Curis, Inc.

Q1 2021 Earnings Conference Call

5/12/2021

spk04: Good afternoon, and welcome to QRIS's first quarter 2021 earnings call. All participants will be in listen-only mode. Should you need assistance, please signal a conference specialist by pressing the star key followed by zero. After the company's prepared remarks, call participants will have an opportunity to ask questions. To ask a question, you may press star, then one on your touchtone phone. To withdraw your question, please press star, then two. Please note, this event is being recorded. I would now like to turn the conference over to the company's Chief Financial Officer, Bill Steinkraus. Please go ahead.
spk02: Thank you, and welcome to QRIS's first quarter 2021 earnings call. Before we begin, I would encourage everyone to go to the investor section of our website at www.qris.com to find our first quarter 2021 earnings release and related financial tables. I would also like to remind everyone that during the call, management will be making forward-looking statements, which are based on our current expectations and beliefs. These statements are subject to certain risks and uncertainties, and actual results may differ materially. For additional details, please see our SEC filings. Joining me on today's call are Jim Denser, President and Chief Executive Officer, and Bob Martel, Head of R&D. We will also be available for a question and answer period at the end of the call. I'd now like to turn the call over to Jim. Jim?
spk07: Thank you, Bill. Good afternoon, everyone, and thank you for joining us today. Every day at Keras, we push to develop the next generation of transformative targeted cancer therapies that will meaningfully improve and extend patients' lives. In the first quarter of 2021, we took important steps towards that goal, building upon the exciting progress we made last year and expanding into additional areas where we believe we can make a difference. Our novel small molecule IRAC4 inhibitor, CA4948, is currently being evaluated in three clinical studies. First, the Phase 1-2 monotherapy study in AML-MDS I just mentioned. Second, the Phase 1-2 study in combination with ibrutinib for patients with relapsed or refractory NHL or other hematologic malignancies. And third, the Phase 2 Lucas study evaluating CA4948 in patients with lower-risk MDS, being led by Dr. Uwe Platzbecker of the University of Leipzig. We are especially pleased with the progress of CA4948 and the exciting data update published in the European Hematology Association abstracts this morning. From our Phase I-II monotherapy study in relapsed or refractory acute myeloid leukemia, or AML, and high-risk myelodysplastic syndromes, or MDS. As many of you have been following, the long isoform of IRAC4, or IRAC4L, has been recently identified as the key driver of disease in the majority of patients with AML and MDS. We at QRIS have the first and only drug that directly targets IRAC4 to enter clinical testing for these patients. Today, I am also pleased to announce that we have amended our AML and MDS study to add both a combination dose escalation and a monotherapy dose expansion. Preclinical data supporting the combination study was published by EHOP earlier today and will be presented in a poster presentation at the EHA conference next month. We expect to begin enrollment in this portion of the study in Q3. While there has certainly been a lot of attention on our IRAC4 study, it is important to note that we have also been pleased with patient enrollment in the phase one dose escalation study of our first in-class monoclonal anti-VISTA antibody, CI8993. We look forward to reporting initial clinical data for this study later this year. All told, we opened 2021 with strong momentum following our updates in December at ASH and the successful execution of key strategic financings and partnerships with premier institutions like the NCI and the European MDS Consortium that will support the continued advancement and expansion of our clinical programs. With that, let's dig into some detail on our ongoing clinical programs, starting with the IRAC4 study in leukemia. In April, we were pleased to report that CA4948 had received orphan drug designation from the FDA for the treatment of AML and MBS. This special designation represents a significant milestone for CURUS as we work to advance CA-4948 through clinical testing and, in time, seek to make it available to the patients who need it most. In the EHA abstract published this morning, we were pleased to report that the data in our AML and MBS study continue to exceed our original expectations. showing consistent single-agent efficacy across the spectrum of late-line AML and MDS patients, despite these patients having already experienced several unsuccessful prior lines of therapy. To provide some context, in conjunction with ASH last year, we reported preliminary data from six patients as of a November cutoff showing marrow blast reductions in all six patients with two of the patients demonstrating marrow complete responses and none of the patients experiencing a dose limiting toxicity at either the 200 or 300 milligram BID dose levels. The data published today, which are from 15 patients and the February 8th cutoff, showed bone marrow blast reductions in all tested doses 200, 300, and 400 milligram BID, and in eight of nine evaluable patients with elevated blast counts at baseline. Of these, one patient experienced a full hematologic recovery CR, one patient experienced a CRI with negative minimal residual disease, and two patients had bone marrow CRs. Three of these patients presented with a U2AF1 or SF3B1 spliceosome mutation, and all three of those patients achieved a marrow CR or better, validating our belief that these spliceosome mutations are specific oncogenic drivers of the long isoform of IRAC4, which CA4948 is explicitly designed to target. We were also pleased to see that all patients with objective responses showed signs of hematologic recovery. Delving a bit deeper on this point, the blast reduction data reported in the abstract this morning provide further evidence that CA4948 is effective at reducing a patient's cancer burden. For this late line patient population, having a drug that can safely and effectively get the cancer out is the immediate goal. In first-line patients, those patients whose bone marrow has not been irrevocably damaged by cancer or by prior cytotoxic treatment, it has been shown that if given a drug that reduces the level of leukemic blasts, these patients can achieve clear and substantial hematologic recovery within a few months. For the extremely sick late line population, such as the patients in our study, it is important to remember that their cancer has progressed despite numerous prior lines of therapy. As a result, these patients often have deeply scarred dysfunctional marrow, which may delay or even prevent successful hematologic recovery. It is therefore especially encouraging that we have been able to see signs of hematologic recovery even in these late-line patients after only a few months of treatment. It underscores our optimism that CA-4948 may have both a combo therapy and a monotherapy regulatory path. Overall, we are very pleased with the progress for CA-4948, and we look forward to the EHA conference where we will provide an updated and expanded data set with a later cutoff date to include additional patients, including those enrolled in our 500 milligram BID cohort. In addition, we will provide an update on safety, pharmacodynamic data, including IREC4L expression levels, and further genomics information. We have found that the 500 milligram BID dosing regimen has exceeded the maximum tolerated dose according to protocol guidelines. We observed two patients with dose-limiting toxicities, one of whom had grade three CPK elevation or rhabdomyolysis, similar to what we saw in the NHL study, and the other experienced grade three syncope. Both patients' AEs were reversible and quickly resolved after discontinuation of dosing. Now that we have established the maximum tolerated dose, we will explore the lower dose levels to determine the appropriate recommended phase two dose. I'd like to briefly touch on the preclinical data in our other EHA abstract published earlier today. These data highlighted CA4948's synergistic anti-tumor activity in combination with azacitidine and venetoclax in leukemia cells and will be presented in a poster session at EHA next month. These data demonstrate that CA4948 potentiates anti-tumor activity in certain cell lines resistant to clinically relevant concentrations of azacitidine and venetoclax. Further, CA4948 demonstrated synergistic anti-leukemic activity in combination with venetoclax and azacytidine in AML cell lines. Even before we saw these data, we knew that CA4948 was unique. It is oral. It is disease modifying. It directly targets the key driver of disease, IRAC4L, which is a novel mechanism of action. and it has demonstrated the ability to provide clear and significant single-agent activity without significant myelosuppression, including complete elimination of detectable cancer burden. With the latest preclinical data adding a possible synergistic effect as well, we and our clinical investigators are very excited to explore the combination of CA4948 with azacitidine and venetoclax in the clinic. As I mentioned earlier, this quarter we amended the protocol of our existing study to include expansion cohorts for both monotherapy and combotherapy. The monotherapy dose expansion will begin after the recommended phase two dose is determined and will include four cohorts. Patients with spliceosome mutated MDS, that is relapsed refractory to HMA, patients with MDS without spliceosome mutation that is relapsed refractory to HMA, patients with FLT3 mutated relapsed refractory AML, and patients with FLT3 wild-type relapsed refractory AML. The combo therapy study will start dose escalation at 200 milligrams BID and will include two cohorts. CA4948 plus azacitidine for patients with AML, MDS who are naive to HMA, and a second cohort of CA4948 plus venetoclax for patients with AML or MDS who are naive to venetoclax. We hope that the design of these cohorts will help to identify the most appropriate regulatory path or paths for CA4948. we expect to begin enrolling patients in these combo therapy cohorts in Q3. We may also explore a triple combination of all three drugs of CA4948 plus azacitidine plus venetoclax. But that would of course be dependent upon the initial safety and efficacy results from the two agent combination cohorts. Before moving on from leukemia, I would like to touch briefly on the ongoing IST treating patients with lower risk MDS that we announced in February. The phase two Lucas study is being led by the co-chairman of EHA's scientific working group on MDS, Dr. Uwe Plotzbecker, who will be coordinating this study in 17 sites across Europe to evaluate CA4948 for the treatment of anemia in patients with lower risk MDS. If this study is successful, it could lead to a potential breakthrough in the MDS field. While current EPO-stimulating agents can be effective for patients with lower-risk MDS who have low serum EPO, this effect is often transient and is not disease-modifying, and it does not affect progression to AML and further disease complications. With its direct non-myelosuppressive targeting of IRAC4 and its robust safety profile, we believe CA4948 could potentially offer a safe and transformative disease-modifying alternative for patients at earlier stages of disease. Now moving to lymphoma. In an oral presentation at ASH last December, We reported expanded clinical data from our phase one dose escalation study of CA4948 for the treatment of patients with relapsed or refractory NHL or other hematologic malignancies. These data highlighted durable reductions in tumor burden in six of seven evaluable patients treated with 300 milligrams of CA4948 twice daily following a median of four prior lines of therapy. It is important to reiterate that seeing clear efficacy with a novel monotherapy agent and seeing that this efficacy is durable over such an extended period of time for these extremely sick patients is enormously encouraging and provided powerful affirmation of our intention to launch the current combination study evaluating CA4948 with ibrutinib. This combination study, which began enrolling in Q1, is expected to enroll approximately 18 patients in a 3 plus 3 design with CA4948 doses starting at 200 and escalating to 300 milligrams BID. Ibrutinib dosing will be whatever is appropriate for the patient's respective NHL subtype. We expect to provide an enrollment update for this study as well as initial safety and efficacy data in Q4. Now I'd like to turn to CI8993, our first-in-class monoclonal antibody for the treatment of patients with relapsed or refractory solid tumors. Checkpoint inhibitors that function to enhance T cell priming, such as anti-CTLA-4 antibodies, and checkpoint inhibitors that relieve T cell exhaustion, such as anti-PD1 antibodies, all have two key limitations. First, T cells stuck in a quiescent state cannot be acted upon by these checkpoint inhibitors. Second, myeloid-derived suppressor cells, or MDSCs, actively impair the effectiveness of these checkpoint inhibitors. VISTA is a primary enforcer of T cell quiescence and can sequester a large proportion of T cells in a quiescent state, preventing them from being acted upon by anti-CTLA-4 or anti-PD-1 antibodies. VISTA is also a primary driver of MDSCs. These cells function to promote T cell exhaustion and suppress pro-inflammatory tumor-associated macrophages. Finally, we know that VISTA expression can increase dramatically as a compensatory mechanism during treatment with anti-CTLA-4 or anti-PD-1 therapy. For these reasons, we believe that therapeutic targeting of VISTA will be a crucial addition to the arsenal of immune oncology therapy. We believe CI-8993 is the most advanced anti-VISTA antibody currently in clinical development and has the potential to be a game-changing cancer therapy. The clinical community has already shown a deep excitement and interest in this program, and we look forward to reporting initial clinical data later this year. To wrap up, I'd like to extend my utmost appreciation to the entire QRIS team who have made all of this progress possible. We are eager to build upon our efforts in the quarters to come and advance our next generation targeted cancer programs to help patients in need. With that, I'll turn the call over to Bill to review our financial results for the quarter. Bill?
spk02: Thank you, Jim. For the first quarter of 2021, we reported a net loss of $9.9 million, or 11 cents per share on both a basic and diluted basis, as compared to a net loss of $9.7 million, or 28 cents per share on both a basic and diluted basis for the same period in 2020. Revenues for the first quarter of 2021 were $2.2 million as compared to $2.7 million for the first quarter of 2020. In both cases, revenues comprised primarily of royalty revenues recorded on Genentech and Roche's net sales of AeroVeg. Operating expenses for the first quarter of 2021 were $11 million as compared to $11.2 million for the same period in 2020. Cost of royalty revenues were $.1 million for both the first quarter of 2021 and 2020. Research and development expenses were $6.8 million for the first quarter of 2021, as compared to $7.5 million for the same period in 2020. The decrease for the quarter is primarily attributable to the upfront license fee expense from our option and license agreement with Immunex. related to CI 8993 that occurred during the first quarter of 2020. These costs were partially offset by a $.3 million increase in employee-related cost. General and administrative expenses were $4.1 million for the first quarter of 2021, as compared to $3.6 million for the same period, 2020. The increase in general and administrative expense was primarily driven by higher costs for stock-based compensation, professional and consulting services, partially offset by lower legal costs during the three months ended March 31, 2021. For the first quarter of 2021 and 2020, net other expense was $1.1 million and $1.2 million, respectively. Net other expense primarily consisted of imputed interest expense related to future royalty payments. As of March 31, 2021, there were approximately 91.5 million shares of common stock outstanding. As of March 31, 2021, QRIS's cash, cash equivalents, and investments totaled $168.4 million. We expect that our existing cash and investments should enable us to maintain our planned operations into 2024. With that, I'd like to open the call for questions. Operator?
spk04: We will now begin the question and answer session. To ask a question, you may press star, then 1 on your touchtone phone. If you are using a speakerphone, please pick up your handset before pressing the keys. To withdraw your question, please press star, then 2. At this time, we will pause momentarily to assemble our roster. Our first question comes from Ed White with HC Wainwright. Please go ahead.
spk06: Good afternoon, and congratulations on the data. Very good news. Just the first question, Jim. How should we be thinking of the path forward to approval for monotherapy and combination therapy? Maybe perhaps you can discuss potential timelines to approval in AML and MDS. And, you know, what strategy, either monotherapy or combo, can get 4948 to the market sooner?
spk07: Thanks, Ed. I appreciate the thoughts on the question. You know, it's a little preliminary for us to talk about timelines to approval, but I think our overall approach is really the same approach we outlined in December. We're just, of course, more confident now that the data continues to reinforce it. And that is from initially expecting this was a combo therapy only drug that we were going to have in a selected population of, you know, 50% of the population. the December data and of course now the ASH abstract data seem to support that this is more appropriate for all comers. So I think that that's the primary end use. The other opportunity that was hinted at in December and now we can see more clearly is there may also be a monotherapy path in a selected population and I think now we can say it looks like the spliceosome mutation population would be a good candidate for that. All three of the patients that have a spliceosome mutation in this study so far have seen MeroCR or better. Obviously, given the genomics association, which makes it for a very compelling monotherapy opportunity, and the idea that in a post-HMA setting, there is no other drug approved, we like the chance of that one as well. Which one will go faster? I don't really know. I think the answer at this point is both seem to be very compelling opportunities. Combination therapy, where this gets added to standard of care, and then, of course, monotherapy in a separate population driven by the genomic signature.
spk06: Thanks, Jim. And maybe you could just Give us your thoughts on the size of these dose escalation studies, you know, the cohorts in both combination and monotherapy.
spk07: Yeah, Bob, would you mind taking that one?
spk01: Yeah, so these studies will initially be dose escalation trials using a 3 plus 3 type of design. Fortunately, we're able to start at a very relevant dose that's already been shown to be therapeutically active of 200 milligrams twice daily. And we also have started to define the upper limits as well, as Jim mentioned. You know, we would likely stick within the range of, you know, somewhere in the 200 to 400 range for dosing. So the overall dose escalation for these trials is not likely to take too long.
spk06: Great. Thanks for taking my questions.
spk04: You bet. Thanks, Ed. Excuse me. The next question is from Justin Walsh with B. Reilly Securities. Please go ahead.
spk05: Hi. Congrats on the progress, and thanks for taking the questions. So first, could you guys elaborate on the steps needed to establish the recommended Phase II dose at lower than 500 milligrams BID in AML MDS?
spk07: Sure. Again, that's probably the best question for Bob.
spk01: Yeah, I can do that. So, you know, so far we've seen, you know, really exciting data in a small number of patients. So part of our efforts now will be to look at a variety of different variables, obviously, including pharmacodynamics. We do know, for example, that the pharmacokinetics are very well behaved between, say, the 200, 300, and 400 milligram dose levels. You know, we'll also want to... expand somewhat and further understand the efficacy, perhaps, you know, looking at, you know, perhaps a dosing interval break, things like that. So, all of this will take place in the coming months and hopefully we'll be able to, you know, define a recommended phase two dose going forward, you know, in the near term.
spk07: Yeah, I think if I were to add something to that, Justin, I'd say that, you know, the good news from a timing perspective is we expected to hit MTD. We just didn't know when. The only signal that we had from the NHL study was that it was likely to be CPK elevation of rhabdo, and sure enough, we did see it at 500 in the leukemia study. So I think, you know, now that we've got the MTD in hand, we're at this high-class headache where 200, 300, and 400 all look therapeutic, right? I mean, I know that sounds kind of funny to say that that's your headache, but really it is. So we need to do a little bit of dose exploration at this point to try and figure out, you know, which of these really is the best one to take into phase two. Got it.
spk05: And one more question for me. I saw in the abstract that most of the patients were transfusion dependent, which isn't that strange for a higher risk MDS. I'm just wondering, are you guys tracking this and have you noticed any improvements in transfusion dependence in the MDS patients?
spk07: Yeah, so hold that thought for the more detailed discussion at EHA, but absolutely, in MDS, transfusion dependence is really important. In fact, a clinical endpoint for a study could be reduction of transfusion dependence. So we continue to monitor that. That's something that's to be important not just for our studies but also of course for the the low risk mds study the lucas ist that's being run in europe so hold that thought got it looking forward to it thanks for taking the questions yep thank you the next question is from summit roy with jones trading please go ahead hi everyone congratulations again on a very robust data uh just a couple questions and i
spk03: Absolutely, and I'm not sure how much color you can share with us. Any mutational status on these responders, if we should think they are mostly species of mutants, or it looks like both, could be both FLT3 wild type or mutant, and the split between AML or MDS, how many are from the AMS cohort, the responders, and how many from the MDS?
spk07: Yeah, so we're going to want to... hold off on some of the genomics discussion for the actual EHA presentation. We're going to not go beyond what we've said in the abstract. That said, of course, that's a matter of great interest for us. So you can look forward to having a lot more detailed discussion around that when we get to it.
spk03: Absolutely understandable. Just one last question. When you are setting up 4948 plus AZA in the HMA naive setting, should we think of as frontline patients being included, whoever is not amenable to 7 plus 3 treatment? And how are the physicians going to think whether to put the patient on 4948 AZA versus venetoclax plus AZA in these elderly patients?
spk07: Yeah, you know, why don't we ask Bob, our oncologist, to walk through that. Bob?
spk01: Yeah, so absolutely, you know, azacitidine is may be a viable treatment for first line for patients. So this combination in first line is something that certainly could be considered. One of the advantages that this drug has over venetoclax, for example, is the lack of significant myelosuppression. So this might be a driving factor, especially for a frail elderly patient, for a clinician to choose this combination over venetoclax. As we mentioned earlier, we're also exploring a combination with venetoclax itself and may even consider a triplet combination at some point in the future as well.
spk03: Barry, thank you so much and congratulations again. Thank you, Shivan.
spk04: Again, if you have a question, please press star then one. The next question is from Alethea Young with Cantor Fitzgerald. Please go ahead.
spk08: Hey guys, thanks for taking my question and congrats on the progress with the abstract. A lot of them for me. Thank you. Yeah, good stuff. So the first, I'm going to ask them one by one because I think they're all equally as important. So when you look at the six people you had at ASH, like, you know, when we trace back now to how the CRs have deepened, were those the people that had marrow CRs and they deepened? Or, you know, how should we think about who had the hematologic recovery is the first question.
spk07: Yeah, we haven't gone into the patient-by-patient detail. I'd say hold that discussion, you know, on a deeper level of the data for the EHOC conference. I would say that, you know, the high-level observation is really the most important one, is that, you know, we were very pleased that we're getting blast count reductions. Remember that this drug is, you know, it's an anti-cancer drug. It's not a marrow stimulant. So we weren't really expecting to see heme recovery in this really late-line population. That we started to see it, was fantastic. We would expect that if you can eliminate the tumor burden, and heme recovery is possible, depending upon the health of the marrow, it is the sort of thing that you would expect, you know, might come over time. The fact that we've already seen it is, of course, fantastic. So we'll be following those patients. And of course, the additional ones we put on, you know, on the study in the months to come. And but we're very encouraged by what we're seeing so far.
spk08: So to follow that up, so EHA will get the information patient by patient, but just at a high level, is it fair to assume that, you know, your hypothesis is that responses deepen over time, or can you say that?
spk07: I think the hypothesis is that this drug directly targets the driver of disease, IREC4, or IREC4 long, and that that should lead to the reduction of leukemic blasts, full stop. That's what this drug does. It's an anti-cancer drug. So by hitting the target of disease or the driver of disease, you should see a reduction in cancer burden. And if the patient's marrow is healthy enough, obviously frontline patients, the marrow is going to be much healthier than in late line. The marrow gets damaged over time, not just by the cancer, but frankly by the cytotoxic agents, whether it's chemo or AZA or VEN. All of these agents will cause damage to the marrow. if the patient's marrow is healthy enough to be recovered, we would hope to see it, knowing that that might take some time. But that's going to be, frankly, a patient-by-patient basis, and it's going to depend, of course, how many prior lines of therapy and how deep the cancer has gone in each patient.
spk08: Okay. And so I don't know if you can say this, but can you tell us at what doses those CRs were achieved?
spk07: We will be showing that at the EHA conference.
spk08: Okay. I guess maybe this is more just on the toxin at the higher dose. Can you confirm if there were, whether there are any new responses reported to 500 milligram cohort? Or any more toxicity, I guess, in a way. Like, you know, is it like, yeah, you know what I'm saying.
spk07: Yeah, I know what you're saying. Obviously, I'm trying to balance, you know, the EHA rules, right? We don't want to be bridging the gap between what's in the abstract and what's in the presentation to come. I think what we would say is that we always expected to see talks. We weren't surprised. We were pleasantly surprised that we started to get responses even at the 200 and 300 dose levels. What I can say broadly is that 200, 300 and 400 all look like therapeutic doses. I would say that we, you know, we were pleased that we've now established NTD, and we're now going to try and figure out which of the doses, is there a dose response, is 200, you know, is 300 better than 200, 400 better than 3, remains to be seen. And as Bob said, you know, we may also want to take advantage, now that we're in Phase 1, before we go to Phase 2, of exploring different regimens as well. You know, now is the time to learn that. But for now, I would say we're frankly, you know, in this very high-class headache position of seeing three therapeutic doses and trying to evaluate which of the three is the best one to take into Phase II.
spk08: So when you think about the dose-response curve here, you know, like the 300, 400, now the 500, like, you know, there was a rhabdo at 300, not in this population, mind you, but... You know, do you think that you have a predictable kind of dose response per curve between the 200, 300, and 400 now, and that, you know, basically 500 is where this starts to creep up, or do you think there's more work to be done there?
spk07: Yeah, I would say we still have a pretty small number of patients, I mean, to be fair. I think we're encouraged that across the board all of the doses look to be effective. You know, all of the doses meaning 200, 300, and 400. But gosh, it's such a small number of patients in each one. It's hard to say today that there's clearly dose response and that one dose is clearly preferable to the other two. That's exactly why we've got to continue the dose exploration in the months to come and try to suss that out.
spk08: Okay. And so with these two cases of Ravdo, with the grade 3 one, was there any clinical symptoms? I know with the other one, there was a syncope. But is it drug-related? And if so, can you kind of explain what you think the mechanism of action is?
spk07: Sure. Bob, you're probably the best one to talk to that.
spk01: Yeah, so generally patients who experience this will have some muscle soreness. Maybe they'll notice a little bit of darkening of urine sometimes. In all of the cases, the patients have not had any organ dysfunction like renal failure or anything like that, and they've all recovered fairly rapidly from this. We think in several of the patients, there have been other factors that may have also contributed to that. For example, heavy exercise or on a statin, for example, that has a, you know, warning for rhabdomyolysis. So, you know, it's potential that this drug, you know, pushed those patients to the point where they experienced it. And so from that extent, you know, we do feel that it is drug-related, but other, you know, potential factors.
spk07: Okay, so... I think the primary factor for us, Alethea, in declaring... you know, 400 is our maximum tolerated dose and backing away from 500 was not the syncope, it was the rhabdo because we were looking for it, frankly, after the NHL experience. We did expect to see it. We were pleased that, as Bob said, we believe, based on the NHL study, that if you are on a statin, this may exacerbate that. So if you already have one factor that would push you to CPK elevation, that if you stay on the statin and add our drug, it might push you that much farther in the direction. Same thing with heavy exercise. If you're doing a lot of heavy exercise, maybe this exacerbates that. So we were looking for that effect. And that we did see it didn't surprise us. But, you know, even though it's only one of the two DLTs, that's really the one that in our mind says, okay, we saw what we expected to see. Let's back off to 400. And then, of course, you know, take a look at the other doses as well to see which of those is the best.
spk08: Okay, so with the grade 3 rhabdo that you saw, did anyone have like kind of statin exercise baseline things that would have been on note?
spk01: Yeah, Bob? Yeah, so two of the patients on the lymphoma trials we've mentioned previously, one of whom had the grade 3 rhabdomyolysis was also on a statin and the other patient in that case actually felt quite a bit better after being on the study drug for a short time, went out and exercised heavily and then developed this, you know, muscle soreness and symptoms after that. So we think, so what we've advised, you know, going forward for the clinical trial is for patients, you know, and investigators to discuss with their patients if they are on a statin, whether it's necessary to continue that statin And if they can come off that statin, they would, you know, suggest to do that. Similarly, to avoid extremely vigorous exercise while on the treatment. And we think that might be part of the reason why we, you know, didn't see this side effect until higher doses on the leukemia study.
spk08: Got it. And then maybe my last one. Do you think there's a differential kind of monotherapy response between MDS and AML patients?
spk01: Well, yeah, so, you know, we've, we'll actually give a much more detailed description of the specific patients. But obviously, we've treated both patients so far, and we've seen, you know, achievement of, you know, marrow CRs in both groups of patients. So we'll have to see, you know, the MDS population is the population where these spliceosome mutations are much more common. And you know that, you know, we've announced as part of this presentation that, you know, the three patients who had splice and cell mutations all achieved AmeroCR or better.
spk08: All right, great. I'll hop back in queue. Thanks.
spk06: Thanks, Alicia.
spk04: This concludes our question and answer session. I would like to turn the conference back over to James Denser for any closing remarks.
spk07: Thank you, Operator. I'd just like to thank everybody for joining us on the call today. We greatly appreciate the patients and families participating in our clinical trials. And of course, as I said earlier, I'd like to thank the team of tourists for their hard work and commitment. Also, our partners at Origin, Immunex, and the NCI for their ongoing help and support. We look forward to updating you all again very soon at the EHA conference.
spk04: Operator? The conference is now concluded. Thank you for attending today's presentation. You may now disconnect.
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