Q4 2022 Aptose Biosciences Inc Earnings Call
Speaker 1: Hello, and thank you for standing by. And welcome to Aptos Biosciences Reports for the fourth quarter. Hello, and welcome to Aptos Biosciences Reports for the fourth quarter.
Speaker 1: And year in 2022 conference call.
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Speaker 1: I would now like to hand up the conference over to Susan. Pat Trollow, you may begin. Thank you, Twanda. Good afternoon and welcome to the AppTos Bioscience Disconference call to discuss financial and operational results for the year end in fourth quarter and the December 31st, 2022.
Speaker 1: Earlier today, Aptos issued a press release relating to these financial results. The news release as well as related SEC filings are accessible on Aptos' website. Joining me on today's call are Dr. William G. Rice, Chairman, President, and CEO , Dr. Rafael Bejar, Senior Vice President and Chief Medical Officer, and Mr. Fletcher Payne, Senior Vice President and Chief Financial Officer.
Speaker 1: 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 US and Canadian security laws. Forward-looking statements reflect Aptos' current expectations regarding future events. They are not guaranteed to perform, and it is possible that actual results in performance could differ materially from these stated expectations.
Speaker 1: All forward-looking statements made during this call speak only as of the date they are made. Aptos undertakes no obligation to revise or update the statements to reflect events or circumstances after the date of this call except as required by law. I will now turn the call over to Dr. Rice, Chairman, President, and CEO of Aptos Biosciences. Dr. Rice?
Speaker 2: Thank you, Susan. I want to welcome everyone to our call for the year-end and fourth quarter-end of December 31, 2022.
Speaker 2: First, I'll provide a very quick overview of 2022.
Speaker 2: While the biotech market has been extraordinarily challenging, Aptos continued a steady march forward.
Speaker 2: We extended our cash runway to the end of Q1, 2024. We continued building a talented and experienced team. We created and began testing a new formulation for luxeptinib. And most importantly, we made significant strides in the development of tuspetinib for the treatment of acute myeloid leukemia, or AML.
Speaker 2: When it comes to TUS-Pettinib, or TUS as we call it, I want to emphasize its highly differentiated profile, having demonstrated the potency to achieve complete remissions in very ill relapsor-refractor AML patients.
Speaker 2: while also being safe and well tolerated.
Speaker 2: It's extraordinary for an antilukemic agent to deliver formal responses in such an aggressive cancer without causing the typical toxics of other agents.
Speaker 2: And today we will unpack both the potency and safety attributes.
Speaker 2: both the potency and safety attributes of TUS.
Speaker 2: It's also important to highlight the AML population that has been treated with TUSPAT-NIB to date in our Phase 1-2 Dose Escalation and Dose Exploration trial.
Speaker 2: These are typically third line, fourth line, or beyond, having failed the best available approved therapies and in many cases having failed various investigational drugs or prior hematopoietic stem cell transplants.
Speaker 2: These are incredibly difficult patients to treat and to reverse the disease progression.
Speaker 2: What makes these patients even more difficult to treat is the extreme diversity of highly adverse genetic and epigenetic alterations expressed by their disease.
Speaker 2: If you recall the Admiral trial from just five years ago, during which the commercial dose of guilt-retinib, a FLIT3 inhibitor, was tested for responses in AML, the patients were second line, essentially had not seen other FLIT3 inhibitors and had not seen Venetoclax.
Speaker 2: In contrast, patients entering our trial are far more treatment experienced with half felling prior venetoclax
Speaker 2: 60% failing prior treatment with hypomethylating agents or HMAs, more than a quarter having failed transplants.
Speaker 2: and half of the FLT3 mutant patients having failed prior therapy with a FLT3 inhibitor.
Speaker 2: Nevertheless, TUS has delivered responses with convenient, once daily oral dosing of tablets across four dose levels.
Speaker 2: 160 milligram, 120 milligram, 80 milligram, and 40 milligram, and no DLTs were observed with any of those active dose levels.
Speaker 2: from a mutation sensitivity perspective.
Speaker 2: TUS has shown an unprecedented breadth of activity. TUS delivers responses in FLT3 wild-type patients, as well as it does in FLT3 mutated patients.
Speaker 2: We also have seen responses in AML patients having the very difficult to treat TP53 mutations.
Speaker 2: as well as patients with NPM1 and FLIT3 co-mutations, and patients having alterations in the DNMT3A, RONC1, IDH1, splicing factors, ASXL1, and MLL genes.
Speaker 2: But one of the most interesting observations is the activity in relapsed refractory AML with RAS mutations.
Speaker 2: Mutations in the RAS pathway serve as an escape mechanism to generate resistance to many other problems.
Speaker 2: However, we've measured a 42% overall response rate in patients with RAS mutations.
Speaker 2: including a 29% CR CRH response rate.
Speaker 2: In fact, one patient had a RAS mutation and a mutation in PTPN11, representing a dual mutation in the RAS pathway.
Speaker 2: We will continue to monitor the response rate in RAS-mutated AML patients this year and determine if RAS-mutated relapsed refractory AML patients may represent a population of high and mutt need for future accelerated approval trials.
Speaker 2: As Dr. Behar will describe in further detail in a few minutes, we wrapped up our highly successful Phase 1-2 dose escalation and dose exploration trial. We've treated over 60 patients to date in that trial. We've assembled a strong safety data package.
Speaker 2: We selected safe and effective doses for our single agent and drug combination trials. We demonstrated the ability of TUS to dramatically reduce bone marrow blasts in a high fraction of patients and to achieve formal responses.
Speaker 2: and we initiated our activate dose expansion study of TUS.
Speaker 2: in a single agent and in combination with Venetoclax.
Speaker 2: In the AFTIV8 trial this year, we will enrich certain patient populations to receive monotherapy so that we can collect data to guide our conversations with the FDA to request an accelerated approval path for tests in patients of high and met need.
Speaker 2: In parallel with the activate monotherapy dosing, we will treat a broad array of AML patients with a combination of TUS plus Venetoclax, referred to as the TUS-Vent doublet.
Speaker 2: This TUSVIN doublet is being conducted to support doublet combination registration of trials in second line AML patients.
Speaker 2: and to serve as a bridge to a pilot study of TUS, plus VIN, plus a hypomethylating agent, or the TUS-VIN HMA triplet in frontline AML patients.
Speaker 2: While TUS clearly can deliver responses as a single agent, the ultimate goal in commercial of success of TUS or any drug for AML will be in combination with other drugs.
Speaker 2: As of this week, we have begun enrollment of AML patients on the TUSVIN doublet, and we will place additional patients on this doublet throughout 2023.
Speaker 2: Once we gain experience with the doublet, we plan to initiate the TUS-VIN HMA triplet in frontline patients.
Speaker 2: The future of AML therapy will also revolve around cocktails of drugs and earlier lines of therapy to take patients into deep permissions.
Speaker 2: Such AML cocktails will require the blending of drugs that best can serve broad populations of patients.
Speaker 2: AML cocktails will require the blending of drugs that best can serve broad populations of patients can deliver the permissions.
Speaker 2: and can be tolerated without cardiotoxicity, unnecessarily prolonged myelosuppression, and other complicating side effects. And this precisely describes TUS.
Speaker 2: TUS is positioned to become the ideal partner for addition to the WEN HMA doublet because of its convenience as a once daily oral agent, its broad activity, and its safety profile.
Speaker 2: Together, data to date point TUS toward application as a monotherapy for accelerated approval in relapse to refractory AML.
Speaker 2: as doublet therapy for accelerated approval in second line EML.
Speaker 2: For use in triplet combination and frontline patients.
Speaker 2: as well as your use in maintenance therapy. And Dr. Behar will provide you with additional color of these activities momentarily. Now let me turn briefly to Luxefative. Many of you know what has CG806.
Speaker 2: Lux, as we typically refer to it, is our secondary pipeline program.
Speaker 2: Lux is a clinical stage, small molecule, oral, FLIT3 and BTK kinase inhibitor.
Speaker 2: Lux's ability to target kinases, operative in certain leukemias and lymphomas, led us to develop it in patients with B-cell leukemias and lymphomas and in patients with AML. We already have reported that Lux, administered as our initial first generation or G1 formulation, builds a new
Speaker 2: delivered a CR in an AML patient and a CR in a DLBCL lymphoma patient.
Speaker 2: demonstrating LUX is a clinically active agent. You also are aware that we developed a new formulation of LUX and we call it the G3 formulation because it represents the third generation formulation. In single dose administrations during 2022, in AML and B-cell malignancy patients.
Speaker 2: we determined the G3 formulation achieved up to 18-fold greater absorption than the original G1 formulation.
Speaker 2: Because the highest dose of the original formulation was set at 900 mg,
Speaker 2: we initiated continuous dosing of G3 at an 18-fold lower dose level of 50 milligrams. We continue to collect PK and safety data with G3 and AML patients and the preliminary results suggest continuous dosing of 50 milligrams G3 does indeed deliver roughly equivalent plasma exposures.
Speaker 2: as 900 milligrams of the original G1 formulation.
Speaker 2: That was the target we hope to achieve with the 50 milligrams of G3. Next, we plan to administer a higher dose of G3 to determine if it can achieve even greater plasma exposure levels.
Speaker 2: We will keep you posted on our findings and likely will report preliminary data around EHOP.
Speaker 2: I also want to mention that Aptos and collaborators at UCSD, Dr. Manchu Sonowal and Dr. Stephen Howell, just published an article entitled, Luxetinib Interferes with LEN-Mediated Activation of SICK and Modulate VCR Signaling in Lymphoma in the online journal PLOS One.
Speaker 2: in which we describe the ability of LUX to act on the B-cell receptor pathway at the level of the LCK and LYN or LYNN kinases and to influence downstream BTK activity. This relates to the role of LUX to act on B-cell cancers as well as inflammatory and autoimmunity processes.
Speaker 2: So please take a look at the article if you get a chance. Finally, we often get asked about potential partnerships for TUSP-EdNet. In January during JP Morgan week, TUSP-EdNet was released in November .
Speaker 2: We engaged in productive discussions with several big pharma and biotech companies that further helped to define our priorities and to solidify our clinical plans with Tuspetinib. It's clear what we need to accomplish with the drug that has such an extensive commercial opportunity. We were pleased to see that we're on the radar of these companies and interest in our program is growing.
Speaker 2: The treatment paradigm for AML is shifting toward doublet and triplet therapy, and despite some successes.
Speaker 2: The current combination therapies are somewhat limited by toxicity as I mentioned previously. The proven breadth of activity and superior safety profile of Tuspetinib lends itself to combination therapy, potentially as the drug of choice, addressing the most sizable markets in AML and clearly making TUS a prospective big pharma drug.
Speaker 2: The data we've generated to date have helped us delineate clinical and commercial plans for Tuspatinib in multiple lines of therapy, including its use in doublet and triplet combinations and as maintenance therapy. Our Chief Medical Officer, Dr. Rafal Behar, will speak about our recently initiated ACTIVATE clinical trial.
Speaker 2: of Tuspatinib in AML, as a single agent, and in combination with Venetoclax, as well as our extended clinical plans, which include triplet combination therapy. He also will be available for questions afterwards.
Speaker 2: I now will turn it over to our resident KOL, our Chief Medical Officer, Dr. Rafael Bejar, to talk more about our Taspetinib clinical plans. Raf? Thanks, Bill. In January , we were thrilled to kick off the 120-mg dosing of Taspetinib in the monotherapy arm of the ACTIVATE Phase 1-2 trial.
Speaker 3: As most of you know, we have successfully completed dose escalation and dose exploration stages of our CUS phase 1-2 trial, treating approximately 60 relapsed refractory AML patients who were heavily exposed to multiple agent.
Speaker 3: In fact, as Dr. Rice mentioned, while we were wrapping up the dose exploration part of the study, we took the prudent step of putting additional patients on the lowest 40 milligram treatment group because of the FDA's project optimist that emphasizes dose exploration during early development of oncology products. This experience gave us the additional data needed to support our monotherapy dose selection and was not borne out of the safety concern, rather...
Speaker 3: as higher doses of this bettinib have shown an impressive safety profile. Since we lost the 40 milligram dose level late last year, we have achieved two clinical responses in that low dose group. Both AML patients with unmutated Flut3, including the most recent harboring a challenging TP53 mutation, one of the most highly adverse somatically mutated genes.
Speaker 3: Importantly, this is the second TP53 patient that has achieved a clinical response. The first was at the 80 milligram dose, who achieved an unqualified CR at their best response.
Speaker 3: So we look to enroll more of these patients who with such a poor prognosis have a great unmet need than the activate trial. The activate expansion trial is designed to confirm monotherapy activity through patient enrichment of specific mutationally defined AML populations, including the TP53 mutant patients, as well as split 3 mutated patients who have been failed by prior for 3 inhibitors.
Speaker 3: as supported by an FDA fast track designation and a clinically significant response rate to date.
Speaker 3: These patients continue to have great unmet medical need, and we believe that the ability to rescue these patients and perhaps allow them to receive a central transplant, we have now done with several patients in our study, would allow us a quicker path to registration.
Speaker 3: In addition to being potential accelerated approval pathways for TISP-PETNID, treating these subgroups will provide critical data to inform our continued development path.
Speaker 3: I am pleased to say that we have begun treating patients in the monotherapy arm of the Aptivate trial, and that a growing network of clinical sites and investigators are engaged in enrollment, and that this has been risk. In the Aptivate expansion trial, this specimen also will be tested in combination with the Net-A-Clax.
Speaker 3: Several sites that have regulatory clearance and both drugs in hand, allowing us to initiate patient enrollment on the test then combination earlier this week.
Speaker 3: Having the TESF and combination arm open is an important advance, as this represents an attractive treatment option for patients and their physicians, leading them to enroll earlier in the course of treatment, increasing the likelihood of achieving a meaningful clinical benefit.
Speaker 3: So what is our timeline for our clinical trials?
Speaker 3: Because Aptivate is an open-label trial, we will report data when available at appropriate forums. We will have an update around EHA in June , for example, as we usually do, but because data collection and verification does take time and Aptivate has only been open for a short while, this will be an incremental update. We would expect to have more complete data, particularly for the monotherapy arm.
Speaker 3: at the European School of Hematology meeting, ESH, at the end of October in Estoril, Portugal. Expect more data, including from the TUSVIN combination cohort, to then be updated at ASH in San Diego in December , so 2023 will be a busy year for us. Having tested to SPEDNIB in specific genetically defined populations, we would expect to have sufficient patient data this year.
Speaker 3: then segue to Phase II registration studies to support accelerated approval. As Dr. Rice mentioned, we are including relapse or refractory AML patients with unmutated foot 3, what we often call wild type patients, that have other adverse mutations, exploring safety and activity in these patients with the segment treatment, both as a single agent and in combination with the netaclocks. Identifying meaningful activity in other adverse subgroups could lead to other options for children.
Speaker 3: and in maintenance settings.
Speaker 3: Dr. Nabel Dobber from MD Anderson, who's been one of the investigators pioneering AML combination therapies with Venetoclax, is our lead investigator on UpToDate and is eager, as we are, to see what the spender can do in this setting.
Speaker 3: We'll also highlight a few comments from Dr. Harry Urba of the Duke Cancer Institute during a recent KOL event. He noted that this drug may be better suited for the combinations that we hope to develop than anything we have right now. And he was excited about the apparent lack of viral suppression noted in our clinical study to date.
Speaker 3: And he emphasized that a drug like TUS will have a position mostly because it has better toxicity profiles than the drugs we're using now in terms of mild suppression.
Speaker 3: Clearly, we agree wholeheartedly with Dr. Urba and we believe that potency, breath, and anti-lucanic activity, along with the safety profile, make us better the ideal drug for combination therapy and scalable commercialization. On our website, you can see our projected timeline for ongoing and planned clinical trials. I want to thank our clinical team for their hard work and execution in getting both arms of activated expansion study up and running. We certainly look forward to sharing the data with you.
Speaker 3: Now I'd like to turn the call over to our CFO Fletcher Payne for an update on our financial status. Fletcher. Thanks Raf and good afternoon all. Before we start speaking about the financials, I'd like to introduce to you the newest member of our finance team, Brooks Ensign, who is a VP and controller of Aptos.
Speaker 3: Mr. Ensign has more than 20 years of pharmaceutical industry experience in accounting, finance, corporate development, and he served in this position for multiple public and private companies.
Speaker 4: here at Aptus.
Speaker 3: Let's review the fourth quarter and your end financials. As most of you know from following Aptos, we take a disciplined approach to cash management and always look to prioritize our clinical activities without sacrificing quality of our programs.
Speaker 3: These efforts have extended our cash runway into 2024, and our cash management policies and the actions taken have helped us avoid the financial impact of Silicon Valley Bank's fallout. Now let's review our cash position.
Speaker 3: We ended 2022 with approximately $47 million in cash, cash equivalents, and investments, a decrease of $4.8 million as compared to the previous quarter.
Speaker 5: During the quarter, the net loss was approximately $10 million, translating into approximately negative $0.11 per share loss.
Speaker 5: down from $24.3 million loss from the comparable period in 2021.
Speaker 5: As identified in the income statement, we had no revenues during the fourth quarter of 2022.
Speaker 5: Research and development expenses were $6.8 million for the quarter, down $20.2 million from the same quarter in 2021. Research and development expenses for the full year period ended December 31, 2022, with $28.1 million as compared to $46.7 million in 2018.
Speaker 5: million for the comparative period.
Speaker 5: a decrease of $18 million. That decrease was due to several factors, including a $12 million licensing fee paid to HONMI in the previous year to acquire global development rights for TSEPNA, which comprise the account of Oppen emphasises idiot
Speaker 5: a $5 million cash payment, and a $7 million worth of common shares. Additionally, there were lower costs for the Lux program and 253 program, as well as lower personnel costs. These savings were potentially offset by costs for the Toseptim program that was adopted in 2020.
Speaker 5: G&A expenses were $3.6 million for the quarter as compared to $4.1 million for the same quarter of 2021. G&A expenses for the 12-month period ended December 31, 2022, were $14.5 million as compared with the 12-month period.
Speaker 5: $19.5 million for the comparative period, a decrease of approximately $5 million.
Speaker 5: The decrease was primarily due to a decrease in stock-based compensation expenses offset by higher compensation expenses.
Speaker 5: travel expenses.
Speaker 5: and professional fees.
Speaker 5: As of March 23, 2023, Aptos has 93,005,278 common shares outstanding.
Speaker 5: More detailed information can be found in our filings on agar and cedar. Now let's turn it back to Dr. Weiss.
Speaker 2: Thank you Fletcher. As we open the call for questions, please feel free to pose a question to any of us. Operator, if you could please introduce the first question. Thank you. At this time, I would like to remind everyone how to ask the question.
Speaker 1: To ask the question, please press star 11 on your telephone and then wait for your name to be announced.
Speaker 1: To withdraw your question, please press star 11 again. Please stand by while we compile the Q&A roster.
Speaker 1: Our first question comes from the line of Matthew Beigler with Oppenheimer. Your line is open. Thank you for the question.
Speaker 4: Okay, guys, thanks for the update. Just two for me. I'm wondering, is it too soon to guide on patient numbers for that October update from the activate trial? And then just curious about some of the comments Raph made about the doublet versus the singlet to.
Speaker 4: to set, live and activate. I'm just, I'm curious if you're, if you're concerned that it might be challenging to enroll the monotherapy arm, given that there is a doublet or kind of, how are you approaching that? Or how are you thinking of kind of weeding out patients from one to the other? Thanks. Thanks, Matt. This is Bill. I'll start on that. But your second question is really easy. Doublet versus monotherapy.
Speaker 2: We've had exceptional uptake, rapid uptake, and I think the word that Dr. Behar used was brisk uptake as the monotherapy. We got it up and running first this year. It's been great enrollment pace and we're just now beginning to enroll the doublet.
Speaker 3: In terms of the numbers of patients and all, I'm going to turn that back over to Dr. Behar. We'll be careful not to really bracket them too much, but we'll try to give you a sense. Raf? Yeah, thanks, Matt. And just to follow up on Bill's earlier point about the enrollment to both, the doublet I think is going to be more appealing to investigators than the monotherapy in general. But once both arms are open and those options exist, there will be a random assignment.
Speaker 3: on it but I would say the enrollment has been very good and there certainly will be
Speaker 3: enrollment has been very good and there certainly will be some...
Speaker 3: Again, not bragging too much, maybe 10s of patients on the monotherapy arm and hopefully somewhere between 10 and 20 patients on the doublet arm by the time that we read out near the end of the year.
Speaker 4: All right, great, thanks. Thank you.
Speaker 1: Please stand by for our next question.
Speaker 1: Our next question comes from the line of Shumet Boyd with Jones Trading. Your line is open. Thank you.
Speaker 6: Hi everyone, thank you for the update. Could you give us a little bit more color on the different dose cohort size you're enrolling currently between?
Speaker 6: 40, 80, 120. And then the 100th patient you mentioned, what split his monotherapy and doublet.
Speaker 2: All right, hey, Shumit, this is Bill Rice. So, yeah, we have completed the dose escalation and dose exploration trial. And so I'll ask Dr. Behar to give you a breakdown on the numbers of patients there, and then he can talk about who you have to be.
Speaker 3: So as of the ASH meeting, when we had not yet opened Aptivate, we had treated 60 patients between the dose escalation and what we call the dose exploration. We since treated additional patients in the dose exploration arm, primarily at the 40 milligram dose level, to further characterize that better before Aptivate was opened, where we were then dosing.
Speaker 3: patients ideally exclusively on Aptivate, as studies became online, were able to do that. The dose level that we started Aptivate at for the monotherapy was 120 milligrams. That may change as we learn more about the PK and the activity of the drug.
Speaker 3: but we may move to 80 milligrams for the monotherapy dose, seeing it, the level of activity, whatever we have implemented.
Speaker 3: For the combination study, 80 milligrams will be the starting dose that we've signaled before in combination with the sput with Venetoclax. And as always, that is also subject to change based on the data that we received.
Speaker 6: Right.
Speaker 6: So how are you thinking of presenting the data mid-year or later, second half also? Are you going to do
Speaker 6: oh
Speaker 6: from the ACTIVA trial like...
Speaker 6: the traditional ORR response rate or CR rate over a number of patients treated. And alongside, you're going to show long-term, if any, durability data from the dose escalation expansion part of the trial.
Speaker 3: Traditionally, we have done that kind of more complete update at major medical meetings like EHA and ASH, and I think that that will definitely hold true for ASH. I do think that EHA will be a more incremental update, so there may not be that much level of detail, just because, to be honest, the cutoff date for data to be presented at EHA is about now. I think that that will be a more incremental update, just because, to be honest, the cutoff date for ASH is about now. I think that that will be a more incremental update, just because, to be honest, the cutoff date for ASH is about now.
Speaker 3: So we don't necessarily have a lot more to say than we have said earlier this year in that regard. So we will do an incremental update. We'll certainly highlight any activity or issues that arise in the study around EHA, but expect that larger data package with some of the more detail you just described to have them later in the year.
Speaker 2: Perfect. Thank you so much. Just to add to that, we will have certain scientific findings at EHA that we'll be presenting. That's the plan. As well as some of the additional data, as you said, as we followed some of these patients that have been on the dose escalation, we'll be able to provide that. But then as Dr. Behar said, we just started the activate trial.
Speaker 2: and we'll present the data that are available. It won't be a huge number of patients by that time, but we'll present what we have. Thank you, and congratulations on all the progress. Thank you, Shama.
Speaker 7: Thank you.
Speaker 7: Thank you. Please stand by for our next question.
Speaker 7: Our next question comes from the line of Joe Pangenis with HC Wainwright. Your line is open. Your line is open.
Speaker 3: Hey guys, good afternoon. Thanks for taking the question. So, Bill was wondering maybe if you could do a little benchmarking for the audience about your regulatory plan for the monotherapy armenaptivate. You talked about, you know, since it's mono, you know, potential accelerated approval. So, you know, based on your internal thoughts, regulatory.
Speaker 2: Ah boy, a number of questions there. So first of all, I'm not gonna go too much out on a limb because soon we are gonna be having the...
Speaker 2: the FDA and we've already articulated that to the street. So we'll be speaking with all the parameters you just mentioned for the monotherapy, as well as the doublet data that are coming out. We wanna make sure that as we go to the FDA, by then we will have a number of patients that are already on the monotherapy, the Aptivate trial, make sure that we're doing everything that we should, determine if there are additional parameters we need to measure, so that when we go to them with the data later in the year.
Speaker 2: We'll have everything that we need and hopefully the data will be supportive of going toward an accelerated approval. Whether that's a monotherapy, a doublet, we'll see how those data emerge toward the end of the year. And Raph, is there anything else that you wanted to add to that in terms of regulatory?
Speaker 3: That's a good way to put it. I think that we do need to have that meaning with the FDA to really align ourselves. And depending on what features we agree upon, that'll change the scope of the study. But certainly, an accelerated approval study would be a much smaller study than you would have to do if you did a randomized multi-arm study.
Speaker 2: Yeah, and then also a little bit later in the year as we collect data on the doublet, we want to be able to go to the FDA, present the data there, and hopefully have the ability to move into the triplet draw. Does that answer your question, Joe? No, it does. And I guess maybe just a little for the listeners and everyone.
Speaker 3: and investors in general, you know, benchmarking you would look at from an efficacy standpoint.
Speaker 2: So, yeah, so, Raph, do you want to put that in context relative to the Admiral trial? And Joe, thanks for the question.
Speaker 3: Yeah, exactly. I think that that's the way you need to view it is, you know, what population are we treating and what expectations might they have from alternatives if test-based And remember, these are patients who, if they are Flut3 mutated and have seen Flut3 inhibitors, they've likely been through at least two lines of prior therapy. So they're coming to a third line or beyond. In the second line setting with the Adderall study.
Speaker 3: at the interim analysis for guilt-written, the CR CRH rate was 21%.
Speaker 3: Now later that matured, especially with the inclusion of patients whose best response was measured after transplant, but at the point of that interim analysis that led to the approval of the drug, that was 21 percent. In the second line, the patient's largely naive of other therapies. So we would argue that a meaningful number in the third line setting would be significantly less than that. Perhaps, you know, as well as half of that or somewhere between half to that range.
Speaker 3: Given that the alternatives for those patients at that point are going to be even less effective than they might have been in the second line setting, as they were in the ADML study, where the chemotherapy response rate for CR was about 11%. So, that's the ballpark that we're working with, and what we come down with with the FDA, I think, will then shape the scope of the study, the size, and so on, and that's the discussion we're going to have. Great. Yeah, I think the bar is fairly low for that patient population, as you said, that many of them will have already failed.
Speaker 7: Thank you. Please stand by for our next question.
Speaker 7: Our next question comes from the line of Edward Penhouse with Piper Sandler. Your line is open. Your line is open.
Speaker 8: Thank you very much, and congrats on the little progress. It's going to be an exciting year. I think there was some questions on 2, 3, 5 or 5, 3, 9, where I asked, but I wanted to add it to a luck sort of higher level, how this fits into the treatment power, or how this treats into your development plan.
Speaker 8: And specifically, you know, what are expectations here? Is this a drug that you would consider partnering? Does it ultimately have combinability? Maybe even with five, you know, thanks very much.
Speaker 2: Thanks Ted for the questions. Yeah, we don't get that many questions on Lux anymore, but we're still excited by the drug. Now that we have our new formulation, and especially as we go up to that next higher dose level, that's the plan now, and we hope we get higher exposures as we go into that. But in terms of what we'd like to do with this molecule, I mean, first of all, I must say that Tuspetinib
Speaker 2: our top priority among everything. And it has to be because it is delivering. It's more advanced, it's delivering.
Speaker 2: But TUSP, but LUX, as we move forward, we'd love to see that we're getting the exposure that we want and that the pill burden is also much less, cost of goods much less. If we continue to see activity in AML, we'll see that.
Speaker 2: We have done studies where we put the TUS and LUX together and they are not antagonistic. They also we know have different activities against different kinases. So it may turn out to be like some of the other indications where you have multiple kinases that hit different patients with different mutation profiles.
Speaker 2: But most likely, we likely will move it more toward the B-cell arena and also toward inflammation and autoimmunity because we've been, as you can tell from the publications, we've been digging into that area, understanding it. They're still in need because this drug is different from the other non-covalent BTK inhibitors.
Speaker 2: It hits a different set of kinases. It has different activities. And we believe that if we're able to combine it, for instance, with... be different, we'll end up finding out this, as found in all this.
Speaker 2: with some of these other drugs that are being developed for the B-cell malignancies, like the Venetoclax, for instance, then we believe we can see real activity there. So there are paths forward that do not interfere with Tuspatinib.
Speaker 2: drugs that are being developed for the the B cell malignancies like the Venetoclax for instance then we believe we can see real activity there so there are paths forward that do not interfere with TUSPAD. Does that answer your question?
Speaker 7: Yes, that was very helpful. Thank you. Yeah. All right. Thank you. Thank you. Please stand by for our next question. Our next question comes from Alana Lee-Watsek with Cata Fixtural. Your line is open.
Speaker 9: Hi everyone, this is Rosemary and for Leigh. Thanks for taking my questions. Just a couple here. Firstly, are you able to give some color around the early activity that you see from the monotherapy arm and activate? And then on the RAS pathway, can you talk a bit more about where you can go with this finding if RAS correlates with any other mutations potentially?
Speaker 2: and whether you see mono or combo therapy potential here. Thank you. So I'll, thanks Rosemary for coming on. So I'll start with this and then maybe Dr. Behar will want to jump in. So in terms of early activity, again, it is very early in the activate trial on the monotherapy.
Speaker 2: And as we said in our press release, we are beginning to see what we call an initial anti-leukemic activity. You'll remember we're very conservative on what we say in terms of what we're seeing in the clinic. So yes, if you're asking us, we do see some level of blast reductions. We're not going to be talking about how much or what we're seeing or the number of patients.
Speaker 2: It's just very early, but are we seeing hints of activity beginning? Yes, it's early, but we are. You also asked about the RAS mutations. I find this one very exciting to tell you the truth, because many of the other drugs out there, one of the major escape pathways for other drugs is the RAS pathway. But we've seen activity, CR, CRHs. I mean, these are real responses.
Speaker 2: Inpatients have NRAS, KRAS, and also other mutations within the RAS pathway. So it's a real need that I don't think people have highlighted enough in AML because there hasn't been a really good drug to treat these. But I'm hoping we get more of these patients. I'm hoping that we see activity in these patients. And maybe this will be another indication we can look toward.
Speaker 3: as an accelerated approval, but the data will have to point us in those directions. I'm going to turn it over to Dr. Behar and see if he has any additional comments. I think that was well put. I think what is exciting about the activity in RAS-mutant patients is that RAS mutations in the relapse setting really mean something different than they do in the frontline setting, even drugs like Venetoclax.
Speaker 3: You can get responses in patients who have NRAS in that frontline setting, but when patients relapse, it's typically with an expanded NRAS clone or a new NRAS clone or Flut3 clone that activates that signaling network. So the ability to target patients that have NRAS mutations is exciting, not only to treat potentially refractory patients, but also to treat patients in the frontline and prevent the development of resistance through that pathway. So we're hopeful that it has benefits in both patient populations.
Speaker 3: And Bill, to your point about the activity in the activate study thus far, I'll just point out that patients began enrolling in activate in January . It takes a month before their first assessment takes bone marrow assessment takes place. And then another month before the confirmatory biopsy takes place. So we're just about at that point now for the earliest patients enrolled. So all we can really say is that we've observed activity in terms of peripheral blast productions and.
Speaker 7: and looking at early looks at the bone marrow only, but we'll have more data around that as we get further along. Thank you, Ralph. So, Rosemary, did we answer your questions? Thank you. All right. Thanks for coming on. Thank you. As a reminder, ladies and gentlemen, that's star 11 to ask the question. Please stand by for our next question.
Speaker 7: Our next question comes from the line of Gregory Renza with RBC. Your line is open. Your line is open.
Speaker 3: Hi, guys, it's Anish on for Greg. Congrats on the progress and thanks for taking my question. Just on tests in considering the different aml mutations or sub population studied and with the data to date and which type are you seeing the most responses and as a follow up in which subtype are you seeing greater response with a 40 milligram dosing regimen.
Speaker 3: versus those that require greater exposure slash higher dose for a response with tests? And how might these findings inform regulatory next steps? Thanks so much.
Speaker 3: Good question, but Raf, do you want to jump in on this? I can start. That is a great question. I think that is something that we're very interested in learning. We're limited by a few things. First is patient numbers. Even after treating 60-plus patients, you don't necessarily have that many patients in any particular genetic subgroup when you open a study to all comers.
Speaker 3: predicted to not do as well because of these adverse mutations that they carry. It could be subsets of populations with great medical need. But to be fair, all relapsorfractory HEML patients are a population with great medical need as many can't be cured with conventional therapy. They need to go to some sort of stem cell transplant at that point. So the ones of interest, I think I mentioned NRAS, TP53, FIT3 patients that have exhausted FIT3 inhibitors prior. And I think that the way to thinking about it is that people often say that whiteople
Speaker 3: But there may be others, and it may be combinations of mutations that matter, for example, NPM1 and FLIT3 mutations. We've seen a reasonable response rate in that patient population as well. And the activate study by enrolling additional patients will really give us the confidence that we understand what those response rates are in the different populations. You had asked about differential activity at the 40-milligram dose level. We've reported that there were two responses at that dose level, so again, very small number of patients.
Speaker 7: Thank you. Thanks for coming out. Thank you. Please stand by for our next question. Our next question comes from the line of John Newman with Canna Core. The line is open. The line is open.
Speaker 5: Hi guys, thanks for taking the question. As you move forward with the activate study in terms of...
Speaker 3: the potential for accelerated approval, would you expect that you'll be focusing on a specific mutational type? Or would you be focusing more broadly? Thanks.
Speaker 2: I'll start and then Dr. Behar can come in. Thanks John for coming on. So as we look at the patients being treated with monotherapy, clearly we want to enrich for certain of these populations. The ones that Dr. Behar had mentioned, those that had failed prior FLIT3 inhibitors, those that have TP53 mutations. Now that we've seen some of these data with RAS, we'll ask the investigators to take a look at the data.SE Reality
Speaker 2: if we can try to find patients more like that, and hope to get enough of these patients to be able to go to the FDA and say, hey, there's a real signal here, we'd like to move forward for the accelerated approval. But I also want to emphasize, the doublet is very important for us, because showing that your drug works well and is well tolerated in combination with phenetoclax, that's what's gonna launch us into two different pathways. One is, it's gonna position us for the
Speaker 2: TUS patients for and hopefully we could design it so that we could have an early look at the data accelerated approval as we continue to bring patients on for full approval and to end a doublet trial.
Speaker 3: And I'm sure Dr. Behar can say it far more eloquently. So, would you like to jump in? Yeah. It won't sound as good as it comes from you, Bill, but I will say that the Admiral study is actually a good model for what you might be able to do in a second mind setting, say, for example, with a test-dependent venetoclax tablet, where you have a study that's powered to eventually read out overall survival, but that includes an incremental and interim analysis sleeping taught on the during what that, as it called, SIPs,seed, 1976. Yeah.
Speaker 3: could be compelling enough to seek approval. So that is one option. With the monotherapy study, of course, you're not having anything to compare it to. So we'd just be shooting for a target response rate at that point.
Speaker 2: Thanks for giving us the opportunity to talk about those a little bit John . Any other questions?
Speaker 2: But thanks for giving us the opportunity to talk about those a little bit, John . Thank you. Any other questions?
Speaker 7: No, thank you. Okay. All right. Thank you. Thank you. I'm currently showing no further questions in the queue. I would now like to turn the call back over to Dr. Rice for closing remarks.
Speaker 2: I want to thank everyone for joining us this afternoon and thank you for all the interest in Aptos, the drugs, and the data that we're generating. We're gratified as we look in the rearview mirror of 2022 and we see the clinical progress of Tuspatinib and the strides we're making with the G3 formulation of Lux.
Speaker 2: Yet our eyes now are really looking forward to 2023 and beyond, and we're eager to share data with you during the coming year. Again, we talked about being able to present data at the conferences, but also at the earnings calls as well as in banking meetings. We want to thank our clinical team.
Speaker 2: our investigators, our patients for their help in this important work. We appreciate the support of our shareholders and analysts, and we look forward to keeping you updated on our progress the rest of the year. Thank you, and have a good evening. Thank you. Ladies and gentlemen, that concludes today's conference call. You may disconnect and have a wonderful day.
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Speaker 1: Hello, and thank you for standing by. And welcome to Aptos Biosciences Reports for the fourth quarter.
Speaker 7: and Year-End 2022 Conference Call. At this time, all participants are in a listen-only mode. After the speaker's presentation, there will be a question-and-answer session.
Speaker 7: To ask the question during the session, you will need to press star 1-1 on your telephone and you will then hear an automated message advising your hand is raised. To withdraw your question, please press star 1-1 again.
Speaker 1: I would now like to hand the conference over to Susan Peptralo. You may begin. Thank you, Twanda. Good afternoon and welcome to the APTOS Biosciences Conference call to discuss financial and operational results for the year-end and fourth quarter ended December 31, 2022. Here today, APTOS issued a press release relating to these financial results.
Speaker 1: The news release as well as related SEC filings are accessible on Aptos' website. Joining me on today's call are Dr. William G. Rice, Chairman, President and CEO , Dr. Rafael Bejar, Senior Vice President and Chief Medical Officer, and Mr. Fletcher Payne, Senior Vice President and Chief Financial Officer. Before we proceed, I would like to remind everyone that certain statements made during this call will include forward-looking statements within the meaning of U.S. and Canadian securities.
Speaker 1: and uncertainties, please read the risk factors set forth in Aptos' most recent annual report on Form 10-K and SEC and CDER filings. All forward-looking statements made during this call speak only as of the date they are made. Aptos undertakes no obligation to revise or update the statements to reflect events or circumstances after the date of this call, except as required by law.
Speaker 7: I will now turn the call over to Dr. Rice, Chairman, President, and CEO of Aptos Biosciences. Dr. Rice? Thank you, Susan. I want to welcome everyone to our call for the year-end and fourth-quarter-end of December 31, 2022.
Speaker 2: First, I'll provide a very quick overview of 2022. While the biotech market has been extraordinarily challenging, Aptos continued a steady march forward. We extended our cash runway to the end of Q1 2024. We continued building a talented and experienced team.
Speaker 2: We created and began testing a new formulation for luxefinit, and most importantly, we made significant strides in the development of tuspetinib for the treatment of acute myeloid leukemia, or AML. When it comes to tuspetinib, or TUS as we call it, I want to emphasize its highly differentiated profile, having demonstrated...
Speaker 2: the potency to achieve complete remissions in very ill relaptor refractory AML patients, while also being safe and well tolerated. It's extraordinary for an anti-leukemic agent to deliver formal responses in such an aggressive cancer without causing the typical toxics of other agents.
Speaker 2: And today we will unpack both the potency and safety attributes of TUS. It's also important to highlight the AML population that has been treated with TUS-BETNIB to date in our Phase 1-2 Dose Escalation and Dose Exploration Trial. These are typically third line, fourth line, or beyond, having failed the best available approved therapies.
Speaker 2: and in many cases having failed various investigational drugs or prior hematopoietic stem cell transplants. These are incredibly difficult patients to treat and to reverse the disease progression. What makes these patients even more difficult to treat is the extreme diversity of highly adverse genetic and epigenetic alterations expressed by their disease. If you recall the admiral trial from just five years ago.
Speaker 2: during which the commercial dose of Gilteritinib, a FLIT3 inhibitor, was tested for responses in AML. The patients were second line, essentially had not seen other FLIT3 inhibitors, and had not seen Venetoclax.
Speaker 2: In contrast, patients entering our trial are far more treatment experienced, with half failing prior venetoclax, 60% failing prior treatment with hypomethylating agents, or HMAs, more than a quarter having failed transplants, and half of the FLT3 mutant patients having failed prior therapy with a FLT3 inhibitor.
Speaker 2: Nevertheless, TUS has delivered responses with convenient, once daily oral dosing of tablets across four dose levels, 160 mg, 120 mg, 80 mg, and 40 mg, and no DLTs were observed with any of those active dose levels.
Speaker 2: From a mutation sensitivity perspective, TUS has shown an unprecedented breadth of activity. TUS delivers responses in FLT3 wild-type patients, as well as it does in FLT3 mutated patients. We also have seen responses in AML patients having the very difficult to treat TP53 mutations.
Speaker 2: as well as patients with NPM1 and FLIT3 co-mutations, and patients having alterations in the DNMT3A, RONC1, IDA1, splicing factors, ASXL1, and MLL genes.
Speaker 2: But one of the most interesting observations is the activity in relapsed refractory AML mutations with RAS mutations.
Speaker 2: Mutations in the RAS pathway serve as an escape mechanism to generate resistance to many other drugs. However, we've measured a 42% overall response rate in patients with RAS mutations.
Speaker 2: including a 29% CR CRH response rate. In fact, one patient had a RAS mutation and a mutation in PTPN11, representing a dual mutation in the RAS pathway.
Speaker 2: We will continue to monitor the response rate in RAS-mutated AML patients this year and determine if RAS-mutated relapsive refractory AML patients may represent a population of high and met need for future accelerated approval trials. As Dr. Behar will describe in further detail in a few minutes.
Speaker 2: We wrapped up our highly successful Phase 1-2 dose escalation and dose exploration trial. We've treated over 60 patients to date in that trial. We've assembled a strong safety data package.
Speaker 2: We selected safe and effective doses for our single agent and drug combination trials. We demonstrated the ability of TUS to dramatically reduce bone marrow blasts in a high fraction of patients and to achieve formal responses. And we initiated our activate dose expansion study of TUS.
Speaker 2: in a single agent and in combination with Venetoclax. In the AFTIV8 trial this year, we will enrich certain patient populations to receive monotherapy so that we can collect data to guide our conversations with the FDA to request an accelerated approval path for TUS in patients of high and met need. In parallel with the AFTIV8 monotherapy dosing, we will treat a broad array of AML patients with a combination of TUS,
Speaker 2: referred to as the TUSVIN doublet. This TUSVIN doublet is being conducted to support doublet combination registration trials and second line AML patients.
Speaker 2: and to serve as a bridge to a pilot study of TUS, plus VIN, plus a hypomethylating agent, or the TUS-VIN HMA triplet in frontline AML patients.
Speaker 2: While TUS clearly can deliver responses as a single agent, the ultimate goal in commercial of success of TUS or any drug for AML will be in combination with other drugs.
Speaker 2: As of this week, we have begun enrollment of AML patients on the TUSVIN doublet, and we will place additional patients on this doublet throughout 2023.
Speaker 2: Once we gain experience with the doublet, we plan to initiate the TUS-VIN HMA triplet in frontline patients.
Speaker 2: The future of AML therapy will also revolve around cocktails of drugs and earlier lines of therapy to take patients into deep remission.
Speaker 2: Such AML cocktails will require the blending of drugs that best can serve broad populations of patients, and deliver the permissions...
Speaker 2: and can be tolerated without cardiotoxicity, unnecessarily prolonged myelosuppression, and other complicating side effects.
Speaker 2: And this precisely describes TUS. TUS is positioned to become the ideal partner for addition to the then HMA doublet because of its convenience as a once-daily oral agent, its broad activity, and its safety profile. Together, day-to-day, point TUS toward application as a monotherapy for accelerated approval in relapse to refractory AML.
Speaker 2: as doublet therapy for accelerated approval and second line EML, for use in triplet combination and frontline patients, as well as a use in maintenance therapy. And Dr. Behar will provide you with additional color of these activities momentarily. Now let me turn briefly to Luxefative. Many of you know it as CG806.
Speaker 2: LUX, as we typically refer to it, is our secondary pipeline program. LUX is a clinical stage, small molecule, oral, FLIT3, and BTK kinase inhibitor. LUX's ability to target kinases, operative in certain leukemias and lymphomas, led us to develop it in patients with B-cell leukemias and lymphomas, and in patients with AML.
Speaker 2: We already have reported that LUX, administered as our initial first generation or G1 formulation, delivered a CR in an AML patient and a CR in a DLBCL lymphoma patient, demonstrating LUX as a clinically active agent. You also are aware that we developed a new formulation of LUX.
Speaker 2: and we call it the G3 formulation because it represents the third generation formulation.
Speaker 2: In single dose administrations during 2022, in AML and B-cell malignancy patients, we determined that G3 formulation achieved up to 18-fold greater absorption than the original G1 formulation.
Speaker 2: Because the highest dose of the original formulation was set at 900 milligrams, we initiated continuous dosing of G3 at an 18-fold lower dose level of 50 milligrams.
Speaker 2: We continue to collect PK and safety data with G3 and AML patients, and the preliminary results suggest continuous dosing of 50 mg G3 does indeed deliver roughly equivalent plasma exposures as 900 mg of the original G1 formulation. That was the target we hope to achieve with the 50 mg of G3.
Speaker 2: Next, we plan to administer a higher dose of G3 to determine if it can achieve even greater plasma exposure levels. We will keep you posted on our findings and likely will report preliminary data around EHOP.
Speaker 2: I also want to mention that Aptos and collaborators at UCSD, Dr. Manchu Sunawal and Dr. Stephen Howell, just published an article entitled, Luxetinib Interferes with LEN-Mediated Activation of SICK and Modulates BCR Signaling in Lymphoma in the online journal PLOS One, in which we describe the ability of lux to act on the B-cell receptor pathway.
Speaker 2: at the level of the LCK and LYN, or LEN, kinases, and to influence downstream BTK activity. This relates to the role of lux to act on B-cell cancers, as well as inflammatory and autoimmunity processes. So please take a look at the article if you get a chance.
Speaker 2: Finally, we often get asked about potential partnerships for tuspetinib. In January during JP Morgan week, we engaged in productive discussions with several big pharma and biotech companies that further helped to define our priorities and to solidify our clinical plans with tuspetinib. It's clear what we need to accomplish with a drug that has such an extensive commercial opportunity.
Speaker 2: We were pleased to see that we're on the radar of these companies and interest in our program is growing. The treatment paradigm for AML is shifting toward doublet and triplet therapy and despite some successes, the current combination therapies are somewhat limited by toxicities as I mentioned previously. The proven breadth of activity and superior safety profile of tuspetinib lends itself to combination therapy, potentially as the drug of choice.
Speaker 2: addressing the most sizable markets in AML, and clearly making TUS, excuse me, the prospective big pharma drug.
Speaker 2: The data we've generated to date have helped us delineate clinical and commercial plans for tusbetinib in multiple lines of therapy, including its use in doublet and triplet combinations and as maintenance therapy. Our Chief Medical Officer, Dr. Rafael Behar, will speak about our recently initiated activate clinical trial of tusbetinib in AML as a single agent and in combination with venetoclax.
Speaker 2: as well as our extended clinical plans, which include triplet combination therapy. They also will be available for questions afterwards. I now will turn it over to our resident KOL, our Chief Medical Officer, Dr. Rafael Bejar, to talk more about our Tuspendive Clinical Plans. Re Both Steve and Dan Wireless
Speaker 3: Thanks, Bill. In January , we were thrilled to kick off the 120 milligram dosing of the Spetnib in the monotherapy arm of the Aptivase Phase 1, 2 trial. As most of you know, we have successfully completed dose escalation and dose exploration stages of our TUS Phase 1, 2 trial. Treating approximately 60 relapsed refractory AML patients who were heavily exposed to multiple agents. In fact, as Dr. Rice mentioned, we have completed the Aptivase Phase 1, 2 trial.
While we were wrapping up the dose exploration part of the study, we took the prudent step of putting additional patients on the lowest 40 milligram treatment group because of the FDA's project optimist that emphasizes dose exploration during early development of oncology products. This experience gave us the additional data needed to support our monotherapy dose selection and was not born out of the safety concern. Rather, as higher doses of this bed have shown an impressive safety profile. Since we lost the 40 milligram dose level late last year, we have achieved two clinical responses in that low dose group.
both AML patients with unmutated Flut3, including the most recent, harboring a challenging TP53 mutation, one of the most highly adverse somatically mutated genes. Importantly, this is the second TP53 patient that has achieved a clinical response. The first was at the 80 milligram dose, who achieved an unqualified CR at their best response. So we look to enroll more of these patients who with such a poor prognosis have a great unmet need in the after they trial.
The ACTIVATE expansion trial is designed to confirm monotherapy activity through patient enrichment of specific mutationally defined AML populations, including the TP53-mutant patients, as well as split-3 mutated patients who have been failed by prior for 3 inhibitors, as supported by an FDA fast-track designation and a clinically significant response rate to date.
These patients continue to have great unmet medical needs, and we believe that the ability to rescue these patients and perhaps allow them to receive a central transplant, which we have now done with several patients in our study, would allow us a quicker path to registration. In addition to being a potential accelerated approval pathway for tispenid, treating these subgroups would provide critical data to inform our continued development path.
I am pleased to say that we have begun treating patients in the monotherapy arm of the Apt-V A trial and that a growing network of clinical sites and investigators are engaged in enrollment and that this has been brisk.
In the activate expansion trial, this bed-in also will be tested in combination with Venetoclax. Several sites now have regulatory clearance and both drugs in hand, allowing us to initiate patient enrollment on the TUS-VEN combination earlier this week. Having the TUS-VEN combination arm open is an important advance.
as this represents an attractive treatment option for patients and their physicians, leading them to enroll earlier in the course of treatment, increasing the likelihood of achieving a meaningful clinical benefit. So, what is our timeline for our clinical trials? Because Aptivate is an open-label trial, we will report data when available at appropriate forums.
We will have an update around EHA in June , for example, as we usually do, but because data collection and verification does take time and Aptivate has only been open for a short while, this will be an incremental update. We would expect to have more complete data, particularly for the monotherapy arm, at the European School of Hematology meeting, ESH, at the end of October in Estro Portugal. Expect more data, including from the TUSVIN combination cohort, to then be updated at ASH in San Diego in December .
So, 2023 will be a busy year for us. Having tested to Spetinib in specific genetically defined populations, we would expect to have sufficient patient data this year and then segue into phase two registration studies to support accelerated approval. As Dr. Rice mentioned, we are including relapse or refractory AML patients with unmutated foot 3, what we often call wild type patients, that have other adverse mutations, exploring safety and activity in these patients with Spetinib.
treatment both as a single agent and in combination with the netoclax. Identifying meaningful activity and other adverse subgroups could lead to other options for accelerated approval. The paradigm for the treatment of AML is increasingly moving towards combination therapy. We hope to position dasbetinib as a preferred agent for combination and use in earlier lines of treatment. It is our hope and based on our data thus far is our expectation that we will move forward dasbetinib in a triplet combination.
and in maintenance settings. Dr. Nabel Dauber from MD Anderson, who's been one of the investigators pioneering AML combination therapies in Venetoclax, is our lead investigator on Abtivate and is eager, as we are, to see what the Spendit can do in this setting. We'll also highlight a few comments from Dr. Harry Urba of the Duke Cancer Institute during a recent KOL event. He noted that this drug may be better suited for the combinations that we hope to develop than anything we have right now.
And he was excited about the apparent lack of myelosuppression, noted in our clinical study to date. And he emphasized that a drug like TUS will have a position mostly because it has better toxicity profiles than the drugs we're using now in terms of myelosuppression. Clearly we agree wholeheartedly with Dr. Urba and we believe that potency, breadth, and anti-lucan activity, along with the safety profile, make us better the ideal drugs for combination therapy and scalable commercialization. On our website, you can see our projected timeline for ongoing and planned clinical trials. I want to thank our clinical team for their hard work and execution in getting both arms of activate expansion study up and running.