Aptose Biosciences, Inc.

Hello, and thank you for standing by, and welcome to Aptos Biosciences reports for the fourth quarter and year-end 2022 conference call. At this time, all participants are in a listen-only mode. After the speaker's presentation, there will be a question and answer session. To ask the question during the session, you will need to press star 11 on your telephone, and you will then hear an automated message advising your hand is raised. To withdraw your questions, please press star 1-1 again. I would now like to hand the conference over to Susan Peptralo. You may begin.

Thank you, Tawanda. Good afternoon and welcome to the Aptos Biosciences Conference call to discuss financial and operational results for the year-end and fourth quarter ended December 31, 2022. 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 G. Rice, Chairman, President, and CEO, Dr. Rafael Behar, Senior Vice President, Chief Medical Officer, and Mr. Fletcher Payne, Senior Vice President and Chief Financial 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 achievements 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 annual report on Form 10-K 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. I will now turn the call over to Dr. Rice, Chairman, President, and CEO of Aptos Biosciences. Dr. Rice.

Thank you, Susan. I want to welcome everyone to our call for the year end and fourth quarter end of December 31st, 2022. First, I'll provide a very quick overview of 2022. While the biotech market has been extraordinarily challenging, Aptos continued a steady march forward. We extended our cash runway to the end of Q1 2024. We continued building a talented and experienced team. We created and began testing a new formulation for Luxeptinib. And most importantly, we made significant strides in the development of Tospetinib for the treatment of acute myeloid leukemia, or AML. When it comes to tuspetinib, or TUS as we call it, I want to emphasize its highly differentiated profile, having demonstrated the potency to achieve complete remissions in very ill relapsed or refractory AML patients, while also being safe and well-tolerated. It's extraordinary for an antileukemic agent to deliver formal responses in such an aggressive cancer without causing the typical toxicities of other agents. And today, we will unpack both the potency and safety attributes of TUS. It's also important to highlight the AML population that has been treated with Tuspatinib to date in our Phase 1-2 dose escalation and dose exploration trial. These are typically third line, fourth line, or beyond, having failed the best available approved therapies, and in many cases, having failed various investigational drugs or prior hematopoietic stem cell transplants. These are incredibly difficult patients to treat and to reverse the disease progression. What makes these patients even more difficult to treat is the extreme diversity of highly adverse genetic and epigenetic alterations expressed by their disease. If we recall the Admiral trial from just five years ago, during which the commercial dose of giltaritinib, a FLT3 inhibitor, was tested for responses in AML, the patients were second-line, essentially had not seen other FLT3 inhibitors and had not seen venetoclax. In contrast, patients entering our trial are far more treatment-experienced, with half failing prior venetoclax, 60% failing prior treatment with hypomethylating agents, or HMAs, more than a quarter having failed transplants, and half of the FLT3 mutant patients having failed prior therapy with a FLT3 inhibitor. Nevertheless, TUS has delivered responses with convenient once-daily oral dosing of tablets across four dose levels, 160 milligram, 120 milligram, 80 milligram, and 40 milligram, and no DLTs were observed with any of those active dose levels. From a mutation sensitivity perspective, TUS has shown an unprecedented breadth of activity. TUS delivers responses in FLT3 wild-type patients as well as it does in FLT3 mutated patients. We also have seen responses in AML patients having the very difficult-to-treat TP53 mutations as well as patients with NPM1 and FLT3 commutations. and patients having alterations in the DNMT3A, RONC1, IDH1, splicing factors, ASXL1, and MLL genes. But one of the most interesting observations is the activity in relapsed refractory AML patients with RAS mutations. Mutations in the RAS pathway serve as an escape mechanism to generate resistance to many other drugs. However, we've measured a 42% overall response rate in patients with RAS mutations including a 29% CR-CRH response rate. In fact, one patient had a RAS mutation and a mutation in PTPN11, representing a dual mutation in the RAS pathway. We will continue to monitor the response rate in RAS-mutated AML patients this year and determine if RAS-mutated relapsed refractory AML patients may represent a population of high need for future accelerated approval trials. As Dr. Behar will describe in further detail in a few minutes, we wrapped up our highly successful Phase 1-2 dose escalation and dose exploration trial. We've treated over 60 patients to date in that trial. We've assembled a strong safety data package. We selected safe and effective doses for our single-agent and drug combination trials. We demonstrated the ability of TUS to dramatically reduce bone marrow blasts in a high fraction of patients and to achieve formal responses. and we initiated our Aptivate dose expansion study of TUS in a single agent and in combination with venetoclax. In the Aptivate trial this year, we will enrich certain patient populations to receive monotherapy so that we can collect data to guide our conversations with the FDA to request an accelerated approval path for TUS in patients of high and met need. In parallel with the Aptivate monotherapy dosing, we will treat a broad array of AML patients with a combination of TUS plus venetoclax, referred to as the TUS-VEN doublet. This TUS-VEN doublet is being conducted to support doublet combination registrational trials in second-line AML patients and to serve as a bridge to a pilot study of TUS plus VEN plus a hypomethylating agent or the TUS-VEN HMA triplet in frontline AML patients. While TUS clearly can deliver responses as a single agent, the ultimate goal and commercial success of TUS or any drug for AML will be in combination with other drugs. As of this week, we have begun enrollment of AML patients on the TUS-VEN doublet, and we will place additional patients on this doublet throughout 2023. Once we gain experience with the doublet, we plan to initiate the TUS-VEN HMA triplet in frontline patients. The future of AML therapy will also revolve around cocktails of drugs in earlier lines of therapy to take patients into deep remissions. Such AML cocktails will require the blending of drugs that best can serve broad populations of patients, can deliver deep remissions, and can be tolerated without cardiotoxicities, unnecessarily prolonged myelosuppression, and other complicating side effects. And this precisely describes TUS. TUS is positioned to become the ideal partner for addition to the Venn HMA doublet because of its convenience as a once-daily oral agent, its broad activity, and its safety profile. Together, data to date point us toward application as a monotherapy for accelerated approval in relapsed to refractory AML, as doublet therapy for accelerated approval in second-line AML, for use in triplet combination in frontline patients, as well as use in maintenance therapy. and Dr. Behar will provide you with additional color of these activities momentarily. Now let me turn briefly to Luxeptidib. Many of you know it as CG806. Lux, as we typically refer to it, is our secondary pipeline program. Lux is a clinical stage, small molecule, oral, FLT3, and BTK kinase inhibitor. Lux's ability to target kinases operative in certain leukemias and lymphomas led us to develop it in patients with B-cell leukemias and lymphomas and in patients with AML. We already have reported that LUX, administered as our initial first-generation or G1 formulation, delivered a CR in an AML patient and a CR in a DLBCL lymphoma patient, demonstrating LUX is a clinically active agent. You also are aware that we developed a new formulation of LUX, and we call it the G3 formulation because it represents the third-generation formulation. In single-dose administrations during 2022 in AML and B-cell malignancy patients, we determined that G3 formulation achieved up to 18-fold greater absorption than the original G1 formulation. Because the highest dose of the original formulation was set at 900 milligrams, we initiated continuous dosing of G3 at an 18-fold lower dose level of 50 milligrams. We continue to collect PK and safety data with G3 and AML patients, and the preliminary results suggest continuous dosing of 50 milligrams G3 does indeed deliver roughly equivalent plasma exposures as 900 milligrams of the original G1 formulation. That was the target we hoped to achieve with the 50 milligrams of G3. And next, we plan to administer a higher dose of G3 to determine if it can achieve even greater plasma exposure levels. We will keep you posted on our findings, and likely we'll report preliminary data around EHA. I also want to mention that Aptos and collaborators at UCSD, Dr. Manchu Sonowal and Dr. Stephen Howell, just published an article entitled, Luxeptinib Interferes with Lin-Mediated Activation of Sick and Modulates BCR Signaling in Lymphoma, in the online journal PLOS One, in which we describe the ability of LUX to act on the B-cell receptor pathway at the level of the LCK and LYN, or LIN, kinases, and to influence downstream BTK activity. This relates to the role of LUX to act on B-cell cancers, as well as inflammatory and autoimmunity processes. So, please take a look at the article if you get a chance. Finally, we often get asked about potential partnerships for Tuspatinib. In January, during J.P. Morgan Week, We engaged in productive discussions with several big pharma and biotech companies that further helped to define our priorities and to solidify our clinical plans with Tuspatinib. It's clear what we need to accomplish with a drug that has such an extensive commercial opportunity. We were pleased to see that we're on the radar of these companies and interest in our program is growing. The treatment paradigm for AML is shifting toward doublet and triplet therapy. And despite some successes, the current combination therapies are somewhat limited by toxicities, as I mentioned previously. The proven breadth of activity and superior safety profile of Tuspetinib lends itself to combination therapy, potentially as the drug of choice, addressing the most sizable markets in AML and clearly making TUS a prospective big pharma drug. The data we've generated to date have helped us delineate clinical and commercial plans for Tuspetinib in multiple lines of therapy, including its use in doublet and triplet combinations and as maintenance therapy. Our chief medical officer, Dr. Rafael Behar, will speak about our recently initiated APTIVATE clinical trial of Tuspatinib in AML as a single agent and in combination with Venetoclax, as well as our extended clinical plans, which include triplet combination therapy. He also will be available for questions afterwards. I now will turn it over to our resident KOL, our chief medical officer, Dr. Rafael Behar, to talk more about our Tospetinib clinical plans. Raf?