Hello everyone. Good morning, and thank you for joining H.C. Wainwright's 28th Annual Global Investment Conference, held on September 14 to 16, 2026. My name is Patrick Trucchio. I am a senior healthcare analyst at H.C. Wainwright, and it is our pleasure to host you today. It is my pleasure to welcome Helus' CEO, Michael Halstead, as well as the CMO, Amir Inamdar. For those who are unfamiliar, Helus is a neuropsychiatry company pioneering next generation psychedelics and neuromodulators for mental health. Helus is currently conducting a phase III program evaluating its lead candidate, HLP003, a deuterated psilocin analog for adjunctive treatment of major depressive disorder, MDD, and top-line data is expected later this year in the fourth quarter. Maybe for those who are less familiar, maybe you could introduce us to Helus and where the company stands today.
Sure. Thank you, Patrick. Thank you everyone for joining us today. Michael Halstead, recently appointed CEO of Helus. I joined in August. Very excited to talk about Helus Pharma today. In terms of the company, as you said, we are a mental health-focused company, a platform. We have multiple programs. We are developing novel serotonergic agonists for the treatment of several different mental health indications. Our late-stage program, as you said, is our HLP003 program, that is deuterated psilocin, that we are in phase III development for the treatment of adjunctive major depressive disorder, MDD. Really important indication. I am sure we will dig into that a little later in the talk. That is in phase III development. Our first phase III is expected to read out in the fourth quarter of this year, so a very near term, important event. We also have our HLP004 program that is the molecule is DMT.
It is in development for generalized anxiety disorder, GAD. We completed a phase II signal finding study earlier this year. We are currently finalizing the design of the next trial in that program, and we will be rolling that information out very soon. We also have our earlier stage program, HLP005. That is a library of compounds that I think have real potential in a number of mental health indications. We will be moving forward the lead candidate of that program, expected in 2027. Underneath that platform, I think it is important to note there is a very strong IP foundation. The Helus team has done a very nice job building out our IP portfolio, in particular around the HLP003 program, the HLP004 program, anticipated patent protection to run at least through 2041. So a very nice foundation as we look ahead to both development and then ultimately commercialization.
A lot going on at the company, both at the later stages, the middle stages, and the earlier stages. As I dug in, I got very excited about the potential of the company and really looking forward to moving things ahead here in the near future.
That's really helpful. Maybe just as a follow-up, you can tell us a bit more. You joined recently in August. Maybe tell us a bit more about why Helus and why now? What attracted you to the company?
Sure. I've been in and around industry for about 25 years now, most recently at Intra-Cellular Therapies. That was acquired by Johnson & Johnson in 2025. Following that acquisition, I think I was in the fortunate position to be able to really take my time, do some significant diligence. Wanted to make sure that whatever company I joined, that there was the real potential to make a real impact. In particular, given my over a decade in CNS, just a general focus on mental health, that got connected with the Helus Pharma team, it really just made a lot of sense from all perspectives. When you look at the passion to a person, starting with our Chief Medical Officer, but our founders, all the folks in the company really passionate about mental health and what we're trying to achieve here.
Looking more specifically in terms of the company's assets, their potential, as I said before, a platform here with late stage, mid-stage, early stage, exactly what you'd like to see as you're looking towards building a company for the long term. Also in particular, the HLP003 program, the adjunctive MDD indication. I think that's very promising. Exactly the right area of focus in the MDD space, I can talk more specifics around why that is, I think really a good indication here. But very strong phase II data, both from a drug efficacy perspective, but also durability perspective, durability of effect, and safety and tolerability. So the three key legs of the stool as you think about product potential, most importantly from a patient benefit perspective, but also then from the clinician perspective as well as the commercial perspective.
In terms of the phase III then, really like the way Amir designed the program, really like the way the program's been executed. Really think that there's a real probability of success here. Look forward to providing data in the fourth quarter. So excited about the setup and it's a great team that I'm working with, experienced, competent people. Overall, it was just a very attractive opportunity to make that difference in the mental health space.
Great. Maybe we can dig a little bit more into HLP003 and what is the differentiation of this compound, what is the advantage of deuteration, and maybe you can talk a little bit more about the phase II data, what you saw, and what gives confidence going into the phase III.
Sure, and I will let Amir, our Chief Medical Officer, maybe take most of that as the primary architect. Deuterated psilocin, psilocybin is the parent molecule. It needs to be dephosphorylated in the body, which then gives you the active metabolite, psilocin. We have deuterated psilocin, believe that that provides a number of benefits, including the reduced variability in our preclinical studies, as well as reduced drug load, efficiency of delivery. A lot of positive characteristics as a result of the deuteration, we believe. But maybe, Amir, a little bit on deuteration but then also the phase II.
Yeah, absolutely. Thank you, Michael. Deuteration does stabilize the molecule. We know that psilocin traditionally has been unstable in solution, so the deuteration helps. Because we have the active moiety and not the prodrug, that translates into some meaningful differences. We do see those in our preclinical data. In the preclinical studies, what we have seen is that HLP003 very rapidly gets into the brain, and achieves concentrations that are about 1.5 times higher than Cmax and 2.5 times more than in AUC, which is exposure. That translates clinically, potentially, in a way that we believe is necessary for demonstrating good therapeutic benefit. It gives patients the opportunity to get to a higher level of the drug in the plasma, and we know higher levels of drug in the plasma are associated with a threshold effect, which results in therapeutic benefit.
Those are some of the advantages we see from deuterating the psilocin and using the active drug than the prodrug. We have seen data in phase II. We saw about 13 to 14 points at the two doses, 12 mg and 16 mg, and that was after a single dose of HLP003 and at the three-week time point. A second dose resulted in an incremental benefit of about five points. What we have done in phase III is we have rolled that second dose into the primary endpoint. In phase II, it was the three week after a single dose. In phase III, our primary endpoint will be after the second dose, so it will be able to benefit from the incremental improvement. Not just that, we saw durability of data. We saw out to a year north of 70% remission rates after two doses of 16 mg.
That, of course, needs to translate into phase III. It is a phase II smaller study, but that gives us a lot of confidence that there is a real drug there with the potential to meet a significant unmet need.
Right. Great. Maybe you can walk us through the PARADIGM program for HLP003, APPROACH, EMBRACE, and EXTEND.
Yeah, absolutely. The PARADIGM phase III pivotal program, which will be the basis of our new drug application, consists of two short-term studies and a long-term extension. The two short-term studies are APPROACH and EMBRACE. APPROACH is a two-arm study comparing two administrations of the active 16 mg versus two administrations of inactive placebo given three weeks apart, with a primary endpoint at six weeks and a secondary endpoint at 12 weeks. That gives us some intermediate durability data. It is a randomized double-blind control study. EMBRACE is only different from APPROACH in one respect, which is the introduction of an intermediate 8 mg dose, which gives us the opportunity to attempt to show a dose response in EMBRACE. The combination of these two studies is consistent with what the agency has asked of sponsors in this space to do as part of their phase III program.
Patients from both those trials, APPROACH and EMBRACE, have the opportunity to roll over into the long-term extension, which remains blinded up until such point of time that a patient relapses and requires treatment. We have got criteria to do that, to give them treatment. EXTEND follows them up out to a year. We are trying to replicate or assess what we did in phase II. We will see the durability of effect out to a year, but also because there is an opportunity for retreatment, we will be able to tell what the retreatment needs are, how many doses will be needed, if at all, and what the interval between those doses will be, which is what clinicians like me would like to see in the label.
Right.
Patrick, I think it's important to emphasize for folks that aren't as familiar, of course, this is all administered adjunctively, so patients are on standard of care, your SSRIs, your SNRIs, then HLP003 is administered on top of that in these studies, which really fits in nicely in terms of how clinicians treat patients with depression in this space. Again, going to the benefit of that adjunctive MDD indication.
Can you talk about some of the nuances of the phase II and phase III? First, just the difference in terms of being an adjunctive treatment. What does that actually mean? What implication might that have for the phase III data? As well, being an MDD rather than TRD, what are some of the key differences there? Then ultimately, what is the product profile that's emerging? What does the ideal product profile look like for HLP003?
Sure. Starting with the MDD population. This is approximately 23 million people in the United States suffer from MDD. Of that 23 million, approximately 70% are on standard of care, your SSRIs, your SNRIs. Of that 70%, approximately two-thirds of those aren't getting optimal benefit relief of their depressive symptoms. But often they're getting some benefit. So you think then about a clinician treating a patient with depression. They have the opportunity with adjunctive therapy because, of course, it'll be tested clinically in connection with standard of care to then add that on. So what you're doing is you're getting the advantage of whatever benefit people are getting from standard of care, but then moving them down that path towards hopefully remission with the addition of the adjunctive treatment.
Think about that as opposed to, say, a monotherapy approach where the clinician has to wash the patient off of the standard of care, off of any drugs, start over effectively, see if that new monotherapy actually adds a benefit while the patient's been taken back to the beginning. So the adjunctive approach really, again, continues on that path. You're getting them before they get to treatment-resistant depression, which is about 3 million patients at the end of the spectrum, multiple failures. Where you really see how adjunctive therapy plays out is with the atypical antipsychotics. They've been very successful, notwithstanding the side effect burden of the antipsychotics. I'm very familiar with this because at Intra-Cellular Therapies, we, of course, developed CAPLYTA for adjunctive MDD. There really is a significant side effect burden with the antipsychotics.
If adjunctively you can add on a therapy, you're asking about the product characteristics, a therapy that has the drug efficacy together with durability instead of daily dosing. As Amir said, let's say this is four doses a year. We'll see how it plays out in the phase III, in the long-term extension. Butfour doses a year. Then if you have a safety and tolerability profile that tracks along the lines of what we saw in the phase II, which is no severe AEs related to drug, and the adverse events, mild to moderate, that were transitory, mostly on day one. When I say mild to moderate, think headache, upset stomach, nausea, and high blood pressure. Again, transitory on day of treatment, as opposed to the antipsychotics where you're looking at real severe cardiometabolic, and sexual dysfunction. The laundry list goes on.
Those three key, the efficacy, the durability, and then the safety and tolerability would really be what we would hope would emerge out of our phase III. Again, really like where we're starting from in terms of the phase II data, and we'll be turning over that card hopefully very soon.
Right. Terrific. Could you give us a little more specifics in terms of the timing of the data? Do we know when in the fourth quarter? What data will you have at that point to present to us?
In terms of timing at this point, all we've said is just fourth quarter. Obviously, we announced completion of enrollment at the end of July. So certainly on track with that fourth quarter timeline. In terms of the top line data readout, Amir, do you want to-
Well, it's pretty much what you'd expect with the six-week primary endpoint. We'll also be sharing data from the 12-week secondary endpoint, and then some top-line safety data as well.
Have you discussed what the study is powered to demonstrate?
We have not. It should be pretty standard. You've got 220 patients in the APPROACH, about 110 per arm. When you look at some of the powering assumptions generally that have been published, it should be there or thereabout.
HLP003 has a breakthrough therapy designation, and there's been a number of initiatives from the administration, from the FDA that appear to be favorable towards psychedelic drug development. How are you going to leverage these different or how are you planning to use those levers into your NDA filing? When should we expect that NDA filing?
Sure. We've guided people to anticipated NDA filing in 2028. As you said, given our compound has Breakthrough Therapy designation and the likely review cycle, we would also anticipate approval in 2028. You mentioned the positivity in the space. Perhaps I was remiss in not mentioning that earlier as I was looking at the company. Obviously great dynamics. You're seeing a lot of good data in this space. It's very clear this class of drugs provides a patient benefit. Obviously, all of us need to get through FDA approval process. Really positive developments there, support from the administration, FDA being very constructive. Now we have guidelines from FDA so that everybody understands the path to approval. Really good overall momentum in terms of the space as well.
Just pivoting over to HLP004, can you tell us a little bit more about HLP004 and next steps for this program?
Here I think the buzzwords would be stay tuned. As I said, we've done a lot of work with this deuterated DMT compound. There are a number of promising early-stage studies as well as then our signal finding study earlier this year in phase II. We are finalizing that clinical trial design. It's going to be rolled out to everyone very soon. Definitely think the program has promise and plan to move it forward, but we'll give you more details in the very near future. Also I would say generalized anxiety disorder in general, it's a very important indication. Again, large patient population. There really haven't been significant advances, new treatments in a very long time.
Just a question on the infrastructure. So where are we today with the interventional psychiatry infrastructure, and where do you think we'll be presumably at some point when HLP003 hits the market?
Right. So there are approximately 8,000 clinics currently. J&J's SPRAVATO has done significant work in this area. They're now, I think, up to a $2 billion a year annual run rate. And certainly have done a great job building that infrastructure. You've also got some of the peers in this space that will be slightly ahead of us that will continue to build on that infrastructure. So I think there will be a lot there. Of course, there'll be work that we have to do. We'll be prepared for that. But a nice jumping-off point in terms of what's already been done to date and look forward to moving towards that commercialization process.
Can you talk about the financial runway for the company and how does it see you through these catalysts?
Sure. We have not provided our long-term cash runway guidance yet. Allow me a few more weeks to really dig in, and we'll be rolling out longer-term guidance to folks. But about $166 million on the balance sheet as of June 30. Very comfortable in terms of that cut cash runway to get us through our near-term catalysts, and so in a good place currently, and as I say, we'll provide additional guidance soon.
And just as a final question, what do you think is the most common misunderstanding investors have about Helus today?
I really think it's fully appreciating the platform that we have. Obviously, everybody is focused on HLP003, as rightly so, given the very promising phase II data and given the readout that we expect in Q4. This really is more than a single drug candidate. This is, as I said before, there's a full pipeline here, late stage, middle stage, early stage with IP serving as a foundation to that platform. There's a growth story from a lot of angles and it's incumbent upon us to execute, execute, which is what we'll be focused on in the near and longer term.
Right. Terrific. Well, have to leave it there, Michael and Amir, thank you so much.
Thank you.
Thanks to Helus for joining us, and thanks for everyone for being in our conference. Have a great rest of your day and conference.
Thank you.