Q4 2023 Aptose Biosciences Inc Earnings Call

Operator: 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 and year ended December 31st, 2023. At this time, all participants are in a listen-only mode.

Good afternoon. My name is Jonathan and I will be your conference operator today I would like to welcome everyone to <unk> Biosciences conference call for the fourth quarter and year ended December 31st 2023. At this time all participants are in a listen only mode. After the Speakers' remarks, there will be a.

Operator: 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 one on your telephone. You will then hear an automated message advising that your hand is raised.

<unk> and answer session. If you would like to ask a question. During this time you will need to press star one on your telephone.

Then here an automated message advising your hand is raise if you would like to withdraw your question. Please press star one again.

Operator: If you would like to withdraw your question, please press star 11 again. Thank you. As a reminder, this conference call may be recorded. And now, I'd like to introduce your host for today's program, Susan Pietropaolo. Please go ahead. Thank you, Jonathan.

As a reminder, this conference call may be recorded.

Speaker Change: Now I'd like to introduce your host for today's program Susan Pietro Paolo. Please go ahead.

Susan M. Pietropaolo: Good afternoon, and welcome to the Aptose Biosciences conference call to discuss financial and operational results for the fourth quarter and year ended December 31st, 2023. Earlier today, Aptose issued a press release relating to these financial results. The news release, as well as related SEC filings, are accessible on Aptose's website.

Speaker Change: Thank you Jonathan good afternoon, and welcome to the Atlas.

Speaker Change: This conference call to discuss financial and operational results for the fourth quarter and year ended December 31st 2023 earlier today afterwards issued a press release relating to these financial results news release as well as related SEC filings are accessible on <unk> website. Joining me on today's call are Dr. William Rice Chairman printed.

Susan M. Pietropaolo: Joining me on today's call are Dr. William Rice, Chairman, President, and CEO; Dr. Rafael Bejar, 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 Aptose's 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 Aptose's most recent annual report on Form 10-K and SEC and CEDA filings. All forward-looking statements made during this call speak only as of the date they are made.

Speaker Change: And CEO, Dr. Rafael Bejar, Senior Vice President Chief Medical Officer, and Mr. Fletcher Payne Senior Vice President and 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.

Speaker Change: These statements reflect absolutely 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.

Speaker Change: Bob known and unknown risks uncertainties and assumptions that may cause actual results performance and achievement to differ materially from those expressed.

Speaker Change: To learn more about these risks and uncertainties. Please read the risk factors set forth in that post. This most recent annual report on Form 10-K, and SEC and SEDAR filings.

Speaker Change: All forward looking statements made during this call speak only as of the date, they're made absolutely 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 todays press release and the 10-K for additional information and disclosures regarding today's announcement I will now turn the call.

Susan M. Pietropaolo: 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. We encourage you to refer to today's press release and the 10-K for additional information and disclosures regarding today's announcement. I will now turn the call over to Dr. Rice. Thank you.

William G. Rice: Over to Dr. Rice.

William G. Rice: I want to welcome everyone to our call for the fourth quarter and year ended December 31st, 2023. Today, we will provide updates on our financial status, on the near-term and long-term clinical development plan for our lead agent, TUSPENTENIB, and a quick update on our LUXEPTENIB program. From a financial perspective, during 2023, we financed corporate activities with cash gleaned from our ATM facility, from a committed equity facility, and through a strategic investment by our partner, Honmi Pharmaceuticals. Then, in January of this year, we closed financings with gross proceeds of $13.7 million, inclusive of a $9.7 million public offering, along with a separate $4 million private placement with Honmi. This provided us with more breathing room, and Mr. Fletcher Payne, our CFO and CBO, provided additional financial details in a few minutes.

William G. Rice: Thank you Susan I want to welcome everyone to our call for the fourth quarter and year ended December 31.

William G. Rice: 23.

William G. Rice: Today, we will provide updates on our financial status on the near term and long term clinical development plan for our lead agent.

William G. Rice: And a quick update on our <unk> program.

William G. Rice: From a financial perspective during 2023 refinance corporate activities with cash gleaned from our ATM facility from our committed equity facility and through our strategic investment by our partner Hanmi Pharmaceuticals.

William G. Rice: January of this year, we close financings with gross proceeds of $13 $7 million inclusive of a $9 $7 million public offering along with a separate 4 million private placement with Hanmi pharmaceuticals.

Speaker Change: This was more breathing room Mr. Fletcher.

Speaker Change: Our CFO and CBO provide additional financial details in a few minutes.

William G. Rice: And now I want to pivot to our lead program, TUSPET. So why should you care about TUSPIT? It's because Tusfetanib, or TUS, as we often call it, is a convenient, orally administered, once-daily kinase inhibitor with an excellent safety profile and potent anti-leukemic activity being developed for the treatment of acute myeloid leukemia, or AML. And we believe a Tespitinib-containing triplet regimen can become a new standard of care for the This day will explain why we believe this and how we arrived at this point.

Speaker Change: And I want to pivot to our lead program.

Speaker Change: So why should you care about.

Nicolas: It's Nicolas.

Nicolas: Our task as we often call it.

Nicolas: Early administered once daily kinase inhibitor with an excellent safety profile and potent anti leukemic activity that is being developed for the treatment of acute myeloid leukemia or AML.

Nicolas: And we believe a container.

Nicolas: Containing triplet regimen can become a new standard of care for the frontline treatment of newly diagnosed AML patients across the broadest set of genetic subtypes.

Nicolas: Dave will explain why we believe this and how we arrived at this point.

William G. Rice: First, you're aware that we've been performing studies in relapsed or refractory AML, with Tusvetinib as a single agent and with Tusvetinib in combination with venetoclax, which we refer to as the Tus-Ven-W. The valuable findings gleaned from these studies have now led us to pursue the development of TUSPETNIP as a triplet combination therapy for the The triplet includes TUSPETNIP, the BCL-2 inhibitor, Venetoclax, and a hypomethylating agent, such as Ace-Sodadine, collectively referred to as the TUS-Ven HMA-TRIP. In fact, we just heard from a group of KOLs and AML that they had great enthusiasm for the safety and activity of Tuspetanib. And they believe this is a real drug with the potential to go all the way. These KOLs and our internal team all agree that the immediate focus of Tuspetanib should be primarily on the TusVen HMA trip. And that is precisely where we're focusing our research.

Dave: First youre aware that we've been performing studies and relapsed or refractory AML patients with the <unk>.

Dave: Single agent and in combination with vanilla class, which we refer to as the doublet.

Dave: Doublet.

Dave: The valuable findings gleaned from these studies have now led us to pursue the development of <unk> as.

Dave: As a triplet combination therapy for the frontline treatment of newly diagnosed AML patients as the highest priority. The triplet includes testbed.

Dave: The Bcl two inhibitor <unk> and our heartworm escalating agents such as a Saturday collectively referred to as the test HMA triplet.

Dave: In fact, we just heard from our group of Kols in AML.

Dave: Great enthusiasm for the safety and activity of <unk>.

Dave: And they believe this is a real drug with the potential to go all the way these kols and our internal team all agree that the immediate focus of test.

Dave: Should be primarily on the test ban HMA triplet.

Dave: And that is precisely where we're focusing our resources because this has been the HMA triplet.

William G. Rice: Because this Tuscan HMA triplet has the potential to deliver the greatest patient impact, the greatest commercial impact, and the greatest return to our investors. At the patient level, we believe TUSPENTIN can have its greatest impact in frontline AML by improving response rates, the depths of responses, the durability of responses, quality of life, and long-term survival across a diversity of AML, relative to the current Ben HMA Standard of Care and frontline AML patients who are ineligible for intensive chemotherapy. Plus, the commercial aspect, or impact, of the Tusden HMA triplet and frontline therapy is estimated to exceed $1 billion. And we've heard from many potential partners that the application of the TUSBIN HMA to the frontline market is of primary interest to them.

Dave: Tangela to deliver the greatest patient impact the greatest commercial impact and the greatest return to our investors.

Dave: At the patient level, we believe and have its greatest impact in frontline AML by improving the response rates the depth of responses.

Dave: Durability of responses the quality of life and the long term survival across a diversity of AML patients relative to the current Ben HMA standards of care in frontline AML patients who are ineligible for intensive chemotherapy.

Dave: Plus the commercial aspect or impact of the touch than HMA triplet in frontline therapy.

Dave: Estimated to exceed $1 billion annually and we've heard from many potential partners that the application of the test been HMA to the frontline market.

William G. Rice: Indeed, the safety, breadth, and efficacy profiles of test spetanib today make us believe that test spetanib could be the best agent to combine with Venn HMA, which is the current standard of care. While the goal for the TUSPETNIV program is to move into frontline EML therapy at the triplet, the path to the frontline triplet began with the TUSPETNIV single-agent trial and then transitioned through the TUSPEN doublet trial to understand activities, safety, and contribution of components. With the TUSPETINIB single-agent trial, we completed enrollment of 93 patients across six doses. Tospetnev's single agent achieved an excellent safety profile without many of the key liabilities seen in competing agents.

Dave: Primary interest to them.

Dave: Indeed, the safety and efficacy profiles of tests to date Mike.

Dave: Make us believe that there can be the best agents to combine with even the HMA, which is the current standard of care.

Dave: Well the goal for the <unk> program is to move into frontline AML therapy at the triplet.

Dave: To the frontline terrific again, but the single agent trial, and then transitioned through the doublet trial to understand activities safety and contribution of components.

Dave: With a single.

Dave: Single agent trial, we completed enrollment of 93 patients across six dose levels.

Dave: Single agent achieved an excellent safety profile without many of the key liability seen in competitor agents have demonstrated broad activity across AML populations with that first genetic operations. We observed a threefold lager median overall survival in responding patients relative to non responders.

William G. Rice: It demonstrated broad activity across AML populations with adverse genetic alterations. We observed a threefold longer median overall survival in responding patients relative to non-responders. And 80 milligrams once daily was selected as the recommended phase two dose for single agent therapy. At the 80 milligram dose level, TUSPENTINIB was highly active, achieving high-quality responses with high response rates. We were delighted to see a strong 36% CRCRH rate among all-comer genotypes in patients who had not previously been treated with benetoclax, referred to as ben-naive patients.

Dave: And 80 milligrams once daily was selected as our recommended phase II dose for single agent therapy.

But the 80 milligram dose level test pattern of single agent was highly active achieving high quality responses with high response rates, we were delighted to see a strong 36% CR CRH rate among all comer genotypes in patients who had not previously been treated with banana costs referred to as <unk>.

William G. Rice: Notably, at the 80 milligram dose level, few of the patients had failed prior therapy with venetoclax. However, as we dosed escalated above the 80 milligram dose level, we saw that prior ven failure patients were emerging as a new category of relapsed refractory AML at that point in time. And the proportion of prior ven patients increased dramatically to greater than 80% at the next dose level of 120 milligrams. Once patients fell ill with venetoclax-containing therapy, they were more refractory to all subsequent salvage therapies, including TUSP-Betanib as a single agent. And this led to lower response rates at the 120 milligram dose level and then at the 160 milligram dose level.

Dave: Ben.

Dave: Patients no.

Dave: Notably at the 80 milligram dose level fueled the patients had failed prior therapy with <unk>. However, as we dose escalate even above the 80 milligram dose level. We saw that are been failure patients were emerging as a new category of relapsed refractory AML at that point in time.

Dave: The proportion of prior been patients increased dramatically to greater than 80% and the next dose level of 120 milligrams.

Once patients fill up <unk> containing therapy.

Dave: More refractory to all subsequent salvage therapies, including <unk> as a single agent and this led to lower response rates in the 120 milligram dose level and then in the 160 milligram dose level or.

William G. Rice: Fortunately, there is a silver lining to this change in the reluctant refractory AML patient population and our past scientific conference presidents. We've described how TUSPETINIB targets the venetoclax resistance mechanism and how it works synergistically with venetoclax in animal models. Plus, we've shown that TUSPETINib-resistant AML cells are hypersensitive, 2,000-fold more sensitive to phonetically. Its mechanistic complementarity provided a rationale for us to combine TUSPETinib with Phenetocortinib to evaluate the Tufts fin doublet and the relapsed refractory AML population. In our TUSPAN doublet trial, we now have completed enrollment with 40 milligrams TUSPETINIM and with 80 milligrams TUSPETINIM, combined with 400 milligrams of venetoclax in a total of 79 patients. First, we observed that the excellent safety profile of TUSK VETENIF as a single agent was maintained with the TUSK VEN double.

Dave: Fortunately there is a silver lining to this change in the relapsed refractory AML patient population.

Dave: Our past scientific conference presentation, we've described <unk> targets <unk> resistance mechanism.

Dave: It helps us.

Dave: Volume Synergistically with Benetti class in animal models.

Dave: Plus we've shown that.

Resistant AML cells are hyper sensitive 2000 fold more sensitive to <unk> costs.

Dave: Mechanistic complementarity.

Dave: Provided the rationale for us to combine <unk> with.

Dave: <unk> to evaluate the tustin doublet in the relapsed refractory AML population.

Dave: And our touchpad doublet trial, we now have completed enrollment with 40 milligram dose.

And with 80 milligram dose.

Dave: Combined with 400 milligrams banana clocks and a total of 79 patients.

First we observed that the excellent safety profile a test at the.

Dave: Single Asia was maintained with the tests have been dealt with.

William G. Rice: We observed bone marrow leukemic blast reductions in the majority of patients, including those who failed prior therapies with FLIT3 inhibitors or prior venetofox therapy. And we can continue to see evidence of broad activity across AML patients with a diversity of adverse mutations, including patients who had failed prior therapy with Pineda. We see great promise for the TUS Venn doublet to effectively treat prior Venn failure patients and even become a standard of care for those patients. And there remains a potential accelerated approval path for the TUS and doublet in a molecularly defined subpopulation of relapsed refractory AML, especially if we increase the dosage of TUSPEN and the TUSPEN doublet and demonstrate even greater activity. This has been a source of high interest for KOLs, collaborators, and certain potential partners.

Dave: We observe bone marrow leukemic blast reductions and the majority of patients, including those who have failed prior therapies with flip through inhibitors or prior <unk> therapy.

Dave: And we can continue to see evidence of broad activity across AML patients with a diversity of adverse mutations, including patients who have failed prior therapy with <unk>.

Dave: We see great promise for the Tustin doublet.

Dave: <unk> treat the prior been failure patients and even become a standard of care for those patients and there remains a potential accelerated approval path for the <unk> doublet in a molecularly defined subpopulation of relapsed refractory AML, especially if we increase the dosage of test and.

Dave: And the <unk> doublet and demonstrate even greater activity.

Dave: This has been a source of high interest for Kols collaborators and certain potential partners and as resources become available we would like to pursue the tustin doublet with higher doses of test for.

William G. Rice: And, as resources become available, we would like to pursue the Tusmin doublet with higher doses of Tusvetinib for the relapsed refractory population. However, in the near term, we have chosen to focus our resources on the TUSPIN HMA triplet and frontline AML therapy. So our next step to build value as quickly as possible will be to initiate a tuspetinib plus venetoclax plus azacitidine triplet pilot study in frontline newly diagnosed AML patients and to select the optimal triplet dosage of tuspetinib, which will be driven by CRH rates, MRD negativity, and safety data. After selecting appropriate phase two doses of the triplet, we plan to transition into registrational studies that compare the safety and efficacy of the triplet to the Venn HMA control for frontline newly diagnosed AML patients.

Dave: So the relapsed refractory population.

Dave: However in the near term, we have chosen to focus our resources on the test been HMH triplet and frontline AML therapy.

Dave: So our next step to build value as quickly as possible will be to initiate a test.

Dave: Plus <unk> plus a decidedly a triplet pilot study in frontline newly diagnosed AML patients and to select the optimal triplet dose dosage of <unk>.

Dave: Which will be driven by CR cri rate <unk> negativity and safety data.

Dave: After selecting appropriate 32 doses of the triplet we plan to transition into Registrational studies that compare the safety and efficacy of the triplet to the HMA control for frontline newly diagnosed AML patients.

William G. Rice: I also want to mention that our ongoing BD conference conversations with a number of large pharma companies emphasize a need for the AML therapeutic paradigm to focus on creating more effective, more durable, broader acting, and less toxic frontline cocktails of targeted agents for AML patients. And they point to frontline triplet therapy as the cornerstone of commercial success. It's clear that we can create the greatest value for TUS VETNIP in the shortest period of time, earn the least amount of capital, by performing a TUS VEN HMA triplet pilot study in frontline EML patients, and such data could then support partnerships for later stage development of TUS VETNIP. So this provides you with a framework of our strategic thought process, and Dr. Bejar, our Chief Medical Officer, will provide you with additional clinical insights in perspective in a few minutes.

Dave: I also want to mention that our ongoing BD conference had conversations with a number of large pharma companies emphasize they need for the AML therapeutic paradigm to focus on creating more effective more durable broader acting and less toxic frontline cocktails or targeted agents for AML patients.

Dave: And they point to the frontline triplet therapy as a cornerstone of our commercial success.

Dave: It's clear that we can create.

Dave: <unk> value for <unk> and the shortest period of time for the least amount of capital are performing a test than HMA triplet pilot study in frontline AML patients and such steady for them support partnerships for later stage development of <unk>.

Dave: So this will provide you with a framework framework of our strategic thought process and Dr. <unk>, Our Chief Medical Officer, who will provide you with additional clinical insights and perspectives in a few minutes.

William G. Rice: But first, I also want to mention our other drug, luxeptin. You will recall that LUX, as we often call it, is an oral, highly potent kinase inhibitor that selectively targets defined kinases active in myeloid and lymphoid hematologic malignants. This molecule has been evaluated in a Phase IaB study for the treatment of patients having relapsed or refractory B-cell leukemias and lymphomas, and in a Phase 1 AB study for the treatment of patients with relapsed or refractory AML. Enrollment and initial dosing of patients in the B-cell malignancy trial have now been completed, including 36 patients who were dosed with In this trial, LUX achieved tumor shrinkage among 63% of the available B-cell cancer patients and across dose levels from 450 to 900 mg.

Speaker Change: First I also want to mention our other drug looks at it.

Speaker Change: Recall that looks as we often call. It an oral highly potent kinase inhibitor are selectively targets defined kinases operative in myeloid and lymphoid hematologic malignancies. This small molecule has been evaluated in a phase <unk> study for the treatment of patients, having relapsed or refractory b cell loops.

Speaker Change: <unk> in lymphomas and in a phase one study for the treatment of patients with relapsed or refractory AML and.

Speaker Change: Enrollment and dosing of patients in the B cell malignancy trial have now been completed including 36 patients who were dosed with the original <unk> formulation across five dose levels ranging from 150 milligram to 900 milligrams B I D.

Speaker Change: In this trial <unk> achieved tumor shrinkage amongst 63% of Evaluable b cell cancer patients and across dose levels from 450 to 900 milligrams. This also includes a complete response or CR and a D. L. Bcl patient unimpressive tumor reductions and Follicular lymphoma patients at NSS and then.

William G. Rice: This also includes a complete response, or CR, and a DLVCL patient, and impressive tumor reductions in follicular lymphoma patients, and an SLL patient. Likewise, enrollment and dosing of patients in the AML trial have now been completed. In this trial, AML patients received the original G1 formulation across dose levels ranging from 450 to 900 milligrams BID. Bone marrow blast reductions were observed in 38% of the evaluable FLT3 mutated patients and 50% of the evaluable FLT3 wild-type AML.

Speaker Change: <unk> outpatient.

Speaker Change: Likewise enrollment and dosing of patients in the AML trial now has been completed and.

Speaker Change: In this trial AML patients received the original <unk> formulation across dose levels, ranging from 450 to 900 milligrams.

Speaker Change: Bone marrow blast reductions were observed and 38% of Evaluable flip three mutated patients and 50% of Evaluable <unk> wild type of AML patients in.

William G. Rice: In addition, an MRD-CR, or complete response, occurred in one reslapse-tractor AML patient with a 450 milligram BID dose of the original T1 formulation. Our clinical data demonstrate that LUX is active in AML patients and in B-cell cancer patients, but we were not consistently achieving the desired exposure levels to drive consistent response. Because absorption of the original G1 formulation hampered the effectiveness of LuxEvimid, a new Generation 3, or G3, formulation was developed.

Speaker Change: In addition, and <unk> negative CR or complete response, and one relapsed refractory AML patient occurred with the 450 milligram.

Speaker Change: I'd dosing of the original coupon and formulations.

Speaker Change: Our clinical data.

Speaker Change: Straight debt Lux is active in AML patients and in B cell cancer patients, but we were not consistently achieving the desired exposure levels to drive consistent responses.

Speaker Change: The absorption of the original <unk> formulations hampered the effectiveness of looks at.

Speaker Change: Our new generation three or G. III formulation was developed.

William G. Rice: And now we can report that the clinical evaluation of the G3 formulation also has been completed. First, the G3 formulation was tested in a single-dose bioavailability study in 20 patients, including both B-cell cancer and AML patients, and across five different dose levels, from 10 milligrams to 200. The G3 formulation was then evaluated in relapsed refractory AML patients with continuous dosing using two different dose levels, 50 mg VID and 200 mg VID in a total of 11 patients.

And now we can report that the clinical evaluation of the G III formulation.

Speaker Change: Also has been completed.

Speaker Change: First the <unk> formulation was tested in a single dose bioavailability study of 20 patients included in both B cell cancer, and AML patients and across five different dose levels from 10 milligrams to 200 milligrams.

Speaker Change: These three formulations within evaluated in relapsed refractory AML patients with continuous dosing using two different dose levels 50 milligrams, PID and 200 milligrams PID and a total of 11 patients.

William G. Rice: Recent data show the G3 formulation, dosed at 200 milligrams twice daily, can achieve 2 to 3 micromolar steady-state plasma levels with approximately 10-fold better absorption and, interestingly, even better tolerability than the original G1 formula. This means the G3 formulation achieved our desired plasma exposure benchmark and that the G3 formulation will be the formulation of choice for future studies with LUT. Collectively, these findings demonstrate LUX is a viable drug with a viable formulation and that LUX as the G3 formulation should be advanced into a focused clinical development program, and we are delighted to see a future for LUX. Regarding any next steps with LUX, we are exploring the potential to advance LUX to treat molecularly defined relapsed refractory hematologic malignancy patient populations of high And we are now seeking alternative development paths and collaborations to execute that strategy. I now want to turn the call over to Dr. Bejar, our Chief Medical Officer and resident KOL, for his insights and comments on our data and clinical plans for TUSP-NAP. Thanks, Bill, and good morning from Japan.

Speaker Change: Recent research data showed that G. III formulation dosed at 200 milligrams twice daily.

Speaker Change: <unk> achieved two to three micro molar steady state plasma levels with approximately 10 fold better absorptions and interestingly, even better tolerability than the original <unk> formulation.

Speaker Change: This means that G. III formulation achieved our desired plasma exposure benchmark met the <unk> formulation will be the formulation of choice for future studies with Lux.

Speaker Change: Collectively these findings demonstrate lux is a viable drug with a viable formulation.

Speaker Change: <unk> at the <unk> formulation should be advanced into a focused clinical development program and we are delighted to see a future for logs.

Speaker Change: Regarding any next steps with Lux, we're exploring the potential to advance <unk> to treat molecularly defined relapsed refractory hematologic malignancy patient populations with high unmet need and.

And we now are seeking alternative development paths and collaborations to execute that strategy.

Speaker Change: Now, let's turn the call over to Dr. Bejar, our Chief Medical Officer, and resident Kols for his insights and comments on our data and clinical plans for.

Speaker Change: <unk>.

Thanks, Bill and good morning from Japan.

Rafael Bejar: As Bill mentioned, combination therapy is becoming more and more common for the treatment of newly diagnosed AML. Patients have been tested as triplets with a standard of care backbone of venetoclax with a hypermethylating agent and older patients who are ineligible to receive intensive chemotherapy. There have been promising proof-of-principle successes in treating patients with triplet therapies that include kinase inhibitors like dyspetinib. In fact, our lead investigator, Dr.

Rafael Bejar: As Bill mentioned combination therapy is becoming more and more common for the treatment of newly diagnosed AML.

Rafael Bejar: Patients have been tested as triplets with standard of care backbone venetic wax method agent in older patients who are ineligible to receive intensive chemotherapy.

Rafael Bejar: Had been promising proof of principle successes in treating patients with triple therapies that include kinase inhibitors like dispassionate in fact are the divesting it or Dr. <unk> and his team at the MD Anderson cancer Center have seen impressive response rates nearing 100% with this approach and certain AML population.

Rafael Bejar: Naval Daver, and his team at the MD Anderson Cancer Center have seen impressive response rates nearing 100% with this approach in certain AML populations. However, these types of triple therapies to date are complicated by increased toxicity that require reducing the dose and intensity of each agent and the use of pure FLT3 inhibitors that have been limited only to FLT3-mutated AML, which accounts for just 30% of the population. But, with this paradigm shift, many companies are now expanding their clinical development plans to test their drugs in this type of triplet combination protocol. We've maintained from the start of its development that dyspetinib appears to be an ideal candidate for triple-combination therapy, and our experience to date continues to build and support this strategy. As Bill mentioned, we've taken a deliberate and tiered clinical approach.

Rafael Bejar: However, these types of triplet therapies to date are complicated by increased toxicity that require reducing the dose and intensity of each agent and the use of peer for three inhibitors that had been limited only to play <unk> mutated AML, which accounts for just 30% of the population.

Rafael Bejar: But with this paradigm shift many companies and are expanding their clinical development plans to test their drugs in these type of triplet combination protocol.

Rafael Bejar: We have maintained from the start of its development spend appears to be an ideal candidate for triple combination therapy.

Rafael Bejar: Experienced to date continues to build and support the strategy.

Rafael Bejar: Bill mentioned, we've taken a deliberate and tiered clinical approach.

Rafael Bejar: First, we successfully demonstrated significant activity of TUS in a single-agent dose-escalation exploration trial in a broad relapsed refractory AML population. We completed dose escalation, exploration, and expansion studies with 93 patients treated with TUS, dosed once daily for 28 days without interruption. Anti-leukemic activity that included durable, objective clinical responses was observed at 4 active dose levels, all of which were well-tolerated, with no dose-limiting toxicities in over 70 treated patients.

Rafael Bejar: First we successfully demonstrated significant activity of tests in a single agent dose escalation exploration trial in a broad relapsed refractory AML population.

Rafael Bejar: We completed dose escalation exploration and expansion studies with 93 patients treated with test dosed once daily for 28 days.

Rafael Bejar: Without interruption.

Rafael Bejar: And Dave Leukemic activity that included durable objective clinical responses was observed for active dose levels, all of which were well tolerated with no dose limiting toxicities and over 70 treated patients.

Rafael Bejar: At the 80 milligram dose in the then-naive patient population, TUSPEDNIV had an excellent CR-CRH rate, 50%, 36%, 25% in FLIT3 mutant, overall FLIT3 wild type, overall, and in FLIT3 wild type, respectively. Importantly, tests demonstrated an excellent safety profile with no instances of drug-related QTC prolongation, differentiation syndrome, or muscle damage in any patient, or prolonged myosup As Bill mentioned, we observed broad activity across AML populations at four dose levels. This included patients with adverse genetic alterations in FLUT3, RAS, P50, DMT3A, IDH genes, MPM1 genes, MLL-PTD, and others. Then, in conjunction with the FDA, 80 milligrams once daily was selected as the recommended phase 2 dose for single-agent therapy.

Rafael Bejar: At the 80 milligram dose in the Venn naive patient population to spend it had an excellent CR cri rate, 50%, 36%, 25%.

Rafael Bejar: Flip to Eaton's overall phase III wild type overall, and it's a three well type respectively.

Rafael Bejar: Importantly test demonstrated an excellent safety profile with no instances of drug related UTC prolongation differentiation syndrome or muscle damage in any patient or prolonged suppression in responding patients who had cleared the leukemia.

Rafael Bejar: As Bill mentioned, we observed productivity across AML populations at four dose levels. This included patients with adverse genetic alterations included three rast.

Rafael Bejar: <unk> H genes <unk> genes, MLR DTD and others.

Rafael Bejar: Then in conjunction with the FDA 80 milligrams when standing was selected as the recommended phase two dose where single agent therapy.

Rafael Bejar: As AML care has shifted toward venetoclax-containing combination regimens, we began to find in, are challenging to treat relapsed refractory AML patients who had received and failed venetoclax. This emerging patient population now accounts for a large percentage of relapsed refractory patients entering all AML trials, something we all developing these trials need to consider as Venn failure patients are more resistant to. [inaudible] The purpose of the study was to make a systematic use-based loop of endocannabinoid and endocannabinoid-specific antiretroviral therapy and antidepressants that could In this study, we used a TUS-Ven combination to treat a very ill, prior-Ven-treated AML population, which led us to conduct APTIVATE, our TUS-Ven doublet study in reastrofractory AML. We initiated Aptivate as a doublet study of TUS ven to explore the ability of TUS to treat these venereal patients.

Rafael Bejar: As Emil care has shifted towards venetic racks containing combination regimens, we began defined in our single.

Still challenging to treat relapsed refractory AML population and those patients who had received and failed <unk>.

This emerging patient population now accounts for a large percentage of relapsed refractory patients entering all AML trials something we all developing these trials need to consider as Vin failure patients are more resistant to subsequent.

Speaker Change: Okay. Thank you.

Speaker Change: Okay.

Speaker Change: Okay.

Speaker Change: Yes.

Speaker Change: Okay.

Speaker Change: Thanks.

Speaker Change: Got it.

Speaker Change: Okay.

Speaker Change: Okay.

Speaker Change: Okay.

Speaker Change: Okay.

Speaker Change: Yes.

Speaker Change: Patients to treat Ariel prior been treated AML population, which led us to conduct activate our testbed doublet study in relapsed refractory AML.

Speaker Change: We initiated activate and.

Speaker Change: As a doublet study of test that and to explore the ability of tested treat these <unk> patients.

Rafael Bejar: We completed dose exploration with 40mg, then 80mg, with 79 patients. The test-ven doublet treatment was well-tolerated, with no drug-related deaths and lower rates of febrile ventropenia than observed in other ven combination studies. Response activity of 80 mg TUS and 400 mg VEN was broad-based and was observed in patients with and without a history of venetoclax treatment and in patients with and without FLT3 mutations. Importantly, we observed a dose-response relationship, such that patients receiving 40 milligrams of bispetinib with phonetoclax achieved bone marrow blast reductions but did not achieve formal responses in large numbers. In contrast, many of the patients who received 80 milligrams of Spetnib with Phenetoclax did achieve both bone marrow and diformal responses.

Speaker Change: We completed dose exploration with 40 milligrams than 80.

Graham was 79 patients.

Speaker Change: The test been doublet treatment was well tolerated with no drug related deaths and lower rates a favorable opinion from observing other than combination studies.

Speaker Change: Response activity with 80 milligrams tests and 400 milligrams value was broad based it was observed in patients with and without a history of inadequate treatment and in patients with and without <unk> mutations.

Speaker Change: Importantly, we observed a dose response relationship such that patients receiving 40 milligrams of just bandwidth venetic wax achieve bone marrow blast reductions, but did not achieve formal responses in large numbers.

Speaker Change: Interest many of the patients who received 80 milligrams anticipated with <unk> did achieve both by marathon acreage that formal responses. This combined with a clean safety profile tells us that we should explore even higher to spend at dose levels in combination with <unk> to achieve even greater response rate and more durable responses in this growing exceedingly difficult to treat patient.

Rafael Bejar: This combined with a clean safety profile tells us that we should explore even higher to Spetnib dose levels in combination with Phenetoclax to achieve even greater response rate and more durable responses in this growing and exceedingly difficult to treat patient population. Overall, in AFTIV8, TESFEN demonstrated potent activity across subgroups with adverse mutations, achieving responses broadly in AML with a variety of adverse somatic mutations, and Tess Venn has a favorable safety and tolerability profile. Tispatinib also is convenient as a once-daily oral tablet, Institute for Therapy, where we're now rapidly heading. All of these data from the TUS single-agent and TUS Venn doublet studies have led us into a TUS betanin, venetoclax, azacitidine triplet pilot study in frontline newly diagnosed AML patients ineligible for intensive chemotherapy, with the goal of becoming the... After discussions with our scientific advisors and potential partners, we are prioritizing this study and our clinical team is active in planning to begin the study within the first half of this year.

Speaker Change: <unk>.

Speaker Change: Overall.

Speaker Change: That's been demonstrated potent activity.

Speaker Change: First with adverse mutations achieving responses broadly in AML with a variety of adverse somatic mutations.

Speaker Change: And <unk> has a favorable safety and Tolerability profile.

Also as convenient as a once daily oral tablet and mechanistically targets of <unk> resistance mechanisms.

Speaker Change: Suspended, but even better drugs.

Speaker Change: Excellent for therapy, but we are now rapidly heading.

Speaker Change: All of these data from the single agent and tested and doublet studies have led us into a test pattern fanatical acts as a siding triplet pilot study in frontline newly diagnosed AML patients ineligible for intensive chemotherapy.

Speaker Change: We think all will be coming on.

Speaker Change: Standard relationship.

Speaker Change: After discussions with our scientific advisors and potential partners. We are prioritizing this study and our clinical team is active in planning to begin the study was in the first half of this year.

Rafael Bejar: The high level of interest in seeing TUS developed as front-line therapies, not only because of its safety and combinability but the fact that it has demonstrated activity in FLT3-mutated and FLT3-wild-type or unmutated AML, differentiating it from many of the other compounds being developed by targeting the vast spectrum of AML, not just a narrow target or subset of that group. Our triplet pilot study is being designed as an all-comers trial, and it's designed to combine with standard of care Venn, HMN, and HMNA and to select the optimal TUSVEN-ASA dose to enable further randomized double-blinded clinical studies. We plan to initiate this triplet pilot in frontline newly diagnosed AML patients during the first half of 2024 and expect to see initial findings by ASH 2024. We plan to follow these patients to assess overall survival. While HMA Venn demonstrated a median overall survival of about 14.7 months, not all treated patients benefited equally. Patients with growth factor signaling mutations, such as those in FLT3 ITD, NRAS, and KRAS, had more modest survival.

Speaker Change: The high level of interest in seeing test developed as frontline therapy.

Speaker Change: Because of its safety and combinability with the fact that it has demonstrated activity in <unk>, three mutated and with three wild type <unk> mutated AML.

Speaker Change: Differentiating it from many of the other compounds being developed by targeting the vast spectrum of AML, not just to narrow target or a subset of that group.

Speaker Change: Alright terrific pilot study has been designed as an all comers trial and is designed to combine with standard of care, then Egypt, Germany.

And to select the optimal test than as a dose to enable further randomized double blinded clinical studies.

Speaker Change: We plan to initiate distribute pilot and frontline newly diagnosed AML patients during the first half of 2024.

Speaker Change: And expect to see initial findings by Ash 2024.

Speaker Change: We plan to follow these patients to assess overall survival.

Speaker Change: The HMA then demonstrated a median overall survival of about $14 seven months.

Speaker Change: All treated patients benefited equally patients with growth factor signaling mutations such as those with <unk> ITD and Ras at K Ras had more modest survival <unk> three mutation seem to not benefit from the doublet over <unk> alone.

Rafael Bejar: And those with TP53 mutations seemed to not benefit from the doublet over ASA alone. And based on Tespitinib's mechanism of action, we would hope to see deeper, more durable responses compared to patients receiving the current Ben-HMA standard of care alone, particularly in a subset of patients with these resistance-type mutations. As standard of care for front-line AML patients unfit for chemotherapy, the potential potential impact for TUSPEN is tremendous, addressing a market in excess of $1 billion. We expect that the pilot data could support the launch of TUSPEN HMA registrational programs in 2025.

Speaker Change: And based on <unk> mechanism of action, we would hope to see deeper more durable responses compared to patients receiving the current and HMA standard of care alone, particularly in a subset of patients with these resistant type mutations.

Speaker Change: As standard of care for frontline AML patients unfit for chemotherapy.

Speaker Change: <unk>.

Speaker Change: Okay.

Speaker Change: <unk> participated is tremendous addressing a market in excess of $1 billion.

Speaker Change: We expect that the pilot data could support marketing test spend HMA registrational programs in 2025.

Rafael Bejar: Meanwhile, as resources allow and at the encouragement of KWells, a second priority is to develop the Spend-it, in comics, the TUSFEN doublet, where relapsed refractory first salvage FLIT3 mutant AML. We saw the greatest response rates to the TUSFEN doublet in the AML population with FLIT3 mutations, even if they have been previously treated with a FLIT3 inhibitor. We can envisage an approach where relapsing AML patients with FLIT3 mutations are treated with the TUSFEN doublet and compared to those treated with the current approved standard, a single agent, kilteridinib.

Meanwhile, as resources allow and at the encouragement of Kols, our second priority is to develop <unk>.

Speaker Change: The Comex that test then doublet for relapsed refractory first salvage with <unk> three mutant AML.

Speaker Change: We saw the greatest response rates did the test spend doublet in the AML population with the three mutations even if they had been previously treated with a <unk> inhibitor. We can envision an approach where in relapsed AML patients with <unk> mutations are treated with the test spend doublet and compared to those treated with the current approved standard single agent feel terrific. This isn't it.

Rafael Bejar: This is an avenue that several KOLs would like us to consider, as the current standard of care benefits a minority of treated patients and leaves patients in need of a more likely and more durable response. This is a study we hope to be able to initiate later this year if resources allow. Let me now leave you with a quick summary of why we believe Suspetinib can be the best agent to combine with Ven HMA and why the TusVen AZA triplet can become the standard of care for frontline newly diagnosed AML patients. TUS has an excellent safety profile, without concerns for drug-related UTC prolongation, differentiation syndrome, damage, or prolonged myelosuppression once patients achieve remission. TUS also has broader activity in FLIT3 mutant and FLIT3 unmutated patients compared with other competitor kinase inhibitors, and it is active in patients with a diversity of other adverse mutations. TUS has extended patent coverage that goes well beyond that, and Pettit TUS has the potential for premium pricing.

Speaker Change: Have any of that several kols would like us to consider is the current standard of care benefits a minority of treated patients and these patients in need of more likely and more durable responses.

Speaker Change: The study, we hope to be able to initiate later this year if resources allow.

Speaker Change: Let me now leave you with a quick summary of why we believe suspend it can be the best agent to combine with HMA and wide testbed ease of triplet can become the standard of care for frontline newly diagnosed AML patients.

Speaker Change: <unk> has an excellent safety profile without concerns for drug related UTC prolongation differentiation syndrome.

Speaker Change: Damage.

Speaker Change: The amount of suppression once patients achieved remission.

Speaker Change: <unk> also has broader activity that includes the three mutant and flu <unk> mutated patients compared with other competitor kinase inhibitors and is active in patients with a diversity of other adverse mutations.

Speaker Change: <unk> has an extended patent coverage because well beyond that.

Speaker Change: <unk> has the potential for a premium pricing.

Rafael Bejar: Finally, it's looking more unlikely that approved kinase inhibitors will enter pivotal frontline studies with VennHMA. TUSVENT HMA triplet therapy could serve as an off-the-shelf mutation-agnostic triplet, and E-diphygnostic assays could delay therapy while they identify target mutation profiles before putting patients on treatment. So we believe that TUSS Venn HMA can clearly fill the sizable gaps left by competitors and even combine further with future complementary targeted agents. Now I'd like to turn the call over to our CFO and Chief Business Officer, Mr. Fletcher Payne, for an update on our financial status. Fletcher?

Speaker Change: Finally, looking more unlikely that approved kinase inhibitors will enter pivotal frontline studies with vet HMA.

Speaker Change: Test about HMA triple therapy could serve as an off the shelf mutation agnostic triplet.

Speaker Change: Allowing for rapid deployment solutions will not.

Speaker Change: And thank you for agnostic assays or delay therapy, while they identified target mutation profiles before putting patients treatment.

Speaker Change: So we believe that test then HMA can clearly fill the sizeable gaps left by competitors Steven combined further with future complementary targeted agents.

Speaker Change: I'd like to turn the call over to our CFO and Chief business Officer, Mr. Fletcher Payne for an update on our financial status Fletcher.

Fletcher Payne: Thanks Raf, and good afternoon all. I'd like to start by saying that, in addition to the comments in this call, additional information may be found in today's press release and the 10k file. During 2023, we continue our disciplined financial management of the operation, reduce expenditures on a number of different fronts, and prioritize investments in our clinical programs. As always, we continue to evaluate ways to reuse assets. Also, during the year, we used the ATN facility and our 2023 committed equity facility and entered into an agreement with Harmony Pharmaceuticals to raise a total of $7.3 million of additional capital. This past January, just two months ago, we announced the closing of a $9.7 million public financing, including the full exercise of the overallotment option, and a separate strategic investment of four million dollars in a private placement with Harmony Pharmaceuticals. The gross proceeds from the public offering and the private placement were approximately $13.7 million, excluding unauthorized discounts based on the age of commissions and other offering-related expenses. The total number of common shares outstanding after the closing of the public offering and the private placement, including the Oberlot Man, is 15,706,810. And the warrants outstanding are $8,332,163.

Fletcher Payne: Thanks, Ross and good action now I'd like to start by saying in addition to the comments in this call additional information in today's press release, and the 10-K filed with SEC.

Fletcher Payne: 2023, we continued our disciplined financial management of operation, reducing expenditures on number of different fronts and prioritize investments in our clinical programs as always we continue to evaluate ways to reduce operational expenses.

Fletcher Payne: Also during the year, we used the ATM facility and our 2023 committed equity facility and entered into agreement with Tommy from skills to raise a total of $7 3 million of additional capital. This past January just two months ago, we announced the closing of a $9 $7 million public financing.

Fletcher Payne: Including the full exercise of the over allotment option.

Fletcher Payne: And a separate strategic investment of $4 million.

Fletcher Payne: In a private placement with Hanmi pharmaceuticals.

Fletcher Payne: The gross proceeds from the public offering and a private placement of approximately $13 7 million <unk>.

Fletcher Payne: Excluding underwriting discounts commissions and other offering related expenses.

Fletcher Payne: Total number of common shares outstanding after the closing of the public offering and the private placement, including the over allotment.

Fletcher Payne: $15 million 706 810.

Fletcher Payne: And the warrants outstanding our $8 million 330 to 163 warrants.

Fletcher Payne: Based on current operations, the company expects the cash on hand plus our ATM and committed exit facility will provide the company with sufficient resources to fund planned operations, including research and development through August of 2020. Now, you're probably aware that on February 29th, we received a letter from NASDAQ claiming that the January 2024 private placement of securities behind me violated Rule 5635D of the NASDAQ Listing Rules because we did not obtain shareholder approval prior to such issuance. NASDAQ stated that HOMME's private placement involved the issuance of greater than 20% of our issued and outstanding common shares, with the assumption that it closed on the same date as our public offering. We believe the Harming Private Placement was completed in accordance with the NASDAQ listing rules as it was a separate issue with different deal terms and closed on a different date. The deficiency letter has no immediate effect on the listing of our common shares.

Fletcher Payne: Based on current operations the company expects the cash on hand, plus our.

Fletcher Payne: Our ATM and committed accident severity will provide the company with sufficient resources to fund planned operations.

Fletcher Payne: Including research and development through August of 2024.

Fletcher Payne: Now you are probably aware that on February 29th we received a letter from NASDAQ claim it hit in January 2024, private placement of securities to Hanmi violated rule <unk> 635.

Fletcher Payne: The NASDAQ listing rules, because we did not obtain shareholder approval prior such issuance.

Fletcher Payne: NASDAQ stated that Hermes private placement involved the issuance of greater than 20% of our issued and outstanding common shares.

Fletcher Payne: The assumption that it closed on the same date as our public offering we.

Fletcher Payne: We believe the Hanmi private placement was completed in accordance with the NASDAQ listing rules as a separate issue with different deal terms and closed on a different date.

Fletcher Payne: The deficiency letter has no immediate effect on the listing of our common shares in accordance with the NASDAQ listing rules were kept 45 calendar days or until April 14th 2024 submit a plan to regain compliance.

Fletcher Payne: In accordance with the NASDAQ listing rules, we are given 45 calendar days or until April 14th of 2024 to submit a plan to regain compliance. If NASDAQ accepts the plan, NASDAQ can grant an extension of 180 calendar days from the date of the deficiency letter. We respect NASDAQ's query. We're working with NASDAQ to resolve their concerns and consider available options to regain compliance. I'd like to direct you to review the company's risk factors and the discussions regarding the NASDAQ letter and our going concern footnote in our 10k filings. Now, let's review the year-end 2023 financials. We ended the fiscal year of 2023 with approximately 9.3 million dollars in cash, cash equivalents, and investments.

Speaker Change: Yes, Zach access the plan NASDAQ Grant an extension of 180 calendar days from the date of the deficiency letter.

Speaker Change: Yes.

Speaker Change: Evidence of compliance.

Speaker Change: <unk> respect nasdaq's query or working with NASDAQ resolve their concerns and consider available options to regain compliance.

Speaker Change: I would like to direct you to review the Companys risk factors.

Speaker Change: And the discussions regarding the NASDAQ letter and our going concern footnote in our 10-K filings now lets review the year end 2020 financials. We ended the fiscal year of 2023 with approximately $9 $3 million in cash cash equivalents and investments.

Fletcher Payne: That is a decrease of $27.7 million as compared to December 31 of 2022. The $27.7 million decrease in our cash investments is a result of the use of funds for the ACTIVATE study and operating expenses, which is offset by an increase in cash from certain financing activities. On a cumulative basis through December 31 of 2023, the company had raised a total of $7.3 million. $3 million from the Harmony Subscription, $1.9 million in gross proceeds from the 2022 ATM facility, and $2.1 million in gross proceeds from the Committed Equity facility. After the gross proceeds from the January 2024 financing of $13.7 million, the cash and cash equivalents was $18.6 million.

Speaker Change: That is a decrease of $27 7 million as compared to December 31 of 2022.

Speaker Change: Okay.

Speaker Change: The $27 $7 million decrease in our cash and investments does versus result of use of funds for the activate study and operating expenses, which is offset by an increase in cash from certain financing activities.

Speaker Change: Accumulative basis through December 31, 2022, the company had raid raised a total of $7 3 million.

Speaker Change: $3 million from Hanmi subscription $1 9 million in gross proceeds from the 2022 ATM facility and $2 1 million in gross proceeds from the committed equity facility.

Speaker Change: After the gross proceeds from the January 2020 for financing of $13 7 million the cash cash equivalents.

Fletcher Payne: That's an unaudited, As seen in the income statement, we had no revenues during 2023. During 2023, the net loss was approximately 51.2 million dollars, translating into approximately $7.58 loss per share, compared to $41.8 million loss and $6.80 loss per share from the 2022 annual period. As of March 26, 2024, Aptose has 15,717,701 common shares outstanding.

Speaker Change: Was $18 6 million.

Unaudited results.

As seen in the income statement, we had no revenues during 2023 during 2023 net loss was approximately $51 $2 million translating into approximately $7 58 loss per share compared to $41 8 million loss.

Speaker Change: And six.

Speaker Change: <unk> loss per share from the 2022 annual period.

Speaker Change: As of March 26, 2024, <unk> has 15 million 717.

Speaker Change: Oh, one common shares outstanding.

Fletcher Payne: All references to the losses per share and the shares outstanding have been presented to reflect the 1 for 15 reverse stock split completed on June 6 of 2024. Due to our continuing strategic relationship with HANMI, we are now separately reporting related party R&D from our normal R&D expenses. Related party RMD expenses for Mohammed were $3.5 million for the year in 2023, compared to $3.6 million for the same period in 2022.

Speaker Change: All references to the losses per share in the shares outstanding ever been presented to reflect the one for 15 reverse stock split completed on June six 2024.

Speaker Change: Due to our continuous strategic shift with Hanmi. We are now separately reporting related party R&D from our normal R&D expenses.

Speaker Change: Related party R&D expenses from the Hanmi relationship were $3 5 million for.

Speaker Change: For the year end 2023, compared to $3 6 million for the same period in 2022.

Fletcher Payne: The remaining research and development expenses were approximately $33.3 million for the year ended December 31, 2023, compared to $24.5 million during the year ended December of 2022. Program costs for TISS-Substantive were $24.9 million for the 12 months ended December 31, 2023, compared to $10 million for the 12 months ended December 31, 2023. The higher program costs for TISS-Substantive in the current period represent the enrollment of patients in our APTIV-8 clinical trial, clinical materials, and the healthy volunteer and other expenses related to APTIV-8. Program costs for lexeptinib were $3.5 million for the 12 months ended December 31, 2023 and decreased by approximately $4.9 million compared to the $8.4 million for the 12 months ended December 31, 2022, primarily due to lower clinical trial G&A expenses were $15.6 million for the year to December 31, 2003, compared to $14.5 million for the same period in 2022.

Speaker Change: The remaining research and development expenses were approximately $33 $3 million for the year ended December 31 2020.

Speaker Change: Compared to $24 5 million during the year ended December of 2020 Kids program costs for <unk> were $24 $9 million for the 12 months ended December 31, 2023 compared to $10 million for the 12 months ended December 31.

Speaker Change: 2022 buyer program costs for <unk> in the current period represents the enrollment of patients in our App to date clinical trial clinical materials and the healthy volunteer.

Speaker Change: And other expenses related to efficacy.

Speaker Change: The program.

Speaker Change: Program cost real acceptance for $3 $5 million for the 12 months ended December 31, 2023 and decreased by approximately $4 9 million compared to the $8 $4 million for the 12 months ended December 31 2022.

Speaker Change: Primarily due to lower clinical trial costs lower manufacturing costs as a result of the current G III formulation, which requires less API than the prior formulations G&A.

Speaker Change: G&A expenses were $15 6 million for the year ended December 31 2000.

Speaker Change: Compared to $14 $5 million from same period of 2022.

Fletcher Payne: The increase was primarily due to increased salary expense, higher professional fees, and partially offset by lower stock-based compensation. Now, let me turn it back to Dr. Rice. Thank you, Fletcher. Now we'll open up the call for questions, and please feel free to pose a question to any of us. Operator, if you could, please introduce the question.

Speaker Change: The increase was primarily due to increased salaries expense higher professional fees and partially offset by lower stock based compensation now let me turn it back to Dr. Rice.

William G. Rice: Thank you Felicia now we will open up the call for questions and please feel free to pose a question to any of US operator, if you could please introduce the questions.

Operator: Certainly, and as a reminder, ladies and gentlemen, if you do have a question, please press star one one on your telephone, and our first question comes from the line of Soumit Roy from Jones Research. Your question, please. Good afternoon, everyone.

Certainly and as a reminder, ladies and gentlemen, if you do have a question. Please press star one on your telephone.

William G. Rice: And our first question comes from the line of Shumate Rewey from Jones Research Your question. Please.

Shumate Rewey: Good afternoon, everyone.

Soumit Roy: So I'm trying to understand the strategic path forward. The development of TUS in relapsed refractory AML is on pause, and we are going to see the latest updated data at EHA. Is that correct?

Shumate Rewey: So.

Shumate Rewey: As I'm trying to understand the.

Shumate Rewey: Strategic path forward.

Speaker Change: <unk> development.

Speaker Change: The development cost in relapsed refractory AML is.

On pause and we're going to see the latest update data at <unk> is that correct.

William G. Rice: Currently, we've been treating patients, the relapsed refractory patients. We've completed the enrollment of the patients in both single agent and doublet in the relapsed refractory patients, and we don't plan on putting any more patients on there immediately because our top priority is to put all of our cash and resources into that triplet trial. If additional resources become available, we will move it into a doublet trial in which we increase the dose of Tuspedinib in relapsed refractory patients. And yes, we will be presenting the single agent and doublet data in relapsed refractory patients at the EHA conference in June. Dr. Bejar, did you want to add anything? No, Bill. I think that's accurate.

It is.

Speaker Change: Currently we have been treating patients that relapse refractory patients we've completed the enrollment of the patients in both single agent and doublet in the relapsed refractory and we don't plan on putting any more patients on their immediately because our top priority is to put all of our cash and resources into that triplet trial if additional reach.

Sources become available we will move it into the doublet trial in which we increased the dose.

Speaker Change: The reduction refractory patients and yes, we will be presenting.

Speaker Change: The single agent and doublet data in relapsed refractory patients at the EAA Conference in June Dr May harder do you want to add anything to that.

Dr May: No Bill I think that's actually.

William G. Rice: The goal will be to just escalate in the doublet, as we had a very clean safety profile at the doses that we tested already. But as Bill mentioned, that will depend on additional... Breser, So the strategy to move.

Dr May: The goal will be to dose escalate in the doublet as we had a very clean safety profile at the doses that we tested already.

Dr May: As Bill mentioned that will depend on additional <unk>.

Dr May: Resources.

Dr May: So.

William G. Rice: [inaudible] Resources towards the frontline because the frontline is going to be a much longer trial, and it has to be randomized. Full-Face-to-Trial versus We were expecting that the relapsed refractory setting could have a potential path for accelerator approval. Do you think it's just the clinical benefit you are seeing, and even if you dose escalate, the clinical benefit might not be significant enough to go for the accelerator path? Well, I wouldn't view this as a negative by any means.

Dr May: The strategy to move.

Dr May: To put the Empire.

Dr May: Our resources towards the front line, because frontline is going to be much longer trial that has to be randomized.

Dr May: Full phase II trial versus <unk>.

Dr May: We were expecting the relapsed refractory setting.

Dr May: Have a potential Patrick Flynn approval.

Dr May: Do you think it's just the clinical benefit you are seeing.

Dr May: And even if you dose escalate the clinical benefit might not be significant enough to go forward with active at bats.

Speaker Change: Well I wouldn't view this as a negative by any means so in the relapsed refractory setting we do we saw a dose dependent effect 40 milligrams.

William G. Rice: So in the relapsed refractory setting, we saw a dose-dependent effect at 40 milligrams in combination with venetoclax. We saw activity, but not as extensive. As we went up to 80 milligrams, we saw much more extensive responses in patients. And the good news is we're able to dose escalate even further, we believe, in combination with Tuspetinib, whereas with other drugs you tend to have to dose reduce. So we believe we can get an even higher response rate and greater durability in the relapsed refractory population. And you're right, if we were to move forward there, the next step would be on a potential accelerated approval development path.

Speaker Change: In combination with <unk>.

Speaker Change: We saw activity, but not as extensive as we went up to the 80 milligrams much more extensive responses in patients and the good news is we're able to dose escalate. Even further we believe with in combination with other drugs you tend to have to dose dose reduce so we believe we can get higher response rate greater durability.

Speaker Change: Fair enough refractory population and you're right. If we were to move forward. There. The next step would be in a potential accelerated approval development path and that would be that also would be in a randomized trial.

William G. Rice: And that also would be in a randomized trial. But we believe the greatest value in the near term is in this pilot triplet study frontline, because Tuspetinib really differentiates itself. It's very safe when it's combined with other drugs. It has very broad activity.

But we believe the greatest value in the near term.

Speaker Change: This pilot triplet study frontline.

Speaker Change: Because test spend it really differentiates itself. So it's very safe when it's combined with the other drugs.

William G. Rice: And this is what's needed in frontline therapy, the triplet. And we hear that from all potential partners, as well as the KOLs. Dr. Behar, want to add anything? No, but I think it's exactly accurate.

Very broad activity and this is what's needed in the frontline therapy, the triplet and we hear that from all potential partners as well as the Kols and Nashville.

Speaker Change: Dr <unk>.

Speaker Change: To add anything.

Rafael Bejar: I think that we are excited about the idea of being able to treat these real obstructive factor AML patients and pursue that avenue. But when we think about prioritization, about not just likelihood of success but also scope of the market and potential patient benefit, it is substantially greater in the frontline setting. And much of that is very much driven by what we're hearing from potential partners as to the data that would drive major partners. Thank you. In the front line setting, are you going to...

Speaker Change: No, but I think it's exactly accurate I think that we are excited about the idea of being able to treat these relapse refractory AML patients and to pursue that avenue, but when we think about prioritization.

Speaker Change: Not just likelihood of success, but also scope with market and potential patient benefit it is substantially greater than the frontline setting.

Speaker Change: And much of that is very much driven by what we're hearing from potential partners as to the data that would drive a major partnerships.

Speaker Change: Thanks.

Speaker Change: The front in the frontline setting are you going on.

Rafael Bejar: Put any inclusion criteria or select for FLT3 or P53 mutant patients, which are a little harder to treat? And does the mechanism of classification allow to combine with 7 plus 3 regimen also? Or is it going to be restricted to HMA only? These are great colleagues, quite a bit.

Speaker Change: With any inclusion criteria are select roughly three year <unk> mutant patient, which are little harder to treat and both the mechanism of trusted allowed to combine with seven plus three regimen also as economy risk with HMA run omni.

Speaker Change: Peter.

Speaker Change: These are great.

Quite a bit right now the focus is on those older individuals that are ineligible for induction chemotherapy and we would want to include patients with and without <unk> mutations, but we know that there are other triplet studies that are going to be out in the world.

Rafael Bejar: Right now, the focus is on those older individuals that are ineligible for induction chemotherapy. And we would want to include patients with and without SLID3 mutations, but we know that there are other triplet studies that are going to be out in the world. We don't want to see those patients who could not qualify for those studies. We want to see the broad range of AML.

Speaker Change: So we don't wanted those patients who could not qualify for those studies, we want to see the property and made them out.

Rafael Bejar: So we would include patients that have TP53 mutations, but we would limit their fraction to be representative of what we see in the AML population, which is about 20 to 25 percent of those individuals. So we don't do a trial exclusively in that patient population. And then your question about combining with 7 plus 3, I think that would be very doable for a test, but it would be a great way to go.

Speaker Change: So we would include patients that have <unk> mutations, but we would limit their fraction to be representative of what we see in AML population, which are about 20% to 25% of those individuals. So we don't do a trial exclusively in that patient population.

Speaker Change: And then your question about combining with seven plus three I think that would be.

Speaker Change: Doable for test by debit would be.

Rafael Bejar: There are two reasons that we de-prioritize that at the moment, and one of them is, I think, that low-intensity treatment with venetoclax and hypomethane agents containing regimens is becoming more common, even in individuals who might, patients who you might be able to give chemotherapy to, but you can achieve perhaps similar, if not better, response rates and duration of response even without giving chemotherapy by giving a low- And finally, there already are approved agents in the kinase inhibitor realm in that chemotherapy combination regimen, quisartanib, of course, and mitostaurin. While those studies were approved against a non-targeting kinase-containing regimen, we would have to pursue a registrational strategy against a kinase-containing regimen. So for these reasons, we think that there is a greater viability for going after the chemo-ineligible population first, but we would certainly love to explore combining chemotherapy as well.

Speaker Change: Way to go.

Speaker Change: Two reasons that we'd be prioritize that at the moment and one of which is I think the low intensity treatment with min <unk> highpoint setting agents containing regimens is becoming more common even in individuals who might.

Speaker Change: Let me add that the patients who you might be able to give chemotherapy too that you can achieve perhaps similar if not better response rates and duration of response, even without giving chemotherapy by getting a low intensity therapy and finally, there already are approved agents and the kinase inhibitor realm in that chemotherapy combination regimen.

Speaker Change: Of course, my historic and.

Speaker Change: While those states were approved against Inc.

Speaker Change: Targeting Chinese containing regimen, we would have to pursue a registration strategy against the guidance containing regimen. So for these reasons. We think that there is a greater viability for going after the chemo ineligible population first but we would certainly love to explore combining with chemotherapy as well.

Rafael Bejar: You know, as we look into the, thank you, Dr. Bejar, as we look into the future, we likely will see the triplet combination of targeted agents showing much better, much higher response rates, much greater durability. That's the hope for all of the triplets in patients who are ineligible for chemotherapy. And then once that is proven, we would expect that those triplets would also move over to patients who are chemo ineligible or who are chemo eligible. So we would expect that these triplets of targeted agents would then go across both fit and unfit patients. I got it.

Speaker Change: As we look into the thank you talked about how as we look into the future.

Speaker Change: Likely we will see.

Speaker Change: The triplet combination of targeted agents showing much better much higher response rates much greater durability. That's the hope for all of the triplet and the patients who are eligible for chemotherapy and then once that is proven we would expect that those triplets would also move over to the patients who are chemo analogy.

Speaker Change: Our chemo eligible so we would expect that these triplets are targeted agents would then go across both the.

Speaker Change: Fifth.

Speaker Change: If patients for chemotherapy.

Soumit Roy: And one last question. So, in terms of data readout from the frontline setting, we expect safety readout only towards the end of this year, and efficacy readout is likely to be the end of 2025. Is that the right assumption?

Speaker Change: Got it and one last question. So in terms of data readout for from the frontline setting we equip safety readout on the towards the end of this year and efficacy readout is likely to be the end of 'twenty five.

William G. Rice: I'll jump in first and then Dr. Bejar can come in. So, ultimately, you want to see that you have an extended overall survival in these patients, median overall survival, and you would expect that to be much longer with the triplet. So, by the end of this year, we won't have a full duration of median overall survival, but we should be able to see the CRCRH rates during that period of time, the safety profile, and possibly MRD negativity, because in these patients with the triplet, you tend to see responses very quickly in these patients. And then you want to be able to see that you're also recovering counts. Perhaps Dr. Bejar wants to add to that.

Speaker Change: <unk> assumption.

Speaker Change: I'll jump in on first and Dr. Hart can come in so ultimately you want to see that you have.

Dr. Hart: And extended overall survival of these patients median overall survival and we would expect that to be much longer with the triplet. So.

Speaker Change: By the end of this year, we won't have a whole duration median overall survival, but we should be able to see the CRC RH rates during that period of time, a safety profile and possibly marketing activity because in these patients with the triple if you tend to see the responses very quickly in these patients and then you want to be able.

To see that Youre also recovering accounts, perhaps Dr bejar wants to add to that.

Rafael Bejar: I think we will have early indications of activity. In other studies that have been done with a combination of HMA, VEN, and a kinase inhibitor, for example, the vast majority of responses occurred in the first or second cycle, suggesting that even if we had a handful of patients put on in the first portion of the year, we would have enough follow-up data to see what their likely response rates are. Now fortunately, it takes longer to get survival in this patient population because they do live longer, and we would hope to have more of that data in 2025. And we hope to be able to have multiple dose levels of TUS-Betanib combined into the triplet. We would hope to start out around 80 milligrams, if possible. And then, if that's safe, we'd look to move up.

Rafael Bejar: Yeah, that's exactly right I think we will have early indications of activity.

Rafael Bejar: Okay at other studies that have been done with combination of HMA van kinase inhibitor for example, and the vast majority of responses occurred in the first or second cycle.

Rafael Bejar: Even if we had a handful of patients put on in the first portion of the year that we would have enough follow up data to see what the likely response rates are.

Rafael Bejar: Now Fortunately it takes longer to get survival in this patient population because they do the vulgar and we would hope to have more of that data in 2025.

Rafael Bejar: And we hope to be able to have multiple dose levels of <unk>.

Rafael Bejar: Combine into the triplet, we would hope to start started out around 80 milligrams if possible and then if thats safe, we'd look to move up again with most other drugs. When you combined with the man HMA you have to do dose reductions of that molecule as well as the HMA.

William G. Rice: Again, with most other drugs, when you combine them with Ben-HMA, you have to do dose reductions for both that molecule as well as Ben-HMA. We hope we will not have that issue. We expect that we'll be able to dose 80 milligrams and maintain the label dosing for Ben-HMA.

Rafael Bejar: HMA.

Rafael Bejar: We hope we will not have that issue, we expect that we will be able to dose of 80 milligrams and to maintain.

William G. Rice: So that's the plan. Thank you again for taking all the questions and congratulations on all the progress. Thank you, Shumeit. I appreciate you coming.

Rafael Bejar: <unk> dosing for the HMA, so thats the plan.

Speaker Change: Alright. Thank you again for taking all the questions and congrats on another progress. Thank you I appreciate you coming out.

William G. Rice: Thank you. This does conclude the question and answer session of today's program. I'd like to hand the program back to Dr. Rice for any further remarks. All right. We'd like to thank everyone for joining us this afternoon. As I mentioned earlier, our KOLs believe Tespitem is a real drug that has demonstrated activity across a breadth of genetic subtypes in AML and yet has a surprisingly favorable tolerability profile with no significant safety signals. And these are true differences.

Speaker Change: Thank you. This does conclude the question and answer session of today's program I'd like to hand, the program back to Dr. Rice for any further remarks, alright, we'd like to thank everyone for joining us. This afternoon as I mentioned earlier, our Kols believe tests that it is a real drug has demonstrated activity across a breadth of genetic subtypes in AML.

William G. Rice: It has us approximately favorable tolerability profile with no significant safety signals. In these are true differentiators are eager to initiate this triplet study.

Operator: We're eager to initiate this triplet study with TUSPETINib, which we believe could be the ideal candidate for triplet combination therapy in the rapidly shifting AML treatment lab. As always, we thank our patients, our investigators, and our employees for their important role in this effort. We appreciate our shareholders and analysts who continue to support us, and we look forward to keeping you updated on our progress. Thank you. Thank you, ladies and gentlemen, for your participation in today's conference. This does conclude the program. You may now disconnect. Good day. Thank you for watching!

William G. Rice: Which we believe can be the ideal candidate for triplet combination therapy, Nebraska shifting AML treatment landscape.

William G. Rice: As always we thank our patients our investigators and our employees for their important role in this effort. We appreciate our shareholders and analysts who continue to support us and we look forward to keeping you updated on our progress. Thank you and have a wonderful evening.

Speaker Change: Thank you, ladies and gentlemen for your participation in today's conference. This does conclude the program you may now disconnect good day.

Speaker Change: Okay.

Speaker Change: [music].

Speaker Change: Okay.

Speaker Change: Yes.

Speaker Change: [music].