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Item 1. Business

2023-02-28 compared with 2022-02-24 · 456 added, 366 removed, 1125 unchanged (42% of the section changed)

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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.

Our initial focus is on treatment-resistant depression, or TRD, a subset of major depressive disorder, or MDD, comprising patients who are inadequately served by the current treatment paradigm.

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 .

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.

We have developed a proprietary, high-purity polymorphic crystalline formulation of psilocybin, COMP360.

In 2019, we completed a Phase I 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 IIb studies.

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 IIb clinical trial evaluating COMP360 in conjunction with psychological support for the treatment of TRD.

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.

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.

The topline results from the 233-participant trial showed a rapid and sustained response for patients receiving a single dose of COMP360 psilocybin administered 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 against the 1mg dose of COMP360 in reducing depressive symptom severity after three weeks.

We believe that our COMP360 psilocybin therapy - combining COMP360 psilocybin with psychological support from specially trained therapists - could offer a new approach to depression care.

Globally, more than 320 million people suffer with 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.

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.

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

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

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

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

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

Esketamine was approved in 2019 by the FDA.

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

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

In addition to pharmacotherapies, various forms of somatic intervention are also used, although these treatments tend to be invasive and/or onerous, and there are 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.

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

Psilocybin is considered a serotonergic hallucinogen and is an active ingredient in some species of mushrooms.

While classified as a Schedule I drug, there is an accumulating body of evidence that psilocybin may have beneficial effects on depression and other mental health conditions.

Therefore, the FDA and the US Drug Enforcement Administration, or DEA, have permitted the use of psilocybin in clinical studies for the treatment of a range of psychiatric conditions.

We believe that our investigational COMP360 psilocybin therapy may confer beneficial effects in depression and other mental health conditions through COMP360’s mechanism of action on the central nervous system, or CNS.

By activating the 5-hydroxytryptamine (serotonin) 2A, or 5-HT 2A , receptor, psilocybin and its active metabolite psilocin induce a range of downstream effects that may cause important, sustained changes in brain function.

These effects include altered extracellular release of serotonin and dopamine, changes in brain network connectivity, and increased levels of neuroplasticity, whereby the nervous system is able to reorganize its structure, function, and connections, all of which we believe contribute to our psilocybin therapy’s potential to generate rapid-onset and sustained positive mood effects.

The potential of psilocybin therapy in mental health conditions has been demonstrated in a number of academic-sponsored studies over the last decade.

In these early studies, it was observed that psilocybin therapy provided rapid reductions in depression symptoms after a single high dose, with antidepressant effects lasting for up to at least six months for a number of patients.

These studies assessed symptoms related to depression and anxiety through a number of widely used and validated scales.

The data generated by these studies suggest that psilocybin is generally well-tolerated and has the potential to treat depression when administered with psychological support.

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 believe this support, or therapy, is an integral element of psilocybin therapy.

The psilocybin administration session lasts approximately six to eight hours, with patients supported by therapists in a non-directive manner.

Psilocybin administration sessions are preceded by preparation sessions, in which patients are given a thorough orientation, and followed by integration sessions to help patients process the range of emotional and physical experiences facilitated by COMP360 administration.

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

In 2019, we completed a Phase I trial in 89 healthy volunteers, with our investigational COMP360 psilocybin therapy.

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

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

In August 2020, the FDA approved our request for a 1:1 model of therapist support and we intend to use this model in future clinical trials.

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

We are now undertaking an additional series of safety pharmacology and toxicity studies, to be completed prior to commencement of our anticipated Phase III program.

In 2021, we completed a randomized, controlled, double-blind Phase IIb clinical trial in 233 patients suffering with TRD, in 22 sites across North America and Europe.

This dose-finding trial investigated the safety and efficacy of a single administration of COMP360 combined with psychological support from specially trained therapists.

In order to determine the optimal dose of COMP360, with three doses (1mg, 10mg, 25mg) were explored.

The primary endpoint of this clinical trial was to evaluate the efficacy of COMP360, as assessed by the change in the Montgomery-Åsberg Depression Rating Scale, or MADRS, a widely accepted scale for depression that has been used as a primary endpoint in pivotal trials of other depression treatments.

This trial was designed to capture a statistically significant reduction in MADRS.

We used digital technology in this trial, including an online portal to help patients prepare for their psilocybin experience, and a web-based “shared knowledge” interactive platform to complement therapist training.

On November 3, 2021, we announced that we are conducting a Phase II clinical trial to assess the safety and tolerability of COMP360 psilocybin therapy in post-traumatic stress disorder (PTSD).

The study expands COMPASS’s research pipeline in COMP360 psilocybin therapy.

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

it will begin at The Institute of Psychiatry, Psychology & Neuroscience (IoPPN) at King’s College London.

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 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.

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

The pivotal program design is as follows:

• Pivotal trial 1 (COMP005) (n=255):

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.

• Pivotal trial 2 (COMP006) (n= 568):

a fixed repeat dose monotherapy using three dose arms:

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.

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

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

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

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

Additional IIS studies are underway in a number of other indications including autism, 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.

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Key elements of our strategy to achieve this include:

• Advance our investigational COMP360 psilocybin therapy for the treatment of TRD, including initiating additional and larger clinical trials.

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

We announced positive topline results from these trials in November and December 2021 and intend to initiate a Phase III registrational program, commencing in 2022.

• Advance our Phase 3 registrational program for our investigational COMP360 psilocybin therapy 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.

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 mental health and neurological conditions.

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 investigator-initiated studies (signal-generating studies using our COMP360 psilocybin) and through our Discovery Center which is carrying out preclinical research into new compounds.

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.

In November 2021, we began a Phase II trial of COMP360 psilocybin therapy for PTSD.

This is a multi-center, fixed dose, open label trial of 20 patients.

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

We have expanded our Discovery Center, initially based at University of the Sciences in Philadelphia, to include a network of expert teams across the US, and 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 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 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.

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 plan to set up research facilities and innovation labs, which we refer to as Centers of Excellence, in key markets.

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, in the United States.

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 impact of our investigational COMP360 psilocybin therapy.

• 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 used in our Phase IIb clinical trial, which included a patient portal to help patients prepare for their experience, and a web-based “shared knowledge” interactive platform to complement our face-to-face and clinical therapist training.

In our Phase IIb trial, we collected some patient data in a remote setting using mobile technologies and using a third-party technology that monitors and measures human-smartphone interactions.

Following completion of this trial in 2021, this data may be compared with information collected from validated psychiatric scales, such as MADRS, to develop potential digital applications to help detect early signs of post-treatment relapse and model the course of disease.

We are also developing solutions using AI-assisted therapist feedback and monitoring.

We continue to build an in-house digital team with experts in 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 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.

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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 PTSD for which we are beginning a Phase II clinical trial.

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 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.

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

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

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

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

Esketamine was approved in 2019 by the FDA.

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

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

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.

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.

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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 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.

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.

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

To date, only two pharmacotherapies have been approved specifically for the treatment of TRD in the U.S.

The following table indicates the worldwide estimated patient populations suffering with new onset MDD, persistent MDD and TRD, and the primary treatment options available.

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

Treatment pathway stage New onset depression

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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.

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.

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Total = $211B

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

TRD patients are often unable to perform daily tasks, are less productive at work and have higher rates of unemployment.

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.

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

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

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

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

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

Various forms of somatic intervention are also

used, although there is limited data supporting their long-term benefit.

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

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

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.

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

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

invasiveness of the surgical procedure.

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

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

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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.

Anorexia Nervosa

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

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

It carries the highest mortality rate of all psychiatric disorders.

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

damage to the brain leading to seizures and memory issues;

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

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

Approximately 3.9 million people 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 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.

Psilocybin Therapy

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

In this way, evidence of the

molecular, cellular, and systemic effects of psilocybin in the CNS supports the potential for psilocybin in the treatment of mental health conditions.

In this way, evidence of the molecular, cellular, and systemic effects of psilocybin in the CNS supports the potential for psilocybin in the treatment of mental health conditions.

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

Altered extracellular release of dopamine leads to enhanced positive mood.

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

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

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In turn, this may promote neuron growth and function.

However, non-canonical 5-HT 2A receptor signaling cascades specific to certain cell or tissue types may also exist, as there is evidence of

certain downstream effects of psychedelic agonists occurring via the Gα i/o protein, which typically downregulates signaling pathways related to neurotransmitter release, for example, within neurons.

However, non-canonical 5-HT 2A receptor signaling cascades specific to certain cell or tissue types may also exist, as there is evidence of certain downstream effects of psychedelic agonists occurring via the Gα i/o protein, which typically downregulates signaling pathways related to neurotransmitter release, for example, within neurons.

This diverse range of cellular signaling cascades that may be modulated by psilocin likely underlie some of the local circuit-level effects of the drug.

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Colors represent communities of networks or regions that are more commonly connected to one another than networks in different communities.

Simplified Visualization of the Acute Changes in Brain Network Connectivity

Simplified V isualization of the A cute C hanges in B rain N etwork C onnectivity

Study analyzed fMRI (functional magnetic resonance imaging) data from healthy volunteers to compare resting-state functional brain connectivity after intravenous infusion of placebo and psilocybin.

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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 suggest that psilocybin therapy may exhibit clinical activity in patients with depression and anxiety, when administered with psychological support from specially trained therapists.

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.

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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.

(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.

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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

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.

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Clinical Summary

Our psilocybin therapy combines the pharmacological effects of psilocybin with psychological support from specially trained therapists who are present throughout the psilocybin administration session.

We have developed a proprietary stabilized, high-purity polymorphic crystalline synthesized formulation of psilocybin, COMP360, and are investigating the effectiveness of this psilocybin therapy in TRD and PTSD.

In our Phase I 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.

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

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 IIb clinical trial of our COMP360 psilocybin therapy in 233 patients suffering with TRD, in 22 sites in 10 countries in North America and Europe.

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.

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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 IIb

trial where patients were withdrawn from their ongoing antidepressants prior to COMP360 psilocybin therapy.

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.

In November 2021 we began a Phase II, multi-center, fixed-dose (25mg), open label study to evaluate the safety and tolerability of COMP360 psilocybin therapy in people who suffer with PTSD resulting from trauma experienced as adults.

Psilocybin Therapy Protocol

COMP360 Psilocybin Therapy Protocol

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

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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.

• Psilocybin administration session:

• Psilocybin administration:

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

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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 IIb clinical trial in TRD.

We are currently undertaking an additional series of safety pharmacology and toxicity studies, to be completed prior to commencement of our anticipated Phase III program.

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 I clinical trial of COMP360 administered along with psychological support in healthy participants.

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.

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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)

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

Total number of treatment-emergent AEs reported 91 203 217

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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 I healthy volunteers trial

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

_____________

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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.

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:

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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 IIb Trial of Our COMP360 Psilocybin Therapy in TRD

In 2021, we completed a Phase IIb 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 patients suffering with TRD, across 22 trial sites in 10 countries in North America and Europe.

Results of the study, including additional details, are expected to be published in a peer-reviewed journal.

Phase 2b Trial of Our COMP360 Psilocybin Therapy 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 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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This variable was also being analyzed for change from baseline to Day 2, weeks 1, 6, 9 and 12.

This Phase IIb clinical trial was powered to capture a statistically significant reduction in MADRS.

This Phase 2b clinical trial was powered to capture a statistically significant reduction in MADRS.

Secondary endpoints of the trial included:

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

MADRS response rates

MADRS = Montgomery-Åsberg Depression Rating Scale

MADRS remission rates

MADRS response and remission rates

MADRS = Montgomery-Åsberg Depression Rating Scale

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MADRS = Montgomery-Åsberg Depression Rating Scale.

Number of sustained responders stated in bar.

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

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

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.

On the Positive and Negative Affect Schedule measuring positive and negative affect, patients in the 25mg group had a higher increase in positive affect (eg 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.

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.

On scales measuring anxiety (the Generalized Anxiety Disorder – 7 item scale), self-rated depression (QIDS-SR-16) and functioning (Sheehan Disability Scale and Work and Social Adjustment Scale), a greater improvement was also shown at week 3 by patients in the 25mg group compared with the 1mg group.

A post-hoc analysis of the 19 sustained responders in the 25mg group found that changes in quality of life, self-reported depression severity, and functioning, were clinically meaningful, with mean scores for these patients returning to “normal” levels and maintained to 12 weeks, the end of

A post-hoc analysis of the 16 sustained responders in the 25mg group found that changes in quality of life, self-reported depression severity, and functioning, were clinically meaningful, with mean scores for these patients returning to “normal” levels and maintained to 12 weeks, the end of the trial.

Additionally, sustained responders were found to have clinically meaningful increases in positive affect from baseline at day 2 and week 3.

COMP360 was generally well tolerated, with more than 90% of treatment-emergent adverse events (TEAEs) being mild or moderate in severity.

COMP360 was generally well tolerated, with more than 90% of treatment-emergent adverse events (TEAEs) being mild or moderate in severity and greater than 77% of TEAEs occurring on the day of administration being resolved on the same day or the next day.

179 patients reported at least one TEAE;

the most common TEAEs across treatment groups (>10% overall incidence) were headache, nausea, fatigue, and insomnia.

the most common TEAEs across treatment groups (>10% overall

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

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

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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 detailed case-by-case analysis of safety data found no evidence to suggest, at this time, a causal relationship between these reported adverse events and administration of COMP360.

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;

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

• 27 of the TEAEs of suicidal ideation, suicidal behaviour 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

• 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);

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

• All suicidal behaviours 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 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

Overall, 209 patients completed the study;

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

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

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

Phase 2 study of COMP360 psilocybin therapy 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.

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

There was a rapid response from day 2 to week 3 after COMP360 therapy, which is consistent with the Phase IIb result.

There was a rapid response from day 2 to week 3 after COMP360 therapy, which is consistent with the Phase 2b result.

Change from baseline in MADRS total score

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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.

Ongoing Long-Term Phase II Study:

• A long-term follow-up study of participants who took part in the abovementioned Phase II trials is ongoing.

The outcomes of our Phase II trials will help inform our future clinical development plans.

We will be sharing our data with regulators as part of an ongoing dialogue around our clinical development program, including our Phase III registrational studies.

Long-Term Phase 2 Study

During 2022, we completed a long-term follow-up study of 66 participants who took part in our Phase 2b trial.

Of the 66 participants, 22 participants were in the 25mg group, 19 participants were in the 10mg group, 17 participants were in the 1mg group and 8 participants were in the 25mg plus SSRI group.

The primary endpoint of this Phase 2b follow-up study was the median time to a new depressive event.

The pre-specified primary analysis was of the median time for such an event for all participants in our Phase 2b trial, not only those who took part in the long-term follow-up study.

The median time to a new depressive event was 92 days for the COMP360 25mg group compared to 86 days for the 10mg group and 62 days for the 1mg group.

In an additional post-hoc analysis to support the primary endpoint only including those participants from our Phase 2b study who took part in the long-term follow up study (COMP004) the median time to such an event was longer (189 days) for the COMP360 25mg group compared to the 10mg group (43 days) and the 1mg group (21 days) (patients entering from our Phase 2b study).

Twenty-seven or 40.9% of participants had an adverse event that was ongoing as of, or started, after week 12.

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.

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

The pivotal program design is as follows:

• Pivotal trial 1 (COMP005) (n=255):

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

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

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

We expect top-line data in summer of 2024.

• Pivotal trial 2 (COMP006) (n= 568):

a fixed repeat dose monotherapy using three dose arms:

25mg, 10mg and 1mg.

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.

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

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

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

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

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

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

• We are conducting an open-label, multi-center, fixed-dose study with 20 participants to evaluate the safety and tolerability of COMP360 psilocybin therapy in patients suffering with PTSD resulting from trauma experienced as adults.

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

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

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These institutions include:

Imperial College London, Kings College London, Maryland Oncology Hematology, New York State Psychiatric Institute at Columbia University Medical Center, Sheppard Pratt, UC San Diego School of

Medicine, University of Copenhagen, and University of Zurich.

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

Imperial College London, King’s College London, Maryland Oncology Hematology, New York State Psychiatric Institute at Columbia University Medical Center, Sheppard Pratt, UC San Diego School of Medicine, University of Copenhagen, and University of Zurich.

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.

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

If an IIS using COMP360 produces results with the potential to improve mental health care, we may seek to advance this research through a clinical development program, with the goal of making it available for patients, although we have no pre-existing contractual right to do so.

In addition to providing our IIS researchers with COMP360, we have in the past and may continue to offer support with regulatory submissions.

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

If an IIS using COMP360 psilocybin produces results with the potential to improve mental health care, we may seek to advance this research through a clinical development program, with the goal of making it available for patients, although we have no pre-existing contractual right to do so.

In addition to providing our IIS researchers with COMP360 psilocybin, we have in the past offered, and may continue to offer, support with regulatory submissions.

Through our IIS collaborations, we ultimately hope to bring more innovation to patients, as quickly and safely as possible.

In May 2022, we announced that we would fund an IIS that will use COMP360 psilocybin to explore how COMP360 psilocybin affects specific brain pathways in autistic adults.

The double-blind, randomized, placebo-controlled study will investigate whether there is a difference in the function of serotonin brain networks in autistic and non-autistic adults.

The researchers will use a range of imaging techniques and behavioral tasks to examine how the serotonin system is modulated by COMP360 psilocybin.

This exploratory study is being conducted by a research scientist who is employed by us and is a PhD student at King’s College London.

The study is being conducted at the Institute of Psychiatry, Psychology & Neuroscience (IoPPN) at King’s College London and is co-sponsored by King’s IoPPN and South London and Maudsley NHS Foundation Trust.

It will enroll 70 adult participants, including 40 autistic people and 30 non-autistic people.

Data from IISs

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NCT03429075).

In this randomized, double-blind, exploratory clinical trial, the efficacy and mechanisms of action of COMP360 were compared with those of a 6-week course of the SSRI, escitalopram.

A total of 59 adult participants with MDD of at least moderate severity were randomized to receive either two 25mg doses of COMP360 three weeks apart or 6 weeks of daily escitalopram (10mg for three weeks and 20mg for the following three weeks) alongside two 1mg doses COMP360 three weeks apart.

In this randomized, double-blind, exploratory clinical trial, the efficacy and mechanisms of action of COMP360 were compared with those of a six-week course of the SSRI, escitalopram.

A total of 59 adult participants with MDD of at least moderate severity were randomized to receive either two 25mg doses of COMP360 three weeks apart or six weeks of daily escitalopram (10mg for three weeks and 20mg for the following three weeks) alongside two 1mg doses COMP360 three weeks apart.

In both trial arms, participants received psychological support as part of the trial.

The primary efficacy endpoint of the change from baseline on the 16-item Quick Inventory of Depressive Symptomatology-Self-Report (QIDS-SR-16) showed a 2-point trend in favor of the COMP360 arm which was apparent from week 1.

The primary efficacy endpoint of the change from baseline on the 16-item Quick Inventory of Depressive Symptomatology-Self-Report (QIDS-SR-16) showed a two-point trend in favor of the COMP360 arm which was apparent from week 1.

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

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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.

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)”.

The investigator presented data from this study at the Society of Biological Psychiatry Annual Meeting in the second quarter of 2022.

In this open-label study involving 12 patients with severe treatment-resistant depression, patients received a 25mg dose of COMP360 with psychological support.

All participants had tried at least five antidepressant treatments without success, prior to joining the study.

The researchers found that 58.3% (n=7) of the participants had maintained MADRS response criteria at 12 weeks after COMP360 psilocybin administration, and a quarter had maintained remission (n=3).

There was no increase in the suicidality score based on the MADRS, and no treatment-related serious adverse events were reported throughout the study.

In 2022, the University of California San Diego School of Medicine completed an IIS of COMP360 titled “Evaluation of Psilocybin in Anorexia Nervosa:

Safety and Efficacy.” (ClinicalTrials.gov Identifier:

NCT04661514).

The investigator presented data from this study at the Society of Biological Psychiatry Annual Meeting in the second quarter of 2022.

In this open-label study involving 10 patients with anorexia nervosa, patients received a 25mg dose of COMP360 in conjunction with psychological support.

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).

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;

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.

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:

NCT0443384512).

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.

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 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:

NCT03715127).

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

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

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

At the two-week endpoint, response rates resulted in 58% for MADRS (COMP360 psilocybin:

P = 0.0034) and for BDI in 54% (COMP360 psilocybin:

At the two-week endpoint, remission rates were reported in 54% of patients for MADRS (COMP360 psilocybin:

P = 0.0023) and assessed by BDI in 46% (COMP360 psilocybin:

Adverse events were in line with other studies and included headache, dizziness, nausea and diarrhea.

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

Drug Discovery Center

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

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

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

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

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

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

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

We and USciences can terminate the agreement in the event of a material breach by the other party and

failure to cure such breach within a certain period of time.

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

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

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

Research project with Matthias Grill to develop new product candidates

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 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

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

To date, we have trained more than 150 therapists and assisting therapists, more than 65 of whom have worked or continue to work at the sites which conducted our Phase IIb clinical trial or IISs.

To date, we have trained more than 200 therapists, approximately 65 of whom have been approved to lead sessions independently, and approximately 40 of whom are engaged in our active clinical trials.

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

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• Tier I - Theoretical Training:

Approximately 10 hours of self-paced online learning through our interactive therapist training platform, including video re-enactments of preparation, psilocybin administration, and integration sessions, a psilocybin therapy manual, and an online therapist forum;

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

• Tier II - Practical Clinical Skills Training:

Approximately 30 hours of in-person or remotely-delivered (via Zoom) interactive learning, led by senior-level therapists;

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

• Tier III - Clinical training:

At this stage, therapists review pre-selected sessions from our psilocybin therapy studies and gain direct experience of supporting participants in two psilocybin therapy experiences under the guidance of experienced therapists.

Trainee therapists gain clinical experience as an assisting therapist at their site, and/or have the opportunity to sit in other psilocybin therapy studies run by our academic collaborators, including the Institute of Psychiatry, Psychology and Neuroscience, or IoPPN, at King’s College London, and Sheppard Pratt Health System (Baltimore, Maryland, US);

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.

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

• Tier IV - Continuous Professional Development:

Therapists receive 1:1 mentoring and clinical support from mentors.

This includes feedback from mentors about therapists’ fidelity to the therapeutic model from recorded video/audio footage of sessions (with participant consent).

Additionally, we host a monthly webinar for our therapists that may cover presentations by experts in the field, review of relevant studies and case reviews.

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.

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

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

We are in discussion with academic centers in the US and Europe to establish an accredited training program for psilocybin therapists.

Accrediting the training program would help enable us to meet the needs of any Phase III trials and any post-approval rollout.

In addition, in August 2020, the FDA approved our request for virtual face-to-face training of therapists, with immediate effect.

Conducting a larger part of the therapist training virtually facilitated the training of therapists during the ongoing COVID pandemic and training at scale in general.

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

Using Digital Technology

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

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

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

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

• Collection of measurements in our Phase IIb 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 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 some digital phenotyping information through the measurement of human-smartphone interactions;

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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.

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

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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.

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

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

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For example, upon approval from the U.S.

FDA, we may be entitled to five years of regulatory exclusivity for New Chemical Entity (“NCE”) and upon approval from the European Medicines Agency (“EMA”), we may be entitled to eight years of data exclusivity (i.e., no generic application), and an additional two years of market exclusivity (i.e., no generic marketing).

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).

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US 10,954,259 Crystalline psilocybin;

Pharmaceutical Compositions;

Pharmaceutical formulations;

Method of treating MDD

US 11,180,517 Method of treating treatment-resistant depression ca.2038*

GB 2571696 Method of Manufacture ca.

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

GB 2571696 Method of manufacturing ca.

GB 2572023 Crystalline psilocybin;

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Method of manufacturing

GB 2576059 Pharmaceutical formulations ca.

GB 2588505 Method of manufacturing ca.

GB 2588506 Crystalline psilocybin;

Pharmaceutical formulations;

Method of manufacture

DE 202018006384 Crystalline psilocybin;

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Methods of treating anxiety disorders and other conditions

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

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.

PCT WO2020/212948

Methods of treating neurocognitive disorders and other conditions

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

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

PCT WO2020/212952

Methods of treating depression and other disorders

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

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

PCT WO2022/207746 Pharmaceutical formulations ca.

2042* Applications filed in Taiwan and Argentina.

National Stage Applications to be filed.

*In general, a U.S.

patent, as well as most foreign patents, will expire after 20 years from the earliest effective filing date.

In the U.S., it may be possible to extend the patent term beyond the 20 years by requesting patent term extension (“PTE”) of patents that claim a product requiring regulatory approval prior to sale.

In the U.S., it may be possible to extend the patent term beyond the 20 years by requesting patent term extension, or PTE, of patents that claim a product requiring regulatory approval prior to sale.

PTE restores to a patent owner, patent term which was effectively “lost” due to regulatory review.

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On December 15, 2021, Freedom to Operate, Inc., filed a petition for post-grant review of U.S.

The patent owner’s response is due March 30, 2022.

The USPTO’s decision on whether to institute post-grant review is expected by June 30, 2022.

The patent owner’s response was filed on March 29, 2022.

On June 22, 2022, the USPTO denied institution of the post-grant review.

Freedom to Operate, Inc.

filed a request for rehearing on July 22, 2022, and a request for Precedential opinion panel on August 16, 2022.

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

The patent owner’s response is due April 12, 2022.

The USPTO’s decision on whether to institute post-grant review is expected by July 12, 2022.

The patent owner’s response was filed on April 11, 2022.

On June 22, 2022, the USPTO denied institution of the post-grant review.

Freedom to Operate, Inc.

filed a request for rehearing on July 22, 2022, and a request for Precedential opinion panel on August 16, 2022.

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.

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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No appeal to this decision was lodged within the required 28-day period.

UK patent, No GB2572023, was granted in June of 2020.

UK patent, No GB2572023, was granted in June 2020.

This patent includes claims covering our crystalline psilocybin (including the form used in COMP360), pharmaceutical formulations of crystalline psilocybin, medical uses of crystalline psilocybin (including for treatment-resistant depression), and a method of manufacturing crystalline psilocybin.

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On December 17, 2021, the agency then issued a decision to not initiate revocation proceedings against the patent.

The Company plans to pursue protection of its various trademarks in classes 5, 9, 10, 35, 41, 42, 44 or various combinations thereof.

Our trademark portfolio includes two registered trademarks in the United Kingdom for COMPASS and COMPASS PATHWAYS in Classes 05, 09, 10, 35, 41, and 44 and pending application for C Design in Classes 05, 41 and 44.

In the European Union, a registration for COMPASS and pending application for COMPASS PATHWAYS in Classes 05, 09, 10, 35, 41 and 44 and a pending application for C Design in Classes 05, 41 and 44.

In the United States, pending applications for COMPASS, COMPASS PATHWAYS and C Design in Classes 05, 09, 10, 35, 41, 44 and a pending application MYPATHFINDER in Classes 9 and 42.

The Company also has trademark registrations and pending applications in other countries.

Mark Territory Trademark Application/Registration

Filing/Registration Date Status

COMPASS US 79301429 September 17, 2020 Pending

EU 1568499 May 25, 2021 Registered

UK 3476175 August 10, 2020 Registered

COMPASS PATHWAYS US 79302207 September 17, 2020 Pending

EU 1570415 September 17, 2020 Pending

UK 3476163 August 14, 2020 Registered

US 90801769 June 29, 2021 Pending

US 90801777 June 29, 2021 Pending

EU A0117188 December 10, 2021 Pending

UK A0117188 December 10, 2021 Pending

MYPATHFINDER US 97174167 December 15, 2021 Pending

On November 22, 2022, Porta Sophia filed a Third-Party Observation against international patent application WO2022/207746.

The Company has pursued protection for its trademarks across Classes 5, 9, 10, 35, 41, 42, 44 or various combinations thereof.

Our trademark portfolio includes filings for the COMPASS, COMPASS PATHWAYS, C Design, MYPATHFINDER, and CHANTERELLE marks in the United States, European Union, and United Kingdom, as detailed in the chart below.

The Company owns registrations for the COMPASS, COMPASS PATHWAYS, and C Design marks in the United States, European Union, and United Kingdom;

and for the MYPATHFINDER mark in the United Kingdom.

Applications are pending for the MYPATHFINDER mark in the United States and European Union;

and for the CHANTERELLE mark in the United States.

The Company also owns trademark registrations and pending applications in other countries.

Trademark Application/Registration

Filing/Registration Date

5, 9, 10, 35, 41, 44

February 22, 2022

5, 9, 10, 35, 41, 44

August 10, 2020

COMPASS PATHWAYS

5, 9, 10, 35, 41, 44

February 22, 2022

5, 9, 10, 35, 41, 44

August 14, 2020

5, 35, 41, 42, 44

September 6, 2022

June 29, 2021

June 30, 2022

December 15, 2021

December 15, 2022

October 11, 2022

Government Regulation

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There also are requirements governing the reporting of ongoing clinical trials and completed clinical trials to public registries.

Information about clinical trials, including results for clinical trials other than Phase I investigations, must be submitted within specific timeframes for publication on www.ClinicalTrials.gov, a clinical trials database maintained by the National Institutes of Health.

Information about clinical trials, including results for clinical trials other than Phase 1 investigations, must be submitted within specific timeframes for publication on www.ClinicalTrials.gov, a clinical trials database maintained by the National Institutes of Health.

A sponsor who wishes to conduct a clinical trial outside of the United States may, but need not, obtain FDA authorization to conduct the clinical trial under an IND.

If a foreign clinical trial is not conducted under an IND, FDA will nevertheless

accept the results of the study in support of an NDA if the study was conducted in accordance with GCP requirements, and the FDA is able to validate the data through an onsite inspection if deemed necessary.

If a foreign clinical trial is not conducted under an IND, FDA will nevertheless accept the results of the study in support of an NDA if the study was conducted in accordance with GCP requirements, and the FDA is able to validate the data through an onsite inspection if deemed necessary.

Clinical trials to evaluate therapeutic indications to support NDAs for marketing approval are typically conducted in three sequential phases, which may overlap.

• Phase I— Phase I clinical trials involve initial introduction of the investigational product into healthy human volunteers or patients with the target disease or condition.

• Phase 1— Phase 1 clinical trials involve initial introduction of the investigational product into healthy human volunteers or patients with the target disease or condition.

These studies are typically designed to test the safety, dosage tolerance, absorption, metabolism and distribution of the investigational product in humans, excretion, the side effects associated with increasing doses, and, if possible, to gain early evidence of effectiveness.

• Phase II— Phase II clinical trials typically involve administration of the investigational product to a limited patient population with a specified disease or condition to evaluate the drug’s potential efficacy, to determine the optimal dosages and administration schedule and to identify possible adverse side effects and safety risks.

• Phase III— Phase III clinical trials typically involve administration of the investigational product to an expanded patient population to further evaluate dosage, to provide statistically significant evidence of clinical efficacy and to further test for safety, generally at multiple geographically dispersed clinical trial sites.

• Phase 2— Phase 2 clinical trials typically involve administration of the investigational product to a limited patient population with a specified disease or condition to evaluate the drug’s potential efficacy, to determine the optimal dosages and administration schedule and to identify possible adverse side effects and safety risks.

• Phase 3— Phase 3 clinical trials typically involve administration of the investigational product to an expanded patient population to further evaluate dosage, to provide statistically significant evidence of clinical efficacy and to further test for safety, generally at multiple geographically dispersed clinical trial sites.

These clinical trials are intended to establish the overall risk/benefit ratio of the investigational product and to provide an adequate basis for product approval and physician labeling.

Post-approval trials, sometimes referred to as Phase IV clinical trials or post-marketing studies, may be conducted after initial marketing approval.

Post-approval trials, sometimes referred to as Phase 4 clinical trials or post-marketing studies, may be conducted after initial marketing approval.

These trials are used to gain additional experience from the treatment of patients in the intended therapeutic indication and are commonly intended to generate additional safety data regarding use of the product in a clinical setting.

In certain instances, the FDA may mandate the performance of Phase IV clinical trials as a condition of NDA approval.

In certain instances, the FDA may mandate the performance of Phase 4 clinical trials as a condition of NDA approval.

Progress reports detailing the results of the clinical trials, among other information, must be submitted at least annually to the FDA.

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To support marketing approval, the data submitted must be sufficient in quality and quantity to establish the safety and efficacy of the investigational product to the satisfaction of the FDA.

FDA must approve an NDA before a drug may be marketed in the United States.

The FDA must approve an NDA before a drug may be marketed in the United States.

The FDA reviews all submitted NDAs before it accepts them for filing and may request additional information rather than accepting the NDA for filing.

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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 IV 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.

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.

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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Accelerated Approval is usually contingent on a sponsor’s agreement to conduct additional post-approval studies to verify and describe the product’s clinical benefit.

The FDA may withdraw approval of a drug or an indication approved under Accelerated Approval if, for example, the confirmatory trial fails to verify the predicted clinical benefit of the product.

Under the Food and Drug Omnibus Reform Act of 2022, or FDORA, the FDA is permitted to require, as appropriate, that such trials be underway prior to approval or within a specific time period after the date of approval for a product granted accelerated approval.

Sponsors are also required to send updates to the FDA every 180 days on the status of such studies, including progress toward enrollment targets, and the FDA must promptly post this information publicly.

Under FDORA, the FDA has increased authority for expedited procedures to withdraw approval of a drug or indication approved under accelerated approval if, for example, the sponsor fails to conduct such studies in a timely manner and send the necessary updates to the FDA, or if a confirmatory trial fails to verify the predicted clinical benefit of the product.

In addition, the FDA generally requires, as a condition for Accelerated Approval, that all advertising and promotional materials intended for dissemination or publication within 120 days of marketing approval be submitted to the agency for review during the pre-approval review period.

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The FDA may impose a number of post-approval requirements as a condition of approval of an NDA.

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

In addition, drug manufacturers and their subcontractors involved in the manufacture and distribution of approved drugs 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.

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.

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.

There is also a continuing, annual prescription drug product program user fee.

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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.

In addition to an importer or exporter registration, importers and exporters must obtain a permit for every import or

export of a Schedule I and II substance or Schedule III, IV and V narcotic, and submit import or export declarations for Schedule III, IV and V non-narcotics.

In addition to an importer or exporter registration, importers and exporters must obtain a permit for every import or export of a Schedule I and II substance or Schedule III, IV and V narcotic, and submit import or export declarations for Schedule III, IV and V non-narcotics.

In some cases, Schedule III non-narcotic substances may be subject to the import/export permit requirement, if necessary, to ensure that the United States complies with its obligations under international drug control treaties.

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Whether or not it obtains FDA approval for a product, an applicant will need to obtain the necessary approvals by the comparable foreign regulatory authorities before it can initiate clinical trials or marketing of the product in those countries or jurisdictions.

Specifically, the process governing approval of medicinal products in the European Union generally follows the same lines as in the United States, although the approval of a medicinal product in the United States is no guarantee of approval of the same product in the European Union, either at all or within the same timescale as approval may be granted in the United States.

Specifically, the process governing approval of medicinal products in the EU generally follows the same lines as in the United States, although the approval of a medicinal product in the United States is no guarantee of approval of the same product in the EU, either at all or within the same timescale as approval may be granted in the United States.

It entails satisfactory completion of pharmaceutical development, non-clinical studies and adequate and well-controlled clinical trials to establish the safety and efficacy of the medicinal product for each proposed indication.

It also requires the submission to relevant competent authorities for clinical trials authorization for a marketing authorization application, or MAA, and granting of a marketing authorization by these authorities before the product can be marketed and sold in the European Union or its member states (as well as Iceland, Norway and Liechtenstein).

If we fail to comply with applicable requirements, we may be subject to, among other things, fines, suspension of clinical trials, suspension or withdrawal of regulatory approvals, product recalls, seizure of products, operating restrictions and criminal prosecution.

It also requires the submission to relevant competent authorities for clinical trials authorization and subsequently of a marketing authorization application, or MAA, before the product can be marketed and sold in the EU or any of its Member States.

If we fail to comply with applicable requirements, we may be subject to withdrawal of regulatory approvals, product recalls, seizure of products, operating restrictions and criminal prosecution.

Clinical Trial Approval

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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 current Clinical Trials Directive 2001/20/EC on January 31, 2022.

It overhauls the current system of approvals for clinical trials in the EU.

Specifically, the new legislation, which will be 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.

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.

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.

The 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 offer sponsors the possibility to choose between the requirements of the previous Clinical Trials Directive and the Clinical Trials

Regulation if the request for authorization of a clinical trial is submitted in the year after the new Clinical Trials Regulation became applicable.

If the sponsor chooses to submit under the Clinical Trials Directive, the clinical trial continues to be governed by the Directive until three years after the new Clinical Trials Regulation became applicable.

If a clinical trial continues for more than three years after the Clinical Trials Regulation became applicable, the Clinical Trials Regulation will at that time begin to apply to the clinical trial.

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.

Marketing Authorization

To obtain a marketing authorization for a product in the European Economic Area (comprised of the EU member states plus Norway, Iceland and Liechtenstein), or EEA, an applicant must submit an MAA, either under a centralized procedure administered by the EMA or one of the procedures administered by competent authorities in the EU Member States (decentralized procedure, national procedure, or mutual recognition procedure).

To obtain a marketing authorization for a medicinal product in the European Economic Area (comprised of the EU member states plus Norway, Iceland and Liechtenstein), or EEA, an applicant must submit an MAA, either under a centralized procedure administered by the EMA or one of the procedures administered by competent authorities in the EU Member States (decentralized procedure, national procedure, or mutual recognition procedure).

A marketing authorization may be granted only to an applicant established in the EEA.

The centralized procedure provides for the grant of a single marketing authorization by the European Commission that is valid throughout the EEA and is mandatory for certain products, including products with a new active substance indicated for the treatment of HIV, AIDS, cancer, neurodegenerative disorders, diabetes, auto-immune and other immune dysfunctions, and viral diseases.

Pursuant to Regulation (EC) No 726/2004, 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.

For those products for which the use of the centralized procedure is not mandatory, 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.

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.

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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 will no longer be covered by centralized marketing authorizations (under the Northern Ireland Protocol, centralized marketing authorizations will continue to be recognized in Northern Ireland).

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.

For a period of two years from January 1, 2021, 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.

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.

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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• provides scientific advice at key development milestones, involving additional stakeholders, such as health technology assessment bodies and patients, as needed.

Medicines that are selected for the PRIME scheme are also expected to benefit from EMA’s accelerated assessment procedure at the time of application for marketing authorization.

Medicines that are selected for the PRIME scheme are also expected to benefit from the EMA’s accelerated assessment procedure at the time of application for marketing authorization.

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

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141/2000 and Regulation (EC) No.

847/2000 provide that a product can be designated as an orphan medicine by the European Commission if its sponsor can establish that:

847/2000 provide that a product can be designated as an orphan medicinal product by the European Commission if its sponsor can establish that:

(1) the product is intended for the diagnosis, prevention or treatment of a life-threatening or chronically debilitating condition;

(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 will be of significant benefit compared to products available for the condition.

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

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.

The application for orphan designation must be submitted before the application for marketing authorization.

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

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

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”.

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 drug designation, for example because the product is sufficiently profitable not to justify market exclusivity.

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.

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Pediatric Development

In the EU, companies developing a new medicinal product must agree upon a pediatric investigation plan, or PIP, with the EMA’s Pediatric Committee, or PDCO, and must conduct pediatric clinical trials in accordance with that PIP, unless a waiver applies, (e.g., because the relevant disease or condition occurs only in adults).

The PIP sets out the timing and measures proposed to generate data to support a pediatric indication of the drug for which marketing authorization is being sought.

In the EU, companies developing a new medicinal product must agree upon a pediatric investigation plan, or PIP, with the EMA’s Pediatric Committee, or PDCO, and must conduct pediatric clinical trials in accordance with that PIP unless the EMA has granted a product-specific waiver, a class waiver, or a deferral for one or more of the measures included in the PIP.

This requirement also applies when a company wants to add a new indication, pharmaceutical form or route of administration for a medicine that is already authorized.

The PIP sets out the timing and measures proposed to generate data to support a pediatric indication of the product for which marketing authorization is being sought.

The MAA for the product must include the results of pediatric clinical trials conducted in accordance with the PIP, unless a waiver applies, or a deferral has been granted by the PDCO of the obligation to implement some or all of the measures of the PIP until there are sufficient data to demonstrate the efficacy and safety of the product in adults, in which case the pediatric clinical trials must be completed at a later date.

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 (if any is in effect at the time of approval) even where the trial results are negative.

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.

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

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There is no guarantee that a product will be considered by the EMA to be an innovative medicinal product, and products may not qualify for data exclusivity.

Even if a product is considered to be an innovative medicinal product so that the innovator gains the prescribed period of data

exclusivity, another company may market another version of the product if such company obtained marketing authorization based on an MAA with a completely independent data package of pharmaceutical tests, preclinical tests and clinical trials.

Even if a product is considered to be an innovative medicinal product so that the innovator gains the prescribed period of data exclusivity, another company may market another version of the product if such company obtained marketing authorization based on an MAA with a complete and independent data package of pharmaceutical tests, preclinical tests and clinical trials.

Periods of Authorization and Renewals

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Once renewed, the marketing authorization is valid for an unlimited period, unless the European Commission or the competent authority decides, on justified grounds relating to pharmacovigilance, to proceed with one additional five-year renewal period.

Any authorization that is not followed by the placement of the product on the EEA market (in the case of the centralized procedure) or on the market of the authorizing EU Member State within three years after authorization ceases to be valid (the so-called sunset clause).

Any authorization that is not followed by the placement of the product on the EEA market (in the case of the centralized procedure) or on the market of the authorizing EU Member State (for a national procedure) within three years after authorization ceases to be valid (the so-called sunset clause).

Controlled Drugs Classification

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they are considered to have no legitimate or medicinal use, and can only be imported, exported, produced, supplied and the like under a license issued by the UK Government’s Home Office.

If and when granted a marketing authorization by the MHRA in respect of the UK, psilocybin would still remain a Schedule 1 drug until rescheduled by the UK Government’s Home Office.

If and when granted a marketing authorization by the MHRA in respect of the UK, psilocybin would still remain a Schedule 1 drug unless and until rescheduled by the UK Government’s Home Office.

Unless and until psilocybin is rescheduled under the Misuse of Drugs Regulations 2001, and unless a statutory exemption was to be passed for COMP360 following the grant of a UK marketing authorization and before rescheduling, any prescribing doctors in the UK would require a Home Office license to prescribe COMP360, and similarly any patients to whom COMP360 was prescribed would require a Home Office license to possess COMP360.

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Key obligations include expedited reporting of suspected serious adverse reactions and submission of periodic safety update reports, or PSURs.

In addition, all new MAAs must include a risk management plan, or RMP, describing the risk management system that the company will put in place and documenting measures to prevent or minimize the risks associated with the product.

In addition, all new MAAs must include a risk management plan, or RMP, describing the risk management system that the company will put in place to document measures to prevent or minimize the risks associated with the product.

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

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Finally, the marketing and promotion of authorized products, including industry-sponsored continuing medical education and advertising directed toward the prescribers of products, are strictly regulated in the EU under Directive 2001/83/EC, as amended.

The advertising of prescription-only medicines to the general public is not permitted in the European Union, 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 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.

Brexit and the Regulatory Framework in the United Kingdom

On June 23, 2016, the electorate in the United Kingdom voted in favor of leaving the EU, commonly referred to as Brexit, and the UK formally left the EU (commonly referred to as “Brexit”) on January 31, 2020.

There was a transition period during which EU pharmaceutical laws continued to apply to the UK, which expired on December 31, 2020.

However, 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 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 will continue to apply in Northern Ireland).

The regulatory regime in Great Britain therefore currently aligns with EU regulations, however it is possible that these regimes will diverge 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.

In January 2022, the UK Government announced its intention to begin the legislative process required to facilitate divergence from EU regulations, although it remains unclear at this stage what specific regulations will be affected as a result of this process.

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.

Coverage, Pricing and Reimbursement

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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.

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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In addition, results-based rules of reimbursement may apply.

There can be no assurance that any country that has price controls or reimbursement limitations for pharmaceutical products will allow favorable reimbursement and pricing arrangements for any of our products,

if approved in those countries.

Historically, products launched in the EU do not follow price structures of the United States and generally prices tend to be significantly lower.

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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 civil monetary penalties laws, which impose civil fines for, among other things, the offering or transferring of remuneration, which includes, without limitation, any transfer of items or services for free or for less than fair market value (with limited exceptions), to a Medicare or Medicaid beneficiary that the person knows or should know is likely to influence the beneficiary’s selection of a particular provider, practitioner, or supplier of items or services reimbursable by a federal or state healthcare program;

or property owned by, or under the custody or control of, any healthcare benefit program, regardless of the payor (i.e., public or private) and knowingly and willfully falsifying, concealing or covering up by any trick or device a material fact or making any materially false, fictitious, or fraudulent statements or representations in connection with the delivery of, or payment for, healthcare benefits, items or services relating to healthcare matters.

• The federal Health Insurance Portability and Accountability Act of 1996, or HIPAA, which created additional federal criminal liability for knowingly and willfully executing, or attempting to execute, a scheme to defraud any healthcare benefit program or obtain, by means of false or fraudulent pretenses, representations, or promises, any of the money or property owned by, or under the custody or control of, any healthcare benefit program, regardless of the payor (i.e., public or private) and knowingly and willfully falsifying, concealing or covering up by any trick or device a material fact or making any materially false, fictitious, or fraudulent statements or representations in connection with the delivery of, or payment for, healthcare benefits, items or services relating to healthcare matters.

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;

• 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.

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.

HITECH also increased the civil and criminal penalties that may be imposed against covered entities, business associates and possibly other persons, and gave state attorneys general new authority to file civil actions for damages or injunctions in federal courts to enforce the federal HIPAA laws and seek attorney’s fees and costs associated with pursuing federal civil actions;

• 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) and teaching hospitals, as well as ownership and investment interests held by the physicians described above and their immediate family members.

Effective January 1, 2022, these reporting obligations extend to include transfers of value made during the previous year to certain non-physician providers, such as physician assistants and nurse practitioners;

• 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;

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state and local laws that require the licensure and/or registration of pharmaceutical sales representatives;

and state and foreign laws governing the privacy and security of health information that may be more stringent than those in the United States (such as the European Union, which adopted GDPR, which became effective on May 25, 2018), many of which differ from each other in significant ways and often are not preempted by HIPAA, thus complicating compliance efforts.

and state and foreign laws governing the privacy and security of health information that may be more stringent than those in the United States (such as the EU, which adopted GDPR), many of which differ from each other in significant ways and often are not preempted by HIPAA, thus complicating compliance efforts.

The distribution of pharmaceutical products is subject to additional requirements and regulations, including extensive record-keeping, licensing, storage and security requirements intended to prevent the unauthorized sale of pharmaceutical products.

The full scope and enforcement of each of these laws is uncertain and subject to rapid change in the current environment of healthcare reform.

Federal and state enforcement bodies have continued to increase their scrutiny on interactions between

healthcare companies and healthcare providers, which has led to a number of significant investigations, prosecutions, convictions and settlements in the healthcare industry.

Federal and state enforcement bodies have continued to increase their scrutiny on interactions between healthcare companies and healthcare providers, which has led to a number of significant investigations, prosecutions, convictions and settlements in the healthcare industry.

It is possible that governmental authorities will conclude that our business practices do not comply with current or future statutes, regulations or case law involving applicable fraud and abuse or other healthcare laws and regulations.

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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In the United States and in some foreign jurisdictions, there have been, and likely will continue to be, a number of legislative and regulatory changes and proposed changes regarding the healthcare system directed at broadening the availability of healthcare, improving the quality of healthcare, and containing or lowering the cost of healthcare.

For example, in March 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;

introduced a new methodology by which rebates owed by manufacturers under the Medicaid Drug Rebate Program are calculated for drugs that are inhaled, infused, instilled, implanted or injected;

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;

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expanded healthcare fraud and abuse laws (including the FCA and the Anti-Kickback Statute), government investigative powers and enhances penalties for non-compliance;

expands eligibility criteria for Medicaid programs by, among other things, allowing states to offer Medicaid coverage to additional individuals with income at or below 133% of the federal poverty level, thereby potentially increasing manufacturers’ Medicaid rebate liability;

expands eligibility criteria for Medicaid programs thereby potentially increasing manufacturers’ Medicaid rebate liability;

expands the entities eligible for discounts under the 340B Drug Pricing Program;

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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.

Since its enactment, there have been judicial, Congressional and executive challenges to certain aspects of the ACA.

On June 17, 2021, the U.S.

Supreme Court dismissed the most recent judicial challenge to the ACA brought by several states without specifically ruling on the constitutionality of the ACA.

Prior to the Supreme Court’s decision, President Biden issued an executive order to initiate a special enrollment period from February 15, 2021 through August 15, 2021 for purposes of obtaining health insurance coverage through the ACA marketplace.

The executive order also instructed certain governmental agencies to review and reconsider their existing policies and rules that limit access to healthcare, including among others, reexamining Medicaid demonstration projects and waiver programs that include work requirements, and policies that create unnecessary barriers to obtaining access to health insurance coverage through Medicaid or the ACA.

It is unclear how other healthcare reform measures of the Biden administration or other efforts, if any, to challenge, repeal or replace the ACA will impact our business.

Other legislative changes have been proposed and adopted in the United States since the ACA was enacted.

For example, the Budget Control Act of 2011, among other things, created measures for spending reductions by Congress.

Specifically, the Joint Select Committee on Deficit Reduction was created to recommend to Congress proposals in spending reductions.

Joint Select Committee on Deficit Reduction did not achieve a targeted deficit reduction of at least $1.2 trillion for the years 2012 through 2021, thereby triggering the legislation’s automatic reduction to several government programs.

This includes aggregate reductions of Medicare payments to providers of up to 2% per fiscal year that will, due to subsequent legislative amendments, remain in effect through 2030, with the exception of a temporary suspension from May 1, 2020 through March 31, 2022 due to the COVID-19 pandemic.

Following the temporary suspension, a 1% payment reduction will occur beginning April 1, 2022 through June 30, 2022, and the 2% payment reduction will resume on July 1, 2022.

On January 2, 2013, the American Taxpayer Relief Act was signed into law, which, among other things, reduced Medicare payments to several types of providers, including hospitals, imaging centers and cancer treatment centers, and increased the statute of limitations period for the government to recover overpayments to providers from three to five years.

This includes aggregate reductions of Medicare payments to providers of up to 2% per fiscal year.

Subsequent legislation extended the 2% payment reduction which remains in effect through 2030.

The American Taxpayer Relief Act reduced Medicare payments to several types of providers, including hospitals, imaging centers and cancer treatment centers, and increased the statute of limitations period for the government to recover overpayments to providers from three to five years.

Further, on May 30, 2018, the Right to Try Act was signed into law.

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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.

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;

imposes new manufacturer financial liability on certain drugs under Medicare Part D, allow the U.S.

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.

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.

At the federal level, President Biden signed an Executive Order on July 9, 2021 affirming the administration’s policy to (i) support legislative reforms that would lower the prices of prescription drug and biologics, including by allowing Medicare to negotiate drug prices, by imposing inflation caps, and, by supporting the development and market entry of lower-cost generic drugs and biosimilars;

and (ii) support the enactment of a public health insurance option.

Among other things, the Executive Order also directs HHS to provide a report on actions to combat excessive pricing of prescription drugs, enhance the domestic drug supply chain, reduce the price that the Federal government pays for drugs, and address price gouging in the industry;

and directs the FDA to work with states and Indian Tribes that propose to develop section 804 Importation Programs in accordance with the Medicare Prescription Drug, Improvement, and Modernization Act of 2003, and the FDA’s implementing regulations.

FDA released such implementing regulations on September 24, 2020, which went into effect on November 30, 2020, providing guidance for states to build and submit importation plans for drugs from Canada.

On September 25, 2020, CMS stated drugs imported by states under this rule will not be eligible for federal rebates under Section 1927 of the Social Security Act and manufacturers would not report these drugs for “best price” or Average Manufacturer Price purposes.

Since these drugs are not considered covered outpatient drugs, CMS further stated it will not publish a National Average Drug Acquisition Cost for these drugs.

If implemented, importation of drugs from Canada may materially and adversely affect the price we receive for any of our product candidates.

Further, on November 20, 2020 CMS issued an Interim Final Rule implementing the Most Favored Nation, or MFN, Model under which Medicare Part B reimbursement rates would have been be calculated for certain drugs and biologicals based on the lowest price drug manufacturers receive in Organization for Economic Cooperation and Development countries with a similar gross domestic product per capita.

However, on December 29, 2021 CMS rescinded the Most Favored Nations rule.

Additionally, on November 30, 2020, HHS published a regulation removing safe harbor protection for price reductions from pharmaceutical manufacturers to plan sponsors under Part D, either directly or through pharmacy benefit managers, unless the price reduction is required by law.

The rule also creates a new safe harbor for price reductions reflected at the point-of-sale, as well as a safe harbor for certain fixed fee arrangements between pharmacy benefit managers and manufacturers.

Pursuant to court order, the removal and addition of the aforementioned safe harbors were delayed and recent legislation imposed a moratorium on implementation of the rule until January 1, 2026.

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

Sixty-one employees are engaged in research and development activities and 55 employees are engaged in general administrative functions.

Our employee headcount was 59 as of December 31, 2020, and grew by 97% as of December 31, 2021.

Twenty-two percent of our employees are located in the US, while the remaining 78% are located in the UK.

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

We had 114 employees as of December 31, 2021 and grew by 59% as of December 31, 2022.

As of December 31, 2022, 31% of our employees are located in the US, while the remaining 69% are located in the UK.

We have no collective bargaining agreements with our employees and we have not experienced any work stoppages.

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Mental Health and Wellbeing

As a mental health care company, we strive to be a leader in supporting employee mental health and well-being.

Our aim is to create a workplace which reduces the stigma of mental illness and supports our employees in staying well, physically and mentally.

We offer various resources which include:

• A global employee assistance program run by certified counsellors, offering over 20 sessions annually, available for employees and their families;

• An in-house wellness concierge providing one-on-one appointments, webinars and workshops, ‘community circles’, as well as providing advisory services to our internal employee-led wellbeing club;

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.

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;

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

• community circles, providing a forum for employees to discuss any topic with colleagues, providing open communication and support;

• 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;

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

• company-paid employee health care coverage;

• weekly qualified employee-led yoga sessions;

• ‘Sustainability week’ company closedowns over the summer and year-end holidays.

• 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.

Engagement, Culture and Values

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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.

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 most recent survey indicates that we have a very strong 45% net promoter score.

Our employees have a solid understanding of our vision and mission (97%), how their role contributes to them and high confidence in leadership.

Other notable comments were a shared passion, drive and motivation, acknowledgment of an extremely talented group of people, and a sense of community, with clear alignment to our values;

• Employees’ continued participation in our social, wellbeing, green team, corporate social responsibility, learning and development, and equity, diversity and inclusion groups.

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

• Regular company values workshops for all employees to discuss and bring our values to life;

• Regular company-wide team meetings aimed to connect with each other and receive updates from our CEO and the wider teams;

• A company-wide mentor program;

• Providing various opportunities to stay connected in our hybrid working model, with initiatives such as Friday Fives, randomized five minute ‘water cooler’ Zoom rounds;

Quarterly Qs, a quarterly Q&A session hosted by a panel of Executive Team members with a focus on “ask me anything”;

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;

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 CEO.

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.

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 local communities.

In 2021, we refreshed our focus on Equity, Diversity & Inclusion (EDI), led by our Chief People and Chief Commercial Officers, defining a new global strategy.

Together with our EDI club, a group including various levels across the company, we established our first global EDI policy.

The spirit of our policy is recognizing that our people are our most valuable asset.

The collective sum of individual differences, life experiences, knowledge, inventiveness, innovation, self-expression, unique capabilities, and talent that our employees rigorously invest in their work, represents a significant part of our culture, our reputation, and our vision for a world of mental wellbeing.

Our EDI policy outlines that our initiatives are applicable, but not limited to, our practices and policies on recruiting talent;

compensating, developing, and training employees;

social and recreational programs;

and the ongoing development of a work environment built on the premise of gender, diversity, and mental health equity that encourages and enforces respect, teamwork, flexible work schedules where possible, and, contributions to our communities.

In 2021 we had four main EDI focus areas, primarily aimed around information gathering and analyzing our current processes, given this is a new area for us.

We collaborated on these initiatives alongside the Employers Network for Equality and Inclusion (ENEI), of which we are members, and who serve as our external advisors.

These four focus areas were:

• Building a campaign around employees voluntarily providing their personal demographic information enabling us to begin measuring our workforce and set goals;

• Undertaking a gap analysis on neurodiversity as this topic is of particular interest to us given our industry focus on improving mental health;

• Evaluating our current processes to ensure our suppliers embrace diversity, and

• Engaging the whole company in our journey.

As of D ecember 31, 2021, both our board and executive team had 33% female representation.

39% of our wider leadership team were female.

Overall, our total female representation in the company as of December 31, 2021 was 54%, which is above the 47% aver age ac cording to the 2021 report by Biotechnology Innovation Organization (BIO).

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.

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

Employee Development and Training

We believe that the individual growth of our employees will fuel the company’s growth over time since our talent is experienced in our pioneering work.

We are committed to the continued development of our employees, and in order to support their growth, and to help us identify, foster, and retain high performing employees, we have implemented a number of programs:

• Coaching and career development resources through an external program called Landit, which provides personalized coaching and support for each employee to achieve their career goals;

• Mentoring pairs and circles, providing access to executives and colleagues for mentoring and support;

• Job architecture, providing employees with guidance and clear pathways for developing and progressing in their career;

We believe that the individual growth of our employees will fuel the company’s growth over time since our talent is uniquely experienced in our pioneering work.

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:

• 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;

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

• An annual Learning & Development allowance for each employee to spend on job related training or courses.

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

• 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.

Compensation and Benefits

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

Our compensation packages include base salary, annual bonuses, and stock-based compensation.

We also offer healthcare plans, paid time off, life and disability insurance, income protection insurance, and retirement saving plans.

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.

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.

In 2021, we introduced an employee stock purchase plan, under which eligible employees can voluntarily opt in to buy common stock at a discount from the fair market value of the stock as determined on specific dates twice a year.

We evaluate compensation and benefit offerings on an annual basis to ensure competitiveness of our programs and make adjustments as needed.

Hybrid Culture and COVID-19

We prioritized employee transparency and safety during the pandemic and continue to do so, providing clarity on office closures and evolving guidelines, where possible.

Similar to other companies, we adapted during the COVID-19 pandemic and developed a "ways of working" policy with input and feedback from the team.

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

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

We evaluate our offerings on an annual basis to ensure competitiveness of our programs and adjust as needed.

Ways of Working

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.

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.

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

We combine our ways of working policy with being as transparent as possible and making sure that we communicate openly with each other.

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.

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

Our ways of working policy has been effective for the company as we have maintained productivity and engagement throughout this period.

Transition to U.S.

Domestic Filer Reporting

We determined that, as of December 31, 2021, we no longer qualified as a ‘‘foreign private issuer’’ under the rules and regulations of the SEC.

As a result of this determination, beginning on December 31, 2021, we are no longer entitled to ‘‘foreign private issuer’’ exemptions and we are required to report as a domestic U.S.

filer, including filing Annual Reports on Form 10-K, quarterly reports on Form 10-Q, current reports on Form 8-K and proxy statements under Section 14 of the Exchange Act.

In addition, since January 1, 2021, our ‘‘insiders’’ are now subject to the reporting and short-swing profit recovery provisions contained in Section 16 of the Exchange Act and will be no longer exempt from the requirements of Regulation FD promulgated by the SEC under the Exchange Act.

Moreover, as a domestic filer, we are no longer permitted to follow our home country rules in lieu of the corporate governance obligations imposed by Nasdaq, and are required to comply with the governance practices required of U.S.

domestic issuers.

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.

Corporate Information

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What changed 10-K

Item 1. Business