Welcome to the Cantor Global Healthcare Conference. I'm Pete Stavropoulos, biotech analyst with Cantor. With us, we have Helus, a company I cover. Please introduce Michael Halstead, CEO, and Amir Inamdar. Did I butcher it? Absolutely correct. CMO. Let's start off with the introduction of yourselves, followed by a snapshot of the company, and touch on the milestones that will shape the company over the next 6-12 months. Sure. Thank you, Pete, and thank you everyone for joining us today. Certainly very excited to talk to you about Helus Pharma. Michael Halstead, recently joined the company as the Chief Executive Officer in early August. A quick bit about my background. Been in and around industry for about 25 years. Started way back in the early days as an M&A lawyer. Spent a little less than a decade with Warner Chilcott Specialty Pharma Company. Then moved over to Intra-Cellular Therapies, a CNS-focused company. Was there for, I guess, 12 years. The company was acquired by Johnson & Johnson in 2025. I was the President of ITCI at that point. Then moved over to Helus Pharma, which I'm really excited to tell you about. Just a snapshot of Helus, and we'll get into some details here, I think, as we go. A mental health-focused company, a platform of programs. We're developing novel serotonergic agonists for the treatment of various mental health indications. Our late-stage program is our 003 program. That's deuterated psilocin. We're developing that for adjunctive major depressive disorder. It's in phase III. Really excited about that program and the indication. Hopefully, we'll get a chance to talk about that in a few moments as well. Anticipating our first phase III study to read out in the fourth quarter of this year, so exciting near-term catalyst. Our 004 program is a DMT compound in phase II development for generalized anxiety disorder. We're in the process of finalizing the trial design for our next clinical trial in that program. We'll be communicating the details on that out very soon, so please stay tuned. Our earlier stage programs, 005, we have a library of interesting compounds that I believe have application and real potential in a number of mental health-related treatment areas. The lead compound in that program we would expect to move forward in 2027. Underneath that platform, I would be remiss not to mention we do have a very broad intellectual property portfolio that the team has done a very nice job building over the years. We'll continue to build. In terms of the 004 program and the 003 program, would expect to have patent protection out to at least 2041, so a nice runway there in terms of the development. Of course, long-term commercialization. With that, I'll ask my Chief Medical Officer to introduce himself. Thank you, Michael. Morning, everyone. Great to be here. Amir Inamdar, Chief Medical Officer. My background is in psychiatry. I trained as a psychiatrist and then went on to train in pharmaceutical medicine as well. Started working at, actually, a clinical research site. I've been a study coordinator, I've been an investigator for clinical trials. Really, my pharma career started at GSK. I've been in the industry for over 25 years now. I've worked in all phases of development, starting from identifying targets, candidate selection, first time in human studies, early clinical development, to launching a product in the market as well. The last compound I was part of launching was LATUDA, which now is a blockbuster drug, when I was working at Takeda. Moved from GSK to Takeda based out of the London office, spent some time there, and then moved on to AstraZeneca working there for a few years before Cybin, now Helus, came calling. I've been here at Helus for just under five years now. I look after the medical governance and the clinical development of our programs. Happy to be here. All right. Michael, you recently joined Helus, as you just mentioned, as CEO. You were at Intra-Cellular Therapies when it was acquired by J&J for almost $15 billion. What were some of the key drivers for your decision to join Helus? You stated some of the obvious, but we want to hear about the non-obvious ones. Sure. It was really, I think, a fortunate position following the transaction with Johnson & Johnson that I could really spend significant time being selective, really doing full due diligence process on what the company was that I wanted to join next. Really wanted that to be somewhere where we had a high probability of success, of really making an impact. Have spent obviously over a decade in the CNS space with a focus on depression. Personal connections to the mental health space as well, as so many of us do. Really wanted to find a company in the mental health space. Got connected with the Helus founders, that was a great initial connection. They're very passionate about the mental health space, and that actually tracks through across the company. Every employee, they're motivated to be here. Really nice initial connection, built on that. Then, of course, did, I think, a pretty standard due diligence process on the company. Looked at the company's assets, which I just outlined, the platform that Helus has and the supporting IP. But then also looked at the probability of success, obviously focusing on our CYB003 program, given it is such a near-term significant catalyst. Really dug into not only the phase II data that Amir and his team put together, the accomplishments there, as well as the phase III trial design and how the team has executed on that to get comfortable. I really thought that this was a program that does have a real likelihood of success. Then also evaluated the team. You have a lot of connections in the space, of course, being in it as long as I have in the depression space that is. Really checked out the team to ensure that this was an experienced, competent team that I would work well with over the near and then the longer term. Really got excited about the broad platform and the impact that I really do think that this company has the potential to make in such an important space. You put all that together, I decided that this was the place to invest my most important commodities, my time, my energy, and made the leap. I'll say, we're six weeks in here. Every day has validated all of that diligence that I did up front and really excited about the potential of Helus, both in the near term and then in the longer term, given the breadth of these programs and what I really think they have the potential to do in the mental health space. All right. Thank you very much for that overview. You are developing CYB003 for major depressive disorder. For those that may be new to the story, just sort of walk them through what it is exactly. Why deuterated psilocin? Sure. Our compound for the CYB003 program, deuterated psilocin. You start with the parent molecule, the prodrug, psilocybin. That then needs to be metabolized in the body into psilocin to the active metabolite. We take that active metabolite. We deuterate it. There are a number of benefits, we believe, in connection with that deuteration. The efficiency of delivery, the reduced drug load, and then the reduced variability. All of that we believe beneficial to supporting some of the really impressive data that we have seen so far and as the program moves forward. Maybe, Amir, if you want to speak just briefly to what we have seen with some of our earlier studies. Yeah. The deuteration does result in some very meaningful changes. We have seen this in our preclinical data, where we have seen the drug get into the brain quicker and reach higher levels. From a clinical point of view as well, when you look at the dose we are exploring in phase III, the 16 mg dose, the plasma levels at 16 milligrams are about 1.5x higher in terms of Cmax compared to 25 milligrams of psilocybin, which is generally used in clinical trials. The exposure is about 2.5 times. AUC is about 2.5 times higher. Now, we think that is important, that is meaningful, because it gives the opportunity for patients to reach that level in the plasma, which we believe is necessary for a breakthrough experience, which we also know is necessary for therapeutic benefit. All right. You are in a phase III adjunctive MDD setting. Why go after that setting rather than, say, treatment-resistant depression? As part of it, I should have mentioned this upfront because it was really a key feature as I was looking at the potential of the CYB003 program. That is the choice that the team made, absolutely the right choice, I believe, of focusing on the adjunctive MDD space. This is add-on therapy on top of standard of care. Standard of care for this patient population, think the SSRIs, the SNRIs. There are approximately 23 million people in the U.S. suffering from major depressive disorder. Of that population, approximately 70% are on standard of care. Within that population, approximately two-thirds aren't receiving optimal benefit from the standard of care therapy. If you think then about how clinicians approach this patient population, often people are getting some benefit while not optimal, right? Adjunctive therapy gives the clinician the opportunity to continue down that path towards hopefully remission. You don't have to wash the patient off of drug. That's a lengthy process. You're not starting over then with a new monotherapy, but you're continuing down the path. It really fits well into the treatment PARADIGM. You're getting these patients before they get to the end of the spectrum, treatment-resistant depression, multiple failures. Really accessing the broad spectrum of the patient population. If you look at the antipsychotics, what they've done adjunctively, even with all of the side effect burdens that the antipsychotics have, and look at other therapies, I spent obviously a lot of years dealing with the antipsychotic space. They've been very successful even with that side effect burden in the markets as part of this. We really believe that our product, with all the features, which we'll talk about that hopefully in a little bit, really has great potential as an adjunctive treatment on top of standard of care. All right. The company did conduct a phase II. What were the key data that sort of drove the decision to move forward into a phase III? Sure. I will let Amir speak as the architect, as our Chief Medical Officer, and the clinician. I will let him speak to the specific data. I would just say, high level as I look at this, what are the key features that you are looking for? Drug efficacy, the durability of effect, and then the safety tolerability profile. Looking at the phase II data, again, in the adjunctive setting, so you are adding therapy on top of standard of care, the results that we saw in the phase II, acknowledging it is a phase II, obviously needs to play through in the larger phase III studies, but really great starting point. Just jaw-dropping efficacy data, durability out to a year, and then a very good safety and tolerability profile. Amir, maybe would you like to speak to some of the specifics? Yeah. From a purely drug development point of view, when I am doing early phase studies, I am looking at what is the response to a range of doses. Do you get the drug into the plasma at dose proportional levels? Do the plasma levels increase with increasing dose? We did see that not just in PK, but also in terms of the clinical effects. It was clear that there is a drug here, that if used correctly, should result in clinical benefit. Then, of course, we saw the data. We saw a pretty rapid and dramatic improvement in symptoms of depression with a single dose. We identified a dosing regimen, which was two doses three weeks apart. Then there was the durability data. Out to 12 months, we saw a pretty phenomenal number of patients in remission out to 12 months, and a large drop from baseline in their MADRS scores. You mentioned it is an early study. It is a phase II. Of course, we need to validate it in a larger, well-controlled trial, but the data is there. The data is there enough to convince us to invest into a large phase III adequate, well-controlled study, which is what we are doing now. Okay. Moving on to the phase III study, just go over the design of APPROACH and EMBRACE and sort of what are the questions each of these studies are trying to address. Right. The two studies are part of our PARADIGM program. PARADIGM is the phase III program of pivotal studies, which includes APPROACH and EMBRACE, the two short-term efficacy studies, as well as the long-term extension, which is EXTEND. APPROACH is two arms, an inactive placebo versus the active dose of 16 milligrams, which is the maximum effective dose we found in phase II. It's about 110 patients per arm. Patients receive two doses of the study drug three weeks apart with a primary endpoint at six weeks and a secondary endpoint at 12 weeks. EMBRACE is exactly the same design with one key difference, which is we've introduced an intermediate dose of 8 milligrams. It's three arms, 110 patients per arm. Now, patients who complete or participants who complete both the studies are eligible to roll over into the long-term extension, which remains blinded up until such point of time that patients relapse or need additional treatment. What that allows us to do is look at the durability of that initial effect out to a year. It also allows us to understand whether patients, if they require retreatment, how many retreatments they may require, and what's the durability of those treatments. We allow up to three additional doses in EXTEND. APPROACH gives us efficacy in a placebo-controlled manner, but also importantly gives us placebo-controlled safety data. What EMBRACE does is it gives us. We're attempting to show a dose response there, which is one of the strategies the agency recommends for this class of drugs. The combination of two studies, we believe should be sufficient to help us file for an NDA. All right. Sorry, were you going to say something? I would just add to that, Amir is a very humble person, so I will say what he won't. First, the phase II study, we saw 13 to 14 points of improvement off of the one dose on the MADRS depression scale. It is placebo-adjusted. Really, again, incredible results there. The second dose in the extension saw an additional five points of improvement. So, a really great starting point from the phase II, but really like the phase III design, Amir and his team followed very closely with what worked in phase II as they were designing the phase III. Obviously, they incorporated both doses into the primary endpoint, given the benefits they saw in phase II, so getting the benefit of that. But then most importantly, as he was talking about, or as important, I should say, as he was talking about the phase III program, the team has done a very good job in terms of clinical trial execution, and this is just critical. Perhaps sometimes overlooked as people are thinking about these programs, but really down to the site level, being very involved with the conduct of the trial, ensuring that this clinical trial design that they have put together is in fact being followed. So really pleased with that focus, those efforts that Amir and his team have really been focused on throughout the conduct of the phase III program. Wanted to make sure I gave Amir the credit that he and his team absolutely deserve. Well, I am going to ask him the details. So what learnings from the phase II-B did you actually implement to sort of help you increase the probability of success? Yeah. One of the key features that Michael mentioned was actually folding in the second dose into the primary endpoint, right? Because we did see an incremental benefit of the second dose. So we made sure that that is folded into the primary endpoint assessment. But to me, the most important thing that we did was actually do nothing. In the sense that we kept the design of phase III exactly identical, with one key difference that I will come to the phase II design. And this is a temptation most people normally have when going from phase II to phase III. You want to tweak the design. You want to make it easier to recruit because you are scaling up. There are hundreds of patients versus tens of patients. And that is where you see a lot of erosion of the effect size from phase II to phase III. Now, I'm not saying that won't happen. You'll see heterogeneity in phase III. You'll see some erosion of the effect size. But we've tried to replicate the successful design as much as possible in phase III. What we've done, though, is we've upped the threshold for entry on the MADRS from 21 points to 24 points. What that makes sure is we get the right quality of patients, and quality of patients is absolutely essential. You want the right patients in your trials, because otherwise, of course, you're sacrificing your effect. We have also implemented a number of other measures in terms of ensuring the quality of the study and the quality of the patients. But to me, the most important thing is keep things, if they work, don't change it. That's it. If it's not broke, don't fix it. Yeah. All right. Powering. Is there anything you can say about the powering assumptions? We haven't talked about that publicly, but 220 patients. Look at the effect size that we'll be able to demonstrate with that. You can draw some conclusions from what we've seen in phase II. It's a pretty standard sample size. Okay. For EMBRACE, you have the mid dose, 16 milligrams. Yeah. Then you have the high dose, 60 milligrams. What is the comparison in the study? Is this strictly 16 milligrams to placebo, or is 8 milligrams involved somewhere in there? Yeah. What we are trying to do in EMBRACE is attempting to show dose response. The primary comparison there is between the inactive placebo and the active drug. Of course, we are trying to replicate the efficacy from APPROACH of 16 milligrams in EMBRACE as well. That will be the primary comparison. But we will also compare eight placebo. Okay. Can you talk a little bit about the OLE trial design, what drives administration of an additional dose? Yeah. I always correct people that it's not an open label extension. Sorry It is a long-term extension. Okay. Because the fact is, patients remain blinded in the long-term extension until they need treatment. You may actually have a patient who's received two active doses in APPROACH or EMBRACE, and they go the entire one year without needing additional treatment, and they remain blinded throughout the study. But what EXTEND allows us to do is look at that durability of response over a one-year period. And what it also allows us to do is then administer treatment to patients that relapse and see whether that improves their symptoms back to baseline or to remission, and how long the durability of that effect would be. So it tells you how many doses are required to maintain efficacy or effect out to a year, and what is the retreatment interval. This is absolutely critical information for a clinician like me. You want that in the label. You want to tell clinicians, "This is how to administer the drug." And that's what EXTEND gives us. Also, of course, it gives us long-term safety information, which is important. What exactly triggers redosing or dosing? We've got predefined criteria in the protocol that are based on MADRS thresholds, they're based on pretty clear relapse criteria. They include worsening in symptoms, et cetera, and that is confirmed over a period of two weeks. Pretty standard relapse criteria in long-term extension studies. All right. Is there anything you can say about the completion rate and the blind? Most all of it's going to remain blinded, but before they roll over into extension? Yeah. Those data remain blinded for now, so we aren't able to comment on that. Okay. Top line data, what do we expect to see? Q4, imminent top line data, we will see the six-week primary endpoint. We will also share with you the 12-week secondary endpoint and the standard safety information that typically comes. Okay. How are you thinking about pricing? I am assuming each therapeutic intervention requires two dosings about three weeks apart. Little bit early to comment specifically on pricing. At least let us get through the first phase III readout that we're expecting in Q4. But just more generally, and you mentioned the dosing, we're talking about the durability over a year that we've seen off of just a few doses. We'll see how that plays out in phase III, but would expect similar. If you think about currently the space really, I guess you have to look to SPRAVATO, that's dosed 30- 50 times a year. Compared to if our product has, let's say four dosing regimens over the course of a year, especially with the other product characteristics in terms of efficacy and the safety profile. I think there is really a strong story to put together from a reimbursement perspective. Obviously, those characteristics, from a clinician's perspective, would expect those to be very appealing, and most importantly, from a patient benefit perspective. We'll give you more information on our thoughts on pricing as the story proceeds here. But with SPRAVATO as sort of a baseline, really think that there's a good place for a product with our characteristics in this marketplace. All right. So before we ask the last question, CYB004. I know you mentioned you're going to have updates, but Sure. CYB004, as I said, it's a DMT compound. Some really attractive characteristics there, short acting. We've done a number of earlier studies that suggest real potential and again, another very important indication, generalized anxiety disorder. This is another large patient population. Unfortunately, limited treatment options, and there's been very little innovation in this space in a very long time. So absolutely an unmet need here. In terms of CYB004 specifically, we completed, earlier this year, a phase II signal finding study. What we saw from that study, definitely potential for this drug justifies in my mind, and of course, our clinical team, that this is worthy of investment, has potential. As a result, we're designing the next clinical trial. Stay tuned. That information will be out very soon, but look forward to that. Again, it speaks to the breadth of the pipeline here. Helus is not a single drug candidate. We've got late stage, middle stage, we have earlier stage. I think it's important to view this as the platform that I really think it is, and the potential there is across all of that. Okay. If we're sitting here 12 months from now, what would you like to say are the key value-creating accomplishments that have been over the past year? Sure. I probably can boil it down to three repetitive words: execution, and execution. That's what I'm certainly going to be focused over the near and the longer term. I know that's what Amir and the R&D team are focused on. Specifically, obviously, execution and progress with respect to our CYB003 phase III program. We have the two readouts of those programs. We've guided to an NDA filing in 2028, and we've gotten breakthrough therapy designation. I should have mentioned that upfront. Very important. Not minor feature. Allows for rolling submission. We would also expect approval then in 2028 as well. A lot of progress would be success in terms of the CYB003 program. Advancing that CYB004 program as well, do see real value there. Then building out in an appropriate scaled way the infrastructure at Helus so that we're keeping pace with this clinical execution so that assuming product approval, that we'll be in exactly the right place, have what we need for a successful commercial launch. Obviously, you have to scale that appropriately, but you need to put those building blocks in place. I lived through that process on a very granular level at Intra-Cellular Therapies. So that would also be critical to success over 12 months. Okay. We've reached the end of time. Michael, Amir, thank you very much for attending the Cantor Healthcare Conference. Looking forward to all the progress, both for 003 and 004, and especially for the 003 readout in 4Q. So best of luck to you. Thank you, Pete. Thank you, everyone. Thanks.