Good afternoon, everyone, and thank you for joining us today. Before we begin today's company update, it is essential that we provide you with important cautionary language consistent with certain federal securities laws. Our remarks during today's webcast will include forward-looking statements. Forward-looking statements are not guarantees of future performance and involve known and unknown risks, uncertainties, and other factors that are difficult to predict. Actual results may be materially different from future results expressed or implied by such forward-looking statements. These risks and uncertainties include and relate to, among other things, statements regarding leronlimab's early performance in clinical studies, anticipated and/or continued performance in the same clinical studies, or potential efficacy in certain indications.
Statements regarding the status and potential consequence of regulatory actions and/or government investigations or inquiries, the company's ongoing ability to raise additional capital, that clinical trials may not commence or proceed as planned, that products that appear promising in early trials may not subsequently prove to be viable on safety or efficacy grounds, that products may not receive regulatory approval or market acceptance, that our patents may be challenged and/or unenforceable, that competition may reduce commercial potential of our products, and that the company may experience recalls, manufacturing issues, or other product liability. Although forward-looking statements help to provide complete information about the company, forward-looking statements may be less reliable than historical information. The company undertakes no obligation to publicly update these forward-looking statements except as required by law.
Please refer to our recent quarterly and annual reports filed with the Securities and Exchange Commission for more information about the risks and uncertainties that could cause actual results to materially differ as compared to our current expectations. Once again, thank you everybody for joining us today. I will now turn it over to Dr. Jay.
Thank you, Tyler. I think I'll try to speak a little more slowly than that. Thank you to everyone for joining the call today. I particularly want to, again, thank and acknowledge the many long-term investors who've kept faith with leronlimab during this incredible odyssey. To state the obvious, none of the striking developments we'll review today would have been possible without your steadfast support. During the April investor call, I made two important assertions. First, that CytoDyn was transitioning from a company built on faith and a few ifs into a company with solid and unassailable clinical data. Second, I asserted that leronlimab was delivering results in the clinic at the outer edge of what I thought was even possible. Today, I stand fully behind both of those statements and remain more confident than ever that our investors' patience will soon be rewarded.
On today's call, we'll review some exciting results from the CLOVER study of patients with CRC. Much of these data will be presented by Dr. Ben Weinberg at the European Society for Medical Oncology meeting this Sunday in Madrid. On the call today, we'll focus on biomarker data and early clinical results. We'll also hear some very preliminary thoughts about two patients who are now receiving leronlimab plus a checkpoint inhibitor on the rollover phase of the CLOVER study. Lastly, we'll hear about a special group of CLOVER patients who were treated with leronlimab and then determined to be appropriate candidates for an attempt at a surgical cure. With that, let's begin. Ignacio, I don't think I see your slide.
Yeah. We're showing the executive summary now, Dr. Jay.
Hmm. I see your handsome face, but nothing else.
You can proceed now with the executive summary.
Yeah, I don't see the slide, Ignacio. All right, let me just make do with something else. Sorry. All right, so I'm showing slides off my computer, but I can't see your computer, Ignacio. Leronlimab, as pretty much everyone must know, is a novel drug candidate with multiple demonstrated mechanisms of action, both in inflammation and in oncology. We are focused right now on the development in colon cancer and breast cancer, but also interested in several other solid tumor indications. Any conversation about leronlimab has to begin with a discussion of its safety database. After 1,700 patients have been dosed, we still do not see a recurrent defining safety signal. This is really one of the safest drugs I've ever been involved with, and certainly one of the safest drugs that will ever be presented to the oncology community.
We have promising early readouts from the CRC study we'll review today. Retrospective data in triple-negative breast cancer we've already shared, and expect to have continued readouts supporting the proposed mechanism throughout calendar year 2027. To be clear, there are two tracks, separate tracks in which we're developing leronlimab. One is the "standalone" as a cancer therapy unto itself, which would then be either used as monotherapy or in combination with standard of care, but also as in the prime and pair paradigm, where we use leronlimab to prime a tumor, disrupt a tumor microenvironment, allowing intrusion of the host immune system, causing the cancer, in a defensive way, to express PD-L1, and then pairing leronlimab with a checkpoint inhibitor, which then defeats the PD-L1 attempt to beat back the invading immune system.
We are two tracks with leronlimab, and we'll talk about both standalone as its own anti-cancer therapeutic, and prime and pair as a drug that's meant to be given in combination with immunotherapy. Next slide. We are starting in colon cancer and the CLOVER study, named by Dr. Kasi, is a phase II open- label randomized study comparing 350 mg and 700 mg doses in 60 patients to explore the safety and efficacy of leronlimab administered with the backbone of LONSURF and Avastin in patients with third- line microsatellite stable metastatic colorectal cancer, MSS meaning the 95% of colon cancer that's not treated with immunotherapy. We are very fortunate to have Dr. Pashtoon Kasi as the lead investigator for this study. He's the Medical Director of GI Oncology at City of Hope in Orange County.
The enrollment for this study, as we indicated on the last call, was already completed last April. The endpoints in this study, the primary objective is an evaluation of the efficacy of leronlimab, when given with the current standard of care. The primary endpoint will be the calculated objective response rate, which includes all patients that are either complete responders or patients that have a 30% decrease in the largest diameter of their target lesion as assessed by blinded readers, independent readers. We have a number of secondary exploratory endpoints. Obviously, safety of leronlimab remains important. An evaluation of changes in the circulating tumor DNA, which we'll get into in some detail. A summary of patients who achieve complete response, partial response, stable disease, meaning they didn't quite reach the 30% decrease in tumor diameter, as well as progression- free and overall survival.
As well, we will do a separate assessment in addition to the blinded readers, although I don't think they like that term, but they're masked readers, to treatment assignment. We'll also take into account the local assessments from the local radiologists. As well, we're following PD-L1 levels on circulating tumor cells and evaluating the efficacy of leronlimab now given in a rollover phase to patients with progression who have now increased their dose of leronlimab to 700 mg and added in the checkpoint inhibitor pembrolizumab, to follow them during the randomized phase of this study. On the next slide, we're looking at the baseline characteristics of the CLOVER study. I think this is the first time investigators have seen this.
To our surprise, the CLOVER study was meant to be a study in patients in third- line metastatic CRC, meaning they'd had two prior lines of therapy. Well, as it turns out, the great majority of our patients who entered the study were actually fourth line or later, meaning that starting leronlimab was their fourth line, in the metastatic setting. Indeed, as you'll see, we have patients out to fifth, sixth, seventh, and even ninth line. That was a bit of a surprise, but indicates that the CLOVER study is in a population far more advanced than we had originally anticipated, with about 90% of patients already having been on bevacizumab as well. On the next slide, we had previously shown the data from City of Hope that Dr. Kasi obtained through standard of care using the Signatera assay at Natera.
Then we had this agreement with Natera, which both allowed us to send specimens from the study, where we had baseline and follow-up specimens for their own evaluation using their Signatera exome assay, as well as the agreement to provide a comparator data set, so that we could put these results into context. This slide now provides data in the 28 patients in whom we have a baseline specimen that was obtained within seven days of the baseline visit, as well as a follow-up specimen indicating that at week two, we are seeing a median decrease of 86% across all the patients. I do believe that that is a result that has not previously been shown in colon cancer. So a very exciting signal of early biological activity.
I would point out that the majority of these patients have a RAS mutation, and therefore the activity of leronlimab does appear to be RAS agnostic. On the next slide, not only do we see the activity of leronlimab with these robust, rapid, and steep decreases in DNA, but we have an early signal of a dose response, which grows as our database grows, which is important because it underscores that not only is the efficacy that we're seeing based on DNA being driven largely by leronlimab, but it's actually also being driven by leronlimab dose. That'll be an important piece of information for the FDA to consider as we consider next moves. On the next slide, the DNA results are broken down by prior lines of therapy.
Again, the majority of patients in CLOVER had three prior lines or more, and again, some of these patients, four, fifth, six, and even nine prior lines. The other point this slide makes is that prior treatment with whatever regimen or therapy doesn't impact the subsequent activity of leronlimab, nor would we expect a prior chemotherapy or checkpoint inhibitor to particularly affect the activity of a monoclonal antibody directed at CCR5. Very encouraging.
On this slide, I don't want to steal Reny's thunder, but the agreement with Natera was to run the Signatera assay on our study patients in whom we could obtain baseline and follow-up specimens, and as well for them to generate a database from their database of 140,000 samples in patients with colorectal cancer that would specifically look at third-line patients who received LONSURF and Avastin, so that we could put the CLOVER results into some sort of context. The LONSURF data is on the left, the LONSURF plus Avastin data is the blue bars in the middle, and the CLOVER data is on the right. I'll leave the rest of this for Reny to go into. A preliminary summary from the CLOVER study.
Very satisfied to see 100% of screened patients that had an evaluable sample, which was just about everybody, was deemed to be CCR5 positive as determined by immunohistochemistry. There are a couple important things to say about that. When the CLOVER study started, it was important for CytoDyn that we move quickly, and so I sort of made the decision to lower the threshold for the definition of positivity from the prior definition of 20% expression on the lymphocytes in the tumor microenvironment down to 1%, in the hope that that would expedite enrollment. Indeed, it did. But the other thing is that it greatly expanded the potential population that would be valuable and eligible to receive leronlimab in this setting, and did so by enrolling a population that generated the DNA data that we just shared.
It turns out that even relatively low levels of CCR5 expression in the tumor microenvironment are associated with profound, deep, and rapid declines in circulating tumor DNA. That was a real win for CytoDyn. What remains to be seen is, we will not be using immunohistochemistry as a gating criteria for future studies in oncology, but it remains to be seen to what extent CCR5 evaluation is necessary before treating a patient with leronlimab in the oncology setting. The second bullet point, again, the drug has been extremely well-tolerated. In CLOVER, there have been no serious adverse events related to leronlimab. I just showed you the declines in ctDNA in the first 28 patients evaluated with the Signatera exome with the 86% median decline. Reny will comment on that in just a moment.
Again, looking at early clinical outcome, about three-quarters of the patients who had scans at week eight demonstrate shrinkage or are classified as having stable disease. In this patient population, now fourth-line patients with CRC, that has to be considered a win. We are excited about the observations of increased PD-L1 levels in the majority of patients. We are not getting into that during this ESMO presentation, but we will elaborate more fully during ASCO GI. Speaking to the investigators, these DNA levels do appear to correspond with improving clinical wellbeing, and we have heard reports of patients in less pain and potentially even fewer hospitalizations. Dr. Kasi will be here in a moment to comment on that.
As I mentioned, not only do we have a group of patients who are now on a rollover protocol receiving leronlimab plus a checkpoint inhibitor, but indeed, we have three patients that had received leronlimab that are now referred for curative intent surgery. Dr. Kasi will be able to comment on that as well. With that, on the next slide, the approval of the backbone of LONSURF and Avastin is based on the SUNLIGHT study done several years ago in patients with third-line CRC. That study showed an overall response rate of 6% and had no complete responders, meaning about one in 20 patients had at least a 30% decrease in the diameter of their tumor.
I remain very confident that the data CytoDyn is generating will be able to show an improvement over that current standard of care. Even that standard may have been artificially inflated. A subsequent real-world meta-analysis of real-world data showed that the overall response rate with bev and LONSURF was actually closer to 3%. That is the bar with which the FDA will be judging leronlimab during our application.
On the next slide, when I was a young boy, my mother always told me, "Never compare across studies." But she said, "If you are going to, you better compare across a study where one population has more advanced disease and is doing better than a population with less advanced disease and did worse." That is exactly what we see here, that with CLOVER and the majority of patients already having failed three lines in the metastatic setting, we are seeing certainly very exciting DNA and early responses that appear more dramatic, steeper, and faster than SUNLIGHT, where 90% of the patients had only failed two lines of therapy, and they even had about 5% of patients who had only failed one line of therapy.
It is unclear how many of those first-line failure patients actually contributed partial responses to their conclusion of a 6% overall response rate. But again, it is not ever completely kosher to compare across studies, but if you are going to, it is best to have better data in a more advanced population than the study you are comparing with. On the next slide, I will stop talking and now introduce Reny Aniline. Reny is a lovely and brilliant man. He is [Senior] Director of BioPharma Business Development in Natera. He has been a pleasure to work with as we developed this agreement and partnership between CytoDyn and Natera, and I love listening to Reny speak. Reny, it is yours.
Thank you so much, Dr. Jay. Really excited to be here today. This is some data that is very unprecedented from what I have seen over my years at Natera. I have been here really since we launched our Signatera testing platform in oncology at Natera since 2018. The data that I will be able to share with you is, frankly, I think pretty stunning in terms of the performance of the CLOVER patients that we looked at. If we go on to the next slide, I thought I would start by just contextualizing what we are really looking at, what we are trying to do. What Signatera does is we are looking at circulating tumor DNA that shed from a cancer tumor cell as the cancer is proliferating.
If I keep it very, very basic, if you see ctDNA levels increasing from baseline to on- treatment time point, that is a strong indication that that treatment is not working, not likely to have a strong response to that therapy. If the ctDNA is decreasing, obviously much better. The more decrease you see, typically the better that patient will do. If we can get them to undetectable levels of ctDNA, those tend to be really strong clinical outcomes. So, up is bad, down is good, and clearance is best. The thing that makes ctDNA unique is that from a simple blood draw, we can look at the plasma and measure the ctDNA, and we can see changes in a very, very precise way, literally one molecule of cancer change from one time point to the next that we may look at.
We also see those changes take place sooner than we do imaging. So we will see these molecular changes occur weeks to months before we see the same follow-on clinical data change. So tends to be very prognostic, and have shown many studies where it is predictive of response to treatment. If we move on to the next slide, I will focus on. Oh, other direction, I think. Great. One more. Oh, again. Okay. So we are going to look at real- world data comparator. We mentioned that LONSURF and then LONSURF plus Avastin have been the standard of care in third- line metastatic CRC. What we looked for were patients who had a pre-treatment time point, where we could measure ctDNA at baseline and then had at least one Signatera test performed within the first four weeks of treatment initiation.
On average, when we pulled our cohort, we had greater than three time points per patient during the duration of the standard of care treatment. What we are going to be looking at was what I referenced, molecular complete response, we define as undetectable levels of ctDNA or ctDNA clearance versus baseline. Molecular partial response we define as a greater than 90% reduction in ctDNA compared to baseline. We call molecular stable disease a reduction of 0%-90%, and then molecular progressive disease is where we see that increase in ctDNA as compared to baseline. On the next slide, we will look at the two standard of care treatment options today. LONSURF was the first approved in this setting as a monotherapy. We had 30 patients in our real- world data set to measure LONSURF as a monotherapy.
The majority of patients today would be going on LONSURF plus bev or LONSURF plus Avastin, and we had 75 patients in that cohort. Again, we were assessing baseline versus a Signatera test within four weeks of treatment. What we saw is LONSURF monotherapy had a median increase of 22%, and the LONSURF plus bev had a median decrease of 55%. On the right side, you can see the correlation that we see between a molecular response and a clinical risk-adjusted real- world overall survival. We took survival data, tied it back to the same patient population, and saw how they did. Clearly, those that had a molecular complete response, you see their survival data in the green bar up top, where they are not having events and they are doing well.
You compare that especially to the molecular progressive disease population, where their survival does not look great. When I pitched the concept here to the team at CytoDyn, I talked about what we can do is look at your study data. The Natera lab processed 12 patients that were in the CLOVER trial, and you draw a line where you say, hopefully what we see is we see that the triple combination in the CLOVER study would perform better than the current gold standard of care LONSURF plus bev. If we go to the next slide, like I told the team, I would never have been so bold as to draw the line for the CLOVER study that low, because we just would not expect that in a third-line- plus patient population to see that type of benefit.
In those 12 patients, there was an average of a 93% reduction, and highly statistically significant, as you can see at the top, in terms of those changes. On the right, you can see the zero- to eight-week data and the leronlimab added component maintain that type of response, at least through eight weeks. On the next slide, you can see it by the actual numbers, and that 93% reduction is really stunning. Clearly it is still 12 patients. We are going to be running more in the sample set. But I was reviewing this data with our head of scientific communications, and we both agreed we had never seen metastatic response from ctDNA like we have seen in this cohort of patients. Very excited to be able to share it.
I think I made a comment that you guys need to get out and talk to your investors pretty soon because this data looks really remarkable. Dr. Kasi can talk about the subsequent clinical findings. Certainly, this data definitely is something to be excited about. If you go on to the next slide, the other thing I just want to point out here is that even in that stable disease where we define that again by 0%- 90% reduction, not quite up to the partial response group. You can see that the majority in the CLOVER study had 80%- 90% clearance, so they were right on the fringe there of having a partial response. They also had a higher rate. I think one patient cleared, but that's still, percentage-wise, just about double what the current standard of care does.
This lays it out in terms of a more granular view of the ctDNA decreases between the CLOVER study and the current standard of care options. That's what I have for you. With that, I'll turn it back over to Dr. Jay.
Thank you, Reny. When you first presented that data to the team here at CytoDyn, a collective shiver went through us. It has really been one of the highlights so far in the development of leronlimab to form this partnership with Natera. So thank you for that. Next we're going to ask Dr. Kasi to join the call. I can't say enough about Pashtoon's efforts to help with CLOVER on so many levels. Dr. Kasi is the Director of GI Oncology at City of Hope in Orange County. He has been one of the most proactive PIs I've ever seen. He's here to share his thoughts on, I believe we have four specific areas that we've asked him to comment on. Pashtoon or Ignacio?
Thank you, Dr. Jay. I'll begin with the first question, Dr. Kasi. What are your current clinical impressions as it relates to CLOVER participants at your site?
Yeah, no, thanks for having me on the call. Just a quick comment, as I was listening to Reny and also Jay. ctDNA or circulating tumor DNA has been one area that became my research niche, but I would say more of a clinical niche. I do not know if Reny knows, but I think I was probably one of the first people in the world to order the first Signatera , because once the company was formulated, that did not even have a name at that point in time. Somebody said, "We have an assay that could pick up cancer DNA in the blood." I was like, "Well, we have a hard time picking up cancer DNA in stage four.
How come this assay will pick up cancer DNA when there is leftover cancer in the body?" I was like, "Well, I am all up for the research part." Long story short, here now, it is part of my standard care for my patients because it gives me that insight that, as Reny was showing, sometimes that stable disease is missing the whole clinical picture. The half-life of ctDNA for some of the folks on the call who may not be entirely familiar with compared to tumor markers, is only a few hours. Pretty much if you start something that is effective as early as a few days into therapy, as you can see in the CLOVER study, a couple of weeks into therapy, if a therapy is working, you can see it work.
My clinical impressions, on the first question, builds upon the ctDNA, and actually that also started in one of my first patients that I could see a clinical improvement. But, the CEA, the tumor marker actually went up, and that is why the half-life of some of those markers is long. ctDNA was done to show that I think the benefit that we can see, and it can help accelerate drug development. The clinical impressions of the improvement, decrease in pain, overall quality of life is backed up by the ctDNA data.
Thank you so much, Dr. Kasi. Next question. What are your thoughts on the ctDNA trends observed today on the CLOVER study? Can you expand on that?
Yeah. So back what Reny exemplified, in the refractory setting, unfortunately, these drugs have had FDA approval, but as Jay showed you as well, the real-world response rate is essentially 0%. When patients hear the term that we're going to do LONSURF, TAS-102, or trifluridine with bevacizumab, that's pretty much is a sign that we're running out of options. Same goes for fruquintinib, regorafenib. The response rate, no matter what study you look at, is no more than a single percentage point. They've all been FDA approved because they prolong survival, but they don't necessarily provide clinical meaningful benefit to the point of partial responses or stable disease, even if it is for a long period of time, those are things that are lacking. The fact that you can see this ctDNA trend, why use these drugs on a daily basis?
You saw data from Reny to back it up. I could have subjectively told you that I don't see as much deepening in brisk responses. Now you have real-world data backed by the company that gathers this information in a systematic way to back up the subjective claims that we've been talking since April at the AACR presentation. I think, even when we were presenting the data, the ctDNA results were meaningful, and that's why we wanted to get the word out. The fact that we have now this comparative study, I think this also would really help with drug development, because you could foresee a time where you need these synthetic controls or get a sense of how would have real-world patients performed. I think collaborations like this are key. Thanks to the team for looking into that formally and systematically.
Thanks so much, Dr. Kasi. Next question. What is the current status of the rollover arm regarding patients who are to receive an immune checkpoint inhibitor with leronlimab at 700 mg?
To summarize what the rollover arm means, anybody who might have progression on the current study, as in when they come off based on the previously done clinical and translational data, the idea is could a checkpoint rescue, or as Jay put it, prime and pair or synergize. Also keeping in mind the first batch of patients had the 350 mg dose. Beyond this study as well, you can see a dose response, and also you can see in previous studies as well that the dose matters. Those patients would have an opportunity to get, number one, if they were on the 350 mg, get the 700 mg dose, and even if they were on the 700 mg dose, get the PD-1 checkpoint rescue in the form of pembrolizumab. As of right now, this is officially now live across sites.
There's at least two patients at our site that have started the rollover. We'll have more data to present and follow up at ASCO. All I can say is early signs indicate that this is promising, and we hope to share additional information of future calls or at ASCO GI, hopefully.
Thank you, Dr. Kasi. I know we're running out of time. Last question. Can you give us an update on patients referred from CLOVER to pursue potential curative surgery?
Yeah. So, it's not just about response, but it's also about a clinically meaningful benefit that also stands the test of time. Often, at least in first or second-line therapy, if there is an opportunity for resection or the render to the person what we call no evidence of disease or NED, we always have been trying to do that for our patients with oligometastatic colorectal cancer. Now, keep in mind, these are not patients with standard resectable situation, otherwise they would not have been eligible candidates for surgery.
But the clinical benefit that you saw across so many slides from Jay as well as Reny Aniline, I think the clinically meaningful benefit was, I would say, better than expected and stood longer than expected to allow for that door that was semi-closed by surgery, no surgery now, no surgery ever, to say, "You know what? I think let's go for an operation."
So we've had not just one, but three patients, all of whom who had metastatic colon cancer to the liver, in two patients and one in the lung, where the benefit was better than expected and stood the test of time, where in a good way, it's always a difficult decision to take somebody off of study. But off of study, they could get something that previously was signed off of. So that was one thing that happened in three of the 36 patients enrolled at my site. And hopefully, we'll hear more from other sites, too. But again, in the refractory, heavily pretreated, three, four, five, six, nine lines of therapy patient, that kind of patient does not go for surgery. So the fact that we have three patients rendered NED, we'll see how they do.
But this is something that we would have not seen before and is unprecedented. Also kind of on the rollover arm, there's also something called an extension arm. Patients who are on the study for over a year, we'll allow to continue on the study because in a good way, they're driving benefits, so they should stay on the leronlimab. So I think the extension arm amendment, these three patients being taken off, for a better surgical option that was not at all possible before, are all signs for not just clinically meaningful benefit, but also durable benefit.
Thank you so much, Dr. Kasi. We truly appreciate your time discussing these questions. We'll turn it now back to Dr. Jay Lalezari. Thank you, Dr. Kasi.
Thank you, Ignacio, and thank you very much, Dr. Kasi. The whole CytoDyn family will always be grateful to you for all the contributions you've made, not only to CLOVER, but in other ways to help develop leronlimab as a treatment for patients with colon cancer. It has really been a pleasure. Now, before I turn the call over to our CFO, Robert Hoffman, I have a few closing comments to make. This last month has been a particularly electrifying time at CytoDyn. When Reny and his team first shared their comparator data, as I mentioned, a shiver of excitement went through everyone who works here. That data clearly demonstrates deeper and more rapid DNA declines in the majority fourth-line or later CLOVER patients who received leronlimab with the backbone, compared to Natera's historic database of third-line patients who received the backbone alone.
That analysis should remove any doubt about the robust anti-tumor activity of leronlimab as a standalone agent when added to standard of care in patients with colon cancer. In a moment, Robert will speak to the crucial next steps for advancing leronlimab as an important new therapy for the treatment of colon cancer. In the last week, CytoDyn also received the very preliminary glimpse into the potential of the Prime and Pair approach, combining leronlimab with a checkpoint in the 95% of patients with colon cancer who don't normally respond to immunotherapy. As Dr. Kasi alluded to, the results are very early, but these early results build on the striking retrospective data we've already presented in patients with extremely advanced metastatic triple-negative breast cancer, who enjoyed a sustained remission for over five years after receiving leronlimab with or followed by a checkpoint inhibitor.
Together, these data point to the potential opportunities with Prime and Pair, not only in breast and colon cancer, but also in a host of other cancers not normally treated with checkpoint inhibitor therapy. In the last week, I was also made aware of remarkable data demonstrating that the PD-L1 protein itself plays an important role in mammalian reproduction by protecting a fetus from a mother's own immune system. A growing fetus is a kind of foreign antigen inside a mother's womb, since half its DNA is derived from the father. Researchers have identified high levels of PD-L1 in the placenta at the crucial interface between the fetal and maternal blood flow.
This observation suggests that many cancers, which likewise express PD-L1 to suppress their own host's immune system, are deploying the same strategy that Mother Nature herself first devised as a way to protect a fetus from the inadvertent and harmful effects of a mother's immune system. To me, this observation lends a certain poetic resonance to CytoDyn's Prime and Pair strategy. Indeed, the presence of PD-L1 in the placenta provides a certain biologic credibility to CytoDyn's approach, which apparently has its very roots in mammalian evolution. Like I said, it has been an exciting time here at CytoDyn. Lastly, the day has finally arrived for me to announce a natural and necessary change in leadership at CytoDyn. Management has understood for some time that the remarkable data that is unfolding would eventually require us to install a CEO with expertise in partnership negotiations and other financial arrangements.
To that end, I am very pleased to announce that Robert Hoffman, our current CFO and someone with decades of experience in executive pharma management, has kindly agreed to step into that role, and that Robert's tenure as our new CEO will start tomorrow. By way of closing, let me just say that it has been the privilege of a lifetime to have served as your CEO these last three years. Let me assure you that I will continue my full-time efforts to help develop leronlimab without interruption. But starting tomorrow, I will do so in my new role as Head of Research and Translational Sciences. So from the top to the bottom of my heart, let me thank you all once again for the faith and the trust you placed in me, and your patience and steady support these last three years.
I am 100% certain that none of us will ever forget this incredible journey that we all took together. With that, I will turn the call over to Robert.
Thank you, Dr. Jay, for the kind words. I give you all the credit for stepping in as CEO at a very difficult time and rolling up your sleeves to uncover the important data in triple-negative breast cancer and other solid tumors, including colorectal cancer. Your commitment and dedication to the value of leronlimab is unmatched. I look forward to continuing to work closely with Dr. Jay in his new role focused on scientific innovation and discovery. I look forward to further exploit the utility of leronlimab. As you just heard, we, as well as our partner, are excited about the data we are seeing out of our CLOVER colorectal cancer study. I am looking forward to keeping the study on track to completion. Assuming the data continues to perform as it has thus far, we believe this will prove valuable in our planned discussions with the FDA.
Be it Fast Track designation, Breakthrough Therapy designation, or a path for an Accelerated Approval. I am also looking forward to continuing to build out a world-class team around me to help realize the full potential of leronlimab. In the near term, I will be announcing a well-qualified regulatory affairs professional who will be instrumental over the coming months. We have recently built out other important areas of the organization, including a highly qualified CMC individual. As I previously mentioned, we have an ex-GSK veteran business development individual helping out with business development efforts. Additionally, we will be looking for an oncologist to serve as our Chief Medical Officer in the coming months. The take-home message, we are going to recruit the optimal team to compile the best data package for the FDA potential partners. Let us turn to upcoming milestones.
CytoDyn is presenting updated clinical and biomarker data from its phase II CLOVER study at the ESMO Congress 2026, taking place October 23 to 27 in Madrid, Spain. The poster will be presented by Dr. Benjamin Weinberg of Georgetown University on Sunday, October 25th, 2026. At ASCO GI Cancers Symposium in January 2027 in San Francisco, we will be expanding and building upon data presented at ESMO. Such data will be high-level readouts from across the entire patient population, will provide updated comparisons to real-world data provided by Natera, as well as analysis of results relative to the ever-evolving metastatic colorectal cancer treatment landscape. In terms of other upcoming milestones, as you can see there, we have closed out on a couple rounds of financing. We expect to announce the new head of regulatory affairs to help guide CytoDyn with FDA and partner interactions.
We are looking forward to dosing our first patient in a dose escalation study in metastatic triple-negative breast cancer, as well as the initiation of additional studies in colorectal cancer in the new year. Looking at the balance of the calendar year 2026 and calendar year 2027, in addition to ESMO and ASCO GI, we will be assembling a data package to present to the FDA. In terms of the market opportunity and key takeaways, we have a first-in-class antibody targeting the CCR5 receptor with potential across multiple solid tumors. I believe the well-tolerated safety profile that Dr. Jay mentioned will be valuable in our discussions with the FDA to test leronlimab in earlier lines of therapy for colorectal cancer patients. We continue to look for other ways to work closer with Natera.
You can tell by their excitement that the collaboration is working out quite well to further leverage our existing collaboration. Colorectal cancer is the leading cause of cancer death in the U.S. for people under the age of 50 and continues to grow and is a large market opportunity for CytoDyn. The market is expected to exceed $25 billion globally by 2030. In fact, LONSURF sales totaled approximately $760 million in 2025 and continues to grow in 2026. We look forward to study other large market opportunity solid tumor indications as well. With that, I'll turn it over to Ignacio for the question- and- answer session of the presentation.
Thank you so much, Robert. The first question we have is for Dr. Jay. We received a lot of updates on CLOVER today. What is the status of all the other projects the company has in the works?
Great, and thanks for that question. Indeed, there are many projects underway to explore the full potential of leronlimab and a variety of other indications, and all that's just another reason why I'm so grateful to Robert for stepping in. Starting in CRC, in addition to CLOVER and the rollover protocol, we're launching several other studies in colon cancer with Dr. Kasi, as well as his colleagues at the KLEOS network of academic GI oncology centers. All those studies will look at leronlimab in patients with an earlier stage of colon cancer, where one could quite reasonably expect even more dramatic results than we've shown today. I'm happy to announce that the contract negotiations for all of these studies are already underway.
CytoDyn is also excited to be working with the PRE-ISPY n etwork on a pilot study of leronlimab plus checkpoint inhibitor in third-line patients with metastatic CRC. The design of that protocol is just now being finalized, and we hope to begin enrollment before the end of the year. Also, and lastly in colon cancer, we're launching a crucial translational collaborative study with Dr. Kasi at City of Hope and Dr. Otto Yang at UCLA, who will examine tumor tissue obtained from study patients to more clearly define the impact of leronlimab on key efficacy metrics, such as CD8 T-cell infiltration into the tumor, as well as repolarization of tumor macrophages and reversal of immune exhaustion within the tumor microenvironment. These data will be of keen interest to various partners who want to evaluate the overall potential of leronlimab in solid tumor oncology.
CytoDyn is also aggressively moving forward in breast cancer. I am pleased to announce that the PRE-ISPY group has finalized their protocol in women with metastatic TNBC, and that study will begin enrolling shortly and will evaluate leronlimab plus a checkpoint inhibitor along with either TRODELVY or the combination of gemcitabine and carboplatin as first or second-line treatment in the metastatic setting. In both colon and breast, we are moving up into earlier and earlier lines of therapy. In keeping with that, as soon as the PRE-ISPY group completes their first dosing cohort, the parent I-SPY network plans on initiating a study of true leronlimab monotherapy in the neoadjuvant setting and will expand the study population to include all women with newly diagnosed HER2- negative breast cancer.
Leronlimab moving into an earlier line of therapy, and I think given the efficacy signals we are seeing, combined with this wonderful safety profile, that is exactly where it belongs. All the studies that I just mentioned in colon and breast are sponsored by CytoDyn, and I am happy to announce they have enjoyed discounted budgeting by our partners to help CytoDyn move as quickly and efficiently as possible. Those discounts have been appreciated. Even better, in contrast to those projects, all the other projects I will briefly mention are being completely funded in full by outside sources. In oncology, CytoDyn is currently engaged with four different academic groups to look at leronlimab in a variety of different cancers.
That list includes a team at the University of Alabama drafting a protocol for patients with recurrent glioblastoma and a team at the Mayo Clinic drafting a protocol for patients with newly diagnosed pancreatic cancer. We have also begun early discussions with a team at Emory University who want to pursue a study of leronlimab plus a checkpoint inhibitor in patients with refractory head and neck squamous cell carcinoma associated with prior HPV infection. Lastly, a team at the University of Rochester recently shared compelling data demonstrating the critical role CCR5 signaling in the bone marrow plays in the pathogenesis of acute myelogenous leukemia. That team has already begun drafting a protocol and started raising funds to support a pilot study in patients with AML. Incredible. Beyond oncology, there are a number of other exciting initiatives underway.
In the interest of time, I will just mention one of those projects. The Cornell study for patients with mild to moderate Alzheimer's disease is now about halfway enrolled. It is interesting, though extremely preliminary, to note that two patients who recently completed 12 weeks of dosing have themselves requested ongoing access to leronlimab due to their own subjective impression of clinical improvement. We are obviously eager to review the objective readout from this study, which will include an objective radiologic endpoint and should become available within four months of the last patient being enrolled. We are anxious to see enrollment continue and note that the study is open and the study team has been open to enrolling patients from outside the tri-state area. There are more studies underway, but I think I already sound like a crazy person.
In the interest of time, I'll leave it there. Ignacio?
Thank you so much, Dr. Jay. The next question from the audience is a very direct one. Is the CLOVER study going to beat the SUNLIGHT trial?
When I look into my crystal ball, I'm extremely hopeful that we will. I think the data that Reny showed that not only was the DNA declines with CLOVER deeper and steeper than the comparator, but that the data he already has showing that deeper, steeper declines translate into better overall progression-free and overall survival. It only seems reasonable to assume that we should be able to easily clear the bar of the 3% on the real-world data or the 6% from SUNLIGHT. The biggest issue for us will be to reconcile all the reports of partial responses, sometimes which are different between the central and the local sites. I know the team is busy working on that. I remain extremely optimistic that CLOVER will come in and surpass the current standard of care.
Thank you so much, Dr. Jay. Our next question from the audience is for Reny from Natera. Reny, can you tell us how do the results in CLOVER compare to ctDNA activity Natera has seen across its historical database?
Yeah. Happy to address that. I think one of the best studies you could look at was published in Nature Cancer. It's Bratman et al. in the INSPIRE study. This was looking across different tumor types in metastatic disease after a few lines of therapy, looking at pembrolizumab KEYTRUDA monotherapy. There were 94 subjects in that study, and we saw 30 of the 94 had an increase in ctDNA, so roughly a third. 12 of the 94 had a ctDNA clearance, which actually resulted in 100% of those 12 patients had an overall survival benefit while in the study. That was pretty remarkable. This is after just two to three cycles of pembrolizumab, so it was highly predictive of response. That actually led to Natera getting Medicare reimbursement approval for monitoring immunotherapy treatment and using Signatera to monitor the response.
The remaining patients had a decrease, but not a clearance. Obviously did better than those that had an increase, but not as good as those that had the full undetectable levels. I think that's one of the closer comparators that I could point you to. Again, here we saw, remember, zero of the 12 had any increase in ctDNA. Almost all of the patients had 80% or more reduction, and I think there was just one outlier that had maybe a 20% or 30% reduction. So that gives you good context to what else has been published.
Thank you so much, Reny. Our next question is for Robert, the recently appointed CEO. Given the recent financing activity you mentioned, can you tell us what is the current cash runway for the company?
Oh, thank you for that question. We did report cash on our 10-Q, which is at August 31st, of $16.4 million. We did have a little money come in after for the financing, so on a pro forma basis, cash of $18.3 million. That cash will last us into the second half of 2027. That is really important as we continue to move forward and hopefully be in a position to negotiate with potential partners from a position of strength, having a more solid balance sheet in that regard.
Thank you, Robert. Final question. Now that you've been appointed CEO, can you tell us a little bit more about your intentions in the first 100 days, and what are your suggested keys to success for CytoDyn?
Good question. Over the next 100 days, I will continue to focus on supplementing and building out the team around me to put CytoDyn in the best position possible for upcoming interactions with the FDA and potential partners. As I mentioned earlier, I will continue to focus on continued execution of the CLOVER study to get that to completion. I will continue to tell the story about the potential of leronlimab. You heard a lot of different potential, not only from Natera, from Reny, from Dr. Jay, but also from Dr. Pashtoon Kasi. I will continue to communicate that at industry conferences, including Wall Street analysts and potential partners, and I will continue to explore the potential with Dr. Jay other ways to realize the full value of leronlimab.
Thank you, Robert. We can now proceed with your closing remarks as we are at 5:00 P.M. on the dot Eastern Time, 2:00 P.M. Pacific Time.
Thank you. As we wrap up today's update, I want to take a moment to express how genuinely excited and honored I am to step into the role of CEO. I have tremendous appreciation for the opportunity in front of us. I don't take lightly the responsibility that comes with leading this company at such an important point in its history. What excites me most is not simply where we stand today or I believe we can take it from here. We have a compelling molecule, a clear path forward, a team of talented, dedicated individuals who believe deeply in what we're working to accomplish. I also want to express my sincere appreciation to our shareholders, many of whom demonstrated extraordinary patience, loyalty, and conviction in CytoDyn's potential.
That support is not lost on me. I will recognize that the simple best way to honor it is through discipline, execution, meaningful progress, and ultimately results. I believe we have a tremendous opportunity to complete something special here. My commitment is to approach that opportunity with urgency, accountability, transparency, and an unwavering focus to maximize shareholder value. I am energized by the challenges ahead and confident in the people around me and incredibly optimistic about CytoDyn's future. Thank you for your continued trust and support. I could not be more excited for what is ahead. Thank you for attending today's call.
Thank you so much, everyone, for your participation. This concludes CytoDyn investor update webcast. You may now disconnect.