207th Annual Global Investment Conference. My name is Charles Wallace, and I'm with the Equity Research Team. It's my pleasure to welcome Zentalis Pharmaceuticals, ticker ZNTL. Zentalis is a clinical-stage biopharmaceutical company, and their lead asset, azenosertib, or ZN-c3, is a potentially first-in-class and best-in-class WEE1 inhibitor being developed for the treatment of cancer. In particular, the drug is being developed as a monotherapy in platinum-resistant ovarian cancer. From the company, I'm excited to introduce the CEO, Julie Eastland. Julie, the floor is yours.
Thank you for having us. Thank you for the invite, and thank you to all of you who are here today. I appreciate the opportunity to give you an overview of Zentalis and, in particular, azenosertib. We are going to talk a little bit today about forward-looking statements. Before we begin, I want to make note that these forward-looking statements contain risks and uncertainties, and these may cause actual results to materially differ from forecasts or estimates. For all the risks associated with Zentalis and azenosertib, we refer you to our filings with the SEC, including our 10-Qs and our 10-Ks. Today, I am going to touch on the body of data that we have generated so far with azenosertib. I am also going to talk with you today about what we are doing at the moment and what we plan to do in the future.
To date, we have developed an extensive data set for azenosertib as a potential best-in-class small molecule oral non-chemo option for patients who are cyclin E1 positive in the platinum-resistant ovarian cancer setting or PROC setting. In our studies at doses of 400, we saw response rates over 30% and duration of response over six months. This is in comparison to current standard of care in this setting, which is single-agent chemotherapy, which typically has low response rates of 4% to 13%. This is quite an important advancement for patients in this setting, in particular in this biomarker-selected population. We will talk a little bit more about that here in a couple of minutes. Today, we have been very intentional and very focused on setting a strategy that lets us move azenosertib forward in our first potential commercial indication, which again is in cyclin E1 patients in the PROC population.
So far today, the interim data that we presented, and for your reference, there is a large body of that data that is in our corporate presentation on our website. I would also refer you to our webcast that we provided in January that went through the data in detail. We have seen over multiple clinical studies meaningful activity of azenosertib in this population. We have also established levels of cyclin E1 overexpression that correlate to meaningful activity in this patient population. We have developed with an IHC assay a proprietary cutoff to show the correlation of benefit of azenosertib to this particular group of patients. We are currently enrolling our registration trial for accelerated approval. This is called the Denali study.
It's a multi-part trial, and we're currently enrolling part two, which we have discussed with the agency, and we'll talk about that design and where we're at in that trial. For the future anticipated milestones coming up, we plan to have a discussion with the agency this year regarding the phase three confirmatory trial in the same population that will serve as full approval should the data be positive, in addition to the accelerated approval trial that's currently enrolling. We'll have more input from the FDA this year on that. In addition, by the year-end 2026, we've made note that we expect to have top-line data from the Denali part two trial, which again is the trial that we believe is registration intent for accelerated approval in this patient population. With that, we'll turn our attention to what does this cyclin E1 mean?
I think this was a real opportunity, being first-in-class, is always an opportunity to provide an understanding of what the opportunity for patients are in this setting. Cyclin E1 overexpression can be driven by a number of factors. Mostly well-known right now is gene CCNE1 gene amplification, and we'll talk about that in a minute. Protein expression can also be driven by other transcription factors or by the lack of protein degradation. On the right-hand side of the slide, we focus in on the CCNE1 gene amplification. I think it's important to note that in our data that we've generated based on our proprietary cutoff of patients with cyclin E1 positive expression, that gene amplification doesn't always tell the whole story. You can see on the pie chart there on the left that patients who have gene amplification, about 85% of those were positive for the cutoff.
Yet there was still a portion of those patients that didn't have high levels of cyclin E1 expression. Conversely, for patients who had non-amplified gene CCNE1, there were over 40% of those patients that actually did have high levels of cyclin E1 expression. The takeaway in the message here is that this is not all about CCNE1 gene amplification. This is about protein expression of cyclin E1. This is an opportunity for us to continue to educate and drive this message home in the market as well as with our physicians. That's important because this is very much an unmet need. This is a biomarker-selected population that has no targeted therapies and does represent a very large portion of the total PROC population. Here we see about 50% based on our cutoff of the population may be served by azenosertib in this setting.
That represents about 21,500 cyclin E1 positive patients. Again, the companion diagnostic is ready to use, and we're using that as a prospective entry criteria into our registration studies. I think a correlate here that really helps us to be excited around this particular opportunity is looking at other biomarker-selected populations in this setting, most notably the folate receptor alpha patients, where ELAHERE has made a significant improvement in patients' lives as well as a significant uptake of the market. However, there's only about 35% of the opportunity there where we see a potential 50% of the opportunity for azenosertib. This does underscore the desire and the demand for biomarker-selected agents in this setting. Just one minute on platinum-resistant ovarian cancer overall.
I won't focus on this whole chart, but certainly as patients cycle through chemotherapy through first and second-line maintenance and move into the PROC setting, there is a high unmet need here for these patients where the only thing that's available to them is non-platinum chemotherapy. That's the current standard of care outside, of course, ELAHERE if you're a folate receptor alpha high patient. The response rates again here are very low, 4% to 13% response rates for single-agent chemo. The duration of response is quite low, PFS being less than four months. Clearly, there's opportunities not only in the broader population in this setting, but certainly for the cyclin E1 patients, which tend to have a poorer prognosis than the overall population.
I'm just going to spend two slides talking about the data that we presented earlier this year that just gives you the foundation as to why we're excited about running the Denali trial, the registration intended trial. This slide here looks at an integrated analysis across three of our historical studies: our 001 trial, which was the dose escalation study for azenosertib across multiple tumor types; the MAMATH trial, which had single-agent ZN-d5 in it, which is post-PARP; and then, of course, the Denali trial, the first part of that trial, which enrolled 100 patients at 400 milligrams. What you see in this chart is an integrated analysis of patients who've received 300 and 400 daily doses, five days on, two days off. We're comparing the tolerability profile here, and we'll look at the clinical activity next.
Across the board, what we really have is a comparable and manageable tolerability profile at these two doses across these studies. We feel very manageable regardless of whether it's 300 or 400. I want to next point to the clinical activity that we saw on this integrated analysis. First off, you can see that while there were roughly 20 patients at the 300 and roughly 70 patients, a little bit less at the 400, these are patients who met the cyclin E1 expression cutoff, again, the proprietary cutoff, that had an opportunity to receive at least one dose in the intent to treat and one scan in the response-evaluable population. Importantly, you see the large body of data for 400 milligrams over 300. That's merely the fact that we had 100 patients at the 400 milligrams in the Denali trial.
Regardless of 300 or 400, you see deep and meaningful responses across these populations. For 400 milligrams, you see response rates well above 30% here, especially in the 400 integrated analysis arm. Importantly, consistently across all three studies, we saw response rates above 30% in each of those trials. We think that this is an important agent. We're certainly excited about the opportunity to look at this. As you can see, because of the amount of data at 300 versus 400, and again in different populations in different studies, we then turned our attention to Denali part two, and we made some changes going into that trial. Here you see the schematic for the Denali part two accelerated approval study.
The reason we are looking at 300 and 400 in a randomized fashion, one-to-one in this trial, is because we need to comply with Project Optimist, and we need to show these doses in the same entry-level criteria, keeping in mind that patients at the 300 milligram dose in prior studies had seen anywhere from 1 to 13 prior lines of therapy. In this trial, what we will do is look at platinum-resistant ovarian cancer patients who've had 1 to 3 prior lines of therapy, so fewer lines of therapy than even in the Denali part 1B study. If patients have had prior ELAHERE, then that would be 1 to 4 prior lines for those patients. Importantly, we are using our IHC assay with our proprietary cutoff to select patients prospectively for enrollment in the trial.
These eligibility criteria will then allow patients to come into the trial, be randomized one-to-one to 300 or 400, and we'll continue to enroll and follow patients while we select the dose of interest and have conversations with the FDA. Once the FDA is aligned with dose selection, we'll continue to enroll in this trial. It's called a seamless design, so we don't lose time. That means that at whatever given selected dose plus the additional enrollment in the second part of this trial, that will represent about 100 patients in an accelerated approval trial where the primary endpoint is ORR and duration of response, of course, and PFS are followed. This is a design that we have met with the agency around. This is aligned with the agency's view of accelerated approval in this high unmet need population.
Of course, along the lines with guidance for accelerated approval, we'll also be talking to the agency about the phase three confirmatory study, which is obviously a study that is randomized against standard of care. The specifics around that will be forthcoming, once we have more conversations with the FDA this year. We will have a conversation, as I mentioned, after the part 2A in the accelerated approval trial with the FDA, and we'll be talking with them to align around the dose selection. We will likely only have clinical data in this trial after parts 2A and 2B are complete because all the patients will be part of our filing package for accelerated approval. As I mentioned, we expect top-line data from this part two in Denali by the end of 2026. We'll also begin enrolling the phase three confirmatory trial alongside that.
I just want to take one minute and mention the importance of lines of therapy. I think it's probably fairly common to believe that patients in earlier stage of disease may do better in clinical studies. What we've done here with all the caveats of a post-hoc analysis and small patient numbers, but we have looked across the trials to ask the question, will patients with fewer lines of therapy do better? What we see here is whether it's response-evaluable or intent to treat and duration of response, we see that fewer lines of therapy can have a meaningful difference in the patients that were in our trial.
Of course, we'll see if this plays out in the Denali trial, but it certainly is encouraging to know that both management of additional supportive care in the Denali part two, as well as fewer lines of therapy and prospectively enrolling patients with cyclin E1, give us the best opportunity to see robust responses and a meaningful change in the treatment paradigm for patients in this setting. Just in summary, in terms of our pipeline, I think I've probably been clear that our focus today is azenosertib in the cyclin E1 positive PROC setting. This really is our first foray into a label for azenosertib, but it doesn't mean we are stopping there. There is certainly an opportunity with this WEE1 inhibitor to be important in a number of different tumor settings in combination or as a single agent.
We continue to complete studies that were started looking in other tumor types and looking at combinations, including a combination arm with bevacizumab in our earlier ovarian line setting. As we get signals here, if there's capital to allocate, we'll be encouraged to do that. Importantly, our cash runway, which we announced at the end of the second quarter, was $300 million and would provide us with funding into late 2027, supporting this initial march of azenosertib into the PROC setting. Should we have funds after that, we'll continue to explore in other settings. We think there's a large opportunity for azenosertib beyond PROC, but we first want to get this across the finish line into as many patients as possible.
Just in summary and focus, strategic focus in this setting, potentially being both first-in-class, but certainly best-in-class WEE1 inhibitor based on the large body of data that we've seen and executing on our registration trial for accelerated approval while we launch the phase three study for azenosertib next year. There is certainly a high unmet need for these patient populations, especially this biomarker-selected group. Our cash runway supports us not only through the top-line data of accelerated approval at the end of 2026, but into late 2027, where we'll continue to enroll and move the program forward in this setting, including the phase three randomized study. That concludes the presentation today. I don't know if there's Q&A on tap, but happy to answer a few questions. My amazing team is here in the room as well, so they can be of help.