Healthcare equity research team. Our next presentation is by Walter Klemp, Founder, CEO, and Chairman of Moleculin Biotech. Moleculin's lead investigational drug is Annamycin, a phase II stage next-generation anthracycline designed to avoid multidrug resistance and eliminate cardiotoxicity typically associated with anthracyclines. Wally, please take it away and introduce us to the company.
Thanks, Vernon. Before we get started, I do need to remind everyone that Moleculin is publicly listed, and I'll be making forward-looking statements as a part of this presentation. You can access all of the latest information and our SEC filings on our website at moleculin.com. Now, to get started, I think it's important for me to give a brief review of what our drug, Annamycin, is and why it's so important, especially in acute myeloid leukemia, or AML. The most important class of drugs to date for AML, as well as many other tumors, is anthracyclines. In fact, anthracyclines have been a cornerstone of chemotherapy or cancer treatment for over fifty years now. But there's been very little in terms of the advancement of anthracyclines, except for some improvements in drug delivery.
Until now, there really hasn't been a successful effort to actually improve the efficacy and safety of anthracyclines with true breakthroughs in chemical structure. But Annamycin changes all this, and, in fact, this is the first real breakthrough in 50 years. Moleculin's proprietary anthracycline is what we believe to be a true disruptor in what otherwise is a very well-established class of drugs. Based on our clinical trials to date, we believe it may be safer and more effective than any currently approved anthracycline, period, and we believe it fills an unmet need for more than half of the AML population, and it has uses far beyond AML.
Now, even though I'm gonna focus today's discussion on AML and the recent advancements we've made, including the upcoming launch of our pivotal phase 3 clinical trial that we call the MIRACLE Trial, we shouldn't lose sight of the fact that we do have an active clinical trial in sarcoma as well. We frankly believe that a lot of biotechs, small biotechs, would give anything to have the data that we've amassed to date. Annamycin has been able to generate a 60% CRC rate in second-line patients, and that includes a 50% CR rate in combination with another 10% CRi. Now, for those that aren't that familiar with the AML space, these are way better numbers than any other drug approved for relapsed or refractory AML.
A conservative estimate says that Annamycin should be able to more than double the number of patients achieving complete remission compared to all of the approved targeted therapies combined, and this is possible in part because of Annamycin's complete lack of cardiotoxicity. We've treated over 80 patients so far across multiple studies, and we've yet to see any indication of cardiotoxicity. Now, what's important here is that all of this puts us on a course to begin a pivotal registration study this year with the potential for securing an accelerated approval pathway from regulators. So we are now a phase III company. We have data that outperforms every asset approved in AML to date, and we're doing this in a space where lesser assets sold in 2021 for $2 billion, and we've established what we believe is a pathway to approval.
Now, look, Annamycin is anything but a me-too product. Its lack of cardiotoxicity, combined with its greater potency and lack of cross-resistance with currently prescribed anthracyclines, really puts it in a class by itself, and while this is true for a wide range of potential indications, it's especially meaningful in AML. But the absence of cardiotoxicity, we believe, will be a real game changer, and that's because currently used anthracyclines are so cardiotoxic that the FDA stipulates lifetime maximum exposure levels. In fact, if a patient is dosed beyond the 550-milligram per square meter limit, there's a 65% chance of a cardiac event, and if that patient goes beyond 850 milligrams, the risk is 100%, and there's even an 8% chance of outright heart failure.
So we believe those risks can now be eliminated with the use of Annamycin. In fact, in the gold standard animal test for chemotherapy cardiotoxicity, where doxorubicin has shown 100% cardiotoxicity, Annamycin is 0% cardiotoxic. But Annamycin gives up nothing in terms of efficacy compared with the most commonly used anthracycline, doxorubicin. Annamycin outperforms dox head-to-head in a highly aggressive AML mouse model, and when we combine Annamycin with cytarabine in the same model, we see significant synergies with the combination, and that outperforms cytarabine alone by over 240%. Now, it's this combination, and we call AnnAraC, that has been the focus of our latest AML clinical trial, MB-106, and as of today, that trial has produced some impressive results, especially in second-line patients.
Now, we think this is particularly important given the magnitude of the unmet need for second-line therapies in AML. Now, for those of you that aren't familiar with the disease, AML is a type of cancer, specifically a hematologic malignancy, that starts in the blood-forming cells in the bone marrow, and it leads to rapid growth of abnormal, generally immature white blood cells, and this occurs to the detriment of normal blood formation. If you can't form normal red blood cells, white blood cells, and platelets, it manifests as symptoms, including profound fatigue, frequent infections, and easy bruising and bleeding. There are about one hundred and sixty thousand cases worldwide and about twenty thousand newly diagnosed patients each year in the U.S. alone. Unfortunately, the five-year survival overall remains at less than 30%.
AML represents a significant unmet need for more effective and tolerable therapies, particularly in older adults and also in the relapsed and refractory setting. Now, Vernon, I know that you understand this well, but for the audience, we wanna make sure that they understand. We believe the most important immediate commercial opportunity for Annamycin is that it fills an unmet need for more than half of AML patients. Based on our clinical trials to date, Annamycin has delivered more than double the complete remission rate of any treatment for relapsed/refractory AML. Now, look, the leukemia community is truly grateful for the important contributions of existing anthracyclines, as well as Venetoclax, and more recently, targeted therapies. Let's face it, the sad truth is that all of these drugs combined help only about 40% of the AML populations.
So per industry guidelines, including the NCCN, the rest, nearly 60% of all AML patients, they're left to clinical trials or palliative care, and the primary reason for this is relapse from or resistance to existing therapies. And this is where Annamycin's lack of cross-resistance comes into play, and it shows in what we believe are the remarkable efficacy numbers that we've delivered to date. Now, look, a lot of attention has been focused on the promise of targeted therapies, and in fact, five new drugs have been approved on that basis. But these drugs are only helpful to those patients who happen to have just the right genetic mutations to qualify for these targeted therapies. And this means that over 50% of all AML patients are ineligible for approved targeted therapies today.
This, by itself, presents an enormous opportunity for us, as we believe AnnAraC has the potential to treat all comers in second line. What's more, the actual performance of these targeted therapies is nowhere near the levels we're seeing with Annamycin. To show just how much better we believe Annamycin is compared with the best alternative approved treatments for relapsed refractory AML, let's just look at how many patients actually benefit. All of the targeted therapies combined, they're able to help about 13% of second-line AML patients in the aggregate. But the performance we produced with the MB-106 trial suggests that Annamycin should be able to more than double that success rate. And if you're thinking that the relatively low performance bar set by targeted therapies means that they don't have as much market value, well, think again.
I mean, the mid pharma company Servier paid $2 billion for Idhifa and Tibsovo. Those are two drugs that, in the aggregate, help about 4% - 4% of the second-line AML population. We're currently showing a performance from Annamycin that's ten times that number. And when you translate all of what we just stated into market value, the potential for shareholders here, we believe, is enormous. I mean, market caps and recent exits in this space have been 10 to 1,000 times greater than our current market cap. And as we've said many times recently, we believe this disparity in value that's reflected on this slide, it just can't last, and the ultimate exit value for Moleculin shareholders may be measured in the billions. Thankfully, now we have the regulatory visibility we needed to give people a realistic timeline for this to happen.
Now, focusing in on our path to the positive data that we generated, this is a summary of the three clinical trials we've conducted in AML patients so far. I wanna keep this brief, so let's just characterize the first two AML clinical trials as establishing safety and efficacy for Annamycin as a single agent. Even though the efficacy numbers were encouraging, the preclinical research we sponsored at MD Anderson Cancer Center made it clear that we could expect even better results by combining Annamycin with Cytarabine. For the most part, and folks who have been following Moleculin have already seen these remarkable efficacy numbers, especially in second-line subjects. But now we've added two more subjects. Now, I will say, they weren't second line, so they didn't change the second-line outcome.
But what did change is to add another third-line subject, and we're now showing the combined results for second and third line, where the n equals fourteen and the CRC rate is 50%. What's also changed is our median durability of remission, which has increased to seven months, and we've been able to characterize anecdotally that these outcomes, they appear to be agnostic to prior therapy, and importantly, they've resulted in MRD-negative test results in 78% of responders. Now, I know you know this, Vernon, but for the audience, MRD stands for Measurable Residual Disease, and it's gained in popularity among investigators as a strong prognostic indicator. Simply put, the prevailing opinion is that MRD-negative patients are more likely to have long-term positive outcomes than those who tested MRD positive. Compared to available treatments for relapsed/refractory AML-...
78% MRD negative is an impressive outcome. We've also gained some insight supporting our belief that Annamycin is genotype and mutation agnostic. In fact, 89% of our complete remissions came from subjects with cytogenetics and mutations that are generally considered difficult to treat and are associated with poorer outcomes. So put it this way, we've taken some of the most severe AML patients, and we've given the majority of them the most hoped-for outcome: durable, complete remission, and for many, a pathway to a curative bone marrow transplant. So that brings us to the launch of our phase 3 pivotal trial. Officially, we're calling it the Moleculin Relapsed/Refractory AnnAraC clinical Evaluation, and that is quite a mouthful, so we've shortened that to an acronym that we call the MIRACLE Trial.
Now, overall, we strongly believe that the recent end of Phase 1b/2 meeting that we had with the FDA significantly de-risked the development program for Annamycin. Importantly, we presented the FDA with data from 84 patients, including reports by an independent expert in the field of cardiac damage from anthracyclines. And by the way, those reports indicated a complete lack of cardiotoxicity from Annamycin. Now, these data and reports were reviewed by both the Hematology Oncology Division and the Cardio-Renal Division, which is considered the ultimate authority within the FDA regarding the cardiotoxicity of drugs that are seeking approval. As a result of the review, the FDA has now agreed to allow AML patients in the U.S. to be treated for the first time above the current lifetime maximum allowable anthracycline dose limit.
That opens the door for us to finally bring Annamycin back to the U.S. for all future clinical development, which reduces the time and complexity of ultimately gaining an approval. Now, at the specific recommendation of the FDA, we're planning the MIRACLE Trial to be an adaptive phase 3 trial design, where the first seventy-five patients will be randomized to receive HiDAC, which is high-dose Ara-C, plus either placebo, a hundred and ninety milligrams per square meter of Annamycin, or two hundred and thirty milligrams per square meter of Annamycin. For the second portion of the trial, approximately a hundred and twenty patients will be randomized to receive HiDAC plus either placebo or whichever dose of Annamycin is found to be optimal, based upon the interim look at the data from the first seventy-five patients.
Now, the selection of an optimum dose will be based not only on the absence of dose-limiting toxicities, but also on the overall balance of safety, pharmacokinetics, and efficacy, of all data obtained from the initial 75 patients. Now, this is consistent with the FDA's new Project Optimus initiative, but of critical importance here is the primary endpoint, and that's planned to be complete remission at approximately one month. Now, this is especially important because of the speed with which we can evaluate performance and the fact that based on our data to date, we have a very high degree of confidence in the ability of Annamycin to outperform the comparator arm, specifically HiDAC, using that endpoint.
Now, the secondary endpoints of durability and remission are also important, but they won't be the basis for approval, and therefore, this design significantly shortens and de-risks our potential path to approval. It is important to note that the FDA does not distinguish between second, third, and further lines of therapy in the NDA process, and they've requested that we also provide randomized data for third-line, as well as second-line subjects. To accommodate this, we're also facilitating the establishment of an optimum dose. We're gonna conduct the Miracle Trial in only second-line patients, and then we're gonna follow on with a similar trial we're calling MIRACLE 2 , that only enrolls third-line subjects.
Now, we estimate this second trial will be approximately a 200-subject trial, randomizing one-to-one between the optimum dose of Annamycin established in the initial Miracle Trial and placebo, both combined with high-dose Ara-C. So look, one thing we cannot stress enough is how much we believe this trial design has de-risked our path to approval. As you can see from this chart, the historical performance of HiDAC is very well-established at around 17%-18%. In comparison, Annamycin's performance in combination with HiDAC in our most recent trial was more than double that level. Now, all of today's discussion is really a prelude to the potential approval of Annamycin. We also think from an investor perspective, that what's about to unfold has potentially massive value inflection potential.
We believe this is the case because the next major events, the triggers of the pivotal phase 3 MIRACLE trial, the output from the trial, and the potential for an NDA submission, they all represent the opening of an exit window for our shareholders. Even though today's presentation is solely focused on AML, please don't forget that Annamycin has potential uses far beyond just this one indication. Based on our current sarcoma trial and other preclinical studies, we believe Annamycin could play a significant role in the treatment of all cancers, all the ones listed here, right? Just as other currently approved anthracyclines do today. Importantly, our data indicates that Annamycin should be safer and maybe more effective than those other anthracyclines....
Okay, including cash as of June 30, 2024, plus the proceeds of our recently announced financing, we have an adjusted pro forma cash balance as of the end of Q2 of approximately $15 million. Now, this adjusted cash balance will take us into the first quarter of 2025, but including future milestone-based warrants, we have the potential for another $11 million of potential aggregate gross proceeds upon the exercise in full. And I would be remiss, though, if I didn't acknowledge the gap demonstrated between the performance of our lead drug and where our market cap is today, which in my opinion, is simply no longer justified. Now, we believe once the market awakens to this new reality, a more appropriate trading range will be established, and this isn't just talk.
I've been investing my own after-tax dollars in Moleculin stock because of my belief in what I'm saying. In fact, I've personally invested over $300,000 over the last year and a half, and the rest of our management team has been investing alongside me. Look, we are believers, and we are committed to making this a success. Just to be clear for investors, we've included in this presentation a table of upcoming milestones, and I won't go through them here, but as always, this presentation is available for everyone's review on our website. Look, becoming a phase III company has been, I mean, such a sought-after goal for us, Vernon. It's hard to believe we're actually here. You know, we believe the valuation disparity that's persisted to date just can no longer be justified.
But most importantly, we believe we're on the cusp of improving and frankly saving thousands of lives by positioning Annamycin for new drug approval. So thank you and to your audience for taking time to learn more about Moleculin and Annamycin.
Yeah, well, I look forward to helping you grow the story and grow awareness of Annamycin. Wally, specifically, thank you for helping us learn about Moleculin Biotech. Your presentation of Annamycin and its differentiation versus traditional anthracyclines is very intriguing, and we look forward to further updates on its advancement into the pivotal MIRACLE Trial later this year. To everyone attending online, thank you. We appreciate your time, and hope you are gaining valuable insights and ideas into investment opportunities that we believe are represented by the 500-plus companies participating at our conference this year.