Aptose Biosciences Q4 2023 Earnings Call Transcript

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Provided by Quartr
March 26, 2024

There are 6 speakers on the call.

Operator

Good afternoon. My name is Jonathan, and I will be your conference operator today. I would like to welcome everyone to Aptose Biosciences' Conference Call for the Q4 and Year Ended December 31, 2023. At this time, all participants are in a listen only mode. After the speakers' remarks, there will be a question and answer session.

Operator

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 Pietrofalo. Please go ahead.

Speaker 1

Thank you, Jonathan. Good afternoon, and welcome to the Aptose Biosciences conference call to discuss financial and operational results for the Q4 year ended December 31, 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. Joining me on today's call are Doctor.

Speaker 1

William Rice, Chairman, President and CEO Doctor. Rafael Behar, Senior Vice President, Chief Medical Officer and Mr. Fletcher Payne, Senior Vice President, Chief Financial Officer and Chief Business Officer. Before we proceed, I would like to remind everyone that certain statements made during this call will include forward looking statements within the meaning of U. S.

Speaker 1

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 ks and SEC and SEDAR filings.

Speaker 1

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 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 ks for additional information and disclosures regarding today's announcements. I will now turn the call over to Doctor. Rice.

Speaker 2

Thank you, Susan. I want to welcome everyone to our call for the Q4 year ended December 31, 2023. Today, we will provide updates on our financial status, on the near term and long term clinical development plan for our lead agent, tasvetinib, and a quick update on our luxepatinib 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 Hanmi Pharmaceutical. Then in January of this year, we closed financings with gross proceeds of $13,700,000 inclusive of a $9,700,000 public offering along with a separate $4,000,000 private placement with Hanmi Pharmaceutical.

Speaker 2

This provided us with more breathing room and Mr. Fletcher Payne, our CFO and CBO, provide additional financial details in a few minutes. I now want to pivot to our lead program, tusvetinib. So why should you care about tusfetinib? It's because tusfetinib or TUS as we often call it, is convenient, poorly administered, once daily kinase inhibitor with an excellent safety profile and potent antileukemic activity that is being developed for the treatment of acute myeloid leukemia or AML.

Speaker 2

And we believe a tasatinib 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. And today, we'll explain why we believe this and how we arrived at this point. First, you're aware that we've been performing studies in relapsed or refractory AML patients with tusapetinib as a single agent and with tusapetinib in combination with venetoclax, which we refer to as the TUSVIN doublet. The valuable findings gleaned from these studies have now led us to pursue the development of tusvetinib as a triplet combination therapy for the frontline treatment of newly diagnosed AML patients as the highest priority. The triplet includes tusvetinib, the BCL-two inhibitor venetoclax and a hypomethylating agent such as acetonid, collectively referred to as the tuspvin HMA triplet.

Speaker 2

In fact, we just heard from a group of KOLs in AML that they have great enthusiasm for the safety and activity of tuspedinib 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 tusvetinib should be primarily on the TUS Bend HMA triplet. And that is precisely where we are focusing our resources because this Tustin 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 tesmetinib can have its greatest impact in frontline AML by improving the response rates, the depth of responses, the durability of responses, the quality of life and the long term survival across the diversity of AML patients relative to the current BIN HMA standard of care and frontline AML patients who are ineligible for intensive chemotherapy. Plus the commercial aspect or impact of the TUS BIN HMA triplet and frontline therapy is estimated to exceed $1,000,000,000 annually.

Speaker 2

And we've heard from many potential partners that the application of the TUS Bend HMA to the frontline market is of primary interest to them. Indeed, the safety, breadth and efficacy profiles of tasvetinib today make us believe that tesapetinib can be the best agent to combine with the VIN HMA, which is the current standard of care. While the goal for the tesbethinib program is to move into frontline EML therapy at the triplet, the path to the frontline triplet began with the tuspinitinib single agent trial and then transitioned through the tuspin doublet trial to understand activities, safety and contribution of components. With the tusvetinib single agent trial, we completed enrollment of 93 patients across 6 dose levels. Tuxvetinib single agent achieved an excellent safety profile without many of the key liabilities seen in competitor agents.

Speaker 2

It demonstrated broad activity across AML populations with adverse genetic alterations. We observed a 3 fold longer median overall survival in responding patients relative to non responders and 80 milligrams once daily was selected as the recommended Phase 2 dose for single agent therapy. With the 80 milligram dose level, tuspentanib single agent was highly active, achieving high quality responses with high response rates. We were delighted to see a strong 36% CRCRH rate among all covered genotypes in patients who had not previously been treated with venetoclax referred to as been naive patients. Notably, at the 80 milligram dose level, few of the patients had failed prior therapy with venetoclax.

Speaker 2

However, as we dose escalated above the 80 milligram dose level, we saw that prior VIN failure patients were emerging as a new category of relapsed refractory AML at that point in time. And the proportion of prior VIN patients increased dramatically to greater than 80% and the next dose level of 120 milligrams. Once patients fell of venetoclax containing therapy, they are more refractory to all subsequent salvage therapies, including tusbetinib 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. Fortunately, there is a silver lining to this change in the relapsedrefractory AML patient population. In our past scientific conference presentation, we've described how tusbetinib targets the venetoclax resistance mechanism and how tuspetinib combines synergistically with venetoclax in animal models.

Speaker 2

Plus, we've shown that tuspetinib resistant AML cells are hypersensitive, 2,000 fold more sensitive to venetoclax. This mechanistic complementarity provided a rationale for us to combine tuspedinib with venetoclax to evaluate the tuxpin doublet in the relapsed refractory AML population. In our Tuspend Doublet trial, we now have completed enrollment with 40 milligram tuspendinib and with 80 milligram tuspendinib combined with 400 milligrams venetoclax in a total of 79 patients. First, we observed that the excellent safety profile of tuspatinib as a single agent was maintained with the tuspen doublet. We observed bone marrow leukemic blast reductions in the majority of patients, including those who failed prior therapies with FLT3 inhibitors or prior venetoclax therapy.

Speaker 2

And we continue to see evidence of broad activity across AML patients with a diversity of adverse mutations, including patients who have failed prior therapy with venetoclax. We see great promise for the TUS Bend doublet to effectively treat the prior bend failure patients and even become a standard of care for those patients. And there remains a potential accelerated approval path for the TUSPEN doublet in a molecularly defined subpopulation of relapsed refractory AML, especially if we increase the dosage of tuspedib and the tuspedoublet and demonstrate even greater activity. 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 tuspen doublet with higher doses of tusvetinib for the relapsed refractory population.

Speaker 2

However, in the near term, we have chosen to focus our resources on the Tuspend HMA triplet and frontline AML therapy. So our next step to build value as quickly as possible will be to initiate a tuspentanib plus venetoclax plus apacitidine triplet pilot study in frontline newly diagnosed AML patients and to select the optimal triplet dosage of tuspatinib, which will be driven by CRH CRH rates, MRD negativity and safety data. After selecting appropriate Phase 2 doses of the triplet, we plan to transition into registrational studies by comparing the safety and efficacy of the triplet to the VIN HMA control for frontline newly diagnosed AML patients. I also want to mention that our ongoing BD 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 the frontline triplet therapy as the cornerstone of a commercial success. It's clear that we can create the greatest value for tuspatinib in the shortest period of time, earning for the least amount of capital by performing a tusbend HMA triplet pilot study in frontline AML patients and such data could then support partnerships for later stage development of tuspedinib.

Speaker 2

So this provides you with a framework of our strategic thought process and Doctor. Behar, our Chief Medical Officer, will provide you with additional clinical insights and perspectives in a few minutes. But first, I also want to mention our other drug, Luxeftabib. You will recall that Luxe, as we often call it, is an oral highly potent kinase inhibitor that selectively targets defined kinases operative and myeloid and lymphoid hematologic malignancies. This molecule has been evaluated in a Phase 1ab study for the treatment of patients having relapsed or refractory B cell leukemias and lymphomas and in a Phase 1ab study for the treatment of patients with relapsed or refractory AML.

Speaker 2

Enrollment and in dosing of patients in the B cell malignancy trial has now been completed, including 36 patients who were dosed with the original G1 formulation across five dose levels ranging from 150 milligrams to 900 milligrams BID. In this trial, Luxe achieved tumor shrinkage among 63% of the evaluable B cell cancer patients and across dose levels from 450 milligrams to 900 milligrams. This also includes a complete response or CR in a DLBCL patient and impressive tumor reductions in follicular lymphoma patients and an SS SLL patient. Likewise, enrollment and dosing of patients in the AML trial now has been completed. In this trial, AML patients received the original G1 formulation across dose levels ranging from 450 to 900 milligrams BID.

Speaker 2

Bone marrow blast reductions were observed in 38% of the evaluable FLT3 mutated patients and 50% of the evaluable FLT3 wild type AML patients. In addition, an MRD negative CR or complete response in 1 relapsedrefractory AML patient occurred with a 4 50 milligram BID dosing of the original T1 formulation. Our clinical data demonstrate that LUXE 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. Because absorption of the original G1 formulation hampered the effectiveness of Luxepinib, a new generation 3 or G3 formulation was developed. And now we can report that the clinical evaluation of the G3 formulation also has been completed.

Speaker 2

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 5 different dose levels from 10 milligrams to 200 milligrams. The G3 formulation was then evaluated in relapsedrefractory AML patients with continuous dosing using 2 different dose levels, 50 milligrams BID and 200 milligrams BID in a total of 11 patients. Recent data showed the G3 formulation dosed at 200 milligrams twice daily can achieve 2 to 3 micromolar steady state plasma levels with approximately 10 fold bitter absorption and interestingly even better tolerability than the original G1 formulation. 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 Luxe. Collectively, these findings demonstrate Luxe is a viable drug with a viable formulation and that LUXE has the G3 formulation should be advanced into a focused clinical development program and we are delighted to see a future for LUXE.

Speaker 2

Regarding any next steps with LUXE, we are exploring the potential to advance LUXE to treat molecularly defined relapsedrefractory hematologic malignancy patient populations of high unmet need. And we now are seeking alternative development paths and collaborations to execute that strategy. I now want to turn the call over to Doctor. Behar, our Chief Medical Officer and resident KOL for his insights and comments on our data and clinical plans for tasvetinib. Raf?

Speaker 3

Thanks, Bill, and good morning from Japan. 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 standard of care backbone of venetoclax with a hypomethylating agent in older patients who are ineligible to receive intensive chemotherapy. There have been promising proof of principal successes in treating patients with triple therapies that include kinase inhibitors like tasplatinib. In fact, our lead investigator, Doctor. Navel Dahmer and his team at the MD Anderson Cancer Center have seen impressive response rates nearing 100% with this approach in certain AML populations.

Speaker 3

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 taspenib appears to be an ideal candidate for

Speaker 4

triplet combination therapy and our experience to date continues

Speaker 3

to build and support the therapy and our experience to date continues to build and support the strategy. As Bill mentioned, we've taken a deliberate and tiered clinical approach. First, we successfully demonstrated significant activity of TUS in a single agent dose escalation exploration trial in a broad relapsedrefractory 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.

Speaker 3

At the 80 milligram dose in the VEN naive patient population, tisbetinib had an excellent CR, CRH rate, 50%, 36%, 25% in FLT3 mutants, overall FLT3 wild type overall and in FLT3 wild type, respectively. Importantly, TESS demonstrated an excellent safety profile with no instances of drug related QTC prolongation, differentiation syndrome or muscle damage in any patient or prolonged myosuppression in responding patients who had cleared the leukemia. As Bill mentioned, we observed broad activity across AML populations at 4 dose levels. This included patients with adverse genetic alterations in FLT3, RAS, TNF, DMT3A, IDH genes, NPM1 genes, MLL, TTD and others. Then in conjunction with the FDA, 80 milligrams once daily was selected as the recommended Phase 2 dose for single agent therapy.

Speaker 3

As AML care has shifted toward venetoclax containing combination regimens, we began to find in our single challenging to treat relapsedrefractory AML population in those patients who had received and failed venetoclax. This emerging patient population now accounts for a large percentage of relapsedrefractory patients entering all AML trials, something we all developing these trials need to consider as then failure patients are more resistant to to treat very ill prior VEN treated AML population, which led us to conduct Aptivate, our TUS ven doublet study in reoscerefractory AML. We initiated Aptivate as a doublet study of TUS ven to explore the ability of TUS to treat these then failed patients. We completed dose exploration with 40 milligrams and then 80 milligram with 79 patients. The TUS VEN doublet treatment was well tolerated with no drug related deaths and lower rates of febrile neutropenia than observed in other VEN combination studies.

Speaker 3

Response activity of 80 milligrams TUS and 400 milligrams 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 dispetinib with venetoclax achieved bone marrow blast reductions, but did not achieve formal responses in large numbers. In contrast, many of the patients who received 80 milligrams tasplatinib with venetoclax did achieve both bone marrow and the deformable responses. This combined with a clean safety profile tells us that we should explore even higher suspended dose levels in combination with venetoclax to achieve even greater response rate and more durable responses in this growing and exceedingly difficult to treat patient population. Overall, in ACTIVATE, test VEN demonstrated potent activity across subgroupers with adverse mutations, achieving responses broadly in AML with a variety of adverse somatic mutations.

Speaker 3

And testven has a favorable safety and tolerability profile. Tuspendib also is convenient as a once daily oral tablet and mechanistically targets the venetoclax resistance mechanisms. This makes tuspendib an even better drug for therapy, but we're now rapidly heading. All of these data from the TUS single agent and TUS van doublet studies have led us into a tuspetinib, venetoclax azacitidine triplet study in frontline newly diagnosed AML patients ineligible for intensive chemotherapy with the goal of becoming the standard of the patient. 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 3

The high level of interest in seeing TUS developed as frontline 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 TRIPLETE pilot study is being designed as an all comers trial and is designed to combine with standard of care VEN HMN and to select the optimal tusavanazadeose to enable further randomized double blinded clinical studies. We plan to initiate this TRIPA pilot in frontline newly diagnosed AML patients during the first half of twenty twenty four and expect to see initial findings by ASH 2024. We plan to follow these patients to assess overall survival, While HMA then 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, KRAS had more modest survival.

Speaker 3

And those with TP53 mutations seem to not benefit from the doublet Oparaisa alone. And based on tasbetinib's mechanism of action, we would hope to see deeper, more durable responses compared to patients receiving the current VENHMA standard of care alone, particularly in a subset of patients with these resistance type mutations. As standard of care for frontline AML patients unfit for chemotherapy, the potential and historical impact for Tuspendtib is tremendous, addressing a market in excess of $1,000,000,000 We expect that the pilot data could support launching Tuspend HMA registrational programs in 2025. Meanwhile, as resources allow and at the encouragement of KOLs, a second priority is to develop the spend Incomix, the tuscan doublet for relapsedrefractory first salvage FLT3 mutant AML. We saw the greatest response rates to the tuscan doublet in the AML population with FLT3 mutations, even if they have been previously treated with a FLT3 inhibitor.

Speaker 3

We can envision an approach wherein relapsing AML patients with FLT3 mutations are treated with a tuxpin doublet and compared to those treated with the current approved standard, a single agent kilteritinib. 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 more likely and more durable responses. 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 agent combined with VEN HMA and why TUS VENAZAT 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.

Speaker 3

TUS also has broader activity that includes FLT3 mutant and FLT3 unmutated patients compared with other competitor kinase inhibitors and is active in patients with a diversity of other adverse mutations. TUS has an extended patent coverage that goes well beyond that. And TUS has the potential for premium pricing. Finally, it's looking more unlikely that approved kinase inhibitors will enter pivotal frontline studies with VENHMA. Test VENHMA triplet therapy could serve as an off the shelf mutation agnostic triplet allowing for rapid deployment as physicians will not into diagnostic assays or delay therapy while they identify target mutation profiles before putting patients on treatment.

Speaker 3

So we believe that TUS Svan 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 4

Thanks, Raf, and good afternoon all. I'd like to start by saying that in addition to the comments on this call, additional information may be found in today's press release and the 10 ks filed with the SEC. During 2023, we continued our disciplined financial management of operation, reduced expenditures on a number of different fronts and prioritize investments in our clinical programs. As always, we continue to evaluate ways to reduce operational expenses. Also during the year, we used the ATM facility and our 2023 committed equity facility and entered into agreement with Tommy Pharmaceuticals to raise a total of $7,300,000 of additional capital.

Speaker 4

This past January, just 2 months ago, we announced the closing of a $9,700,000 public financing, including the full exercise of the overallotment option and a separate strategic investment of $4,000,000 in a private placement with Harmony Pharmaceuticals. The gross proceeds from the public offering and the private placement were approximately 13,700,000 excluding underwriters, discounts, placement, agent 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 overallotment is 15,706,810 and the warrants outstanding are 8,000,000 332,163 warrants. 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 2024. Now you're probably aware that on February 29, we received a letter from NASDAQ claiming that the January 2024 private placement of securities to Hanmi violated Rule 5635D of the NASDAQ listing rules because we did not obtain shareholder approval prior to such issuance.

Speaker 4

NASDAQ stated that Harmony'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 that Harmony Private Placement was completed in accordance with the NASDAQ listing rules as it was a separate issuance with different deal terms and closed on a different date. The deficiency letter has no immediate effect on listing of common shares. In accordance with the NASDAQ listing rules, we are given 45 calendar days or until April 14, 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 of evidence of compliance.

Speaker 4

We respect NASDAQ's query. We're working with NASDAQ to resolve their concerns and consider available options to regain compliance. I would 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 10 ks filings. Now let's review the year end 2023 financials. We ended the fiscal year of 2023 with approximately $9,300,000 of cash, cash equivalents and investments.

Speaker 4

That is a decrease of $27,700,000 as compared to December 31, 2022. The $27,700,000 decrease in our cash and investments is a result of 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, 2023, the company had raised a total of $7,300,000 $3,000,000 from Harmony subscription, $1,900,000 in gross proceeds from the 2022 ATM facility and $2,100,000 in gross proceeds from the committed equity facility. After the gross proceeds from the January 2024 financing of $13,700,000 the cash, cash equivalents was $18,600,000 That's an unaudited result. As seen in the income statement, we had no revenues during 2023.

Speaker 4

During 2023, the net loss was approximately $51,200,000 translating into approximately $7.58 loss per share compared to $41,800,000 loss and $6.80 loss per share from the 2022 annual period. As of March 26, 2024, Aptose has 15,000,000 717 1,701 common shares outstanding. 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, 2024. Due to our continuous strategic relationship with Harmony, we are now separately reporting related party R and D from our normal R and D expenses. Related party R and D expenses from the Harmony relationship were $3,500,000 for the year end 2023 compared to $3,600,000 for the same period in 2022.

Speaker 4

The remaining research and development expenses were approximately $33,300,000 for the year ended December 31, 2023, compared to $24,500,000 during the year ended December of 2022. Program costs for tisuximab were $24,900,000 for the 12 months ended December 31, 2023, compared to $10,000,000 for the 12 months ended December 31, 2022. The higher program costs for TASUTA in the current period represent the enrollment of patients in our ACTIVATE clinical trial, clinical materials and the healthy volunteer and other expenses related to the FOV8 in development program. Program costs for loxetinib were $3,500,000 for the 12 months ended December 31, 2023 and decreased by approximately $4,900,000 compared to the $8,400,000 for the 12 months ended December 31, 2022, primarily due to lower trial costs, lower manufacturing costs as a result of the current G3 formulation, which requires less API than the prior formulations. G and A expenses were $15,600,000 for the year ended December 31, 2023 compared to $14,500,000 for the same period of 2022.

Speaker 4

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 Doctor. Rice.

Speaker 2

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 questions. Certainly.

Operator

And our first question comes from the line of Soumit Roy from Jones Research. Your question please.

Speaker 5

Good afternoon everyone. So as I'm trying to understand the strategic path forward, the development of TAS in relapsed refractory AML is on pause and we are going to see the latest updated data at EHAI, is that correct?

Speaker 2

It is. 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. 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 the doublet trial in which we increase the dose of tuspedinib in the relapsedrefractory patients.

Speaker 2

And yes, we will be presenting the single agent and doublet data in relapsedrefractory patients at the EHA conference in June. Doctor. Behar, did you want to add anything to that?

Speaker 3

No, Bill. I think it's accurate. 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. But as Bill mentioned, that will depend on additional resources.

Speaker 5

So the strategy to move to put the entire resources towards the frontline, because frontline is going to be a much longer trial. It has to be randomized. It's full Phase III trial versus we were expecting the relapsedrefractory study could have a potential path for Xcerra 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 accelerated path?

Speaker 2

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 in combination with venetoclax. 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 tuspatinib whereas other drugs you tend to have to dose reduce.

Speaker 2

So we believe we can get an even higher response rate, greater durability in the relapsedrefractory 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. But we believe the greatest value in the near term is in this pilot triplet study frontline, because tasplatinib really differentiates its self. It's very safe when it's combined with the other drugs. It has very broad activity and this is what's needed in the frontline therapy, the triplet.

Speaker 2

And we hear that from all potential partners as well as the KOLs in AML. Doctor. Mayhar, want to add anything?

Speaker 3

No, Bill. I think it's exactly accurate. I think that we are excited about the idea of being able to treat these relapsed refractory AML patients and to pursue that avenue. But when we think about prioritization, not just likelihood of success, but also scope of market and potential patient benefit, it is substantially greater in the frontline setting.

Speaker 2

Yes. And much of that is very much driven by what we're hearing from potential partners as to the data that would drive major partnerships. Anything else?

Speaker 5

In the frontline setting, are you going to put any inclusion criteria or select for FLT3 or p53 mutant patient, which are little harder to treat? And does the mechanism of trastatinib allow to combine with 7 plus 3 regimen also? Or is it going to be restricted to HMA then only?

Speaker 3

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 FLT3 mutations. But we know that there are other triplet studies that are going to be out in the world. So we don't want those patients who could not qualify for those studies.

Speaker 3

We want to see the broad range of AML. 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 are about 20% to 25% of those individuals. So we don't do a trial exclusively in that patient population. And then your question about combining with 7 +3, I think that would be very doable for tesbattenib, it would be a great way to go. There's two reasons that we've deprioritized that at the moment and one of which is I think that low intensity treatment with venetoclax and hypomethane agents containing regimens is becoming more common even in individuals who 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 intensity therapy.

Speaker 3

And finally, there already are approved agents in the kinase inhibitor realm in that chemotherapy combination regimen, quisartinib, of course, and mitostorin. And 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 with chemotherapy as well.

Speaker 2

Yes. As we look into the thank you, Doctor. Behar. As we look into the future, we likely will see the triple combination of targeted agents showing much better, much higher response rates, much greater durability. That's the hope for all of the triplets in the patients who are ineligible for chemotherapy.

Speaker 2

And then once that is proven, we would expect that those triplets would also move over to the patients who are chemo eligible. So we would expect that these triplets of targeted agents would then go across both the fit and unfit patients for chemotherapy.

Speaker 5

Got it. And one last question. So in terms of data readout for 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 2

I'll jump in on first and then Doctor. Behar can come in. So ultimately, you want to see that you have an extended overall survival of these patients, median overall survival. 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 the responses very quickly in these patients.

Speaker 2

And then you want to be able to see that you're also recovering the counts. Perhaps Doctor. Behar wants to add to that.

Speaker 3

That's exactly right. I think we will have early indications of activity looking at other studies that have been done with combination of HMA then, a kinase inhibitor, for example, and the vast majority of responses occurred within the 1st or second cycle, suggesting that 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 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.

Speaker 2

And we hope to be able to have multiple dose levels of tasbatinib 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. Again, with most other drugs when you combine with the VEN HMA, you have to do dose reductions both that molecule as well as the VEN HMA. We hope we will not have that issue.

Speaker 2

We expect that we'll be able to dose the 80 milligrams and to maintain the label dosing for the VEN HMA. So that's the plan.

Speaker 5

Thank you again for taking all the questions and congrats on all the progress.

Speaker 2

Thank you, Shmit. Appreciate you coming on.

Operator

Thank you. This does conclude the question and answer session of today's program. I'd like to hand the program back to Doctor. Rice for any further remarks.

Speaker 2

All right. We'd like to thank everyone for joining us this afternoon. As I mentioned earlier, our KOLs believe tasetim is a real drug that's demonstrated activity across a breadth of genetic subtypes in AML, yet has a surprisingly favorable tolerability profile with no significant safety signals and these are true differentiators. We're eager to initiate this triplet study with tusvetinib, which we believe can be the ideal candidate for triplet combination therapy in the rapidly shifting AML treatment landscape. As always, we thank our patients, our investigators and our employees for their important role in this effort.

Speaker 2

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.

Operator

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

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Earnings Conference Call
Aptose Biosciences Q4 2023
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