COMPASS Pathways Plc

Thank you for standing by. My name is Luella, and I will be your conference operator today. At this time, I would like to welcome everyone to the Compass Pathways third quarter 2024 investor call. All lines have been placed on mute to prevent any background noise. After the speaker's remarks, there will be a question and answer session. If you would like to ask a question during this time, simply press star. followed by the number 1 on your telephone keypad. If you would like to withdraw your question, press star 1 again. Thank you. I would now like to turn the call over to Steve Schultz, Senior Vice President of Investor Relations. Please go ahead.

Welcome all of you and thank you for joining us today for our third quarter 2024 results conference call. Again, my name is Steve Schultz, Senior Vice President of Investor Relations at Compass Pathways. And today I'm joined by Kabir Nath, our Chief Executive Officer, Laurie Engelbert, our Chief Commercial Officer, and Terry Luxem, our Chief Financial Officer, who will be giving prepared remarks, as well as Dr. Guy Goodwin, our Chief Medical Officer, and Dr. Michael Gold, our Chief R&D Officer, who will join us for Q&A. The call is being recorded and will be available on the Compass Pathways Investor Relations website shortly after the conclusion of the call and will be available for a period of 30 days. 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 most recent quarterly report on Form 10Q, 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 as of any subsequent date. We specifically disclaim any obligation to update or revise any forward-looking statement, even if our estimates or assumptions change. I'll now hand the call over to Kabir Nath.

Thank you, Steve. Good day, everyone, and thank you for joining us. Let me begin by welcoming Laurie to her first quarterly call with Compass. As I said on our August call, we're pleased to have such an exceptional leader join the company and round out our executive team. Laurie brings deep strategic and commercial experience, having most recently launched Orvelity at Axome. That experience will be valuable as we prepare for the commercialization of Comp360, and we're thrilled that she has joined us. In a moment, I'll ask Laurie to update you on the commercial landscape and our commercial preparation, which we know are areas of major interest and focus for our investors. And as usual, Terry will provide you with a financial update. First, though, I want to address questions around the anticipated disclosure of our pivotal Comp 360 trials. On our August earnings call, we pushed the anticipated six-week disclosure date for the Comp 005 trial back to the end of this year or early next year. Based on our recruitment to date, it now looks unlikely that we will be able to disclose the six-week data in the first quarter, and we're therefore updating our guidance for the six-week 005 data to the second quarter of 2025 to give us more assurance. Our top priority is is completing our phase three trials, and we're doing everything we can to ensure that sites recruit as quickly as possible while maintaining the integrity and quality of the trial. Mike Gold, who came on board in May, has significant drug development experience in neuroscience and is spending much of his time on the ground with the sites, which has given us new insights into some of the challenges and helped us to refine our plans. We're the first company to conduct such large psychedelic trials. And we did not have the benefit of prior comparable phase three timelines to base our assumptions on. Our phase three enrollment projections were based on the phase two B enrollment curve. And while we did factor in some new aspects of the phase three trials into our projections, there've been a number of items related to the complexity of the trials that we're now learning along the way. The Phase 2b was a simpler protocol, with all active arms, a single dose, and blinded for just 12 weeks. Comp005, on the other hand, is a 52-week trial, blinded for the first 26 weeks, and has multiple parts where additional doses can be given, which significantly increases the logistical complexity for sites to schedule patients and therapists, as well as for patients themselves. These complexities are specific to the clinical trial setting, but have resulted in inexperienced sites carefully managing patient flow as they become more proficient. Mike and his team are paying close attention to the needs of each site and are providing the necessary resources to support them on a case-by-case basis. This hands-on approach is working, and we'll be continuing to dedicate all our focus to successfully completing these trials. There continues to be significant demand from patients at the top of the funnel, and it's a matter of blocking and tackling and helping sites get patients through the process as quickly as possible. Beyond timing for the trial, we're also frequently asked what data we will be disclosing with the 005 six-week data readout. Please remember that while the primary endpoint is at six weeks, the trial remains ongoing and blinded through 26 weeks. Therefore, we're going to be limited in what we can release at six weeks so that we maintain the integrity of blinding as much as possible. We will disclose three key efficacy measures for the six-week endpoint. The madras effect difference between the arms, p-value, and confidence intervals. We believe that these data should provide investors with a clear understanding of the treatment effect, and if positive, provide an important validation of the positive phase 2b treatment result. From a safety standpoint, we'll provide a high-level assessment from the independent DSMB, which looks at unblinded data on a regular basis to monitor safety risks for patients in the trial. Suicidality is an inherent feature of TRD, and suicidal ideation is expected in this population. As part of the DSMB assessment at the time of the data readout, they will also comment on whether they're seeing any imbalance in suicidal ideation. At this six-week endpoint, we will not be able to provide secondary endpoints or in-depth safety tables as that would require further unblinding. Let me now turn to the COMP006 trial, which is our second Phase III trial. As a reminder, 006 has three active dose arms of 1 mg, 10 mg, and 25 mg, with the same three-part structure as 005, with the primary endpoint at the end of Part A at 6 weeks, a fully blinded Part B through 26 weeks, and an open-label Part C through 52 weeks. In the 006 trial, each participant gets two doses of Comp360 three weeks apart at the start of the trial. The recent Lycos Adcom and the fact that they received a complete response letter provided key insights into the FDA's thinking and some of the challenges faced by this new class of drugs. While most of the FDA and Adcom concerns were specific to Lycos and their MDMA-assisted therapy program, there was a high degree of scrutiny regarding unblinding, which is very relevant to our studies. While both the 005 and 006 trials are blinded to 26 weeks, the 006 trial, with its three active arms, is designed to minimize the risk of unblinding as participants know they will receive a dose of COM360. With a 15% cap on recruitment of patients with prior psychedelic drug experience, it will be difficult for the overwhelmingly psychedelic-naive participants to determine which dose they received, particularly between the 10 and 25 milligram doses, which is what we saw with the overlapping responses between 10 and 25 milligrams in our Phase IIb trial. We believe that this is an effective strategy to maintain blinding, and given the importance of the 006 trial for COMPASS to gain valuable regulatory and commercial insights around redosing and durability, we want to ensure that we preserve that through the blinded portion of the trial. We've therefore made the very difficult decision to further protect the blinding of the 006 trial and only release data after the 26-week time point has been reached for all patients. While recruitment for 006 has been going well so far at the sites that are up and running, We're still working through some site initiations in Europe, some of which have taken longer than projected. And we're also relying on a number of the U.S. sites from 005 to rollover to 006. Therefore, taking into consideration the shift of disclosure to the 26-week time point for 006, as well as potential unpredictability in recruitment, we now expect to disclose data for 006 in the second half of 2026. While we have a better understanding of the variables impacting enrollment, we're continuing to actively consider all other opportunities to accelerate this trial. We remain fully confident in the potential impact psilocybin can have for patients. We want to do everything we can to ensure a successful development and regulatory outcome for Comp360, and we believe that these steps give us the best chance. In parallel to optimizing our regulatory strategy, we're also focused on building a robust commercial strategy and adequately preparing the market for a potential paradigm-changing treatment and that's where Laurie is focused. I'll now turn it over to her to go through some of the observations since joining.