Good morning, everyone, and thank you for taking the time today. I'm [uncertain] , CEO of Healis, and we're here today to discuss the results from our most recent Phase II signal detection study in Generalized Anxiety Disorder. Just a quick platform overview. As many of you know, we have two proprietary clinical programs, CYB003 and CYB004 in major depressive disorder and GAD with positive Phase II data. Our lead program, CYB003, has been granted FDA Breakthrough Therapy status and is in Phase III for adjunctive treatment of MDD. We have a differentiated platform with potential to expand in additional indications affecting a lot of people in the United States with a very high unmet need. We also benefit from strong IP with over 350 filed patents, 100 of which are already granted.
As I mentioned, our pipeline consists of two late-stage clinical development programs in CYB003 and CYB004. Importantly, we have a major catalyst upcoming in Q4 this year with the APPROACH top line data, our first phase III trial in MDD. Today, we'll discuss our top-line data in CYB004 in Generalized Anxiety Disorder. Let's get right into the CYB004 data. We believe we have an emerging best-in-class profile with CYB004. We're going to walk you through data from the phase I in healthy volunteers and also the phase II results in patients with moderate to severe GAD. We've had a very good outcome in both studies. In the phase II, we show a clinically meaningful 10-point reduction in HAM-A at 6 weeks, and we see that quite rapidly by day two.
It's really imperative that you understand this was done on top of standard of care in moderate to severe GAD. These patients are already on pharmacotherapy. They're partial responders, it's notoriously difficult to move the needle with them. These patients in our study, on average, had been diagnosed with GAD more than 10 years ago and are not in remission. These are very difficult patients to move the needle on, we have shown a significant signal in this patient population. We had great durability in this trial through at least six months with approximately 70% response and 40% remission rates. We also have a favorable AE profile, which is transient and mild to moderate AEs with no drug-related SAEs or suicidality. We also have a discharge readiness by 3 hours based on our phase I data with acute effects lasting around 90 minutes.
Of course, based on our ability to design novel compounds, we have composition of matter through 2041. This allows us to invest in molecules in a significant way over time. The company has a history with DMT. Seven trials now over a very long period. This is the first time this molecule in this formulation, deuterated intramuscular, DMT, has been in humans, and we'll walk you through that data. Needless to say, we've built up quite an institutional knowledge from all seven studies. The two studies you're about to see were run in parallel, which is a bit unusual. The PK profile here underscores what the company has been able to do by taking DMT and engineering it, so it has strong drug-like properties.
I wanna take a minute to emphasize this is the capability the company has that we have shown repeatedly that we can execute against. On the right-hand side, you see two lines. That first dark line is IV DMT. You see it has a spiky PK profile. The rapid on, rapid off is, generally speaking, not optimal for psych drugs. It leads to many AEs and, in some cases, craving and addiction. You will see what the company has been able to do through deuteration and formulation. You see a blunted Cmax, a shifted Tmax to the right, and a larger Area Under the Curve, exactly what we were aiming for. This is what a real drug looks like. I point this out because the company has been able to do this repeatedly. This is the second time.
Our pipeline molecules behind us are all similar in that they exhibit drug-like properties. In this particular case, the idea was to still have a rapid peak, but also have it last for 60-90 minutes to have a favorable experience for the patient, meaning that the patient would have time to actually do the psychological work through emotional breakthroughs or a mystical experience. We think this is a winner, and we'll show you why in the next slide. Here we have the phase I data on CYB004, which exhibits linear, predictable, and reproducible pharmacokinetics and pharmacodynamics. On the left side, you have the PK curves. You see this wonderful dose proportionality in plasma concentrations, exactly what we were looking for in the profile of this drug. The rapid onset, the longer time to Cmax, and the increased Area Under the Curve.
On the right-hand side, you see one of our important pharmacodynamic measures, which is the Emotional Breakthrough Inventory or EBI. EBI is a measure of whether the patient had an emotional breakthrough during therapy. We use it as a potential predictor of therapeutic response. Importantly, in our Phase II signal detection study in GAD, we saw correlations between EBI scores and HAM-A. We set a cutoff at 60% or more on EBI to ascertain a robust emotional response, which is what this chart on the right is showing you in healthy volunteers. What you see across the dose ranges is a dose response, but you don't see a great difference between 2 and 20 milligrams. Recall these studies were the first time this molecule in this formulation was in humans, and the drug at both those levels did result in meaningful effects.
You do see a difference between placebo 2 and 20, which is worth keeping in mind as we go through our phase II data. As I said earlier, we have the potential for rapid discharge by three hours. This is based on a Readiness for Discharge Questionnaire in the phase I study. We think commercially this is very important as it fits within the existing SPRAVATO interventional psychiatry clinical workflows. Now moving to our phase II top line data in GAD. As many of you know, there's been a high patient burden and a real unmet need in GAD as there have been very few therapies over the years. There's now over 20 million GAD patients in the U.S., and the majority of those patients are poorly served.
Two-thirds of them experience no relief on it initially on standard of care, about 60% of the patients with anxiety do not adhere to their therapy because of side effects. The average time to discontinuation is quite rapid at 90 days due to the safety and efficacy issues. The last approved drug was Cymbalta as monotherapy in 2007. Importantly, no approved adjunctive therapy treatment exists to date because it's very hard to show a signal in these patients. Keep that in mind as we go through our data. This is the design of our Phase II signal detection study, which was double-blinded. O-four was administered adjunctively on top of standard of care in 36 patients with moderate to severe GAD.
There was two to one randomization between 20 milligrams and 2 milligrams. Our primary endpoint at 6 weeks was change in baseline from HAM-A, with our secondary endpoint at 12. The study also has observational follow-up after the 12 weeks for up to one year. We do not have all that data quite yet. We will share what we have collected so far. It was designed as a signal detection study. It was not powered to show separation between the two doses. As I said earlier, it was designed to mimic real-world treatment paradigm because in fact, we wanna know this drug is going to work commercially for patients. These are our baseline patient characteristics. I'll just point you to the HAM-A at baseline, which is approximately 22.
These were moderate to severe patients, again, on standard of care that are quite difficult to move as they are partial responders. The reality is no one's been able to move them and there are no approved adjunctive therapies as I stated before. This is our AE profile where both doses were well tolerated. Adverse events were transient with no drug-related serious AEs. Two milligrams did record fewer psychiatric AEs. Looking across the data coming out of these studies, these patients still had meaningful subjective experiences on two milligrams. CYB004 demonstrated a rapid and profound effect on top of standard care. We saw great durability through six months. On the left-hand side, you have the six-week data. You see this rapid onset of effect on the left-hand side. There's a large drop in HAM-A for both two and 20 milligrams.
You see that again after the second dose on day 22. At our primary endpoint, as we said, we have this very nice effect of 10 points on the HAM-A in difficult to treat patients, all on top of standard of care. Again, as a reminder, we were not powered to show separation. On the right-hand side, you see the durability of this effect, the blue box being the treatment period. When you get out to both 6 weeks and 12 weeks and 24 weeks, you see a sustained reduction in HAM-A. This is not like placebo, which generally after the treatment period begins to drift back to baseline. A great outcome here from a durability perspective as well. The reductions in HAM-A resulted in an excellent response and remission rate at both 6 weeks and 6 months.
On the left-hand side, you see the 20 milligram and 2 milligram doses split out, and you see a significant response and remission rate. Those responses and remission rates held up in a pooled analysis through six months with nearly 70% responders and 40% remitters. We do also have some patients who have made it to one year. There are five, four of whom are remitters with an average HAM-A score of four, which is very promising, although early. Again, no observed regressions at baseline like placebo. Just for comparison, to put this in context, this is a meta-analysis. Just a health warning here. You know, these are studies that were run separately, and we did aggregate them as a meta-analysis into a monotherapy average.
On the left-hand side, you see the monotherapies that have been approved over the last 40 years, an average, then you see the average for those monotherapies. You see a relatively high placebo rate of 8.6, then an average placebo-subtracted monotherapy drug effect of 3.4. The ability to actually show a signal on top of that standard of care of 10.4, we think is remarkable. This signal gives us confidence that we can move forward with the program. We believe this profile translates into an emerging best-in-class profile as a short-acting treatment for psychiatric conditions, particularly GAD. We have acute effects that last only 90 minutes, which allow for a rapid discharge by three hours. We think it fits well within the current interventional psychiatry model, which is a real advantage commercially.
It's a single treatment cycle, two doses, three weeks apart, instead of chronic dosing like SOC with AEs that are transient and mild. We also have tremendous durability out to six months and probably beyond. Importantly, we've trialed this drug in a real-world population that's already on standard of care, and those are the type of patients that will actually be coming into the clinic. Of course, we have excellent intellectual property through 2041. In summary, at Cybin, we've shown two positive Phase programs that are now in late-stage development in very large markets, MDD and GAD. We have catalysts coming, including the CYB003 program, for which the APPROACH Phase III top line data is expected at the end of the year.
We have great IP with over 350 filed patents, many of which are granted, and the trials to date have yielded compelling results that we believe have the potential to help many patients. We look forward to updating you on both of these programs over the course of the year. Thank you.