Good afternoon. My name is Jonathan, and I will be your conference operator today. I would like to welcome everyone to the Aptose Biosciences Conference Call for the Fourth Quarter Ended December 31, 2021. At this time, all participants are in a listen-only mode. After the speakers’ remarks, there will be a question-and-answer session. [Operator Instructions] Thank you. As a reminder, this conference call is being recorded. I would now like to introduce your host for today’s program, Susan Pietropaolo from -- please go ahead.

Thank you, Jonathan. Good afternoon, and welcome to the Aptose Biosciences conference call to discuss financial and operational results for the year ended fourth quarter ended December 31, 2021. Earlier today, Aptose issued a press release related to these financial results. The news release as well as related SEC filings are accessible on Aptose’s website. Joining on today’s call are Dr. William G. Rice, Chairman, President and CEO; Dr. Joti Marango, Senior Vice President, Chief Financial Officer and Chief Business Officer; and Dr. Rafael Bejar, Senior Vice President and Chief Medical 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 Aptose’s current expectations regarding future events but 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 Aptose’s most recent annual report on Form 10-K and SEC and SEDAR filings. All forward-looking statements made during this call speak only as of the date they are made. Aptose 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 Aptose Biosciences. Dr. Rice? Dr. William G. Rice: Thank you, Susan. I’d like to welcome everyone to our call for the year-end and fourth quarter ended December 31, 2021. In today’s call, I’ll give you a quick recap of highlights for 2021, a status update on our clinical programs and an outline of the key milestones we anticipate in 2022. To remind you, Aptose is a clinical-stage precision oncology company, developing highly differentiated oral kinase inhibitors for the treatment of patients with hematologic malignancies. And today, you’ll find that we are visibly upbeat about our progress in our molecules, HM43239 and luxeptinib. I also want to stress a few actions that illustrate our team’s foresight, which position the Company and our drug candidate for success. First, in 2020, we raised capital for before some thought necessary. And last year, even with a strong balance sheet, we began a meticulous process to focus resources on the value-driving programs and to streamline expenses, not by cutting corners, but by carefully evaluating the essential needs of our programs. This was implemented strategically to extend cash runway but without undermining company capabilities or value. Through reprioritization and streamlining of our pipeline programs, we now have extended our cash runway into the fourth quarter of 2023, which we believe goes well beyond a series of potential value-building updates from our clinical programs in this year and in the next year. Second, for luxeptinib or just lux, more than two years ago, we recognized the potential need for an improved formulation as we move the original formulation through the clinic and demonstrated lux as an active molecule. We built our CMC team and initiated development of the G3 formulation because we believe such a formulation could improve the opportunity for lux to demonstrate greater exposure and more responses and to deliver greater value to patients, to the Company and to shareholders. And we now are evaluating G3 formulation in humans. Third, we initiated a deliberate asset search more than two years ago that led to the licensing of HM43239, or just 239, as we’ll refer to it. Now, 239 has moved to the forefront of our pipeline. As a more advanced derisked asset with proven clinical activity, 239 literally added a well-tolerated and effective drug with significant value to our pipeline overnight, and 239 continues to demonstrate value to patients and to impress us and our clinical investigators. And fourth, before we even took control of the 239 clinical trial, we led efforts to rapidly increase the available clinical supply. We also began to expand the number of clinical sites and to introduce protocol amendments to increase the number of AML patients in the cohort expansions. This was done to deliver additional responses to select multiple doses that could serve as effective expansion doses as a single agent and in combination with other agents and to identify genotypically enriched AML populations for upcoming expansion trials that could serve as populations for accelerated approvals. I also want to acknowledge that we recognize our messaging now focuses far more on 239 ahead of lux. That is because 239 entered AML patients a year ahead of lux, and 239 already has delivered safety and efficacy data that place it on a fast track. While we will continue to prioritize the more mature 239, we continue to believe in lux, and we want to give the best possible chance to succeed as we assess our new G3 formulation. So big picture, because we are forward-looking, we are in the fortunate position of having two well-differentiated oral kinase inhibitors for the treatment of hematologic malignancies, and we will allow the clinical data, the patient needs and the maturity of the agents to drive the path forward. Collectively, as you know, we take a very disciplined approach to how we run our business and our studies. And our investment in this approach has begun to bear fruit and place the Company in a bullish position in 2022. But before we go there, let’s recap 2021. During 2021, Aptose continued to dose escalate in the lux clinical trials in both, acute myeloid leukemia, or AML, and B-cell cancer patient populations. In June, we presented data for both programs concurrently with our participation in the European Hematology Association, or EHA, 2021 Virtual Congress. We reported that in AML, the first two cohorts delivered encouraging antileukemic activity in multiple patients, including a heavily pretreated AML patient that experienced a durable MRD negative complete remission. In B-cell cancers, intermediate doses have delivered clear signals of clinical activity, including tumor reductions across different B-cell malignancies. The reversal of disease growth upon intrapatient dose escalation and longer times on drug suggested that even aggressive disease may be successfully challenged with higher exposure levels of lux. Reminiscent of solubility properties of the BTK inhibitor, ibrutinib, our original formulation of lux had low solubility, which forced us to continue to escalate the dose of lux to seek higher exposures that may demonstrate superior activity. So, it was good timing in parallel that the dose escalation of lux in patients with B-cell malignancies and AML, we made significant progress in the development of a next-generation formulation, which we call G3. We have been working to optimize the lux formulation, as I said, for more than two years. And we announced that in preclinical studies, the new G3 formulation had effectively addressed the solubility issues of the original lux formulation and delivered up to 30-fold greater exposure on a per milligram basis of drug administered. We’ll talk more about G3 in our 2020 update for lux in a few minutes, but now back to Q4 of 2021. During the fourth quarter of 2021, we delivered additional good news. In November, we entered into an exclusive worldwide license agreement with the Hanmi Pharmaceutical Company to develop and commercialize 239. Oral 239, our new lead molecule, is clinically validated as a myeloid kinome inhibitor that potently inhibits kinases operative in AML with adverse mutation profiles, including FLT3, SYK, mutant forms of c-KIT and JAK kinases. This kinase inhibitory profile enables 239 to suppress resistance conferring mutant forms of FLT3 and growth factor pathways such as the JAK/STAT and the MAP kinase ERK pathways that confer resistance to other agents. 239 already has delivered complete remissions in a diversity of relapsed/refractory AML patients and an ongoing international Phase 1/2 clinical trial as Dr. Bejar, our Chief Medical Officer, will describe to you in a few minutes. Importantly, 239 delivered meaningful clinical benefit to all responders, either through bridging them to a stem cell transplant or by providing a durable response over time. In an oral presentation at ASH in December of 2021, Dr. Naval Daver from MD Anderson Cancer Center, lead investigator for the 239 trial, delivered the first public release of promising clinical results from the ongoing clinical trial. Dr. Daver reported that 239 demonstrated multiple complete remissions, or CRs, in patients with relapsed/refractory AML with highly adverse mutations, thereby allowing us to identify genotypically defined AML populations with high unmet medical need for potential accelerated development and to establish that 239 has strikingly broad activity across patients with diverse genotypic backgrounds. During the fourth quarter, we worked closely with Hanmi and principal investigators to ensure a smooth transition of the clinical trial to Aptose, and you will hear more about the 2022 activities for 239 in a moment. As you are aware, at the end of 2021, we also announced the discontinuation of the clinical development of APTO-253. The decision followed prioritization of the Company’s other more advanced pipeline candidates and allows us to operate efficiently as we devote our focus and resources toward the development of our kinome inhibitors, 239 and lux. Collectively, we took steps to advance and derisk our pipeline to prioritize our most actionable programs, to reduce any nonessential expenses, to accelerate patient enrollment and add clinical sites and to place the Company in a position of strength for 2022 that allows for delivery of value-driving milestones within our cash runway. We have a clear vision of our clinical strategy and objectives for the development of 239 and lux as we continue to execute and advance these clinical programs. And I’m pleased with the rapid progress and the position we’ve created for Aptose during the first part of 2022. In particular, we expect 2022 to be an important year for 239. So, let’s have our Chief Medical Officer, Dr. Rafael Bejar, move directly into the update for 239. Raf? Dr. Rafael Bejar: Thank you, Bill. Let’s take first a moment to talk about what differentiates 239 from other kinase inhibitors. In our last call, we described a very impressive preclinical profile of 239, superior to gilteritinib as a single agent and when combined with venetoclax or azacitidine. This myeloid kinome inhibitor is a highly effective FLT3 inhibitor, inhibiting both wild type and all other mutant forms of FLT3 tested. But 239 is more than just an inhibitor of FLT3 as it also inhibits other oncogenic signaling pathways, including the downstream SYK, JAK/STAT and ERK kinase, MAP kinase pathways. This kinase inhibitory profile of 239 already has translated into strong antileukemic activity in a diverse array of AML patients, delivering multiple CRs in the Phase 1 trial thus far, and it has been well tolerated to date with only mild AEs and no DLTs through the completed dose level of 160 milligrams. I just want to remind you that our Phase 1/2 clinical study uses the traditional 3 plus 3 dose escalation protocol, but the structure allows us to expand out and add additional groups of patients to a dosing cohort. Most patients have been treated at the 80-milligram dose level at which we already have reported five composite complete remissions, or CRCs, which encompass four unqualified complete remissions and one complete remission with incomplete hematologic recovery known as the CRi among a diverse group of refractory AML patients with a series of highly adverse co-mutations. This includes patients with mutations in the TP53, NPM1, RAS and IDH2 and patients with wild-type FLT3 or in patients harboring the ITD or tyrosine kinase domain forms of FLT3. As one would hope, this includes FLT3 mutant patients previously treated with approved FLT3 inhibitors, which is gilteritinib and midostaurin. This is an increasingly common, highly treatment refractory subgroup that could serve the population with unmet medical need ideal for accelerated approval. Among the patients with FLT3 mutations, two experienced a complete remission and one at CRi. One patient carried FLT3-ITD and NRAS co-mutation, and they achieve a complete remission and bridge to a stem cell transplant. The second patient carried a FLT3-ITD and an NPM1 mutation achieved a complete remission and also bridge to a stem cell transplant. And the third patient harbored a tyrosine kinase domain mutation of FLT3 and had failed prior therapy with both, midostaurin and gilteritinib. This patient achieved a complete remission with a single agent 239 and also bridge to a stem cell transplant. Then there were two patients with FLT3 wild-type AML and highly adverse co-mutations that also experienced complete responses or complete remission. One patient with wild-type FLT3 presented with a highly adverse genotype, defined by a TP53 mutation in a complex karyotype. Patients with this mutational background typically do not respond to therapy or relapse quickly after treatment even if they do. While this patient was considered unfit for a stem cell transplant due to age, the patient achieved a complete remission on 239 and enjoyed a duration of response that exceeded one year. This example speaks to the breadth and durability that 239 is capable of. Another patient also with a wild-type FLT3 carry the IDH2 mutation, and after achieving a complete remission, was also taken to a stem cell transplant. In fact, 4 out of the 5 patients who achieved complete remissions either with CR or Cri, 80 milligrams were bridged to allogeneic stem cell transplantation, a potentially curative procedure. And the one patient with the TP53 mutation I mentioned was ineligible for transplant experienced a very significant clinical benefit with a durable complete remission lasting more than a year. And I’m happy to report that we recently completed enrollment of the 120-milligram dose cohort expansion arm and very happy to report that from the early data, we’ve observed an additional CRi in a patient with relapsed AML. While we are not providing further details of the patients at the 120 milligram dose level at this time, these observations illustrate strong antileukemic activity at multiple dose levels. These data also grow our list of adverse AML genotypes that appear to respond to 239, including patients that carry abnormalities in the MLL gene and mutations of [indiscernible]. And these are important messages to communicate as this is a very relapsed/refractory population to treat. We plan to disclose data specifics concurrently with EHA in June, but a key takeaway here is that our treatable patient population appears to be expanding as we identify additional genotypes that are responding to the drug. And this is going to be important for the theme of the future of 239. In this trial, our enrollment has been brisk, and we are now focused on populating the 160-milligram dose cohort expansion. Why would we do this instead of simply moving on with our lowest dose of demonstrated remissions? It’s because these dose expansions have helped us uncover the genetic breadth of AML patients responding to 239. We are encouraged by what we are seeing in patients with challenging highly adverse mutations, some of which we may require higher doses of the 239 to respond. In short, we want to continue exploring the full potential of 239 as we prepare for our next set of clinical trials and make sure that we don’t leave any unexplored clinical activity on the table. That said, we have identified two well-tolerated inactive doses, 80 milligrams and 120 milligrams. It could serve as our go-forward dose to take into expansion trials. We continue to explore the 160-milligram dose, so we may select the optimal expansion dose and select genetically defined AML patient population to initiate fixed dose expansion trials with an eye towards accelerated registrational pathways. So now, let’s recap key messages for 239. To summarize, at an early dose level, 239 has shown broad activity across several major AML genotypes. While 239 represents a genotype-agnostic profile, we’ve identified several genotypes with high unmet clinical need that we believe can leverage -- we can leverage for accelerated development and marketing approvals with an intent to later expand the label to additional genotypes. A potential minimum therapeutically effective dose has already been identified to take into expansion trials. However, because of the favorable safety profile to date, we are exploring higher doses and dose expansions across a diverse set of AML patients that will allow us to select the optimal expansion dose. Based on the strong signals already seen to date as well as the new lessons from these later cohorts and expansions, we are planning registration-directed development for 239. This includes ongoing studies of 239 as a single agent in particularly difficult to treat and genetically enriched subpopulations for a single agent expansion trial this year. In addition to our single agent studies, we are planning combination studies that would allow 239 to complement existing therapies and move into earlier lines of treatment. Okay. Now, on to a quick review of luxeptinib. Just as a reminder, lux is the only known clinical agent that potently inhibits both FLT3 and BTK with a precision that avoids known targets that are often associated with toxicities, giving a broad therapeutic potential across the spectrum of lymphoid and myeloid hematologic malignancies. In both of our Phase 1a/b studies, lux has been generally well tolerated dose levels of 450, 600, 750 and 900 milligrams BID over multiple cycles and is currently being dosed at 900 milligrams BID in both studies. Target engagement at BTK and FLT3 and antitumor activity, including dose and exposure dependent tumor reductions, have been observed in multiple patients collectively between the studies, including patients with follicular lymphoma, diffuse large B-cell lymphoma, CLL and AML. In preclinical studies of AML, lux triggered profound apoptosis and demonstrated in vivo tumor eradication. We have continued to push the dose of lux in order to reach the exposures that would demonstrate this kind of activity in patients. A new better absorbed formulation of lux, G3, may help deliver on that promise. As we mentioned at the intro of this call, preclinical studies, G3 has been shown depending on the species and dose to deliver from 10- to 30-fold greater exposures of drugs than the original formulation. And I’m pleased to report that with strong execution from our team, we have started administering single doses of 50 milligrams of G3 in an ongoing clinical program. After patients received a single dose and samples are collected for PK evaluation, they go on to the original formulation of lux for a direct comparison. At this time, they are going into the 900-milligram BID cohort of the original formulation where we can collect additional safety and efficacy data from these patients. A preliminary look at the PK data available to date suggests that G3 delivers rapid absorption with improved exposure on a per milligram administered basis as compared to the original lux formulation. While very preliminary, these data are encouraging. We plan to continue evaluation of G3 in a sufficient number of patients to determine if G3 is truly a superior formulation of lux for our patients. We do hope G3 will reduce significantly the pill burden and the amount of drug substance administered to patients, and this could be a meaningful step for the advancement of lux to the clinic. As always, new formulation work, and its translation from preclinical models to the clinic comes with many uncertainties and risks. And there’s no guarantee of success. For this reason, we are being diligent and not rushing our enrollment in evaluation of patients dosed with G3. We plan to share more details on our experience with G3 in the clinic in the second quarter. We are pleased by the progress across our clinical programs and that the safety and tolerability of our drug candidates, 239 and lux, have allowed continued dose escalation in our ongoing trials. As we treat more patients with higher doses, we are generating additional pharmacokinetic and pharmacologic data that we look forward to providing further updates. For more information on all of our ongoing clinical trials, for clinical sites that are recruiting patients, please visit clinicaltrials.gov. Let me now turn it back to Dr. Rice. Bill? Dr. William G. Rice: Thanks, Raf. Before we speak to the financials, let’s take a quick look at our upcoming anticipated milestones. For 239, we currently are dosing at the 160-milligram dose cohort expansion, which is enrolling well, and we expect to bring further data in a greater number of patients, which will help us determinate go-forward dose for expansion trials. As Dr. Bejar mentioned, the 80-milligram and 120-milligram doses already could serve in this capacity, and we want to understand if the 160-milligram dose also could serve at the expansion dose. And we plan to communicate the selection of our optimal expansion dose to you soon. Soon, we also plan to communicate our selection of genetically enriched AML populations for the expansion trials and registration paths. We expect to initiate those fixed dose expansion trials in these enriched populations during the second half of this year. Regarding date of release, we are planning a top line readout of data for presentation concurrent with the EHA meeting in June, and we plan to reserve full clinical data set for presentation concurrent with ASH in the fourth quarter. For lux, we will keep you posted on the clinical trials in B-cell cancers and AML and our observations with the new G3 formulation. Expect updates around scientific meetings similar to what we’ve done in the past as well as banking conferences and earnings calls. I now will turn the call over to Dr. Joti Marango, our Chief Financial Officer and Chief Business Officer, so he may review our financial results. Joti? Dr. Joti Marango: Thank you, Bill, and good afternoon, everyone. We ended December 31, 2021 with approximately $79.1 million in cash, cash equivalents and investments, which we expect can support operations of the Company into the second half of 2023. During the quarter, we utilized approximately $16 million of cash in operating activities, which were attributable to increased activities surrounding 806, 253, general and administrative purposes as well as the in-licensing of 239. Moving on to the income statement. We had no revenues for the fourth quarter of the year ended December 31, 2021. Research and development expenses were $20.2 million for the quarter and $46 million for the year. G&A expenses were $4.1 million for the quarter and $19.5 million for the year. Our net loss was $24.3 million or $0.27 per share for the quarter and $65.4 million or $0.73 per share for the year. More detailed information can be found in our filings on EDGAR and SEDAR. I will now turn the call back over to Dr. Rice. To you, Bill. Dr. William G. Rice: Thanks, Joti. As we open the call for questions, please feel free to pose a question to any of us. Operator, if you could, please introduce the first question.

Certainly. Our first question comes from the line of Ted Tenthoff from Piper Sandler.

So, I had a quick question with respect to the new CRi that you discussed with 239. Was that a deepening response to the prior PR, or was that a new responder? Dr. William G. Rice: Hi Ted. Thanks for coming on the question. No, that was an entirely new patient, the CRi. Dr. Bejar, would you like to add to that, please? Dr. Rafael Bejar: Nothing much more to add. Yes, it was different patients, and the patient that was previously reported is having a PR.

Great. And then, can you give us a sense with respect to the update at EHA? Will it be more on the 80, 120, will we get any 160 data yet? Dr. William G. Rice: Well, clearly, we’ll present all the data we have at the 80- and the 120-milligram expansions, and we hope to have the 160 fully enrolled by then. No guarantees. But I think you note, Ted, we tend to be very disciplined on this. We provide as much information as we can once we’ve completed enrollment on a cohort. So, we’ve done that in the dose escalation from 20 milligrams up to 160 milligrams, provided information there once we’ve completed enrollment. And then, when we had completed the 80 milligrams, we gave you the information there, but not on the 120. But now we’ve completed the 120. We’re beginning to release information as the data are emerging from that 120, and we hope to have that 160-milligram dose cohort -- the expansion completed by then. Again, no guarantees on that because there’s -- it’s not that far away, and we have a number of patients to go. But hopefully, we’ll be able to give you more information on the 160.

Our next question comes from the line of Gregory Renza from RBC Capital Markets.

Hi. [Indiscernible] on for Greg. Thank you for taking our questions. And congrats on the progress. Maybe first on 239. Wondering, could you please provide some color around the profile of that patient with BRL in the 120 mg cohort? Maybe just general or qualitative color and how that compares with the rest of the cohort? Should we expect more patients to have a similar profile? Thank you. Dr. William G. Rice: So, far the information that we are providing at this point is we spoke about -- it allowed us to understand there are a few more of the genetic alterations that this drug can target. We mentioned the MLL and one of the other genotypes, and we’ve talked a bit about the CRi. We -- it took time to make sure that the patient had achieved the CRi. We waited to get that confirmed. And then, you always hope to see will that deepen? How will that change over time? But at this point, we’re not providing any additional information at the time. We’ve confirmed these data at this point in time, and we hope that all continues well with this patient and others. But these are some of the early data that are beginning to emerge in the 120-milligram. I was going to ask if Dr. Bejar or Dr. Marango want to add to that. Dr. Rafael Bejar: I would just emphasize the point you made, Bill, that we do take the time to confirm that a patient is truly in remission before declaring it, and that usually means waiting an additional cycle, repeating a bone marrow biopsy. And we do always look at the genetics of the patient’s disease. And as you mentioned, many of these patients have very adverse co-mutations, and they included mutations like in [indiscernible] and TP53. And in this patient, in particular, as we announced today, the patient had an abnormality of MLL an MLL-PTD, which is a very adverse finding in both MDS and AML. Dr. William G. Rice: Yes. Thank you. Yes. What’s interesting is many drugs that will go through clinical development tends to narrow the patient population that you believe you can treat. But in this case, it continues to expand, and that’s an important message here that as we begin to treat more and more patients, it looks like the potential treatable patient population is continuing to expand. So, that’s good news for us. And thank you for the call today.

Our next question comes from the line of Joe Pantginis from H.C. Wainwright.

I have -- wanted to focus on screening and enrollment question regarding lux. So first, if I heard you guys correctly, you’re currently enrolling the 900-milligram BID arm for both studies. And I guess, I would ask it this way. How -- have you seen any inflection or change of the slope or what have you regarding being able to identify patients? And what I’m getting at, and hopefully, it’s not too convoluted, is potentially any harder to find patients for that arm of the study because you’re looking to get them on the G3 arm of the study, and doctors might be waiting to be on G3, for example. Dr. William G. Rice: Yes. Thanks, Joe. A couple of ways to respond to that. First of all, it is heavy PK sampling, very quickly. So, the way the study is designed -- and we’ve talked about this. So, the first dose that we gave to a patient, they get a single capsule of 50 milligrams of G3, and then we do PK sampling over the next 72 hours so that we can fully understand the pharmacokinetic profile. And it is a dense PK ambling, especially during the first 24 hours. And then after 72 hours, we give them a single dose of the current dose of the original formulation of G1. And at this point, that’s 900 milligrams. We follow the PK over the next 24 hours. Again, heavy PK sampling -- dense sampling, and then they go on the BID dosing of 900 milligrams. So yes, not every patient wants to undergo that dense PK sampling. But I think it’s going to make it easier from this point forward, now that we have data that we can present to the site and actually show them that what we’re seeing is very encouraging. What we wanted to accomplish with this new formulation is that we get rapid emulsification in the stomach and rapid absorption, and we clearly could see that. And so, we’re very happy with what we saw there. Again, it’s one patient. We’re happy with what we saw, but we can’t take it too far. Encouraging, but we still have a ways to go to fully understand the dose dependency of this new G3 formulation. But the clinical sites now, I think, are going to be more enthused, and they are bringing forward patients for this new G3. They definitely are.

Our next question comes from the line of Matt Biegler from Oppenheimer.

I just had a big -- kind of a big picture question here on your current thinking for the market opportunity for 239 outside of FLT3. Bill, you just mentioned expanding, which is obviously a good thing that we don’t see very often with drug development. I know we’ve got responses now in NPM1 IDH. I think you mentioned there’s a new one in MLL. So, I’m just kind of curious where you think the biggest opportunity is. Some of these, obviously, are indications where there’s other drugs in development for that have also shown promise. So, I’m just kind of curious what your thoughts are on the largest unmet needs in AML. Thanks. Dr. William G. Rice: Sure. Thanks, Matt. This drug does inhibit FLT3. It actually inhibits FLT3 exceptionally well, the wild type and the mutant forms. But we were not interested in just getting another FLT3 inhibitor, to be quite candid. And we even total Hanmi that. What made this drug interesting is the fact that, yes, it does inhibit the FLT3, and then it also inhibits very effectively certain of these other targets, and then we’re able to follow these pathways in the cell. And these are the pathways that -- so it’s kind of like guacamole. You might have done FLT3, but one of these other pathways, whether it’s the RAS, AKT, MAP kinase, all these different various pathways can emerge rescue the cells or it might be the MCL1 BCL-2 metabolism, all of these. So to sell as many ways to get around a drug. And we clearly could see that this drug was inhibiting many of these pathways simultaneously and making it difficult to get around the drug. So yes, we do see activity in patients that have the FLT3 mutations, but also in the wild type. And as patients get treated with more and more drugs over the years, you’re going to find more and more different mutation profiles and more patients that are refractory and resistant to the drugs. So, our eyes are into the future, looking to see what types of patients are going to emerge in the next 2 to 3 years. What are the patient needs there? What are the mutations? And these are very adverse co-mutations that we’re seeing in the patients. And this is where we see this drug, as I mentioned, the expanding potential for the populations to be treated beyond the FLT3, as you mentioned, the MLL and all the various types of mutant forms. So we’re very happy with what we’re seeing. And I’m going to ask Dr. Bejar to say that a bit more eloquently. Dr. Rafael Bejar: I’m not sure it’s possible to be more eloquent than you, Bill. But I’m going to build up one of your points that you just made in that there are multiple FLT3 inhibitors out there, and they all have slightly different patterns of kinase activity. And I think it’s important that a kinase inhibitor do target some of the common mechanisms of resistance that can emerge. And for drugs that only target the ITD, for example, mutations in FLT3 itself in the tyrosine kinase and a mutation are examples of that. And fortunately, 239 has great activity against both the ITD and the tyrosine kinase domain mutation. So if we’re shutting off that particular pathway. But I also think that it has the ability to target patients that have been previously treated with approved agents or other FLT3 inhibitors out there just because it does have a slightly different kinase profile. And I think the particular pattern, the SYK, JAK and mutant forms of KIT are great targets to hit, while also sparing those kinases that might cause more toxicity, they were to be inhibited too strongly. So I think we have not just the same patient populations that are treated by other agents, but we have patient populations that have become refractory to those agents that we might have activity in. And that’s a population of really great unmet medical need that I think will allow us an opportunity to get in the clinic sooner than if we had to go a more traditional frontline route or something like that. Dr. William G. Rice: Yes. That’s a very important point. Let me just build on that very quickly because as we look to go -- and we would hope to move this drug forward toward rapid approvals, the accelerated approval, but that means you have to identify the patients with high unmet medical need. Well, we’ve already done that. We already see several populations that have that unmet medical need, and we hope to be able to then drive those forward toward the accelerated approval pathways. But since we also see activity in the FLT3 wild type and other populations, you want to be testing the drug in those patients in parallel so that you can begin to expand the label out later. So, those are our plans with 239. I hope that answers your question.

Yes. That makes sense. Maybe if I could just squeeze in a quick follow-up. I apologize if I missed this. But, can you confirm if the new complete responder at 120 was a FLT3 mutant, or were they a FLT3 wild type? Dr. William G. Rice: We haven’t released that information yet. So, we’ll have to go back and take a look at when we’re going to release all that information. EHA is coming up soon. But either way, what it does, it proves this drug is active at multiple dose levels and expands out the population. So either way, we’re thrilled with what we’ve seen.

Our next question comes from the line of Soumit Roy from Jones Research.

Hi. Congratulations from me, too. Great detail. Trying to understand what would be -- in the future, most of the patients that are on CR are progressing into stem cell transplantation. So, you think this is going to be the paradigm where DOR of about 2 to 3 months and patients become transplant eligible and they were going to transplantation? Is that how you’re looking at in these relapsed/refractory setting? Dr. William G. Rice: Yes, please. Dr. Rafael Bejar: I can jump in here. You’re absolutely right that we have seen a pattern of that. And this is actually an issue even for midostaurin in the RATIFY [ph] trial where many of the patients were going into stem cell transplantation more than they would have predicted. And in part, it speaks to the activity of the drug that allows the patients to get into a stage where a transplant becomes a feasible option. So, as a clinician, I’m thrilled to see that. I think that if we could offer our patients a potentially curative procedure to treat such a terrible disease that we should be doing that. So, I’m encouraged by that activity. I think it’s a positive. However, not every patient will have that as an option. So either transplant isn’t -- they don’t have a donor or they are in a condition where a transplant makes sense for them. We do want to have patients that have durable responses to these oral agents that can really greatly improve their quality of life and the duration of life. And we did have the one patient who was ineligible for stem cell transplant that had a profile that you would have predicted, had a very early relapse risk. And that patient was on a single daily oral agent for over a year with relapsed/refractory [indiscernible] AML. So, we need more patients and more experience to really understand what the duration of response is likely to be, but I was very encouraged by seeing that activity there. And I never upset when we get a patient to transplant in 2 or 3 cycles. Dr. William G. Rice: Yes. It’s a great point. So yes, we want to see the drug as durable in the patients that are ineligible for transplant. But really, what we’re looking for is survival here. So anything that we can do to enhance the survival of these patients, that’s our mission.

Right. So, in terms of a confirmatory trial, do you think the survival, which would include now the transplantation, would come into effect or it could get accelerated approval based on response rate or MRD negative status or firsthand transplantation and then OS would be looked at as a complementary trial? How do you envision that? Dr. William G. Rice: Those will be conversations we will have with the agency, the FDA. But Dr. Bejar, would you like to address that one, too? Dr. Rafael Bejar: Yes. I would say for those populations with unmet medical need, they have -- there is precedence for getting approval based on surrogate end point short of overall survival. And we are paying special attention to those endpoints that the FDA considers important in that regard and so the patient populations that might fit that need. And I think down the road, ultimately, a confirmatory trial will have to improve overall survival in this patient population that has certainly short OS. I mean even in the patients that were treated in the trial, unfortunately, those patients improve their overall survival, but it wasn’t a cure for them either. So, we certainly have a lot of patients that we can help here. Dr. William G. Rice: Yes. The good news is we’re not asking a question, is this an active drug? We see there’s activity there. We’re actually now talking about what are the endpoints for getting approval. So, that just tells you how far we’ve come very quickly with this drug.

Thank you. We have time for one further question. Our final question for today comes from the line of Matthew Cross from Allegiance Global Partners.

Hey, guys. Good afternoon. Congrats on the new CR for 239 for me as well. For the sake of time, I will skip a housekeeping question, but I’ll just ask kind of a two-parter on lux. Bill, you commented on kind of PK sampling for the G3 moving into in G1 in the current study of lux. I was curious, and I don’t know if these -- this kind of 2-part question is something that you can answer now or something that you can guide towards what we may see midyear. But I was curious if in that PK sampling you’ve seen so far, any kind of equivalency or near there in terms of exposure when patients are moving from the 50-milligram G3 to the 900-milligram G1? And kind of related to that, while you’re exploring the PK for G3, and that is, I assume, kind of the focus right now, do you envision kind of pausing lux G1 and keeping at that 900-milligram dose so you’ve kind of explored what’s going on with G3, or would you expect to continue dose escalating G1 at the same time? Thanks. Dr. William G. Rice: Well, there are -- Matt, there are a few questions in there. Because we’re speaking about limited data with G3, I’ll be cautious. What I can say again is we did see that rapid rise of the absorption that we have never seen with the G1. So, it was clearly being solubilized while being absorbed well. And again, we were comparing a 50-milligram dose of G1 to 900 milligrams, 18-fold more of the G1. And we were very happy with the exposure that we saw there with that one dose. And even up to 72 hours, we could see that there was some drug left in the system. Again, limited data. And so, we don’t know if that’s going to continue. But yes, we were pleased with the profile that we saw. And now we need to understand whether or not we get any exposure if we continue to dose escalate. So, we’re enthused with what we saw, but we just don’t know. Now, in terms of going forward, those patients, currently, we’re dosing the G1, collecting the data and then they get 900 milligrams. So, the patient that we -- patients we envision into the future are going to be into the near future are going to be treated with the 900 milligrams of G1 on a BID dose thereafter. That allows us to collect a great deal of additional data at 900 milligrams BID. That’s actually a lot of G1, 1.8 grams a day, and then compare that to the G3 exposure levels. And then, hopefully, as the year goes on here, we’ll have enough patients to be able to do the PK modeling and tell us whether or not we can truly go toward continuous dosing that gives us the exposures that we believe, and then hopefully transition over to G3 only. But that depends on the data. We’re hopeful, but the data will guide us in that direction. And we will continue to provide the data as much as we can as we go forward. Did that answer your question, Matt?

Understood. Yes, it does for now, Bill. I look forward to a few more answers middle of the year. I’ll keep it going. Dr. William G. Rice: Looking forward to showing you the graphs. All right. Thanks, Matt.

Thank you. This does conclude the question-and-answer session of today’s program. I’d like to hand the program back to Dr. William Rice for any further remarks. Dr. William G. Rice: Well, I’ll keep this short. I just want to thank everyone for joining us this afternoon. We believe that both 239 and the lux are really remarkable assets that will bring significant value to Aptose and to our shareholders. We want to thank our employees for their dedication and commitment to the Company as well as the patients we serve. And I’m really proud to be part of this team and grateful for the effort. We’re also grateful for all of our shareholders and our clinical investigators. And we do look forward to updating you more on our existing pipeline and exciting pipeline in the coming days. So, thank you, everyone. Have a wonderful evening.

Thank you, ladies and gentlemen. That concludes today’s conference. You may all disconnect, and have a wonderful day.