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spk06: Thank you. Good afternoon. My name is Chris, and I'll be your conference operator today. I would like to welcome everyone to Apto's Biosciences conference call for the third quarter ended September 30, 2020. At this time, all participants are in a listen-only mode. After the speaker's remarks, there will be a question and answer session. If you would like to ask a question during this time, simply press star followed by the number one on your telephone keypad. If you would like to withdraw your question, please press the pound key. Thank you. And as a reminder, this conference call may be recorded. I would now like to introduce Ms. Susan Pietropaolo. Please go ahead.
spk01: Thank you, Chris. Good afternoon and welcome to the Aptos Biosciences Conference Call to discuss financial and operational results for the third quarter ended September 30th, 2020. I am Susan Pietropalo, a communications representative for Aptos Biosciences. Joining me on the call today are Dr. William G. Rice, chairman, president, and CEO, Mr. Gregory Chow, executive vice president and chief financial officer, Dr. Yodi Morongo, senior vice president and chief business officer, Dr. Rafael Behar, senior vice president and chief medical officer, Do you all hear that?
spk03: No, we can hear you.
spk01: Before we proceed, I would like to remind everyone that certain statements made during this call will include forward-looking statements within the meaning of U.S. and Canadian securities laws. Forward-looking statements reflect Aptos' current expectations regarding future events. but are not guarantees of performance, and it is possible that actual results and performance could differ materially from the stated expectations. They involve known and unknown risks, uncertainties, and assumptions that may cause actual results, performance, and achievement to differ materially from those expressed. To learn more about these risks and uncertainties, please read the risk factors set forth in Aptos' most recent annual report on Form 10-K and SEC and CEDAR filings. All forward-looking statements made during this call speak only as of the date they are made. Aptos undertakes no obligation to revise or update the statements to reflect events or circumstances after the date of this call, except as required by law. I will now turn the call over to Dr. Rice, Chairman, President, and CEO of Aptos Biosciences. Dr. Rice?
spk03: Thank you, Susan. I'd like to welcome everyone to our call for the third quarter ended September 30, 2020. We are well into the year, which for Aptos has been a year of advancing our clinical programs. with our recently initiated AML clinical trial, we now have three clinical studies underway. Two studies with our FLIT3 and BTK kinase inhibitor CG806. One study in patients with acute myeloid leukemia, or AML, and the other study in patients with chronic lymphocytic leukemia, or CLL, and non-Hodgkin's lymphomas. And the third trial is ongoing with our MYC inhibitor, APTO253, in patients with AML and MDS. We now are at a point where we are operating smoothly across the board, expanding our drug substance and drug product manufacturing, working with our clinical sites to enroll the right patients for each trial, accelerating the pace of development, and treating a spectrum of patients with very challenging relapsed or refractory hematologic cancers. The third quarter was one of blocking and tackling to position our agents for success. We expect the rest of 2020 to be one of continued executions. especially as we treat more patients at higher doses and begin to generate additional pharmacokinetic and pharmacologic data. And before we discuss the progress in each of our three clinical programs, let me remind you that ASH is only a few short weeks away. So today we will keep our remarks at high level and qualitative, and then we will aim to share more quantitative findings during ASH. Having said that, first let's start with our most recent news. In October, we announced the initiation of dosing in our Phase 1 AB clinical trial of CG806 in patients with relapsed or refractory AML, which, as you know, is a very serious cancer of the bone marrow and blood and that carries a poor prognosis. CG806, or just 806, inhibits the wall type and mutant forms of FLT3 and BTK and suppresses select clusters of kinases that drive oncogenic signaling pathways that are operative in AML, including the FLT3, PDGFR-alpha, CSF1 and R, AKT, RAS, ERK, STAT, and SICK pathways. And by the way, when we refer to SICK, that is the spleen tyrosine kinase inhibitor, spelled S-Y-K, not S-I-C-K. As you will recall, 806 is the only known clinical agent that potently inhibits both FLT3 and BTK, which gives it a broad therapeutic potential across the spectrum of lymphoid and myeloid hematologic malignancies, including AML. Our AML trial is a Phase I AB multicenter open-label dose escalation study of safety, pharmacodynamics, and pharmacokinetics of CG806 and ascending cohorts with a 3 plus 3 design to determine the maximum tolerated dose or the recommended Phase II dose in patients with relapsed or refractory AML. We've highlighted this before, but I want to quickly remind you again that these relapsed or refractory patients are very ill, and before joining the 806 trial, they already have been treated with and failed other FLT3 inhibitors such as giltritinib and or monostorin and other drugs such as venetoclax and have failed or are intolerant to the available approved therapies. The standard of care for relapsed or refractory AML patients is insufficient for many patients. often not durable and or leading to resistance. So despite recent advances, there remains a tremendous unmet need in relapsed or refractory AML patients. In this AML trial with 806, the FDA allowed us to skip the two lowest dose levels of 150 milligrams and 300 milligrams and to initiate dosing at a starting dose of 450 milligrams BID, which, as I mentioned in our last call, was good news for Aptos and for 806. We requested the 450-milligram starting dose in AML patients because that dose, when administered to CLL patients in a separate clinical trial, appeared safe, well-tolerated, and achieved plasma levels that effectively inhibited phosphoflit-3 activity, which is a key driver of AML. Also, at the 450-milligram dose in humans with CLL, we observed steady-state plasma levels in the same range as the exposure levels observed in our preclinical work that led to cures of AML in mice and with no observed toxicity. It was these observations in their totality that led to the starting dose of 450 milligrams. I'm pleased to report that since we announced dosing of our first patient in the AML trial, we efficiently enrolled additional patients in this cohort. Investigators at major clinical sites are eager to place their relapsed or refractory AML patients on 806 and they have patients available when slots open. The trial design is the traditional 3 plus 3 dose escalation, but it also allows us to enroll more than the minimum three patients at each dose, if appropriate. Five clinical sites currently are screening patients for the trial, including high-caliber academic cancer centers and specialty care regional sites. Having several highly engaged clinical sites now treating patients, we are pleased with the pace of enrollment. Some of you have asked us specifically which type of AML patients have been enrolled in the study. It always has been our intention, and now we are enrolling patients having AML with the FLT3 ITD mutation, referred to as FLT3 positive AML, as well as patients with wild-type FLT3. In addition, we believe 806 is a compelling candidate for the fragile AML patient population, and we are hopeful that 806 can provide benefit to the very ill, relapsed, and refractory AML patients. We will share up-to-date specifics on the AML trial at a corporate update that we plan to hold during the ASH timeframe. For more information on the AML trial and clinical sites that are recruiting patients, please visit clinicaltrials.gov. Now let's turn to our ongoing Phase I AB dose escalation study of 806 in patients with B-cell malignancy. including CLL and non-Hodgkin's lymphomas, again, in relapsed and refractory patients who have failed or are intolerant to current therapies. Since our last call, we escalated to the fifth dose level of 750 milligrams, and we continue to treat patients at the 600 milligram and 750 milligram dose levels. Importantly, at the 750 milligram dose, we are focusing exclusively on and enrolling only relapsed or refractory CLL patients. A CLL is where we have observed indications of on-target activity in prior patients. To date, in addition to inhibition of BTK and the induction of on-target lymphocytosis that we reported previously, we have observed nodal reductions in CLL patients. We fully understand that these are deep refractory patients that may require extended time to truly respond, if ever, but we are hopeful that such findings will portend formal responses as we accrue additional CLL patients over time. And we plan to provide you with additional color during ASH, which is just a few weeks away. Depending on the level of clinical activity in specific subgroups in this dose escalation phase, we may enroll patients across expansion studies that include subpopulations with different genotypic or phenotypic properties. In conjunction with the CLL trial, And to facilitate expansion studies, we have developed a scaled-up manufacturing process for 806 capsules and are transitioning to machine-filled capsules, also called automated-filled capsules, and these are being introduced into the trial. This step reduces risk to the 806 program and will allow us to place additional cancer patients on 806. For more specific information on the B-cell malignancy trial and the clinical sites that are enrolling patients, please visit clinicaltrials.gov. Again, we will share a more in-depth update of our entire 806 program with you during ASH. Speaking of ASH, we also announced last week in a press release we will be presenting two posters on Saturday, December 5th, one on CG806 and one on APTO 253. And there will be another poster on CG806 presented on Sunday by our research partners at the City of Hope and the Oregon Health and Science University, or OHSU. Details are in a press release that we distributed last week, and the abstracts themselves are now available online. Overall, we continue to execute carefully and diligently in multiple parallel programs, and we believe this ASH conference represents yet another milepost in our steady development of 806. As we have stressed before, we believe that 806 is a drug candidate like no other, with singular biology and a broad array of potential indications. Based on our work to date, we remain confident in the potential of 806 to manifest benefit for cancer patients and build value for Apto's shareholders. Now let me bring you up to date on the status of Apto253, our second clinical candidate currently in a Phase 1b trial for AML and MDS. To remind you, Apto253, or just 253 as I'll call it, is a MYC inhibitor, and the MYC oncogene is a major driver of cancer cell proliferation, including hematologic cancers. In fact, it is one of the most coveted drug targets in cancer, and researchers have been seeking a safe MYC inhibitor for many years. Per our Phase I clinical protocol, 253 is being administered once weekly over a 28-day cycle at ascending doses. In patients with relapsed or refractory AML or high-risk MDS, until the maximum tolerated dose is reached. The study is designed to then transition as appropriate to single agent expansion cohorts in AML and or MDS. I'm pleased to report that our phase one clinical trial of 253 is progressing well. Thus far, we have completed the 28 dosing in the first four dose cohorts. Since our last call, we've enrolled multiple patients at dose level five of 150 milligrams per meter squared. which is a 50% increase over that of dose level 4, and 253 continues to be well-tolerated. Despite interest in MYC inhibition as a target, 253 has been advancing quietly under the radar screen, partly because nobody knows what to expect clinically from a MYC inhibitor. We're learning more as we proceed, and we continue to believe P253 is an interesting and valuable asset worthy of investment. At these higher doses, we hope to see sustained MYC inhibition and begin to see clinical responses. We'll be able to talk to you more about 253 during our event at ASH. For those of you interested in learning more about the trial specifics and enrollment criteria, please visit clinicaltrials.gov. Finally, let me just quickly touch on other corporate highlights. We're grateful to be a part of recent and upcoming healthcare banking conferences. During the quarter, we presented at the Canaccord Genuity H.C. Wainwright, Cantor, and Oppenheimer conferences, where we hosted a full schedule of one-on-one meetings. We also have been invited to the Stiefel Healthcare Conference, where we will be hosting one-on-one meetings next week, and we will be participating in the Piper-Sandler Healthcare Conference in early December. I now will turn the call over to our Executive Vice President and Chief Financial Officer, Mr. Greg Chow, who will review results for the quarters.
spk05: Thank you, Bill, and good afternoon, everyone. We entered the quarter with approximately $133 million in cash, cash equivalents, and investments, compared to approximately $83 million at June 30 of this year. During the quarter, we utilized approximately $8.3 million of cash in operating activities, which were attributable to activities surrounding 253 and 806, as well as general and administrative purposes. Based on current operations, cash on hand at September 30 provides the company with sufficient resources to fund all planned company operations, including research and development, into Q1 of 2023. Moving on to the income statement, we had no revenues for the quarter. Research and development expenses were $7.5 million for the quarter and attributable to 806 and 253 clinical trial costs. Manufacturing of drug product for clinical trials, including continuing development on improving GMP formulations for 806 and 253. and personnel costs for headcount supporting clinical trials and manufacturing activities and research studies. General and administrative expenses for the quarter were $5.8 million, and our net loss for the quarter was $13.2 million, or 15 cents per share. More detailed information can be found in our filings on EDGAR and CDER. I will now turn the call back over to Dr. Rice. Bill?
spk03: Thank you, Greg. I'll remind everyone that on the line we also have with us Dr. Yodi Morongo, our Chief Business Officer, and Dr. Rafael Behar, our Chief Medical Officer. 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.
spk06: Thank you. At this time, I would like to remind everyone that if you would like to ask a question, please press Start on the number one on your telephone keypad. We'll pause for just a moment to compile the Q&A roster. Your first question comes from the line of Gregory Renza with RBC Capital Markets. Your line is now open.
spk08: Hey, good afternoon, good evening, Bill and team. Congratulations on all the progress, and thanks for taking my questions. Bill, I just wanted to start, of course, just the natural question is really some of the expectations that you are able to set for the upcoming event and ASH data. Now, I do respect that. your acknowledgement of speaking more qualitatively, but maybe we can just start on the AML side, as you mentioned, certainly enrolling in October. Maybe just remind us some of those data collection points and what you think could be meaningful or what to look out for just in light of where we will be just several weeks post the start of those patients in the trial. Thank you.
spk03: All right. Hey, Greg, thanks for joining us and thanks for the question. So in particular on the AML side, yes, as we look back to the third quarter, we had the IND allowed that allowed us to go into the AML patient population. We then had to, as I mentioned, the blocking and tackling, get all the clinical trials up and running, ready the sites, IRB approvals. And in the era of COVID, it's a little bit more challenging, but the team did that, and we actually enrolled our first patient during Q3. Since that time, we've had active enrollment. The clinical sites have been very active. I'm not speaking directly to the number of patients that we've put on the study yet. I can say it's definitely more than one. Hopefully, we'll be able to collect sufficient data between now and then to give you a snapshot of what we're seeing in these patients. Of course, we hope that the drug is going to be well-tolerated. We're at the 450-milligram dose level. It has been tolerated well in the past at that dose level. But this is a new patient population, and these patients are very sick. So that's the first we hope to see that. We will watch for the pharmacokinetics, determine whether or not it is equivalent to the pharmacokinetic parameters that we saw in the CLL trial. And then beyond that, we will watch for any of the other CBC counts. Hopefully we'll be looking at the blast counts of the patients. But I'll also remind you that these patients, as they come off their other studies and wash out, these patients progress very rapidly. These are very sick patients. Oftentimes during that two-week washout, they go on hospices. But then you get them on the trial, and during those first couple of weeks while you're treating them, you're allowing your drug to get up to its steady state levels. And we typically don't reach that until the end of week one or week two. So we hope the patients are able to stay on during that period, give the drug time to reach those steady state levels, and we actually hope to see some level of benefit in these patients. I don't know if we'll have time on these patients to really see if there are any truly meaningful data, but we're several weeks away. We will continue to collect the data between now and then, and then we'll indicate where we are at that time. I don't want to either over-promise or under-promise. What we'll do is present you what we have at that time. But I will remind you that the data will not be, quote, verified because it takes at least a month looking back at your clinical trials and the sites to collect the data, verify it through your clinical operations group, and then be able to present verified data. So anything that we discuss will be non-verified and preliminary data at that time. But we are very hopeful for the AML. Hope that answers your question.
spk08: It sure does, Bill. And if I may, just one follow-up on the CLL. Si, I think you just remind us and certainly heard the commentary on, you know, expansion potential of cohorts and subpopulations. Could you just remind us of your latest strategy on the plans for a 900-meg dose level on the cohort there, just in terms of how we'd be thinking about that, of course, you know, with respect to understanding cards have to turn over in the current dosing levels. But I just want to get a refresh on your thoughts there. Thank you.
spk03: Well, in this protocol, we do have the ability to go to a 900 milligram dose level if the 750 milligram dose level is determined to be safe. That requires three patients to complete at least 28 days of dosing. Currently, we're at the 750 milligram dose level. We haven't released any additional information on that level or the lower dose levels, the 600 milligrams, except to say that we do have patients on the 600 and the 750 dose. During ASH, we will be presenting data that we have on these patients. In particular, we want to be able to show that the pharmacokinetics, we want to hopefully show that these are rising as we continue to dose escalate the patients. And then we'll be able to speak to whether or not we'll be able to go up to the 900 milligram level or not. If we are, if everything is safe, and if we are able to move up, we will, provided we are continuing to get increased levels of exposure as we've gone from 150, 300, 450, 600, and 750. If we can show that we're continuing to get additional exposure, then we would go up to 900. If it turns out that for some reason we cannot go to 900, we would look to 750 to say, is that our recommended Phase II dose? If for some reason 750 turned out to be too toxic for some reason, then we would back down to the 600, which we have shown is safe. So all of those are possibilities at this time. That's correct.
spk08: Thanks, Bill. Looking forward to the updates in December.
spk06: Thank you. Thank you. And your next question comes from the line of John Newman with Kenaccord. Your line is now open.
spk11: Hi, guys. Thanks for taking my question, and looking forward to the data upcoming at ASH here. Bill, I just wondered if you could comment. I think during your prepared remarks, you talked about some nodal reductions in CLL patients. Just wondering if you could elaborate on that just a little bit more
spk03: Sure, John. Thanks for the question. So we refer to these as nodal reductions. Of course, some people call them nodal reductions. Some call them tumor reductions. So whenever a patient comes on the study, they get their initial scan before they start dosing with any of the drugs. And at that point, they identify the target lesions that they're going to follow throughout the therapy. And typically, these are lymph nodes. And so we will refer to them as either nodal increases, nodal reductions. And I'm gonna be really careful here because we don't want to overplay this or underplay it. So we've been asked repeatedly whether or not we're getting nodal reductions in any of these patients. And what I can say is, yes, we have seen reductions in more than one patient. But as of yet, they are not at the level of formal responses. If they were, we would have said formal responses. So we have cautious optimism that we have been able to see some decreases, but again, we're very realistic. These are deep, relapsed, refractory patients who have failed all the drugs out there, including many of our competitor drugs, before they come on to our trial. Where we have seen reductions, we would be thrilled if those reductions continue and if they ever reach the target. the level of a formal response. But they may not. They may plateau off, or the patients could continue to progress at any time. So that's why we're being very careful and very candid in saying, yes, we've seen notable reductions, but it is not at the level, the formal level, of a true reduction at this point. Did that adequately answer your question, or did you want to follow up?
spk11: Yes, and I had one quick additional question, which was for the AML study you mentioned at the beginning of the call that you are looking to enroll both FLT3 ITD patients as well as wild type. Is there any specific ratio that you're looking to achieve, or are you simply looking to include both types of patients with those mutational steps?
spk03: Well, again, we've been very upfront about this, and we believe this drug can treat patients with both wild type as well as FLT3 positive with the ITD mutation in FLT3. We would like to keep, at least in the early dose cohorts, the number of wild type patients, FLT3 wild type, to a minimum. We'd like to get one, maybe two on there, but we'd like to have the majority of the patients be FLT3 positive patients. Why? Why? We know that the patients who are FLT3 positive tend to react or respond more quickly to a FLT3 inhibitor. And so I hate to use the word low-hanging fruit, but it really is. Those would be what you would expect to be the most responsive patients to a FLT3 inhibitor. So we clearly want to get multiple FLT3 positive patients on each of these dose levels. But as we go, we continue to dose escalate and get to the higher dose levels. And once we're able to show activity in the FLT3 positive patients, assuming that we will, we would then want to transition over and get more of the FLT3 wild-type patients on the study as we continue to dose escalate, because it might take additional levels of drug to be effective against the patients with wild-type FLT3.
spk11: Great. Thank you.
spk06: Thank you, John. Thank you. And our next question comes from the line of Alethea Young with Cancer Fitzgerald, your line is now open.
spk04: Hi, thank you for taking my question. This is Emily on for Alethea. I was just wondering, what have you learned from the CLL study so far that has kind of helped you speed up the process and AML besides the starting dose that you mentioned? And how many more patients do you think you could potentially enroll in the CLL study by NASH? Thank you.
spk03: Hi, Emily, and please tell Alethea we said hi. So what did we learn? So as you said, the starting dose, that was very important for us. But also from the plasma that we collected from those patients, we learned that the exposure levels were at or above the levels that gave us true responses in animal models. So they cured animals of AML. That was FLT3 ITD or FLT3 positive AML in mice. And we're achieving those exposure levels in humans. The other thing is, in the humans, when we collect the plasma, we bring those back to the laboratory and put them on reporter cells. We have reporter cell systems now that allow us to look at FLT3 wild type and FLT3 ITD, FLT3 positive cells. And we've been able to see that we can turn off the fossil FLT3 activity in those cells, whether it's ITD or wild type. But beyond that, we were able to, the plasma, not we, the plasma was able to turn off the the activity of other of these pathways that I mentioned earlier, whether it's the PDGFR-alpha, SICK, ERK, STAT, all these various pathways downstream. So that's what gives us comfort that once we go into AML patients, we hope that the drug is at a level that can then have those effects in an AML patient, and hopefully we can begin to see responses in those patients over time. In terms of the number of patients, we haven't disclosed that yet publicly, so we'll be disclosing the number of expected CLL patients as well as AML patients during ASH.
spk04: Okay. Thank you.
spk06: Thank you. Thank you. And our next question comes from the line of Joe Panzini with HC Wainwright. Your line is now open.
spk07: Hey, guys, good evening. Thanks for taking the question. Bill, I wanted to take the commentary you had on the nodal responses just a little further, if I may, but I suspect my question might fall into the quantitative range, not the qualitative. So I was just curious if you could describe maybe how many responses, when they were seen within the treatment time period for the patients, and at what doses.
spk03: Yeah. Hi, Joe. It's great to hear your voice, and I'd be disappointed if you didn't ask that question. But you are right. That falls into the quantitative arena. Dr. Behar will be presenting those data during ASH. He has a video presentation. But I will remind you that we won't have all the up-to-date information at that time. He has to record the presentation on the 18th of November, which means you have to back up in time about a month or so to validate all the data, the scans. So he will be able to incorporate some of the data into that presentation. And then around that presentation, which actually will be presented, I believe, on what, the November 4th and 5th, those timeframes, excuse me, December 4th and 5th, those timeframes. We will provide you with any additional updated information that we have at that time. Again, we hope to see some continued reduction in those, but absolutely no guarantee. And I don't want to, as I said earlier, either over or under promise there. It's just this is what we have. It's not yet at the level of formal response. But once you start seeing this effect, you believe you're getting into the area, the exposure levels that may be able to deliver responses if you get the right patients on and they're on for the right amount of time. But we'll provide as much data as we can, quantitative data, at the time of bash. But thank you, Joe, for asking.
spk07: No, totally understood. Thanks a lot, guys.
spk06: Sure. Thank you. And our next question comes from the line of Matt Begler with Oppenheimer. Your line is now open.
spk09: Hey, guys. Thanks for taking my questions. Sorry to beat a dead horse here, but just on the nodal responses, is the fact that you're seeing lymphocytosis precluding your ability to classify the nodal responses as objective responses, or is blood counts not at all a factor here?
spk03: No, as we've said before, we've achieved dose levels or exposure levels that inhibit BTK and that give us the on-target lymphocytosis. So that tells us we're hitting the target and other pathways too. But that doesn't tell you whether or not you're going to get responses in a patient. Sometimes you get lymphocytosis and it will then diminish and then you'll get responses. Sometimes you'll get responses without lymphocytosis. Sometimes the lymphocytosis will occur, and it will not drop down, and you get responses. So it is specific to each patient, the response of your drug. And so there's no cut and dry type of pattern that we could expect. So perhaps Dr. Behar could expand on that a little bit to give you his thoughts.
spk02: Yeah, I think the way you stated it is exactly right, that in order to have a PR for a CLL patient, or following the IWCLL criteria, there's several different aspects there that need to be met. And it may be different aspects for different patients that are the limiting ones before you can say that a patient has had a formal response. It could be the lymph node size. It could be organomegaly. It could be the lymphocyte count. And they're not necessarily the same for each patient.
spk03: Thank you, Dr. Beckmar. Did that answer your question?
spk09: Yes. That's very helpful. I was a little confused because I've seen some studies report a PR with lymphocytosis, and I wasn't sure if that was different than a nodal response, but it sounds like it's different.
spk03: Okay. Well, you can get a reduction in 50% of the nodal size, and that would be a nodal PR, even with the continuation of lymphocytosis.
spk09: Got it. Got it. And just quickly, can you confirm when the first marrow response assessment is in the AML trial?
spk03: No, we can probably speak to that a little bit more when we get out to ASH. Typically, it will be a couple of months out. Depending on what you see in the patient, the physician will make a decision. If you're several months out, typically, let's say two cycles out, if you're really seeing something in that patient that they want to make a judgment call, then they might want a bone marrow at that time. But if they're not seeing anything, then they would likely wait. Dr. Behar may also want to opine on that.
spk02: I would just add experience from other FLIP3 inhibitor studies and how long it has taken the average time to see a response. The median time for some of these studies was between two and three cycles of therapy, so two and three months of therapy. It might be when you expect to see most patients to respond who are going to respond.
spk09: Thank you. Got it. Thanks, guys. Looking forward to Ash. Okay. Look forward to seeing you. Thank you.
spk06: Thank you. And again, ladies and gentlemen, if you would like to ask a question at this time, please press star and then the one key on your touchtone telephone. Our next question comes from the line of Matthew Cross with Alliance Global Partners. Your line is now open.
spk10: Hey, guys. Thanks for the pre-ASH update and for taking a couple of questions from me. Really just a couple of clarifications on my end. I think going back to John's question regarding the FLT3 status of patients who may be enrolling in the AML trial and looking at some screening around that or maybe at least some targets for what kinds of patients you'd like to see. I just wanted to confirm, you mentioned, Bill, the focus on having some wild-type patients, some FLT3 ITDs. Does that exclude, I guess, should we be thinking about this as FLT3 positive versus wild type, or would that also include beyond ITD, TKD, and some of these more rare subtypes therein as you're looking to meet those kinds of populations?
spk03: Well, hi, Matt. Great of you to drill down into the details. Yes, when people typically say FLT3 positive, typically they are referring to the FLT3 ITD. So I like to break it out personally and say either FLT3 ITD or FLT3 TKD. We would like to have some of those patients on study. And what we're gonna find is these patients have been treated with so many drugs, other FLT3 inhibitors, venetoclax, all the various drugs out there and combinations. They are going to have a variety of mutations. You might find some that have the ITD plus TKD mutations. They may have the TKD but not the ITD. It depends upon the sequence of drugs that they've had in the past. So over the period of this trial, we would love to see a variety of these patients, those that have RAS mutations, P53 mutations, IDH1, so all the various mutation types. But at least initially, we wanna make sure that we can get some FLT3 positive patients in there, the FLT3 ITD patients that are most likely to be able to have a response to the drug. especially at the lower doses here, the 450. Once we get into the higher doses, maybe up to 750 or so or above, at that point we might be able to see activity with the patients that have a variety of these other mutations along with the platelet-3-IGD. Fair enough?
spk10: Fair enough. Yeah, no, thanks for correcting me on the nomenclature, and that makes perfect sense. Then I guess on the B-cell side, in your remarks, you'd mentioned looking to focus at the 750-milligram dose level exclusively on CLL, which I know you've kind of echoed in the past, wanting to at least steer the trial investigators towards looking at those patients in particular at these higher dose levels. It looked like, and this is obviously dated, but in the abstract, you had an MCL patient and a Waldenstrom's patient come on, So I guess just thinking specifically about the 750 milligram group and that CLL focus, is that something that would be really more of a preference communicated to these sites or something that might be in the form of a full protocol amendment around enrollment criteria for maybe those dose levels going forward?
spk03: Another drill-down question. So, yeah, when I talk about the third quarter, it was blocking and tackling. So this is one of the decisions we made. So getting up to the higher dose levels, all the way up through 600 milligrams, we accepted a variety of different types of patients, a variety of different lymphomas, CLLs, SLLs, all of them, to try to get to that higher dose level as quickly as possible, and hopefully to be able to keep some patients on there. But once we reached the 750 milligram dose level, we made a decision that at that dose level and beyond, we're gonna focus exclusively on the CLL patients at this point. We did go back and we've communicated that to the sites as a preference. It's not always what they want to hear because they also have lymphoma patients they'd like to get on there. But they understand what we're doing, they're understanding why, and these are the patients that are most likely to give nodal reductions, types of responses, so that you can determine whether or not your drug actually has activity in this patient population. And then it makes it a more developable drug. I know it's not a real word, but developable for these other types of lymphomas going forward. So that's where we are right now. Again, that did slow the accrual because we're not taking the lymphomas anymore. We're focusing on the CLL patients. And we also observed that a lot of these patients are very sick, patients that are failing the other drugs that are out there, competitor drugs. But we're happy to get these patients. We're hopeful that we can provide them to get them stabilized and then hopefully over time to be able to show benefit.
spk10: Okay, great. Thank you for having good answers, as always, to me getting into the nitty-gritty a bit. And looking forward to the full details next month.
spk03: Absolutely. Thanks so much, Matt.
spk10: Thank you.
spk06: I'm not showing any further questions on the phone at this time. I would now like to turn the call back to Dr. Rice for any closing remarks.
spk03: All right, I want to thank all of you for joining us this afternoon. I'm very proud of our organization, the people, the investigators who are really top-notch at all these clinical sites, and importantly, the patients and their family. Everyone who's participated in these trials and advancing our important work, whether it's the clinical trials or related to manufacturing, we appreciate the support of all of our shareholders and the analysts who are coming on here today and digging into the data, and we look forward to keeping you apprised for our progress And I want to say thank you and have a good evening, everyone.
spk06: Ladies and gentlemen, that concludes today's conference call. You may disconnect. Everyone have a wonderful day. you music music
spk00: Thank you. you
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