Back to the Guggenheim Healthcare Innovation Conference. My name is Eddie Hickman. I am one of the biotech analysts here. I am joined today by Helus Pharma CEO, Michael Halstead. Michael, thank you so much for joining us. Been a big year for the company, lots of changes, so maybe spend a few minutes introducing yourself and telling everyone here a little bit about the company.
Sure. Thank you, Eddie, and thank you everyone for joining us today. Always excited to be here talking about Helus Pharma. The mission of the company is to improve the treatment of mental health conditions. We are currently developing novel serotonergic agonists for various mental health conditions. We have a platform of programs. Our 003 program is deuterated psilocin for the adjunctive treatment of major depressive disorder. That is in phase III. We have an upcoming readout of our first phase III trial anticipated in later this quarter. We also have a phase II program that is deuterated DMT in development for the treatment of generalized anxiety disorder. Then we have an earlier 005 program, which is a library of preclinical compounds. We think that there is potential there in a number of therapeutic areas, looking to move the lead candidate forward in that program in 2027.
A lot going on with the company. I joined as the CEO in August of this year, and really excited about both the team, all the work that has been done to date, and certainly looking forward to our readout later this quarter.
Yeah, very exciting readout coming soon. Obviously, lots of talk on exactly when the data will come, but maybe let us step back a little bit and tell us about exactly who these patients are, what the design of the trial is, and then sort of where you were when you finished enrollment and where you are in the database lock for when we should expect to see some numbers.
Sure. Importantly, this is for the adjunctive treatment of major depressive disorder. Maybe just a little bit about the disease state. MDD impacts approximately 22 million patients in the United States. Approximately 70% of those patients are on standard of care, so that's your SSRIs, your SNRIs. Of the patients on standard of care, approximately 66% are not getting adequate relief from standard of care. Often they're getting some benefit, but they need additional treatment. The way clinicians approach these patients, they have sort of two options. One is to wash the patients off of standard of care. That can be a four to six-week process, potential withdrawal there, and then start over with a monotherapy approach. Obviously, depression is a complicated disease state, so not every patient responds to monotherapy.
Often, the way clinicians treat these patients is they continue them on standard of care, and then they add a treatment on adjunctively to hopefully move that patient down the path towards remission. To date, there are only five approved adjunctive treatment options. Those are the atypical antipsychotics, and they do have some efficacy, but significant side effect burden. As we look at our 003 program as an adjunctive treatment, really excited about the potential product characteristics that we could see here. Obviously, has to play through in our upcoming phase III readout. But in phase II, saw really significant efficacy, saw durability off of two doses out to a year, and then also saw a very favorable tolerability profile, mild to moderate adverse events, primarily transitory on day of treatment, and you only have a few days of treatment.
Really think that this has the potential to provide significant patient benefit and a great option for clinicians as they're looking to treat these patients following that adjunctive approach. We completed enrollment in July. The process has been proceeding according to our plans. As I say, haven't provided any additional guidance other than we are on track for our expected data readout later this quarter. Certainly excited to get the data and excited to provide it out to the industry.
What day in July? Just kidding.
May have gotten that question once or twice.
I think a really important thing that you noted there that I want to just sort of zoom in on is the fact that these are adjunctive patients that are not required to fail a certain number of SSRIs, they're not washing off. These are patients that are on a current treatment that may be working for them. They're getting some benefit, but just not all. As we think about that, not just from the patient perspective from this upcoming trial, how should we think about what the placebo rate could be, these remission and response rates, as we compare them to something that might be in TRD or a much more sort of severe depression? Are those sort of easily comparable, or what's different about 003 in that sense?
I think that is important perspective that people do need to keep in mind. This is an adjunctive trial. As you said, every patient in the trial has to be on a stable dose of their antidepressant medications, has to have been stable dose for at least four weeks. They remain on their background therapy throughout the trial, and then 003 is then administered to show an effect on top of that standard of care. You need to look at this in the adjunctive setting. You're trying to show a benefit on top of, for a patient that has already received, is already getting some benefit from standard of care often, as opposed to a monotherapy where the patient is washed off of their antidepressant and started over.
Or the TRD patient population, which that is two or more failures on an antidepressant, very challenging patient population there.
How does that treatment paradigm work currently when there are five atypical antipsychotics approved for adjunctive, but there's also Spravato approved for TRD in these treatment centers? How do physicians think about when to add on and when to change gears?
Right. As I said, right now, their only indicated options are the atypical antipsychotics that are indicated for adjunctive use. How we think about this in the case where if we were to be approved for the adjunctive treatment, you have the potential for a clinician to have the option of not only efficacy, but then also long-term durability and a safety tolerability profile that's very favorable. If you have a patient that either is not responding to the atypical antipsychotic that's being administered adjunctively, or that patient can't tolerate the side effects because, of course, the side effect burdens for the atypical antipsychotics, very significant, weight gain, cardiometabolic, tardive dyskinesia, movement disorders, sexual dysfunction. These are significant side effects that really impact patient quality of life.
For a clinician to have the option of an adjunctive treatment with the product characteristics that we hope will translate through in our phase III program, we think could be very compelling, provide a significant patient benefit.
To confirm, that's the same patient population you looked at in phase II with this drug. Remind us what other, if any, changes besides having a larger trial for phase III, what is different about the phase III study from what you showed in phase II?
Significantly, the team really followed the trial design that worked in phase II, as I think I mentioned.
Yep.
Very significant efficacy results, durability, as well out to a year. And the team followed that formula that worked in phase III. You always like to see that, keep it as consistent as possible. The one change that I would highlight that I view as a very positive change is in the phase II trial, it was one dose administered at study start. The primary endpoint was then measured at week three. After the primary endpoint, an additional dose in the phase II was administered and saw then durability, an additional five points of improvement on terms of efficacy, but then also saw durability out to a year. Not surprisingly perhaps, in the phase III, we incorporated the two doses into the primary endpoint.
In the phase III, patients are dosed at study start, again at three weeks, and then efficacy is measured at six weeks, and then there is a secondary endpoint at 12 weeks, no additional doses, but at 12 weeks, you get that longer term durability data.
Yeah, and I think we've talked a lot about in the last six months or so about what a good expectation and a bar for success is. But I think you've articulated this several times in the last month or so, that this four to five adjunctive bar is appropriate. But beyond that, how should we think about durability in terms of how to compare? Obviously, this isn't a daily oral pill like those types of competitors. So, in reality, it might be competing with whether it's Spravato or whether it's COMP360 or one of the others. So how should we think about that difference in terms of patients needing to move to a whole another paradigm versus just another oral?
Right. First, we do believe the relevant competitive set here is the atypical antipsychotics. We believe labels are going to be very important in this space. The only labeled drugs for the adjunctive treatment of MDD are the five atypical antipsychotics. I do think you make an important point. People, of course, focus on efficacy, rightly so, but when clinicians are making prescribing decisions, of course, they look at all of the things that impact the patient, that go to not only efficacy, but then compliance, patient's quality of life. That durability off of what in the phase II, it was two doses. We will talk a little bit about our long-term EXTEND study when patients between the pivotals and the EXTEND study could potentially have a total of five doses.
Regardless, it's a small number of doses. If you see that long-term durability, obviously that's very favorable from a patient compliance perspective. Then again, the tolerability, going to the quality of life for the patient, very significant as the clinician is making prescribing decisions.
Yeah. I want to hone in on the tolerability piece, because I think oftentimes you talk about tolerability, but there's also safety,
Sure
sort of two separate things. What should we think about on the day of treatment, what kinds of sort of tolerability issues could sort of derail a great patient perspective? Then what is a safety concern that really might be super concerning for physicians thinking about moving a patient to something like this?
Right. I think the takeaway so far, certainly what we saw in the phase II, is the very favorable tolerability, and that these really were primarily transitory on day of treatment. In terms of the specifics, the adverse events, mild to moderate, we are talking about nausea, headache, elevated blood pressure. But again, transitory primarily on the day of treatment, and you only have a few days of treatment. So, certainly a favorable tolerability profile, and from a clinician perspective, and the experience in the clinic, would be hopeful that that is a very positive backdrop.
We talk about functional unblinding a lot, and we know you have a second phase III, which you can talk about in terms of adding sort of a half dose or a lower dose, maybe not an ineffective dose, but to find a dose response. Anything we can learn from this study, or we should expect in terms of what that placebo could look like in terms of the functional unblinding piece?
Sure. Placebo response has been a real challenge in drug development in the depression space for a very long time. We have seen between 10 and 12 points of placebo response is sort of what people expect with your traditional depression trial. In the psychedelic space, placebo response has been very well controlled. If you look at the late-stage trials, the larger late-stage trials, whether that is in MDD or TRD that our peers have done, you have seen between one and five points of placebo response. In our phase II, we saw approximately three points. So, it has been relatively well controlled for the psychedelic space. These are, of course, they are dosed intermittently. You raise the point of functional unblinding. Obviously, FDA has provided guidance in terms of how it would like sponsors to deal with that.
As you mentioned, having a lower dose active comparator in our EMBRACE trial, we do have three arms in that trial, so similar to APPROACH. There is, of course, the 16 mg arm, there is the placebo arm, but then in EMBRACE, there is the eight mg arm as well to serve as that active comparator, potentially show a dose response, and to further provide information in terms of functional unblinding. But again, overall, placebo response has been well controlled in the psychedelic space to date.
On the safety piece, I think there's competitor psilocybin, which is not psilocin, different compound, but maybe lumped together by many. We don't need to get too much into the biology here, but they obviously had some potential issue with suicidality. How should we think about whether that should read through from molecule to molecule, or whether that's just a secondary effect of running a depression trial?
Yeah. Unfortunately, of course, suicidality is, in some respects, a feature of depression, of the MDD population. I don't think it surprises clinicians or FDA that occasionally you do see suicidality in these trials. We obviously didn't see it in our phase II, and then our phase III trials, of course, have your standard safety data monitoring board that regularly evaluates any safety reports for signs of a signal. Obviously, we completed enrollment in the trial, and so we'll proceed from there.
Yeah. We're looking forward in the coming days or weeks to seeing those data. Beyond that, you obviously have Breakthrough Therapy Designation, so there's discussions with the FDA on what a package would look like, and you talked about EMBRACE and then EXTEND. What does your ideal NDA package look like for 003?
Right. Although everybody is, of course, focused on our first phase III APPROACH and the anticipated readout this quarter, as I mentioned, we do have a full phase III program. EMBRACE is ongoing. Have not yet provided specific guidance as to when that will read out, but we'll look to, one, to get a little more enrollment information. We'll look to provide more precise timing in the near term on the timeline for EMBRACE. From both APPROACH and EMBRACE, patients have the option to roll over into the long-term safety trial, EXTEND, and that will be 52 weeks of It's a blinded trial, so getting the highest quality data we can there. Patients roll over.
They can get up to three additional doses during that 52-week trial, so we'll get some very good durability data as well as information to inform prescribers on dosing, how often, et cetera. All that will form the basis for our NDA, which we've guided. We anticipate filing that in 2028. As you mentioned, we do have Breakthrough Therapy Designation for the program, for the molecule, so that would expect rolling submission there, so also would anticipate approval in 2028 as well. But have the full standard program to support that submission.
What do those discussions say about on the safety database? Obviously, it's unique in the sense that it's sort of an acute treatment, but you hope to be able to retreat and make it sort of a chronic treatment for certain patients. Is there a sort of a number of retreatments that they have to see or a number or a sort of safety database beyond the final treatment that they're looking for?
Our discussions with FDA have obviously led us to the guidance that we've given in terms of a 2028 submission. But I would say that I view that long-term trial, the EXTEND trial, as very significant information for the clinician.
Yeah.
Right? To be able to have that database, those results to inform prescribing decisions, I think is going to be very impactful beyond, obviously, what we need for the NDA package, but I think will be very helpful to clinicians as they move forward as well.
Great. In our last few minutes here, I want to get into the second program, 004. You had some data earlier in the year, but how is that program sort of taking shape now that you have a plan for a phase II? What changes have you made? What is the sort of key focus or key thing that you need to show in phase II to move forward?
Right. We did have a signal finding study, and maybe I should start with 004, as I mentioned earlier, is deuterated DMT, shorter-acting compound that we did a phase II. We have done a number of phase I studies and then a phase II signal finding study in GAD. The results from that gave us confidence that we should move the program forward. We just, I think at our investor day a couple weeks ago, provided details on the next phase II study, which is going to be a monotherapy study, 144 patients target. It will be 30 mgs of DMT in one arm, placebo in the other arm, and would anticipate initiating that trial in the first quarter of next year. Then once we get some enrollment information, then we will provide people with guidance as to when we would expect that trial to read out.
Why monotherapy here, and what is different about GAD from a standpoint versus adjunctive MDD?
Yeah. MDD, there are 25 or 30 monotherapy treatments approved for MDD, and there is only the five atypical antipsychotics that are approved for adjunctive. I distinguish that from GAD. GAD, about 20 million people suffering from that in the U.S. There is only five therapies approved for monotherapy. I think the last drug approval there was almost two decades ago, and there is just a significant unmet need there as a monotherapy. So we really think that our 004 program has real potential there.
Yeah. Is there anything that you hear from KOLs about this type of population and how willing they are for an intramuscular delivery, right? Because it's not an oral, it's not an intranasal or an inhaled version. It's a little bit more invasive. So I'm wondering if that's something that ever comes up in sort of thinking about this patient. I know if you have anxiety, it may be a needle in your
Yeah. So first is the significant unmet need, right? As I said, there's just a real need for safe, effective therapies.
Yep.
Remember, this is administered in a clinic. It is an IM administration, but again, would expect limited number of doses, so diminished burden from the patient perspective. They've already elected to go to the clinic, so they get the IM injection and go through the treatment. Given the potential benefits, we think that this therapy has real potential in a patient population that really needs it, where there just hasn't been any innovation in a long time.
Yeah. No, I think we can see that in competitor market caps, is that GAD is valued very highly. Final question is on the financial position. Obviously, finishing out of phase III, have a second one ongoing, and then this phase II started. So how will you capitalize and much does the burn rate look like in the next year?
Sure. I think the last financials we filed, approximately $165 million on the balance sheet, and certainly capitalized through our near-term milestones. Obviously, the APPROACH readout and then our 004 trial, the initiation there. In terms, have not provided long-term runway guidance yet. I expect to do that. I just needed to dig in a little more and get real confidence around the numbers so that whatever we do communicate, we can stand behind over the duration here. But certainly well capitalized over the near term.
Awesome. Thank you so much for being here. That's all the time we have.
Appreciate it. Thank you.