Aptose Biosciences, Inc.

Good afternoon. My name is Josh, and I will be your conference operator today. I would like to welcome everyone to the Aptos Biosciences conference call for the first quarter ended March 31st, 2024. At this time, all participants are in a listen-only mode. After the speaker's remarks, there will be a question-and-answer session. If you would like to ask a question during this time, you will need to press star 1-1 on your telephone. You will then hear an automated message advising your hand to raise. If you would like to withdraw your question, please press star 1-1 again. Thank you. As a reminder, this conference call may be recorded. I would like to introduce Ms. Susan Pietropalo. Please go ahead.

Thank you, Josh. Good afternoon, and welcome to the Aptos Biosciences conference call to discuss financial and operational results for the first quarter ended March 31, 2024. Earlier today, Aptos issued a press release relating to these financial results. The news release as well as related SEC filings are accessible on Aptos' website. Joining me on today's call are Dr. William Rice, Chairman, President, and CEO, Dr. Rafael Behar, Senior Vice President, Chief Medical Officer, and Mr. Fletcher Payne, Senior Vice President, Chief Financial Officer, and Chief Business Officer. Before we proceed, I would like to remind everyone that certain statements made during this call will include forward-looking statements within the meaning of U.S. and Canadian securities laws. Forward-looking statements reflect Aptos' current expectations regarding future events. They are not guarantees of performance, and it is possible that actual results and performance could differ materially from these stated expectations. They involve known and unknown risks, uncertainties, and assumptions that may cause actual results, performance, and achievement to differ materially from those expressed. To learn more about these risks and uncertainties, please read the risk factors set forth in Aptos' most recent quarterly report on Form 10-Q, and SEC and CEDAR filings. All forward-looking statements made during this call speak only as of the date they are made. Aptos undertakes no obligation to revise or update the statements to reflect events or circumstances after the date of this call, except as required by law. We encourage you to refer to today's press release and the 10-Q for additional information and disclosures regarding today's announcements. I will now turn the call over to Dr. Wright.

Thank you, Susan. I want to welcome everyone to our call. the first quarter ended March 31st, 2024. Our last call was only about a month and a half ago, so we've decided to switch up our conference call format today to include a selection of slides that can provide you with a better understanding of our clinical strategy to focus the development of TUSPETNIB as a triple drug combination or triplet frontline therapy to treat newly diagnosed AML patients. TUSPETNIB, or TUS as we refer to it, is Aptos' lead clinical asset, TUS is being combined with venetoclax, or VEN, and a hypomethylating agent, or HMA. This forms the TUS-VEN-HMA triplet drug combination that is being developed for frontline therapy to treat newly diagnosed AML patients. VEN-HMA is currently the standard of care therapy for newly diagnosed AML patients, and TUS is being bolted on the VEN-HMA standard of care to boost the activity and to do so safely. And importantly, we expect to report clinical data with the TUS-BEN HMA triplet and the newly diagnosed AML patients during the second half of this year. We all know AML is a highly aggressive cancer of the blood and bone marrow, and that unmet need still exists for the relapsed or refractory patient population and for the newly diagnosed population. I'll remind you, when we began clinical trials with TUS as a single agent and with the TUS-BEN doublet, in the relapsed or refractory AML population, as is the case with many other new cancer drugs. Yet, we've always planned to move TUS-Betnib into frontline therapy for newly diagnosed AML patients. Our trials with TUS single agent and with the TUS-Bend doublet in relapsed or refractory patients are now completed. The single agent and the doublet demonstrated excellent safety profiles and distinguished TUS-Betnib from other agents. Just as important, we observed responses in patients with wild-type FLT3, patients with mutated FLT3, patients with mutated TP53 and RAS genes, patients who failed prior therapies with venetoclax, hypomethylating agents, FLT3 inhibitors, and chemotherapy, and those who had failed prior stem cell transplants, illustrating cuspetinib-achieved responses across a remarkable diversity of AML populations. During Q1 of this year, we presented our clinical findings to the FDA as part of a protocol amendment to allow for evaluation of the TUS-DEN-HMA triple drug combination for the frontline therapy of newly diagnosed AML patients. That protocol for the triplet in frontline therapy is now open, and our clinical team is engaging clinical sites and preparing to initiate dosing of patients on the study. I want to explain why we've accelerated our strategy to focus on the frontline triplet in newly diagnosed AML patients. As we began to share safety and efficacy data from the TUS and TUS-N trials and relapse to refractory AML patients with our KOLs and pharma, it became clear that the greatest unmet medical need and greatest opportunity in AML is the development of a superior frontline therapy for the treatment of newly diagnosed AML patients. It also became clear that the unique safety and broad efficacy properties of test metinib fit the desired profile of a third agent to add to the ven plus HMA standard of care backbone and assemble a superior triplet for the frontline therapy. Before we go further, let's first recognize that progress has been made with the introduction of venetoclax to the ven HMA doublet. And this was a major advancement in the treatment of AML. However, the complete remission response rates are still too low and survival is still too short in frontline therapy. And we all want to see a more effective frontline. But there was another important factor leading our KOLs, pharma, and our internal team to focus on frontline therapy. While venetoclax treatment has resulted in more responses in frontline therapy, there is a double-edged sword with venetoclax. It turns out that relapsed or refractory patients who have failed prior venetoclax treatment respond poorly to salvage therapies, and even if they achieve a response, their survival timeline is grim, on the order of a few months. This tells us we need a new frontline strategy that may be able to help avoid rapid failure of venetoclax-based therapies. So what we need is an exceptional third agent that can boost response rates of VEN plus HMA, prolong the duration of responses and survival, improve quality of life, treat a broad spectrum of AML genetic subpopulations, and minimize the likelihood of patients becoming resistant to venetoclax. This is a tall order, and other potential third agents in development may only address specific genetic subpopulations, while other agents bring their own complicating toxicities to the triplet. This has opened the door for Tospetinib to address the greatest single opportunity in AML, which is the development of a superior frontline therapy to treat newly diagnosed AML. Tospetinib is a natural third agent for addition to venetoclax and HMAs. Tospetinib has an excellent safety profile as a single agent and in combination with venetoclax and HMAs and with other drugs. Tospetinib enhances antiloquemic activity when combined with venetoclax and HMAs. Tospetinib has a very broad scope of activity across genetic subgroups of AML, even those who have high-risk mutations in the TP53 and Ras genes. And Tospetinib targets known venetoclax resistance mechanisms and may help minimize the rapid onset of drug resistance. Because of this unique safety, activity, and mechanistic profile of TUS-Fetnib, we're developing the TUS-VIN HMA triplet to become a new standard of care therapy to address the safety, scope, and survival needs of newly diagnosed AML patients. I now want to present just one more slide because it's important to understand how TUS-Fetnib works and how TUS plus VIN show mechanistic complementarity and may minimize drug resistance. And I'll illustrate these mechanistic interactions with a cartoon on the right side of the slide. As you can see, AML cells upregulate key oxygenic signal transduction pathways to drive excessive proliferation and cell division. At the same time, AML cells avoid cell death by modifying the expression of anti-apoptotic proteins such as MCL1 and BCL2. Often in AML, the BCL2 protein is upregulated. Venetoclax is administered to patients to target the BCL2 and enable the AML cells to die more readily. However, Venetoclax alone has minimal efficacy in AML. That's why Venetoclax is combined with the hypomethylating agents to achieve clinical remissions. Unfortunately, over time, the cells can modify a number of key pathways, to generate resistance to venetoclax. Multiple mutations can occur simultaneously in the FLT3 and KIP receptor kinases, in the JAK kinases of the JAK-STAT pathway, and in the RASMAP kinase pathway, all leading to upregulation of the MCL1 anti-hepatotic protein. Collectively, these alterations allow AML cells to drive cell division and avoid cell death even in the presence of venetoclax. Now let's look at the effects of tespetinib. Tuspetinib directly inhibits the FLT3 kinase, the mutant form of KIT, the SICK and JAK kinases in the JAK-STAT pathway, and the RSK2 kinase downstream in the RAS-MAP kinase pathway, and indirectly reduces MCL1 expression. It's this mechanistic complementarity that can make tuspetinib and venetoclax such a powerful combination tool against AML. And Dr. Behar will describe how we plan to use these agents together more effectively to treat AML. With that, I'll now turn it over to Dr. Behar, Aptos' chief medical officer and resident KOL, for his insights into the AML patient journey and to take you through our clinical plan that is already well in place. Raf?