Thank you for joining the H.C. 2024. My name is Joshua Corson, and I'm an H.C. Wainwright Equity Research Associate. So today, I would like to introduce our presenter, Conley Chee, who is the President and CEO of Syros Pharmaceuticals, which specializes in the development of small molecule medicines to control gene expression in patients with blood disorders. The floor is yours.
Thanks, Josh, and thanks, Wainwright, for the opportunity to share our story. As Josh mentioned, my name is Conley Chee. I'm the CEO of Syros Pharmaceuticals. This is not working. Can we go to the next slide? The next slide says, forward-looking statements. Do I point at something? Might be a battery issue. Doesn't look like there's- Change the batteries. The light's not on, so- The green? The green. No, there's no light. Maybe it's off. No, on the side of the clicker. It's on. But that might not work. Should I just keep going? I'll just turn it off and on and see what happens. No. Maybe we have to get rid of the OK portion of that. How about I start, and we'll see where we go without slides? How's that? All right, so forward-looking statements will be made during this presentation.
A full list is not shown on the screen and can be found on our website as well. And so the story of Syros started about eleven years ago, and we took what we thought was a relatively interesting and novel approach. Rather than trying to treat cancer by focusing on targeted mutations that affected gene disruption or gene dysregulation, we focused on the non-coded portion of the genome, the portion that we felt actually regulated the expression of genes. And so with all of that work, a discovery was made, which is now well known as super enhancers. And over the past eleven years, we've built our portfolio around this concept, having now three programs. First is a phase II-ready CDK7 oral therapy, which we feel could be best in class.
We also have an oral phase III ATO or arsenic trioxide program that could really benefit APL patients. But the program that everyone... Oh, thank you. Okay, you guys can't see this, but at least I'll cheat. The program that everyone wants to talk about is actually our lead program, which is tamibarotene. It is interesting for a few reasons. One is that it has a fairly novel mechanism of action. It's a RARA agonist, and I'll explain more in a minute what that is. It's currently being developed in a pivotal phase III in high-risk MDS. And now, high-risk MDS is an area of great unmet need. There's roughly 18,500 patients in the U.S. and in Europe that are diagnosed annually, and there hasn't been a treatment in decades.
And so, upon successful data, we really could be a first to market for this, this really large group of patients that hasn't really seen any innovation for decades. We've assembled a tremendous leadership team with deep experience in terms of both developing this type of programs as well as launching in the U.S., and so we're gearing up for that as well. All right, so again, you can't see this, but the timing of our pivotal is really important. This is Q4 of this year, so we're talking about weeks away, in which we'll read out the primary endpoint in this pivotal trial, which is our CR.
Again, upon positive data, we plan to fully launch this ourselves in the U.S., file for an NDA, obviously, and we're gearing up to do that, and I can talk a little bit more about that, as we progress. Maybe a few words on high-risk MDS. First, again, great unmet need, 18,500 patients, in the U.S. and in Europe, and these are, elderly patients that are actually treated in the community. It's a dysregulation or a sort of a disorder of the bone marrow that doesn't allow for normal maturation and differentiation of the red cells, white cells, and the platelets. And so what happens is these patients, suffer mortality and morbidity. It's quite a poor prognosis.
And the current treatment is, again, azacitidine, which is a hypomethylating agent, and it has a CR rate currently of 17%. And most of these patients don't live past a year and a half, and so we need to do better for these patients. And this is where sort of tamibarotene comes in. And so the mechanism, and it's really hard to describe without a slide, but I'm gonna try. Imagine in the normal process, you have retinoic acid attached to RARA, which is retinoic acid receptor alpha, right? They attach, normalize, the myeloid cells differentiate and mature into all of these lines of cells. In RARA overexpression, there's many more of these RARAs. Now, there's not enough retinoic acid to attach and drive normal progression, and so what happens is these extra RARA cells, they're not inert.
They actually stop the progression of this normal process. Tamibarotene comes in, and it's a little counterintuitive, but it's an agonist. It attaches to the extra RARAs, normalizes the process, and drives everything forward. And what we found in higher-risk MDS is that there's 50% of patients that have this overexpression. And so coming from a person that's launched many targeted therapies, some of which are quite rare, it's often hard to sort of convince physicians to hunt for that needle in the haystack, if you will, in terms of a targeted therapy, and this is where some of these therapies have stumbled in the past. What we see here is a 50% positivity rate, and so a majority of their patients will have this RARA overexpression.
And if we can offer a highly efficacious drug that's also quite manageable from an adverse events profile, I think it's a very compelling argument for physicians. Just to go through the efficacy of what we've seen so far. We've tested tamibarotene as a single agent in relapse refractory HR-MDS, and what we saw was a 60% hematologic response rate, and we even had one patient have a sustained marrow CR in that single agent. We've also tested it in AML, and this is where there's a bit of a continuum of disease because what happens with patients with MDS is many of them will progress to AML, almost half of them, and so it's a continuation of disease. We tested tamibarotene plus azacitidine, which is the doublet that we're going to test currently in our pivotal trial.
We utilized that in AML, and what we saw was a 67% CR/CRI rate or a 50% CR rate. We then looked at the subset of patients in AML that had what we call low blast count, so 20%-30% low blasts. These are very similar to high-risk MDS patients. In fact, years ago, they used to be called high-risk MDS patients, and there was a recategorization. What we saw in this group was a 67% CR rate. And when you think about the bar that we're trying to overcome in high-risk MDS, azacitidine alone is 17% CR rate, so there's quite a delta there. As well, we saw an 87% CR rate overall. Sorry, 89% of the CRs also had deep molecular and cytogenetic CRs in this group.
The responses were irrespective of mutation or cytogenetic risk. That's a question we get a lot, and 72% of patients had transfusion independence. Also, to note is we have a very fast-acting doublet here in that most of the responses we've seen, the median response time is 1.2 months, so just over a cycle. It's equally important, other than the efficacy, is actually the adverse event profile of tamibarotene. This drug has been utilized in over 1,000 patients in Japan for APL. We've now tested it as a single agent and a doublet with azacitidine, and we've actually utilized it as a triplet with venetoclax, azacitidine, and tamibarotene.
In all of these cases, what we saw were highly manageable adverse events and actually no additive events, particularly around myelosuppression, which is really important with this group of patients. Again, these patients are elderly, but they're being treated in the community, so an oral therapy that's easily manageable would be of high value in this patient group. All right, let me describe the phase III trial design. It's a placebo-controlled, double-blinded, randomized two to one, azacitidine plus tamibarotene versus azacitidine. A global trial, 120 sites, 13 countries, with the primary endpoint of being CR. The trial progresses to OS at 550 patients, but the CR is our primary endpoint, and that's what we'll read out in Q4 or mid-Q4 of this year.
If it's positive, what we've had discussions with FDA, and they've confirmed on multiple occasions, is that a CR with supportive duration, and of course, safety, is sufficient for review of approval, either a full approval or accelerated approval, so that's really important. Also to note, the CR endpoint is over 90% powered. Again, this design is really, in the FDA's eyes, the gold standard in terms of how to set up a trial in this area. In fact, they issued guidance earlier this year describing this one trial, which you can't see. This one trial design where a surrogate endpoint is met, it's sufficient for review, and that's followed up in the same trial with a confirmatory efficacy rate, such as OS. Why are we so confident that it will work in high-risk MDS? It's a few things.
One is, again, the safety profile is immaculate. It's very easy to manage and high quality of life, which is very important for this patient population, and this is where several of the trials recently have failed in higher-risk MDS, and so certainly, we're not expecting that level of safety concern. Again, we have single-agent activity at 60% hematologic response rates with relapsed refractory MDS, with a mCR. We have a doublet in AML that has shown 67% CR/CRI and 50% CR rate, and then in the population, which is lower blast AML, so blasts of 20%-30%, which are very similar to higher-risk MDS, we saw a 67% CR rate, and by contrast, azacitidine, which is the standard of care, again, is 17% CR rates.
And so again, this is due to read out in Q4 of this year, or mid-Q4 of this year. And so you can imagine with the timing, we're continuing to now gear up for a pre-launch in terms of our activities and our planning. We have, again, a leadership team with deep experience. We now know, based on some of our work in terms of the market, that we will require a highly focused, relatively small sales force to really cover this targeted group of physicians. We have distribution, et cetera, planned going forward, and we also have in place, in terms of a plan, a very efficient infrastructure to support all of this work. And of course, testing is important.
So to continue to sort of set the foundation for patient identification and to ensure that at launch, we have broad access to our RARA overexpression test is highly important as well. So let me stop there, 'cause I know that was a lot, with, particularly without slides, and see if there's any questions, from the audience.
Yeah, I'd like to thank our presenter for a very informative presentation, and I'd like to open up the floor if anyone has any questions they'd like to ask. All right. Well, thank you, Conley, for speaking at our conference this year. We really appreciate it. And feel free to reach out to management over the next-