Let me know when. Oh, I am live. There I go. I can hear it.
Good afternoon, everyone, and thank you for joining the H.C. Wainwright 26th Annual Global Investment Conference. We thank you for your attendance and hope that you have an enjoyable day. With that said, I'd like to introduce our presenter, Curis.
Thank you very much. Appreciate having us at the conference this year. So I'm going to walk through over the next 25 minutes or so a summary of our progress to date. Although it's not advancing. It's not advancing? There we go. Okay. So before we begin, I'd like to remind everyone that during the presentation, we will be making forward-looking statements, which are based on our current expectations and beliefs. These statements are subject to certain risks and uncertainties, and the actual results may differ materially. For additional details, please see our SEC filings. So Curis has a broad pipeline of novel cancer treatments, and over the last eighteen months, we've focused our efforts on emavusertib, the first-in-class, and we believe best-in-class IRAK4 inhibitor.
IRAK4 is an interesting target in the context of oncology, with broad application in NHL, AML, and solid tumors. Today's discussion will focus on three of our ongoing clinical trials. First, a phase I/II study in primary CNS lymphoma of emavusertib in combination with ibrutinib. Second, a phase I/II study in relapsed refractory AML for patients with targeted genetic mutations, specifically FLT3. And third, a phase I study in frontline AML of emavusertib in a triple combination with venetoclax and azacitidine for all comers, regardless of mutation status. In today's presentation, we will review our combination data in NHL, our monotherapy data in AML, and we'll have a brief overview of our recently initiated combination study in frontline AML.
With over two hundred patients dosed so far, we're very encouraged by the emerging safety and efficacy profile of emavusertib and the potential of this novel IRAK4 inhibitor to add to the current standard of care in NHL, AML, and solid tumors. So in our current studies, we're pursuing opportunities in primary CNS lymphoma, FLT3 AML, and frontline AML. As we look forward to expanding into additional indications in NHL, we generally prioritize NHL subtypes with a high incidence of MYD88 mutation and/or sensitivity to Toll-like receptor signaling. These are indications such as Waldenstrom's, and ABC DLBCL. Other indications, like marginal zone and mantle cell lymphoma, are also of high interest due to their sensitivity to TLR signaling and also their high unmet need. So now let's dive into our NHL program.
IRAK4 is a compelling target in NHL because of its ability to downregulate NF-kappa B in a way that's independent from and synergistic with the standard of care in NHL. NF-kappa B overactivity is what's driving disease in patients with NHL, and there are two pathways driving that overactivity. One is the BCR pathway, which you see on the left-hand side. That's addressed by BTK inhibitors. On the right-hand side is the TLR pathway. That's addressed by emavusertib. There are a lot of BTK inhibitors. It's an $11 billion business today. There is only one IRAK4 inhibitor in advanced clinical studies. That's emavusertib. So this slide highlights some of the preclinical work that we've published that validate emavusertib's mechanism. As you can see in the graphic on the right, blocking either the BCR pathway with ibrutinib or the TLR pathway with emavusertib decreases tumor volume.
But blocking both pathways, treating with the combination of emavusertib plus ibrutinib, shows the deepest reduction in tumor burden. So we have four key steps in our NHL strategy. First, demonstrate safety. Second, demonstrate single-agent activity. Third, identify the best population for proof of concept and pursue the fastest path to first label. And then fourth, with proof of concept established, pursue a partnership to expand broadly across NHL and maximize our commercial potential. So this is the NHL safety table. It was presented at ASH last December. It includes 19 patients treated in our phase I-B study of emavusertib in combination with ibrutinib. The combination was well-tolerated, has an acceptable safety profile, and at the current dose of 200 milligrams BID, there were no DLTs observed.
You can find a copy of this table on the clinical outcomes poster from ASH 2023 in the Scientific Resources section of our website.... Step two of our strategy is demonstrate single-agent activity. The graphic on the left shows the anticancer activity that we observed in the phase I study evaluating emavusertib as monotherapy in multiple NHL subtypes. One of these patients, a Waldenstrom's patient, was especially interesting, as they ended up being a single-patient case study in dose response, and you see that patient in the graphic on the right. This patient started at 50 milligrams and achieved a clear reduction in disease burden with each increase in dose, eventually achieving PR and still on treatment nearly three years later. Step three of our strategy is to identify the best NHL subtype for proof of concept and pursue the fastest path to first label.
The data on this slide were presented at ASH last December. There are a couple things of note. First, the data support the mechanisms thesis. That is to say that blocking both the BCR path and the TLR path is better than blocking either one alone. With ibrutinib monotherapy, you typically see PRs but not CRs. With the combination, we're seeing CRs. Second, we're seeing responses in ultra-orphan diseases like primary CNS lymphoma, where the unmet need is significant, where there are no effective treatments for patients who have failed on BTK inhibitor in monotherapy. In primary CNS lymphoma, patients typically receive, in the frontline setting, high-dose methotrexate, radiation, and chemo. When they relapse, NCCN guidelines recommend a BTK inhibitor, and published data suggest 52% of these patients can achieve an objective response. Patients in our study are in salvage line.
They've progressed after being treated with that BTK inhibitor. You would expect, of course, that treating or re-treating these patients with a BTK inhibitor after they've just failed on it, it shouldn't be effective. You would expect the response rate would be zero. But emavusertib's mechanism suggests that blocking both the BCR path and the TLR path, adding emavusertib to the BTKI regimen, is synergistic, and we see that. In our early data, this thesis is holding up. These patients are able to achieve objective response. As you saw in the prior slide, our early data show that we were able to get three responses in our first five relapsed refractory PCNSL patients. That's roughly a 50% ORR. We find that very encouraging. Enrollment in the study is ongoing, and we're looking forward to updating those data at ASH later this year.
Step four of our strategy is to pursue a partnership and to expand into additional NHL indications. Some indications, like Waldenstrom's, ABC DLBCL, and MCL, are orphan indications and characterized by high sensitivity in TLR signaling. Others, like CLL, are much larger indications and represent an excellent opportunity to pursue with a partner. So that's it for the NHL story. At this point, I typically pause for questions, but for now, why don't we just move to AML? As we dive into AML, we find that IRAK4 inhibition, and emavusertib specifically, have very encouraging potential. From the beginning, we knew IRAK4 could be an important target in AML. So when we designed emavusertib, we wanted a molecule that hit IRAK4 hard.
Once we had that, we looked to engineer in other targets, targets like FLT3, CLK, to expand the molecule's potential to treat a wide range of cancers. As we'll see in the coming slide, this strategy has proven especially useful in the context of AML. The red and blue graphic on the left uses data from the Cancer Genome Atlas, and it shows why IRAK4 is such an important target in AML. Its oncogenic isoform, IRAK4 long, is expressed in nearly all patients with AML. The graphic on the right shows how knocking out IRAK4 stops oncogenic activity. You see that in the box in the upper right. In the lower right, we add back IRAK4 short, wild type. Has no effect, but when you add back IRAK4 long, the oncogenic isoform of IRAK4, you see a clear restart of leukemic activity.
Of course, IRAK4 is not the only driver of disease in AML, but it is an important driver, and it is expressed in nearly every patient, and the current standard of care doesn't address it. Similar to our NHL program, we have five key steps in our AML strategy. First, demonstrate safety. Second, demonstrate single-agent activity. Third, identify the best population for proof of concept and pursue the fastest path to first label. Fourth, proceed simultaneously in the frontline setting with a combination regimen. Fifth, with proof-of-concept data in hand, pursue a partnership to maximize the commercial potential. So step one is safety. We've treated 123 patients so far in our monotherapy study in doses ranging from 200 to 500 milligrams BID. This safety table, which was presented at ASCO and EHA earlier this summer, is consistent with our prior findings.
Emavusertib is well-tolerated, has no dose-limiting myelosuppression. Step two of our strategy is demonstrate single-agent activity. As we saw earlier, IRAK4 is an important driver of disease in nearly all AML patients. In the gray waterfall on the left, we see single-agent activity across the entire patient population, regardless of dose level, regardless of mutation status. The blue waterfall chart on the right enriches for dose and mutation status. That is, it shows patients treated at the recommended phase II dose who also have a FLT3 mutation. As you would expect, the anticancer activity increases significantly, and we'll dig deeper into this population in a few slides. Step three of our strategy is identify the best population for proof of concept and pursue the fastest path to first label. For monotherapy, as you might expect, that turns our focus to FLT3 AML.
So this graphic comes from the 2019 Melgar paper, and it does a great job of articulating the synergy between IRAK4 and FLT3, as it describes how IRAK4 is the escape mechanism for FLT3 inhibition. In the graphic, we can see that blocking either IRAK4 or FLT3 in monotherapy can lead to a nice initial reduction of tumor burden, but sadly, this effect is typically temporary, and the cancer quickly returns. But when you combine the two, when you combine IRAK4 and FLT3, which is what you see in the blue line at the bottom, the response is deeper and longer. In emavusertib, we have a drug that combines both IRAK4 and FLT3 inhibitor in one molecule. So this slide includes data for 12 patients with FLT3 AML, and it was presented earlier this summer, again, at ASCO and EHA.
As you know, the standard of care for unfit patients in AML is Aza-Ven. AML patients with a FLT3 mutation are typically also treated with a FLT3 inhibitor, and the leading FLT3 inhibitor today is gilteritinib, which was approved with a CR/CRh rate of 21% in a predominantly FLT3-naive patient population. It's important to note that most of the patients in our study had already been treated with a FLT3 inhibitor, so rechallenging with another FLT3 inhibitor is unlikely to work. But when we treat these patients with emavusertib, again, which is blocking both FLT3 and its IRAK4 escape path, we're seeing very encouraging results. As we look at the swimmer plot for these data, we see the durability of the response, including in one patient who achieved a CR and went to transplant.
While patients proceeding to transplant technically lower a study's duration of response, it's obviously a terrific outcome for the patient, so we were very glad to see that. These data are still early, so it's obviously hard to assess the median durability of the CRs, but we're very encouraged by what we're seeing so far. As we summarize our AML progress to date, we've demonstrated safety, we've demonstrated single-agent activity, and we've identified a path to first label in AML, so now let's turn to our recent move into the frontline setting. In the frontline setting, we're enrolling all comers, regardless of mutation status, with a triple combination, adding emavusertib to Aza-Ven.
We see the red and blue graphic on the left, same graphic we saw earlier, showing, of course, why IRAK4 is such a great target in AML because its oncogenic isoform, IRAK4L, is expressed in nearly all patients. The graphic in the middle shows the preclinical data that test this thesis. So when you treat AML with standard of care with Aza-Ven, you do get a nice reduction in tumor burden. When you add emavusertib to it in a triple combination, the synergy is clear. On the right-hand side, of course, we have a placeholder for what the triple combination data will look like. This is the study that we just started. We're in the initial phase. We're focusing right now on safety. We're enrolling patients who have already achieved a CR on Aza-Ven, but are still MRD positive. They still have minimal residual disease.
Of course, we hope that adding emavusertib to the regimen will help them get to MRD negativity, but the primary goal is to isolate the safety effect of adding Ema to Aza-Ven. We've begun enrollment, and we would expect to have initial safety data either late this year, you know, Q4 or Q1. That's really it for the leukemia story. In most oncology settings, IRAK4 is a novel target that looks to combine with really well with standard of care. Emavusertib's additional targeting of FLT3 on top of IRAK4, I think, gives it an additional advantage in the setting of AML.
So I mentioned at the beginning of this presentation that the primary focus of our work has been in NHL and AML, but we are also working with several partners in academia and at the NCI on our potential for emavusertib in solid tumors. In preclinical studies, emavusertib has been shown to potentiate both chemotherapy and immunotherapy in solid tumor malignancies. Ema's being currently evaluated in five investigator sponsored trials that you can see here in solid tumors. We would expect preliminary data on these beginning in 2025 , and as these data mature, we hope to gain a better sense of emavusertib's position in the competitive landscape and certainly the scope of its potential in solid tumors. So now that we've walked through the potential of Ema in NHL, AML, and solid tumors, let's walk through some of the high-level corporate items.
We finished Q2 with $28 million, and we have a strong IP position, with comp of matter extending to 2035, and that's before any extensions. Our existing cash enables us to achieve three key milestones: combination data in relapsed refractory PCNSL, monotherapy data in relapsed refractory AML, and initial safety data with the Ema Aza-Ven combination. In closing, we all know that novel targets in biotech, especially ones with wide commercial potential, are rare. All of us at Curis are grateful for the opportunity to develop this first-in-class, and we believe best-in-class, novel therapy for patients with cancer. So thank you, Wainwright, again, for having us. Thank all of you who are watching today. We appreciate your time and your interest, and we look forward to providing you an update in the near future.