mental health care is significant, given that current treatment options are ineffective for millions of people.

Our vision is a world of mental wellbeing – a world in which mental health isn’t simply the absence of mental illness, but the ability to flourish.

We want to help reduce the stigma surrounding mental health, to acknowledge that “everyone has a story,” and to develop paradigm-changing new treatments for those who are not helped by existing treatment options.

Our mission is to accelerate patient access to evidence-based innovation in mental health.

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• Advance our Phase 3 registrational program for our investigational COMP360 psilocybin treatment for the treatment of TRD.

In 2021, we completed a randomized, controlled Phase 2b clinical trial in 233 TRD patients, in 22 sites across North America and Europe and a Phase 2 exploratory trial in 19 TRD patients.

We announced positive top-line results from these trials in November and December 2021.

The results from our Phase 2b clinical trial were published in the New England Journal of Medicine in November 2022.

We commenced our Phase 3 registrational program and expect to report top-line data from our COMP005 study in the fourth quarter of 2024 and from our COMP006 study in mid-2025.

• Expand our investigational COMP360 psilocybin treatment into new indications.

We believe that our investigational COMP360 psilocybin treatment may confer beneficial effects in other areas of high unmet need in mental health.

We are conducting Phase 2 trials evaluating COMP360 psilocybin treatment in PTSD and anorexia nervosa.

In addition, we are generating preclinical and clinical data to further our mechanistic understanding and explore the potential benefits of our COMP360 psilocybin treatment in other indications.

We are performing some of these studies ourselves and some through collaborations with academic institutions, including through IISs.

The outcomes of these studies will help inform which indications we may pursue.

• Explore other compounds to address areas of unmet need.

Our internal discovery efforts are focused on value propositions that meet unmet patient needs and ensure differentiation against our COMP360 psilocybin treatment and the broader competitive landscape.

Ongoing research on prodrug development has led to a number of potential candidate leads being identified that we plan to continue through further research-based development.

The outcomes of these studies will help inform which compounds and drug candidates we may pursue.

• Maximize the reach and value of our investigational COMP360 psilocybin treatment by creating a new model for mental health care.

In 2021, we completed a randomized, controlled Phase 2b clinical trial in 233 TRD patients, at 22 sites across North America and Europe.

We announced positive top-line results from this trial in November 2021, the results of which were published in the New England Journal of Medicine in November 2022.

Based on the results from the Phase 2b trial, we advanced clinical development in TRD and our Phase 3 registrational program is ongoing.

We are nearing completion of enrollment in our first pivotal study in TRD, COMP005, and expect to report top-line 6-week data in the second quarter of 2025.

We expect to report 26-week data from our COMP006 study in the second half of 2026.

• Expand our investigational COMP360 psilocybin treatment into new indications, with our next focus on advancing a late-stage development program in PTSD.

We believe that our investigational COMP360 psilocybin treatment may offer beneficial effects in other areas of high unmet need in mental health.

Following positive Phase 2a results in May 2024 and securing additional funding in the first quarter of 2025, we are now in the process of designing a late-stage program in PTSD.

• Maximize the potential to reach patients and realize the value of our investigational COMP360 psilocybin treatment by creating a new approach to treating mental health conditions.

We retain global development and commercialization rights for our investigational COMP360 psilocybin treatment and are developing a commercial rollout plan in the event we are granted approval from regulatory authorities, working with payors to enable reimbursement and with health systems to enable broad patient access.

We engage with the broader healthcare ecosystem to drive innovation in research in mental health and inform models for delivery for COMP360 psilocybin, including to gather evidence to optimize our therapy model, training of therapists, and prototype digital technology solutions to improve patient experience and outcomes.

We established a Center of Excellence, with The Sheppard Pratt Institute for Advanced Diagnostics and Therapeutics, in Baltimore, Maryland and The Center for Mental Health Research and Innovation with King’s College London and South London and Maudsley NHS Foundation Trust, or SLaM.

Recently, we entered into research collaborations with Hackensack Meridian Health, a leading not-for-profit health care organization in New Jersey, and Greenbrook TMS, which operates through 130 company-operated treatment centers throughout the United States, to research and investigate models for the delivery of scalable, commercial COMP360 treatment within healthcare systems, assuming FDA approval.

• Use digital technology to improve access to and the impact of our investigational COMP360 psilocybin treatment.

We are exploring ways to use digital technology to make our treatment delivery model more scalable, and to improve patient experience and outcomes.

We plan to build upon the technologies we are deploying during our clinical trials, including our myPathfinder app, which is designed to help patients prepare for their COMP360 psilocybin treatment experience, and Therapist COMPanion a web-based “shared knowledge” interactive platform to complement our face-to-face and clinical therapist training.

We are also developing Chanterelle, our AI (which we refer to as Augmented Intelligence as well as Artificial Intelligence) and analytics solution through which we aim to generate novel insights into the predictors and drivers of therapeutic outcomes, the patient experience, and therapist performance.

We believe this may enable us in the future to offer a personalized, preventative and predictive care model.

The following table summarizes the status of our pipeline:

Delivering COMP360 is expected to require the ability to implement COMP360 seamlessly within a provider’s operating practice.

In order to ensure we understand implementation challenges, we have entered into agreements with several representative healthcare delivery centers such as Hackensack Meridian Health, a leading not-for-profit health care organization in New Jersey, and Greenbrook TMS (acquired by Neuronetics, Inc.

in December 2024), which operates a network of treatment centers throughout the United States.

The purpose of these agreements is to research and investigate models for the delivery of scalable, commercial COMP360 treatment within different types of healthcare delivery systems, assuming FDA approval.

We are currently focusing our efforts on progressing our Phase 3 clinical program in TRD and starting a late-stage development program in PTSD.

The following table summarizes the status of all our pipeline assets:

Investigational COMP360 Psilocybin Treatment

We are developing our investigational COMP360 psilocybin treatment for the treatment of a range of mental health conditions, with an initial focus on TRD.

There is a large unmet need for new therapies to improve the response rate and durability of response for patients suffering with TRD.

We believe our investigational COMP360 psilocybin treatment, if successfully developed and approved, represents a promising therapeutic option for TRD, as well as potentially for other mental health and neurological conditions, including PTSD and anorexia nervosa.

There is a large unmet need for new treatments to improve the response rate, remission rate, and durability of response for patients suffering with TRD.

TRD is a subset of MDD.

MDD is a condition characterized by a persistent feeling of sadness and heightened negative emotions.

It is considered a unipolar condition, suggesting a distinction between MDD and bipolar depression, the latter of which is often associated with an emotional state fluctuating between depression and hypomania or mania.

MDD is a chronic, relapsing, recurring and serious mental health condition associated with high mortality rates, morbidity and diminished quality of life.

The World Health Organization, or WHO, estimates as of 2023 that approximately 280 million people worldwide are suffering with MDD.

Due to the limitations of existing treatments, nearly one-third of those suffering with MDD are not adequately helped after two or more existing depression treatments.

It is considered a unipolar condition, which is a distinction between MDD and bipolar depression, the latter of which is often associated with an emotional state fluctuating between depression and hypomania or mania.

MDD is a chronic recurring and serious mental health condition associated with high mortality rates, morbidity and diminished quality of life.

The World Health Organization estimates as of 2023 that approximately 280 million people worldwide are suffering with MDD.

The National Institute of Mental Health estimates as of 2021 that MDD affects approximately 21 million adults in the U.S.

It is estimated that approximately 10 million adults with MDD in the U.S.

are treated with medication and that approximately 1/3 of these medication-treated MDD patients, or approximately 3 million patients, are considered to have TRD.

Due to the limitations of existing treatments, approximately one-third of adults with MDD will not respond to oral antidepressants and are considered to have TRD.

TRD is defined as inadequate response to two oral medications.

This condition is referred to as TRD.

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Patients suffering with depression are treated through a variety of approaches, each of which can have significant shortcomings in certain subsets of patients.

Most pharmacotherapies for depression employ the same mechanism of action, targeting the modulation of the brain’s neurotransmitter monoamine levels, and have exhibited limited efficacy in a significant portion of patients and can result in high relapse rates.

There are only two pharmacotherapies specifically approved for TRD in the US:

esketamine, and a combination of olanzapine (an atypical antipsychotic) and fluoxetine (a selective serotonergic reuptake inhibitor).

Most pharmacotherapies for depression target the modulation of the brain’s monoamine receptor system, and have exhibited limited efficacy in a significant portion of patients and can result in high relapse rates.

There are only two medicines approved by the FDA for TRD in the US:

esketamine and the fixed combination of olanzapine/fluoxetine (fluoxetine a selective serotonergic reuptake inhibitor).

Esketamine was approved in 2019 by the FDA.

Mixed efficacy and limited durability were observed in clinical trials, as well as potential side effects, including dissociation and cognitive impairment.

The olanzapine-fluoxetine combination has also shown mixed efficacy and can commonly lead to side effects such as dizziness, drowsiness and weight gain.

In addition to pharmacotherapies, various forms of somatic intervention are also used, although these treatments tend to be invasive and/or onerous, and there is limited data supporting their long-term benefit.

In addition to pharmacotherapies, various forms of somatic intervention are also used, although these treatments tend to be

invasive and/or onerous, and there is limited data supporting their long-term benefit.

Psychotherapy is another common treatment approach, but it requires a significant time commitment and is subject to large variability in availability and administration.

Despite the range of treatments and therapies currently available for depression, patients suffering with TRD

continue to be underserved, prolonging a significant health, social and economic burden.

Despite the range of treatments and therapies currently available for depression, patients suffering with TRD continue to be underserved, prolonging a significant health, social and economic burden.

We believe patients suffering with TRD need a paradigm-shifting treatment that can deliver rapid and sustained relief of their depression.

The following table, which is based on data from the Star*D trial conducted by the National Institute of Mental Health in 2006, indicates the worldwide estimated patient populations suffering with new onset MDD, persistent MDD and TRD, and the primary treatment options available.

Treatment pathway stage New onset depression

Major depressive disorder (MDD) Persistent depression

Major depressive disorder (MDD) Treatment-resistant depression (TRD)

Line of therapy First line Second line Third line +

Patients (worldwide) 320 million 200 million 100 million

(~33% of total)

Available treatments • Antidepressants

• Psychological interventions eg, CBT*

• Antidepressants

• Antidepressant combinations

• Psychological interventions

• Antidepressants

• Augmentation therapy (antidepressants, mood stabilizers, anticonvulsants, atypical antipsychotics.

• Somatic therapy (rTMS*, tDCS*, ECT*, DBS*)

• High-intensity psychological interventions

% relapse 60-70% 50-75% 80-90%

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* CBT = cognitive behavioral therapy;

rTMS = repetitive transcranial magnetic stimulation;

tDCS=transcranial direct current stimulation;

ECT=electroconvulsive therapy;

DBS=deep brain stimulation.

Table adapted from Rush, A.

J., Trivedi, M.

H., Wisniewski, S.

R., Nierenberg, A.

A., Stewart, J.

W., Warden, D., ...

Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps:

a STAR* D report.

American Journal of Psychiatry, 163(11), 1905-1917.

Limitations of Existing Therapies for Depression

Because depression has biological, social, psychological, environmental, genetic, and stress-related determinants, many of which co-occur, treatment options are wide-ranging and often combined.

Current pharmacological and non-pharmacological treatments, such as antidepressants and psychotherapy, respectively, are well-established and efficacious for a subset of MDD patients.

However, many patients experience relapses.

Clinicians lack high-quality evidence and often rely on a trial-and-error approach, course correcting as patients experience these relapses or difficult side effects.

Current pharmacological and non-pharmacological treatments, such as antidepressants and psychotherapy, are well-established and efficacious for a subset of MDD patients.

However, many patients fail to experience any benefit or have only a partial response and often relapse.

Clinicians often rely on a trial-and-error approach, course correcting as patients experience these relapses or difficult side effects.

Experts are beginning to recommend a shift to more multi-modal treatments where different types of therapy are delivered concomitantly (i.e., a mix of pharmacotherapy, psychological/behavioral, and device interventions).

Patients suffering with TRD are treated through a variety of approaches, each of which is associated with significant shortcomings.

Consequently, there remains a need for a fast-acting, tolerable treatment that provides a durable response.

Despite the condition’s largely heterogeneous nature, most pharmacotherapies for depression use the same mechanism of action, targeting the modulation of the brain’s neurotransmitter monoamine levels.

As evidenced by the low response and high relapse rates, these treatments are not effective for a large number of patients.

Various forms of somatic intervention are also used, although there is limited data supporting their long-term benefit.

Esketamine, a TRD therapy, demonstrated mixed efficacy in its pivotal clinical trials, with rapid relapse rates even with adjunctive antidepressants and protracted withdrawal reactions.

Patients suffering with TRD are currently treated through a variety of approaches, each of which is associated with significant shortcomings.

Consequently, there remains a need for a fast-acting, tolerable treatment that provides a durable response in this patient population.

Despite the condition’s largely heterogeneous nature, most pharmacotherapies for depression use the same mechanism of action, targeting the brain’s various monoaminergic neurotransmitters.

As evidenced by low response and high relapse rates, currently approved treatments are not effective for a large number of patients.

We believe currently available options do not adequately meet the needs of patients suffering with TRD and there is a significant need for a new therapeutic approach.

The following table includes representative ranges and approximate costs in the U.S.

market for existing treatments of depression as well as their methods of delivery.

Therapy Route Frequency and duration Strategy ¹

Reimbursement ²

Approximate annual cost per patient ³

Antidepressants:

SSRI/SNRI* Oral 1/day, chronic Mono/

Adjunctive therapy Broad $12 - $8,300

Atypical antipsychotics Oral 1/day - chronic Adjunctive therapy Broad $55 - $20,700

CBT Face-to-face or online 10-20 sessions, 3-4 months Mono/ Adjunctive therapy Broad Averaging $1,000

Esketamine Intranasal 25 - 50 sessions/year, under supervision of a healthcare professional

Adjunctive therapy Limited $33,000 - $45,000

Ketamine** Intravenous 25 - 30 administrations

Adjunctive therapy No $2,500 - $5,000

rTMS Magnetic brain stimulation without anesthesia 5 sessions/ week, 6 - 7 weeks (30 - 35 sessions)

Mono/Adjunctive therapy Limited $6,000 - $12,000

ECT Electric brain stimulation under anesthesia 3 sessions/ week, 4+ weeks Mono/Adjunctive therapy Limited $15,000 - $30,000

VNS Electric pulses sent to the brain Duration varies from patient to patient – stimulator must first be implanted and given at a starting low dose every 5 minutes from day to night Mono/Adjunctive therapy Limited $40,000 - $45,000 for surgical implementation (excluding costs of post-operative device adjustments)

DBS Electrical impulses to the brain through implanted electrodes 3-6 hour operations;

follow up visits Mono/Adjunctive therapy Limited $200,000 - $250,000 for surgical implementation (excluding costs of battery replacements required every 12-24 months costing ~$95,000 for hardware replacement and surgery)

_____________

established common pharmacotherapies for depression;

common psychotherapy for depression;

novel pharmacotherapies for depression;

somatic therapies for depression

* SSRI = selective serotonergic reuptake inhibitor;

SNRI =serotonergic norepinephrine reuptake inhibitor;

** Ketamine is prescribed off-label and is not approved for the treatment of depression

Based on a year of treatment, 150mg/day, augmentation with fluoxetine for U.S.

or citalopram for UK 2.

Government reimbursement or private insurance coverage;

Assumes one treatment course over the year, direct treatment cost only (not related provider cost or total healthcare costs) and where applicable, estimated cost range includes branded and generic treatments.

Pharmacotherapies

There are five main categories of antidepressants available on the market.

These are selective serotonergic reuptake inhibitors, or SSRIs, and serotonergic norepinephrine reuptake inhibitors, or SNRIs, atypical antidepressants, monoamine

oxidase inhibitors, or MAOIs, and tricyclic antidepressants, or TCAs.

These are selective serotonergic reuptake inhibitors, or SSRIs, and serotonergic norepinephrine reuptake inhibitors, or SNRIs, atypical antidepressants, monoamine oxidase inhibitors, or MAOIs, and tricyclic antidepressants, or TCAs.

These are frequently used in first- and second-line treatment of depression and can also be used after this point.

Studies have shown that approximately 50% of patients are not helped by their initial antidepressant treatment.

This figure rises to as high as 70% for subsequent treatments.

Currently approved antidepressants have significant limitations, including delayed onset of action, poor therapy adherence rates and various side effects.

The onset of action for the most commonly used antidepressants is typically between two and three weeks.

Adherence levels are relatively low, with approximately 50% of individuals in primary and psychiatric care not adhering to their prescribed antidepressant medication.

The Star*D trial conducted by the National Institute of Mental Health in 2006 indicates that only approximately 37% of patients achieve remission with their initial antidepressant treatment and once a patient progresses to third and fourth line, their remission rates drop to 14% and 13% respectively.

Currently approved antidepressants have significant limitations, including delayed onset of action, poor therapy adherence rates and substantial side effects.

The onset of action for the most commonly used antidepressants is typically between six and eight weeks.

Adherence levels are low, with average adherence rates for oral anti-depressant medications over twelve months being approximately 25%.

There is limited evidence to effectively guide clinical decisions following non-response or partial response to first-line antidepressant medications.

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Partial response or lack of response thereafter is recommended to be addressed by combining antidepressants from different pharmacological classes, or augmenting with an alternative medication, primarily with atypical antipsychotics, but also mood stabilizers, anticonvulsants, thyroid hormones and stimulants, and N-methyl-D-asparate, or NMDA, antagonists.

Antipsychotics, such as olanzapine, quetiapine and aripiprazole are typically used as adjunctive therapies when there is a lack of notable efficacy with an antidepressant.

Antipsychotics, such as olanzapine, quetiapine, cariprazine and aripiprazole are routinely used as adjunctive therapies when there is a lack of notable efficacy with an antidepressant.

There is an approved combination of olanzapine and fluoxetine (an SSRI) for TRD.

However, using antidepressants and antipsychotics together can have serious side effects, such as weight gain, other metabolic complications, sedation, extrapyramidal side effects (movement disorders), and QTc prolongation, which means the ventricles of the heart take longer than usual to recharge between beats.

Psychotherapies (Including Cognitive Behavioral Therapy, or CBT)

Psychotherapy is a form of talk therapy often recommended as first-line treatment in mild depression and often used as adjunctive therapy for MDD patients.

Two frequently used psychotherapies for depression are CBT and interpersonal therapy, or IPT.

CBT focuses on changing negative thought and behavior patterns.

IPT also looks at negative thoughts and behaviors, but only as they apply to interpersonal relationships and social functioning.

The incremental efficacy of psychotherapy in more severe cases and in later lines of treatment remains questionable.

Psychotherapeutic approaches can be effective for many individuals but require a significant time commitment from patients and are subject to variability in their availability and delivery.

Esketamine/Ketamine

Ketamine is an NMDA receptor antagonist that has been used for several decades in sedation, anesthesia and chronic pain.

The S-enantiomer of ketamine, esketamine, is administered intranasally as a spray and has been approved by the FDA to treat TRD (2019) and depressive symptoms in adults with MDD with acute suicidal ideation or behavior (2020).

There are mixed efficacy results associated with the use of esketamine.

Ketamine and esketamine require multiple administration sessions and are associated with a high abuse potential.

Esketamine treatments typically need to be frequently administered, in a controlled environment under medical supervision.

Ketamine is an NMDA receptor antagonist that has been approved by the FDA for use for several decades in sedation and anesthesia.

The S-enantiomer of ketamine, esketamine, is administered intranasally as a spray and has been approved by the FDA to treat TRD in conjunction with an oral antidepressant (2019), to treat depressive symptoms in adults with MDD with acute suicidal ideation or behavior (2020) and as a monotherapy to treat patients with TRD (2025).

Ketamine and esketamine require multiple administration sessions.

Both are DEA Schedule III products indicating potential for abuse.

There are mixed efficacy results associated with the use of esketamine and esketamine treatments require frequent administration in a

controlled environment under medical supervision.

This frequency makes administration costly for payors and burdensome for patients.

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These therapies are generally administered in inpatient settings.

Somatic and device-related interventions like ECT and VNS are associated with significant adverse reactions and interventional concerns, such as use of general anesthesia and memory loss in the case of ECT, and surgical intervention and infection risk with VNS implantation.

Limitations of rTMS include inadvertent seizures, pain, face twitching and application discomfort.

Similarly, DBS has the potential to cause pain and seizures as well as a high risk of infection due to the invasiveness of the surgical procedure.

Somatic and device-related interventions like ECT and VNS are associated with significant adverse reactions and interventional risks, such as use of general anesthesia and memory loss in the case of ECT, and surgical intervention and infection risk with VNS implantation.

Limitations of rTMS include seizures, pain, face twitching and application discomfort.

Similarly, DBS has the potential to cause pain and seizures.

These treatments are typically reserved for patients who have not been helped by other treatments, and are characterized as high-cost treatment options with reimbursement limited for a subset of these therapies.

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Post Traumatic Stress Disorder

PTSD is a serious mental health condition that can impact quality of life and lead to diminished cognitive and psychosocial functioning, fractured relationships, inability to maintain employment, substance abuse, high healthcare utilization costs, increased depression, and suicide risk.

Like TRD, PTSD is a heterogeneous syndrome that can impact quality of life and lead to diminished cognitive and psychosocial functioning, fractured relationships, inability to maintain employment, substance abuse, high healthcare utilization costs, increased depression, and suicide risk.

In some people, PTSD can be difficult to distinguish from anxiety and/or depression.

PTSD can occur in people who have experienced or witnessed a traumatic event, such as a natural disaster, serious accident, war or rape.

People who experience PTSD may relive their traumatic experience(s) through nightmares and flashbacks, have difficulty sleeping, and feel detached or estranged.

People who experience PTSD may relive their traumatic experience(s) through nightmares and flashbacks, have difficulty sleeping, experience intrusive thoughts and feel detached or estranged.

Some people with PTSD experience symptoms immediately after the event, while for others symptoms may appear years later.

It is estimated that approximately 311 million people will experience PTSD at some point during their lives.

It is estimated that approximately 311 million people globally will experience PTSD at some point during their lives.

Only 20 -30% of patients treated with currently approved pharmacological interventions for PTSD will reach full remission.

Anorexia Nervosa

Anorexia nervosa is a serious mental health condition characterized by severe restriction of calorie intake and a preoccupation with weight and shape.

People with anorexia nervosa generally restrict their caloric intake, types of food they eat, and might engage in purging behaviors, such as strenuous exercise, vomiting, and laxatives misuse.

It carries the highest mortality rate of all psychiatric disorders.

This high mortality rate is explained in part by the physical complications (muscle and bone problems, such as osteoporosis;

damage to the brain leading to seizures and memory issues;

and heart problems including heart failure) and in part by an increased rate of suicide;

approximately 20% of deaths in anorexia nervosa are thought to result from suicide.

Approximately 3.9 million people globally suffer from anorexia nervosa as of 2019;

it has a lifetime prevalence of approximately 4% in females.

There are no pharmacological treatments approved to treat anorexia nervosa and psychological treatments have relapse rates as high as 52%.

In the U.S., approximately 13 million people suffer from PTSD every year.

PTSD disproportionately affects certain demographics including women, people from different racial and ethnic backgrounds and military veterans.

The total economic burden for PTSD in the US surpassed $232.2 billion in 2018, or $19,630 per individual with PTSD.

Psilocybin Therapy

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There is an accumulating body of evidence that psilocybin may have beneficial effects on depression and other mental health conditions.

We believe the benefits of psilocybin are largely derived from its mechanism of action.

We believe that there are multiple mechanisms of action for psilocybin that could provide clinical benefit.

As shown in the graphic below, by activating a distinct set of receptors in brain areas critical to mood and cognition, psilocybin acts to induce a range of downstream effects that may have important, sustained effects on brain function.

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Stimulation of 5-HT 2A receptors results in downstream cascades via G-protein signaling.

Altered extracellular release of dopamine lead s to enhanced positive mood .

Simultaneous effects involving multiple neurotransmitters and neuronal activation/signaling.

Down-regulation of the default mode network, or DMN, and de-synchronization of cortical activity as well as the emergence of new patterns of functional connectivity across the brain.

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In particular, many of the prominent acute effects of psilocybin, such as changes in emotion and cognition, are thought to be mediated by 5-HT 2A receptor stimulation, an interpretation that is supported by the fact that blocking the 5-HT 2A receptor prevents the psychedelic effects of psilocybin in humans.

This mechanism of 5-HT 2A receptor stimulation is also implicated as a possible component of the antidepressant action of SSRIs, although these operate by inhibiting reuptake of serotonin by presynaptic neurons.

This mechanism of 5-HT 2A receptor stimulation is also implicated as a possible component of the antidepressant action of SSRIs, although these are thought to operate by inhibiting reuptake of serotonin by presynaptic neurons.

In contrast, psilocin is believed to initiate an antidepressant effect by directly activating this receptor.

The relevance of 5-HT 2A receptors in modulating depressive symptoms may also be supported by the fact that these receptors are abundantly expressed in multiple areas of the brain that have important roles in regulating cognitive and emotional processing.

For instance, 5-HT 2A receptors are predominantly expressed in cortical pyramidal neurons, the most abundant type of neuron found in the human cerebral cortex, and thus may be implicated in executive function.

Additionally, 5-HT 2A receptors are expressed in other key regions of the brain, like the hippocampus and nucleus accumbens, which are associated with crucial biological functions like memory and reward processing, respectively.

The relevance of 5-HT 2A receptors in modulating depressive symptoms may is supported by the abundant expression of these receptors in areas of the brain that have important roles in regulating cognitive and emotional processing.

Additionally, 5-HT 2A receptors are expressed in other key regions of the brain, like the hippocampus and nucleus accumbens, which are associated with functions like memory and reward processing, respectively.

Cellular Effects:

Activation of Downstream Signaling Cascades

Activation of 5-HT 2A receptors by agonist ligands such as psilocin can modulate a number of downstream signaling cascades to alter the structure and function of neurons, which are the primary signaling components of the CNS.

The 5-HT 2A receptor is a G-protein coupled receptor, which means that it predominantly relays signals through a family of proteins called G-proteins.

receptor is a G-protein coupled receptor, which means that it predominantly relays signals through a family of proteins called G-proteins.

Specifically, the main signaling cascade downstream of 5-HT 2A receptors occurs via the Gα q/11 protein and leads to increased intracellular calcium release within the cell.

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The activation of neurons, or depolarization, corresponds to positive ions flowing into these cells, which ultimately drives signal transmission and communication between neurons.

Neuroplasticity refers to the ability of the nervous system to reorganize its structure, function, and connections.

Neuroplasticity refers to the ability of the nervous system to reorganize its structure and connections leading to new or adapted functions.

This can involve the generation of new neurons, changes in neuron morphology and connectivity, and neurobiochemical changes in receptor and neurotransmitter levels.

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The fact that EGR-1 and EGR-2 appear to be induced specifically by psychedelic compounds suggests that these genes could be relevant to the acute and sustained effects of these drugs.

Alterations in neurotransmitter release are another local circuit-level consequence of psilocin that may be relevant to its psychoactive and mood effects.

Specifically, evidence from rodent studies suggests that psilocybin may alter extracellular release of serotonin and dopamine in brain areas such as the prefrontal cortex .

By virtue of the extracellular neurotransmitter release changes in certain brain areas, which have established roles in, for example, executive function, psilocybin may drive positive mood effects.

Systemic Effects:

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These brain network alterations may indicate the emergence of novel patterns of connectivity upon decoupling of the DMN and could lead to longer-term changes, such as altered emotional processing, that may ultimately affect behavior.

Investigational COMP360 Psilocybin Treatment Clinical Development Programs

Investigational COMP360 Psilocybin Clinical Development Programs

COMP360 is our proprietary psilocybin formulation that includes our pharmaceutical-grade polymorphic crystalline psilocybin, optimized for stability and purity.

Our investigational COMP360 psilocybin treatment comprises administration of our COMP360 with psychological support from specially trained therapists with specific professional and educational qualifications.

We are conducting clinical trials in TRD, PTSD and anorexia.

COMP360 Psilocybin Treatment Protocol

Our psilocybin treatment comprises administration of COMP360 with psychological support from specially trained therapists.

Psychological support is designed to facilitate patient safety and optimal therapeutic outcomes.

Our psychological support model is manualized and standardized for consistent delivery across all our trial sites.

Our model is delivered over three different phases:

preparation, the COMP360 administration session, and integration.

Our psilocybin treatment takes place over a period of several weeks, and comprises:

We have conducted and/or are conducting clinical development programs in TRD, PTSD and anorexia nervosa.

In our clinical trials, health care professionals, who possess an active license in good professional standing and have the relevant education, experience and training, are engaged and adhere to the below protocols, which are designed to monitor and safeguard clinical trial participants during their psychedelic experience.

We have a manualized and standardized process to train healthcare professionals for consistent delivery across all our trial sites.

An outline of the support model used in our clinical trials and our training program was published in January 2025 in the peer-reviewed American Journal of Psychiatry.

Our trial protocols provide that such support is delivered over three different phases:

preparation, the COMP360 administration session, and post-administration follow-up (integration).

• Preparation:

The objectives of the preparation sessions are to establish a therapeutic alliance between the patient and therapist, and to demonstrate and practice the skills of self-directed inquiry and experiential processing, which we believe are critical for embracing the psychedelic experience in the psilocybin administration session.

The objectives of the preparation sessions are to establish a therapeutic alliance between the patient and healthcare professional, and to demonstrate and practice the skills of self-directed inquiry and experiential processing, which we believe are critical for embracing the psychedelic experience in the psilocybin administration session.

We have created an online preparation platform and MyPathfinder app for patients where they can learn more about what to expect from the experience and how to prepare for it.

• Psilocybin administration:

A psilocybin administration session lasts approximately six to eight hours and a therapist and assisting therapist are present throughout the session.

The therapist’s goal during the session is to establish psychological safety, minimizing anxiety and encouraging openness to all emerging experiences.

The session takes place in a room designed to be ambient, comfortable and calming.

Patients wear eyeshades to help them focus internally, lie on a bed, and listen to a carefully curated music playlist through a high-quality sound system and earphones.

• COMP360 administration:

A COMP360 administration session lasts approximately six to eight hours and at least one healthcare professional is present throughout the session to monitor and safeguard participants in our clinical trials.

The healthcare professional’s goal during the session is to establish psychological safety, minimize anxiety and encourage openness to all emerging experiences.

The session takes place in a room designed to have a comfortable and calming ambience.

Patients wear eye shades to help them focus internally, lie on a bed, and listen to a carefully curated music playlist through a high-quality sound system and earphones.

After the acute effects of psilocybin subside, patients are evaluated for safety and discharged.

• Post-administration integration:

The objectives of integration sessions are to help patients process the range of emotional and physical experiences facilitated by the psilocybin session and to generate insights that can lead to cognitive and behavioral changes.

We believe psilocybin treatment can give patients a sense of agency, whereby they feel separate from their symptoms and empowered to make changes in their lives.

Therapists in our clinical trials are required to have an active unrestricted professional license to practice as a clinical psychologist, psychiatrist, social worker or mental health counselor.

Therapists must also meet the required training and credentialing standards to practice psychotherapy in their region.

Those who have active, unrestricted professional licenses as mental health nurses or any other mental health professional may be eligible to practice as a therapist in our clinical trials, subject to fulfilling criteria around equivalent clinical experience and psychotherapy training as the professionals listed above.

Our method of psychological support is based on our current understanding of psilocybin’s potential to generate new insights and perspectives leading to reduced rigidity in thinking.

This modification of thought patterns can be uncomfortable or anxiety-provoking.

Therapists refrain from intervening with the patient’s experience, unless required for safety reasons.

Such an approach differs from some forms of psychotherapy which can be more directive and interventional.

Our therapist training program sets out a formal and scalable methodology for psychological support delivered during the psilocybin treatment.

It will continue to evolve as we progress COMP360 psilocybin treatment through clinical trials, but this manualized approach to the training program is an important first step in reducing variation in psychological support and setting out a framework for training and evaluation of this support.

Details of the program were published in February 2021 in the peer-reviewed journal Frontiers in Psychiatry.

• Post-administration follow-up (integration):

The objectives of the follow-up sessions are to help patients process the range of emotional and physical experiences facilitated by the psychedelic experience and to integrate any new insights that can lead to cognitive and behavioral changes.

We believe COMP360 psilocybin can give patients a sense of agency, whereby they feel separate from their symptoms and empowered to make changes in their lives.

The methods used in our clinical trials are based on our current understanding of psilocybin’s potential to disrupt dysfunctional neural pathways, to allow patients to generate new insights and perspectives leading to reduced negativity or rigidity in thinking.

This rapid modification of thought patterns can be uncomfortable or anxiety-provoking.

In our clinical trials, healthcare professionals refrain from intervening with the patient’s experience, unless required for safety reasons.

Phase 2b Trial of Our COMP360 Psilocybin Treatment in TRD

In 2021, we completed a Phase 2b international multi-site, randomized, controlled, double-blind, dose-finding clinical trial to assess the safety and efficacy of active doses of COMP360 (10mg or 25mg) compared with 1mg COMP360, administered with psychological support, in 233 patients suffering with TRD, across 22 trial sites in 10 countries in North America and Europe.

In November 2022, The New England Journal of Medicine , the world’s leading peer-reviewed medical journal, published the positive results from our Phase 2b trial of COMP360 psilocybin treatment for TRD.

Patients who are on serotonergic medications were expected to taper off their medicine at least two weeks prior to the baseline (Day -1) visit.

Prior to administration, patients received at least one, and up to three, preparatory sessions with an assigned therapist, in order to be informed and prepared for the COMP360 psilocybin session.

During the COMP360 psilocybin session, a single dose of COMP360 was administered to patients.

The objective was to provide a safe and supportive environment during the session.

Patients received two post-administration integration sessions with their therapists in which the psychedelic experience was discussed.

Patients were followed up for 12 weeks, with a visit the day after administration followed by an additional six visits, weekly for the first three weeks, and every three weeks for the remaining nine weeks.

In 2021, we completed a Phase 2b international multi-site, randomized, controlled, double-blind, dose-finding clinical trial to assess the safety and efficacy of active doses of COMP360 (10mg or 25mg) compared with 1mg COMP360 in 233 patients suffering with TRD, across 22 trial sites in 10 countries in North America and Europe.

In November 2022, The New England Journal of Medicine published the positive results from our Phase 2b trial of COMP360 psilocybin treatment for TRD.

Participants who were on serotonergic medications were required to taper off their medicine at least two weeks prior to the baseline (Day -1) visit.

Prior to administration, participants received at least one, and up to three, preparatory sessions with an assigned healthcare professional, in order to be informed and prepared for the COMP360 psilocybin session.

During the COMP360 psilocybin session, a single dose of COMP360 was administered to participants.

The objective was to provide a

safe and supportive environment during the session.

Participants received two post-administration follow-up (integration) sessions with their healthcare professionals in which the psychedelic experience was discussed.

Participants were followed for up to 12 weeks, with a visit the day after administration followed by weekly visits for the first three weeks, and visits every three weeks for the remaining nine weeks.

Primary, secondary and exploratory endpoints

The primary endpoint of this trial was the change in the MADRS total score from baseline to week 3.

MADRS is assessed by independent raters in native language and is a widely accepted assessment of mood disorders.

MADRS, as assessed by independent raters in native language, is a widely accepted assessment of mood disorders.

This variable was also being analyzed for change from baseline to Day 2, weeks 1, 6, 9 and 12.

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• The proportion of participants who had a sustained response at week 12.

Sustained response was defined as the proportion of patients fulfilling response criteria at any visit up to and including week 3, that also fulfills response criteria at all subsequent visits up to and including week 12;

Sustained response was defined as the proportion of participants fulfilling response criteria at any visit up to and including week 3, that also fulfills response criteria at all subsequent visits up to and including week 12;

• Time to event measures:

including restarting of antidepressant medication for any reason, suicidality, hospitalization for depression, and relapse from a previous response to COMP360 psilocybin treatment.

Safety and tolerability of COMP360 in patients suffering with TRD was assessed based on AEs, vital signs, clinical laboratory assessments, ECG findings and suicidal ideation/behavior (measured using the Columbia-Suicide Severity Rating Scale, or C-SSRS score, at all visits).

The safety and tolerability of COMP360 in study participants was assessed based on AEs, vital signs, clinical laboratory assessments, ECG findings and suicidal ideation/behavior (measured using the Columbia-Suicide Severity Rating Scale, or C-SSRS score, at all visits).

The trial also assessed exploratory endpoints including, but not limited to, quality of life (EQ-5D-3L), functional impairment (Sheehan Disability Scale, SDS), psychosocial functioning (Work and Social Adjustment scale, WSAS), cognition (Digit Symbol Substitution Test, DSST), anxiety (Generalized anxiety disorder, GAD-7), and self-reported depression severity (QIDS-SR-16).

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We recruited a total of 233 adult patients with TRD into the trial.

We define TRD patients as those who meet Diagnostic and Statistical Manual of Mental Disorders, 5 th Edition, or DSM-5, diagnostic criteria for a single or recurrent episode of MDD without psychotic features, who have not responded to an adequate dose and duration of two, three, or four pharmacological treatments for the current episode of depression.

We define patients with TRD as those who meet Diagnostic and Statistical Manual of Mental Disorders, 5 th Edition, or DSM-5, diagnostic criteria for a single or recurrent episode of MDD without psychotic features, who have not responded to an adequate dose and duration of two, three, or four pharmacological treatments for the current episode of depression.

Clinical findings

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MADRS = Montgomery-Åsberg Depression Rating Scale

At week 3, 36.7% (29 patients) in the 25mg group were responders (defined as a ≥50% decrease in MADRS total score from baseline), compared with 17.7% (14 patients) in the 1mg group.

Furthermore, 29.1% (23 patients) in the 25mg group were in remission (defined as a MADRS total score ≤10) at week 3, compared with 7.6% (6 patients) in the 1mg group.

week 12, 20.3% (16 patients) in the 25mg group were sustained responders (defined as meeting the MADRS response criteria at week 3 and week 12, and at least at one visit out of week 6 and week 9) compared with 10.1% (8 patients) in the 1mg group.

At week 3, 36.7% (29 patients) in the 25mg group were classified as responders (defined as a ≥50% decrease in MADRS total score from baseline), compared with 17.7% (14 patients) in the 1mg group.

Furthermore, 29.1% (23 patients) in the 25mg group were deemed to be in remission (defined as a MADRS total score ≤10) at week 3, compared with 7.6% (6 patients) in the 1mg group.

At week 12, 20.3% (16 patients) in the 25mg group were sustained responders (defined as meeting the MADRS response criteria at week 3 and week 12, and at least at one visit out of week 6 and week 9) compared with 10.1% (8 patients) in the 1mg group.

MADRS response and remission rates

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Patients meeting the MADRS response criteria at any visit up to and including week 3 and at all subsequent visits up to and including at week 12, and who did not start any new treatments for depression.

As well as looking at clinician-rated depression severity on the MADRS, the trial explored other aspects which are recognized as being important for patients with TRD - and essential to recovery - including positive and negative affect, anxiety, self-rated depression severity, quality of life, functioning and cognition.

As well as looking at clinician-rated depression severity on the MADRS, the trial explored other aspects recognized as being important for patients with TRD - and essential to recovery - including positive and negative affect, anxiety, self-rated depression severity, quality of life, functioning and cognition.

These exploratory measures also showed that patients in the 25mg dose group of COMP360 psilocybin treatment reported benefits on those measures over those in the 1mg group.

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incidence) were headache, nausea, fatigue, and insomnia.

There were 12 patients who reported treatment-emergent serious adverse events (TESAEs).

These TESAEs included suicidal behavior, intentional self-injury, and suicidal ideation, which are regularly observed in a TRD patient population.

There were 12 patients, 5 patients in the 25 mg group, 6 patients in the 10 mg group and 1 in the 1 mg group, who reported treatment-emergent serious adverse events (TESAEs).

These TESAEs included, among others, suicidal behavior, intentional self-injury, and suicidal ideation, which are regularly observed in a TRD patient population.

Two thirds of the patients had previous thoughts of wishing to be dead, as assessed by a suicidality scale completed during patient screening;

this included all patients reporting one of these adverse events, meaning that patients who experienced these events during the trial had said in patient screening that they had had suicidal thoughts prior to the trial.

• There was no difference between the three groups post-administration in scores from item 10 on the MADRS, which measures suicidality and was assessed by a blinded remote rater;

mean scores across treatment groups were lower than baseline at all subsequent time points

• 27 of the TEAEs of suicidal ideation, suicidal behavior and intentional self-injury occurred across 17 patients, with seven patients in the 25mg group, six in the 10mg group, and four in the 1mg group

• 14 of these events of suicidal ideation, suicidal behavior and intentional self-injury were reported as TESAEs;

these occurred across nine patients, with four patients in the 25mg group, four patients in the 10mg group, and one in the 1mg group

• The majority of these TESAEs (10 events out of 14) occurred at least one week after the COMP360 psilocybin session

• All suicidal behaviors occurred at least one month after the psilocybin treatment session and all patients reporting these events were non responders at their last assessment prior to the event or at the time of the event

Overall, 209 patients completed the study;

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Phase 2 Study of COMP360 Psilocybin Treatment as Adjunct to SSRI Antidepressants

In addition to our completed Phase 2b trial, we have also completed a Phase 2 trial of the safety and efficacy of COMP360 in TRD patients when administered as an adjunct to SSRIs.

Results of this study were published in the Nature journal Neuropsychopharmacology in July 2023.

In addition to our completed Phase 2b trial, we also completed a Phase 2 trial of the safety and efficacy of COMP360 in TRD patients when administered as an adjunct to SSRIs.

Results of this study were published in Neuropsychopharmacology in July 2023.

This open-label study included 19 patients from clinical sites in Ireland and the United States.

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Clinical Findings

The baseline MADRS score of patients entering the study was 31.7, representing moderate to severe depression.

At week 3, 8 of the 19 patients (42.1%) were responders and all 8 were also remitters.

The baseline MADRS score of participants entering the study was 31.7, representing moderate to severe depression.

At week 3, 8 of the 19 participants (42.1%) were responders and all 8 were also remitters.

The mean reduction from baseline observed in MADRS total score was 14.9 at week 3.

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Phase 3 Registrational Program and Supportive Studies

We commenced our Phase 3 program evaluating our COMP360 psilocybin treatment in TRD.

Our Phase 3 program evaluating our COMP360 psilocybin treatment in TRD is ongoing.

The Phase 3 program is composed of two pivotal trials, each with a long-term follow-up component.

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a single dose (25mg) monotherapy compared with placebo.

This trial is designed to replicate the treatment response seen in our Phase 2b trial (n=233).

We plan to conduct the COMP005 study mostly at sites in the U.S.

We expect to report top-line data in the fourth quarter of 2024.

We are conducting the COMP005 study at sites in the U.S.

We are nearing completion of enrollment and expect to report top-line six-week data in the second quarter of 2025 and then the 26-week 005 data once all participants in the 006 trial have completed Part A of the ‘006 trial.

• Pivotal trial 2 (COMP006) (n= 568):

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25mg, 10mg and 1mg.

We expect to report top-line data by mid-2025.

This trial is designed to investigate whether a second dose can increase therapeutic response.

We are conducting this study at sites in the U.S., UK, Canada and Europe.

We expect to report 26-week data by the second half of 2026.

• The primary endpoint in both pivotal trials is the change from baseline in MADRS total score at week 6.

Each of these trials will have a pivotal component and a long-term follow-up component.

The long-term follow-up component in both trials is similar.

The long-term follow up component will include a 26 week extension where patients will remain in their original assigned treatment arms and patients who meet criteria for re-treatment will have the option to receive a further treatment session according to their assigned dose.

This will be followed by a 26 week open label component during which all patients who meet criteria for re-treatment will have the option to receive a 25mg dose of COMP360 psilocybin.

We believe that this design will enable us to characterize better the durability of COMP360 administration.

During the first quarter of 2023, we commenced a Phase 2 (n=102) study to investigate the safety and tolerability of COMP360 psilocybin treatment in patients with major depressive disorder, or MDD.

Each of these trials has three parts:

Part A is the primary efficacy portion at Week 6, Part B is a blinded 20 week portion and Part C is a 26-week open-label portion.

In Part B, participants who complete Part A will be followed for 20 weeks and those who meet criteria for re-treatment will have the option to receive an additional treatment dose according to their assigned dose.

Participants who complete part B and go into Part C during which participants who meet criteria for re-treatment may receive a 25mg dose of COMP360 psilocybin.

We believe that this design will enable us to appropriately characterize the efficacy, safety and durability of COMP360 administration.

During the first quarter of 2023, we also commenced a Phase 2 (n=102) study to investigate the safety and tolerability of COMP360 psilocybin treatment in patients with major depressive disorder, or MDD.

In addition, pharmacokinetics of COMP360 psilocybin treatment will be investigated.

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Phase 2 Study in PTSD

We conducted a Phase 2 clinical trial to assess the safety and tolerability of COMP360 psilocybin treatment, administered with psychological support, in people with PTSD, as a result of trauma experienced as adults.

We completed a Phase 2 clinical trial to assess the safety and tolerability of COMP360 psilocybin treatment, as a monotherapy in participants with PTSD, as a result of trauma experienced as adults.

It was a multicenter, fixed-dose open label study.

Participants were required to taper off their medicines.

Twenty-two participants received a single 25mg dose of investigational COMP360 psilocybin treatment.

In line with the study design, participants are being monitored for a 12-week period post dosing.

We plan to announce safety and efficacy data over that period in the spring of 2024.

In line with the study design, participants were monitored for a 12-week period post dosing.

In May 2024, we reported top-line results from this study.

The study met its primary safety endpoint and available secondary efficacy endpoints.

Administration of COMP360 was well-tolerated, with a safety profile consistent with previous studies.

The key findings include:

• Administration was generally well tolerated, with no serious adverse events observed.

There were no treatment-emergent serious adverse events.

Treatment-emergent adverse events included headache (n=11 or 50.0%), nausea (n=8 or 36.4%), crying (n=6 or 27.3%), and fatigue (n=6 or 27.3%).

There were two adverse events of suicidal ideation that resolved during the study.

The first was a moderate and transient event which resolved on administration day in a patient who went on to be a responder, and it was deemed to be related to study drug.

The second event was mild and occurred at week 7 in a non-responder, resolved during the study, and was deemed to be possibly related to study drug.

Both participants had previous history of suicidality as measured by the Columbia-Suicide Severity Rating Scale.

• Durable improvement in symptoms from baseline observed following a single administration.

Improvement in mean CAPS-5 total score from a baseline of 47.5 was observed (29.9 point reduction at week 4 and 29.5 point reduction at week 12).

• Improvement over time in Sheehan Disability Scale (SDS) measure of functional impairment over 12 weeks.

From a mean SDS total score of 22.7 at baseline, there was a 11.7 point reduction at week 4 and a 14.4 point reduction at week 12.

• High and sustained rates of response and remission relative to baseline, with early onset of symptom improvement.

Response, as defined by patients experiencing a ≥ 15-point improvement on CAPS-5 score, was 81.8% at week 4 and 77.3% at week 12.

Remission, as defined by CAPS-5 total score of ≤ 20, was 63.6% at week 4 and 54.5% at week 12.

• No patients withdrew from the study and no patients returned to antidepressant medication treatment during the trial.

The open-label, multi-center, phase 2 safety study evaluated investigational COMP360 psilocybin treatment in 22 patients with PTSD resulting from trauma in adulthood.

Participants received a single 25mg dose along with psychological support.

Psychological support was provided by a licensed medical professional to ensure patient safety, which consisted of preparing participants for the treatment session, observing and being present with patients during the session and supporting them after the session.

Primary endpoint was safety at week 12;

available secondary endpoints were change in CAPS-5 from baseline and change in SDS total score from baseline.

The mean baseline severity of symptoms was a baseline of 47.5 (minimum of 25;

maximum of 64) CAPS-5 total score, which is considered severe.

The CAPS-5 assessment involves a structured interview that provides a PTSD diagnosis and measures symptom severity.

The average age of participants at the time of screening was 39 and patients diagnosed with complex PTSD were excluded from study eligibility.

The study was conducted at The Institute of Psychiatry, Psychology and Neuroscience at King’s College London, Icahn School of Medicine at Mount Sinai in New York and Sunstone Therapies in Rockville, Maryland.

Phase 2 Study in Anorexia

We are conducting a double-blind randomized controlled Phase 2 clinical trial investigating the safety and efficacy of COMP360 psilocybin, administered with psychological support, in people with anorexia nervosa.

It is a multicenter study and will enroll 60 patients.

W e had experienced some delays due to challenges in recruiting and screening participants for our Phase 2 trial in anorexia nervosa.

To address these challenges, we amended the trial protocol and adjusted our procedures.

We closed enrollment in the second half of 2024 for a double-blind randomized controlled Phase 2 clinical trial investigating the safety and efficacy of COMP360 psilocybin in participants with anorexia nervosa.

It is a multicenter study and enrolled 32 patients.

We expect to report data from this study in 2025.

Other Indications:

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Adjusted-response rates for QIDS-SR-16 (defined as ≥50% reduction from baseline in the QIDS-SR-16 total score) at week 6 were 70.2% for the COMP360 arm vs.

48.0% for the escitalopram arm and adjusted-remission rates (defined as a QIDS-SR-16 total score ≤5) at week 6 were 57.1% and 29.1%, respectively.

48.0% for the

escitalopram arm and adjusted-remission rates (defined as a QIDS-SR-16 total score ≤5) at week 6 were 57.1% and 29.1%, respectively.

For the MADRS – a more widely used and accepted clinician-rated scale which Compass is using as the primary endpoint in their clinical trials – a least square means treatment difference of -7.2 was found.

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The primary aim of this study was to assess the safety and tolerability of a single 25mg dose of psilocybin in participants with anorexia nervosa based on adverse events, changes in vital signs, electrocardiograms and clinical laboratory tests.

Forty percent (n=4) experienced clinically meaningful reductions at the 3-month follow-up, based on

global score on the Eating Disorder Examination (EDE).

Forty percent (n=4) experienced clinically meaningful reductions at the 3-month follow-up, based on global score on the Eating Disorder Examination (EDE).

Participants demonstrated nominally statistically significant reductions in shape concerns on the EDE at the 1-month follow-up (mean change from pre-treatment=1.3;

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The investigator published data from this study in The Lancet (Von Rotz et al, Lancet 2023;

In this double-blind, randomized clinical trial, 52 patients with major depressive disorder were randomized 1:1 to receive either a single, moderate dose (0.215 mg/kg body weight) of COMP360 psilocybin or placebo in conjunction with psychological support.

this double-blind, randomized clinical trial, 52 patients with major depressive disorder were randomized 1:1 to receive either a single, moderate dose (0.215 mg/kg body weight) of COMP360 psilocybin or placebo in conjunction with psychological support.

MADRS and Beck's Depression Inventory (BDI) scores were assessed to estimate depression severity and the primary endpoints were defined as changes from baseline to two weeks after the administration of COMP360.

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Preclinical and Drug Discovery Programs

Prior to our strategic reorganization in the fourth quarter of 2024 and decision to stop all non-COMP 360 preclinical activities to allow us to focus entirely on advancing development of our investigational COMP360 psilocybin treatment, we progressed a number of preclinical initiatives during 2024.

We retain rights to these preclinical assets and may in the future decide to resume our preclinical activities.

Mechanistic Studies

We are working with academic researchers and CROs to investigate the mechanistic characteristics of psilocybin treatment.

We have also established a network of PhD studentships predominantly within the United Kingdom (namely at the following universities:

University of Oxford, University of Bristol, University of Reading and University of Southampton) to research elements of this work.

We continue to work with a small group of academic researchers and CROs to investigate mechanistic characteristics of psilocybin treatment.

We currently have a network of studentships predominantly within the United Kingdom (namely at the following universities:

University of Oxford, University of Bristol, University of Reading and University of Southampton, University of Cardiff) to research elements of this work.

Our mechanistic research utilizes our COMP360 and currently focuses on the following themes:

• Study of the mechanisms by which psilocin, the active moiety of our high-purity polymorphic crystalline formulation psilocybin, and other psychedelic agents engage receptors in recombinant cell-based assays (collaboration with Professor Trevor Sharp, University of Oxford).

The aim here is to understand which systems are optimal to use for discovery research, and to understand further how different drugs may influence receptor-mediated signal transduction;

• Through collaborations with the University of Bristol (Professor Matt Jones, in particular) and CROs (e.g.

Neurotar and Synapcell), we are also investigating the integrated electrophysiological response to psychedelic administration, to determine how changes in neuronal excitatory activity mediate brain-wide changes in resting state network activity;

• Preclinical academic collaborations with the University of Bristol, Harvard University, Oxford University and the Southern Denmark University to study the effects of our high-purity polymorphic crystalline formulation of psilocybin on a number of different aspects of behavior, including affective bias, reward learning and compulsive behavior that may provide insights relevant to information processing alterations frequently observed in mental health conditions;

• Collaborations with the University of Reading and the University of Southampton also focus on understanding what the potential role of inflammatory modulating processes might be in the mechanism of action of COMP360;

• A study of the sustained effects of our high-purity polymorphic crystalline formulation psilocybin through the investigation of short- and long-term changes in gene expression (mRNA) and epigenetic regulation (miRNA and DNA methylation) as part of ongoing work with CROs (Sygnature and ActiveMotif)

• A healthy volunteer study with Imperial College London, investigating the acute and long-term psychological and brain effects of psilocybin treatment, using COMP360.

These studies will further our understanding of the mechanism of action and inform our decisions over which other indications to explore, beyond TRD and PTSD.

• Study of the mechanisms by which psilocin, the active moiety of our high-purity polymorphic crystalline formulation of psilocybin, and other psychedelic agents engage receptors in recombinant cell-based assays (collaboration with Professor Trevor Sharp, University of Oxford).

The aim here is to understand which systems are optimal to use for discovery research, how different drugs may influence receptor-mediated signal transduction, and how mechanisms of biased agonism may play into mechanistic effects;

• Through collaborations with the University of Bristol (Professor Emma Robinson and Professor Jack Mellor , in particular), we are also investigating the integrated electrophysiological response to psychedelic administration, to determine how changes in neuronal excitatory activity mediate brain-wide changes in resting state network activity and how these influence sustained changes in behavior;

• Preclinical academic collaborations with the University of Bristol, Harvard University, Oxford University and the Southern Denmark University have studied the effects of our high-purity polymorphic crystalline formulation of psilocybin on different aspects of behavior, including affective bias, reward learning and compulsive behavior that may provide insights relevant to information processing alterations frequently observed in mental health conditions.

In particular, work at the University of Oxford (collaboration with Professor Mark Walton) is utilizing novel behavioral pharmacological techniques to assess the impact of our high-purity polymorphic crystalline formulation of psilocybin for effects on cognitive flexibility at periods hours to days after administration.

Collaborations with the University of Cardiff (Professor Dominic Dwyer) will also consider effects of COMP360 on measures of affective behavior and anhedonia in transgenic mice carrying disease-relevant genetic mutations, and integrate these findings with cellular and electrophysiological changes;

These studies will further our understanding of the mechanism of action for COMP360 and could inform our future decisions over which other indications, if any, to explore, beyond TRD and PTSD.

Drug Discovery Center

On August 5, 2020, we established a Drug Discovery Center under a sponsored research agreement with the University of the Sciences in Philadelphia, Pennsylvania (which merged into Saint Joseph’s University in 2022), or USciences, to focus on developing optimized psychedelic and related compounds targeting the 5-HT 2A receptor, which is believed to mediate the potential therapeutic effects of psychedelics.

Pursuant to the agreement, USciences is performing research services on our behalf, and has granted us an exclusive, royalty bearing, worldwide license, including rights to sublicense, all jointly held intellectual property for any and all purposes, and a non-exclusive, fully paid-up, worldwide license to any pre-existing intellectual property utilized over the course of performing the services.

Under the agreement, we will pay a one-time research service fee of an estimated $0.5 million and tiered payments upon completion of certain milestones by USciences up to an aggregate of $0.9 million per licensed product covered by a valid claim of a patent included in the intellectual property rights licensed to us under the agreement, as well as a low single-digit royalty percentage on annual net sales of licensed products covered by a valid claim of a patent included in the intellectual property rights licensed to us under the agreement , subject to certain reductions.

Further to the strategic reorganization we announced in the fourth quarter of 2024 and our decision to stop non-COMP360 preclinical and discovery work and focus all our resources on advancing development of our investigational COMP360 treatment, this agreement with USciences was not renewed and will terminate in the second quarter of 2025.

Pursuant to the agreement, USciences performed research services on our behalf, and granted us an exclusive, royalty bearing, worldwide license, including rights to sublicense, all jointly held intellectual property for any and all purposes, and a non-exclusive, fully paid-up, worldwide license to any pre-existing intellectual property utilized over the course of performing the services.

As of December 31, 2024, we had identified one compound under this agreement.

If in the future we decide to resume development efforts for this compound, we would be obligated to make tiered payments upon completion of certain milestones to USciences for up to an aggregate of $0.9 million per licensed product covered by a valid claim of a patent included in the intellectual property rights licensed to us under the agreement, as well as a low single-digit royalty percentage on annual net sales of licensed products covered by a valid claim of a patent included in the intellectual property rights licensed to us under the agreement, subject to certain reductions.

In addition, USciences is entitled to a low double-digit percentage of sublicense revenue for agreements entered into prior to a Phase 2 trial, and a mid-single-digit percentage of sublicense revenue for agreements entered into after the start of a Phase 2 trial.

Unless earlier terminated, the agreement terminates upon the expiration or revocation of the last valid claim of any patent included in the joint intellectual property .

We and USciences can terminate the agreement in the event of a material breach by the other party and failure to cure such breach within a certain period of time.

Additionally, we and USciences can terminate the research service in the event of a material safety or regulatory issue with respect to the research service.

We may also terminate the research service at will upon sixty (60) days prior written notice to USciences.

USciences can terminate the research service if such services would materially and negatively interfere with its operations or upon the continuation of a force majeure event.

There are no current licensed patents or patent applications under the sponsored research agreement.

Ongoing research on prodrug development has led to a number of potential candidate leads being identified that we plan to continue through further research-based development.

Ongoing research on prodrug development led to a number of potential candidate leads being identified.

We retain rights to these potential candidates and in the future to the extent that we decide to resume non-COMP360 preclinical activities we may continue such potential candidates through further research-based development.

Delix Therapeutics

On March 6, 2020 we made a strategic investment to acquire 1,250,000 shares of series seed preferred stock in Delix Therapeutics, Inc., a drug discovery and development company researching novel small molecules for use in CNS indications.

Delix Therapeutics develops non-hallucinogenic psychoplastogens, which are molecules capable of promoting neural plasticity without hallucinogenic effects, by modifying existing psychedelics.

These compounds may have potential for a range of neuropsychiatric conditions.

Therapist Training

Our therapist training program was originally designed by experts from the fields of psychology, psychiatry and psychedelic therapy research.

We are continuously evaluating opportunities to improve the quality and scalability of our therapist training program.

To date, we have trained more than 300 therapists, approximately 150 of whom have been approved to lead sessions independently, and approximately 100 of whom are engaged in our active clinical trials.

This number will increase as more sites open for our Phase 3 clinical trials in TRD as well as our other clinical trials.

Therapists are often referred to us by clinical trial sites and are employed by the sites.

Details of our therapist training program were published in February 2021 in the peer-reviewed journal Frontiers in Psychiatry.

Our core training curriculum consists of:

• Tier I - Theoretical Training:

Approximately five hours of self-paced online learning through our interactive therapist training platform, including a therapist manual, videos illustrating the competencies required from therapists throughout preparation, psilocybin administration, and integration sessions with study participants, and self-assessed knowledge checks;

• Tier II - Practical Clinical Skills Training:

Approximately 30 hours of live, remotely-delivered (via Zoom) interactive learning, led by therapist trainers;

• Tier III - Clinical training:

At this stage, therapists review a selection of session recordings from our previous clinical trials (on our interactive therapist training platform), and support one participant in a COMP360 psilocybin treatment study alongside a therapist qualified to lead sessions independently.

Following completion of Tier III, therapists are able to lead sessions independently;

• Tier IV - Continuous Professional Development:

Therapists receive mentoring and support throughout their participation in our clinical studies.

Mentors have access to recordings of sessions (with participant consent) led by their mentees, and are therefore able to provide adequate feedback to ensure fidelity to the psychological support model.

Our therapist training program is currently available to professionals involved in our ongoing studies.

As we scale, we may expand our training to a larger pool of qualified healthcare professionals.

On March 6, 2020 we made a strategic investment to acquire 1,250,000 shares of series seed preferred stock in Delix Therapeutics, Inc., a clinical-stage neuroscience company developing novel neuroplasticity-promoting therapeutics for psychiatric and neurological disorders..

Using Digital Technology

We believe digital technology will change the way patients access psychotherapy services and manage their mental health conditions.

We anticipate software applications will enhance activities traditionally done with an in-person therapist.

We also believe remote consultations will help to remove barriers to accessing treatment such as stigma or lack of transportation.

Furthermore, digital tools will enable greater self-care, as they support patients managing depressive episodes on their own and will be used to complement and augment psychotherapy and pharmacological treatments.

Working with third parties, we currently use digital technology in a number of ways:

We believe digital technology can help increase patient access to mental health treatment and services and manage their mental health conditions.

Furthermore, digital tools have the potential to enable greater self-care, as they may support patients managing depressive episodes on their own and may complement and augment psychotherapy and pharmacological treatments.

Working with third parties, we currently use digital technology in our clinical trials in a number of ways:

• An online and mobile app preparation platform for participants in our TRD trial to educate them and help prepare them for their psilocybin experience;

• A web-based “shared knowledge” interactive therapist training platform, complementing our comprehensive face-to-face training program;

• A web-based “shared knowledge” interactive healthcare professional training platform, complementing our comprehensive face-to-face training program;

• Collection of measurements in our clinical trials, including remote data collection using mobile devices so patients do not need to travel into study sites for all in-clinic visits;

• Collection of some digital phenotyping information through the measurement of human-smartphone interactions;

• Harnessing AI and natural language processing capabilities to potentially characterize the mechanism of change and assess therapist fidelity to our treatment protocol for psychological support.

We are building an in-house digital team with experts in digital technology, engineering, and AI, which we refer to as augmented intelligence as well as artificial intelligence.

We will continue to collaborate with other digital companies to research, develop and ultimately commercialize proprietary digital technology solutions that have the potential to complement and augment our investigational COMP360 psilocybin treatment.

We believe this may enable us to offer a personalized, preventative and predictive care model.

• Harnessing AI and natural language processing capabilities to potentially characterize the mechanism of change and assess fidelity to our treatment protocol for psychological support.

We have built an in-house digital team with experience in digital technology, engineering and AI, which we refer to as augmented intelligence as well as artificial intelligence.

This team has focused on researching and developing proprietary digital tools and technology to test evidence-based methods for assessing mental health treatments.

We are exploring externalizing this team and these technologies and the associated intellectual property to a new company established by our co-founders, George Goldsmith and Ekaterina Malievskaia that could potentially support an evidence-based approach for any company developing or delivering mental health treatments.

We expect to have a final decision on this externalization in the second quarter of 2025.

Manufacturing and Supply

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We use additional contract manufacturers to fill, label, package, store and distribute our drug product.

We currently rely on a single supplier for our API but have identified additional

manufacturers who have the appropriate experience and expertise to act as back-up suppliers of API and fill-and-finish services.

We currently rely on a single supplier for our API but have identified additional manufacturers who have the appropriate experience and expertise to act as back-up suppliers of API and fill-and-finish services.

We believe we maintain sufficient supply of API to avoid any material disruptions in the event of any need to replace one or more of our suppliers.

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In select geographies outside the U.S., we may enter into commercialization collaborations with third parties who have complementary commercial capabilities.

Upon any approval, we intend to offer a range of services to enable the safe and effective use of COMP360 with psychological support in clinical practice.

These services are expected to include therapist training, information and education for patients and healthcare providers, and implementation support for treatment centers, such as guidance on procurement and installation of equipment, certification, and quality assurance.

In order to create a new mental health care model, we have established Centers of Excellence to serve as research facilities and innovation labs.

In January 2021, we established our first Center of Excellence, with The Sheppard Pratt Institute for Advanced Diagnostics and Therapeutics, in Baltimore, Maryland, in the United States.

In strategic collaboration with King’s College London and South London and Maudsley NHS Foundation Trust, or SLaM, we opened The Center for Mental Health Research and Innovation with an overarching goal of accelerating patient access to evidence-based innovation in mental health care by driving forward research in psychedelic therapies through, among other things, the development of working model psychedelic treatment clinics, therapist training programs, conducting clinical trials, and data analysis.

We recognize that COMP360 psilocybin treatment, if approved, represents a new approach for many clinical practices and that delivering COMP360 is expected to require the ability to implement COMP360 seamlessly within a provider’s operating practice.

In order to ensure we understand implementation challenges, we entered into agreements with different types of healthcare delivery centers, including Hackensack Meridian Health, a leading not-for-profit health care organization in New Jersey, and Greenbrook TMS (acquired by Neuronetics, Inc.

in December 2024), which operates a network of treatment centers throughout the United States, to research and investigate models for the delivery of scalable, commercial COMP360 psilocybin treatment within various types of healthcare delivery systems, assuming FDA approval.

We have established Centers of Excellence to serve as research facilities and innovation labs.

In strategic collaboration with King’s College London and South London and Maudsley NHS Foundation Trust, or SLaM, we opened The Center for Mental Health Research and Innovation with an overarching goal of accelerating patient access to evidence-based innovation in mental health care by driving forward research in psychedelic therapies through, among other things, the development of working model psychedelic treatment clinics, training programs, conducting clinical trials, and data analysis.

The Center currently serves as a clinical trial site for our Phase 3 COMP006 trial.

Recently, we entered into research collaborations with Hackensack Meridian Health, a leading not-for-profit health care organization in New Jersey, and Greenbrook TMS, which operates through 130 company-operated treatment centers throughout the United States, to research and investigate models for the delivery of scalable, commercial COMP360 psilocybin treatment within healthcare systems, assuming FDA approval.

Our industry is characterized by many newly emerging and innovative technologies, intense competition and a strong emphasis on proprietary product rights.

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Several biopharmaceutical companies have therapies in clinical development for TRD.

We are aware that Supernus Pharmaceuticals and Neurocrine Biosciences, among others, are developing treatments for TRD or inadequate response to treatment in major depressive disorder.

We are aware that Supernus

Pharmaceuticals, Neurocrine Biosciences, GH Research and Beckley Psytech, among others, are developing treatments for TRD or inadequate response to treatment in major depressive disorder.

Multiple somatic therapies are also used in TRD, such as ECT and rTMS.

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We also face competition from 501(c)(3) non-profit medical research organizations, including the Usona Institute.

In March 2024, Usona Institute announced the launch of its Phase 3 trial evaluating the efficacy and safety of psilocybin 25 mg in as a treatment for major depressive disorder, which is expected to enroll approximately 240 adult patients.

Usona has 26 clinical trial sites, continues to progress its Phase 3 trial and expects to complete the primary endpoint in its Phase 3 trial in April 2025 and the long-term follow-up portion of its Phase 3 trial in April 2026.

Such non-profits may be willing to provide psilocybin-based products at cost or for free, undermining our potential market for COMP360.

In addition, a number of for-profit biotechnology companies or institutions are specifically pursuing the development of psilocybin to treat mental health illnesses, including TRD.

In addition, a number of for-profit biotechnology companies or institutions are specifically pursuing the development of psilocybin to treat mental health illnesses, including Cybin Inc.

In March 2024, Cybin announced the design of its Phase 3 program for its deuterated psilocybin analog for the adjunctive treatment of major depressive disorder, which includes two Phase 3 trials and is expected to enroll approximately 550 adult patients.

In November 2024, Cybin announced the initiation of its Phase 3 program.

We are aware of other organizations or institutions evaluating the use of psilocybin in mental health and neurocognitive conditions.

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Patents and Patent Applications or PCT National Stage Applications

US 10,519,175 Methods of treating treatment-resistant depression ca.2038* Applications filed in Australia, Brazil, Canada, China, Colombia, Eurasian Patent Organization, European Patent Office, Indonesia, Israel, India, Japan, Republic of Korea, Mexico, Malaysia, New Zealand, Philippines, Saudi Arabia, Singapore, Thailand, and South Africa.

US 10,519,175 Methods of treating treatment-resistant depression ca.2038* Australia, Brazil, Canada, China, Colombia, Eurasian Patent Organization, European Patent Office, Hong Kong, Indonesia, Israel, India, Japan, Republic of Korea, Mexico, Malaysia, New Zealand, Philippines, Russia, Saudi Arabia, Singapore, Thailand, and South Africa.

US 10,947,257 Oral dosage forms of crystalline psilocybin;

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