Hi. Hello, everyone. Welcome back. Thank you very much for staying with us. Our next presenter is Doug Drysdale, CEO of Cybin. They are working on a deuterated, oral deuterated psilocybin for major depressive disorder. They're gonna start a phase III trial second half of this year. It's a massive market, and they also have an IV deuterated DMT for generalized anxiety disorder in phase II a in 2024.
Doug, thank you very much for joining us this afternoon. I very much appreciate it. If you'd be so kind, if you give their, give our listeners a little background on yourself, a little background on Cybin, and then we'll go into walking through the programs.
Sounds good, Jim, and thanks for having us on today. Much appreciated. Look, my background, I've spent over 30 years building drug development companies of some form or other. This is my fourth time in the CEO seat, and about four years now, a little over four years at Cybin.
In that time, we've gone from inception to about to start phase III, so that's pretty rapid, considering how long it normally takes to develop drugs. We've also, in that time, taken the company public. We've completed two acquisitions, one in the U.K. and one in the U.S. w e've built a really extensive IP estate as well, with more than 50 patents granted and still 170 patents pending.
This is really a testament to the team that we've built. It's a team of very experienced drug developers that have managed more than 60 INDs with the FDA and have had over 37 exits. P retty good track record of creating value for themselves and for, and for shareholders as well. You know, we've got-
A good job on the phase IIIs or the phase I/II trials as well.
I think we're very excited about those results. You know, what we've been focusing on is what I would describe as interventional psychiatry, specifically depression and anxiety disorders. These are modified versions of classical psychedelic drugs. We've developed a deuterated version or deuterated analogue of psilocybin and a deuterated version of DMT.
You know, the goal there has been to optimize the pharmacokinetics without changing the underlying pharmacology. And what we see from these molecules is really rapid effects on symptoms within a day, rather than, say, six weeks that it takes for current treatments, which is why we're calling them interventional, because it works so quickly. N ot only that, we're seeing very durable effects as well. B enefits lasting for months at a time from just one or two doses.
This really is a potential paradigm shift in the way we treat these behavioral health conditions.
Our last presenter was working on non-opioid sodium channel for opioids. Opioids are very effective, but they have their side effects. Walk us through psilocybin and DMT. They're very effective, but also side effects to keep an eye on.
From a side effect point of view, from CYB003, deuterated psilocybin analogue, it's very well tolerated. Of course, we'll only be dosing this two to four times a year, so the opportunity for side effects is much reduced compared to chronic treatments. E ven within those dosing sessions, we see no serious adverse events at all, just mild to moderate transient side effects.
A very well-tolerated safety profile. Our deuterated analogue is not a prodrug. We've removed the metabolic step, and that's also removed some of the interpatient variability. As I mentioned, we're about to start phase III in depression this summer, based on some phase II results that were frankly quite remarkable.
In the phase II program, we gave just two doses of CYB003, three weeks apart, and we gave those to a group of severely depressed patients. We were recruiting moderate to severe depressed patients, but the group we ended up treating were severely depressed. We saw, after just two doses, 75% of those patients in remission from their depression, which is unlike anything that's approved today.
R emarkably, when we followed up four months later, we still had 75% of patients in remission. Very exciting. We're continuing to follow up with these patients. We're hoping to see continued long-term, durable efficacy, as we follow up over the next several months. phase III starting this summer.
The first study, U.S. site, site recruitment is pretty much complete at this point, and I'd expect that we would have top-line data read out within 18-24 months for CYB003. Then the second program, CYB004, is a deuterated version of DMT, and here we've taken a molecule that is typically very, very short-acting, you know, 5-10 minutes, and we tried to extend the time of the time after peak.
W e've developed an intramuscular formulation. We get patients up into peak DMT space very rapidly, and then once they get past that, the tail is where the extension really happens and is where the psychological work seems to happen. T his has resulted. We've run five studies so far across DMT and deuterated DMT.
We know a lot about PK/PD. We know a lot about the dosing needed, formulation, and route of administration. T his intramuscular formulation is giving us about a 90-minute experience, so very scalable, fits really well into the current sort of esketamine infrastructure that exists today. W e've got, of course, positive proof of concept data, phase II data in MDD and anxiety symptoms with non-deuterated DMT.
T hat gives us a lot of confidence in this program, phase II program. T he phase II study for CYB004 is underway. We're studying patients with generalized anxiety disorder. We see that as a gateway to all of the anxiety disorders, which affect 18 or 19% of the population, so the most prevalent set of mental health disorders.
Top line safety and efficacy data for CYB004 around year-end 2024.
Let's go back to CYB003, the psilocybin, if we could. I was talking with someone else about the data you'd put out, the psilocybin data, the early data, the three, I think the three-week data in last October. In the note, someone, they were saying, "Oh, that's only short-term data." Then the four-month data came out looking as good, if not better, than the three-week data. Can you walk the listeners through how you guys sort of cracked that nut?
The three-week data, it was very impressive. We saw a 14-point reduction in MADRS score from a single dose, measured at three weeks, compared to placebo. H ighly statistically significant. Our theory from the outset, though, was that two doses would not only be more effective, but would lead to more durable effects.
W e've seen with regular psilocybin, single dose, effects that wear off after four or six weeks or so, or begin to regress in any case. Y ou know, in talking to payers, in talking to providers, you know, onset of effect is important, but durability is more important, durability of effect. W e gave two doses. The second dose was three weeks after the first dose, and with the second dose, we saw an incremental improvement in symptoms.
We had 14 points compared to placebo, from the first dose, actually 17 points from baseline. And with the second dose, we reduced again by another five or six points, so an incremental benefit from the second dose. But then, as you said.
Well, the real benefit is looking at durability of effect, and as we look out over four months, that 22-point reduction or so that we're seeing with two doses is sustained over four months. Essentially, with both doses, 12 mg and 16 mg, those MADRS scores are flat. They're not regressing at all. W e're hopeful, and we're confident that we'll at least have benefits to at least six months.
This could be a dosing regimen that's perhaps twice a year or maybe less frequent than that, which is obviously quite a big change from the way we treat depression today.
How would you, could you lay out sort of the expectations for design for the phase three trial? How similar to the phase two, phase one slash two?
Two studies. The first one will be very similar to the phase II study, and that will be comparing two active doses of CYB003 to two doses of placebo, and with a primary endpoint at six weeks. Like in the phase II, these will be moderate to severe patients with MDD, and they'll also be on stable doses of background antidepressants, SSRIs, SNRIs.
W e're positioning CYB003 as an adjunctive therapy, so patients don't have, and providers don't have to go through the sometimes challenging process of titrating off their background treatments. T hat'll begin in the summer. The second study, as the FDA wishes, has a design. So really similar to the first study, except there's a mid dose.
That we'll have our active dose, a mid dose, and then a placebo dose across three arms. Again, two doses, I mean, the active, the mid, and the placebo with a primary endpoint at six weeks. Then from each of these two phase III studies, patients will roll over into a long-term extension, and we'll follow up patients for up to a year after that.
Of course, that'll allow us time to look at relapse rates and re-dosing, net requirements over the course of a year. That'll give us really a lot of information on what the dosing schedule should look like in the real world.
On the two phase IIIs, I think the phase I/II you started it somewhere mid-2023, your data the end of mid- to end of 2024, or start of 2024, excuse me. Is that how long relatively you think the phase IIIs will be from start to finish the data? Will you run them concurrently, or will you run them back to back?
They'll be slightly staggered, so, three to six months between them. Just logistically, obviously, we're gonna have to recruit a number of additional sites for the second program. T hat'll take a little bit of time to do that. 18 to 24 months for each of those studies, 24 months at the conservative end of things. You know, our CROs always like to be conservative.
As you say, in the phase II, we were really quite fast with recruiting. One of the benefits here with our patient population is, one, it's MDD patients, not TRD, so it's a larger population, a less challenging population. And then we're also not asking patients to come off their background medications, and the time, of course, it takes to do that.
It's sometimes difficult to get patients to come off of their background treatment if they think they're getting a placebo or a chance of getting a placebo in the study. A llowing them to stay on their stable doses, I think, will help with recruitment. 18 to 24 months, we should have top-line data from the first study, sort of early to mid-2026.
The phase IIa in deuterated DMT, you said GAD underway, data? They said by the end of this year, potentially, and then a phase III, perhaps, first half, mid next?
The study's underway. We're using the same sites that we used for our CYB003 phase II, so they're experienced, and, we're obviously very happy with them. Their recruitment last time was pretty rapid. But still expect data around year-end, and of course, then we'll take that to FDA, have our end of phase II meeting, following that, and then move into a phase III sometime next year.
You're running, you ran some good data on the IV and IM SPL028 data. Will you run the uncertain to try to get to an IM dosing, or is IV the best way to go?
No, we're going straight to IM, straight to intramuscular. I mean, IV is quite challenging. It takes a higher trained level of staffing. IV infusion requires a special pump and equipment and a technician to manage it. So that's difficult for these behavioral health centers or psychiatry centers, where they just don't have that kind of equipment or staff.
W e're moving to an IM dose in this phase II study. That should be like a simple shot in the arm, like a flu shot. Pretty easy to give. You know, technicians in CVS can do that. T here's a lower level of training and skills required, and it gets people into that DMT space very rapidly.
Walk us through a little big picture. These are obviously drugs of these drugs have got a history. All drugs have history, these in particular. Walk the listeners through sort of how you navigate that part. I know that the cannabis space went through it years ago and successfully come through. Do you think that's an example for psilocybin and DMT to follow?
Well, I think the cannabis space, in many ways, is an example of what not to do in the sense that, by going mainstream and retail now, it's sort of removed a lot of the incentive or motivation to develop cannabinoids into pharmaceuticals, into drugs. I don't see things going that way with psychedelics. You know, what we've seen here is FDA being really quite supportive with a number of breakthrough therapy designations being granted.
I don't see that there's a huge level of motivation for politicians and policymakers to suddenly reschedule psychedelics ahead of having any, you know, safety and efficacy data. W e have a pretty well-defined pathway through FDA, good, clear guidance from them on clinical design. We've had our end of phase II meetings, so we know what they want.
Our breakthrough therapy designation allows us to be more collaborative and ask more questions and get buy-in from FDA along the way. W hen we do get to the point of proving these treatments are safe and efficacious, then DEA is obligated to reschedule. I don't see this going down the same path as cannabis because there's no real motivation to make that change outside of, you know, the FDA pathway.
I'll say that I think over the last several years, much of the stigma around these treatments, the misinformation that's happened in the 1970s or has started to fade away. In mainstream circles, I hear people talking about psychedelics for mental health. I think in the psychiatric community, there's strong acceptance that these molecules have efficacy. I think in the investor community, there's been... it's been accepted for quite a while that these treatments work.
Now I think what we're seeing is investors getting more excited by the commercial potential. I think the commercialization pathway was a little unclear to some investors, but seeing the infrastructure build around Esketamine, and not only the infrastructure now with 3,500 centers around the country, but a clear reimbursement pathway, and excitement from payers, you know, I think that's removed, I think, the last perceived hurdle from investors, which is why we've seen some very large fundraising happened in the last several months.
Well, no doubt. We always like to wrap up. Actually, before we go to the wrap up, we've got about five minutes. Would you care to talk about your preclinical candidates now? You certainly got plenty on your plate to handle with the two phase IIs and phase IIIs.
We do. Obviously, scaling from phase II to a large phase III program takes a lot, so that's really the focus. And we do have some preclinical candidates, but I would say that our priority is likely to be additional indications, right?
U nlike many other molecules that it may work for one or two different disease states, we've seen evidence that these treatments can work in a whole range of additional indications. W e don't necessarily need to go and develop more interventional psychiatry treatments when we can add additional indications to the current programs. That said, we do have a continuing preclinical effort.
It's been largely focused around a group of phenethylamines, where we had a very large paper recently published in the Journal of Medicinal Chemistry that outlines and characterizes a range of phenethylamines. These are molecules that are somewhat related to MDMA. We've chosen those that are less amphetamine-like and more tryptamine-like, and we've been looking at their activity at lower doses, at chronic doses, or sort of intermittent dosing levels.
We see some indication that there might be benefit from these molecules in a number of neurological conditions, so potentially neuropathic pain or Parkinson's disease or MS or Alzheimer's. We've got a way to go before we can make those determinations and select a candidate and select an indication.
Very exciting stuff that I think is, not necessarily within our wheelhouse of psychiatry, but something that we'd be excited to partner with another company on in terms of looking at these neurodegenerative disorders.
We're getting towards the end of our 20 minutes. I'd like to wrap with a balance sheet discussion. You guys are in an enviable position for a smaller cap, well, not small, some companies out there, smaller cap, with the recent raise. Can you walk through sort of your cash position and where that gets you to currently, and your thoughts on that going forward?
Sure. W e're wrapping up our quarterly financials as we speak, so we'll be releasing those in the next few weeks. As you say, though, we clearly have a healthy balance sheet. We raised $150 million in March of this year, and we haven't even sort of begun the larger studies yet, so we're obviously well-capitalized. C ertainly enough to get us through this phase III study I mentioned, and the phase II study for GAD as well. P lenty of cash on the balance sheet for now, and some exciting milestones coming up in just a few months.
Well, Doug, thank you very much for your generosity with your time this afternoon. I very much appreciate you walking our listeners through the story. Thank you very much.
Thanks for having us, Jim, and thanks to AGP.