Prepared remarks
Good morning, and thank you for joining us. This is an important quarter for Cybin, one that sets the stage for an active year of milestones. In September, Doug Drysdale stepped down as Chief Executive Officer. On behalf of the Board and the company, I want to thank Doug for his contributions. As Co-Founder and Executive Chair, I stepped in as Interim CEO while maintaining continuity and momentum. The Board's search for a permanent CEO is underway. Through this transition, our priorities remain the same: patient-focused rigorous science, disciplined execution, and clear communication. We have tightened operational cadence and disclosure discipline, and we'll be adding targeted talent and scientific advisory board expertise to support late-stage execution and launch readiness. Our strategy starts where care happens in the clinic. What I mean by this is that we are designing therapy days that fit within existing schedules with short predictable sessions and a staff-light workflow that clinic teams can run without new infrastructure. From there, our focus turns to maintaining wellness. Durability is built into the plan with an efficient retreatment approach that aims to reduce visit burden compared with today's multi-visit standards, so clinics can scale capacity and patients can plan their lives. Progress with regulators follows the same discipline. We move step by step anchored in data rather than speculation, and we'll communicate milestones as they are achieved. The capital plan matches that pace. Following our recent $175 million financing, we are focusing on advancing our programs towards major data readouts. With that context, let me turn to the quarter and the progress we've made. Before we proceed to the agenda, a brief overview of our pipeline. For those of you who are new to the Cybin story, we have 2 lead programs. CYB003, our proprietary deuterated psilocin analog, is in Phase III studies for potential adjunctive treatment of major depressive disorder. And CYB004, our deuterated dimethyltryptamine or DMT program for the potential treatment of generalized anxiety disorder, is in Phase II. Clinically, our Phase III CYB003 program, which has received breakthrough therapy designation in major depressive disorder, has continued to progress, including being granted additional clearances to commence EMBRACE, our second Phase III study in new geographies. In generalized anxiety disorder, the Phase II 004 study completed enrollment and remains on track for our first calendar quarter 2026 top-line readout. Amir will share more details about both programs shortly. At the same time, we advanced preparations for scale, including manufacturing and commercial groundwork aligned to a practical clinic workflow. We also strengthened our capital position with the closing of a significant registered direct offering, which provides flexibility to execute through upcoming milestones with clear internal decision dates by program. Across both programs, we are deploying capital with discipline. We are prioritizing global site activation and conduct for EMBRACE and APPROACH, database lock and analysis for CYB004, and manufacturing readiness for CYB003. With that framework in mind, I'd like to turn the call over to our Chief Medical Officer, Amir Inamdar, to review our clinical and regulatory process. He'll begin with CYB003 in major depressive disorder, focusing on that study status, global footprint, and how the design supports real-world clinic operations and durable outcomes. Dr. Inamdar will then review CYB004 in generalized anxiety disorder, including trial design, operational status following enrollment completion, and the timing and scope of the next data update.
Thank you, Eric. Our Phase III PARADIGME program is moving forward as planned. Dosing is underway in APPROACH across U.S. sites, and participants have rolled over into EXTEND to generate durability data once the double-blind period concludes. In parallel, EMBRACE has been cleared to commence in the United States, U.K., multiple countries in the European Union, and Australia, giving us a truly global footprint. The study targets approximately 330 participants across about 60 clinical sites and is structured with 3 arms to evaluate 2 active doses against placebo in patients with depression whose symptoms remain inadequately controlled on background therapy. The primary endpoint is the change from baseline in MADRS total score at 6 weeks after the first dose. The design is built for clinical reality. CYB003 is intended to run as a predictable staff-light session that fits within existing clinic infrastructure. Prior clinical data showed sustained response and remission at 12 months after 2 16-milligram doses, and our extension work is aimed at translating that durability into an efficient retreatment approach that reduces visit burden compared with today's multi-visit standards. On the regulatory front, our posture remains conservative and specific. Near-term touch points focus on clean study conduct, global site activation, and data quality reviews as we advance towards pivotal readouts. In anxiety, the work is tracking on schedule. We have completed enrollment in the randomized double-blind Phase II study of CYB004 and remain on track for top-line data in the first calendar quarter of 2026. The study evaluates 2 intramuscular doses given 3 weeks apart, with efficacy assessed at 6 and 12 weeks and optional follow-up out to 12 months. The design permits concomitant antidepressants or anxiolytics and allows comorbid depression, which helps the results reflect real clinical populations. Just as importantly, intramuscular administration supports short, predictable sessions that fit a standard clinic day, so sites can manage throughput with existing rooms and personnel. The protocol also captures information to guide an efficient retreatment approach if patients need it, aligning durability with practical clinic operations. I will now turn the call back to Eric to discuss the platform and commercial readiness.
Thank you, Amir. Our focus is to make these therapies workable in the real world, not just on paper. Achieving that goal begins with dependable supply. With Thermo Fisher in place for both drug substance and capsule drug product in the United States, we have a manufacturing footprint sized for Phase III and commercialization, which gives sites the predictability to plan therapy days within their existing four walls. From there, we extend into the clinic. Through our partnership with Osmind, we have access to a broad network of psychiatric practices, point-of-care software, and real-world data, so clinics can map out our protocols onto the schedules they already run. Staggered starts, defined observation windows, and clear rule definitions are intended to support predictable session scheduling within existing rooms and teams without requiring new infrastructure. Throughput only matters if the session itself is practical. CYB003 is designed to fit into a standard interventional psychiatry day, offering predictable timing for patients and staff. CYB004 delivered intramuscularly targets a brief clinic experience that simplifies room turnover and staffing compared with all-day alternatives. The combination is intentional: one program is suited to establish clinic rhythms, while another is built for speed and simplicity, both aiming to raise capacity without increasing complexity. Durability is the other half of practicality. Phase II CYB003 data showed sustained response and remission at 12 months after just 2 doses, and our extension work is there to translate that durability into an efficient retreatment approach. The goal is fewer visits and more efficient planning for clinics and payers alike with clear criteria for when patients should return, how long a session should take, and how that fits across a full clinic day. We're advancing this platform with a conservative regulatory posture and a disciplined capital plan. Underpinning it all is steady leadership. We manage the CEO transition in an orderly way. The permanent CEO search is active, and our governance cadence and disclosure discipline keep the organization aligned as we execute towards the next 2 major data events. Before I turn the call over to Greg Cavers, our CFO, let me touch on our capital structure. Last month, we closed a registered direct offering with participation from prominent institutional healthcare investors. The structure paired common shares with prefunded warrants with a partial warrant, aligning capital to near-term objectives and giving us the flexibility to execute. As noted earlier, this was an important step for Cybin. The financing provides the resources to advance our ongoing Phase II and Phase III trials towards key data readouts. We have used a portion of the net proceeds from the financing to repay the outstanding convertible debentures to High Trail. For the avoidance of any doubt, this debt has been fully retired in full. We believe that participation from such high-quality institutions in the financing reflects confidence in our science, our programs, and our ability to deliver. I'd like to take this opportunity to thank our new investors as well as existing shareholders and investors for their continued support of our mission. We could not be happier with the partners that came into this financing and all prior financings that drive our programs forward. Capital deployment is paced to measurable milestones. For CYB003, funds support global Phase III execution and manufacturing readiness, so sites have reliable supply and predictable therapy days. For CYB004, resources are directed to database lock, protocol-specified analysis, and operational lift to top line. Corporate use remains limited and targeted. The plan bridges us to the next 2 major data events while preserving flexibility. From the path, we will adjust with discipline and continue to communicate clearly about our progress and next steps. I will now hand it off to Greg Cavers, our CFO, to walk through our second quarter financial results.
Thank you, Eric. During the quarter, cash-based operating expenses consisting of research, general, and administrative costs totaled $28.5 million for the quarter ended September 30, 2025, compared to $18.2 million in the same period last year. Net loss was $33.7 million for the quarter ended September 30, 2025, compared to a net loss of $41.9 million in the same period last year. Cash flows used in operating activities were $34.5 million for the quarter ended September 30, 2025, again, compared to $19.1 million in the same period last year. Operating loss was $28.9 million and net loss for the quarter was $33.7 million or $1.39 per basic and diluted share based on a weighted average share count of 24.2 million shares. We ended the quarter with cash, cash equivalents, and investments of $83.8 million. Subsequent to quarter end, we closed a financing of $175 million, which together with our quarter-end balance provides flexibility to execute our plan. We continue to allocate capital to measurable milestones, and corporate uses remain limited and targeted. Based on our current operating plan, we expect our cash resources to fund key data readouts in 2026 and fund operations into 2027. I will now hand it back over to Eric for closing remarks.
Thank you, Greg. In the quarters ahead, our focus is execution against measurable milestones across the business. For CYB003, we will continue dosing in APPROACH and expand EMBRACE site activation across clear geographies, keeping study conduct and data quality at the center of the plan as we progress towards a Phase III top line in Q4 of 2026. For CYB004, the path runs through database lock protocol-specified analysis and preparation of a clear top line package in the first quarter of 2026. In parallel, we will advance commercial and manufacturing readiness, so sites have reliable supply and a practical clinic day model as data matures, and we will continue to pace investment to milestones. This forward plan also includes leadership. The CEO search is active and progressing, and we'll provide an update when there is news. Day-to-day execution remains stable under the current structure with operating cadence and disclosure discipline intact. Taken together, clinical progress, measured capital deployment, commercial preparation, and leadership continuity position the company to navigate the next 2 data events and the steps that follow. To summarize, we have executed through a leadership transition, advanced our late-stage programs, strengthened the balance sheet, and prepared for scale with a model built for clinical reality. The work ahead is clear: deliver clean data on time, maintain a conservative and specific regulatory posture, and keep capital focused on milestones that move the programs forward. I want to thank all of our employees, investigators, investors, partners, and most importantly, the patients and families who make this progress possible. We look forward to updating you as we meet our milestones. Operator, please open the phone line for questions.
Questions and answers
This is Sarah on for Pete. Two questions from us. One on the CYB004 and the other one on the CYB003 program. First off, around CYB004 and GAD, you completed enrollment in early September. Congratulations on that. And you have a readout on 1Q '26, where you enrolled a total of 36 patients. What would you like to see from this study that would give you confidence to move forward into Phase III? Is it statistical significance on the primary endpoint? Is it directional data suggesting improvement sufficient? And then what can we expect to see in 1Q? Are you going to provide the 6-week data for the primary endpoint, HAM-A? Or will you provide efficacy data through 12 weeks?
I can take that one. Thank you, Sarah, for the question. And yes, we've completed enrollment in that study. As you probably know, it's a study with 2 arms, 1 low dose arm, which potentially is sub-psychedelic, and a full threshold dose. We look at that as a sort of dose-response type of study. We would love to see some separation between the 2. As you state there, directional data is what we are looking for, a trend in change or trend in separation between the 2 and also within subject differences in change from baseline, at least with the threshold dose. This is a proof-of-concept study, not necessarily designed as a fully powered study. But if we see a statistically significant difference, we'll be thrilled. But as you say, directional data, trend in improvement, and a dose response between the 2 arms is what we are looking for. And we'll share this in first quarter. We will aim to share HAM-A data out through 12 weeks.
Awesome. And then one more question from me. The Phase II CYB003 data suggests that 2 doses may keep patients in remission for up to a year commercially. And then taking into account the psychologic experience associated with psilocin, what do you see as the minimum durability threshold needed to compete with SPRAVATO? And how are you thinking about the trade-off between durability versus time spent in clinics from both a payer perspective and reimbursement?
Yes. I mean when you look at the guidance that the agency provides for evaluation of these therapies, they want data up to 12 weeks, which is 3 months. We will be thrilled to see effects that are maintained out to 3 months. We are hoping for better. As you know, with our Phase II data, we showed durability out to a year. But based on what is the expectation of the agency, 12 weeks at a minimum would be great.
Congrats on all the progress. I just wanted to get a clarification on the CYB004 program, just in terms of what we should expect as far as statistical powering and the definition of clinically meaningful HAM-A improvement? And then separately, I'm just wondering for CYB003, what operational milestones remain to complete enrollment in APPROACH and are site activations tracking to plan?
As I stated earlier, it's not a formally powered study. We would, however, be looking at an improvement from baseline within the subjects across the arms. A clinically meaningful effect would be somewhere around 4 to 5 points on the HAM-A. A trend to difference between the 2 arms would be important as well because we want to look at some dose response between the 2 arms. CYB003 is tracking as planned. So we remain on target to complete enrollment by the mid of next year and deliver top-line data by the end of next year.
Great. I have a separate question regarding the progress of our programs as they move into late-stage development. What has been your engagement with payers at this point regarding CYB003 and CYB004? Additionally, considering the emerging product profiles for both compounds, how do you plan to position them in the market compared to existing options for treatment-resistant depression such as SPRAVATO? Specifically, I'm interested in your thoughts on early payer engagement and how you view the product positioning of both compounds, as well as other products currently in development.
Thanks for that, Patrick. I'll take this one. So I mean, as you might imagine, at this stage, it's a little bit early, but payer engagement, of course, has begun. Commenting further, I guess, on how that develops and how ultimately with SPRAVATO, you could compare to the commercial landscape is something that we'll continue to assess as we get further into trial results and market understanding.
While George is reconnecting, we have been conducting some initial market research. However, as George mentioned, it's a bit early for CYB004. We envision both programs fitting into the emerging interventional psychiatry model, which has been initiated with SPRAVATO, establishing a necessary infrastructure. We see these as intermittent treatments that will align with this model, allowing patients to receive treatment in a clinic on an as-needed basis before returning for additional doses. The infrastructure is already in place. We believe that with the GAD for CYB004 and the adjunctive and inadequate responder for CYB003, we are addressing the needs of the most challenging and resource-intensive patients typically seen in psychiatric practices.
This is Laura Suriel on for Jim Molloy. So for the ongoing APPROACH trial, you mentioned how you're planning to have a total of 45 clinical trial sites within the U.S. So you may just provide a bit more detail on the criteria behind choosing these sites and the activation process involved and also as well as when you might think you have all 45 of these sites fully activated and onboard for the study?
Yes. So I can take that. So we are using a mixture of sites that are experienced in clinical trials and a smaller proportion of sites that are less experienced in psychiatry trials. We also have a mixture of sites that are experienced in conducting trials with psychedelics, and then there are other sites that we have included that are experienced in CNS trials in general, but not necessarily psychedelics. As you can imagine, with the number of clinical trials ongoing right now in psychedelics, there is, of course, competition for resources at sites, and we've been very careful in selecting sites that one either have a proven track record of delivering high-quality data or have the necessary experience and expertise in the psychiatry space in general in other trials, and we are confident that they will deliver good quality data. You referred to the number of sites. Yes, we've got 45 sites selected for this study. Virtually all of them are onboarded by now. What's important is with the number of sites that we have activated, we still remain on track to deliver or complete enrollment by mid of next year with top-line data by the end of the year. Yes. For CYB005, we are doing a number of preclinical profiling studies to characterize the receptor profile, the brain penetration, as well as the primary and secondary pharmacodynamics with a range of compounds in that class, which we believe would be well suited to address some of the neuropsychiatric conditions where there is significant unmet need. So that work is ongoing. And when there is information to share with the market, we will do so.
Congrats on all the progress. Just 2 for me. How much visibility do you have into the blinded baseline patient characteristic data from the APPROACH study? And can you talk at all about how this patient population will differ from a TRD population as it relates to baseline? And secondly, what agreement do you have with the FDA related to the safety database for CYB003 and what you'll need to provide a regulatory filing? Is there a minimum number of retreatments per year needed in EXTEND?
Thank you. As the trial is ongoing, the data is blinded, and we conduct necessary checks within that framework, which serve as quality controls. Since this is a pivotal trial, we are being particularly cautious with the data. There are built-in checks in the database that flag any concerns regarding data quality, and any issues are immediately brought to our attention. So far, we haven't encountered any flags, which gives us confidence that the data quality is being upheld. As for the differences from the TRD population, this patient group is earlier in the treatment cycle, consisting of individuals who are inadequately responding. They may have failed one treatment or perhaps are on a second treatment without sufficient response, but they haven't fully failed. This represents about two-thirds of the overall depression population, as these patients are in the initial stages of treatment, while TRD encompasses the remaining one-third after multiple treatment attempts. Regarding the safety database, its structure is influenced by the frequency of treatment administration. Given that this is an intermittent treatment, we've communicated with the agency during our breakthrough therapy designation discussions that the data we will provide from the three studies should be adequate to support an NDA. However, this is contingent on findings from the long-term extension study related to treatment frequency.
Thank you. Yes, we repaid High Trail $20 million, and the repayment fee ended up being 10%.
Yes. I just wanted to get maybe just one tiny detail on the loan repayment. If you could clarify how much was repaid and what was the prepayment penalty or the early repayment fees?
Nice to see the progress. I have 3. On CYB003, during your pivotal trial program, how important is it that patients remain compliant with their background antidepressant use?
Sorry, I was speaking on mute, Sumant, taking that question. For our patients in the APPROACH study and EMBRACE, because this is adjunctive, the instructions to the patients and requirements in the protocol is that they remain on their background antidepressant medication. We do not expect them or advise them to come off their antidepressant medication during the treatment period. Right now, yes, intramuscular is the route of administration that we plan to progress in Phase III. It's a very convenient form of administration, which also gives us what we need in terms of the plasma exposures and the acute experience, which cannot be achieved with something like oral. With oral, the elimination is pretty rapid. CYB004 does not reach the plasma concentrations necessary for therapeutic efficacy. That we are achieving with intramuscular. It's well tolerated. So that is what we are going to take into Phase III.
And maybe I can also add that the intramuscular route is one that, as we are aware from our market research with the interventional psychiatry clinics, is one that is also being used currently by interventional psychiatrists administering ketamine. And so that gives us some confidence that it is a route that will reach adoption in the market.
And with regards to your question regarding CEO qualities, I mean, we've been at it for only about 8 weeks right now. The Board is spearheading that process, and at the moment, we're looking for the qualities that this company and its shareholders deserve: a successful steward of capital that investors can feel confident in, someone that has executed in the past, bringing a novel drug to market ideally through commercialization, an individual that has transacted and dealt with big pharma in the past as well. These are all table stakes for us and the next individual that will be sitting in the chair. No further remarks. I just want to thank everybody for attending the call today. It's been a very exciting time for Cybin, and we look forward to delivering some fantastic updates for everybody in the future. Thank you all for your support.
Thank you, ladies and gentlemen. This does conclude today's program, and we appreciate your participation. You may disconnect at any time.