Aptose Biosciences, Inc.

Good afternoon. My name is Antoine Alexander, and I will be a conference operator today. I would like to welcome everyone to the Aptos Biosciences reports results for the first quarter ended March 31st, 2023. At this time, all participants are in listen only mode. After the speaker's presentation, there will be a Q&A session. To ask a question during this session, you need to press star one one on your telephones. You will then hear an automated message advising your hand is raised. To withdraw your question, please press star 1-1 again. Please be advised that today's conference is being recorded. I would now like to introduce Ms. Susan Petropalo. Please go ahead.

Thank you, Antoine. Good afternoon and welcome to the Aptos Biosciences conference call to discuss financial and operational results for the first quarter ended March 31st. 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 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 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. The first quarter ended March 31, 2023. Frankly, our year-end conference call was held just over a month ago, so today we will provide you with an incremental but important update. Plus, we also are planning a corporate update around the European Hematology Association, or EHA, conference in June, where we plan to provide additional data. Before I get into the findings with our pipeline, I'll remind you again that we continue to tighten our belts to most efficiently invest our current cash into the essentials related to maintaining key personnel and advancing our key pharmaceutical assets. As with any biotech company in the current market, we continue to pursue strategies to finance our programs without punitive financing terms that are pervasive in many of today's financings, and we continue to pursue partnering activities that can provide strategic support to our programs, and we expect to say more about these topics in the coming days. So now let's hit the headlines for today. First, the dose escalation and dose exploration trial with Tospetinib has been completed, and Tospetinib delivered clinical responses as a monotherapy over four dose levels in very difficult to treat populations of patients with relapsed or refractory AML. Second, dosing of the combination of Tospetinib and venetoclax, referred to as the TUS-VEN doublet, is underway for relapsed or refractory AML patients in our Aptivate expansion trial. Third, we already are seeing brisk enrollment of the Tuspetinib monotherapy arm and of the Tusven doublet arm in the Aptivate expansion trial, and we already have seen early signs of clinical activity. Fourth, the superior safety profile of Tuspetinib continues to be observed, including a reduced risk of myelosuppression with prolonged dosing. Fifth, continuous dosing with the Luxeptinib, yes, Luxeptinib, with the G3 formulation is ongoing. And finally, I'll remind you that we have our annual shareholders meeting planned for May 23rd in just a few weeks. So having delivered the headlines, now I want to provide a few details relating to our lead agent, Tuspetinib. This oral small molecule kinase inhibitor was licensed from Hanmi Pharmaceutical in South Korea. We took over the development range for Tuspetinib in January of last year, just five quarters ago. We applaud our partners at HONME for creating this remarkable molecule with a unique kinase targeting pattern that continues to deliver clinical findings that inspires to view Tospetinib as a potentially playing several key roles in the future treatment regimens of patients with AML and potentially other hematologic malignancies. Tospetinib was created as a once-daily oral myeloid kinase inhibitor to treat patients with AML. and we continue to be emboldened by what we're seeing with every emerging piece of data. By targeting all forms of FLT3, the thick kinase, JAK1 and JAK2, RSK1 and 2, and the mutant forms, but not the wild-type form of KIT, Tospetinib delivers a kind of multi-drug therapy in one tablet that can suppress multiple oncogenic pathways that typically lead to disease progression and relapse. As I mentioned on our last call, we wrapped up a successful dose escalation and dose exploration phase 1-2 trial with Tuspatinib, where we observed responses across four dose levels and across a broad range of very ill and difficult-to-treat AML patients that had been failed by other therapies. Plus, Tuspatinib was remarkably well-tolerated. As a follow-on to the dose escalation and dose exploration trial, we initiated the Activate Phase 1-2 Expansion Trial during the first quarter of this year. In the APTIVATE trial, relapsed or refractory AML patients are being treated with tuspetinib as a monotherapy or with tuspetinib and venetoclax as a doublet therapy. With the monotherapy arm, the APTIVATE expansion trial is designed to confirm monotherapy activity through patient enrichment of certain mutationally defined AML populations, including TP53 mutant patients, FLT3 mutant patients who have been failed by a prior FLT3 inhibitor, as supported by FDA fast-track designation and the clinically significant response rate to date, and possibly RAS-mutated patients that have emerged as sensitive to Tuspetinib. A successful monotherapy arm may provide options for accelerated approval of Tuspetinib in relapsed or refractory AML. And while it's too early to glean formal response data from the first set of patients treated with tuspetinib monotherapy on the Aptivate trial, I can say that we already have begun to see clear antileukemic activity. With a combination arm, the Aptivate expansion trial is designed to evaluate tuspetinib in combination with venetoclax. Several weeks ago, we told you that sites had begun patient enrollment on the TUS-VEN combination. I'm really pleased to announce today that the rate of accrual in this trial has been far more brisk than expected. There's tremendous enthusiasm from investigators, and since our last call, we have dosed a number of patients in the TUS-VEN doublet combination cohort. Here, too, it's too early to draw any firm response conclusions, but thus far, during the early weeks of dosing, the TUS-VEN doublet is being well-tolerated, and we already are observing blast reductions in patients. Investors' confidence in this trial is due in part to the remarkable safety of the tesfetanib to date. I'm happy to confirm that during the most recent safety review held at the end of the first quarter, that unique safety profile of tesfetanib continues with no concerning trends. The importance of a good safety profile cannot be underestimated, as we get questioned all the time, especially because several other AML drugs approved or in development may be limited by toxicities caused by the need for high plasma exposure levels and the excessive suppression of a single target required to elicit responses. For example, published reports show that certain FLT3 inhibitors, such as giltritinib, to achieve clinical responses require plasma exposure levels that cause near-complete inhibition of the FLT3 target in AML cells, as measured by a classic plasma inhibitory activity, or PIA, assay on reporter cells. Unfortunately, plasma levels of such a drug that requires complete inhibition of the target would also be expected to cause excessive inhibition of the same target in normal cells and lead to toxicities. And that's exactly what's observed clinically. In contrast, Tospetinib employs a different strategy to simultaneously suppress a handful of oncogenic kinases that drive pathways critical for leukemogenesis. Using the same classic PIA assay, we see that the plasma from patients treated with tuspetinib can deliver near complete inhibition of FLT3 and STAT5. However, in patients who achieve clinical responses with tuspetinib, complete inhibition of the single target is not required. Rather, clinical responses with tuspetinib can be achieved with 50% to 80% inhibition of FLT3 and the downstream STAT5 signaling. The difference is that tuspetinib can induce clinical responses by incrementally suppressing several oncogenic pathways simultaneously, rather than requiring complete inhibition of any one target. Consequently, Tospetinib appears to achieve clinical responses at lower exposures, thereby avoiding many of the toxicities observed with competing agents. And it's this favorable safety pattern that differentiates Tospetinib from its competitors. I'll also remind you that Tospetinib has shown activity in wild-type AML. which accounts for 70% of the AML population, thereby significantly extending the market potential for this drug. And this, too, is a key differentiating feature of Tospetinib. We've said it before, but Tospetinib's safety profile with its broad activity make it the ideal candidate for combination therapy and frontline therapy, and that is where we're ultimately moving towards. Dr. Behar will speak more about our plans for Tospetinib and combination therapy in the treatment of AML in just a moment. But now just a quick mention of Luxeptinib, our secondary pipeline program. You're aware that our G3 formulation of Luxeptinib is being administered to AML patients at the 50 milligram dose level, which is roughly equivalent to the 900 milligram dose level of the original G1 formulation. We continue to collect PK and safety data, and our plan is to escalate dosing to determine if G3 can deliver greater plasma levels. Preclinically, Luxeptin is an extraordinary molecule, and so we're giving the G3 formulation every chance to succeed. And finally, I'll mention our planned upcoming milestones as we march toward key catalysts for the year. First, our end-of-phase one meeting with the U.S. FDA is scheduled during the second quarter of this year. The meeting is designed to ensure that we're in agreement on Tuspatinib clinical study parameters and next steps in the development of the Tuspatinib program. Second, around the time of the EHA Congress in June, we plan to present clinical findings to include tuspetinib dose escalation and dose exploration findings in relapsor-refractor AML patients and our preliminary findings in patients dosed with monotherapy tuspetinib and the TUSVEN doublet in the AFTAVATE trial. Third, around the European School of Hematology, or ESH, meeting in October, we plan to present maturing tuspetinib clinical data set. Fourth, around the 65th Annual Society of Hematology or ASH annual meeting and exposition in December, we plan to present an even more robust and more mature clinical data set with tuspetinib. And fifth, during the fourth quarter of this year, we plan to discuss strategies for potential future monotherapy accelerated development of tuspetinib for doublet phase 2 development of TUS-BEN, and for a polytriplet development with TUS-BEN and a hypomethylating agent. Let me now hand it over to Dr. Rafael Bejar, our chief medical officer, to go into more detail about the APTIVATE clinical trial of TUS-BEN and AML, and to go over the clinical plans and timelines with you. Raf?