Moleculin Biotech, Inc. H.C. Wainwright 28th Annual Global Investment Conference

Walter? Thank you, Ahmed. Before we start, a reminder that Moleculin is publicly listed, and I'll be making forward-looking statements.

Our latest information and SEC filings are on our website at moleculin.com. Let me start with the punchline, because everything that follows supports this page. Annamycin is positioned to potentially become the first ever non-cardiotoxic anthracycline, now in a pivotal FDA-guided Phase III trial for relapsed/refractory AML. In June, we got our initial unblinded look at the first 45 subjects, and the Annamycin arms delivered a complete remission rate three times higher than control. That was after just a single cycle of treatment. That matters because almost every comparable trial allows multiple cycles, which yield better results, just like Annamycin did in its Phase II trial. On safety, zero cardiotoxicity detected across 90 independently reviewed patients, and Annamycin is generally more tolerable than currently approved anthracyclines.

We're roughly 80% recruited in Part A, and we see base case peak revenue of about $900 million in AML alone, and nearly $10 billion across the entire pipeline. That's the story. Now let me unpack it. Our C-suite brings over 200 years of combined drug development experience, seven FDA approvals, and two big pharma exits. Since our 2016 IPO, we've supported 18 clinical trials, including the pivotal trial we're running today. We've also invested roughly $2 million of our own after-tax money in Annamycin, down to the VP level. Management now has over an 18% beneficial interest. For my part, I exited my last startup to AbbVie for nearly $600 million, then the largest pre-revenue valuation in its class.

Dr. Don Picker led the team that created and won approval for carboplatin and cisplatin, the first metals-based drugs that the FDA ever approved, both blockbusters, and then exited to Bristol Myers Squibb. Dr. Paul Waymack, our Senior CMO, is ex-FDA, and his own approvals include arsenic trioxide, now first-line treatment for acute promyelocytic leukemia. He also trained the FDA cardiology team leader that's now opining on our drug safety. Adriano Treve recently retired as head of Roche's Eastern European and Western Asian operation. He brings a big pharma perspective and expands our partner network. Moleculin is technically a portfolio company. Three distinct technologies, all discovered at MD Anderson, all with the potential to combine in future therapies. That said, we've focused our resources on Annamycin. WP1066 and WP1122 move at grant speed on investigator-initiated work at Northwestern, Emory, and UNC Chapel Hill.

That is development that we get without spending our own capital. Today is all about Annamycin, and the message here is that although our pivotal trial is in AML, Annamycin has broad potential indications, hence our activity in soft tissue sarcoma, pancreatic cancer, and pediatric AML. I firmly believe that very few companies are positioned for the market cap breakout that we are. Annamycin is a patent-protected, disruptive technology, bringing superior safety and efficacy to a huge unmet need, with phase II efficacy better than any approved second-line AML therapy. Unlike a year ago, this is not about what a phase III might show. We have data in hand, with a second readout at the end of the year. This is a billion-dollar market where recent exits have shown strong revenue multiples.

Where most AML drugs are limited to a narrow mutation-defined indication, Annamycin's breadth represents 10 times the growth potential beyond AML alone. Let me set the stage for how big the AML opportunity is. The gold standard remains 7+3. That is seven infusions of cytarabine alongside three infusions of an anthracycline, usually daunorubicin. Response rates are very high, usually within the first 21-day cycle, and durable responders typically go on to a curative bone marrow transplant. But this standard of care has some problems. First, it is highly toxic, so only about half of AML patients, usually those under 65, are considered fit enough to withstand it. Second, relapse rates are also very high, so little more than a third actually reach the potentially curative bone marrow transplant, and 20% of those transplants fail.

So that leaves about 14 out of every 100 patients actually cured through 7+3. Unfit patients get venetoclax plus a hypomethylating agent, usually azacitidine, hence Ven-Aza. Outcomes are similar, but they take much longer, and venetoclax failures typically survive only about 2.5 months. So most AML experts consider these some of the hardest cases in relapsed refractory AML. That is why 7+3 is still preferred where you can use it, because if it fails, there is still time for something else. But that second attempt generally will not be more 7+3. By then, the patient is likely resistant, and cardiotoxicity comes into play. Then the targeted therapies. Well, the big promise for more than 10 years. Unfortunately, they just did not deliver. Only about nine out of 100 patients reaches a durable outcome that way.

Added up across every approved pathway, only about 38 of 100 AML patients reach a durable outcome. That is an unmet need of roughly 60%. In our trials, Annamycin with cytarabine, or AnnAraC, produced complete remission in about half of second-line patients. So that is the sweet spot for Annamycin. Now, to understand why Annamycin is potentially disruptive, remember how important anthracyclines still are. They are the most critical part of 7+3, and roughly half of all cancers and about 60% of pediatric cancer treatments still use an anthracycline today. But they are extremely toxic, so toxic that the FDA sets a lifetime maximum on anthracycline exposure. Go over that limit, and there is a 65% chance of heart damage. Even within the limits, 60% of childhood cancer survivors develop cardiac dysfunction. As you saw, 50%-60% of adult AML patients cannot be given an anthracycline at all.

Jazz Pharma paid $1.5 billion for the last incremental improvement in AML-based anthracyclines, a drug that did nothing for cardiotoxicity and added 3.5 months survival. The message, anthracyclines are critical to patient care, and there is tremendous room for a true disruptor. Annamycin's next-generation status is both a tremendous opportunity and it is a real challenge. Many academicians roll their eyes the moment we say anthracycline until they see how different Annamycin is. This is an entirely new chemical entity with significant structural changes. Among them is an added iodine atom, which radically changes both the structure and the lipophilic nature of the active ingredient. We then position that API inside a unique multilamellar lipid delivery system, which further enhances lipophilicity and supports the lack of cardiotoxicity already inherent in the molecule.

It also helps explain Annamycin's accelerated cellular uptake and its organotropic ability to target organs that current anthracyclines just cannot reach. This slide puts Annamycin side by side with the doxorubicin class of anthracyclines. A few rows deserve specific attention. Let us start with half-life. Annamycin clears in 1-2 hours. Conventional anthracyclines linger for 1-2 days. Net charge at physiologic pH is neutral for us, cationic for them. We believe those two properties alone drive much of the safety and tolerability story. Additionally, we use a 5+3 regimen, even further lessening the toxicity that patients have to endure. On cardiotoxicity, none detected across 90 independently reviewed patients at cumulative doses up to almost 3,000 milligrams per square meter. Compare doxorubicin, where congestive heart failure is estimated at about 5% at 400 milligrams and nearly 50% at 700 milligrams per square meter.

Annamycin also avoids MDR1 resistance mechanisms. It has no vesicant activity, no tissue necrosis on extravasation, and no central line required. Alopecia runs about 7% versus 60%-100%. Severe mucositis was zero of 22 patients in our phase II, against 16%-26% for intensive 7+3. Our shelf life is 5 years versus about 2. Row after row, this is not incremental. It is a game changer. Convincing Key Opinion Leaders that there can actually be a better anthracycline, it is a real challenge. Every AML thought leader now recognizes, however, that targeted therapies have failed to deliver on their promise, and we need a better solution. But when they first hear the word anthracycline, they assume Annamycin is old technology, and there is outright disbelief that any anthracycline can truly be this safe. Every physician on this slide started from that disbelief.

But once they saw the science and the clinical performance, every one of them became a strong supporter. Dr. Martinelli in Bologna calls it a potential game changer. Dr. Andreeff at MD Anderson calls the data striking and notes that it holds up even in venetoclax-treated patients. Dr. Tallman and Dr. Cherry make similar points about the unmet need. There used to be one universal caveat, though, and that is could the phase II numbers we generated, could they be replicated or did we just get lucky? As you will see, we have now begun to answer that question. So let me summarize what we believe makes Annamycin a disruptor. First, Annamycin is positioned to become the first ever non-cardiotoxic anthracycline. We have treated more than 100 patients, most dosed over the lifetime maximum, and some as high as 5 times that limit with zero cardiotoxicity.

Those data have been independently reviewed by the Cleveland Clinic and by the FDA. That alone changes who you can treat. The old definition of unfit no longer applies, and for the first time, it opens the door to anthracycline maintenance therapy. Second, for all its safety improvements, Annamycin appears to give up nothing in terms of efficacy. In fact, just the opposite. In our phase II combination trial, we saw 60% CRC and 50% CR, 13-month durability, and overall survival of 15 months. We were mutation agnostic with high response in venetoclax failures. Third, it avoids the resistance mechanisms that typically defeat current anthracyclines, and it lacks cross-resistance with them, with venetoclax, and with cytarabine. Fourth, the lipid delivery system supports rapid cellular uptake and organotropism, specifically targeting certain organs.