Q3 2021 Compass Pathways PLC Earnings Call

[music].

Ladies and gentlemen, todays conference is scheduled to begin shortly please continue standby and we thank you for your patience again todays conference is scheduled to begin shortly please continue to standby. We thank you for your patience.

Operator: gentlemen today's conference is scheduled to begin shortly please continue to stand by we thank you for your patients again today's conference is scheduled to begin shortly please continue to stand by we thank you for your patience

unknown: Bhopal, Ande, and so on the same end up. I'm gonna be able to be. I'm gonna.

Operator: Ladies and gentlemen, thank you for standing by, and welcome to the Compass Pathways third quarter 2021 investor call. At this time, all participants are in listen-only mode. After this speaker presentation, there will be a question and answer session; to ask a question during the session, you will need to press Star 1 without a phone and to redirect your question; If you require technical support at any time, please press the. I would like to hand the conference over to your speaker today. Steve Schultz, please go ahead.

[music].

Ladies and gentlemen, thank you for standing by and welcome to combat pathways third quarter 2021 investor call.

At this time, all participants are no listen only mode.

After the speaker presentation, there will be a question answer session.

I ask a question during the session you will need to press star one.

One just on its own.

And your question.

And you're quite right.

Just any time, please press star zero.

I'd now like to hand, the conference over to your speaker today.

Stephen D. Schultz: Thank you, operator. Welcome all of you, and thank you for joining us today for our conference call today, which will combine both the third quarter 2021 results and the much anticipated Comp 360 Phase 2B top line results. We were able to combine these two events as they coincided from the timing standpoint. Again, my name is Steve Schultz.

Please go ahead.

Thank you operator welcome all of you and thank you for joining us today for our conference call today, which will combine both the third quarter 2021 results and the much anticipated comp 360 phase to be topline results, we're able to combine these two events as they coincided from a timing.

Standpoint.

Again my name is Steve Schultz I'm, the senior Vice President of Investor Relations of Compass pathways and today I'm joined by George Goldsmith, Chairman and Chief Executive Officer, Dr Guide Goodwin, our Chief Medical Officer.

Stephen D. Schultz: I'm the Senior Vice President of Investor Relations and Compass Pathways. And today I'm joined by George Goldsmith, Chairman and Chief Executive Officer, Dr. Guy Goodwin, our chief medical officer, and Pierce Morgan, our chief financial officer.

Here's Morgan, our Chief Financial Officer.

Stephen D. Schultz: The call is being recorded, and it will be available on the Compass Pathways Investor Relations website shortly after the conclusion of the call. We hope you've had a chance to read the two press releases issued earlier today, one on the Phase 2B clinical results, and the other covering our third quarter results. We've also posted a presentation in the investor section of our website in the event section that supports the top line Phase 2B data presented in this webcast, so you can follow along.

The call is being recorded and it will be available on the compass pathways Investor Relations website. Shortly after the conclusion of the call.

We hope you've had a chance to view the two press releases issued earlier today one on the phase two B clinical result, and the other covering our third quarter results. We've also posted a presentation to the investors section of our website in the events section that supports the top line phase <unk> data presented in this webcast. So you can follow.

Along.

Stephen D. Schultz: There's also an excellent Comp 001, Phase 2B Hub, on our website in the clinical section, and I encourage you to check that out as well. Before we begin, let me remind everyone that during the call today, the team will be making forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 as amended. You should not place undue reliance on these forward-looking statements. Actual events or results could differ materially from those expressed or implied by any forward-looking statements as a result of various risks, uncertainties, and other factors, including those risks and uncertainties described under the heading risk factors in our annual report on Form 20F, filed with the U.S. Securities and Exchange Commission earlier today and in the subsequent filings made by Compass with the SEA. Additionally, these forward-looking statements represent our views only as of today and should not be relied upon as representing our views at any subsequent date. We specifically disclaim any obligation to update or revise any forward-looking statement.

There was also an excellent comp 001 phase to be hub on our website in the clinical section and I encourage you to check that out as well.

Before we begin let me remind everyone that during the call today the team will be making forward looking statements within the meaning of the private Securities Litigation Reform Act of 1995 as amended.

Should not place undue reliance on these forward looking statements actual events or results could differ materially from those expressed or implied by any forward looking statements. As a result of various risks uncertainties and other factors, including those risks and uncertainties described under the heading risk factors in our annual report.

On form 20-F filed with the U S Securities and Exchange Commission earlier today and in subsequent filings made by Compass with the SEC.

Additionally, these forward looking statements represent our views only as of today and should not be relied upon as representing our views at any subsequent date.

We specifically disclaim any obligation to update or revise any forward looking statements.

Unknown Executive: With that, I'll now hand the call over to our chairman and CEO, George Goldsmith. Thank you, Steve, and welcome everyone. I'm pleased to be here today to present both the top line results of our Phase 2B clinical trials of investigational, comp 360 psilocybin therapy, and therapy, and our third quarter results in one webcast, which I hope makes it more convenient for all of you. Before going into the results to be, which I know is the star of the show today, let me first begin today's call with a business update on our recent progress.

With that I'll now hand, the call over to our chairman and CEO George Goldsmith.

Thank you, Steve and welcome everyone I'm pleased to be here today to present, both the topline results of our phase two b clinical trials of investigational comp 360 suicide in therapy, and our third quarter results and one webcast, which I hope makes it more convenient for all of you.

Before going into the phase to be result, which I know is the star of the show today, Let me first.

Let's begin today's call with a business update on our recent progress I will then Goodwin, our chief Medical officer to discuss the topline results of the comp 360 trial and piers Morgan, our Chief Financial Officer to provide a financial review, we will then open the call to questions.

Unknown Executive: I will then ask Guy Goodwin, our chief medical officer, to discuss the top line results of the Compt 360 trial, and Pierce Morgan, our chief financial officer, to provide a financial review. We will then open the call to questions. This has been an exciting quarter.

This has been an exciting court. So we've made great progress on numerous fronts.

Unknown Executive: We've made great progress on numerous fronts. Last month, we presented positive data from an open-label investigator-sponsored study from the Maryland Oncology Hematology Group at the Aqualino Cancer Center in Rockville, Maryland. In this study, the team also pioneered simultaneous group administration, with two to four participants being given psilocybin at the same time, with one-to-one therapist support. This tested the value of group support for cancer patients with moderate major depressive disorder, as well as the potential for increased scalability in providing psilocybin therapy in real-world settings.

Last month, we presented positive data from an open label investigator sponsored study from the Americas, Maryland Oncology Hematology group at the actual you know cancer Center in Rockville, Maryland.

In this study the team also pioneered simultaneous group administration with two to four participants being given suicide, but at the same time with one to one therapy support yes tested the value of group support for cancer patients with moderate major depressive disorder as well as the potential for increased scalability and providing.

Suicide in therapy in real World settings. Most importantly, some participants benefited from this study whilst expanding our knowledge on how to improve future research for this population of special interest in M D.

Unknown Executive: Most importantly, some participants benefited from this study, whilst expanding our knowledge on how to improve future research for this population's special interest in MDD. In our goal to continue to expand our development pipeline, last week we announced the launch of a study in post-traumatic stress disorder, or PTSD. This will be a Compos-sponsored Phase 2 program and should begin in the next month or so.

And our goal to continue to expand our development pipeline and last week, we announced the launch of a study in post traumatic stress disorder or PTSD and this will be accomplished sponsored phase II program and should begin in the next month or so over 350 million people worldwide suffer with PTSD within individual lifetime.

Unknown Executive: Over 350 million people worldwide suffer with PTSD, with an individual lifetime prevalence of 7.3%. In addition to the Comp 360 development programs that include our academic programs, we continue to expand our leadership and pre-clinical research, exploring new psychedelic compounds through the Compass Discovery Center, a network of leading scientists from the University of the Science at Philadelphia, UC San Diego School of Medicine, and the Medical College of Wisconsin. Notably, we have engaged Hamilton Morris, the research scientist and filmmaker, as a full-time consultant who will be working primarily at the Compass Discovery Center.

Prevalence of seven 3%.

In addition to the comp 360 development programs that include our academic programs. We continue to expand our leadership in preclinical research exploring new psychedelic compounds through the Congress Discovery Center network with leading scientists from the University of the science, its Philadelphia UC, San Diego School of Medicine, and the medical.

College, Wisconsin.

Notably we have engaged Hamilton Morris the research scientists and filmmaker as a full time consultants, who will be working primarily with the content Discovery Center Hamilton, who will be advising Congress on research related to new psychedelic compounds that could be developed into therapies in areas of unmet mental health need.

Unknown Executive: Hamilton will be advising Compass on research related to new psychedelic compounds that could be developed into therapies in areas of unmet mental health needs. This early stage work will enable us to broaden our portfolio beyond Com 360 Philoide and Fair. In September, we announced the acquisition of an intellectual property portfolio, including patent applications, covering a variety of psychedelic and empathogenic substances, some of which are pro-drugs, pharmacologically inactive compounds which are metabolized inside the body to produce an active drug.

This early stage work will enable us to broaden our portfolio beyond O 360 suicide in therapy.

In September we announced the acquisition of an intellectual property portfolio, including patent applications, covering a variety of psychedelic and pathogenic.

Substances, some of which are pro drugs pharmacologically inactive compounds, which are metabolized inside the body to produce an active drug.

Unknown Executive: The IP was developed together with inventor Dr. Matthias Grill, who will be working with Compass on an exclusive research project to develop new products in Canada. We plan to move some of these compounds into clinical development within the next two years, further expanding our leadership in this area of science. We also continue to grow our capabilities in digital and clinical innovation. Our digital team now comprises over 20 data scientists, engineers, developers, and designers.

The IP was developed together with adventure Doctor with highest grill, who will be working with Congress on an exclusive research project to develop new product candidates. We plan to move some of these compounds into clinical development within the next two years further expanding our leadership in this area of science.

We also continue to grow our capabilities in digital and clinical innovation. Our digital team now comprises over 20 data scientists engineers developers and designers. They are working on developing tools to improve the patient experience train and support therapist and explore digital behavioral markers. Some of these tools will be incorporated into future.

Unknown Executive: They are working on developing tools to improve the patient experience, train and support therapists, and explore digital behavioral markers. Some of these tools will be incorporated into future clinical trials. Our clinical innovation team is also growing to refine our psychological support model across the and prepare for the increased therapist training requirements across our expanding portfolio of studies. Before I hand the call to Guy to talk about our Phase 2B data, let me say, on behalf of the Compass Pathways founders, Nekaterina Malievka, Lars Vilda, and myself, we applaud the extended team of so many people who worked on this trial, including clinicians, comp Most importantly, we want to thank the patients who participated in the trial, enabling us to advance the understanding of how we can help out. I want to especially recognize two stands.

Nicole trials.

Our clinical innovation team is also growing to refine our psychological support model across indications and.

To prepare for the increased therapist training requirements across our expanding portfolio of studies.

Before I hand, the call to Guy to talk about our phase <unk> data, let me say on behalf of the compass pathways founders EQECAT arena, and while the FCO Lawrenceville and myself, we applaud the extended team with so many people who worked on this trial, including clinicians compas employed and our clinical research organization partner worldwide critic.

Trials. Most importantly, we want to thank the patients who participated in the trial, enabling us to advance the understanding of how we can help others.

I want especially recognize.

<unk>.

Congress is SVP of clinical operations for her incredible contribution. This was a complicated a novel trial and it was expertly managed in the midst of a global pandemic across 22 sites 10 countries and seven languages, it's an extraordinary accomplishment and creates a foundation for expansion of our clinical development program across.

Unknown Executive: Compass's SDP of clinical operations for her incredible contribution. This was a complicated and novel trial, and it was expertly managed in the midst of a global pandemic across 22 sites, 10 countries, and 7 languages. It's an extraordinary accomplishment and creates a foundation for expansion of our clinical development program across indications of significant unmet needs. Thank you, Sue.

Patients with significant unmet need thank you Sue.

This achievement would not have been possible had it not been for those who were exploring psilocybin therapy before Congress and we want to recognize those researchers like new shoulders, we stand today.

These include Robin Carhartt Harris, David not Rolling Griffith, George Greer, Charles Grom, and Dave Nichols, among others I also want to personally recognize country for her leadership.

The design of our.

Program and training protocol without her insight and determination accomplished would not be here today with that let me now hand over to Guy who will provide a more detailed view of these results Guy.

Unknown Executive: This achievement would not have been possible had it not been for those who were exploring psilocybin therapy before Koppas, and we want to recognize those researchers on whose shoulders we stand today. These include Robin Carhart Harris, David Knuck, Roland Griffiths, George Greer, Charles Grob, and Dave Nichols, among others. I also want to personally recognize TACHA for her leadership in the design of our Program and Training Protocol. Without our insight and determination, Compass would not be here today. With that, I now hand over to Guy, who will provide a more detailed view of these results. Thank you, George.

Okay.

Thank you George.

Pleasure to speak to everyone. Today I'll review the positive data generated from the 360 phase two b clinical trial comp 001.

Our interest bearing but that's fine that's fine.

That Steve referred to earlier.

Slide two is why don't I stop our country 60 psilocybin therapy.

Country 60, psilocybin therapy consists of two components. The first is the investigational drug itself, which is presented in oral capsule.

And the second is the psychological support which consists the preparation phase support jewelry sell assigned in administration and the subsequent integration.

This in total is the psilocybin therapy, because it's being tested in this study.

It is important to point out that this approach has developed has an integrated therapy and the results from this trial and can only be interpreted in this context.

Guy Goodwin: It's a pleasure to speak to everyone today and review the positive data generated from the Comp 360 Phase 2B clinical trial, Comp 0.01. I'm referring to the slides on our website that Steve referred to earlier, and slide two is where I start, our Comp 360 psilocybin therapy. Our Com 360 psilocybin therapy consists of two components. The first is the investigational drug itself, which is presented in an oral capsule. And the second is psychological support, which consists of the preparation phase, support during psilocybin administration, and subsequent integration.

Fulfill assignment on their own or with some alternative therapy protocol are unlikely to be comparable.

Slide three is 001 study design and endpoints.

Looking at the trial design and endpoints you will see that all patients with screen and subsequently entered into the study within three to six weeks.

This preparatory period was to allow the managed withdrawal of antidepressant, which the patient may have been taking.

Bear in mind that these patients were all resistant to treatment with previously administered anti depressants.

But we'll have to be washed out people will come 360 could be administered.

The randomization walk to one of three doses.

What might a one milligram 10 milligram or 25 milligram account 360 <unk>.

Guy Goodwin: This in total is the psilocybin therapy that is being tested in this study. It is important to point out that this approach has been developed as an integrated therapy, and the results from this trial can only be interpreted in this context. Other forms of psilocybin on their own or with some alternative support therapy protocol are unlikely to be comparable.

Ministers as you can see here on Taiwan.

The effects of the treatment intervention when measured on day two at week two week three week six week nine and week 12.

Primary endpoint was designated the change in the mattress school the gold standard rating scale for depression.

<unk> three with a further important outcome at week 12 for the same measure to assess durability of effect random.

Randomization was equal to three arms of the study.

Guy Goodwin: Fly 3 is Comp 001, Study Design and Endpoints. Looking at the trial design and endpoints, you will see that all patients were screened and subsequently entered into the study within three to six weeks. This preparatory period was to allow the managed withdrawal of antidepressants that the patients may have been taking. Bear in mind that these patients were all resistant to treatment with previously administered antidepressants and therefore had to be washed out before Compt 360 could be administered.

Fortunately the mattress school was SaaS by independent Raters, who remote from the trial site in blind to intervention and study design.

Tiddly creates a tricky blind.

Slide four shows participant disposition and demographics.

In all 233 patients were randomized and they were on.

<unk> to the three arms of the study has shown on the slide.

Number two in each arm, where it's falling.

For the high dose 25 milligrams.

79 patients for the intermediate dose 10 milligrams 75 patients until the low dose one milligram 79 patients.

All of these patients the majority completed the study.

<unk> discontinued in each of the five and the 25 milligram.

90 10.

And 10 milligram.

So we know that there were more withdrawals can be arms with low dose treatment.

Guy Goodwin: The randomizations were to one of three doses, which were either one milligram, 10 milligrams, or 25 milligrams of Comp 360 and were administered, as you can see here on day one. The effects of the treatment intervention were measured on day two, at week two, week three, week six, week nine, and week 12. The primary endpoint was designated the change in the Madras score, the gold standard rating scale for depression, at week three, with a further important outcome at week 12 for the same measure to assess durability of a say. Randomization was equal to three arms of the study. Importantly, the Mavre score was assessed by independent raters who were remote from the trial site and blind to intervention and study design, effectively creating a triple blind.

The reasons for the withdrawals as shown on this line.

In all there were 131 patients from Europe, and 102 from North America.

We were delighted to see that 94% of the patients had no. Prior psilocybin experience. So this concern, but generally still assigned the naive patient population.

This is a percentage which reflects community certainly.

In country.

The participant demographics status.

Gender race weight and baseline depression severity.

Well balanced across the three groups.

We're moderately or severely depressed and of course met criteria for treatment resistant depression.

Slide five shows the primary endpoint of change from baseline in Madras total school.

And the primary endpoint in this trial is the change from baseline in the mattress total score of three weeks. We are pleased to report a statistically significant primary endpoints of three weeks.

That is the comparison 25 milligram with one milligram and the magnitude of six six points in the mantra.

On a P value less than 0.001.

Guy Goodwin: Slide 4 shows participant, disposition, and demographics. In all, 233 patients were randomized, and they were allocated to the three arms of the study, as shown on the slide. The numbers in each arm were as follows.

Additionally, there was a rapid onset of action early as day two.

Thanks was studied with statistically significant treatment differences between the 25 and the one milligram group apparent from day to three to six weeks.

In contrast, the 10 milligram dose showed an intermediate response with two five points on the mattress and was not statistically distinguishable from one milligram dose.

Guy Goodwin: With a high dose, 25 milligrams, 79 patients. For the intermediate dose, 10 milligrams, 75 patients, and for the low dose, 1 milligram, 79 patients. On these patients, the majority completed the study; a few discontinued in each of the arms, five in the 25 milligram arm, nine in the 10 milligram arm, and 10 in the one milligram. So we know that there were more withdrawals in the arms with lower dose treatment, and the reasons for the withdrawals are shown on the slide. In all, there were 131 patients from Europe and 102 from North America.

Three weeks all subsequently.

Slide six shows the key secondary endpoints mattress responders.

Looking at the key secondary endpoints. The first chose mattress responders Madras responders were defined as patients with experienced a 50% or more reduction in symptoms at any particular time point.

And you can see the results presented go day two week, one week three week six week nine and week 12 across its grown.

Every case the color code remains the same with 25 milligram dose showing the blue columns tend.

10 milligrams the green.

One milligram as the gray.

It will be evident from this plot that there was an important numerical difference between the 25 and the 10, one milligram doses at all time points.

Guy Goodwin: We were delighted to see that 94% of the patients had no prior psilocybin experience, so this confirmed the generally psilocybin-naive patient population. And this is a percentage which reflects community surveys in Western countries.

The most important thing we three with.

36, 7% that is 29 79 patients had shown a response at that time point in the 25 milligram group.

Guy Goodwin: The participant demographics, that is, age, gender, race, weight, and baseline depression severity, were all well balanced across the three groups. Patients were moderately or severely depressed, and they, of course, met criteria for treatment-resistant depression. Slide 5 shows the primary endpoint, the change from baseline in the matter of the total score at three weeks. We are pleased to report a statistically significant primary endpoint at three weeks.

This compares with about half the response rate and the others.

Two groups.

But one O. There were $26 79 patients. So 32, 9% of the 25 milligram group the continued to show a response.

Time points.

Again this was twice the number shown the patients in the 10 milligram and one milligram groups.

We believe this is evidenced with durability of response to the 25 milligram dose of <unk> 360, Philosophy's Duncan.

Slide seven shows the key secondary endpoint is an address remittance.

Looking at some of the niches studies were defined as patients that any particular visit chosen manto score of 10 or less this is.

Guy Goodwin: That is the comparison of 25 milligrams with 1 milligram as a magnitude of 6.6 points in the madras and a P value of less than 0.001. Additionally, there was a rapid onset of action seen as early as day two, and the effects were sustained with statistically significant treatment differences between the 25 and the 1 milligram group, apparent from day 2 through to 6 weeks. In contrast, the 10 milligram dose showed an intermediate response of 2.5 points on the mad risk and was not statistically distinguishable from one milligram dose at three weeks or subsequent. Slide 6 shows the key secondary endpoints, Madras Responders. Looking at the key secondary endpoints, the first chose Madras responders.

A particular clinical interest because it is evidenced that beneficial reduction of symptoms to normal level.

You can see here with the same color coding for the results from different days.

The rate per admission in the 25 milligram group three weeks with 29, 1%.

Weeks the rate was 26, 6%.

So bear in mind this represents 23% and 21 patients respectively, who remained without additional treatment and were in remission at week, three and 12 by contrast, the numbers and the other treatment groups on loan.

Slide eight.

Titled Mattress sustained responders.

A further way of evaluating durability of response is to look at patients who individually met response criteria.

In a moment.

So both <unk> and.

And week 12, together with at least one other visits at week six or week nine.

When you select that patient group, they reps that represent 24, 1% or 19 of the 79 patients entering the treatment arm with 25 milligrams and as you can see less than half that number in the 10 milligram and one milligram arms.

Guy Goodwin: Madras responders were defined as patients that experienced a 50% or more reduction in symptoms at any particular time point. And you can see the results presented for day two, week one, week three, week six, week nine, and week 12 on this graph. In every case, the color code remains the same, with 25 milligram doses showing as the blue columns, 10 milligrams as a green, and 1 milligram as the grey.

Yeah.

Slide nine shows safety ease of treatment emergent adverse events.

Looking at the safety profile and the treatment emergent adverse events recorded in that study.

And over 90% of cases were mild or moderate severity.

The patients reporting a serious treatment emergent adverse events with five patients in the 25 milligram six and the 10 milligram and one in the one milligram Hum.

As expected the total number of adverse events was slightly higher than the 25 milligram group.

The other group.

Further analysis on the onset and duration of the treatment emergent adverse event is underway.

Guy Goodwin: It will be evident from this plot that there is an important numerical difference between the 25 and the 10 and 1 milligram doses at all time points, the most important being at week three, where 36.7%, that is, 29 of 79 patients, had shown a response at that time point in the 25 milligram group. This compares with about half the response rate in the other two groups.

A particular interest will of course be the onset and duration.

We are showing here treatment emergent events over the whole duration of the study at 12 weeks. This total includes all events that are likely to be related to the psychedelic experience on the dosing guy.

We know from our healthy volunteer studies and from the literature.

Expect this.

On that day that would have to be taken into consideration in evaluating the results of this trial.

Slide 10 shows the most frequent treatment emergent adverse events ordered by the 25 milligram arm and at least.

Guy Goodwin: At week 12, there were 26 of 79 patients, or 32.9% of the 25 milligram group, that continued to show a response at this time point. Again, this was twice the number shown for the patients in the 10 milligram and 1 milligram groups. We believe this is evidence for durability of response to the 25 milligram dose of COMP 360 psilocybin therapy. Slide 7 shows the key secondary endpoints as an address rent

At least 5% any treatment group.

The most frequent adverse effects are shown here by the 25 milligram arm.

We are showing all of those adverse events that was shown by at least 5% in any treatment group.

The most prevalent headache, nausea and fatigue.

Together with insomnia, and then a variety of other adverse effects, which may well be relates to move these.

These are regularly observed in many clinical trials in depression.

Next slide slide 11 shows treatment emergent serious adverse events.

Ordered by 25 milligram arm.

Guy Goodwin: Looking at Madras Ramith's, these were defined as patients that, at any particular visit, show a Madras score of 10 or less. This is of particular clinical interest because it is evidence of beneficial reduction of symptoms to normal levels. You can see here, with the same color coding for the results from different days, that the rate for remission in the 25 milligram group of three weeks was 29.1%. For 12 weeks, the rate is 26.6%.

When looking at treatment emergent serious adverse events. This is ordered again by the 25 milligram arm there were relatively few events reported how.

As you can see a number of them relate to suicidal behavior silicon.

Michael Ideation drug withdrawal on self injury.

This can all be common in patients with treatment resistant depression.

The number of events include some cases and in individual patients.

Essentially pumped at the episode with John Nevertheless, Classifieds, a separate event school complete clarity.

Guy Goodwin: So bear in mind this represents 23 and 21 patients, respectively, who remained without additional treatment and were in remission at week 3 and 12. By contrast, the numbers in the other treatment groups are lower. Slide 8, titled Madras Sustained Responders. A further way of evaluating durability of response is to look at patients who individually met response criteria at a minimum of three business days. So both week three and week 12, together with at least one other visit at week six or week nine.

As shown on slide 12 in conclusion. This is the largest randomized controlled double blind psilocybin therapy trial ever conducted and it showed rapid and sustained response to the 25 milligram dose level of 360 <unk> assigned in therapy.

It's also worth noting that this is a multi center study it involved multiple patient populations recruited through conventional medical care systems and very few of the patients had chronic psilocybin experience.

Contrast to previous Investor initiated studies.

We expect the top line data with secondary analysis will provide the springboard for phase III development.

Guy Goodwin: When you select that patient group, they represent 24.1% or 19 of the 79 patients entering the treatment arm with 25 milligrams, and as you can see, less than half that number in the 10 milligram and 1 milligram parts. Slide 9 shows safety.

Study achieved its primary endpoint with 25 milligrams, achieving a significant treatment difference minus six six unchanged baseline from mattress schools, when compared with the one milligram dose at week three.

The P value for this effect was less than 0.001.

The 10 milligram interestingly it did not show a statistically significant difference at week three compared with the one milligram dose the numerical difference being minus two five points.

Guy Goodwin: These are treatment emergent adverse events. Looking at the safety profile and the treatment emergent adverse events recorded in the study, which were in over 90% of cases were of mild or moderate severity, The patients reporting a serious treatment emergent adverse event were five patients in the 25 milligram arm, six in the 10 milligram arm, and one in the one milligram arm. As expected, the total number of adverse events was slightly higher in the 25 milligram group than either of the other groups.

The 25 milligram group demonstrated a significant decrease from baseline and the mattress total score the day. After 360 administration and three the 25 milligram group showed a 12 point reduction from baseline in the mattress total school.

Secondary end points.

Couple of a number of Madras responders and sustained responded with same with the 25 milligram dose compared with the one milligram and there was a rapid development of permission from day two to week three.

Number of patients who showed a response was $29 79 patients in the 25 milligram arm and $23 79 patients were still in remission at week three nine.

Guy Goodwin: Further analysis on the onset and duration of the treatment immersion adverse events is underway. Of particular interest will, of course, be the onset and duration, because we are showing here treatment emergence events over the whole duration of the study of 12 weeks. This total includes all events that are likely to be related to the psychedelic experience on the dosing day. We know from our healthy volunteer studies and from the literature that we should expect adverse events on that day.

19 patients with 79 patients from the 25 milligram group with sustained responders at week 12.

Regarding safety country, 60 is generally well tolerated and the majority of the treatment emergent adverse events were mild to moderate in severity.

We are particularly interested in understanding reports of suicide, Vanity and suicide behavior and treatment groups.

Finally, let me Echo Georges Thanks to the team of clinicians and especially on patients who were involved in this trial with this result, we are one very important step closer to our goal of providing patients with a novel and potentially life changing option for many individuals who currently have very few options.

Guy Goodwin: That has to be taken into consideration in evaluating the results of this trial. Slide 10 shows the most frequent treatment immersion adverse events ordered by the 25 milligram arm, and those were at least 5% in any treatment group. The most frequent adverse effects are shown here ordered by the 25 milligram arm. We're showing all those adverse events that were shown by at least 5% in any treatment group. The most prevalent are headache, nausea, and fatigue, together with insomnia and then a variety of other adverse effects, which may well be related to mood.

Thank you and let me now hand over the call to payers for the financial review Peter.

Thank you Guy.

The company continues to maintain a strong financial position with cash and cash equivalent of $294 million at September 30 of 2021, compared with $193 million at December 31, 2020.

This is expected to fund our operations into 2024.

I will now recap our financial results for the three and nine months ended September 32021.

Guy Goodwin: These are regularly observed in many clinical trials in depression. Next slide, slide 11, shows treatment emergent serious adverse events, ordered by 25 milligram arc. When looking at treatment emergent serious adverse events, this was ordered again by the 23 milligram arm. There were relatively few events reported, but as you can see, a number of them relate to suicidal behavior, suicidal ideation, drug withdrawal, and self-injury. These can all be common in patients with treatment-resistant depression. The number of events includes some cases in an individual patient and are essentially part of the same episode, which are nevertheless classified as separate events for complete clarity. The conclusion is shown on slide 12.

The loss from operations for the three months ended September 32021.

$21 8 million.

Compared with $13 5 million for the prior year period, the loss from operations increased noncash share based compensation expense of $2 $3 million for the three months ended September 30 of 2021.

With $5 $2 million noncash share based compensation in the prior period.

The net loss was $15 8 million.

The eight loss per share for the three months ended September 32021.

With a net loss of $16 $7 million or $1 30 loss per share during the same period in 2020.

The loss from operations for the nine months ended September 32021 to $54 9 million compared.

Compared with $39 9 million for the prior year period.

The loss from operations included non cash share based compensation expense of $5 9 million for the nine months ended September 32021, compared with $16 $6 million non cash share based compensation in the prior period.

Guy Goodwin: In conclusion, this is the largest randomized controlled double-blind psilocybin therapy trial ever conducted, and it showed a rapid and sustained response for the 25 milligram dose level of comp 360 psilocybin therapy. It's also worth noting that it was a multi-centre study. It involved multiple patient populations recruited through conventional medical care systems, and very few of the patients had prior psilocybin experience, in contrast to previous investor-initiated studies. We expect the top line data with secondary analysis will provide the springboard for phase three development.

Research and development expenses for the nine months ended September 32021.

$34 million, an increase of $11 $6 million compared with the nine months ended September 30 of 2020. This increase in research and development expenses compared to the prior year period was primarily attributable to an increase in development personnel and consulting expenses as the company continues to expand its activities.

Including lunch menus trial in PTSD preparing for phase III trials in TRP and expanding our digital activities.

General and administrative expenses were $24 $5 million for the nine months ended September 30 of 2021, compared with $21 $1 billion for the same period in 2020.

Guy Goodwin: The study achieved its primary endpoint, with 25 milligrams achieving a significant treatment difference of minus 6.6 on change of baseline from Madras scores when compared with the 1 milligram dose at week three. The P value for this effect was less than 0.001. The 10 milligrams, interestingly, did not show a statistically significant difference at week three compared with the one milligram dose, the numerical difference being minus 2.5

The increase of $3 $4 million and general and administrative expenses compared to the prior year period was primarily attributable to increases in personnel costs to support our growth initiatives, including our transition to a public company.

Increased insurance and other costs of operating as a listed company, partially offset by a decrease in noncash share based payments.

The net loss was $46 $1 million or $1 17 loss per share for the nine months ended September 32021, compared with a net loss of $41 5 million or $3.90 loss per share during the corresponding period in 2020.

Guy Goodwin: The 25 milligram group demonstrated a significant decrease from baseline in the Madras total score the day after Compt 360 administration, and at week three, the 25 milligram group showed a 12-point reduction from baseline in the Madras total score. Secondary endpoints suggest that the number of Madras responders and sustained responders was seen with the 25 milligram dose compared with the 1 milligram dose, and there was a rapid development of remission from day two to week three.

Thank you and I'll now hand, the call back to George.

Thank you both.

We're now working to schedule, an end of phase II meeting with the FDA as quickly as possible I remind you that we have breakthrough therapy designation, which can provide us with a more rapid and open dialogue with the FDA.

Our immediate goal is to present these data to the FDA and gain agreement on a phase III program designs, we were reporting on our progress in future Communications. In addition, we expect the SSRI drug drug interaction studies to be completed by the end of this year, which will provide important information about the potential influence of concomitant <unk>.

That's all I use with our <unk> com 360, so assignments here if.

You will recall that our phase <unk> study did wean patients off of their SSRI therapy prior to the Cop 360 Psilocybin administration.

Guy Goodwin: The number of patients who showed a response was 29 of 79 patients in the 25 milligram arm, and 23 of 79 patients were still in remission at week three. 19 patients of the 79 patients from the 25 milligram group were sustained responders at week 12. Regarding safety, Compt 360 is generally well tolerated, and the majority of treatment-emergent adverse events were mild to moderate in severity. We are particularly interested in understanding the reports of suicidality and suicide behavior in treatment groups.

Sure.

Overall. This trials result was consistent with the data we saw coming from the Imperial College, London study in April and the recent accurately know cancer center data, which should save the patients saw a rapid and sustained effect with a generally well tolerated safety profile. We believe this consistently supports our assertion that comp.

360 therapy can potentially bring a new approach.

Now, we may be able to treat patients for whom for whom few options exist today and todays results continues to bolster our leadership in this field to.

To be clear all of our efforts are aligned with our commitment to think differently about mental health and to follow up those thoughts with well executed actions.

Guy Goodwin: Finally, let me echo George's thanks to the team, our clinicians, and especially our patients who were involved in this trial. With this result, we are one very important step closer to our goal of providing TRD patients with a novel and potentially life-changing option for many individuals who currently have very few options. Thank you, and let me now hand over the call to the peers for the financial review.

The Adidas great patients are suffering we have to provide them with new tools and the most responsible way that means we now understand who can benefit from our work and who cannot at this point, we are working day and night to ensure we expand our understanding.

Thank you for your time today, we will now open the line for questions operator.

Thank you ladies and gentlemen, we will now begin the question answer session.

As a reminder, if you wish to ask a question. Please press star one on your telephone keypad.

Unknown Executive: Thank you, Guy. The company continues to maintain a strong financial position with cash and cash equivalents at $294 million at September 30, 2021, compared with $193 million at December 31, 2020. This is expected to fund our operations into 2024. I will now recap our financial results for the three and nine months ended September 30, 2020.

Well pause for just a moment to compile the Q&A roster.

Your first question.

Comes from <unk> <unk> from Cowen Your line is open.

Hi, Richard Good morning, everyone.

Hi, good morning, and congratulation on the entire dataset.

But especially that when theirs.

Analysis.

My first question.

The second one really take your first question on slide 11.

At Ta.

<unk> said that your preferred terms.

Can you go into a little more detail about what we're seeing around.

Unknown Executive: 30th, 2021.

Unknown Executive: The loss from operations for the three months ending September 30, 2021 amounts to $21.8 million, compared with $13.5 million for the prior year period. The loss from operations includes non-cash share-based compensation that is $2.3 million for the three months ended September 30, 2021, compared with $5.2 million for the prior period. The net loss was $15.8 million or 38 cents a loss per share for the three months.

The individual behaviors like when did they occur where are these patients.

Responders all the meters.

And what are they on rescue meds.

Actually I think I can.

Yes, that'll behavior self injury and concerning to investors.

Great Guy.

So the suicidal behavior really reported at least one month after the administration of treatment and they occurred in patients who were essentially non responding.

On the suicidal ideation with a little different.

And that was at least in one case, it's quite early on in the treatment process. Because these numbers are very small and our plan is to look at them in as much detail as we can but in addition in the secondary analyses to look at the Columbia suicide scales with collecting on every patient.

Unknown Executive: of September 30th, 2021, compared with a net loss of $16.7 million, or a $1.30 loss per share,

At every visit that will give us I think a much more accurate understanding of the relationship between treatment and suicidal both experiencing suicidal ideation and suicidal action.

Unknown Executive: per share during the same period in 2020. The loss from operations for the nine months ended September 30th, 2021, amounted to $54.9 million, compared with $39.9 million for the prior year period. The loss from operations included non-cash share-based compensation expense of $5.9 million for the nine months ended September 30th, 2021, compared with $16.6 million in non-cash share-based compensation in the prior period. Research and development expenses for the nine months ended September 30th, 2021 amounted to $30.4 million, an increase of $11.6 million compared with the nine months ended September 30th, 2020.

The intention of self injury is that I guess, an aspect of that is overlapping with the suicidal behavior and suicidal ideation.

We actually don't believe it does it's classified in that way, but it represents really quite trivial.

Self harm at me scratching or banging my head, both very simple things that really don't carry any.

Suicidal threats or intense but they aren't quite common in depression depressive populations well described.

I'm afraid they are just part of the picture for these patients and part of that suffering.

Got it and a very quick follow up George and guide you.

You have your dose now.

And do you think that.

Phase III with the skills or powering a phase III for durability, whether its week eight of the 12 would make sense for phase III from a reimbursement perspective.

Unknown Executive: This increase in research and development expenses compared with the prior year period was primarily attributable to an increase in development, personnel, and consulting expenses as the company continues to expand activities, including launching a new trial in PTSD, preparing for phase three, and TRD, and expanding our digital activities.

Yes, we think we conclusively have our dose and in speaking with payers and others. We haven't included even in our phase <unk> trial, how economic related measures quality of life measures.

And we will be discussing all of that since we go into our phase III design windows, who advise us on payer metrics et cetera, we've been working with payers and health technology assessors here in Europe. Since 2016, so we're well aware of their requirements and we expect to be able to address that in a well powered study but.

Unknown Executive: General and Administrative expenses were $24.5 million at the nine months end of September 30th, compared with 21.

Our phase III program won't have to be agreed and discussed which we've been discussing already with regulators on both sides of the Atlantic and we will look forward now to bring in these data.

Unknown Executive: with $21.1 million for the same period in 2020. The increase of $3.4 million in general and administrative expenses compared to the prior year period was primarily attributable to increases in personnel costs to support our growth initiatives, including our transition to a public company, increased insurance and other costs of operating as a listed company, partially offset by a decrease in non-cash share-based payments.

<unk> been agreed that programming swiftly moved into its execution.

Great. Thanks, I'll hop back in the queue.

Thank you.

Thank you so much.

Next question from Josh <unk> from Evercore ISI. Your line is open.

Great. Thanks, so much for taking the question how are you thinking about ways to.

Preserve effect beyond that.

Just a few weeks either with use of adjuvant therapies or patient selection tool to optimize for durable. Thank you.

Unknown Executive: The net loss was $46.1 million, or $1.17 loss per share, for the nine months ending on September 30th, 2021, compared with the net loss of $41.5 million, or $3.90 loss per share, during the Corrits.

Josh I'll start the answer and handoff to Guy, but I think it's a really important question and we started this whole program. Our whole goal is to identify who responds and who doesn't and who responds longer who needs additional support to that end. What we've done is actually recorded every therapy interactions. So we have.

<unk> learning I look at your transcripts across the trial participants really starting to understand the deeper level.

Unknown Executive: per share during the corresponding period in 2020. Thank you, and I'll now hand the call back. Thank you both. We're now working to schedule an end-of-phase two meeting with the FDA as quickly as possible. I remind you that we have breakthrough therapy designation, which can provide us with a more rapid and open dialogue with the FDA. Our immediate goal is to present these data to the FDA and gain agreement on a phase three program design.

Couple of parrot patterns, including changes to patient narrative therapist actions that are being correlated with particular outcomes. This is unprecedented data and we will be digging deep into that to look at how we can in fact optimize therapy and develop as we've said from the beginning our more.

More precise and predictive model of care.

So what type of therapy. So we are looking deeply at these data to keep in mind. We just received the data about 48 hours ago. So there's a lot of work to do we're just reporting topline today.

Unknown Executive: We will report on our progress in future communications. In addition, we expect the SSRI Drug Drug Interaction Study to be completed by the end of this year, which will provide important information about the potential influence of concomitant SSRI use with our Compt 360s, so Simon Thera. You will recall that our phase 2B study did wean patients off their SSRI therapy prior to the COPS 360 psilin administration session.

Do you have anything else to add.

I think I would just underline that the way in which the study was designed as the psychological support it's essentially safety around the administration of the medications. So this is a type of the medication in isolation, it's pretty remarkable that we get these effects after single dose up to 12 weeks clearly if we if we are.

We are working with colleagues within the company to look at digital support mechanisms and monitoring which may very well have carried the promise that we can improve outcomes through that sort of approach.

Suddenly be considering that in the future.

Operator: Overall, this trial's result is consistent with the data we saw coming from the Imperial College London study in April and the recent Acalino Cancer Center data, which is to say the patients saw rapid and sustained effects with a generally well-tolerated safety profile. We believe this consistently supports our assertion that Compt 360 therapy can potentially bring a new approach to how we may be able to treat patients for whom few options exist today.

I actually just also say that this is the data set that we developed in close collaboration with payers and regulators to get both sides of the Atlantic.

Countries to answer the fundamental questions. When we couldnt do that unless we really looked at the dose finding and single dose and its durability. Only then can we look at how we can identify the patients who have different experiences and look at how to optimize that experience to maximize the outcome and the duration.

Got it and when do you when do you expect to have some of the additional analysis completed and full data presentation.

We will be working on that hard.

Doing it as soon as possible, but we don't have a date, but.

We're going to be added.

Hence to being bigger.

Super Thanks, so much.

Thank you so much any other question.

Operator: And today's result continues to bolster our leadership in this field. To be clear, all of our efforts are aligned with our commitment to think differently about mental health and to follow up those thoughts with well-executed action. The need is great. Patients are suffering. We have to provide them with the new tools in the most responsible way. That means we must understand who can benefit from our work and who cannot. We are working day and night to ensure we expand our understanding. Thank you for your time today. We will now open the line for questions.

Next question from Charles Duncan Your line is open.

Okay Super.

Thank you George and team congratulations on a.

Rigorously conducted trial clearly seminal event for the field. Thanks for taking the question. My first question is regarding next steps on sizing and timing and I know you need to do.

Discuss this with the agency.

Could you imagine being able to.

Outline of protocol or even up.

Operational wise next step a next maybe a phase III by roughly mid 'twenty two.

We can certainly imagine many stages and Thats one were focused on imagine easy to use your term.

Operator: Thank you, ladies and gentlemen. We'll now begin the question and answer session. As a reminder, if you wish to ask a question, please press star 1 on your telephone, hold on. We'll pause for just a moment to compile the Q&A. Your first question comes from Wittu Beral from Kowen. Your line is open.

Our very heavily recruiting sites that lithia preparing our phase III infrastructure to build on our really robust phase two infrastructure that all work is also in process, but again, we can't anticipate what the agency the FDA and DMA and HRA will say as we review these data so.

We are ready to hit the go fast because we do whenever we get the word from the agencies, but we will be reviewing this very rapidly with them.

unknown: Hi Richard. Good morning, everyone. Hi Richard. Good morning.

Okay. That's good second question is regarding any phenotypic factor just I understand that.

unknown: Congratulations on the entire data set, not just the top line, but especially that remitters analysis. I have my first question, and I'll keep the second one really tight. My first question is slide 11, the TAE, and the VEDER preferred terms. Can you go into a little more detail about what was seen around the individual, behaviors, like, when did they occur? Were these patients responders or remitters, and were they on rescue meds? I actually think I can. It was said that behavior, self-injury, and ideation, I think, are the most concerning to

Is fresh data.

So probably havent done the analysis.

But is there anything that you are in particular interested in such as prior lines or time since their science diagnosis.

May have drove responses in terms of either the primary endpoint or durability anything that you're particularly interested in looking at our.

You have seen.

Well again, I'll start that and then hand off to golf.

I think a few things we are really important to US one was that this study actually use patients who were referred based on medical records. So we have a validated.

Relative to those background information that back with information will be used in future analyses obviously.

Guy Goodwin: So the suicidal behaviors were really reported at least one month after the administration of treatment, and they occurred in patients who were essentially non-responding. The suicidal ideation was a little difference, and that, at least in one case, was quite early on in the treatment process. Of course, these numbers are very small, and our plan is to look at them in as much detail as we can, but in addition, in the secondary analyses, to look at the Columbia suicide scales that were collected on every patient at every visit. That will give us, I think, a much more accurate understanding of the relationship between treatment and suicidality, both suicidal ideation and suicidal action.

One of the things that was really important to us to be able to demonstrate that these benefits could happen to people who had.

No prior experience or 94% of our sample had no prior suicide and experience quite at odds with the prior studies and the.

<unk> of our therapists in all of our centers also.

Prior psychedelic experience. This was so important for us to generalize and all of those population, which is approximately the same as our study about 90 plus percent who haven't had these experiences so to be able to demonstrate that this works in that environment, It's really important for scalability and more.

To help the most patients possible guy.

Yes, Justin.

To say that obviously, we're aware of existing data suggests that <unk> 10 to a limited extent predict treatment response from baseline measures and we have those baseline measures and there's also of course emerging interest in biomarkers.

Guy Goodwin: The intentional self-injury. Is that, I guess, an aspect that is overlapping with suicidal behavior and suicidal ideation?

Looking at the measures that we have in that category as well, but as you rightly said at the beginning we're not yet in a position to comment on that we're just going to be very excited to follow up and look at those questions and answer them for you.

Guy Goodwin: We actually don't believe it does. It's classified in that way, but it represents really quite trivial self-harm. It means scratching or banging the head or very simple things that really don't carry any suicidal threat or intent, but they are quite common in depressive populations. They're well described, and I'm afraid they're just part of the picture for these patients as part of their suffering. Got it. And a very quick follow-up, Georgian Guy. Do you have your dose now? And do you think that a phase three with the dose, or powering a phase three for durability, whether it's week eight or week 12,

Okay last quick question, then I'll hop back in the queue, referring to slide six and seven in terms of remit or.

Responders and remainder is it looks like week, nine or six and nine numerically or a little bit less in week 12, and I guess I'm wondering if you think that's an artifact of the remote.

Yeah.

Remote visits or if theres something else going on there with the drug it's hard to imagine what that might be but tell us about that and tell us how you would you.

Use those learnings and the future trial designs.

Well I think in general we feel that the data from six to nine six to 12 weeks.

Unknown Executive: or V12 would make sense for phase three from a reimbursement perspective.

Slightly more difficult to interpret because the there was additional treatment going on in the three treatment arms with some of the patients.

Unknown Executive: Yes, we think we definitively have our dose. And in speaking with payers and others, we have included, even in our phase-to-be trial, health economic-related measures, quality-of-life measures, and we'll be discussing all of this as we go into our phase three design with those who advise us on payer metrics, etc. We've been working with payers and health technology assessors here in Europe since 2016. So we're well aware of their requirements, and we expect to be able to address those in a well-powered study.

So that's a factor that we've had to consider and we were gonna have to analyze more closely. So I think we feel very confident about the statistical difference is up to six weeks.

That would encourage.

We see no treatment.

But we need to understand the whole data set we're gonna have to take into account. The fact that antidepressants were available for use in some cases, we used no three arms of the study.

I should also.

One other thing we need to look at this study was conducted through the very depths.

<unk>.

People being locked down it will be also looking at.

Are there any effects of when the lockdown whats occurring on patient populations et cetera, because that's quite an unusual events purely iPad mini mental health to call out for people. So.

Unknown Executive: But obviously, our Phase 3 program will have to be agreed and discussed, which we've been discussing already, with regulators on both sides of the Atlantic. And we'll look forward now to bringing these data to then agree that program and swiftly move into its execution. Great, thanks. I'll hop back in

We are going to be looking at that it's an unusual thing to have to consider that trial, but it's a very meaningful ones. So standby.

Okay. Thanks, George Thanks, guys. Thanks for the clarity and presenting the state a very nice.

Thank you Charles.

Youre welcome.

Thank you so much next question from Oscar.

unknown: Thank you. Thank you so much. Next question from Josh Schimmer from Avercore, ISI: your line is open.

Sir your line is open.

Hi, congratulations on data and really impressive I wanted to ask about.

unknown: Thanks so much for taking the question. How are you thinking about ways to preserve the effect beyond the first few weeks, either with the use of adjuvant therapies or patients?

Patients who had to discontinue anti depressants prior Q D.

The administration's passing 60.

Any additional details on these patients and perhaps.

Unknown Executive: for patient selection to optimize for a durable effect. Thank you.

Unknown Executive: Josh, I'll start the answer and hand off to Guy, but I think it's a really important question. When we started this whole program, our whole goal was to identify who responds and who doesn't, and who responds longer, and who needs additional support. To that end, we've actually recorded every therapy interaction, so we have machine learning out, looking at transcripts across the trial, the trial participants, really starting to understand the deeper level of patterns, including changes to patient narratives, and therapist actions that are then correlated with particular outcomes.

Regarding washout periods in response rates and better rates.

I've got a follow up.

Yes, well, we will all the patients were washed out for months depressed.

We will be giving further details as to how long it took.

And what the delays were between initiating that and the actual dosing day in due course, but you asked a very interesting question of course, there's a lot of interest in the effects of the discontinuation, but we think that there's continuing patients who were <unk>.

Tiny symptomatic treatment resistant proved to be relatively straightforward to generalized rather grossly, but nevertheless, generally successful unacceptable patients and as you can see many of them stayed off over the next 12 12 weeks as well.

Got it.

Unknown Executive: This is unprecedented data, and we'll be digging deep into that to look at how we can, in fact, optimize therapy and develop, as we've said from the beginning, a more precise and predictive model of care with psilocybin therapy. So we're looking deeply into these data. Keep in mind, we just received the data about 48 hours ago.

And just quickly can you remind us what biomarkers are looking at thank you.

We have polymorphism in the five Ht receptor that may be of interest to the drug action.

And we're also interested in an inflammatory biomarker, which.

Will be informative as well.

Okay, great. Thanks congratulations.

Thank you. Thank you.

Thank you so much.

Next question from Patrick Jones Your line is open.

Thanks, Good morning.

Unknown Executive: So there's a lot of work to do. We're just reporting top. Go ahead, you have anything else to have? I think I just underline that the way in which this study was designed is that the psychological support is essentially safety around the administration of the medication. So this is a test of the medication in isolation. It's pretty remarkable that we get these effects after a single dose after 12 weeks.

Congrats on that.

Hi, I have a follow up question on the suicidal behavior. So I'm just wondering what was the protocol definition in terms of.

How far out post.

The exploratory session could be considered attributable to the treatment is there a limit to that is that within the 12 weeks and is that something thats consistent across these studies or was this you need two phase <unk> trial for <unk> 16.

Unknown Executive: Clearly, if we are working with colleagues within the company to look at digital support mechanisms and monitoring, which may very well have to carry the promise that we can improve outcomes through that sort of approach, and we'd certainly be considering that in the future. I should also say that, you know, this is the data set that we developed in close collaboration with payers and regulators, again, on both sides of the Atlantic and in over 10 countries, to answer the fundamental questions.

I mean any time in the 12 12 weeks at any time in the 12 weeks that there was a suicidal.

Asian or behavior. It was recorded on the timing of course is recorded.

In terms of frequency. We will then complete please very low numbers Nike estimates very uncertain and they are comparable with in fact, the majority of your studies ever conducted and in depression.

Meta analysis, which suggested that the average rate.

Suicide events at various times.

About 3%.

Actively treated patients so we seem to be aligned more or less with that kind of rate.

Unknown Executive: And we couldn't do that unless we really looked at the dose finding and a single dose in its durability. Only then can we look at how we can identify patients who have different experiences and look at how to optimize that experience to maximize that experience to maximize the outcome and the duration. Thank you. What do you expect to have some of the additional? We'll be working on that hard and doing it as soon as possible. We don't have a date, but you know us; we're going to be more intense and bigger.

This is a group where you would expect to see.

Emergent suicidology.

At risk because.

Our history and so on.

Got it that's helpful. And then I'm just wondering if there was any any learnings from this study are some of the others that have read out recently in terms of the <unk>.

Usability of simultaneous treatment or therapy.

I'm also wondering if you think you would need a separate phase III trial to assess the feasibility of simultaneous.

Or could this potentially be.

Our treatment arm in the phase III program.

I don't think we're at a stage, where we can answer that question. We do we will have experience of administering 25 milligrams.

unknown: Thank you so much. Next question from Charles Duncan: your line is open.

The suicide gene therapy to patients who are still taking ssris and a small open label study, which which will report relatively soon.

unknown: Okay, super, thank you, George and team. Congratulations on a rigorously conducted trial. It's clearly a seminal event for the field. Thanks for taking the question. My first question is regarding next steps on sizing and timing, and I know you need to discuss this with the agency, but could you imagine being able to outline a protocol or even operationalize a next step, maybe a phase three, by roughly mid-22.

We then administrations.

We'll then be in a position to make an informed judgments about the rest of your question.

Yes.

And then just just one last one in.

In terms of the PTSD trial, if you can just discuss again there too any learnings you can take from the from the CRD phase III trials in other trials that prove that more or even the program with MDMA and how are you.

How should we kind of expect.

Element in the PTSD trial for progressive.

Well I'm not sure what the learnings that I think will relate to the therapy provision we have an enormous amount of data that we will be able to analyze that.

Unknown Executive: We can certainly imagine many things, and that's one we're focused on imagining, to use your term. We are very heavily recruiting sites and looking at preparing our phase 3 infrastructure to build on our really robust phase 2 infrastructure. That will work is all in the process, but again, we can't anticipate what the agency, the FDA, and the EMA and MHRA will say as we review these data. So we are ready to hit the go fast button as we do. do so whenever we get the word from the agencies. But we will be reviewing these very rapidly with them.

I think the path the interactions between the patient from the therapists in this study.

Every single administration in fact, all of the sessions with therapists with recorded and we have really sophisticated approaches ongoing to analyze the interactions and the key themes have come out and that's going to shape, how we deliver our treatment.

Program in the future.

With the specific lessons with PTSD.

Equipment and so on we will we're doing the study to find out about it.

Great. Thank you yeah can I just go on there.

I would just say that as we pursue areas of high unmet need in multiple indication areas. Our focus is to be a learning organization and continue to apply.

Unknown Executive: Okay, that's good, George. Second question is regarding any phenotypic factors. I understand that this is fresh data, so I probably haven't done the analysis, but is there anything that you're in particular interested in, such as prior lines or time since diagnosis that may have driven responses in terms of either the primary endpoint or durability, anything that you're particularly interested in looking at, or you've seen? Thank you.

Apply learnings in real time, so that we can actually progress all of our clinical studies and benefit patients as much as possible. So we are very much looking at building. These stair cases smaller studies into larger studies and drive learning.

Terrific. Thanks, so much.

Thank you.

Thank you next question from cement Kulkarni Your line is open.

Good morning, Thank you for taking my questions and for all the companies will conduct must be an exciting day for patients.

The induction protocol T I D.

Three questions I'll ask them individually first.

Based on what you know Novocure phase <unk> data in hand are there any specific variables that can instantly see in terms of needing adjustment for your upcoming phase two program.

Unknown Executive: Again, I will start that and then hand it off to Guy. I think a few things were really important to us. One was that this study actually used patients who were referred based on medical records, so we have a validated background, and that background information, or that background information will be used in future analyses, obviously. One of the things that was really important to us was to be able to demonstrate that these benefits could happen to people who had no prior experience, or 94% of our sample had no prior psilocybin experience, quite at odds with the prior studies And the majority of our therapists in all of our centers also have no prior psychedelic experience.

Scott do you want to start with that.

I don't think instantly, we see anything we need to adjust but obviously, we're reflecting on a whole series of issues that are raised particularly when we look at the secondary analyses.

Do you what is your reaction George that's mine.

It's mine as well again these are very very fresh results. We have the largest data set ever created in this area, we have incredible team statisticians and data scientists.

We're really looking at all of that and taking that into discussions with regulators and devising the path forward.

Got it my second question.

So again.

No no.

No I was just going to say that you. Appreciate the topline results are all driven by a very very strict and conservative analysis plan.

No.

We've got some sort of limitation on how far along.

Immediately reacted differently.

Understood.

Question, given your work with patients physicians payers and other components of the supply chain. So far what do you think would be the sweet spot for durability and company, 60% at the end of June.

Unknown Executive: This was so important for us to generalize to all of the population, which is approximately the same in our study, about 90 plus percent, who haven't had these experiences. So to be able to demonstrate that this works in that environment is really, really important for scalability and more importantly to help the most patients possible guide. Yeah, just to say that obviously, we're aware of existing data that suggest that one can, to a limited extent, predict treatment response from baseline measures, and we have those baseline measures.

Well I think that.

Everyone's dream is to actually look at how we can predict and prevent relapse.

And we're hard at work looking at new tools that might help with that and digital phenotyping.

But I think that people understand today.

Credibly difficult patient population to support and serve that was a single administration.

Monotherapy.

We see great promise that three weeks as well as 12 weeks considering the lives of these people. So we will be in lots of discussions and I think we'll come back to that question with more information not too distant future, we start finalizing our phase III plans.

Unknown Executive: And there is also, of course, emerging interest in biomarkers, and we'll be looking at the measures that we have in that category as well. But, as you rightly said at the beginning, we're not yet in a position to comment on that. We're just going to be very excited to follow up and look at those questions and answer them for you.

My last question is.

Should we expect to see any difference in response to company 60 based on the specific antidepressants are faced by patients in the past.

We have no idea of what to expect because it's an empirical question that unfortunately, we have data to be able to answer it.

unknown: Okay, last quick question, then I'll hop back in the queue, referring to slides six and seven in terms of remitters or responders and remitters. It looks like weeks nine or six and nine, numerically, are a little bit less than week 12.

Thank you.

Thank you. Thank you your next question from Bert Hazlett.

Your line is open.

Thank you and my congratulations on a well conducted study and an important one just one or two questions to try to better understand the patient characterization that study.

Do you could.

Could you would you be able to provide baseline madras rates for either the study as a whole.

unknown: And I guess I'm wondering if that's an artifact of the remote, you know, remote visit or if there's something else going on there with the drug. It's hard to imagine what that might be. But tell us about it and tell us how you would use those learnings in future trial design.

Or any of the particular groups.

Yeah Yeah.

Got it.

It's on it's on slide five if you wonder I forgive me.

It's written rather small and it's very easy to make.

All the data that's on slide five that you requested that okay. Thank you and then just with regard to geographical.

Guy Goodwin: Well, in general, we feel that the data from six to nine, six to 12 weeks becomes slightly more difficult to interpret because there is additional treatment going on in the three treatment arms with some of the patients. So that's a factor that we've had to consider, and we're going to have to analyze more closely. So I think we feel very confident about the statistical differences up to six weeks but that we're encouraged by the groups who received no treatment.

Uh huh.

Groups are there any notable similarities or differences within the particular patient groups either in North America or in the U S.

Excuse me Erin.

Yeah.

We will be looking at that with great interest.

But we have not yet.

I think just wondering.

Go ahead go ahead. Please. Please go I was just going to say whats really remarkable about this is we've trained therapists in seven languages 10 countries.

<unk> demonstrated this results across the board, it's going to be fascinating to look at all sorts of.

So in terms of demographic.

Demographics countries et cetera, but we were amazed and I think also amazed at the level of recruiting and engagement we have in the Netherlands.

Guy Goodwin: But we need to understand the whole data set; we're going to have to take into account the fact that antidepressants were available for use and, in some cases, were used in all three arms of the study. I should also add that there is one other thing we need to look at. This study was conducted during the very depths of the pandemic, with people being in lockdown. And we'll also be looking at whether there are any effects of when the lockdown was occurring on patient populations, et cetera, because that's quite an unusual event.

From our sites.

And so I think that was also a very interesting characteristics given the availability of.

Other substances.

There. So this is clearly a high unmet need.

The high level of interest in the trial.

And then just thank you for that and just one more from me with regard to the serious treatment emergent adverse events.

Do you have any more information at all with regard to the time course of those events.

Guy Goodwin: Apparently, it had many mental health problems to qualify for people. So we are going to be looking at that. It's an unusual thing to have to consider in a trial, but it's a very, meaningful one. So stand by. Okay, thanks, George.

Just a general characterization, where they closer to the administration and and maybe waned further on or just again any any anecdotal characterization you might be able to make with regard to those.

unknown: Okay, thanks, George. Thanks, Guy. Thanks for the clarity in presenting this data. Very nice.

If it wasn't simple every patient that tends to have their own complexity as you probably appreciate the suicidal behavior all occurred at least a month.

unknown: Thank you so much. Next question from Esther. Esther Hong, your line is open. Hi, congratulations on the data, really impressive. Wanted to ask about patients who had to discontinue antidepressants prior to the administration of Comp 360. Any additional details on

The administration.

So we can we can certainly say that from this data.

Some of the.

Some of the ideation.

Close a couple of cases.

But I think I would emphasize again that we will get much finer grain.

So when we look at the ratings of suicide download we will have in the secondary analysis. Then we'll certainly let you have that information as soon as we have it.

unknown: patients and perhaps regarding washout periods and response rates and remitter rates.

Thank you very much for that and congratulations again.

Guy Goodwin: and remitters, and then I've got to follow up.

Thank you next question from Brian Russo from open Helmer Your line is open.

Guy Goodwin: Yeah, well, we will, all the patients were washed out of antidepressants, and we will be giving further details as to how long it took and what the delays were between initiating that and the actual dosing day in due course. But you ask a very interesting question; of course, there's a lot of interest in the effect of discontinuation. But we think that discontinuing treatment in patients who were highly symptomatic and treatment resistant proved to be relatively straightforward to generalize rather grossly but nevertheless generally successful and acceptable to patients. And as you can see, many of them stayed off for the next 12, 12 weeks as well.

Alright, thanks for taking the question.

Just wanted to ask in terms of the placebo effect was that based on literature and your expectation is mostly in line.

Based on the potential negative placebo effect here in the Triple Blind that you mentioned.

Well we.

We had nothing really to to go on so it has not.

I mean, there has been other studies, but that usually been crossover study.

So we have to really think through from the from the stock when we designed the study.

All of the patients were obviously.

For pad in such a way that they their expectation was that they would have a psychedelic experience and so on.

Our assumption was that there would be an appreciable nocebo effect.

Guy Goodwin: And then, just quickly, can you remind us what biomarkers you're looking at? Thank you.

In the group, who got one milligram.

But at the same time, we also knew that they were getting the wrap around and psychological support.

Guy Goodwin: We have a polymorphism in the 5HT2A receptor that may be of interest to the drug action, and we're also interested in an inflammatory biomarker that will be informative as well.

Extremely positive and could be regarded as placebo.

So we did with the reason we do experiment to find out what happened then.

This is what happened and we will we will try and interpret this as best we can.

Thank you.

unknown: Great, thanks. Congratulations. Thank you.

Yeah.

Thank you so much.

Question from Oliver <unk> P. Ross your line is open.

unknown: Thank you. Thank you.

unknown: Next question from Patrick Trujillo: the line is open.

Yes, good morning.

Hi, Good morning, George how are you.

Good to hear from you.

Guy Goodwin: Thanks, good morning, and congrats on the data. I have a follow-up question on the suicidal behaviors. I'm just wondering what the protocol definition is in terms of how far out post the exploratory session could this be considered attributable to the treatment? Is there a limit to that, or is it within the 12 weeks?

You know Jordan both usage of.

That you think you have to divide them.

The 25 milligram dose.

Do you would you exclude maybe repeat dosing with in the clinical trial.

Right now what we're doing is.

Trying to understand is we said each patient's experience.

I think that that will help inform thoughts along that line, but I think what we really needed to do with this trial is to actually establish the level of understanding of durability up to three months of a single dose.

Guy Goodwin: And is that something that's consistent across CRD studies, or was this unique to phase 2 B trial for Com 360? At any time in the 12 weeks, at any time in the 12 weeks that there was suicidal ideational behavior, it was recorded, and the timing, of course, is recorded. In terms of frequency, although these very low numbers make the estimate very uncertain, they are comparable with, in fact, the majority of studies ever conducted on depression.

That will help inform a tremendous amount of analytics moving forward and then I think we'll step back and look at what's required I do know that we think if we have in the 20 <unk> century, the ability to predict relapse to preempt yet that's really it.

The goal for us and so we're hard at work looking at those kinds of things we're growing anything around at this point, obviously lots to do and lots to discuss with regulators.

Guy Goodwin: There's a recent meth analysis that suggested that the average rate of suicidal events at various times was about 3% in actively treated patients. So we seem to be aligned more or less with that kind of race.

Yes, and the last question is how many.

Concessions are integrating.

This protocol George.

There were two.

And do you think that that number it efficient.

Again, we have an amazing team working on all the transcripts all the interactions and create either empirical response to that question. So.

Guy Goodwin: And, of course, this is a group where you would expect to see emergent suicidality as a risk because of their history and so on. That's helpful. And then I'm just wondering if there were any learnings that emerged from the study or some of the others that have come out recently in terms of the feasibility of simultaneous treatment or therapy. I'm also wondering if you think you would need a separate phase-through trial to assess the feasibility of simultaneous therapy, or could this potentially be a separate treatment arm in the phase-3 program? I don't think we're at a stage where we can answer that question yet.

I think that one of the things that's really important is that when.

When you look at a very fine grained precision approach to this patient by patient so that we can really develop.

For everyone and anyone and I think this is really where we're headed.

So.

Again be doing all of those analyses.

Sharing what we learned and inform your future plans.

Thank you so much Georgia and congratulations.

Thank you.

Thank you so much.

Next question from Nina that can meet all your line is open.

Hey, guys. Thanks for taking my question.

So I just wanted to ask about the youth.

Rescue meds.

The follow up period, I guess can you talk a little bit more about when patients were allowed to start taking rescue meds and then anything you can share at this point on the actual rate of use of rescue medicine, the different arms that'd be great. Thank you.

Guy Goodwin: We will have experience of administering 25 milligrams of psilocybin therapy to patients who are still taking SSRIs in a small open-label study, which will report relatively soon. We'll then be in a position to make an informed judgment about the rest of your question. Yes, that makes sense.

Sure I, just think that Guy would you talk you should probably be clarifications to start with a clarification of rescue versus other medications.

Yeah, so our.

Our understanding of rescue would be the use of medications on the day of the study the value of the dosing.

And as.

If my memory serves I think there was only a single example, where that was necessary.

Unknown Executive: And then just one last one if I made, just in terms of the PTSD trials, you can just discuss that again too. Any learnings you could take from the TRD phase 2B trial of the other trials to that program or even a program with MDMA and how, you know, how should we kind of expect the case of enrollment in the PTSD trial to progress? Well, I'm not sure, but the learnings will, I think, relate to therapy provision.

That means that we were successful at delivering the actual dosing day without having to rescue patients from the experience. So we think that the therapist did a great job.

The other sense in which the rescue medications is that these patients had been withdrawn from anti depressants. So we had to expect in advance that they would be a pressure for them to go back on to antidepressants.

They showed no response, so a limited response to treatment.

And that would apply in all three arms of the study of course.

However, we did encourage the clinicians entering the trial to give the treatments of trial up to three weeks as far as they could and then after that they were free to use medication. If they felt it was clinically indicated.

Unknown Executive: We have an enormous amount of data that we will be able to analyze that can take apart the interactions between the patients and the therapists in this study. In fact, all of the sessions with the therapists were recorded, and we have really sophisticated approaches ongoing to analyze the interactions, and the key themes have come out. And that's going to shape how we deliver our treatment program in the future. With the specific lessons for PTSD and recruitment and so on, we will, we're doing the study to find out about, Great.

So we've got a picture that we've not yet fully annualized.

A number of the patients returning to antidepressant treatment.

And when we fully understand the patents.

We will publish them.

I don't know, whether you understand more about that but.

No I think thats sufficient.

Thank you.

Thank you so much.

Your next question from Michael how can there rich.

Okay.

Hey, guys. Thanks for taking the question.

Unknown Executive: Thank you. I just want to say that, you know, as we pursue areas of need in multiple indication areas, our focus is to be a learning organization and continue to apply learnings in real time so that we can actually progress all of our clinical studies and benefits as much as possible. So we are very much looking at building these staircases, smaller studies into larger studies, and driving learning.

So I wanted to.

Ask if you could put the data in a bit of context, because it seems like the magnitude of the result is not as high as previous studies could this be somewhat owing to the.

This is a single dose protocol and considering that the patients and the clinicians were psychedelic naive.

Be viewed as a more conservative study to establish that.

Baseline for comp 360, which could be improved in a more optimized setting.

unknown: Thank you. Next question from Cement. Goal Carney, your line is open. Good morning, thank you for digging up a question.

Yeah.

I think that's a really really hard question to answer.

So first of all I think that.

unknown: Good morning, thank you for taking my questions and for all the companies' work on what must be an exciting day for patients who might see another treatment option for TRD. I have three questions, and I'll ask them individually. First, based on what you now know with your phase 2B data in hand, are there any specific variables that you instantly see in terms of needing adjustment for your upcoming phase 3 program?

We simply.

Did this study to address all of the regulatory and payer concerns about whether this was actually a generalizable model or not and I think we can feel confident in saying. This is a generalizable model and in fact may be optimized and various ways that we're investigating.

But I do think that what really distinguishes. This study is a multicenter. It was not it was done by <unk>.

With a great deal of clinical and scientific Equipoise, which you know is something we could do at this scale of it is very difficult to do at a single site study environments.

Guy Goodwin: God, do you want to start with that? I don't think we need to adjust anything immediately, but obviously, we're reflecting on a whole series of issues that are raised, particularly when we look at the secondary analysis. What is your reaction, George? That's mine. Yeah, it's mine as well.

And we use this triple blinded model, where we had an independent rater, calling each patient in their native language.

Completely blinded to the study. So this was the bit that said, we can really count on these results just because of the independent assessment using the gold standard matrix. So we think that this is a great place to start program that we're interested in optimizing.

Unknown Executive: Again, these are very, very fresh results. We have the largest data set ever created in this area. We have an incredible team of statisticians and data scientists, and we're really looking at all of that and taking that into discussions with regulators and devising the path forward.

Alright. Thank you and then I wanted to ask about how clinically meaningful the absolute reductions in Madras and matters score which were.

Around I think minus.

All of that week, three and that stays around minus 10 at week 12, and how does that compare to ssris.

unknown: Got it. My second question is:

unknown: No, it's fine. No, I was just going to say that, you know, the top line results are all driven by a very, very strict and conservative analysis plan. So, you know, that's a sort of limitation on how far one can immediately react to differences.

Guy, which I can take that.

Yeah well.

I mean, I think I think just what.

What do you make it the average change in the population is obviously very much to do with how you interpret clinical trials. The experience of individual patients is something that I suppose more concerns me and so I think when you look at this data and see the highlights of remit those up to 12 weeks, that's something that I take away, particularly clinically significant.

unknown: Okay. So second question, given your work with patients, physicians, pairs, and other components of the supply chain so far, what do you think would be the sweet spot for durability and Com 360 therapy in the real world?

The comparison between different Delta.

<unk> called is quite interesting, but its difficult when the trial is quite.

Hi, Duane.

We show that our effects sustained from day to day.

Unknown Executive: Well, I think that, you know, everyone's dream is to actually look at how we can predict and prevent relapse. And we're hard at work, looking at new tools that might help with that in digital phenotyping. But I think that people understand today that this is an incredibly difficult patient population to support and serve. And with a single administration, monotherapy, we see great promise for three weeks as well as 12 weeks, considering the lives of these people. So, you know, we'll be having lots of discussions, and I think we'll come back to that question with more information in the not too distant future as we start finalizing our PACE 3 plans.

The effects of Ssris Athene, usually by day five week six so in a sense. They only look at the interval over which with showing statistically significant results and you can probably see that just eyeballing. The dates are on slide five the difference between 25 milligrams and one milligram.

At that point, it's still around five or something.

On the mattress side looks sick and the usual reported six weeks an SSRI trials on average is somewhere between two and three.

I think in terms of comparison as far as I am prepared to make them.

That would be the comparison I would make but of course, we're looking at a T. I D population.

There are various caveat surround around that population not responding at all to ssris.

unknown: And my last question is, should we expect to see any difference in response to Com 360 based on the specific antidepressants used or failed by patients in the past? We have no idea.

By definition to fail to respond to ssris or <unk>.

It's a little it got slightly academic after a while that sort of comparison.

Okay.

Alright. Thank you and then just one more quick one.

unknown: We have no idea what to expect because it's an empirical question, and fortunately, we have data to be able to answer it.

I'll jump in the queue.

So the suicide already considering that that was largely a month after COVID-19 related to our sense of hopelessness in patients.

unknown: Thank you. Let's continue with your next question from Berg Haslett. Your line is open.

Nothing worked for them, so far and now they've tried salad dive in.

unknown: Thank you, and my congratulations on a well-conducted study and an important one. Just one or two questions to try to better understand the patient characterization in the study. Would you be able to provide baseline madras rates for either the study as a whole or any of the particular groups? Yeah, I think it's a super-bang.

They didn't respond to that either.

Well I think thats, a consideration we will certainly be taking into a deep dive into the data in the future to an interesting possibility.

Yeah.

Yeah, and I think you'll have to do.

We will have to look also at.

<unk>.

The level of expectation that.

As set in the General press.

Guy Goodwin: Yeah, it's on slide five, if you're wondering. Oh, forgive me. It's written rather small.

No.

This is something really important to take responsibility for that.

Okay.

Guy Goodwin: It's very easy to miss, but it's in all the data that is on slide five that you requested. Okay, thank you. And then, just with regard to geographical groups, are there any notable similarities or differences within the particular patient groups, either in North America or in the U.S. Or excuse me, Erin. We'll be looking at that with great interest, but we haven't done that yet.

There are no kind of see as the study indicates about.

Yeah.

Any other questions.

Thank you so much no further question at this time Steve.

Sure, Let me hand, it back to George for closing remarks, please George.

I just wanted to thank everyone for their interest and participation and support.

This is something that is going to be at the start.

Unknown Executive: I think what's really important, Go ahead. Go ahead. Please, please go ahead.

Really developing what we view as a.

Way to transform the patient experience and mental health work on it and we're working at how we can help reduce suffering at scale and appreciate all of your interest and support thank you very much.

Unknown Executive: I'm just going to say what's really remarkable about this is that we've trained therapists in seven, 10 countries and demonstrated these results across the board. It's going to be fascinating to look at all sorts of cuts in terms of demographics, countries, etc. But we were amazed and, I think, also amazed at the level of recruiting and engagement we had in the Netherlands from our sites. And so I think that was also a very interesting characteristic given the availability of other substances. That's there. So this is clearly a high unmet need and a high level of interest in the trial. And then just thank you for that, and just one more for me.

That does conclude our conference for today. Thank you for participating you may all disconnect.

[music].

Yes.

Okay.

Yes.

[music].

Unknown Executive: With regard to the serious treatment-emergent adverse events, do you have any more information at all with regard to the time course of those events, just in general characterization, were they closer to the administration and maybe waned further on? Or just, again, any anecdotal characterization you might be able to make with regard to those? It wasn't simple.

Guy Goodwin: Every patient tends to have their own complexity, as you probably appreciate. The suicidal behaviors all occurred at least a month after the drug administration. And so we can certainly say that from this data. Some of the ideation occurred closer to home, in a couple of cases. But I think I would emphasize, again, that we will get much finer-grained data when we look at the ratings of suicidality that we will have in the secondary analysis, and we'll certainly let you have that information as soon as we have it. Thank you very much for that, and congratulations again.

unknown: Thank you. Next question from Frank Cilbrispo from Openheimer: your line is open.

unknown: Hi, thanks for taking the question. Just wanted to ask, in terms of the placebo effect, was that based on literature and your expectations, mostly in line, just based on the potential negative placebo effect here and the triple blind that you mentioned? Well, you know, we really had nothing to go on.

Guy Goodwin: There had not been, there had been other studies, but they'd usually been crossover studies. So we had to really think this through from the start when we designed the study. All of the patients were obviously prepared in such a way that their expectation was that they would have a psychedelic experience. And so our assumption was that there would be an appreciable nocebo effect in the group who got one milligram. But at the same time, we also knew that they were getting wraparound psychological support that's, you know, extremely positive and could be regarded as placebo. So we did, the reason we do experiments is to find out what happened, and you know, this is what happened, and we will try and interpret this as best we can.

[music].

unknown: Thank you so much. Next question from Almer Priya P. Ross: your line is open.

unknown: Yes, good morning, Guy, good morning, George, how are you? Hi, good to hear from you. Yes, George, you mentioned that you think you have the right bill.

Unknown Executive: The 25 milligram dose. Would you, maybe, exclude repeat dosing within the clinical trial?

Unknown Executive: Right now, what we're doing is trying to understand, as we said, each patient's experience. And I think that that will help inform thoughts along that line. But I think what we really needed to do with this trial was to actually establish a level of understanding of durability up to three months of a single dose.

Unknown Executive: That will help inform a tremendous amount of analysis moving forward. And then, I think we'll step back and look at what's required. And I do know that I think if we have in the 21st century the ability to predict relapse and to preempt it, that's really the goal for us, and so we're hard at work looking at those kinds of things, not rolling anything in around at this point. Obviously, lots to do and lots to discuss with great Yes, and the last question is, how many sessions?

Unknown Executive: Sessions of integration where there is a protocol, George. There were two.

Unknown Executive: And do you think that that number is efficient? Again, we have an amazing team working on all the transcripts, all the interactions, and creating an empirical response to that question. So I think that one of the things that's really important is that we look at a very fine-grained precision approach to this, patient by patient, so that we can really develop a plan for everyone and anyone. And I think this is really where we're headed. So we're going to again be doing all those analyses and sharing what we learn and your future plan. Thank you so much, George, and congratulations.

unknown: Next question from Nina, the three-ed-oh, your line is open. Hey guys, thanks for taking my question. So I just wanted to ask about the use of rescue meds just in the follow-up period. I guess you could talk a little bit more about when patients were allowed to start taking rescue meds, and then anything you can share at this point about the actual rates of use of rescue meds and the different arms. That would be great.

Guy Goodwin: Sure, I just think that Guy, when you talk, you should probably make a clarification, or start with the clarification of rescue versus other medications. Yeah, so our understanding of rescue would be the use of medications on the day of the study, the day of the dosing. And as my memory serves, I think there was only a single example where that was necessary.

Guy Goodwin: So, you know, that means that we were successful at delivering the actual dosing day without having to rescue patients from the experience. And we think that the therapist did a great job. The other sense in which there are rescue medications is that these patients had been withdrawn from antidepressants. So we had to accept in advance that there would be pressure for them to go back on endodepressants if they showed no response or limited response to our treatment.

Guy Goodwin: And that would apply in all three arms of the study, of course. However, we did encourage the clinicians entering the trial to give the treatments a fair trial for up to three weeks as far as they could. And then after that, they were free to use medication if they felt it was clinically indicated. So we've got a picture that we've not yet fully analyzed of a number of patients returning to antidepressant treatment. And when we fully understand the patterns, we'll publish them.

[music].

unknown: I don't know whether you want to say any more about that, George. No, I think that's sufficient. Thank you so much. For your next question from Michael Okunewitch, your line is open.

unknown: Hey guys, thanks for taking the question. Sure. So I wanted to

unknown: I ask if you could put the data in a bit of context because it seems like the magnitude of the result is not as high as previous studies. Could this be somewhat owing to the fact that this is a single dose protocol, and consider

unknown: And considering that

Unknown Executive: I think that's a really, really hard question to answer. So, first of all, I think that we simply did this study to address all of the regulatory and payer concerns about whether this was actually a generalizable model or not. And I think we can feel confident in saying that this is a generalizable model. And, in fact, they could be optimized in various ways that we're investigating.

unknown: But I do think of what really distinguished this study is that it was multi-center. It was done by, with a great deal of clinical and scientific equipment, which, you know, is something we could do at this scale that's very difficult to do in single site study environments. And we used this triple-blinded model where we had an independent raider calling each patient in their native language completely blinded to the study. So this was the bit that said we could really count on these results just because of the independent assessment using the gold standard mattress. So we think that this is a great place to start from, and you bet we're interested in optimizing. All right, thank you. And then I wanted to ask about how clinically meaningful it is.

Guy Goodwin: meaningful, the absolute reductions in the Madras score, which were around, I think, minus 12 at week three, and that stays around minus 10 at week 12. And how does that compare to FSRIs?

Guy Goodwin: Guy, I would like to take that. Yeah, well, I think just what you make of the average change in the population is obviously very much to do with how you interpret clinical trials. The experience of individual patients is something that, I suppose, more concerns me. And so I think when you look at this data and see the highlights of remissors after 12 weeks, that's something that I take away as particularly clinically significant. The comparison between different deltas, as they're sometimes called, is quite interesting, but it's difficult when the trial. months device is not quite the same way.

Guy Goodwin: And you'll appreciate that our effects are seen from day two. The effects with SSRIs are usually seen by day or by week six. So in a sense, they only look at the interval over which we're showing statistically significant results. And you can probably see, just by eyeballing the data on slide five, that the difference between 25 milligrams and one milligram at that point is still around five. Or something on the madras, five or six.

Guy Goodwin: And the usual report is six weeks in an FSRI trial, on average, is somewhere between two and three. So I think in terms of comparison, as far as I'm prepared to make them, that would be the comparison I would make. But of course, we're looking at a TRD population. There are various caveats around that population, not responding at all to SSRIs, that by definition have failed to respond to FSRIs. So, you know, this gets a little, it gets slightly academic after a while, those sorts of comparisons.

unknown: All right, thank you. And then just one more quick one, and I'll jump in the queue.

unknown: For the suicidality, considering that that was largely a month after, could that be related to

unknown: a sense of hopelessness and patience that nothing had worked for them so far, and now they'd tried Salas Dibin, and they didn't respond to that either.

[music].

Guy Goodwin: Well, I think that's a consideration we'll certainly be taking into our, you know, deep dive into the data in the future. It's an interesting possibility, we breathe. Yeah, and I think that we can help. We will also have to look at the level of expectation that is set in the general press. This is something really important to take responsibility for. Thank you.

unknown: There are no panaceous in this study, as indicated.

unknown: Thank you so much. There are no further questions at this time, Steve.

Operator: Sure, let me hand it back to George for his closing remarks. George. I just want to thank everyone for their interest, participation, and support. This is something that is going to be the start of really developing what we view as a way to transform the patient experience in mental health. We're on it, we're working on how we can help reduce suffering at scale, and appreciate all of your interest and support. Thank you very much. That does include our conference for today.

Unknown Executive: That does include our conference for today. Thank you for participating. You may all disconnect.

Operator: I don't know. and Thank you. Thank you. Thank you Thee and and and Thank you, Thank you, and so on the Thank you.

Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you.