Hello, everyone, and welcome to the 7th Annual H.C. Wainwright NeuroPerspective Summit. My name is Patrick Trucchio. I'm a Senior Healthcare Analyst at H.C. Wainwright. We have a robust agenda at the conference this year with more than 25 companies presenting, with their sessions available on demand through the conference portal. In addition, we're expecting a full day of panels and fireside chats with world-class KOLs on June 15th for the in-person portion of the conference, with a broad CNS drug development across multiple indications from depression, epilepsy, to BBB delivery. And with that said, it's my pleasure to welcome Healist Pharma, a clinical stage pharmaceutical company committed to helping minds heal by developing proprietary NSAs or novel serotonergic agonists. These are synthetic molecules designed to activate the serotonin pathways that are believed to promote neuroplasticity. And from the company, I'm excited to introduce Chief Medical Officer Amir Anamdar. Welcome to the panel, or welcome to the conference. So just for our audience who may be less familiar with Helis, if you could provide an overview of Helis today and your vision for positioning Helis across the interventional psychiatry space. Yeah, great.
Thank you for inviting me here. Great to be here and chatting with you, Patrick. As you said, we are a biopharmaceutical company that are developing novel serotonergic agonists. So these are molecules with agonistic activity at multiple serotonin receptor subtypes, including receptors within the 5-HD1 and 5-HD2 families. And activation of these receptors is believed to engage downstream signaling and cellular pathways associated with neuroplasticity, including mechanisms that are involved in synaptic adaptation and neural network remodeling. And we believe these neurobiological effects contribute to the therapeutic potential of novel serotonergic agonists. So we are a clinical stage company. We've got two programs in the clinic, HLP-003 for major depressive disorder and HLP-004 for generalized anxiety disorder. O3 has FDA breakthrough therapy designation, and it's in phase three for adjunctive treatment of MDD. Both are deuterated analogs of naturally occurring compounds, and deuteration of these compounds is intended to optimize the physical chemical properties, help with commercial scaling, and create differentiated IP for these molecules. Our portfolio includes about 350 patent applications, about 100-plus granted patents, including U.S. composition of matter. This is coverage for 2003 as well as 2004 until at least out to 2041, which gives us the ability to add indications. And our early clinical data is demonstrating that this class has transdiagnostic applicability in psychiatry, which is where we want to be. we want to be at the forefront of helping people with mental health conditions and improving their
lives. Right. Terrific. So maybe just moving then on to HLP 003 in MDD, maybe walk us through maybe some background on HLP 003. And then as well, maybe you can walk us through the phase three paradigm program uh yeah that you know and what distinct question does the program which includes um approach and embrace and extend what specific questions are these um uh trials answering
yeah so uh hlpo3 is a deuterated analog of a silicon um what deuteration does is it's intended to change the physical chemical properties of this naturally occurring novel serotonergic agonist. We've completed phase one and phase two. We did a study in major depressive disorder with O3 as an adjunctive to background antidepressant medication, where we showed effects ranging from 13 to 14 points with just a single dose of HLPO3 at the three-week end point. Based on this, we got an FDA, BTD designation, and subsequently we designed a phase three program, which is called Paradigm. As you referred to three studies, Approach, Embrace, and Extend. Approach is a two-arm study, and it compares two administrations of 16 milligrams of HLPO3 given three weeks apart with two administrations of an inactive placebo. The intention here in this study is to show primarily efficacy in the short term, which is six weeks, which is what the FDA wants, and durability out to a secondary endpoint of 12 weeks. And in addition, we will also collect safety data. And having a placebo allows us to compare placebo-controlled safety data. This is one of the two studies that the agency wants as part of a new drug application for this class of drugs. So the second study is EMBRACE. It is a three-arm study. Again, looking at short and intermediate-term efficacy, same, two doses of 16 milligrams of HLPO3 given three weeks apart. We also have an intermediate dose arm of eight milligrams in this study. again, two doses, three weeks apart, and an inactive placebo arm, two administrations, three weeks apart. Both these are double-blind control studies. The intention with Embrace is to try and, of course, replicate the efficacy in approach. You need to show efficacy in two studies, but also an attempt to show some sort of a dose response. It's not necessary to show dose response, what the agency wants us is to attempt at least. And given the methodological challenges in this class of drugs, the lower dose or the intermediate dose of O3 acts as its
own comparator. Right. Yeah. That's really helpful. And I was actually, it's a good segue, because I wanted you to talk a little bit more about the comparator strategy and approach and And how we should think about functional and blinding and expectancy effects.
Yeah. And what we have taken is essentially the FDA guidance on this class of drugs and applied it exactly. And as part of our BTD discussions, we've vetted those. So in terms of comparators, approach does a very pure active versus placebo comparator. That's the best way of showing a large effect size, but also placebo control safety. Embrace uses an intermediate dose as a dose response, but also its own comparator. And we use an inactive placebo as well. Now, you referred to functional unblinding. I always, when I am asked this question, I always remind people that functional unblinding is inherent in psychiatry or CNS drugs. Now, good example, sedatives, opioids, antipsychotics, they all cause functional unblinding. But with novel serotonergic agonists, because of the expectancy combined with functional unblinding, it creates some challenges with respect to doing clinical trials. And there is a recipe for addressing these challenges, which has been given to us in the FDA guidance. Combination of two studies is one approach. We, of course, use remote and independent blinded raters. This is the single most important strategy to address issues related to functional unblinding. We also have some safeguards in place during dosing sessions, which makes sure that the clinical staff do not get unblinded. And one other strategy is looking at intermediate term data and the long term data. So 12 weeks endpoint and the long term data from X10 is basically designed to outlast any expectancy bias.
Right. That's helpful. And the approach top line data, I believe, is expected in the fourth quarter of 2026. Is that data still on track? And what data should we expect at that readout?
Yeah, absolutely. It's still on track. We aim to deliver top-line data by the end of this year. What you should expect to see is data on the primary endpoint, which is the six weeks, and secondary endpoint, which is the 12 weeks, in terms of efficacy. So drug placebo difference in the Madras. You'll also get some data on responder remitter rates, as well as key safety data. And as time passes, we get closer to it. We'll provide further updates on exactly what will be shared as part of the top line readout closer to the time.
And how are you thinking about what constitutes a win for approach? What's the bar on efficacy and durability for both, you know, regulatory perspective, but then as well from a, you know, sort of a clinical perspective?
If I see what we saw in phase two, I will be over the moon. That was quite phenomenal, like 12 to 14 points. But we have to be realistic, and we've seen this in clinical trials, having done this for over two and a half decades. I know when you go from small studies to larger studies, you can expect, with that scaling, some erosion of the effect size. So, as I said, same results would be excellent. But even if you have the effect size from phase two, which is generally a rule of thumb, it would still be class leading. To put that into context, of course, most adjunctive treatments, I think we have to remember this is adjunctive as well, where effect sizes are traditionally quite small. And most adjunctive treatments will deliver only about two to four point separation versus placebo. So if I see something that is even half of my phase two data, I will be thrilled. I remain cautiously optimistic. I think one other endpoint that I am curious and keen on is the key secondary endpoint. That's up to three months, which will give us intermediate durability data.
And I think that will be for regulators as well as the payers. That makes sense. And maybe you could talk a little bit about the safety profile, what you've seen so far, and what safety domains matter most in phase three? Should we be looking at things like cardiovascular effects, you know, suicidality, or any other, you know, acute anxiety, other DDI, anything that we should be looking for?
yeah i mean all all safety matters uh with patients when it comes to clinical trials safety has to be the single most important uh factor we we do want to characterize these drugs accurately so as to be able to provide the prescribers with a very clear picture of what they should expect in the clinic when they administer the drugs we also need information to educate the patients before they select treatment with this uh with this class of drugs So, all domains remain important. The FDA and us as well are quite keen on collecting data on abuse liability. This is something we are doing quite closely. We are collecting all adverse events. In the past, there has been some confusion with some players around collecting whether events that are on target pharmacology, whether they should be reported as adverse events or not. And we've had those discussions with the agency and we are essentially collecting everything irrespective of whether those are expected effects or not. Typically, what we expect with this class of drugs is a transient physiological effect. So cardiovascular in that sense, blood pressure, heart rate, we will collect all of those. We are collecting all of those psychological adverse events as well. We will collect all of those, you know, things like changes in perception, thought, et cetera, even though these are on target effects, expected pharmacology, but we're still collecting those, anxiety, et cetera. You mentioned suicidality, I think, and this is kind of a known feature in the mental health conditions, including depression. I mean, it's part of the illness where people feel, you know, lack of optimism for what's going to happen in the future, you know, hopelessness, helplessness. These are features of depression. So one would expect to collect these kind of data to make sure patients are safe. but with adjunctive our indication of adjunctive we also need to be keen on looking at drug-drug interactions so we are collecting those data as adjunctive as well both pre-clinically as well as in phase three and we'll make those part of our package to to the FDS part of the new drug application. Right that's interesting
And can you talk about how you're leveraging the breakthrough therapy designation in your FDA interactions, how this impacts things like meeting cadence, alignment on endpoint safety, package, durability evidence, or post-approval expectations?
Yeah, absolutely. I think we are in a very privileged position with the breakthrough therapy designation, which, of course, allows us access to guidance from senior FDA staff on a regular basis. But typically every six months, we are taking full advantage by having regular meetings. What this allows us to do is to continuously update the agency on the progress of our programs. The agency also wants to know we are making full use of the breakthrough therapy designation. So we regularly update them. We also then work with them to continuously streamline and adapt our clinical program. Whether that is through discussing about how to go through a rolling review process or when to submit data in what time frame or an expedited time frame. Based on that, we remain on target to deliver an NDA in 2028.
right terrific and so how then should we think about the two-dose induction period concept
versus a single dose paradigm yeah um mechanistically we believe that you know the first dose may open a period of increased psychological and neurobiological flexibility during which participants can then begin to reframe their maladaptive patterns of thought The second dose, which we gave about three weeks apart, is believed to help reinforce, deepen and consolidate that process. And we believe that the robust durability that we have seen may be related to the second dose. I mean, the phase two data clearly showed an incremental benefit from a second dose. We also, based on some limited data, saw quite extensive durability out to the 12-month mark. So we believe that a single dose may not be sufficient, and the second dose allows us to maximize the benefits of acute dosing.
Right. That's interesting. And just, you know, HLP-003 is being developed as adjunctive treatment for moderate to severe MDD rather than TRD. Can you talk to us a little bit about the differences between these disease areas and depression and your reasoning, you know, for positioning in this way? And how we should think about the, you know, ultimately the label if we're looking very far ahead, you know, from a regulatory and commercial perspective?
Yeah. I mean, treatment-resistant depression. Depression is a spectrum. And response to treatment is, again, on a spectrum, some people will respond to the first medication that they receive. Some respond to a second line. And then there is, unfortunately, a group of people who do not benefit from multiple different treatments. And these are what we normally refer to as treatment-resistant depression patients. We've, however, chosen to study patients earlier in their treatment journey. And we've also chosen to study patients in an adjunctive indication. So we don't require patients to stop their ongoing antidepressant medication. O3 is given as an adjunctive because this represents a real world population where as much as 70% of treated patients who remain on background antidepressant treatment, whether they are SSRIs or SNRIs, they do not respond adequately to treatment. So with patients not having to come up with their antidepressants, we don't have the risk of inducing what could be a very nasty withdrawal syndrome. It also will reduce friction for prescribers, you know, if approved, you know, if patients don't really need to be titrated of their background antidepressant medication. So this MDD space adjunctive represents a large addressable patient population compared to treatment resistant depression. So this basically offers us a broader commercial reach, which is why we've chosen to be in the syndication.
Yeah, that's helpful. And maybe just one last one on 003. If we look further ahead to the future, potential commercial launch, what part of Spravato's infrastructure and as well, maybe the other psychedelic treatments that may be approved before, what part of that infrastructure do you see as an advantage initially and through later stages of commercialization?
yeah i i mean we are kind of fortunate that spruvato's uh done that you know groundwork for uh interventional psychiatry this interventional psychiatry with not just spruvato clinics as ketamine clinics but also centers that offer rems ect and other interventional treatments has grown as a modality of treatment for patients with mental health condition. And, you know, in the U.S. alone, there are over 6,000 certified spruato or esketamine treatment centers. They help with, of course, the infrastructure that is established. The healthcare system is established. They potentially establish some reimbursement pathways that could be utilized by therapies like OO3. They've laid the foundation for a likely REMS program and set up specialty pharma distribution systems, which may be leveraged by us. We, of course, may reduce some of the burden with OO3 on the clinic and the patient with much fewer visits compared to Spravato. So yeah, I think we are kind of in a great situation right now with this interventional psychiatry framework having been already established by Spravato.
Right. Terrific. And then maybe moving on to HLP004 and generalized anxiety disorder or GAD, maybe you could give us some background on 004 and what you've seen in the data so far.
Yeah, so O4 is deuterated dimethyltryptamine. We've been studying this quite extensively over the past few years. We've kind of established a large body of evidence by conducting almost seven studies between ourselves and what was done formerly at Small Pharma, which we acquired a few years ago. And what we've been able to do is understand the route of administration, optimize a great patient experience. O4 is administered as an intramuscular injection with a rapidly acting or rapidly efficacious in terms of pharmacodynamic effects and short lasting duration of effect. In the work we've completed, we've done some work with generic DMT where we saw in patients with depression improvements in symptoms of anxiety, which is one of the reasons we selected generalized anxiety as our indication for HLPO4. We've conducted a study in GAD with two doses of HLPO4. We saw beneficial effects of dosing with HLPO4 at two different dose levels. We found also that the magnitude of effect was correlated with subjective effects. And we've learned quite a bit to set us up for the next stage of development with HLP04 in GED.
Terrific. And maybe you can just, you know, tell us a little bit about the expected development plan for 004. How should we think about the regulatory path from here?
Yeah, I mean, we are finalizing our plans right now, reviewing them with our scientific advisory board. We're going to come and share updates with you and externally as soon as that process is complete.
Right. Terrific. And then, you know, maybe just as a as a last question, maybe you can talk about a little bit about, you know, the cash runway for the company and which catalysts, you know, does that runway get you to? and, you know, what do you think, you know, investors may be underestimating or misinterpreting about the story at this stage? So kind of a three-part question there for the last one, just cash runway, you know, what are the expectations on cash? Which catalyst should we be looking for over the course of that runway and any sort of, you know, anything that investors
are missing? Yeah, maybe I'm not the best person to talk about money. And well, I think it will be problematic if your chief medical officer starts doing cash run with stuff. But I know you've got enough to take us well into our near term milestones, which most important of which is the top-line data on HLP03. So we've got great data coming up, hopefully. I think that data will speak for itself. And we know we are doing great on recruitment. We are going to get there before the end of this year. And once those data are out, I think we can have that conversation again. Terrific. Sounds great.
Great. Thank you so much to Amir and to Helis Pharma for joining us at the conference. Very exciting time for Helis with just, I think, a sort of a paradigm shifting readout coming later this year. So really excited for that. And thank you for everyone else for joining us at the conference. Have a great rest of your day and conference.
Thank you, Patrick. Great to be here.