Moleculin Biotech, Inc.

Greetings and welcome to the Molecular and Biotech Quarterly Update Conference Call and Webcast. At this time, all participants are in listen-only mode. If anyone should require operator assistance, please press star zero on your telephone keypad. A question and answer session will follow the formal presentation. You may be placed into question queue at any time by pressing star one on your telephone keypad. As a reminder, this conference is being recorded. It's now my pleasure to introduce your host, Janine Thomas, Investor Relations. Please go ahead, Janine.

Thank you, Kevin. Good morning and welcome, everyone. At this time, I would 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 to 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 Investors 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 of that any independent source or verified any information obtained from third party source. Any data discussed regarding clinical trials and progress are considered preliminary and subject to change. This morning joining us on our call from Moleculin's leadership team are Walter Klempp, Chairman and Chief Executive Officer, Dr. John Paul Ramack, Senior Chief Medical Officer, and Jonathan Foster, Executive Vice President and Chief Financial Officer. I would now like to turn the call over to Mr. Klimt. Wally, please proceed.

Thank you, Janine. Well, investors who've been following our presentations are not new to this, but we are resolute in our belief that our current market cap is nowhere close to reflecting the value of a phase three company like Moleculin, especially in light of how much risk we believe we have removed from the pathway to approval. Ultimately, we believe that just creates more opportunity for investors today. And I'm confident that as our miracle trial unfolds, the magnitude of this opportunity will become more apparent. If you're new to molecular and asking why this opportunity even exists, we believe that for nearly a decade now, the AML space has been betting on a big payoff from targeted therapies. Excuse me. But the reality is that these new targeted therapies simply haven't delivered. In fact, they've been a big disappointment. And it's evidenced by the fact that venetoclax, which is a non-targeted chemotherapy, has created far more value in the last five years than all of the targeted therapies combined in AML. Now, the fact is that anthracyclines continue to be among the most used and most effective cancer therapies available. They're used in 32% of breast cancers, half of all AML patients, 70% of lymphomas, and actually 60% of all childhood cancers. So if you're looking for a true disruptor opportunity, the Anamycin story deserves your attention. What we believe we have is a safer, more effective anthracycline than has ever been possible. And it's enabling clinicians to treat with higher dosages and for a greater number of cycles than was ever thought feasible. And we aren't just filling an unmet need for more than half of AML patients. We're talking about potential uses far beyond just AML. Now, in this presentation, we're focusing just on the latest updates. So if you're new to Moleculin, I urge you to review our online presentations and watch our explanatory videos. With that said, though, just to hit the high spots of the Moleculin opportunity, the key takeaways from this slide are that unlike currently available anthracyclines, anamycin was designed to be 100% non-cardiotoxic. It avoids cross-resistance with the leading AML drugs, which means it has the potential to work when the others fail. And anamycin is patent-protected through 2040, which is a remarkably long remaining patent life for a Phase III cancer drug. And in part because targeted therapies have been such a disappointment, We still have almost 60% of the AML population without an acceptable treatment option. There is still an incredible unmet need in AML. So let me now ask our Senior Chief Medical Officer, Dr. Paul Waymack, to provide an update on patient data and our startup of the Phase III Miracle Trial. Paul?

Thank you, Wally. Well, as Wally said, there is an incredible unmet need in AML. And specifically, it is for those patients who either don't respond or quickly relapse after first-line induction therapy. As you can see from our most recent Phase II data, this is where anamycin excels. As previously reported, we saw a 50% complete remission rate in these second-line patients, which is more than double the performance you would expect from existing therapies. Since their last update, the bone marrow transplants in subjects with a response have increased to four of the nine patients. This is remarkable for second-line patients as bone marrow transplants is the key to potentially long-term durability, as you will see in the next slide. And the durability of these responses just keeps getting better. We're now up to a median of eight months and still climbing. In addition, these responses are considered high-quality complete responses by the hematology community, with 78% of them recorded as negative in terms of measurable residual disease, and now with 44% of our responders bridging to a potentially curative bone marrow transplant. Again, for second-line subjects, we believe that our durability is shaping up as truly a game changer. Of course, it's this remarkable response rate that led FDA to encouraging us to use an adaptive trial design for our phase three approval trial, as we call it, the miracle trial. For those new to this trial, it begins with a Part A, which is designed to establish an optimum dose for animicin, and then it expands that dose into additional subjects in Part B. This trial design is responsive to a new FDA initiative called Project Optimus, the purpose of which is to avoid simply defaulting to the maximum tolerated dose and instead seeks a balance between safety, tolerability, and efficacy. It's worth clarifying, though, that we don't view this dose optimization process as resulting in any increased risk in approval risk. To the contrary, the FDA actually specified the two doses they would prefer to see compared as the two doses in the MB106 trial that demonstrated both efficacy and safety, and they're leaving it up to us as the sponsor to ultimately choose between the 190 milligram per meter squared and the 230 milligram per meter squared dosing regimens. Also, our initial PK analysis, that is pharmacokinetic analysis, showed that there is no correlation between area under the curve or concentration maximum and the change from the 190 to the 230 dosing regimens. or in layman's term, the increase in dosage doesn't appear to increase the amount of drug in circulation. And this corroborates our clinical findings to date, as we have seen strong efficacy at both dose levels. So, to be clear, we don't see the optimization process resulting in any increased risk in this trial. In fact, it's just the opposite. To facilitate the dose selection, the data must be unblinded early, which we believe dramatically reduces risk for our investors.

Yes, that's absolutely right, Paul. Remember, most phase three approval trials leave investors and prospective big pharma partners in the dark for years. until the data can finally be unblinded. Our ability to unblind early because of this adaptive design means we won't have to wonder whether our phase three trial is tracking with endpoint expectations. And by the way, we're still looking at additional ways to improve early visibility in this trial, so stay tuned for additional updates on this. This becomes even more meaningful when you look at the endpoint we need to hit. Look, let's face it, biotech is a high risk business, which is why the potential upside returns can be astronomical. In oncology, it's estimated that only about 40% of phase, 45% of phase three trials will succeed. And the vast majority of those that fail do so because of a lack of efficacy. That's why it's so critical for investors to understand just how much we have de-risked our Phase III trial. The FDA is asking us to compare to one of the few standards of care that is approved for use in second-line patients. It's called high-dose ARAS-C or HIDAC. Now, this is great news for us because the efficacy of HIDAC in this class of patients is well documented and very consistent with a CR rate of around 17 to 18%. That means the performance of Anirac, that's what we call the combination of anamycin plus HIDAC, is almost three times greater than HIDAC alone. As a comparison, one of our key opinion leaders in the AML space recently commented that the new drug approvals in AML are justified if the new drug is at least 30% better than the standard of care comparison. Well, by this standard, we are over 280% better. But there is likely less risk than even this massive disparity in performance suggests. That's because of how HIDAC was measured in these prior large studies. In the MIROS study you see on the left, patients were allowed two cycles of treatment in order to reach a CR. And in the classic one trial, they were allowed even more, up to 120 days of treatment before reaching their endpoint. In contrast, our CRs were accomplished in less than 49 days with just one cycle of treatment. What this means is that the performance delta between test and control could be even greater than we're predicting. So now let's look at the potential impact this endpoint could have on the timing of approval. And let me caveat, this is not the plan, it's just a look at some potential upside. We had an investor recently challenge us on our trial design. Now he had a decent understanding of statistics and said, if your performance is expected to be so much better than HIDAC, why do you have 330 patients in the total trial? Shouldn't you be able to achieve statistical significance with closer to 100 patients? The answer is that this is what big pharma has asked us to do. In our discussions with prospective partners, we have heard more than once that these players have been burned by buying into a phase three trial only to end up having the trial miss its endpoint because they didn't have sufficient subjects to power the trial because the delta between test and control ended up being closer than management estimated. In essence, small biotech teams facing tight budgets and timelines get lured into overly optimistic assumptions that result in underpowered studies. Big Pharma would much rather buy into a longer, more expensive study that they believe has a higher likelihood of success. And that's what we tried to do here. But what happens if our numbers play out closer to what history suggests? What if at the unblinding of 90 patients, we're really outperforming HIDAC by 280%? Well, under those circumstances, assuming drug safety is also in line with our experience to date, it's very likely that our independent data monitoring committee could conclude that continuation of the control arm of the trial would be considered unethical. And at that point, we would likely request a type A meeting with the FDA to discuss converting part B of our trial into a smaller single arm study designed to complete the safety analysis and satisfy DEI requirements. Essentially, it could take a year or more off of the approval timeline and virtually eliminate any remaining efficacy related approval risk. Now, in no way are we asking investors to plan on this, but we want to make sure you understand how dramatic the upside could be here. What we are saying is if you want something to worry about regarding molecular, it shouldn't be the traditional efficacy risk associated with most phase three trials. Our biggest focus right now needs to be on recruitment because the pace of recruitment is going to drive our data milestones. We are in a race. to open sites and start recruiting patients just as quickly as we can to ensure that we get to the interim data readouts that everybody wants to see. To date, we have 60 sites interested and 17 more sites we're targeting. And you can see by this map that this is happening on a global scale. But Paul and I are committed to ensuring these sites are engaged and productive. To that end, we are actively physically visiting any of these sites that we think could be big producers to make sure their facilities and systems are up to the task and that the principal investigators understand the science and the protocol and are truly bought in to the importance of this trial. It takes a lot of effort to meet face-to-face with every one of these investigators, but we believe it will pay off in terms of the data readouts.

Wally, hold on. I know you were going to skip this part, but I'm sorry to interrupt. Look, I got to point out to everybody on this call what you and Paul did the last few weeks. I know you weren't going to do it, but look, they believe in animizing so much they went into a country at war and another where they were experiencing riots, war and riots, Ukraine and Georgia. Wally and Paul spent two nights in a bomb shelter in Kyiv just to be able to meet the investigators face-to-face. They went from there to Tbilisi, right in the middle of the rioting in the streets, I think over the contested presidential election. So I ask the analysts and the people on this line, how many senior management teams do you know that would do this all at their own personal risk to ensure the success of a cancer drug? Think about it.

Sorry, Wiley. Thanks, John. Well, the fact is my wife wasn't very happy about it. And look, maybe it was a little extreme, but as you said, John, we believe deeply in anamycin, and we are all committed to doing what has to be done to get this drug approved. This is a fight worth winning, and we believe we're going to win. Now, we've been focusing 100% on AML today. but we should never forget that anamycin has potential applications far beyond AML. In fact, the growth potential is probably in the range of 20 times that which would come just from AML. And successful drugs in the AML space are often valued in the billions. So, John, let's go back to you and ask you to wrap things up here with the review of the financial situation.

Sure, Wally. We ended the quarter with $9.4 million in cash on hand, enough to reach into Q1 of 2025. Using our fully diluted shares outstanding, which includes the pre-funded warrants, our market cap is roughly $15.9 million. Our stock has about 40,000 shares traded on average each day. So we got to go back to the miracle chart where we have some key inflection points coming. And as Wally said, we're looking to add more. Let's discuss the key milestones in our plan. First of all, look for more information on contracting and recruitment of sites later this year. And then the first subject treated in MIRACLES should occur in the first quarter of 2025. Then we'll have a look at the overall CR rate and recruitment update in the second half of 2025. This should allow us to interpret the CR rate on possible sets of the trial. North of 20-25%, given the historical CR rate of HIDAC, as Wally mentioned, should indicate the efficacy of anamycin as it were. It will take us approximately $15 million to get to this point. Then the big data readout in mid-2026, interim primary efficacy and safety data on the first 75 to 90 patients, That readout, in my opinion, will really show people the possibility and the risk associated with the success of the trial. This should, I'm sorry, mid-2026 is the interim data readout, and then that, you know, that cascades into a lot of action as we finish Part B and we start enrollment of Miracle-2. For third-line subjects, And then in 2028, we have the primary efficacy data point for second-line subjects. And having that final primary efficacy data for those second-line subjects will allow us in the second half of 2028 to begin submission of a rolling NDA for the treatment of relapsed refractory for accelerated approval on the primary endpoint of CR from this miracle trial. So to conclude, as Wally has already described, the MIRACLE trial is unlike any other Phase III trial that I know of. It is substantially de-risked and provides many informative key data points along the way. And we're looking to improve that visibility, as Wally mentioned. Wally?

Yeah, thanks, John. Before we conclude, let's see if we can address questions from the analyst community. Jeanine?

All right, Kevin, can you please open up for Q&A?

Certainly. When I'll be conducting your question and answer session, if you'd like to be placed in the question queue, please press star 1 on your telephone keypad. A confirmation tone will indicate your line is in the question queue. You may press star 2 if you'd like to remove your question from the queue. For participants using speaker equipment, it may be necessary to pick up your handset before pressing star 1. One moment, please, while we poll for questions. Our first question today is coming from Jonathan Ashwell from Rawlton. Your line is now live.

Thank you. Good morning, guys, and I have four questions for you. The first is you last reported a median OS of greater than or equal to six months in 10 second-line patients, but I don't see an updated number there. Is there any update to that median OS currently?

Yeah, so, Paul, do you want to just resummarize what's in the swimmers chart? Because we've made a lot of progress since that last report.

Our overall median survival now is over seven months in this population, which, again, is far greater by almost a factor of two than what the literature would suggest, would predict.

Yeah, yeah. Yeah, it's a highly conservative trial, I think, given what you have to hurdle. I think it's well-designed, the Miracle trial. Anyway, so why was Miracle enrollment bumped? And maybe you've explained this before in a different form. You know, from 40 to 45 for the first look, you said 75 before, but now you're saying, you know, 90, like the 10Q says 90, the PR says 75 to 90. And then I had in a prior note that after that, when you determine the optimal dose, I had 120 and, you know, 120 is now 240 to be enrolled. I'm just kind of curious, you know, what specifically led to that increase at all three of those looks?

Yeah, I think there's several factors at work here. Let me start backwards and say that the issue about 120 versus 240, I think, has to do with the specific paragraph descriptions. It's always been 120... 120 per treatment arm, but we're always afraid that people will read that as 120 in total. So we've tended to default to describing it as 240. So we haven't increased, we haven't doubled the size of the trial. We've just made sure that people aren't being misled between 120 per treatment arm and 240 in total for Part B. So that's what's going on there. As it relates to the number in Part A, it has been moving around, and part of what's been moving it around is optimizing statistics. One of the things that, I mean, the reality is in order to, I mean, you know this, Jonathan, global clinical trials like this are extremely complex. When you've got 60 to 90 treatment sites, and on six different continents, it gets complicated fast. And so you can get buried in all the startup requirements because every one of those hospitals has to have a contract negotiated, there's ethics review boards, there's a lot of lead time. And so none of those processes can happen until you put a stake in the ground and say, here's our protocol. Well, the biostatistics analysis goes on and on and on for a long time because there's a lot of refinement in what-if analysis. But we didn't want to wait for all of that what-if analysis in order to get the contracting and ethics reviews started. And so we put a stake in the ground and said, this is good enough for now, but we'll continue to refine the actual numbers of the trial as we get closer to the starting line. And that work is still ongoing. So we could have some minor tweaks as this gets closer to the start. But if anything right now, and we kind of embedded this in the presentation, we're expecting that if anything, we may have some opportunities for even earlier visibility than is currently expected. So just stay tuned as we get that completely refined.

Yeah, it's definitely wise to do everything you can to not, you know, swing and miss at that accelerated approval opportunity. Absolutely. It's just a lot of lead time more than waiting for Q40. The last one, I mean, the third one's a little nitpicky. Is the 3Q24 R&D, is that a new run rate or does that include a lumpy slug of anamycin production? I'm going to let her run over the time.

Yeah, yeah, sorry to jump in there, but... Yeah, that was a slug of anamycin production as well as some sponsored research really accelerated at MD Anderson. We've had some additional programs going on there, so we accelerated some sponsored research there as well.

Okay. And, John, again, what is the number of shares from prepaid warrants that's not in your $3 million November 1 share count? Roughly $2 million. And I was kind of curious. Roughly two? Okay. And then the last part of that is why is that $3 million November 1 count so much lower than the average weighted for the third quarter of 3.7?

Well, because the warrants that we issued in August as part of the August deal are now above water. And so now the warrants count in the fully diluted basis.

Okay. That's all. Thank you, guys. Sure.

Thank you, Jonathan.

Take care.

Thank you. As a reminder, that's star one to be placed into question queue. Our next question is coming from Jason McCarthy from Maxim Group. Your line is now live.

Hi, guys. Thanks for taking the questions, and congrats on the progress.

Hey, thanks, man.

Yeah, I was just wondering how much do you expect the phase three to cost? John, you want to tackle that? I was afraid you were going to do that. Well, as Wally mentioned... As Wally mentioned, even going into the recruitment, the number of sites you need for recruitment, you really have to start off with a plan and keep refining it. As you saw on the chart, one of the key things into the cost of the trial is where are we performing the trial. Per patient costs in the U.S. are 10 times or more greater per patient which you have to pay the institution. than what you have in Eastern and Western Europe. I mean, Western Asia. Eastern Europe, Western Asia. I would say a good run rate is essentially what I stated earlier. You're talking about $15 million for about every three quarters. You'll have some lumps in there for anamycin production. And so you just take that to 2028, but if we're able to shorten it, as Wally mentioned, that will have a huge impact. So we're refining those numbers as we refine the sites and what areas we're going to. If you'll note, we do have South Korea on that map, but really not participating in a lot of sites in the Pacific Rim really helps the budget from a standpoint of having CRAs in that area and and drug inventory in that area as well. So more visibility as we move forward. Got it. And then just as far as the STS program, so that's likely final data in first half 25, moving to a pivotal after, but is this something you guys would look forward to doing your own or seek a partner?

So we've really committed to the notion that we would like to find a partner for that project. Obviously, there's enough cost associated with the miracle trial that that's where our focus needs to be in terms of our internal resources. So we basically said, look, any other major undertakings like an STS pivotal trial, we're going to want to work with an outside funding source, maybe in that case an investigator-sponsored trial, that kind of thing.

Okay, got it. Thanks for taking the questions. You bet.

Thank you. Next question is coming from Vernon Bernardino from HC Wayne. Your line is now live.

Good morning, Molly and John. Thanks for taking my question. Hi, Vernon. Hi. You've never mentioned this before, but I was wondering if you have pursued or perhaps intend to pursue discussion with the FDA on a special protocol assessment for the MIRACL trial.

So, you know, we've had a number of discussions about that. But, you know, let me hand this over to Paul to talk about our present thinking about special protocol assessments.

Thanks for the question. Very insightful. And when we went to the end of Phase 1-2 meeting with FDA, we broached the subject of should we submit a protocol for special protocol assessment. And they advised not to do that. It was a very amicable meeting. And they advised not to do it because it takes time. You have to create the protocol, submit it. There's a review period, a discussion period. It adds many months. And they said they would be more than happy to review it, but they recommended not doing it because at the end of the meeting, we were all in agreement. There were no contentious issues. So the thought was, why delay things for many months when we're in full agreement?

I see. So that's a very positive.

There's also a factor, Vernon, and you've probably run into this before, but it tends to tie your hands a little bit because in order for an SPA to be worth anything, to have any real intrinsic value, you cannot deviate from the the strict confines of the protocol that's agreed to in that letter. And so the point Paul was really making was there's a lot of additional delay and lead time to get to that. And then your hands are kind of tied because essentially anything you want to change in the future negates that SPA. And it's like starting over again. There are circumstances where an SPA is probably in the very best interest of the company to protect themselves. But like Paul said, you know, we sort of feel like we've got the FDA on our side here in terms of the trial design and how to get to approval. And so it just did not appear to be worth both the lead time and then the risk that if you want to tweak the protocol, you know, along the way, you've got a problem.

Okay, thank you. I appreciate the additional insight into the phase three trial design process. You bet.

Jeanine, other questions?

Thank you. We've reached the end of our question and answer session. I'd like to turn the floor back over for any further closing comments.

Well, you know, I appreciate everybody making time for an update on Moleculin. I'd just like to leave you with this. AML drugs that are close to approval have consistently been valued in the billions of dollars. And we believe the only rational reasons to be bearish about an asset like anamycin that's in phase three are that, A, you doubt the ability to hit the endpoint, B, you doubt the likelihood of approval if that endpoint is hit, or C, you doubt the marketability of the drug once it's approved. Well, we've shown you the data that explains why we believe with a very high degree of confidence that we will hit the endpoint of this trial. And we've explained that this is the endpoint that the FDA has requested for approval. And we have KOLs on record saying that just a fraction of our expected performance should be sufficient for approval. And finally, I can tell you without reservation that every single investigator we've met with, and we're now well into the dozens, has agreed that anamycin has the potential to fill a desperate, unmet need for AML patients. And to be clear, they've all said they would expect to use it extensively in their practice. We simply need to execute on our strategy, and that's exactly what we're doing. I can't wait for the next update. In the meantime, have a great week.

Thank you. That does conclude today's teleconference and webcast. You may disconnect your line at this time and have a wonderful day. We thank you for your participation today.