Moleculin Biotech, Inc.

Hello, and welcome to the Moleculin Biotech fourth quarter and full year 2024 update conference call and webcast. A question and answer session will follow the formal presentation. As a reminder, this conference is being recorded. At this time, I'd like to remind our listeners that remarks made during this webcast may state management's intentions, beliefs, expectations, or future projections. These are forward-looking statements and involve risks and uncertainties. Forward-looking statements on this call are made pursuant of the safe harbor provisions of the federal securities laws and are based on Moleculin's current expectations and actual results could differ materially. As a result, you should not place undue reliance on any forward-looking statements. Some of the factors that could cause actual results to differ materially from these contemplated by such forward-looking statements are discussed in the periodic reports Moleculin files with the Securities and Exchange Commission. These documents are available in the investor section of the company's website and on the Securities and Exchange Commission's website. We encourage you to review these documents carefully. Additionally, certain information contained in this webcast relates to or is based on studies, publications, surveys, and other data obtained from third-party sources and the company's own estimates and research. While the company believes these third-party sources to be reliable as of the date of this presentation, it does not independently verify and makes no representation as to the adequacy, fairness, accuracy, or completeness of, or that any independent source have verified any information obtained from third-party source. Any data discussed regarding clinical trials and progress are considered preliminary and subject to change. Joining us on today's call from Moleculin's leadership team are Walter Klimt, Chairman and Chief Executive Officer, Dr. John Paul Weymack, Senior Chief Medical Officer, and Jonathan Foster, Executive Vice President and Chief Financial Officer. Now let's turn the call over to Walter Klemp, Chairman and CEO. Wally, please proceed.

Thank you, Operator. Good morning, everyone, and thanks for joining us today. I'd like to kick things off with a brief overview of where we are. The entire Moleculin team has been laser-focused on the launch of the Miracle Phase 3 Pivotal Trial for Anomycin. Now, this is a study designed to win approval for anamycin in combination with cytarabine for the second-line treatment of relapsed and refractory AML patients. This is a global study with sites planned for the U.S., Europe, and the Middle East. Twenty-five sites have been selected to date, and we've already announced regulatory and ethics approval in our first European country. and we expect several more in second quarter. Patient screening has already begun, and we still expect our first patient to be treated yet this quarter. Now, in terms of managing expectations, I should point out that the US will likely be one of the last countries to begin enrolling in this trial. Now, that's not unique to our trial, but rather it's a function of the fact that the approval process between institutional review boards, ethics committees, and hospital contract negotiations just takes longer than in most other countries. We do already have our first IRB approval in the US, but in terms of overall timelines, you should expect the non-EU and Middle Eastern countries like Ukraine, Egypt, and Georgia to start first, followed by the more traditional EU member states, and then finally the US. One of the most Important and exciting aspects of the MIRACLE trial is the amount and timing of visibility that molecular stakeholders will have. Unlike most pivotal phase three trials, we will have multiple unblindings of data so that there is line of sight to exactly how we're tracking. The first of these will be when we reach 45 subjects, and we expect to achieve that before the end of this year. Then there will be a second unblinding at the end of Part A of the trial at between 75 and 90 subjects. That should be in the first half of 2026. Part of the reason we expect this to happen so quickly is that the primary endpoint is complete remission after just one cycle, which is approximately one month. So roughly 30 days after the 45th subject is treated, we will be able to see how the drug is performing. The other really exciting part of this is how much we already know about anamycin in second line AML patients. As Paul will discuss in his segment, our phase two data just keep getting better. Overall survival keeps climbing at 11 months and durability has reached nine months and is still climbing. As a reminder, The performance of anamycin in our latest phase two trial was better than any drug ever approved for second line AML patients. Also, as we discussed, as disclosed recently, our latest analysis shows that anamycin overcomes resistance to venetoclax in AML and is delivering durable, complete remission in patients where venetoclax has failed. And through all of this, we continue to see a complete absence of drug-related cardiotoxicity. As I mentioned at a recent conference, the latest anamycin results were frankly so good that a lot of industry players simply didn't believe them. But I can say with confidence that that is beginning to change. A number of key opinion leaders in the US and Europe have now reviewed the data in detail, and have even discussed the results with the investigators in the trial, who, by the way, span seven sites in two different countries. These experts are now recognizing the significance of the data and the potential importance of anamycin for AML patients. And they are now speaking out about the game-changing implications of what, if approved, will be the first ever non-cardiotoxic anthracycline. Let me now hand the call over to our senior chief medical officer, Dr. Paul Waymack, to discuss our clinical activity in more detail. Paul?

Thank you, Wally. Well, as we have noted during prior updates, there is an incredible unmet need in AML. And especially for those patients who either don't respond to initial therapy, that is, they're refractory to current therapies, or quickly relapse after first-line induction therapy. And you can see from our Phase II data obtained in our MB106 clinical trial, this is where anamycin excels. As we have previously reported, we achieved a 50% complete remission rate in these second-line patients. We treated with anamycin plus high-dose sayotirabine. which is more than double the performance you would expect from existing therapies. And the durability of our responses continues to improve. As Wally mentioned, our median progression-free survival has now increased to nine months, with our overall survival amongst second-line therapy patients at 11 months. And as we previously reported, 78% of them were recorded as negative in terms of measurable residual disease. So, for second-line therapy patients, we believe that our durability is shaping up as truly a game changer. This 50% CR rate in second-line therapy with anamycin plus high-dose cytarabine compares very favorably to a 17 to 18% CR rate reported in two large recent clinical studies in patients with refractory and relapsed AML. And I should note that in both of these studies, the control arm used high-dose cytarabine, the exact same control arm we intend to use in our Phase III study. Moving on to our new Phase III study, the MIRACLE trial, it was designed after an end of Phase I-II meeting with FDA. It is to be a randomized study comparing the dosing regimen with which we had great success in our MB106 study, that is, anamycin plus high-dose cytarabine with the control arm of placebo plus high-dose cytarabine. We chose this design because FDA encouraged it and because two recent large randomized clinical trials in refractory and relapsed AML patients, that is the MIROS and CLASSIC-1 clinical trials, which are the ones we mentioned in the prior trial, used it and both achieved approximately a 17.5% CR rate among patients randomized to receive high-dose Cytarabine plus placebo. To that end, we can expect we will need for our anamycin plus high-dose Cytarabine treatment arm to beat a 17.5% CR rate to a statistically significant degree for our drug to be approved by FDA for marketing. And again, in our MB106 study, this combination of high-dose cytarabine plus anamycin achieved a 50% CR rate. For our phase three study, as I noted, we will be comparing anamycin plus high-dose cytarabine against placebo plus high-dose cytarabine. During part A of the study, we will have two different anamycin treatment arms, a 190 milligram per meter square treatment arm and a 230 milligram per meter square treatment arm. There will be unblinding of the data in part A after the first 45 patients have completed their efficacy analyses, and the second unblinding after between 75 and 90% of patients have completed their efficacy analyses. These interim looks at the data are in part to determine which of the two anamycin dosing regimens will be taken to completion of the study. And the primary efficacy endpoint is the rate of complete remission of leukemia at approximately day 35. All patients will be eligible for standard treatments after completion of their experimental therapy. We have already had one site that has been activated and believe that we may begin treating our first patient before this quarter is over. As I previously noted, Part A of the study will determine which of the two animizing dosing regimens take all the way through to completion of Part B. Part B will randomize 222 patients to receive placebo plus high-dose cytarabine or animicin plus high-dose cytarabine using whichever animicin dosing regimen Part A found to be superior. The next slide documents our timeline. I should note, as shown on this slide, that there is a small possibility that the results from our analyses at the end of Part A could be so definitive so as to confirm the efficacy of anamycin plus high-dose cytarabine. If this were to happen, then we might be able, for ethical reasons, to complete Part B as a single-arm study. Let me note that although we have had no major clinical updates since our MD106 study completed enrollment last year, we have been quite busy clinically designing our phase three study, obtaining regulatory approval for conducting the study on multiple continents, and signing up various hospitals and investigators to participate. As of today, we have approximately 25 sites selected to participate in the study, and another approximately 45 who are in the process of completing the selection process. And we still believe that we can begin treating the initial patient in our MB108 study in this order. John, let me pass the baton off to you now.