We're going to get started with our next session. I'm Andrew Tsai, Senior Biotech Analyst at Jefferies, and thanks for tuning in. It's my pleasure to have Eric So, Interim CEO of Helus, joining me. Welcome, Eric.
Thank you, Andrew. Thanks for having me. Pleasure to be here.
Why don't you give us an introduction about Helus? What are you working on? What are you trying to achieve? The milestones over the next 6- 12 months would be helpful.
Sure. Helus Pharma is what we call a novel serotonergic agonists company that's focused on mental health. Colloquially, folks have referred to it as the psychedelic space. I don't necessarily think that that's fair or 100% applicable to us because what we do that is different from some of our peers is we actually modify these compounds, through deuteration amongst other techniques, to try and change the metabolic profile of these compounds to give what we hope is benefits, like better brain penetration, durability, impact on the duration of the treatment time. We have two programs. For example, our first is in major depressive disorder. That is a big milestone coming up in Q4 of this year, where we read out our top-line phase III, our first phase III on that, which we expect to be quite transformative as far as value for the company.
There we're using a deuterated psilocin molecule, psilocin being obviously the dephosphorylated form of psilocybin. We've seen some incredible results there that have translated into longer durability, incredible remission rates north of 71%, even after 12 months. What we do with our second compound, which is focused on generalized anxiety disorder, is something called deuterated DMT. We use deuteration in that scenario to actually extend the duration of therapy for that molecule. Some may know of DMT as the active ingredient in ayahuasca. You might have seen some videos of ceremonies where people take it and they start vomiting and have a bad reaction. That's because the plasma spike that they experience is a bit extreme for them.
Through deuterating of that compound, what we're able to do is extend the window to about 90 minutes, smooth out that plasma curve, and have them have a better experience while not taking away from the therapeutic aspects. That's a phase II program. As it relates to kind of near term and longer term milestones over the next 12- 24 months, we obviously expect top-line phase III on the HLP003 MDD program, which has Breakthrough Therapy Designation. We also expect to submit NDA on that by 2028. Obviously, we'll continue the HLP004 program is a bit early stage still, but I think shows some tremendous promise as a short-acting compound in this space.
Great. Thank you for that overview. Maybe high level, maybe talk about how the regulatory environment in this space has evolved over the years and for you, at your company, what has your own experience been like with FDA so far?
The experiences with FDA have been phenomenal. We were able to get Breakthrough Therapy Designation, as I mentioned, under the Biden administration. That was further continued under the Trump administration. The access that we have at FDA is absolutely amazing. They've been very instrumental in helping us design and architect what they want to see out of these trials and have been very responsive to us. I think furthermore, what's quite interesting about the current climate is obviously we know the voucher program, the Priority Review Voucher program, came into play by the White House a couple of weeks back. Helus was one of three companies that were called out in the White House press release, specifically, which I thought was great. I think that's definitely shown a changing of the times, at least as it appears to stigma, and looking at these compounds.
Obviously, there had been a long history in stigma around the war on drugs. I think we've definitely seen progress and changes there. I can tell you that interest in this space, even by big pharma, has escalated considerably since that announcement. I do think that it's really ultimately motivated by wanting to change and transform outcomes for patients. I think there are those who would believe that it was simply a political move. I like to remind folks that that program is about companies that had achieved Breakthrough Therapy Designation, that had large unmet needs, that had companies with decent data and safety profiles. It's really about changing and shortening the administrative review of those companies post-data.
Although Helus was called out at the time in that announcement, I do think it was probably premature for us if we had gotten a voucher because you do only have two years to use it and have two phase IIIs in that time. I do think that that would be nice to have when we announce our top-line phase III. If anything, I do think it signals further underlying desires by FDA and the administration to really look at patient outcomes, which goes very well with the philosophies for Helus. The company's called Helus Pharma. It's not called Treat Us Pharma. We are ultimately engaged in transforming outcomes for patients.
Thanks. I think investors have also felt more comfortable on the commercial side of things too, commercialization with the SPRAVATO possibly being a nice proof point, doing $2 billion run rate right now. Going back to the psychedelic space, Compass could actually be approved soon. What can you leverage from the SPRAVATO infrastructure? What can you leverage from Compass's build-out?
Sure.
Anything that you envision?
Yeah. I think obviously SPRAVATO's doing tremendous things. I like to remind folks that they got to a slow start because they got started during the pandemic, obviously. At $2 billion run rate, that's a blockbuster right now. I think some distinctions and opportunities as it relates to SPRAVATO, and just so you know, one of the folks that helped architect their rollout has actually joined our company as an advisor as well. I think they gave us some great insights on learnings and advantages that we may have. Yes, there are a lot of interventional psychiatry clinics that they're currently utilizing, that they have penetration in about 5,000 or 6,000, about 8,000 that exist across the United States right now. Patients are obviously opting for it. There's REMS programs and reimbursement around it.
SPRAVATO is something that scores something around the range of a four-point difference on the MADRS point separation from baseline; it is a substance that you got to take 30-50 times a year, depending on the patient. Not a tremendous amount of durability. I do remind folks that this is for treatment-resistant depression, the commercial success definitely tells us there's an appetite to use that drug, it is significantly above the current standard of care. Furthermore, as it relates to the reimbursement, if you actually look at the $2 billion number, that works out to around 40,000, 50,000 patients that they're currently helping. In an indication like TRD, where you're looking at almost 3 million people who suffer from that, to be objective, I think we could and should be doing better.
What are some of the barriers that we've learned from SPRAVATO that stop it from helping more people? I think it's the redosing regimen there. Clinics are now inundated with patients that they're constantly redosing as opposed to treating new patients. Therein lies the opportunity, and an opportunity for Compass to step in. Although Compass, through its phase III, and just you know, we wish Compass all the best of luck, and hope that they get through, get approved, and help set the stage for this space. I think that even at 3.6 or 3.8 points, depending on the study that they're showing as far as separation is concerned, I do think the fact that there is hopefully more durability, we haven't seen evidence of a lot of tremendous durability, but we have seen signs that it is better than SPRAVATO.
I think that represents a difference that patients are willing to try and that doctors are willing to prescribe for. How does that set the stage for us? In our phase II, we saw at our primary endpoint, north of 13 points of separation from MADRS. We saw long-term durability over 12 months that saw the score and separation reach almost 23 points, which is unprecedented. That being said, of course, we're a major depressive disorder, which obviously is a $23 million, roughly, million American addressable market size in the United States, we think that there's a larger market there.
Furthermore, I think with that degree of separation, even if we were to experience a halving of our results, not saying that we will, but even if we did, like Compass saw translating their phase II to phase III, we'd still be the best drug on the market by quite a bit. Where I think our real advantage is we know that on two doses, at least in our phase II data, that we have durability of effect to around 12 months. What we have done as it relates to conversations with those clinics, those same clinics that are currently offering SPRAVATO, is they're telling us that if our drug does what we think it does, that even if they didn't have the infrastructure, they'd be willing to invest in it to offer our drug.
What they feel is that, one, on just two doses, they could obviously treat more patients and see more patients, which is very important. Second of all, with that level of durability and not having to constantly redose patients, they'd be making more money. It's very useful for folks that are offering your product to be incentivized to do so. I think one thing that Helus has always tried to do is be sensitive to the needs of patients, providers, and payers. On the patient side, efficacy, durability, definitely doing better for patients there and their outcomes. For providers, obviously, the dosing regimen, the durability are strong. We also want to highlight the fact that we are one of the only adjunctive therapies that will be coming to market. Currently, Compass and others are monotherapies. What is the impact of adjunctive?
One of the benefits of the modifications that we've done to the compound is we've seen far fewer drug-drug interactions. What does that mean? It means that it's safer to administer with background medication. One thing that we talk about at Helus is the fact that we like to test our drugs in the real world. Ultimately, if you're dealing with severely depressed patients, we feel that it's unlikely that they wouldn't be on background medication. When you think about doctors and patients and safety, a doctor may realize that perhaps antidepressants are not necessarily helping their patients a lot. At least they're not doing themselves harm. What is the impact, potentially, of titrating a patient off of drug and washing them out for three months going to do? With ours, they don't need to ask the question. It's very low friction.
They can say that there's good data behind this. It seems that the patient would experience an acute and transformative effect. We feel that it's a lot easier to offer that. From a commercialization perspective, I think that gives us a major advantage. A second advantage that we have over some of our peers is our intellectual property. Having north of 350 patent filings, of which over 100 have been granted, we have a definitive lock on dominant IP in the sector. How does that translate? It allows us to commercialize for a much longer period of time than the seven-year marketing exclusivity that some of our peers will get. We will have over double the period of time to commercialize. We're good on those until at least 2041 before any patent restoration on those periods.
I think the commercial landscape, SPRAVATO, has shown us that there is an opportunity, and I think Compass will show us that they can take advantage of that, and I feel that we will compete very well in that space.
Very clear. Thank you. phase III data in Q4, I think its primary endpoint should be six weeks long. It is two up-from-dosing. That's a little bit different from phase II, where it was a single dose out to week three as the primary endpoint. My question is, two doses should ensure and maximize the chances of getting efficacy not only at week 6 but out to week 12 and even longer, like you said earlier.
Yeah, we feel so. There will be a single dose on day one, 16 mg, and then a second dose on day 21. We feel that to a certain extent, these drugs have a certain threshold effect. We feel that at 16 mg, we have a potent drug, especially with the modifications that are made to it. We feel that giving that second dose really reinforces the durability. Obviously, these patients remain on background medications as well, so there's no interruption there. What we saw in durability was extraordinary, nothing short of extraordinary, and we hope to see similar results translate in the phase III. Even if it wasn't as long as 12 months, we have reason to believe that obviously it'll last past the primary and secondary endpoints for quite a while after that.
Great. One more time, 12-week-long study, you've guided to Q4. I guess if I did my math correctly, I think you need to maybe complete enrollment, I don't know, by September or August time. Are you on track to complete enrollment?
We are definitely on track to complete enrollment. I love doing the math. My parents would be proud of me doing math as well. I can tell you that we're very pleased. In fact, May was a banner month. We actually exceeded our forecast in May for patient recruitment. We've set ourselves up well for June with number of patients in screening. When we look at the traditional pass rate on those patients, I can say that we're doing well and expect to have a banner June. We are very confident in delivering on time.
Great. Like you mentioned, phase III is almost all the time bound to degrade from phase II. I know you showed a very strong effect size from phase II. How did you power the study exactly?
We haven't formally disclosed our powering assumptions. I didn't necessarily say invariably there will be a degrade in the results. I'd say that even if there was one.
Okay.
We're starting from a very good position. That said, even though we haven't disclosed our powering assumptions, I think we can all do some math: 220 patients, 110 in a placebo, 110 active. You can probably establish from that and extrapolate the effect size that we're going for. Let's just say we're sufficiently powered and maybe even a little overpowered.
Okay. Very good. When I look at your placebo arm from phase II, it was maybe around two, three-point reduction. In MDD, I typically think placebo behaves maybe closer to nine or 10. Maybe talk us through why you think that was the case, and where do you think the phase III placebo could trend instead of minus two points , minus three points , for instance.
Sure. I think there's some distinctions, and I think psychedelic trials in general have not been strangers to those types of placebo responses. I think the one thing that you get from patients who are taking a daily dose of an antidepressant, for example, they have that certain expectation placebo effect that they're continually taking something, so there should be an effect. I don't think we necessarily see that here because you're taking two doses, and they're sufficiently separated by three weeks. In fact, the curve that we saw in placebo response was kind of the ideal one. An initial view that something was happening, and then past the three-week point, it drifted back to where it was at baseline, whereas we saw significant separation on the active arm. I don't have reason to necessarily believe that things will be different this time around.
As it relates to the placebo effect, it's kind of interesting. I can tell you that even patients who are not on active allege that they have an experience on visual analog scale, et cetera. If anything, I think that's behaving exactly how you want to see it.
Great. When you top-line the data in Q4, would you consider sharing a cut of the open label extension that follows week 12, just to help us elucidate what the durability after two upfront doses could look like? If not, when would you consider sharing open label extension data?
That is a point, and I saw your piece this morning. That is a point of discussion for us and FDA. There are those who believe perhaps that we are a blinded long-term extension as opposed to an open label. Let's just say that we're maybe a little bit premature on that now as we get closer to data, and at least past recruitment. We may be able to share more, obviously want to do that in consultation with FDA. Obviously, we're always excited to share more if we can, but we want to be respectful of the blinding and the powering of the study.
Okay. Remind us, on safety, what you saw in phase II, anything to note? For instance, did you see signs of suicidal ideation at all in phase II?
Yeah, we did not see any of that in phase II. It was extraordinarily safe and well-tolerated. Any AEs at all, which related to, let's say, blood pressure, which might have increased, not to the point of a brisk walk, let's say, all subsided after treatment. That said, suicidal ideation is not an uncommon thing to MDD or TRD trials. Compass has dealt with that to a certain extent. We don't expect to see anything terrible in this trial and would expect these to continue to be well tolerated and safe in patients.
Great. What is the total monitoring time for your program? I believe Compass psilocybin is around six hours. I'm just curious how long.
Obviously, as it relates to trial design, we err on the side of caution. As it relates to monitoring, I think this will change in the universe of practice. I can tell you we reach peak effects in about 90 minutes, and then there's two-hour monitoring post that. In a four to six-hour window, I think is not unreasonable. We'll see that at least in the phase III, subject obviously to modification in practice. I do think that FDA is receptive in some of the suggestions that they've had as it relates to monitoring and session monitors. It's probably guided by some other experiences, like with potentially some other companies, like Lykos, for example, that are not applicable in our situation.
I see. Can you describe the treatment journey for the patient that day? Is there any preparation involved before they dose, integration after they dose, b ecause I ask because other companies.
Sure.
Might be employing that?
Yeah. We want to make it very clear that we have measured drug effect here. We're not doing any form of psychotherapy or psychedelic talk therapy or anything like that. We have our program, EMBARK, which is done to ensure that the patient is prepared for the experience, not unlike what an oncologist would tell somebody before they're going for chemotherapy. There is no active therapy during the session. It's an experience where they wear a blindfold and have headphones on. It is an internal experience to the patient.
Great. The second phase III also has started. When is the data, in your view?
Yeah. We launched that earlier this year, and that continues to recruit as well and do well. Like I said, we've guided to NDA submission in 2028 and approval in 2028, because we also have rolling review via virtue of our Breakthrough Therapy Designation. The precise timing of the end of the second phase III, it kind of depends on recruitment, et cetera, but we are still maintaining target on 2028 NDA approval.
Okay. Thank you. In the second phase III, it's actually two drug arms versus placebo, 16 mg and 8 mg. Do you expect 8 mg to do something in between?
Yeah. Just to be clear, in that second phase III study, we have three- arms: placebo, 8 mg, 16 mg. The trial wasn't designed to power to show separation between 8 mg and 16 mg, but what the purpose around that behind is to kind of address FDA's, how should I say, inherent desire to give as low a dose as humanly possible. Now, we obviously know that this is safe and tolerable at 16 mg. I think if anything, if the 8 mg shows some degree of efficacy, that simply gives doctors more options potentially to prescribe a range potentially on the label. We'll see what happens there.
I think obviously the key is that first phase III, where we see or hope to see significant separation and material separation from baseline, which I think obviously sets up our thesis around how we believe this drug is a good one and better than most.
Okay. Very good. Speaking of the label, should your compound be approved, what do you think is the dosing protocol going to read? Or what are you hoping? Does two times upfront, retreat as needed after 12 weeks? Or is there something different?
Obviously, that is still premature. We'll see, we haven't even completed the first phase III yet, so we'll have to see what FDA says about that as well and what we see there. What we hope would be something along the lines of adjunctive MDD and two doses, either 8 mg- 16 mg or 16 mg and 16 mg. We'll see what the durability shows us in the studies, and what other potential label claims we could make.
Yeah. In terms of the staffing requirement in your clinical studies, can you describe how many people are monitoring?
Are they monitoring in person? Can they monitor remotely? Will that be different in the real world?
Yeah. Again, we've done this in accordance with FDA guidelines for our phase III study. We have two monitors, one in person, one remote. Again, perhaps some of this was guided by what we saw in some other companies' trials. At least that's what we currently have in place. Could that change in practice in the future? Absolutely. I think, given the fact that this is, like you said, a kind of inward experience, doesn't require any talk therapy during, it would be possible to potentially monitor several patients simultaneously, and it could very well transform how care is deployed. I often tell people that what's important is patient outcomes. There's a difference between health span and lifespan. Over the last 20 years, we've probably figured out ways to make people live longer or at least stop them from dying.
We haven't necessarily explored ways to improve their quality of life, and that's ultimately what we want to do here. If that means a paradigm-shifting drug or treatment, and that necessitates a paradigm-shifting change in how we deliver that care, it's ultimately the outcomes that we're guided by and what we're motivated to achieve.
Mm-hmm. Have you by chance done some payer work around this, your program? There's the drug reimbursement and the monitoring reimbursement.
On the monitoring side, what is your best understanding on reimbursement? Will payers reimburse for the entire four to six hours for your program, and why?
Yeah. I think, obviously, CPT codes exist already. We've seen them used in SPRAVATO. I think they currently contemplate at least one hour of initial coverage. I think I see a paradigm where you'd see a stacking of those potentially to reimburse for the whole session. Obviously, what we've seen in the case of SPRAVATO is that it is reimbursed, and they have a number, up to, like I said, 30 - 50 treatments a year, and that two hours is reimbursed. I don't see a reason why a therapy and drug that ultimately involves less patient time in the chair over the course of a year wouldn't be similarly reimbursed. Obviously, we'll see what happens with FDA, and we have folks like Compass, as you say, and like I said, we appreciate everything they do because they kind of pave the way.
Then we can take advantage of the learnings there to access the market as quickly as we can.
Okay, great. Maybe one question on your other program, HLP004.
Your deuterated DMT program that reported phase II data earlier this year. What are the next steps for this exactly? Is all your focus going to be in MDD in the meantime, kind of thing?
Yeah. Clearly, our focus here is the HLP003 program and that data readout in Q4, which we feel will be a transformative event for the company. HLP004 is a great compound, and we feel that it could very well be one of the greatest short-acting compounds out there. What we saw in our phase II was obviously signs of efficacy and durability. Do we have to do more work on the dosing side of things? Absolutely. What we want to do is be responsible about the capital that we have and be responsible to shareholders, and they expect us to deliver and execute on HLP003, which includes EMBRACE as well as APPROACH. Obviously, we don't want to skip a step or a beat on the second phase III.
That said, it is responsible for us to also examine the HLP004 program and what can be done there. I can tell you with that scientific advisory committee and board that we have and all the smart people that we have at our disposal, that we will be examining a design to bring that forward as well in a fiscally responsible way, while also at the same time respecting the timelines and the ability to capitalize on the market. Also, say that you will be hearing from us soon on that. Maybe that's a teaser for a movie or something like that.
The best is yet to come. I think we have a great year ahead of us, especially with HLP003, as well as potentially some further insights on HLP004.
Okay. Well, thank you, Eric, for sharing all the updates, and best of luck on the data readout later this year.
Thank you so much, Andrew. It's been a real pleasure being here. Thank you.
Thanks.