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Item 1. Business

2024-02-29 compared with 2023-02-28 · 318 added, 609 removed, 972 unchanged (49% of the section changed)

We are a mental health care 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 therapies, and are pioneering the development of a new model of psilocybin therapy, in which our investigational COMP360 psilocybin is administered in conjunction with psychological support.

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.

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 therapy - 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, anorexia-nervosa and post-traumatic stress disorder, or PTSD .

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.

Early signals from academic studies, using formulations of psilocybin not developed by us, have shown that psilocybin therapy may have the potential to improve outcomes for patients suffering with TRD, with rapid reductions in depression symptoms and effects lasting up to six months, after administration of a single high dose.

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

In 2019, we completed a Phase 1 clinical trial administering COMP360, along with psychological support, to 89 healthy volunteers.

In this trial, we observed that COMP360 was generally well-tolerated and supported continued progression of Phase 2b studies.

We also demonstrated the feasibility of administering COMP360 psilocybin to up to six healthy participants simultaneously, with 1:1 support.

In November 2021, we announced positive topline results from our Phase 2b clinical trial evaluating COMP360 in conjunction with psychological support 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.

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

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 topline 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 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.

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

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

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 the Company’s Phase 2b trial (n=233).

We expect top-line data in summer of 2024.

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/or improve responses observed in our Phase 2b trial and explore the potential for a meaningful treatment response from repeat administration of COMP360 10mg.

We expect top-line data by mid-2025.

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

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

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.

• 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.

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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, body dysmorphic disorder, suicidal ideation and severe TRD.

The need for innovation in mental health care is significant, given that the current 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.

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.

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Key elements of our strategy to achieve this include:

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

• 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 topline results from these trials in November and December 2021.

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 topline data from our COMP005 study in the summer of 2024 and from our COMP006 study in mid-2025.

• Expand our investigational COMP360 psilocybin therapy into new indications.

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

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

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

We are performing some of these studies ourselves and some through collaborations with academic institutions, including through IISs and through our Discovery Center which is carrying out preclinical research into new compounds.

The outcomes of these studies will inform which indications, compounds and therapies we may pursue.

• Explore other compounds and therapies to address areas of unmet need.

We established our Discovery Center, initially based at University of the Sciences in Philadelphia, to include a network of expert teams across the United States, and we are focused on developing optimized psychedelic and related compounds targeting the 5-HT2A receptor, which is believed to mediate the potential therapeutic effects of psychedelics.

We have also acquired an intellectual property portfolio including patent applications covering a variety of psychedelic and empathogenic substances, and we are working on an exclusive research project with inventor Matthias Grill PhD, founder and CEO of MiHKAL GmbH in Basel, Switzerland, to develop new product candidates.

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.

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

We retain global development and commercialization rights for our investigational COMP360 psilocybin therapy 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 have and may in the future continue to set up research facilities and innovation labs, which we refer to as Centers of Excellence, in key markets.

Through these, we also intend to gather evidence to optimize our therapy model, training and certification of therapists, and prototype digital technology solutions to improve patient experience and outcomes.

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

We believe the Centers of Excellence will give us a firm foundation from which to grow and develop potential new business models as we seek to expand access to our investigational COMP360 psilocybin therapy, if approved.

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

We are exploring ways to use digital technology to make our therapeutic 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 therapy 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 an 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 to offer a personalized, preventative and predictive care model.

Our Market Opportunity

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

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.

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:

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 therapy, if successfully developed and approved, represents a promising therapeutic option for TRD, as well as potentially for other mental health and neurological conditions, including anorexia nervosa and PTSD.

MDD and TRD Prevalence

Globally, more than 320 million people suffer from MDD.

The economic burden of MDD in the United States, accounting for comorbid physical and psychiatric conditions, is estimated to be over $200 billion per year.

TRD, a condition affecting the approximately 100 million patients worldwide who are not helped after two or more existing depression treatments, has even greater economic and societal cost than non-TRD MDD.

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.

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.

This condition is referred to as TRD.

TRD has greater economic and societal cost than non-TRD MDD.

TRD patients are often unable to perform daily tasks, are more likely to receive disability or welfare benefits and more frequently have co-occurring conditions compared with non-TRD MDD patients.

Direct medical costs for TRD patients are estimated to be two to three times higher than for non-TRD MDD patients, caused by, among other factors, increased rates of hospitalization and longer average hospital stays.

In several studies, the direct medical costs for patients with TRD were significantly higher than those for non-TRD MDD patients, driven by, among other factors, increased rates of hospitalization and longer average hospital stays.

Patients with TRD have a higher all-cause mortality compared with non-TRD MDD patients.

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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 are 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 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.

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

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 2015 that more than 320 million people worldwide are suffering with MDD and that MDD currently accounts for an average of 7.5% of years of life lost due to disability globally, as defined by disability-adjusted life years, or DALYs, or the sum of years of healthy life lost to either mortality or non-fatal illness or impairment.

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.

This condition is referred to as TRD.

We estimate the TRD population to be approximately 100 million people globally, based on the most recently available data in 2010.

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.

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

Economic and Societal Burden

The economic burden of MDD in the United States, accounting for comorbid physical and psychiatric conditions, is estimated to be over $200 billion per year as of 2010.

Approximately 47% of this figure is attributable to direct costs including outpatient, inpatient, emergency, medical and pharmaceutical cost, while the rest is attributable to indirect costs, including loss of productivity, absenteeism and suicide.

Between 2005 and 2010, the economic burden of MDD rose by $37.3 billion, an increase of 21.5%.

A large proportion of this increase can be attributed to direct costs such as outpatient and inpatient medical

services, with an increase of 27.5% from $77.5 billion in 2005 to $98.9 billion in 2010.

This figure demonstrates that the economic burden of MDD is large, and we believe it is likely to continue to grow over time.

Economic Burden of Individuals with MDD

(U.S., 2010) in $B

Total = $211B

TRD patients are often less productive at work and have higher rates of unemployment.

They are also more likely to receive disability or welfare benefits than non-TRD MDD patients.

Employees suffering with TRD have higher rates of workplace absenteeism compared with those without a mental health condition.

In addition, co-occurring conditions, such as hypertension, anemia and diabetes, are more common in TRD patients versus non-TRD MDD patients.

Direct medical costs for TRD patients are estimated to be two to three times higher than for non-TRD MDD patients.

An analysis from commercial claims and Medicare/Medicaid data in the United States points to average annual healthcare costs of between $17,000 and $25,000 per TRD patient per year.

This compares with less than $10,000 per year for non-TRD MDD patients.

TRD patients have higher prescriptions costs, more doctor visits and increased rates of hospitalization.

TRD patients also have, on average, twice the number of inpatient visits compared with non-TRD MDD patients and, on average, their hospital stay is approximately 36% longer.

Every year, approximately 800,000 people die from suicide globally.

For each adult suicide death, estimates suggest there may have been more than 20 other attempts.

Patients with TRD have a higher all-cause mortality compared with non-TRD MDD patients.

Research conducted in 2018 suggests that the proportion of patients suffering with TRD attempting suicide at least once during their lifetime could be as high as 30%.

Existing Therapies for Depression

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.

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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

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

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

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

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

Esketamine Intranasal Up to 56 sessions/year, under supervision of a healthcare professional Adjunctive therapy Limited $33,000 - 49,000

Ketamine** Intravenous Up to 9 injections Adjunctive therapy No $2,500 - 5,000

rTMS Magnetic brain stimulation without anesthesia 5 sessions/ week, 4-5 weeks Mono/Adjunctive therapy Limited $6,000 - 12,000

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

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Government reimbursement or private insurance coverage;

Assumes one treatment course over the year, direct treatment cost only (not total healthcare costs).

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.

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

This frequency makes administration costly for payors and burdensome for patients, resulting in limited clinical adoption and patient access.

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

Somatic Therapies

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

Based on early signals from psilocybin therapy studies (using a different formulation of psilocybin from COMP360), which showed a rapid reduction in depression symptoms and effects lasting up to six months for some patients following administration of a single high dose, we believe psilocybin therapy has the potential to transform the current paradigm for TRD and other mental health and neurological conditions.

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.

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.

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.

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

Anorexia Nervosa

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

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

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%.

Post traumatic stress disorder

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.

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.

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

Psilocybin Therapy

History of Psilocybin Usage

Psychedelics are a class of psychoactive drugs that act primarily through an agonist action on neurotransmitter receptors and cause psychological, visual and auditory changes, as well as an altered state of consciousness.

Prior to psychedelics being classified as Schedule I drugs in the early 1970s, clinical research in psychedelics was widespread, with more than 40,000 patients suffering with mental health conditions participating in clinical studies and case reports.

Accumulating evidence suggests that many psychedelic drugs may have psychopharmacological effects on the brain, including increasing the number, density and connections of neurons.

This body of evidence has driven a resurgence of interest in the evaluation of psychedelic drugs for therapeutic use to treat a range of mental health conditions.

A number of major academic institutions - Imperial College London, Johns Hopkins University, and Mount Sinai Health System - have established dedicated psychedelic research centers in the last two years.

Psilocybin is considered a serotonergic hallucinogen, along with other tryptamines such as dimethyltryptamine, or DMT, ergolines such as lysergic acid diethylamide, or LSD, and phenethylamines such as mescaline.

It is an active ingredient in some species of mushrooms and was first isolated from psilocybe mushrooms by Dr.

Hofmann and synthesized in the late 1950s.

While classified as a Schedule I drug, the FDA and DEA began permitting the use of psilocybin in clinical studies for the treatment of a range of psychiatric conditions in the 1990s.

Psilocybin has been researched as a potential treatment for a range of CNS diseases for over 60 years.

Mechanism of Action

Mechanism of Action of Psilocybin

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

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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 predominately 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.

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.

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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.

Psilocybin Academic Studies

The therapeutic potential of psilocybin in depressive and anxiety conditions has been demonstrated in a number of academic-sponsored studies over the last decade.

In these studies, psilocybin, when administered in conjunction with psychological support, provided rapid reductions in depression symptoms after a single high dose, with antidepressant and anxiolytic effects occurring on the day of administration and lasting up to the six-month follow-up period for a number of participants.

These studies used a range of widely used and validated scales to assess symptoms related to depression and anxiety.

Some of these scales are self-reported and others are rated by clinicians.

These studies have shown psilocybin to be generally well-tolerated, with low toxicity and no serious adverse events, or SAEs, reported.

The low toxicity profile of psilocybin is corroborated by early non-clinical studies that indicate that very high levels of psilocybin, in excess of 200mg/kg when administered intravenously, are required to induce toxic effects in rodents .

A 2004 study estimated a lethal dose to be 6,000mg of psilocybin in an average, healthy 70kg adult, which vastly exceeds a therapeutic dose range.

Psilocybin is categorized as a Schedule I drug in the U.S.

and a Class A drug in the UK, due to its abuse potential reported in the 1960s.

However, despite evidence of recreational use of natural sources of psilocybin, a recent and comprehensive review used the structure of the eight factors of the U.S.

Controlled Substance Act to assess the abuse potential of medically administered psilocybin.

It suggested that in a medical context psilocybin does not have a high abuse potential and that there is no clear evidence for a physical dependence potential, based on animal and human data.

The totality of these data suggests that psilocybin therapy may exhibit clinical activity in patients with depression and anxiety, when administered with psychological support from specially trained therapists.

The table below summarizes the key findings from academic-sponsored studies that we believe support the use of psilocybin therapy for treating mental health conditions.

None of these studies used COMP360.

University of California Los Angeles

New York University

Johns Hopkins Griffiths et al

Imperial College London

Carhart-Harris et al

Johns Hopkins

Disorder Anxiety related to advanced-stage cancer Anxiety or depression related to cancer Anxiety or depression in life-threatening cancer TRD MDD

Design Double-blinded, placebo-controlled Randomized, double-blinded, placebo-controlled Randomized, double-blinded Open-label Randomized

Dose 14mg/70kg 21mg/70kg Low (1 or 3mg/70kg) High (22 or 30mg/70kg) 10mg and subsequently 25mg 20mg/70kg (first)

30mg/70kg (second) (b)

Outcome measures BDI, STAI, POMS HADS, BDI, STAI GRID-HAM-D, HAM-A QIDS-SR-16 GRID-HAM-D

Safety findings No SAEs attributed

to psilocybin

administration No SAEs attributed

to psilocybin

administration No SAEs attributed

to psilocybin

administration No SAEs attributed

to psilocybin

administration;

only mild and transient

adverse events No SAEs attributed to psilocybin administration

findings • BDI:

30% improvement at 1 and 6 months vs baseline and significant reduction from mild to minimal depression

Trend reduced adverse mood at week 2, returned to baseline at 6 months

Sustained decrease in trait anxiety sub-score at every time point for 6 months

• Significant reductions (mild/moderate to normal/minimal) in HADS, BDI and STAI measures

• ~60-80% of participants continued with clinically significant responses on depression and anxiety measures

• At 5 weeks and 6 months, 92% and 79% of high-dose participants, respectively, continued to show clinically significant responses on depression and anxiety measures

• QIDS-SR-16 scores showed significant improvement at all post-treatment time points

• Max effect at 5 weeks with 65% response (including 20% remission)

• No patients sought conventional antidepressant treatment within 5 weeks after psilocybin therapy

• 71% of participants had a clinically significant response in depression scores at both 1 and 4 weeks.

58% and 54% achieved clinical remission at 1 and 4 weeks respectively

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(a) “N” numbers indicate the number of patients that completed at least one administration session.

In some studies, not all administration sessions and/or follow-up measures were completed for all patients.

Reasons provided for patients not completing the studies included patients becoming too ill due to cancer progression, death due to cancer, or resumption of antidepression medications.

(b) Some patients received the 20mg/70 kg dose again for their second dose.

As used herein, “clinically significant response” is defined as a >50% reduction in depression or anxiety scores relative to baseline.

“Clinical remission” in the Davis et al study is defined as GRID-HAMD scores <7.

Responses and remission shown for Davis et al study are for “Immediate treatment” group that had already received psilocybin therapy.

Abbreviations:

BDI, Beck Depression Inventory;

GRID-HAM-D, GRID Hamilton Depression Rating Scale;

HADS, Hospital Anxiety and Depression Scale;

HAM-A, Hamilton Anxiety Rating Scale;

HAM-D, Hamilton Depression Rating Scale;

STAI, State-Trait Anxiety Inventory;

POMS, Profile of Mood States questionnaire;

QIDS-SR-16, Quick Inventory of Depressive Symptomatology

University of California Los Angeles, Grob et al, 2011 - Existential Distress:

Feasibility and Safety for Cancer Patients

In this 2011 study, 12 patients with anxiety related to advanced stage cancer (defined as diagnosis of acute stress disorder, generalized anxiety disorder, anxiety disorder due to cancer, or adjustment disorder with anxiety) underwent two experimental sessions spaced several weeks apart.

In one session, each patient received 14mg/70kg psilocybin and in the other session each patient received a placebo control (250mg niacin), and the order in which they were administered was randomized.

The BDI, POMS and STAI scoring scales were assessed one day before, one day after, and two weeks after each session.

Each measure was assessed again once a month for up to six months after the final session.

There was a trend showing decreased BDI scores at two weeks compared to one day before the first session.

BDI scores were reduced by almost 30% at one month after the second treatment.

This change was sustained and became significant at six months.

The POMS indicated a trend for reduced adverse mood tone at two weeks after the first session compared to one day prior to psilocybin treatment.

Although no significant changes were observed on the STAI state anxiety score, a sustained decrease that was significant at one and three-months post-treatment was evident on the STAI trait anxiety score.

No SAEs were attributed to psilocybin administration.

Significant Reduction in BDI Scores at Six Months Post Treatment Compared with Baseline

Graph displays changes in depression severity represented by Beck Depression Inventory (BDI) score between baseline and six months following second administration session.

A reduction in BDI score was reported at the six month timepoint, compared to baseline.

Effect sizes not reported.

P-value = 0.03, calculated by performing a t-test to compare the six month score with one day before the first administration.

Adapted from Grob et al 2011.

New York University, Ross et al, 2016 – Existential Distress

This 2016 study recruited 29 patients with life-threatening cancer and clinically significant anxiety or depression (defined as a primary diagnosis of acute stress disorder, generalized anxiety disorder, anxiety disorder due to cancer, or adjustment disorder with anxiety and/or depression).

Patients underwent two administration sessions, one in which 21mg/70kg psilocybin was administered and one in which they received a placebo (250mg niacin).

The administration sessions were spaced seven weeks apart and the order in which they were administered was randomized.

Baseline measurements were collected two to four weeks prior to the first session.

Statistically significant reductions in measures of anxiety and depression were observed up to 26 weeks following the second dose in patients who received psilocybin first, compared with baseline.

Although no significant changes were observed in the placebo-first group prior to crossover, these patients also experienced statistically significant, sustained reductions in a majority (five out of six) of anxiety and depressions measures following psilocybin treatment.

At 26 weeks following the final treatment, both groups exhibited antidepressant or anxiolytic, or reduction of anxiety, response rates of 60-80% across a variety of measures, including BDI remission and response rates as well as HADS, as demonstrated in the following graphic.

No SAEs were attributed to psilocybin administration.

Statistically Significant Decrease in HADS Depression Scores at 26 Weeks Post Treatment

Graph illustrates changes in mean HADS Depression scores in niacin-first (blue) and psilocybin-first (purple) groups between baseline and 26-weeks after second treatment.

The psilocybin-first group exhibited significant reductions in depressed symptoms compared to the placebo group after the first administration session.

The niacin-first group also showed significant reductions in depressive symptoms 26 weeks after receiving psilocybin compared with baseline.

*p<0.05, **p<0.01, ***p<0.001, calculated by performing between-group t-tests.

Solid symbols indicate significant within-group differences versus baseline.

Data shown as mean ± Standard Error (SE).

Adapted from Ross et al, 2016.

Johns Hopkins University, Griffiths et al, 2016 - Existential Distress

This 2016 study enrolled 51 patients with life-threatening cancer and a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) diagnosis that included anxiety and/or mood symptoms.

The patients were randomized to receive either a low (1 or 3mg/70kg) or a high (22 or 30mg/70kg) dose of psilocybin first.

At a second administration session five weeks later, patients who had received the low dose first were given a high dose, whereas the high-dose first group were given a low dose of psilocybin.

In the high-dose first group, psilocybin treatment resulted in significant reductions in measures of depression and anxiety at five weeks following the first session.

Of the high-dose first group, 92% showed a clinically significant response (≥50% reduction in GRID-HAMD depression scores relative to baseline) at this five-week timepoint, compared with 32% of the low-dose first group.

These significant changes were sustained at the six-month follow-up in both groups, with 79% of the high-dose first group and 77% of the low-dose first group continuing to show clinical response.

More than two thirds of patients described psilocybin therapy as among the top five most meaningful experiences of their lives, alongside the birth of a child or the death of a parent, six months after their psilocybin therapy session.

No SAEs were attributed to psilocybin administration.

Statistically Significant Reductions in Depression and Anxiety (GRID-HAMD) Sustained Six Months Post Treatment

Graph displays changes in GRID-HAMD scores between baseline and six months following first treatment, in groups receiving psilocybin low dose first or psilocybin high dose first.

These changes demonstrate the antidepressant effect of psilocybin in this population and supported greater efficacy for the high dose of psilocybin.

*p<0.05 and +p<0.05, calculated using planned comparison t-tests.

Asterisk indicates significant difference between the groups following session 1 (Post 1) and cross denotes significant difference between scores at Post 1 and Post 2 timepoints in the group that received the psilocybin low dose first.

Data shown as mean ± SEM.

Adapted from Griffiths et al, 2016.

Imperial College London, Carhart-Harris et al, 2016, 2018 - TRD

In this study, conducted in 2016, 20 TRD patients with moderate to severe depression were dosed with 10mg psilocybin and 25mg psilocybin in two separate administration sessions that occurred one week apart.

All patients received the lower dose in the first session.

Among the 19 patients who completed the entire follow-up period, a statistically significant reduction in depressive symptoms was observed for up to six months, compared with baseline.

The maximum effect size (on the QIDS-SR-16) was observed at five weeks post-treatment, at which point nine patients met the criteria for response (≥50% reduction in BDI score compared with baseline).

No patients had sought conventional antidepressant treatment within five weeks of receiving the high psilocybin dose.

Only mild and transient adverse events were observed and no SAEs were attributed to psilocybin administration.

Significant Reduction in Depressive Symptoms Observed up to Six Months Post Treatment

Graph shows changes in depression severity represented by QIDS score between baseline and six months after the second treatment.

These changes demonstrated a significant reduction in depressive symptoms following psilocybin treatment in TRD.

Effect size comparing pre- to post-treatment scores is represented by Cohen’s d values in red.

Adapted from Carhart-Harris et al 2018.

Johns Hopkins University, Davis et al, 2020 - MDD

This study analyzed data from a total of 24 MDD patients who were randomized into two groups.

One group received treatment immediately following baseline measurements (“immediate treatment”), while a waitlist control group received treatment eight weeks after baseline measurements (“delayed treatment”).

Each patient received 20mg/70kg psilocybin in a first session and either 20 or 30mg/70kg psilocybin in a second administration session.

The authors reported significant differences between the two treatment groups in depressive symptoms measured using the GRID-HAMD at one and four weeks post-treatment (when the “delayed treatment” group were still awaiting their first administration session), caused by a decrease in scores of the “immediate treatment” group.

In addition, at four weeks following treatment, 71% and 54% of study participants met the criteria for clinically significant response (>50% reduction in GRID-HAMD depression scores relative to baseline) and remission (GRID-HAMD scores <7), respectively.

Significant Reduction in Depressive Symptoms Observed up to Four Weeks Post Treatment in Immediate Treatment Group Compared with Delayed Treatment Group

Graph shows depression severity represented by GRID-HAMD score between baseline and at one and four weeks post-treatment of the “immediate treatment” group.

Effect size (Cohen’s d):

1 week = 2.5, 4 weeks = 2.6.

Graph created based on data from Davis et al 2020.

Our Investigational Psilocybin Therapy - COMP360

Clinical Summary

Investigational COMP360 Psilocybin Treatment 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 therapy comprises administration of our COMP360 with psychological support from specially trained therapists with specific professional and educational qualifications.

We are investigating the safety and effectiveness of our COMP360 psilocybin therapy in TRD, anorexia nervosa and PTSD.

In our Phase 1 clinical trial in 89 healthy participants, completed in 2019, we observed that COMP360 was generally well-tolerated, with no serious adverse events and no clinically relevant negative short- or longer-term effects on cognition or emotional processing.

According to analyses in this exploratory study, for the duration of the trial, there were no negative effects on cognition (measured up to four weeks from administration) based on a range of validated measures from the Cambridge Neuropsychological Test Automated Battery, or emotional processing (measured up to 12 weeks from administration), based on widely accepted clinical and academic tests.

The trial also demonstrated the feasibility of administering COMP360 psilocybin to up to six healthy participants simultaneously, with 1:1 support.

I n 2021, we completed a large-scale randomized, controlled, double-blind Phase 2b clinical trial of our COMP360 psilocybin therapy in 233 patients suffering with TRD, in 22 sites in 10 countries in North America and Europe.

This is the largest psilocybin trial completed to date.

This dose-finding trial investigated the safety and efficacy of COMP360 in TRD, and aimed to determine the optimal dose of COMP360, with three doses (1mg, 10mg, 25mg) explored.

In November 2021, we announced positive topline results from this trial which showed a rapid and sustained response for patients receiving a single dose of COMP360 psilocybin with psychological support.

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

In December 2021 we announced the results from our exploratory study of COMP360 psilocybin therapy in conjunction with SSRI antidepressant use.

This single-arm open label study of 19 patients with TRD taking concomitant SSRI therapy with

COMP360 psilocybin therapy using a single dose of 25mg saw comparable treatment outcomes to patients in our Phase 2b trial where patients were withdrawn from their ongoing antidepressants prior to COMP360 psilocybin therapy.

The results of this study challenge the widely held belief that the use of serotonergic antidepressants together with psilocybin could interfere with psilocybin’s therapeutic effect and provide a strong signal that COMP360 psilocybin therapy could be an adjunctive treatment to SSRI antidepressants as well as a monotherapy.

This could be helpful for some patients with TRD for whom antidepressant withdrawal is a difficult step.

COMP360 Psilocybin Therapy Protocol

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

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.

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preparation, the COMP360 administration session, and integration.

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

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

• 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.

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

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:

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

Therapists in the clinical development program of COMP360 psilocybin therapy for TRD are required to have an active unrestricted professional license to practice as a clinical psychologist, psychiatrist, social worker or mental health counselor.

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.

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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 in psilocybin therapy.

It will continue to evolve as we progress COMP360 psilocybin therapy 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.

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.

Preclinical and Clinical Experience

Preclinical Studies

We previously conducted a series of in vitro and in vivo toxicology studies, including tests for studies evaluating genotoxicity and cardiotoxicity.

The results of these studies allowed us to begin our Phase 2b clinical trial in TRD.

The required series of in vitro and in vivo safety and toxicology studies is continuing as planned, permitting an efficient start to our Phase 3 program.

Healthy Volunteers Trial

In 2019, we completed a Phase 1 clinical trial of COMP360 administered along with psychological support in healthy participants.

The trial recruited 89 healthy participants, of which 41 were females and 48 were males, with an average age of 36 years.

This double-blind, placebo-controlled trial was the largest randomized controlled trial of psilocybin at the time, and the first to simultaneously administer psilocybin, with 1:1 support from therapists in a clinical research setting.

The trial was conducted at the Institute of Psychiatry, Psychology and Neuroscience, King’s College London and it was peer-reviewed and published in The Journal of Psychopharmacology in January 2022.

Prior to administration, participants took part in a two-hour preparatory group session.

Participants were randomized to three arms:

placebo, 10mg or 25mg doses of COMP360 in a 1:1:1 ratio.

COMP360 was administered orally and 1:1 psychological support was given to up to six participants simultaneously at the facility.

Participants were followed up for 12 weeks following drug administration and completed safety assessments, using a range of validated measures of cognitive function and emotional processing.

Key Enrollment Criteria

Participants were males or females aged between 18 to 65 years of age.

Participants with a current diagnosis or past history of schizophrenia, psychosis, bipolar disorder, delusional disorder, paranoid personality disorder, schizoaffective disorder, borderline personality disorder, major depressive disorder, panic disorder, generalized anxiety disorder, obsessive-compulsive disorder, eating disorder, or body dysmorphic disorder, were excluded.

Patients with first-degree relatives with the aforementioned conditions, or a past history thereof, were also excluded.

Additionally, participants were not deemed eligible if they met criteria for current, or history of, substance abuse or dependency, had taken psychiatric medications within one year of enrollment or had prior exposure to psilocybin within one year of signing the informed consent.

Clinical Findings

There were no SAEs reported, and no adverse events, or AEs, led to withdrawal.

A total of 511 AEs were reported throughout the 12-week duration of the trial.

The tables below summarize the most frequently reported AEs, including AE profile by treatment group, as well as ranking the most frequently reported AEs based on the COMP360 25mg psilocybin arm, by group:

Placebo (n=29) 10mg COMP360 (n=30) 25mg COMP360 (n=30)

Total number of treatment-emergent AEs reported 91 203 217

Total number of treatment-emergent AEs reported deemed to be related or possibly related to study treatment 77 188 208

Number of treatment-emergent adverse events (AEs) reported by treatment group in our health volunteers trial.

Most Frequently Reported AEs (MedDRA Code) a in our Phase 1 healthy volunteers trial

_____________

a Ranked by incidence in the 25mg COMP360 group

b Includes auditory, gustatory, olfactory, tactile, and visual hallucinations

AE, adverse event;

MedDRA, Medical Dictionary for Regulatory Activities

COMP360 induced expected psychedelic experiences that generally resolved on the day of administration.

In previous third-party studies, these have been found to correlate with therapeutic effect.

Of all AEs, 68% reported as starting and resolving on the day of administration The median duration of AEs in all treatment arms across the 12-week trial was one day.

Above Figure:

Most frequent AEs:

onset and duration by treatment arm in our healthy volunteers trial.

There were 57 AEs reported of “mood altered,” of which only two related to negative alterations in mood.

One of these was in the placebo arm (“negative mood,” which started and resolved on the day of dosing) and one in the COMP360 10mg psilocybin arm (“feeling moody or sensitive,” which started on Day 2 and resolved eight days later).

25mg COMP360 (n=30) 10mg COMP360 (n=30) Placebo (n=29)

Any “mood altered” AE 15 (50.0) 13 (43.3) 6 (20.7)

Introspection 7 (23.3) 5 (16.7) 1 (3.4)

Reflections 3 (10.0) 2 (6.7) 2 (6.9)

Increased empathy 2 (6.7) 3 (10.0) 0

Sense of oneness 1 (3.3) 4 (13.3) 0

Introspection/reflection 1 (3.3) 1 (3.3) 1 (3.4)

Laughter 1 (3.3) 1 (3.3) 0

New perspective 1 (3.3) 1 (3.3) 0

Awareness of importance of considering others 1 (3.3) 0 0

Clarity of thought 1 (3.3) 0 0

Contemplative state 1 (3.3) 0 1 (3.4)

Increased compassion 1 (3.3) 0 0

Increased creativity 1 (3.3) 0 0

Increased sense of connectedness 1 (3.3) 0 0

More socially upbeat 1 (3.3) 0 0

Reflections and new perspectives 1 (3.3) 0 0

Sense of oneness and connectedness 1 (3.3) 0 0

Being less judgmental 0 1 (3.3) 0

Feeling more moody/sensitive 0 1 (3.3) 0

Feeling rested 0 1 (3.3) 0

Increased wit 0 1 (3.3) 0

Reflections and new perspectives on relationships and society 0 1 (3.3) 0

Sense of oneness 0 1 (3.3) 0

Calm 0 0 1 (3.4)

Feeling of adrenaline release 0 0 1 (3.4)

Negative mood 0 0 1 (3.4)

Unusual appreciation of music 0 0 1 (3.4)

_____________

Reported “mood altered” AEs ranked by incidence in the COMP360 25mg group in our healthy volunteers trial.

“Mood altered” AEs were grouped into this MedDRA preferred term post hoc, while retaining the non-MedDRA AE description originally reported by the participant/investigator.

Participants completed a range of assessments of cognitive function and emotional processing.

These included a range of validated measures of cognition from the Cambridge Neuropsychological Test Automated Battery, or CANTAB, including, amongst others, tasks of spatial working memory, rapid visual information processing and paired associates learning.

Small differences in cognitive outcomes were seen between the groups, but no negative trends were identified.

Assessments of emotional processing included, amongst others, tasks of social cognition such as the Pictorial Empathy Test, the Reading the Mind in the Eyes Test, the Scale of Social Responsibility, the Social Value Orientation, and the Toronto Empathy Questionnaire.

There were no consistent negative trends in emotional processing outcomes to suggest that either COMP360 dose had short- or longer-term effects on these indicators.

According to analyses, we found no negative trends on cognition or emotional processing.

This trial suggests that COMP360 was generally well-tolerated in healthy volunteers.

There were no SAEs and analyses assessing cognitive and emotional functions showed no clinically-relevant negative short- or longer term effects on cognition or emotional processing of COMP360.

The trial also showed the feasibility of simultaneous administration of COMP360 in up to six people in the same facility, with 1:1 therapist support, which we believe could accelerate future clinical trials and commercial scale-up.

Phase 2b Trial of Our COMP360 Psilocybin Therapy in TRD

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 therapy 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.

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• 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 therapy.

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).

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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 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.

Clinical findings

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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.

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.

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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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.

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

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.

On the Positive and Negative Affect Schedule measuring positive and negative affect, patients in the 25mg group had a higher increase in positive affect (e.g., including feeling interested, excited, strong) and a greater decrease in negative affect (including feeling distressed, upset, afraid) on the day after COMP360 administration and at the questionnaire’s final administration at week 3.

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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.

Further, a detailed case-by-case post-hoc analysis of safety data did not establish a causal relationship between these TEAEs of suicidal ideation, suicidal behavior and intentional self-injury and administration of COMP360.

The events occurred in all treatment groups and at a range of onset times and durations;

the majority occurred more than a week after the psilocybin session.

• 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;

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• 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 were reported as treatment-emergent serious adverse events (TESAEs);

• 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 therapy 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

• 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;

there were five withdrawals from the 25mg group, nine from the 10mg, and 10 from the 1mg.

Phase 2 study of COMP360 psilocybin therapy as adjunct to SSRI antidepressants

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, including additional details, will also be published in a peer-reviewed journal.

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

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

The primary endpoint was the change in baseline MADRS total score at 3 weeks in patients having 25mg COMP360 psilocybin therapy given in augmentation with their existing SSRI antidepressant regimen.

The primary endpoint was the change in baseline MADRS total score at 3 weeks in patients having 25mg COMP360 psilocybin treatment given in augmentation with their existing SSRI antidepressant regimen.

Clinical Findings

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Change from baseline in MADRS total score

COMP360 psilocybin therapy using a 25mg dose also showed overall signals of improvement in most other measures including improvement in anxiety, clinician and self-rated depressive symptoms, and positive and negative affect.

25mg COMP360 psilocybin therapy was generally well-tolerated when it was administered simultaneously with the patient’s existing SSRI treatment.

COMP360 psilocybin treatment using a 25mg dose also showed overall signals of improvement in most other measures including improvement in anxiety, clinician and self-rated depressive symptoms, and positive and negative affect.

25mg COMP360 psilocybin treatment was generally well-tolerated when it was administered simultaneously with the patient’s existing SSRI treatment.

There were no TEAEs classed as serious (life threatening, leading to disabilities, hospitalization or in general medically significant) and no TEAEs related to suicidal ideation or behavior or intentional self-injury.

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In addition, a lower proportion of participants started new treatments for depression in the 25mg and 10mg arm compared to the 1mg arm.

Suicidality was recorded as an adverse event twice in 25mg group, twice in the 10mg group, and once in the 1mg group.

outcomes of the long-term follow-up study informed the design of our Phase 3 registrational program, including investigating whether a second administration of COMP360 may achieve improved durability, response and remission outcomes.

Phase 3 Registrational Program

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

Suicidality was recorded as an adverse event twice in the 25mg group, twice in the 10mg group, and once in the 1mg group.

The outcomes of the long-term follow-up study informed the design of our Phase 3 registrational program, including investigating whether a second administration of COMP360 may achieve improved durability, response and remission outcomes.

Phase 3 Registrational Program and Supportive Studies

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

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

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

We expect top-line data in summer of 2024.

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.

We expect top-line data by mid-2025.

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

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

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

The design of these studies reflects protocol amendments that we are implementing, in part, to reflect our re-estimation of sample size for COMP005 and to incorporate long-term follow-up into both pivotal studies.

Our re-estimation of the sample size for COMP005 was based on recent data from the University of Zurich’s placebo-controlled study of COMP360 in MDD and further analysis of our Phase 2b data, with specific focus on participants in the 1mg arm who had a minimal psychedelic experience.

In January 2023, we submitted the protocol amendments for COMP005 to the FDA and requested feedback, and the FDA has indicated that they plan to provide feedback by March 20, 2023.

We will consider any comments we receive.

We recently submitted protocol amendments for COMP006 to incorporate long-term follow-up into this study following the same design principles reflected in the COMP005 protocol amendments that are already under review by FDA.

Additional clinical trials

Beyond TRD, we are evaluating COMP360 psilocybin therapy for the treatment of anorexia nervosa and PTSD.

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.

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

We expect to submit the results of this study as part of our submission package for approval of COMP360 psilocybin treatment in TRD.

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.

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

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.

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

To address these challenges, we are making amendments to our trial protocol to reduce the trial burden for this highly vulnerable patient population.

As a result, we no longer expect to have data from this trial available in 2023, as we had originally expected.

We are also conducting a Phase 2 clinical trial to assess the safety and tolerability of COMP360 psilocybin therapy in PTSD.

It is a multicenter, fixed-dose open label study and will enroll 20 participants.

We expect data from the PTSD study by the end of 2023.

Expansion Opportunities

The active metabolite of psilocybin, psilocin, is a partial agonist at several 5-HT receptors, including the 5-HT 2A receptor.

The 5-HT 2A receptors are abundantly expressed in multiple areas of the brain that have important roles in cognitive and emotional processing and could impact a range of cognitive and mental health conditions.

We therefore believe psilocybin could have transdiagnostic utility and intend to explore various expansion opportunities beyond our core program of developing our psilocybin therapy for TRD.

For example, we are conducting an additional study to evaluate the safety and tolerability of COMP360 psilocybin therapy in patients suffering from PTSD.

We are also investigating the potential benefits of compounds other than psilocybin through our Discovery Center, a research collaboration with University of the Sciences in Philadelphia, Pennsylvania, US;

UC San Diego, School of Medicine, in San Diego, California, US;

and Medical College of Wisconsin in Milwaukee, Wisconsin, US.

See “—Drug Discovery Center”.

Mechanistic Studies

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

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.

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), human induced pluripotent stem cell-derived neurons (collaboration with Professor Stephen Haggarty, Massachusetts General Hospital - Harvard Medical School) and also native tissues.

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;

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

Neurotar and Ulysses Neuroscience), 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, 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 an academic collaboration with the University of Bordeaux, France;

• A healthy volunteers study with Imperial College London, investigating the acute and long-term psychological and brain effects of psilocybin therapy, 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.

Other Indications:

Preclinical Studies

Through collaborations with academic institutions, we are generating preclinical and clinical data to explore the benefits of our psilocybin therapy in indications outside TRD.

We work with CROs and academic institutions, including the University of Bristol and the University of Bordeaux, in conducting preclinical studies.

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.

Other Indications:

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The indications previously explored or currently being explored in these IIS signal-generating and mechanistic studies include:

anorexia nervosa, autism, bipolar type II disorder, body dysmorphic disorder, chronic cluster headache, depression in cancer, MDD, severe TRD, and suicidal ideation.

anorexia nervosa, autism, bipolar type II depression, body dysmorphic disorder, chronic cluster headache, depression in cancer, MDD, severe TRD, and suicidal ideation.

We supply our IIS researchers with COMP360 psilocybin and encourage the open publication of all study findings.

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In this open-label study involving 30 patients with a cancer diagnosis and MDD, patients received a 25mg dose of COMP360 in conjunction with psychological support.

Patients began with an average MADRS score of 25.9, representing moderate depression and after COMP360 psilocybin therapy, the average score decreased by 19.1 points.

Patients began with an average MADRS score of 25.9, representing moderate depression and after COMP360 psilocybin treatment, the average score decreased by 19.1 points.

A sustained response (a decrease of ≥50% in the MADRS total score from baseline observed at any visit up to and including week 3, and also fulfilled at week 8) was seen in 24 patients;

15 patients showed remission of depressive symptoms (a MADRS score <10) one week after a single dose of COMP360, which was sustained up to eight weeks.

COMP360 psilocybin therapy was found to be generally well-tolerated with no treatment-related serious adverse events.

COMP360 psilocybin treatment was found to be generally well-tolerated with no treatment-related serious adverse events.

Adverse effects on the day of dosing were transient and as expected in line with other studies included headache, changes in sensory perception, and mood alteration.

Top-line results were published in JAMA Oncology in April 2023 and the full results and methodology from this study were published in Cancer in December 2023.

In 2022, Sheppard Pratt Health System completed an IIS of COMP360 titled “An Open Label Study of the Safety and Efficacy of COMP360 in Participants With Severe Treatment-Resistant Depression (P-TRD)”.

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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;

p=0.028) , and

nominally statistically significant reductions in eating concerns on the EDE at the 3-month follow-up (mean change from pre-treatment=1.1;

p=0.028), and nominally statistically significant reductions in eating concerns on the EDE at the 3-month follow-up (mean change from pre-treatment=1.1;

Changes in weight concerns on the EDE were approaching nominal statistical significance at the 3-month follow-up but were not statistically significant (mean change from pre-treatment=1.2).

COMP360 psilocybin therapy was well-tolerated with no treatment-related serious adverse events reported.

COMP360 psilocybin treatment was well-tolerated with no treatment-related serious adverse events reported.

In July 2023, the results of this study showing the potential of investigational COMP360 psilocybin treatment in anorexia nervosa were published in Nature Medicine .

In 2022, Sheppard Pratt Health System completed an IIS of COMP360 titled “The Safety and Efficacy of Psilocybin in Participants With Type 2 Bipolar Disorder (BP-II) Depression.” (ClinicalTrials.gov Identifier:

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The investigator presented data from this study at the Annual Meeting of the American College of Neuropsychopharmacology (ACNP) in December 2022.

In this open-label study involving 14 patients with type 2 bipolar disorder, patients received a 25mg dose of COMP360 with psychological support.

The study found that 86% (12 out of 14) of the participants met response and remission criteria for the MADRS scale at 12 weeks after COMP360 psilocybin therapy.

In this open-label study involving 14 patients with type 2 bipolar depression, patients received a 25mg dose of COMP360 with psychological support.

The study found that 86% (12 out of 14) of the participants met response and remission criteria for the MADRS scale at 12 weeks after COMP360 psilocybin treatment.

There was no increase in the suicidality score based on the MADRS, no manic symptoms and no unexpected adverse events or difficulties with the dosing sessions reported throughout the study.

No treatment-related serious adverse events were reported.

In December 2023, the results of this study demonstrating the potential of investigational COMP360 psilocybin treatment in type 2 bipolar depression were published in JAMA Psychiatry .

In 2022, University of Zurich completed an IIS of COMP360 titled “Phase II, Randomized, Double Blind, Placebo Controlled, Parallel Group, Single Center Study of Psilocybin Efficacy in Major Depression.” (ClinicalTrials.gov Identifier:

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No cases of suicidal behavior occurred during the trial period of approximately one month and no treatment-related serious adverse events were reported.

Preclinical and Drug Discovery Programs

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.

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

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;

• 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.

Drug Discovery Center

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

In February 2021, we expanded the Discovery Center through a collaboration with laboratories at UC San Diego, School of Medicine (San Diego, California, US), and Medical College of Wisconsin (Milwaukee, Wisconsin, US).

Scientists from these teams will work with us and the team from USciences, from their different locations, in a virtual network.

In September 2021, we acquired an intellectual property, or IP, portfolio including patent applications covering a variety of psychedelic and empathogenic substances at a cost of $1.2 million.

The IP was developed together with inventor Matthias Grill PhD, founder and CEO of MiHKAL GmbH in Basel, Switzerland, who will be working with us on an exclusive research

project to develop new product candidates.

The substances covered in the IP portfolio include a variety of psychedelic and empathogenic compounds, some of which are prodrugs, or pharmacologically inactive compounds which are metabolized inside the body to produce an active drug.

The new substances include novel derivatives of known compounds, increasing the confidence in therapeutic effects and safety profile while offering optimized characteristics.

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.

Delix Therapeutics

On March 6, 2020 we made a strategic investment to acquire an 8% (on a fully diluted basis) shareholding in Delix Therapeutics, Inc., a drug discovery and development company researching novel small molecules for use in CNS indications.

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.

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Therapist Training

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

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.

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• Tier III - Clinical training:

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

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 group mentoring and support throughout their participation in our clinical studies.

Mentors have access to video/audio 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.

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 mental healthcare professionals.

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

Using Digital Technology

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

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

• 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;

• Collection of measurements in our Phase 2b clinical trial, including remote data collection using mobile devices so patients do not need to travel into study sites for all in-clinic visits;

• 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;

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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 therapy.

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

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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.

Commercialization

If our COMP360 psilocybin therapy is approved, we plan to use our own sales and marketing capabilities, targeting public and private healthcare providers and clinic networks in the U.S.

and major European markets.

In select geographies, including Asia and South America, we may enter into commercialization collaborations with third parties who have complementary commercial capabilities.

If our COMP360 psilocybin treatment is approved, we plan to use our own sales and marketing capabilities, targeting public and private healthcare providers and clinic networks in the U.S.

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.

Centers of Excellence

In line with our ambition to create a new mental health care model, we intend to establish Centers of Excellence to serve as research facilities and innovation labs.

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 March 2022, we announced a strategic collaboration with King’s College London and South London and Maudsley NHS Foundation Trust, or SLaM, to establish 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.

Our potential future Centers of Excellence will be designed to model the “clinics of the future,” and through them we intend to gather evidence to shape our therapy model and prototype digital technology solutions to improve patient experience and support therapists.

Methodologies developed in the Centers of Excellence will be shared with our partner clinics.

Centers of Excellence will allow us to test and establish a new blueprint for innovative care models that can be licensed or franchised to existing behavioral health providers, community mental health teams, private clinic networks, partial hospitalization programs, and intensive outpatient programs.

We intend to establish additional Centers of Excellence for several purposes, including:

• Conducting clinical trials, including proof of concept studies, to refine our therapeutic model;

• Participating in late-stage trials as a clinical trial site;

• Training and certifying therapists who are supporting or will support our clinical trials;

• Generating and collecting safety and other data, as well as (licensable) intellectual property;

• Developing and testing digital technology solutions to improve patient experience;

• Strengthening our regional presence as a scientific and clinical resource by showcasing what we believe to be the future of mental health care, fostering relationships with stakeholders including patients, providers, payors and public policymakers;

• Refining our approach to delivering our investigational COMP360 psilocybin therapy safely and cost-effectively.

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.

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.

While we believe that our investigational COMP360 psilocybin therapy represents a fundamental shift in the treatment paradigm relative to other TRD treatments, we face potential competition from many different sources, including major pharmaceutical, specialty pharmaceutical and biotechnology companies, academic institutions, governmental agencies and medical research organizations.

Any product candidates that we successfully develop and commercialize, including our investigational COMP360 psilocybin therapy, will compete with the standard of care and new therapies, both pharmacological and somatic, that may become available in the future.

While we believe that our investigational COMP360 psilocybin treatment represents a fundamental shift in the treatment paradigm relative to other TRD treatments, we face potential competition from many different sources, including major pharmaceutical, biopharmaceutical, specialty pharmaceutical and biotechnology companies, academic institutions, governmental agencies and medical research organizations.

Any product candidates that we successfully develop and commercialize, including our investigational COMP360 psilocybin treatment, will compete with the standard of care and new therapies, both pharmacological and somatic, that may become available in the future.

Currently, only two pharmacotherapies are approved for TRD in the U.S.:

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Because TRD, by definition, encompasses patients who have not been helped after two or more MDD therapies, antidepressants indicated for use in MDD are frequently prescribed, combined or augmented with a second agent to treat TRD patients.

Several biopharmaceutical companies have therapies in clinical development.

We are aware that Sage Therapeutics and Axsome Therapeutics, among others, are developing treatments for TRD.

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.

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

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Patents and Other Intellectual and Proprietary Rights

Obtaining, maintaining and defending patents and other intellectual property (“IP”) rights, whether independently or in collaboration with our partners, are of key importance in the protection and commercialization of the Company’s innovative therapies.

We shall continue to seek patent, trademark, and trade secret protection of our innovations in the U.S., EU, UK, and other selected jurisdictions.

Obtaining, maintaining and defending global patents and other intellectual property (“IP”) rights, whether independently or in collaboration with our partners, are of key importance in the protection and commercialization of the Company’s innovative therapies and technology solutions.

We shall continue to seek global patent, trademark, and trade secret protection of our innovations in the U.S., EU, UK, and other key jurisdictions.

This includes pursuing patent protection for our novel high-purity polymorphic crystalline psilocybin and related manufacturing processes, pharmaceutical compositions, formulations, and methods of treatment of psychiatric and neurological indications, including TRD, MDD, PTSD, and anorexia.

This also includes pursuing trademark protection for the Company’s various marks.

Upon regulatory approval in a particular jurisdiction, we will also seek to meaningfully protect our innovations by asserting available regulatory exclusivity including regulatory data protection and market exclusivity.

For example, upon approval from the U.S.

FDA, we may be entitled to five years of regulatory exclusivity for New Chemical Entity, or NCE, and upon approval from the European Medicines Agency, or EMA, we may be entitled to ten years of regulatory exclusivity.

We will also defend our patents and other IP and proprietary rights as need be if and when we are subjected to third-party challenges (e.g., litigation, post-grant review, inter-partes review, oppositions).

FDA, we may be entitled to five years of regulatory exclusivity for New Chemical Entity, or NCE, status and upon approval from the European Medicines Agency, or EMA, we may be entitled to ten years of regulatory exclusivity.

We will defend our patents and other IP and proprietary rights as appropriate if and when we are subjected to third-party challenges (e.g., litigation, post-grant review, inter-partes review, oppositions).

Patents and Patent Applications

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US 11,505,564 Method of manufacturing ca.2038*

US 11,629,159 Crystalline psilocybin;

Pharmaceutical formulations ca.

US 17/990,979 Crystalline psilocybin;

Pharmaceutical formulations ca.

US 18/135,265 Crystalline psilocybin;

Pharmaceutical formulations ca.

GB 2571696 Method of manufacturing ca.

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2040* Applications filed in U.S., Australia, Canada, China, European Patent Office, Japan and Republic of Korea.

US 17/540,962 Method of treating PTSD ca.

US 11,564,935

Method of treating PTSD ca.

US 11,738,035 Method of treating anorexia ca.

PCT WO2020/212948

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2040* Applications filed in U.S., Australia, Canada, China, European Patent Office, Japan and Republic of Korea.

US 17/604,610 Method of treating depression ca.

PCT WO2020/212952

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PCT WO2022/207746 Pharmaceutical formulations ca.

2042* Applications filed in Taiwan and Argentina.

National Stage Applications to be filed.

2042* Applications filed in U.S., Taiwan, Argentina, Australia, Canada, China, European Patent office, Japan, and Republic of Korea.

US 18/285,109 Pharmaceutical formulations ca.

*In general, a U.S.

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The USPTO Board denied the request for Precedential Opinion Panel (POP) review on February 10, 2023.

The USPTO Board has not yet issued a final decision on the request for rehearing.

On May 23, 2023, the USPTO Board denied the request for rehearing.

On December 22, 2021, Freedom to Operate, Inc., filed a petition for post-grant review of U.S.

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The USPTO Board denied the request for Precedential Opinion Panel (POP) review on February 10, 2023.

The USPTO Board has not yet issued a final decision on the request for rehearing.

On May 23, 2023, the USPTO Board denied the request for rehearing.

UK patent, No GB2571696, was granted in May 2020 with claims directed to large scale manufacture of psilocybin, psilocybin made by said process and formulation comprising psilocybin made by said process.

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The clinical stage of development involves the administration of the product candidate to healthy volunteers or patients under the supervision of qualified investigators, who generally are physicians not employed by or under the trial sponsor’s control, in accordance with GCP requirements, which include the requirements that all research subjects provide their informed consent for their participation in any clinical trial.

Clinical trials are conducted under protocols detailing, among other things, the objectives of the clinical trial, administration procedures, subject selection and exclusion criteria and the parameters and criteria to be used in monitoring safety and evaluating effectiveness.

Clinical trials are conducted under protocols detailing, among

other things, the objectives of the clinical trial, administration procedures, subject selection and exclusion criteria and the parameters and criteria to be used in monitoring safety and evaluating effectiveness.

Each protocol, and any subsequent amendments to the protocol, must be submitted to the FDA as part of the IND.

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The FDA must make a decision on accepting an NDA for filing within 60 days of receipt, and such decision could include a refusal to file by the FDA.

Once the submission is accepted for filing, the FDA begins an in-

depth substantive review of the NDA.

Once the submission is accepted for filing, the FDA begins an in-depth substantive review of the NDA.

The FDA reviews an NDA to determine, among other things, whether the drug is safe and effective for the indications sought and whether the facility in which it is manufactured, processed, packaged or held meets standards designed to assure the product’s continued safety, quality and purity.

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An approval letter authorizes commercial marketing of the drug with specific prescribing information for specific indications.

Even if the FDA approves a product, depending on the specific risks to be addressed it may limit the approved indications for use of the product, require that contraindications, warnings or precautions be included in the product labeling, require that post-approval studies, including Phase 4 clinical trials, be conducted to further assess a drug’s safety after approval, require testing and surveillance programs to monitor the product after commercialization, or impose other conditions, including distribution and use restrictions or other risk management mechanisms under a REMS, which can materially affect the potential market and profitability of the product.

distribution and use restrictions or other risk management mechanisms under a REMS, which can materially affect the potential market and profitability of the product.

The FDA may prevent or limit further marketing of a product based on the results of post-marketing studies or surveillance programs.

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A drug is eligible for Fast Track designation if it is intended to treat a serious or life-threatening disease or condition and demonstrates the potential to address unmet medical needs for such disease or condition.

Fast Track designation provides increased opportunities for sponsor interactions with the FDA during preclinical and clinical development, in addition to the

potential for rolling review once a marketing application is filed.

Fast Track designation provides increased opportunities for sponsor interactions with the FDA during preclinical and clinical development, in addition to the potential for rolling review once a marketing application is filed.

Rolling review means that the agency may review portions of the marketing application before the sponsor submits the complete application.

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Furthermore, Fast Track designation, Breakthrough Therapy designation, Priority Review and Accelerated Approval do not change the scientific or medical standards for approval or the quality of evidence necessary to support approval, though they may expedite the development or review process.

Orphan Designation

Under the Orphan Drug Act, the FDA may grant orphan designation to a drug intended to treat a rare disease or condition, which is generally a disease or condition that affects fewer than 200,000 individuals in the United States, or 200,000 or more individuals in the United States and for which there is no reasonable expectation that the cost of developing and making a drug available in the United States for this type of disease or condition will be recovered from sales of the product.

Orphan drug designation must be requested before submitting an NDA.

After the FDA grants orphan drug designation, the identity of the drug and its potential orphan use are disclosed publicly by the FDA.

Orphan drug designation does not convey any advantage in or shorten the duration of the regulatory review and approval process.

Orphan drug designation entitles a party to financial incentives such as opportunities for grant funding towards clinical trial costs, tax advantages and user-fee waivers.

If a drug that has orphan designation subsequently receives the first FDA approval for the disease or condition for which it has such designation, the drug is entitled to orphan drug exclusivity, which means that the FDA may not approve any other applications to market the same drug for the same indication for seven years, except in limited circumstances, such as a showing of clinical superiority to the drug with orphan exclusivity.

Competitors, however, may receive approval of different drugs for the indication for which the orphan drug has exclusivity or obtain approval for the same drug but for a different indication for which the orphan drug has exclusivity.

Orphan drug exclusivity also could block the approval of one of our therapeutic candidates for seven years if a competitor obtains approval of the same drug as defined by the FDA or if our therapeutic candidate is determined to be contained within the competitor’s drug for the same indication or disease.

If a drug designated as an orphan drug receives marketing approval for an indication broader than what is designated, it may not be entitled to orphan drug exclusivity.

Orphan drug status in the European Union has similar, but not identical, benefits.

US Post-Approval Requirements for Drugs

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For example, the FDA may require post-market testing, including Phase 4 clinical trials, and surveillance to further assess and monitor the product’s safety and effectiveness after commercialization.

In addition, drug manufacturers and other entities involved in the manufacture and distribution of approved drugs, and those supplying products, ingredients, and components of them, are

required to register their establishments with the FDA and certain state agencies and are subject to periodic unannounced inspections by the FDA and certain state agencies for compliance with ongoing regulatory requirements, including cGMPs, which impose certain procedural and documentation requirements.

In addition, drug manufacturers and other entities involved in the manufacture and distribution of approved drugs, and those supplying products, ingredients, and components of them, are required to register their establishments with the FDA and certain state agencies and are subject to periodic unannounced inspections by the FDA and certain state agencies for compliance with ongoing regulatory requirements, including cGMPs, which impose certain procedural and documentation requirements.

Failure to comply with statutory and regulatory requirements may subject a manufacturer to legal or regulatory action, such as warning letters, suspension of manufacturing, product seizures, injunctions, civil penalties or criminal prosecution.

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Manufacturers must submit periodic reports to the DEA of the distribution of Schedule I and II controlled substances, Schedule III narcotic substances, and other designated substances.

Registrants must

also report any controlled substance thefts or significant losses, and must obtain authorization to destroy or dispose of controlled substances.

Registrants must also report any controlled substance thefts or significant losses, and must obtain authorization to destroy or dispose of controlled substances.

Imports of Schedule I and II controlled substances for commercial purposes are generally restricted to substances not already available from a domestic supplier or where there is not adequate competition among domestic suppliers.

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State authorities, including boards of pharmacy, regulate use of controlled substances in each state.

Failure to maintain compliance with applicable requirements, particularly as manifested in the loss or diversion of controlled substances, can result in enforcement action that could have a material adverse effect on our business, operations and financial condition.

operations and financial condition.

The DEA may seek civil penalties, refuse to renew necessary registrations, or initiate proceedings to revoke those registrations.

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Furthermore, the applicant may only start a clinical trial at a specific study site after the relevant independent ethics committee has issued a favorable opinion.

In April 2014, the EU adopted the new Clinical Trials Regulation (EU) No 536/2014, which replaced the previous Clinical Trials Directive 2001/20/EC on January 31, 2022 and overhauls the system of approvals for clinical trials in the EU.

In April 2014, the EU adopted the Clinical Trials Regulation (EU) No 536/2014, which replaced the previous Clinical Trials Directive 2001/20/EC on January 31, 2022 and overhauls the system of approvals for clinical trials in the EU.

Specifically, the new legislation, which is directly applicable in all EU Member States (meaning that no national implementing legislation in each EU Member State is required), aims at simplifying and streamlining the approval of clinical trials in the EU.

For instance, the new Clinical Trials Regulation provides for a streamlined application procedure via a single-entry point (instead of submitting applications separately to each national competent authority and ethics committee in the Member States in which the trial will be conducted) and strictly defined deadlines for the assessment of clinical trial applications.

For instance, the Clinical Trials Regulation provides for a streamlined application procedure via a single-entry point (instead of submitting applications separately to each national competent authority and ethics committee in the Member States in which the trial will be conducted) and strictly defined deadlines for the assessment of clinical trial applications.

The Clinical Trials Regulation also makes it more efficient for EU Member States to evaluate and authorize applications together, via the Clinical Trials Information System.

The transitory provisions of the new Clinical Trials Regulation provide that, by January 31, 2025, all ongoing clinical trials must have transitioned to the new EU Clinical Trials Regulation.

The transitory provisions of the Clinical Trials Regulation provide that, by January 31, 2025, all ongoing clinical trials must have transitioned to the new EU Clinical Trials Regulation.

Marketing Authorization

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For those products for which the use of the centralized procedure is not mandatory, pursuant to Regulation (EC) No 726/2004, applicants may elect to use the centralized procedure where either the product contains a new active substance indicated for the treatment of diseases other than those on the mandatory list, where the applicant can show that the product constitutes a significant therapeutic, scientific or technical innovation, or for which a centralized authorization would be in the interest of public health.

Our investigational COMP360 psilocybin therapy, as a new active substance indicated for the treatment of treatment-resistant depression, will have the option to be filed through the centralized procedure.

Under the centralized procedure, the Committee for Medicinal Products for Human use, or the CHMP, which is the EMA’s committee that is responsible for human medicines, is responsible for conducting the assessment of whether a medicine meets the required quality, safety and efficacy requirements, and whether it has a positive risk/benefit profile.

Our investigational COMP360 psilocybin treatment, as a new active substance indicated for the treatment of treatment-resistant depression, will have the option to be filed through the centralized procedure.

medicine meets the required quality, safety and efficacy requirements, and whether it has a positive risk/benefit profile.

Under the centralized procedure, the maximum timeframe for the evaluation of an MAA is 210 days from the receipt of a valid MAA, excluding clock stops when additional information or written or oral explanation is to be provided by the applicant in response to questions asked by the CHMP.

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If the CHMP accepts such a request, the timeframe of 210 days for assessment will be reduced to 150 days (excluding clock stops), but it is possible that the CHMP may revert to the standard time limit for the centralized procedure if it determines that the application is no longer appropriate to conduct an accelerated assessment.

Now that the UK (which comprises Great Britain and Northern Ireland) has left the EU, Great Britain is no longer be covered by centralized marketing authorizations (under the Northern Ireland Protocol, centralized marketing authorizations continue to be recognized in Northern Ireland).

All medicinal products with a current centralized marketing authorization were automatically converted to Great Britain marketing authorizations on January 1, 2021.

Until December 31, 2023, the MHRA may rely on a decision taken by the European Commission on the approval of a new marketing authorization in the centralized procedure, in order to more quickly grant a new Great Britain marketing authorization.

A separate application will, however, still be required.

On January 24, 2023, the MHRA announced that a new international recognition framework will be put in place from January 1, 2024, which will have regard to decisions on the approval of marketing authorizations made by the EMA and certain other regulators.

Now that the UK (which comprises Great Britain and Northern Ireland) has left the EU, Great Britain is no longer covered by centralized marketing authorizations (under the Northern Ireland Protocol, centralized marketing authorizations currently continue to be recognized in Northern Ireland).

On January 1, 2024, a new international recognition framework was put in place by the MHRA, under which the MHRA may have regard to decisions on the approval of marketing authorizations made by the EMA and certain other regulators.

The MHRA also has the power to have regard to marketing authorizations approved in EU Member States through decentralized or mutual recognition procedures with a view to more quickly granting a marketing authorization in the United Kingdom or Great Britain.

The decentralized marketing authorization procedure allows an applicant to apply for simultaneous authorization in more than one EU Member State of medicinal products that have not yet been authorized in any EU Member State and that do not fall within the mandatory scope of the centralized procedure.

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Where, during the course of development, a medicine no longer meets the eligibility criteria, support under the PRIME scheme may be withdrawn.

Orphan Drug Designation

Orphan drug designation must be requested before submitting an NDA.

After the FDA grants orphan drug designation, the identity of the drug and its potential orphan use are disclosed publicly by the FDA.

Orphan drug designation does not convey any advantage in or shorten the duration of the regulatory review and approval process.

Orphan drug designation entitles a party to financial incentives such as opportunities for grant funding towards clinical trial costs, tax advantages and user-fee waivers.

If a drug designated as an orphan drug receives marketing approval for an indication broader than what is designated, it may not be entitled to orphan drug exclusivity.

Orphan drug status in the European Union has similar, but not identical, benefits.

Orphan Designation

Regulation (EC) No.

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(2) either (i) such condition affects no more than five in ten thousand persons in the EU when the application is made, or (ii) it is unlikely that the marketing of the product in the EU, without the benefits derived from orphan status, would generate sufficient return to justify the necessary investment in its development;

and (3) there exists no satisfactory method of diagnosis, prevention, or treatment of such condition

authorized for marketing in the EU or, if such method exists, the product would be of significant benefit compared to products available for that condition.

and (3) there exists no satisfactory method of diagnosis, prevention, or treatment of such condition authorized for marketing in the EU or, if such method exists, the product would be of significant benefit compared to products available for that condition.

An orphan designation provides a number of benefits in the EU, including fee reductions, regulatory assistance and the ability to apply for a centralized marketing authorization.

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The grant of a marketing authorization for an orphan medicinal product leads to a ten-year period of market exclusivity.

During this market exclusivity period, neither the EMA nor the European Commission or the Member States can accept an application or grant a marketing authorization for the same therapeutic indication in respect of a “similar medicinal product”.

During this market exclusivity period, neither the EMA nor the European Commission or competent authorities of the Member States can accept an application or grant a marketing authorization for the same therapeutic indication in respect of a “similar medicinal product”.

A “similar medicinal product” is defined as a medicinal product containing a similar active substance or substances as contained in an authorized orphan medicinal product, and which is intended for the same therapeutic indication.

The market exclusivity period for the authorized therapeutic indication may, however, be reduced to six years if, at the end of the fifth year, it is established that the product no longer meets the criteria for orphan designation, for example because the product is sufficiently profitable not to justify market exclusivity.

There are also limited derogations from the ten-year period of market exclusivity pursuant to which the European Commission may grant a marketing authorization for a similar medicinal product in the same therapeutic indication.

There are also limited derogations from the ten-year period of market exclusivity pursuant to which marketing authorization may be granted for a similar medicinal product in the same therapeutic indication.

These are where:

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Further, the obligation to provide pediatric clinical trial data can be waived by the PDCO when this data is not needed or appropriate because the product is likely to be ineffective or unsafe in children, the disease or condition for which the product is intended occurs only in adult populations, or when the product does not represent a significant therapeutic benefit over existing treatments for pediatric patients.

Products that are granted a marketing authorization with the results of the pediatric clinical trials conducted in accordance with the PIP are eligible for a six-month extension of the protection under a supplementary protection certificate or SPC (provided an application for such extension is made at the same time as filing the SPC application for the product, or at any point up to 2 years before the SPC expires), even where the trial results are negative.

Products that are granted a marketing authorization with the results of the pediatric clinical trials conducted in accordance with the PIP are eligible for a six-month extension of the protection under a supplementary protection certificate or SPC (provided an application for such extension is made at the same time as filing the SPC application for the product, or at any point up to two years before the SPC expires), even where the trial results are negative.

In the case of orphan medicinal products, a two year extension of the orphan market exclusivity may be available.

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Data and Market Exclusivity

In the EU, innovative medicinal products approved on the basis of a complete independent data package qualify for eight years of data exclusivity upon grant of a marketing authorization and an additional two years of market exclusivity pursuant to Regulation (EC) No.

In the EU, innovative medicinal products approved on the basis of a complete and independent data package qualify for eight years of data exclusivity upon grant of a marketing authorization and an additional two years of market exclusivity

pursuant to Regulation (EC) No.

726/2004, as amended, and Directive 2001/83/EC, as amended.

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The regulatory authorities may also impose specific obligations as a condition of the marketing authorization.

Such risk-minimization measures or post-authorization obligations may include additional safety monitoring, more frequent submission of PSURs, or the conduct of additional clinical trials or post-authorization safety studies.

minimization measures or post-authorization obligations may include additional safety monitoring, more frequent submission of PSURs, or the conduct of additional clinical trials or post-authorization safety studies.

RMPs and PSURs are routinely available to third parties requesting access, subject to limited redactions.

Furthermore, the manufacturing of authorized products, for which a separate manufacturer’s license is mandatory, must also be conducted in strict compliance with the applicable EU laws, regulations and guidance, including Directive 2001/83/EC, Directive 2003/94/EC, Regulation (EC) No 726/2004 and the European Commission Guidelines for Good Manufacturing Practice.

Furthermore, the manufacturing of authorized products, for which a separate manufacturer’s license is mandatory, must also be conducted in strict compliance with the applicable EU laws, regulations and guidance, including Directive 2001/83/EC, Directive (EU) 2017/1572, Regulation (EC) No 726/2004 and the European Commission Guidelines for Good Manufacturing Practice.

These requirements include compliance with the EU cGMP standards which mandate the methods, facilities and controls used in manufacturing, processing and packing of products to assure their safety and identity.

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The advertising of prescription-only medicines to the general public is not permitted in the EU, or in the UK under the Human Medicines Regulations 2012.

Although general requirements for advertising and promotion of medicinal products

are established under EU Directive 2001/83/EC as amended, the details are governed by regulations in each EU Member State and can differ from one country to another.

The aforementioned EU rules are generally applicable in the EEA, which consists of the EU Member States, plus Norway, Liechtenstein and Iceland.

Although general requirements for advertising and promotion of medicinal products are established under EU Directive 2001/83/EC as amended, the details are governed by regulations in each EU Member State and can differ from one country to another.

The aforementioned EU rules are generally applicable in the EEA (which consists of the EU Member States plus Norway, Iceland and Liechtenstein).

Reform of the Regulatory Framework in the European Union

The European Commission introduced legislative proposals in April 2023 that, if implemented, will replace the current regulatory framework in the EU for all medicines (including those for rare diseases and for children).

The European Commission has provided the legislative proposals to the European Parliament and the European Council for their review and approval.

In October 2023, the European Parliament published draft reports proposing amendments to the legislative proposals, which will be debated by the European Parliament.

Once the European Commission’s legislative proposals are approved (with or without amendment), they will be adopted into EU law.

Brexit and the Regulatory Framework in the United Kingdom

The UK formally left the EU (commonly referred to as “Brexit”) on January 31, 2020 and the EU and the UK have concluded a trade and cooperation agreement, or TCA, which was provisionally applicable since January 1, 2021 and has been formally applicable since May 1, 2021.

The TCA includes specific provisions concerning pharmaceuticals, which include the mutual recognition of GMP, inspections of manufacturing facilities for medicinal products and GMP documents issued, but does not foresee wholesale mutual recognition of UK and EU pharmaceutical regulations.

At present, Great Britain has implemented EU legislation on the marketing, promotion and sale of medicinal products through the Human Medicines Regulations 2012 (as amended) (under the Northern Ireland Protocol, the EU regulatory framework continues to apply in Northern Ireland).

Except in respect of the new EU Clinical Trials Regulation, the regulatory regime in Great Britain therefore largely aligns with EU regulations, however it is possible that these regimes will diverge more significantly in future now that Great Britain’s regulatory system is independent from the EU and the TCA does not provide for mutual recognition of UK and EU pharmaceutical legislation.

The TCA includes specific provisions concerning pharmaceuticals, which include the mutual recognition of GMP, inspections of manufacturing facilities for medicinal products and GMP documents issued, but does not provide for wholesale mutual recognition of UK and EU pharmaceutical regulations.

Except in respect of the EU Clinical Trials Regulation, the regulatory regime in Great Britain therefore largely aligns with EU regulations, however it is possible that these regimes will diverge more significantly in future now that Great Britain’s regulatory system is independent from the EU and the TCA does not provide for mutual recognition of UK and EU pharmaceutical legislation.

However, notwithstanding that there is no wholesale recognition of EU pharmaceutical legislation under the TCA, under a new international recognition procedure mentioned above which was put in place by the MHRA on January 1, 2024, the MHRA may take into account decisions on the approval of a marketing authorization from the EMA (and certain other regulators) when considering an application for a Great Britain marketing authorization.

On February 27, 2023, the UK government and the European Commission announced a political agreement in principle to replace the Northern Ireland Protocol with a new set of arrangements, known as the “Windsor Framework”.

This new framework fundamentally changes the existing system under the Northern Ireland Protocol, including with respect to the regulation of medicinal products in the UK.

In particular, the MHRA will be responsible for approving all medicinal products destined for the UK market (i.e., Great Britain and Northern Ireland), and the EMA will no longer have any role in approving medicinal products destined for Northern Ireland.

A single UK-wide marketing authorization will be granted by the MHRA for all medicinal products to be sold in the UK, enabling products to be sold in a single pack and under a single authorization throughout the UK.

The Windsor Framework was approved by the EU-UK Joint Committee on March 24, 2023, so the UK government and the EU will enact legislative measures to bring it into law.

On June 9, 2023, the MHRA announced that the medicines aspects of the Windsor Framework will apply from January 1, 2025.

Coverage, Pricing and Reimbursement

Significant uncertainty exists as to the coverage and reimbursement status of any product candidates for which we obtain regulatory approval.

In the United States and markets in other countries, sales of any psilocybin therapy for which we receive regulatory approval for commercial sale will depend, in part, on the availability of coverage and reimbursement for our products from third-party payors, such as government health care programs (e.g., Medicare, Medicaid), managed care providers, private health insurers, health maintenance organizations, and other organizations.

In the United States and markets in other countries, sales of any psilocybin treatment for which we receive regulatory approval for commercial sale will depend, in part, on the availability of coverage and reimbursement for our products from third-party payors, such as government health care programs (e.g., Medicare, Medicaid), managed care providers, private health insurers, health maintenance organizations, and other organizations.

These third-party payors decide which medications they will pay for and will establish reimbursement levels.

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Third-party payors may also limit coverage to specific products on an approved list, or formulary, which might not include all of the FDA-approved products for a particular indication.

A decision by a third-party payor not to cover or not to separately reimburse for our medical products or therapies using our products could reduce physician utilization of our products once approved and have a material adverse effect on our sales,

results of operations and financial condition.

If there is coverage for our product candidates, or therapies using our product candidates by a third-party payor, the resulting reimbursement payment rates may not be adequate or may require co-payments that patients find unacceptably high.

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Our product candidates may nonetheless not be considered medically necessary or cost-effective.

If third-party payors do not consider a product to be cost-effective compared to other available therapies, they may not cover the product, after approval, as a benefit under their plans or, if they do, the level of payment may not be sufficient to allow a company to sell its products at a profit.

level of payment may not be sufficient to allow a company to sell its products at a profit.

A decision by a third-party payor not to cover a product could reduce physician utilization once the product is approved and have a material adverse effect on sales, our operations and financial condition.

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Healthcare providers, physicians, and third-party payors will play a primary role in the recommendation and prescription of any products for which we obtain marketing approval.

Our business operations and any current or future arrangements with

third-party payors, healthcare providers and physicians may expose us to broadly applicable federal and state fraud and abuse laws, as well as other healthcare laws and regulations.

Our business operations and any current or future arrangements with third-party payors, healthcare providers and physicians may expose us to broadly applicable federal and state fraud and abuse laws, as well as other healthcare laws and regulations.

These laws may impact, among other things, our business or financial arrangements and relationships through which we research, as well as market, sell and distribute the psilocybin therapies for which we obtain approval.

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The federal Anti-Kickback Statute has been interpreted to apply to arrangements between manufacturers on one hand and prescribers, purchasers, and formulary managers on the other.

A person or entity does not need to have actual knowledge of the federal Anti-Kickback Statute or specific intent to violate it to have committed a violation.

A person or entity does not need to have actual knowledge of the

federal Anti-Kickback Statute or specific intent to violate it to have committed a violation.

Violations are subject to significant administrative, civil and criminal fines and penalties for each violation, plus up to three times the remuneration involved, imprisonment, and exclusion from government healthcare programs.

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Similar to the federal Anti-Kickback Statute, a person or entity does not need to have actual knowledge of the statute or specific intent to violate it in order to have committed a violation;

certain covered healthcare providers, health plans, and healthcare clearinghouses as well as their respective business associates and their covered subcontractors relating to the privacy, security and transmission of individually identifiable health information.

• HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act of 2009, or HITECH, and its respective implementing regulations, which imposes, among other things, certain requirements on certain covered healthcare providers, health plans, and healthcare clearinghouses as well as their respective business associates and their covered subcontractors relating to the privacy, security and transmission of individually identifiable health information.

Among other things, HITECH makes HIPAA’s privacy and security standards directly applicable to business associates, those independent contractors or agents of covered entities that create, receive, maintain, transmit or obtain protected health information in connection with providing a service on behalf of a covered entity.

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• The federal Physician Payment Sunshine Act, created under the Patient Protection and Affordable Care Act, as amended by the Health Care and Education Reconciliation Act, collectively, the Affordable Care Act, or ACA, which requires applicable manufacturers of drugs, devices, biologics and medical supplies for which payment is available under Medicare, Medicaid or the Children’s Health Insurance Program to report annually to CMS, information related to payments or other transfers of value made to physicians (defined to include doctors, dentists, optometrists, podiatrists and chiropractors), certain other licensed health care practitioners, and teaching hospitals, as well as ownership and investment interests held by the physicians described above and their immediate family members;

• Federal government price reporting laws, which require us to calculate and report complex pricing metrics in an accurate and timely manner to government programs;

• Federal government price reporting laws, which require us to calculate and report complex pricing metrics in an accurate and timely manner to government programs, where such reported prices may be used in the calculation of reimbursement and/or discounts on approved products;

• Federal consumer protection and unfair competition laws, which broadly regulate marketplace activities and activities that potentially harm consumers;

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If our operations, including our arrangements with physicians and other healthcare providers and entities, such as our Centers of Excellence or therapists, are found to be in violation of any of such laws or any other governmental regulations that apply to us, we may be subject to significant penalties, including, without limitation, administrative, civil and criminal penalties, damages, fines, disgorgement, contractual damages, reputational harm, diminished profits and future earnings, the curtailment or restructuring of our operations, exclusion from participation in federal and state healthcare programs (such as Medicare and Medicaid), imprisonment, and additional oversight and reporting obligations if we become subject to a corporate integrity agreement or similar settlement to resolve allegations of non-compliance with these laws and the curtailment or restructuring of our operations, any of which could adversely affect our ability to operate our business and our financial results.

If any of the physicians or other healthcare providers or entities with whom we expect to do

business, including our Centers of Excellence and therapists, are found to be not in compliance with applicable laws, they may be subject to similar actions, penalties and sanctions.

If any of the physicians or other healthcare providers or entities with whom we expect to do business, including our Centers of Excellence and therapists, are found to be not in compliance with applicable laws, they may be subject to similar actions, penalties and sanctions.

Ensuring that our current and future business arrangements with third parties, and our business generally, comply with applicable healthcare laws and regulations, as well as responding to possible investigations by government authorities, can be time- and resource- consuming and can divert a company’s attention from its business.

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For example, in 2010, the ACA was enacted, which, among other things, increased rebates for drugs sold to Medicaid programs owed by most manufacturers under the Medicaid Drug Rebate Program and extends the rebate program to individuals enrolled in Medicaid managed organizations;

imposes mandatory discounts for certain Medicare Part D beneficiaries in which manufacturers must agree to offer 50% (increased to 70% pursuant to the Bipartisan Budget Act of 2018, or BBA, effective as of January 2019) point-of-sale discounts off negotiated prices of applicable brand drugs to eligible beneficiaries during their coverage gap period as a condition for manufacturers’ outpatient drugs coverage under Medicare Part D;

imposes mandatory discounts for certain Medicare Part D beneficiaries in which manufacturers must agree to offer 70% point-of-sale discounts off negotiated prices of applicable brand drugs to eligible beneficiaries during their coverage gap period as a condition for manufacturers’ outpatient drugs coverage under Medicare Part D;

subjects drug manufacturers of certain branded prescription drugs to new annual, nondeductible fees and taxes;

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created a new requirement to annually report the identity and quantity of drug samples that manufacturers and authorized distributors of record provide to physicians;

created a new Patient Centered Outcomes Research Institute to oversee, identify priorities in and conduct comparative clinical effectiveness research, along with funding for such research;

created a Patient Centered Outcomes Research Institute to oversee, identify priorities in and conduct comparative clinical effectiveness research, along with funding for such research;

and established the Center for Medicare and Medicaid Innovation at CMS to test innovative payment and service delivery models to lower Medicare and Medicaid spending.

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There is no obligation for a drug manufacturer to make its drug products available to eligible patients as a result of the Right to Try Act.

On March 11, 2021, President Biden signed the American Rescue Plan Act of 2021 into law, which eliminates the statutory Medicaid drug rebate cap, currently set at 100% of a drug’s average manufacturer price, for single source and innovator multiple source drugs, beginning January 1, 2024.

Due to the Statutory Pay-As-You-Go Act of 2010, estimated budget deficit increases resulting from the American Rescue Plan Act of 2021, and subsequent legislation, Medicare payments to providers will be further reduced starting in 2025 absent further legislation.

These laws and regulations may result in additional reductions in Medicare and other healthcare funding and otherwise affect the prices we may obtain for any of our product candidates for which we may obtain regulatory approval or the frequency with which any such product candidate is prescribed or used.

The Inflation Reduction Act of 2022, or IRA, includes several provisions that may impact our business to varying degrees, including provisions that reduce the out-of-pocket cap for Medicare Part D beneficiaries to $2,000 starting in 2025;

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government to negotiate Medicare Part B and Part D price caps for certain high-cost drugs and biologics without generic or biosimilar competition, require companies to pay rebates to Medicare for certain drug prices that increase faster than inflation, and delay the rebate rule that would limit the fees that pharmacy benefit managers can charge.

Further, under the IRA, orphan drugs are exempted from the Medicare drug price negotiation program, but only if they have one rare disease designation and for which the only approved indication is for that disease or condition.

If a product receives multiple rare disease designations or has multiple approved indications, it may not qualify for the orphan drug exemption.

The overall impact that the IRA will have on our business and the healthcare industry in general is not yet known.

Further, under the IRA, orphan drugs are exempted from the Medicare drug price negotiation program, but only if they have one orphan designation and for which the only approved indication is for that disease or condition.

If a product receives multiple orphan designations or has multiple approved indications, it may not qualify for the orphan drug exemption.

The implementation of the IRA is currently subject to ongoing litigation challenging the constitutionality of the IRA’s Medicare drug price negotiation program.The overall impact that the IRA will have on our business and the healthcare industry in general is not yet known.

Moreover, payment methodologies may be subject to changes in healthcare legislation and regulatory initiatives.

For example, CMS may develop new payment and delivery models, such as bundled payment models.

Recently, there has been

heightened governmental scrutiny over the manner in which manufacturers set prices for their marketed products.

Recently, there has been heightened governmental scrutiny over the manner in which manufacturers set prices for their marketed products.

Such scrutiny has resulted in several recent U.S.

Congressional inquiries and proposed and enacted federal and state legislation designed to, among other things, bring more transparency to drug pricing, review the relationship between pricing and manufacturer patient programs, reduce the cost of drugs under Medicare, and reform government program reimbursement methodologies for pharmaceutical products.

In addition, President Biden has issued multiple executive orders that have sought to reduce prescription drug costs.

In February 2023, HHS also issued a proposal in response to an October 2022 executive order from President Biden that includes a proposed prescription drug pricing model that will test whether targeted Medicare payment adjustments will sufficiently incentivize manufacturers to complete confirmatory trials for drugs approved through FDA’s accelerated approval pathway.

Although a number of these and other proposed measures may require authorization through additional legislation to become

effective, and the Biden administration may reverse or otherwise change these measures, both the Biden administration and Congress have indicated that they will continue to seek new legislative measures to control drug costs.

Although a number of these and other proposed measures may require authorization through additional legislation to become effective, and the Biden administration may reverse or otherwise change these measures, both the Biden administration and Congress have indicated that they will continue to seek new legislative measures to control drug costs.

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Human Capital Management

As a mental health care company, we’re dedicated to accelerating patient access to evidence-based innovation in mental health.

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

Our team is the key to our success, and we believe it is essential to invest in building an engaged, diverse, supported, and incentivized workforce who can help us achieve our vision of a world of mental wellbeing.

As of December 31, 2022, we had 181 employees.

134 employees are engaged in research and development activities and 47 employees are engaged in general administrative functions.

As of December 31, 2023, we had 186 employees, of whom 141 employees are engaged in research and development activities and 45 employees are engaged in general administrative functions.

We had 181 employees as of December 31, 2022 and grew by 2.8% as of December 31, 2023.

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We believe our relations with our employees are good.

In 2021, we hired our first Chief People Officer to lead our human capital efforts as described below.

Our primary initiatives in attracting, retaining, and developing our employees include:

Mental Health and Wellbeing

As a mental health care company, we aspire to be a leader in building a workplace that reduces the stigma of mental illness and fosters employee wellbeing.

As a biotechnology company focused on mental health, we aspire to be a leader in building a workplace that reduces the stigma of mental illness and fosters employee wellbeing.

We take a holistic view of wellbeing support that includes mental and physical health support for all employees at Compass.

We offer various wellbeing resources which include:

• a global employee assistance program run by certified counsellors, offering 10+ therapy sessions per issue for team members and their families;

• company-paid employee health care coverage, including access and financial support for a private mental health care in the UK;

• a global employee assistance program run by certified counsellors, offering up to 18 therapy sessions per issue for team members and their families;

• one-to-one confidential wellbeing check-ins, onboarding and offboarding with our wellbeing community lead;

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• group health coaching series to help keep individuals on track towards their health goals;

• team meetings include wellbeing segments facilitated by our wellbeing community lead;

• team meetings periodically include wellbeing segments facilitated by our wellbeing community lead and we use wellbeing team surveys and manager-led discussions during team meetings to identify and overcome any wellbeing issues;

• training for managers on how to address wellbeing issues in their teams and provide support;

• access to a meditation app with weekly group meditation sessions;

• company-paid employee health care coverage;

• weekly qualified employee-led yoga sessions;

• company-wide closedowns over the summer and year-end holidays, to make it easier for team members to disconnect during their time off.

In 2022, we became a member of One Mind at Work and a signatory to their Charter .

One Mind at Work is a global coalition of organizations committed to the development and implementation of a gold standard for workplace mental health and wellbeing.

• company-wide shutdown over the year-end holiday, to make it easier for team members to disconnect during their time off.

In 2023 we signed the StigmaFree pledge organized by the National Alliance on Mental Illness (NAMI), as part of our commitment to a company culture of openness, acceptance, and understanding about employees’ overall mental health and well-being.

NAMI is the largest grassroots mental health organization in the United States dedicated to building better lives for the millions of Americans affected by mental illness.

Engagement, Culture and Values

We strive to attract and retain people who are driven by our mission as well as the motivation to find better ways to help and empower those who are suffering with mental health challenges.

We all share our values of being compassionate, bold, inclusive, and rigorous.

In 2022, we were certified a Most Loved Workplace by Best Practice Institute (BPI) and its Most Loved Workplaces® operation, which is a company that assesses and certifies a company as a workplace employees love based on internal surveys, external public ratings and interviews with corporate officials, ranking number 31 in the UK.

We aim to attract and retain people who are driven by our mission to help and empower those who are suffering with mental health challenges.

We strive to live our values of compassion, boldness, inclusiveness, and rigor.

In 2022 and 2023, we applied to be certified as a Most Loved Workplace by Best Practice Institute (BPI) and its Most Loved Workplaces® operation, which is a company that assesses and certifies a company as a workplace employees love based on internal surveys, external public ratings and interviews with corporate officials, ranking number 67 in the UK.

The list recognizes companies that put respect, caring, and appreciation for their employees at the center of their business model.

We continue to build a positive working culture by:

• Holding annual engagement surveys with results owned by our senior leadership team who are accountable for setting out action plans.

Our 2022 survey demonstrates that we continue to have a very strong 39% net promoter score, compared to a 45% net promoter score in 2021;

• Holding periodic engagement surveys with employees and carrying out action plans to address areas for improvements.

Our 2023 pulse survey demonstrated that we continue to maintain a very strong 52% net promoter score;

according to Qualtrics XM Institute, a score of between 10 to 30% is good and a score of 30% or more is excellent;

We run our engagement and culture survey at least annually in order to continually monitor our working environment, celebrate areas that are working well and take actions to address areas identified for improvement;

• Supporting employees’ participation in our social, wellbeing, environmental, learning and development, and diversity, equity, and inclusion groups.

These groups include junior through executive level employees and employees are responsible for championing various initiatives;

• Hosting annual company values workshops for all employees to discuss our values and bring them to life;

• Holding monthly company-wide team meetings aimed to connect and receive updates from our CEO and the wider teams;

• Providing additional opportunities to stay connected in our hybrid working model, with initiatives such as Friday Fives, randomized five minutes ‘water cooler’ Zoom rounds, ‘lunch and learns’ hosted by various functions;

remote and in-person social events;

and Zoom open ‘office hours’ with our chief executive officer;

• Having exit interviews to understand what we can do better to improve our culture and engagement.

• Holding focus groups with volunteers from across our company to hear their views about what we are doing well as a company and what we could do better to improve engagement;

• Holding periodic company-wide team meetings aimed to connect and receive updates from our CEO and the wider teams, with the opportunity for anonymous question and answer session with management;

• Providing additional opportunities to stay connected in our hybrid working model, for learning and social occasions;

• Holding periodic open ‘office hours’ with our chief executive officer and other members of the executive team;

• Gathering input from new hires and employees who are leaving our company to understand what we can do better to improve our culture and engagement.

Diversity, Equity, and Inclusion

We are united in our resolve to build a safe, diverse, accepting, and inclusive culture in our workplace and have been actively involved in similar efforts in our communities, such as participating in youth mentoring programs and organizing employee charitable donation programs.

Our engagement and culture survey also probes perceptions of equity, diversity and inclusion.

This year we continued work with our Diversity, Equity, and Inclusion (DEI) employee-led committee and collaborated alongside the Employers’ Network for Equality and Inclusion (ENEI), of which we are members, and who serve as our external advisors.

The focus areas of the DEI committee were:

• Continuing a data collection campaign around employees voluntarily providing their personal demographic information, to enable us to begin measuring our workforce diversity and set goals to improve diversity;

• Raising awareness of DEI issues through training.

We hosted training and dialogue sessions for employees to learn about how to think and act inclusively.

We also held periodic workplace harassment training to build awareness and capabilities.

For our leadership team, we held an expert session and conversation about how to lead inclusively;

• Providing a dedicated space for employees to share their experiences, concerns, and suggestions around DEI through our community circles;

• Celebrating Pride Month with a panel and events;

• Making changes to our processes to recruit diverse candidates, including:

◦ We are connecting with experienced partners to support us to diversify our pool of candidates.

We also use job boards dedicated to LGBTQ+, ethnic minorities, and neurodivergent job applicants;

◦ We have improved the accessibility of our website for people with visual impairments.

We also invite candidates to notify us if any disability accommodations are needed in the interview process;

◦ We are a signatory to the UK Disability Confident Scheme, which aims to help organizations employ disabled people.

Disability Confident is creating a movement of change, encouraging employers to think differently about disability and take action to improve how they recruit, retain, and develop disabled people.

This encompasses visible and non-visible disabilities.

As of December 31, 2022, our board had 33% female representation and 39% of our wider executive management team was female.

We are united in our resolve to build a safe, diverse, accepting, and inclusive culture in our workplace and have been actively involved in similar efforts in our communities.

In 2023, we formed our Diversity Council, a cross-functional diverse group of employees empowered to embed diversity, equity and inclusion across our business.

Focus areas of the Diversity Council include diversity in clinical trials, therapist diversity, digital accessibility, patient engagement, education and awareness and inclusive culture, recruitment, and retention.

The council advanced a number of diversity, equity and inclusion initiatives in 2023, including:

• Hosted awareness events, such as Black History Month, Hispanic Heritage Month and Pride Month;

• Refreshed our global diversity, equity and inclusion policy.

The policy covers topics like our practices and policies on recruiting talent, compensation, developing, and training employees.

This policy seeks to support a diverse workforce and ensure that our team members are treated equitably;

• Supported research through a grant to the Grady Trauma Project focused on exploring the healthcare needs and attitudes towards investigational psychedelic treatments in marginalized and underprivileged communities.

The results were published in the Journal of Mood & Anxiety Disorders, and “Perceptions of Psychedelic-Assisted Therapy Among Black Americans” is the first published study exploring Black Americans’ perceptions of psychedelic treatment;

• Collaborated with Phase 3 TRD clinical trial sites to support diversity in recruitment of clinical trial participants to evaluate COMP360 across ethnicities, races, and genders and identified best practices and challenges to increasing representation in clinical trials;

• Engaged patients through the Mental Health Experiences community, a private online group of people with personal experience of TRD.

The community is made up of people from a range of backgrounds, including 42% ethnic minorities and 30% LBGTQ+.

The community discusses different themes, such as the experience of living with depression and barriers to participating in clinical trials.

Listening to people’s lived experiences and using targeted questions helps us understand the unmet needs of patients from various backgrounds and to focus on these needs as we work to develop new treatments;

• Applied a diversity, equity and inclusion perspective to our brand refresh, ensuring our brand is accessible to those with visual impairments.

As of December 31, 2023, our board had 40% female representation and 46% of our wider senior management team was female.

Overall, our total female representation in the company as of December 31, 2023, was 64%, which is well above the 49% average according to the 2022 report by Biotechnology Innovation Organization.

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We are committed to the continued development of our employees, and to support their growth.

To help us identify, foster, and retain high performing employees, we have several programs:

To help us identify, foster, and retain high performing employees, we have a range of resources and initiatives, including:

• Job architecture, providing employees with guidance and clear pathways for developing and progressing their career and twice-yearly promotions cycle;

• A process for performance and development goals that is tied to employees receiving feedback throughout the year and assessing individual performance and rewards at the end of the year;

• Dedicated internal resources to support employees’ personal development and career goals and embed development goals with support of mentoring and other development tools;

• Dedicated internal resources, including regular webinars to support employees’ personal development and career goals and embed development goals with support of mentoring and other development tools;

• Talent reviews, a twice-yearly process to assess and calibrate talent for the purposes of rewards and development;

• Specialized negotiations and communications skills training courses delivered by an external resource;

• A learning curriculum of courses on offer delivered by external experts to develop specific skill areas;

• An annual learning and development allowance for each employee to spend on personal development/job related training;

• Growth days, in-person quarterly half-day sessions to bring together our early career talent to network, learn, and socialize;

• A special learning series for people managers about how to retain, engage, and motivate.

• In-person quarterly half-day sessions to bring together our early career talent to network, learn, and socialize;

• 1:1 coaching support to facilitate the re-integration of women returning from maternity leave.

Compensation and Benefits

We provide competitive compensation and comprehensive benefits for our employees globally.

Our compensation packages include base salary, annual bonus, annual equity awards, company paid healthcare plans, health screening, generous paid time-off, travel insurance, life/disability and income protection insurance, and retirement saving plans with company matching contributions.

We also have an employee share purchase plan, under which eligible employees have the opportunity to buy our shares through payroll deductions every six months at a discount to the market price at the beginning or end of the each offering period, whichever is lower.

We provide competitive compensation and comprehensive benefits for our employees.

Our compensation packages include base salary, annual bonus, annual equity awards, company paid healthcare plans, generous paid time-off and leave policies, travel insurance, life/disability and income protection insurance, and retirement saving plans with company matching contributions.

We also have an employee share purchase plan, under which eligible employees have the opportunity to buy our shares through payroll deductions every six months at a discount.

Aligned with our values, in 2023, we launched a new policy for family and dependent care and refreshed Maternity (UK), Paternity (UK), Parental Leave (US), and Adoption Leave (UK), which provide support to our multi-generational diverse workforce to care for their families.

We also facilitate a parent and carers group who support each other and recommend policy changes like these to management.

Our compensation and benefits are designed to provide employees with total compensation packages that are competitive with those offered by our peers and other companies with which we compete for talent.

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Keeping our values in mind, we recognize that to be inclusive and compassionate, we should empower everyone to work in the ways that suit them best.

Although many companies have reverted to mandatory office attendance, we have retained a hybrid working model since it is aligned with our values and it is an attractive feature of our employment value proposition.

Our guidelines for ways of working set out core principles around what we expect from each other, rather than enforcing a rigid model.

We believe in each other’s dedication to our mission, and we trust each other to make the best use of our working time.

We look for the proof of that in our achievements, not in our working hours or location of work.

We are bold in doing things differently if that’s what works best, testing new ways of working and adjusting them as we go.

By allowing people to work in the way that suits them, employees have the flexibility to look after themselves.

They can choose whether to work in the office or at home, can go out for a walk or a run in the middle of the day, and they have the flexibility to attend appointments.

We encourage employees to remain connected through virtual, casual and voluntary weekly meetups.

Alongside our ways of working policy, we also have a work-from-home budget for employees to purchase items that will make working at home a more comfortable and ergonomic experience.

We still recognize the importance of connecting face-to-face with colleagues and with our growth in the United States this year we opened our first standalone office in New York City.

We still recognize the importance of connecting face-to-face with colleagues for collaboration and social time in our communal spaces in London, New York, and San Francisco.

Corporate Information

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Item 1. Business