COMPASS Pathways Plc

Good day, ladies and gentlemen, and welcome to the Compass Pathways conference call. At this time, all participants are in a listen-only mode. As a reminder, this call is being recorded. I would now like to introduce your host for today's conference, Stephen Schultz. You may begin.

Welcome, all of you, and thank you for joining us today for our fourth quarter and year-end 2022 results conference call. Again, my name is Steve Schultz. I'm the Senior Vice President of Investor Relations at Compass Pathways. And today I'm joined by Kabir Nath, our Chief Executive Officer, and Mike Falvey, our Chief Financial Officer. Dr. Guy Goodwin, our Chief Medical Officer, is unable to join us today, so Kabir will be covering clinical development. The call is being recorded and will be available on the Compass Pathways Investor Relations website shortly after the conclusion of the call. 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 10-K filed with the U.S. Securities and Exchange Commission 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 statement, even if our estimates or assumptions change. I will now hand the call over to Kabir Nath.

Thank you, Steve. Good day, everyone, and thank you for joining us. We have quite a bit to share with you as we continue to make strong progress across all aspects of our business. During this past quarter, we started our Comp360 Phase III Pivotal Program in Treatment-Resistant Depression, or TRD, a unique achievement, the first ever Phase III trial of psilocybin. As you know, this is a field that holds the potential for significant advances in the treatment of mental health conditions, and we're thrilled to be at the forefront of this potential paradigm shift. Today, we're announcing an important update to the Phase III program we described last fall, starting with our COMP005 trial. As a reminder, this is the single-dose monotherapy trial comparing a 25 milligram dose of COMP360 to a true placebo. We've completed further analysis of our Phase IIb data. with specific focus on the participants in the one milligram arm who had a minimal psychedelic experience, as well as analysis of a recent data from a placebo-controlled study at the University of Zurich using Comp360 in major depressive disorder, or MDD. This data-driven analysis has led to a re-estimation of the sample size for the Comp005 trial and a revision to a lower expected response to true placebo. This allows us to reduce the number of patients required in the 005 trial to 255 from the original 378, while maintaining the power to achieve our objectives. With the reduction in the number of patients, we now expect to complete the pivotal component of this trial, the six-week primary endpoint, by summer 2024. rather than the end of 2024, as we'd previously guided. Additionally, we finalized the plans for long-term follow-up for the Phase III program. Building off the lessons from Comp 004, the long-term follow-up to our Phase IIb study, our strategy is to integrate the follow-up into the two pivotal trials, which we believe will enable a more streamlined design reduced selection bias, and the implementation burden on our patients and clinicians. Again, to remind you, the two pivotal trials are COMP005, which I described just now, and COMP006, a fixed repeat-dose monotherapy trial with three arms. comparing Comp360 doses of 25 milligrams, 10 milligrams, and one milligram, where patients will receive the same dose at day one and at week three. In both trials, we will follow patients up to 52 weeks, building on the six-week pivotal analysis of each trial, which we're calling Part A. The design follows the same principles for each trial. Part B of each trial will follow from the primary endpoint assessment at 6 weeks to 26 weeks. Patients who meet criteria for re-treatment in Part B will have the option to receive a further treatment according to their original allocation in both studies, thus preserving the randomized comparison between arms to 26 weeks. will run from 26 weeks to 52 weeks as an open label component of the trial. Importantly, all patients who meet criteria for re-treatment in Part C will have the option to receive a single 25 milligram dose of Comp360 open label. This option is expected to support patient engagement throughout the entire duration of the trials. It's important to emphasize that there's no change to the primary endpoint of either trial, which is change in mattress from baseline at six weeks, nor to our intention to announce the top line results from the primary endpoint of each trial at that time. We're confident that this trial design will provide insights to key questions on durability of effect and the value of re-treatments. Moreover, TRD often behaves like a chronic condition. By following patients with continuing randomization for 26 weeks, much longer than is conventional in other major depressive disorder trials, we have the potential to generate unique durability and retreatment data which could enhance the value of Comp360. We believe that these amendments will help to generate further evidence that enhances our phase three program and the potential benefit to patients, clinicians, regulators, and payers. We've submitted these protocol amendments to the FDA who have indicated they will come back to us by March the 20th on 005 if they have any further comments following their earlier feedback on durability and retreatment design principles. I remind you that this phase three program is already underway and that it's routine to have an ongoing dialogue with the FDA as we conduct the trials, especially with our breakthrough therapy designation. If we do receive further comments, we will of course consider that feedback. Let me now turn to the broader body of evidence we're developing for Comp360. The phase two PTSD program is progressing with Comp360 dosing of enrolled patients. In December, Data from an exploratory open-label investigator-led initiative in bipolar depression type 2 were presented by the investigator at the annual meeting of the American College of Neuropsychopharmacology. This study investigated the safety and efficacy of a single 25 milligram dose of Comp360 psilocybin therapy in 14 patients. The result showed positive early signals of efficacy with 12 of the 14 patients meeting response and remission criteria for the mattress scale at 12 weeks after Comp360 psilocybin therapy. Notably, no subject had manic or hypomanic symptoms or an increase in suicidal ideation. We believe that these are remarkable data and provide further evidence to support the potential of Comp360 psilocybin therapy for difficult to treat depression. I remind you, though, that this was a small study, and these findings now need to be validated in larger studies. Also, in December, the Zurich study in MDD, which I referenced earlier, was published. This randomized, blinded study enrolled 52 patients, comparing a weight-based variable dose of COMP360 to true placebo. and demonstrated compelling efficacy results with no new safety signal. We see this as further evidence of the potential for Comp360 to help patients living with serious mental illness. Turning to anorexia nervosa, this remains an area of critical unmet need with no FDA-approved pharmaceutical product at the highest mortality rate of any serious mental illness. We're committed to pioneering a robust phase two trial to build on the evidence already generated in investigator-initiated studies. I remind you that there is no significant body of experience available for this indication, so we are on a steep learning curve. We've learned that we need to make amendments to our protocol to better meet the needs of this highly vulnerable patient population. As a result, it's unlikely that we will see top-line data in 2023. Please note that this is a very different patient population from TRD patients, treated largely by different physicians at specialized centers, and that the need to amend this protocol has no impact on our Phase III TRD program. Let me reiterate that we believe the last quarter of 2022 was a quarter of strong progress, capping a year of extraordinary progress for Compass Pathways. Our phase three study, the largest, most robust ever study in psilocybin, is underway. And we're excited to continue the journey to bring Comp360 psilocybin therapy with psychological support to patients. subject to study results and regulatory approval. I'll now hand the call to Mike for the financial overview.