Good morning, and welcome to the Shattuck Labs Investor Conference Call. At this time, all participants are in a listen-only mode. Later, we will conduct a question and answer session, and instructions will follow at that time. As a reminder, this conference call is being recorded. I will now turn the call over to your host, Dr. Taylor Schreiber. Taylor, please go ahead. Thank you, operator. Good morning, everyone, and thank you for joining. I'm Taylor Schreiber, the Chief Executive Officer and Scientific Co-founder of Shattuck Labs. We are excited to provide initial data from the Phase 1b portion of our clinical trial, combining SL-172154 with azacitidine in frontline TP53-mutant AML and higher-risk MDS patients. Throughout today's call, I will refer to SL-172154 simply as 154. The press release reporting top-line results was issued pre-market this morning and can be found on the investor relations section of our website, ShattuckLabs.com. Before we begin, I would like to remind you that today's webcast contains forward-looking statements and would refer you to our most recent 10-Q and other recent filings with the SEC, which are available from the SEC's website or on our corporate website, ShattuckLabs.com. On today's call, we are joined by Dr. Lini Pandite, our Chief Medical Officer, and Dr. Naval Daver, Professor and Director of the Leukemia Research Alliance Program at The University of Texas MD Anderson Cancer Center. After briefly introducing the mechanism of action and clinical development overview for 154, I will turn the call over to Doctors Pandite and Daver. Dr. Pandite will provide an overview of our clinical programs to date. Dr. Daver will then review the data from the Phase 1a dose-escalation study in patients with relapsed refractory AML and higher-risk MDS, shared earlier this week at the 65th annual meeting for the American Society of Hematology. We will then share initial safety and efficacy data from the Phase 1b dose expansion cohorts, combining 154 with azacitidine in patients with TP53-mutant AML and higher-risk MDS. We will then open the call for questions following our prepared remarks. As a reminder, 154 is a dual-sided fusion protein, which inhibits the CD47 checkpoint receptor and also directly activates immune cells by CD40 engagement. Linking these two functions within a single therapeutic differentiates 154 from all other CD47 inhibitors in clinical development. Additionally, we designed 154 to not engage Fc gamma receptors in order to avoid the anemias that have plagued other CD47 agents in the class. 154 is also an ideal combination agent and was designed to enhance the efficacy of tumor-targeted antibodies, antibody drug conjugates, and chemotherapeutic agents. Because of 154 's unique attributes, it is helpful to remember the design rationale of 154 within the context of CD47 inhibition. CD47 is a protein that is highly expressed on the surface of cancer cells. It acts as a 'don't eat me' signal, interacting with signal regulatory protein alpha or SIRPα on macrophages. This interaction prevents macrophages from initiating an immune response toward cancer cells. Blocking the CD47 signal, thus allows macrophages to recognize and engulf cancer cells, promoting an anti-tumor immune response. CD40 is an important activating cell surface receptor, primarily found on antigen-presenting cells, including macrophages, and has the potential to enhance the anti-tumor response. CD40 activation amplifies antigen presentation, resulting in stronger immune responses against cancer cells. Thus, by inhibiting CD47 and blocking the 'don't eat me' signal while simultaneously activating CD40 on macrophages, the dual immune activating mechanism of 154 has the potential to elicit anti-tumor responses with faster kinetics and greater durability than blocking CD47 alone. In data shared earlier this year at the American Society of Clinical Oncology annual meeting from our dose-escalation study in patients with platinum-resistant ovarian cancer, and earlier this week at the ASH meeting, we reported dose-dependent pharmacodynamic activity, including polarization of macrophages to an M1 phenotype, increases in CD8-positive granzyme B-positive tumor cells in the tumor nest, and large increases in the serum concentration of multiple cytokines, including interleukin twelve. These data enabled the selection of a dose to advance into combination studies, and we have recently reported an initial 27% response rate with a combination of 154 and pegylated liposomal doxorubicin in patients with platinum-resistant ovarian cancer. Today, we are excited to complement that early efficacy data in solid tumors with initial efficacy data from our clinical studies in TP53-mutant AML and higher-risk MDS. As a reminder, we are currently enrolling patients across four different cohorts, enabling an assessment of 154 in both heme and solid tumors. First, 154 is being evaluated in a Phase 1b study in patients with platinum-resistant ovarian cancer in combination with either pegylated liposomal doxorubicin or in combination with mirvetuximab soravtansine through a collaboration with ImmunoGen. The interim data we are providing today comes from our Phase 1a/b study in patients with AML and higher-risk myelodysplastic syndrome, both as monotherapy and in combination with azacitidine. Dr. Daver will briefly review the data with relapsed/refractory AML or higher-risk MDS, and then provide an update on the initial data from the expansion cohorts, combining 154 with azacitidine in both frontline TP53-mutant AML and higher-risk MDS. We are very pleased with the momentum in this trial, and enrollment has proceeded very quickly, which we attribute to the high unmet need for these patients and our investigators' enthusiasm regarding the differentiated profile of 154. I will now turn it over to Dr. Lini Pandite, our CMO, who will expand on the encouraging data generated to date. Thanks, Taylor, and good morning, everyone. 2023 was a year of high operational execution, and I'm pleased with the progress we have made, demonstrating initial antitumor activity, safety, and tolerability across several indications. Before I hand over the call to Dr. Daver, I'd like to briefly comment on the recent clinical progress that we made. As a high level, our confidence is bolstered by the interim results, which we announced last month from 154 in combination with PLD in patients with platinum-resistant ovarian cancer and the interim data in TP53-mutant AML and higher-risk MDS that Naval will present. The data in patients with platinum-resistant ovarian cancer are early and require both additional patients and longer follow-up but provide reason for optimism. Notably, an overall response rate of 25%-30% with 154 in combination with PLD is distinct from a benchmark response rate of 4% with PLD alone. These preliminary efficacy data, together with the safety profile, demonstrate the feasibility of combining 154 with PLD as a positive contribution to this backbone therapy. Additionally, last month, we announced initial antileukemic activity, unique pharmacodynamic activity, and an acceptable safety and tolerability profile for 154 as monotherapy and in combination with azacitidine. The observation of a monotherapy response, dose-dependent increases in cytokines, and accumulation of mature myeloid cells in bone marrow support a potential contribution of CD40 stimulation in these heme malignancies. Notably, preliminary data showed antileukemic effects in relapsed/refractory AML patients previously treated with hypomethylating agents and venetoclax and in previously untreated TP53 mutant MDS patients. Today, we will discuss additional data from the frontline expansion cohorts in TP53- mutant AML and higher-risk MDS. With that, it's my pleasure to introduce Professor Naval Daver, Director, Leukemia Research Alliance Program in the Department of Leukemia at The University of Texas MD Anderson Cancer Center. He's a distinguished clinical investigator with a focus on molecular and immune therapies in AML and myelofibrosis, and is principal investigator on more than 25 ongoing institutional, national, and international clinical trials in these diseases. Naval has published more than 150 peer-reviewed manuscripts and is on the editorial board of numerous hematology-specific journals. Naval, please go ahead. Thank you, Lini, and good morning to all. It is important to highlight that the response rates are historically low for heavily treated relapsed/refractory AML and higher-risk MDS patients, especially for those with complex karyotypes and TP53 mutations. These diseases are known to be very aggressive in nature and are very challenging to treat, with poor outcomes with currently available standard therapies. The median survival for TP53 mutated AML, based on recent publications, is six months. The median survival for higher-risk MDS in general is about 16-18 months, but for those with TP53 mutated higher-risk MDS, it is even lower, at around 11-12 months. And these populations represent a very high unmet need for development of novel and tolerable treatment options. We are starting to get a better understanding of why we're seeing such poor outcomes in TP53 mutated patients. As shown here, TP53 is a very pervasive mutation. It impacts cell cycling, it impacts DNA repair, translational effects, metabolism, proliferation, differentiation, and also seems to impact immune system, including the T cell, as well as immune recognition. We and others have published extensively on TP53 and have shown that with many, many of the new available treatments, as well as the standard existing treatments, we have unfortunately not been able to move the needle in this particular molecular subset, with a response rate remaining below 50%, looking at CR/CRi, and a median overall survival of 6-8 months. There was a lot of excitement and hope with the emergence of venetoclax, and venetoclax has shown big improvements in response rates and survivals from many molecular and cytogenetic subsets in the older unfit AML population. Unfortunately, the one molecular group where we have not had as much progress is in TP53. When we look at the data with HMA venetoclax, whether it's from the VIALE-A subset, looking at TP53 mutated, or from a study that we did at MD Anderson using decitabine 10 days with venetoclax, the TP53 mutated AML patients continued to have a very poor survival of less than 6 months. So we do not think that venetoclax is improving the outcome much in TP53, and additional different or novel strategies are needed. I'm now gonna turn to the data that will be shown at this year's ASH 2023 meeting. As of the data cutoff of September 15, 2023, 37 adult patients with relapsed/refractory AML and higher-risk MDS received 154 as monotherapy or in combination with aza in the parallel staggered dose escalation portion of this Phase 1a/b clinical trial. The patients had a median of 2 prior lines of therapy, and except for 5 previously untreated TP53 mutated higher-risk MDS patients, all of the other patients were relapsed/refractory AML or higher-risk MDS patients who had received prior HMA and/or venetoclax. The safety profile was consistent with the safety profile of the individual agents. Infusion-related reactions were the most common 154 -related toxicity. One grade 3 IR was observed at the 6 mg/kg in combination with azacitidine. The 3 milligram per kilo dose of 154 was actually selected for evaluation in combination with aza in the subsequent dose expansion cohorts, and very importantly, no destructive anemia or signals for hemolysis were observed. Here we show the waterfall plots for blast reductions from this cohort of 37 patients. Now I'm gonna transition to the 2 frontline dose expansion cohorts, where 154 is being combined with azacitidine in patients with previously untreated TP53 mutated AML or patients with higher-risk MDS. Building on the previous dose escalation trial, 3 milligram per kilogram was selected as the dose for 154 in this combination. I'm first gonna focus on the frontline TP53 mutated AML cohort. TP53 mutated AML, as has been published, has an immune-infiltrated phenotype, which we believe may allow it to be favorably harnessed and lead to benefit with potential immune-modulating therapies, such as 154. The baseline characteristics of these patients, as well as the number of patients enrolled, are shown here. A total of 14 patients with TP53 mutation or a TP53 deletion with poor prognostic disease characteristics were enrolled in this study. In fact, majority of these patients had complex karyotype with TP53 mutation or deletion and AML, which actually arose as a secondary feature after treatment for a prior malignancy. And this population is recognized to be one of the most high-risk populations in AML, what we call therapy-related AML with a TP53 mutation and/or adverse complex cytogenetics. Historically, for such a population with azacitidine monotherapy, as has been published by us and others, the complete response rate or CR rate is about 10%. Median survival is usually around 5-6 months. Overall, looking at the safety, this appeared to be quite tolerable for the 154 combination in this patient population. Infusion-related reactions, or IRRs, were the most common side effect that was seen. The IRRs were manageable with the use of steroid pre-medication on the day of the 154 treatment. 154 -related grade 3 or 4 AEs were reported in two patients in this frontline cohort. There was one grade 5 AE of cardiac arrest, and this was in a patient with TP53 mutated frontline AML. The patient also had a significant prior history of coronary artery disease, arrhythmia, and hypokalemia in the setting of amiodarone use. As for efficacy, you can see that the combination of 154 and azacitidine actually resulted in blast reductions for 100% of patients who had an on-treatment bone marrow biopsy available. This is very encouraging. Of the 11 evaluable patients, 2 have already achieved a complete response, and a third patient achieved a complete response with incomplete hematological recovery and has been bridged to an allogeneic stem cell transplant. As you can also see in the figure on the left, it's important to note that many of these patients are still early in their treatment course, with trajectories of blast reduction suggesting that further blast reduction may occur and that additional patients who currently have stable disease may soon achieve complete responses, and these patients are being followed closely at this time. Here we look at the kinetics of time to response, as well as time on treatment for this frontline TP53 mutated AML population. What we see is that the median time to complete response was about 4 months for this combination of 154 with azacitidine, and you can see the time on treatment as well summarized for patients in the combination of 154 and azacitidine. Importantly, many patients are still receiving the first few cycles of therapy, and it is encouraging that most of the patients with stable disease and blast reductions have already seen recovery in their peripheral blood platelet or neutrophil counts. We will now turn our attention to the initial results in the frontline higher-risk MDS cohort. This cohort also had quite a high-risk untreated higher-risk MDS population. There were a total of 22 higher-risk MDS patients, and as you can see, 81% of them had complex karyotype with TP53 mutation or deletion, and 32% of these were secondary or therapy-related MDS. This again represents quite a high-risk population for a frontline MDS protocol. The median overall survival for the patients with such factors is usually in the range of 11-12 months, with a response rate of about 20%-22% when looking at treatment as published with azacitidine alone. So this really is a population also of huge unmet need, both for improving response as well as eventually improving overall survival. Consistent with the TP53 mutated AML cohort, 154 had an acceptable safety tolerability in the higher risk MDS frontline cohort. Again, the infusion-related reactions, or IRRs, were the most common 154 -related treatment emergent adverse event. 154 -related grade 3 or 4 AEs were reported in 4 patients. This included IRR in 2 patients and chondrocalcinosis and febrile neutropenia in 1 patient each. There was 1 SAE of grade 2 CRS and 1 SAE of grade 2 maculopapular rash. There were no grade 5 AEs and no evidence of destructive anemia or hemolysis. And similar to the TP53 mutated AML, the immune agonist properties of 154 were apparent and is something we need to monitor going forward, thus far have been manageable with steroid premedications. The data here shows the blast reductions from baseline in the 154 with azacitidine in combination in the higher-risk MDS frontline patients. Importantly, there are already five patients with a complete response and another four patients with marrow CRs in this frontline cohort. This is very encouraging. Importantly, three of the four patients with marrow CRs and both the patients with stable disease have also shown hematological improvement in peripheral blood counts and are close to achieving complete remission. So all in all, it looks like we are seeing a number of patients achieving a response in this frontline higher-risk MDS population enriched with TP53 and complex cytogenetics. Similar to TP53 mutated AML, the median time to complete response for patients treated with azacitidine alone, is approximately four months. As illustrated in the swim lane plot, most of the patients who have been on therapy for four months have achieved a CR in this frontline higher-risk MDS combination cohort, and we believe additional CRs are possible in the patients who are early on in treatment in light of the ongoing blast reduction and peripheral count improvements that we are seeing in some of these patients. Lastly, I kind of wanna discuss where we are with the CD47 SIRP alpha development landscape. As we know, that number of these agents entered clinical trials both in heme malignancies and solid tumor, and a number of these programs have shown mixed results, both in solid tumors and heme malignancy. We have seen issues with toxicity, very specifically anemia, as well as potentially hemolysis with some of these agents, which may have led to potential early discontinuation and lower-than-anticipated outcomes in randomized studies. These safety issues and related clinical challenges, we believe, may be related specifically to particular CD47 antibodies, as well as their sites and mechanism of binding, and may not be inherent to the CD47 SIRP alpha target itself. The emerging data using this combination of 154 and azacitidine is encouraging and distinct from what I would have expected to see in patients treated with azacitidine alone, who bear such high-risk features such as TP53 and complex cytogenetics. Whether or not these early results will be medically meaningful will depend on achieving, of course, meaningful duration of response as the data mature and the cohort increase sizes, as well as, most importantly, in looking at the median overall survival, which has remained quite poor in this high-risk frontline TP53 population. In the TP53-mutated AML cohort, achieving a duration of response of greater than 5 months would be considered to be better than what can be achieved today with existing standard of care and, in my opinion, would validate further development of 154 combination in that population. In the higher-risk MDS patients with TP53 mutation, a duration response of 8-10 months or greater would also be meaningful and, again, in my opinion, would validate requiring further evaluation in that population. All in all, I'm excited to see the current data for the 154 azacitidine combination, and I'm optimistic that these responses will mature over time. With that, I would like to hand the call back to Dr. Schreiber for final comments. Thank you very much. Thank you, Naval. Obviously, we are excited about what we are seeing to date. As a result of the emerging efficacy data and expected high rates of complete remission in both our TP53-mutant AML and higher-risk MDS cohorts, our investigators have encouraged us to increase these cohort sizes in the trial. A trial amendment to enable this was recently approved, and enrollment has resumed to expand the study as our current data matures. One of the aspects of 154 that is becoming more evident relates to the potential contribution of CD40 agonism in the setting of CD47 inhibition. Accumulating clinical evidence now shows the pharmacodynamic contribution of CD40 activation in the peripheral blood, an apparent direct effect on myeloid cell maturation toward an M1 phenotype in both diseased bone marrow and within ovarian tumors, and accumulation of 154 bound to both tumor and immune cells from bone marrow biopsies collected following treatment with 154. The monotherapy response in a heavily pretreated TP53-mutant AML patient is distinct from observations with prior CD47 inhibitors, and we believe the rapid kinetics of blast reduction in frontline TP53-mutant AML and higher-risk MDS patients with poor prognostic features are distinct from what azacitidine has demonstrated in prior studies. The guidance to expand our trials is also partly based on the acceptable safety and tolerability profile observed to date for 154 in combination with azacitidine. Importantly, we are not seeing evidence of destructive anemia that has hampered the development of other CD47 agents and resulted in the opportunity for 154 to be first to market in multiple hematologic indications. Lastly, this slide summarizes our future milestones and what to expect in the busy year ahead. In 2024, we anticipate first additional Phase 1b combination data for 154 in combination with pegylated liposomal doxorubicin in platinum-resistant ovarian cancer patients by mid-2024, including initial response durability. Second, we expect additional Phase 1b combination data for frontline AML and higher-risk MDS, also by mid-2024, and also including initial response durability. And finally, we expect initial Phase 1b combination data for 154 in combination with mirvetuximab, also in platinum-resistant ovarian cancer patients and also mid-2024. Taken together, there are near-term opportunities for 154 to differentiate in both solid tumors and hematologic malignancies. If complete remission rates continue on their current trajectory and are accompanied by durability by mid-2024, 154 will have first-to-market opportunity in both TP53-mutant AML and higher-risk MDS. Before we conclude today's call, I would once again like to thank the patients and their families that have participated in the clinical development of 154 to date, Dr. Daver and the rest of our clinical investigators, our investors, and the entire Shattuck team that have enabled the progress shared today. With that, we are happy to take questions. Operator? Thank you, Taylor. At this time, we will be conducting a question and answer session with our speakers. To our analysts who are joining us live, we kindly ask that you limit your questions to two. Please hold for a brief moment while we poll for questions. Our first question comes from John Miller from Evercore. Please go ahead, John. Hi, guys. Thanks so much for taking my question, and congrats on these updated results. I'd like to ask about the CRs that you've reported, I suppose CRIs, the marrow CRs in either of those cohorts. How many of those reported CRs are in TP53 wild type patients, as opposed to the mutant patients? And then remind us, obviously, the mutant patients that you focused on today are have an especially poor prognosis, but what's the utility of 154 outside of that subgroup, and what should we expect for the broader AML and MDS populations? Thanks very much. Sure. Morning, John. Thanks for the question. So, to address the TP53 mutant question first, in the AML population, 100% of those patients have TP53 mutations with complex karyotypes. Out of the evaluable higher-risk MDS patients to date, only one of those patients has wild-type TP53, and that patient is in a CR. All other evaluable patients have TP53 mutations, most of which also have complex karyotypes. And we, you know, we started in this population with azacitidine alone, because as you heard from Dr. Daver, the overall survival of these patients does not seem to be impacted by adding venetoclax to azacitidine alone. And thus, we expect that a subsequent randomized trial for these folks would be randomized against just azacitidine. In looking at extending these results beyond patients with TP53 mutations, we would be looking to an aza/ven combination, at least in the AML population in those folks. There is a third arm built into this current trial to explore 154 plus ven/aza. You know, we had held off on initiating that arm until seeing efficacy with aza alone, and that's something that we'll certainly be updating you on in 2024. Great, thanks for the questions, John. Our next question comes from Joe Pantginis from HC Wainwright. Please go ahead, Joe. Hi, everybody. Good morning. Thanks for taking the questions, and very nice first looks at the data. So first, I'd love to be able to get from Dr. Daver, you know, some of your additional views or color with regard to your confidence that some of the stable diseases or PRs would, you know, eventually get to CR. And I'm asking from the sense of the kinetics of the responses and MOA of the drug, you know, say, versus the expectations of continuing enhanced responses from other therapeutics. Great, thanks for the question, Joe. Dr. Daver, let me ask you to chime in on that. Looks like we're having an issue with the audio. Joe, let me start, and, hopefully, we'll get him back to answer your question. So as you saw in the kinetics of blast reduction in the TP53-mutant AML folks, many of these folks' bone marrow assessments are, have been collected at the one-month or two-month time point, and show a clear downward trajectory in blasts even at that early stage. And, also, as you heard, the median time to response for AZA and also what was recently reported in JCO for the AZA magro combos is that the median time to CR is 3.7 months in those patients. You know, something that you tackle in these indications is that the bone marrows are usually done after one cycle, and then there's some degree of discretion as to how frequently they're done thereafter. When patients are showing recoveries in their peripheral counts, it's not always the right decision in terms of risk-benefit to the patient to subject them to frequent bone marrows. Clearly, they're improving if the peripheral counts are improving. So that's the situation we're in with many of these folks, where, you know, because the counts are coming up, there's a presumption that the bone marrow is continuing to improve and, therefore, less urgency to do that repeat marrow. Hopefully, we'll get them back in a second, but let's park it there for now, Joe. No, that's great. And I guess, off of that, is the company planning to provide or are you doing any, translational data to support the mechanism of action? And then separately, is there anything that you need to... Are you gonna continue as planned with regard to the continue infusion, say, you know, to address infusion-related reactions, or any mitigation you might be considering, or is it not necessary? It seems like it's not necessary at this point. Sure. So on the translational medicine side, you know, we—as you heard, we're the kinetics of response, you know, now the fact that we've shown 154 present in the marrow and in both the ovarian and in follow-up biopsies collected both from the ovarian patients and now from the AML MDS patients, we're seeing a transition from an M2 to an M1 phenotype in the myeloid compartment in the marrow. All of those things are unlikely to be driven by CD47 alone, and so we'll continue to follow up on those findings and as the number of biopsies grows. And I think that will become more definitive evidence of the contribution of CD40 over time, hopefully accompanied by the increasing CR rates that we're seeing relative to what you'd expect with the benchmarks alone. So we'll continue following up on that. And what was your second question, Joe? Sorry. Just about the infusion-related reaction. Oh, IRR. Yeah. Sorry. So far, these have been. In the dose escalation, we did not use dex as pre-med, and in the dose expansions, we are now using it. And, it has significantly dropped both the frequency and severity of IRRs. Most patients actually don't have IRRs when dex is given as a pre-med. There certainly are some patients that, for reasons we don't fully understand yet, seem to be somewhat hypersensitive to CD40 engagement, and even with dex, they do have IRRs, but the grade of those remains low. So, you know, so far, I think this is something that we'll stick with going forward, and we don't anticipate needing to add anything else at this time. Thank you, Taylor. You're welcome, Joe. Thanks for the questions, Joe. Our next question comes from Kaveri Pohlman from BTIG. Please go ahead, Kaveri. Yeah, good morning, and congrats on the results. Two for me. So, you know, there were some benchmarks provided for CER rates and survival, but, can you provide any color on what kind of stable disease rates AZA provides, since it likely also contributes towards survival? A question for Dr. Daver or anyone who could answer it: Since response rates don't necessarily translate into survival, do you think MRD status and transplant rates are a better predictor of survival in TP53 mutated AML patients? Thank you. Sure. Thanks, Kaveri. So in these folks, you know, what you'll hear from all of the KOLs is that CRs, and some folks even take the position that peripheral count improvements are even more important than CRs. You know, you don't get improvements in your peripheral counts if there hasn't been a debulking of disease in the marrow. And ultimately, when it comes to, you know, transfusion dependence, quality of life, everything else, having improvement in those peripheral counts, you know, really is what moves the needle for these folks. So the, you know, the stable disease that we're seeing is encouraging mostly because of the fact that we're seeing improvements in those peripheral counts at an early point in the treatment course for these folks. you know, if you look at the differences between the 2006 IWG criteria, where these patients are evaluated and the recently updated 2023 criteria of how these patients are evaluated, there's a very heavy emphasis placed in an updated criteria on peripheral count improvements. And they did away with the marrow CRs. So if we were to evaluate our current patients by the 2023 criteria, the CR rates are actually already higher, because of the fact that we're seeing a single and bi-lineage recovery in most of these patients so far. Lini, would you add anything to that? No, that's- Okay. Thank you for the questions, Kaveri. Our next question comes from Marc Frahm from TD Cowen. Please go ahead, Mark. Hey, congrats on the data and, and thanks for taking my questions. If Dr. Daver comes back, this would be for him, but also, certainly, Lini, I think you can answer this, and Taylor. Just, we've seen... It was alluded to in the presentations. We've seen some, you know, encouraging early signals recently in other MDS combo trials, right? Magrolimab being one of them, but some other mechanisms as well, that haven't, yeah, have kind of deteriorated over time and haven't panned out in the randomized. I guess, what gives you the biggest confidence here that this data is kind of on a materially different trajectory? Is, is it the Dr. Daver mentioned the safety that you're seeing. Is it, Taylor, maybe the trajectory, the, of the, you know, the rapidity of the responses that you're seeing? Just what, what kind of puts you into a different ballpark in your mind? Sure. Yeah, thanks, Mark. Let me ask Lini to start that one. So some of the, certainly these are early signals, Mark, that we are seeing. We are seeing reductions in blast counts, which are rapid, especially in this TP53 mutant patient population, that's a rapid reduction. And we are also seeing count recovery. You asked why this hasn't panned out with other agents. So what we have heard, and this is, we have not seen the data from the magrolimab studies as yet, but what we've heard is that, there was an imbalance in the safety in those randomized studies. We've also heard that maybe there were more patients with TP53 mutations in the higher-risk MDS study than because there was another study that was also ongoing, which is the venetoclax azacitidine study in higher-risk MDS. But we haven't seen any of that data to really understand what led to the early data not translating into an improvement in overall survival. With our data, we need to see the durability, and I think that will tell us a lot about how this would translate into overall survival. From a safety standpoint, we are not seeing the hemolytic anemia that was seen with magrolimab. That appears to have been one of the key issues with the safety that led to that imbalance. But again, we do need to see that data from the magrolimab studies to fully understand why the early signals did not translate into overall survival improvement. Yeah. Thanks. That's, that's really helpful. Maybe then also just looking forward, yeah, I, I know you don't have the data quite available yet, but, you know, over time you will be developing MRD data, I believe, in these studies as well. Just, how should we think about that, kind of along the same lines as the last question in, in terms of, you know, what's a good response there and, and, increasing your confidence? Yeah, we are looking at MRD both by flow as well as by NGS. We, we hope to have that data, next year. We have in a very, very early data, we have seen definitely reductions in, a negative, MRD negativity by flow, we have seen. And when looking at NGS, there has been a reduction also in the TP53 mutant, VAF. Again, we need to see the full data set there. Okay. Thank you. Thanks for the questions, Mark. Our next question comes from Carly Kenselaar, from Citi. Please go ahead, Carly. Great, thanks. I'm on for Yigal Nochomovitz this morning. Just 2 questions from us. I guess, first, following up on the last question, just wondering if you can elaborate a little bit more on what you'd be looking to see in terms of durability, and duration of response in future updates to give you further confidence that you're seeing efficacy on top of what you'd expect for azacitidine alone. And then the second question is just on safety. Wondering if you can comment at all on any dose reductions or dose interruptions that occurred during the study. Thank you. Sure. Thanks, Carly. I'll take the first one and then hand it over to Lini. So in the TP53- mutant AML folks, we're looking to, because the overall survival of these folks is 5-6 months, you know, that's obviously where the duration of response benchmark starts for us. And because that full cohort, you know, was enrolled by the end of Q3, we can be confident that we will have a look at that response durability, you know, during Q2 of next year... and, you know, by that point in time, we'll know if we have a drug, if we're extending survival well beyond 6 months in those patients. In the higher-risk MDS population, you know, again, because those initial patients in the full cohort was fully enrolled already, we can draw a line in the sand as to when we're gonna start extending the duration of response beyond that nine-month or so benchmark. And, you know, you can see in the slides, we have one patient who's continuing in a CR already beyond nine months. And to get all of the patients beyond nine months, you know, we're gonna need to get toward the middle of next year. But also by Q2, we're gonna have a very good sense as to, you know, whether patients, you know, 2 through 6, who are also in CRs or near CRs, are remaining on study or not, and whether we are trying to make up ground from a duration of response perspective or whether we're trending ahead, and certainly nice to start ahead with this first patient there. Lini, you wanna address the safety question? Yeah. Yes. So with regard to the interruptions first, if a patient has infusion-related reaction that requires intervention, then the infusion may be interrupted. And so here now with the administration of steroids in all patients with all doses, we have seen a reduction in the interruptions during the infusion. So most of these infusion-related reactions that we have seen since we started the steroids have been grade 1. There have been a couple of patients who have gone on to have grade 2 infusion-related reactions, and there the infusion was interrupted. With regard to the dose reductions, there are 2 patients who were dose-reduced from 3 milligrams to 1 milligram per kilogram. This was a patient... At one point in this study, we were pre-medicating the patients for the first 4 doses, then stopping the steroids and watching to see what would happen. We did have a patient who had a grade 3 infusion-related reaction, and in that setting, we ended up actually reducing the dose to 1 milligram per kilogram. But since then, we have now required all patients to have steroid pre-medication with all doses, and that's really supported by the investigators, who feel that it's very much better tolerated when patients receive steroids prior to the dose. Okay, very helpful. Thank you so much. Thanks for the questions, Carly. Our next question comes from Gil Blum from Needham. Please go ahead, Gil. Good morning, and let me add my congratulations to the results. So maybe just a general question on, you know, therapy and in this patient population. Are you expecting to convert some of these responders to transplant? I know that's a goal of therapy sometimes. Yeah. Yes, so we have seen—I mean, investigators are very keen to take patients to transplant, Gil, if they achieve—when they achieve minimal residual disease, or if and the patient has to have a donor. So we've certainly seen at least one patient who achieved a marrow CR, and since then, actually, we've also heard that that patient's counts had recovered. So the patient was a CR before going to transplant. So that's actually generally what investigators like to do is to take these patients to transplant if they have a donor. Having said that, again, we do have a patient who is now nine months out. This is a patient with TP53-mutant AML that was secondary to prior chemotherapy for lymphoma. That patient remains in a CR and has not been taken to transplant. So there may be reasons there, like comorbid disease or the lack of a donor, where that patient hasn't gone to transplant. Excellent. Just skimming through the entire dataset, you only had one patient that appeared to breakthrough of therapy here. Is there anything interesting about that specific patient who showed blastic progressive disease? Yeah, that- Go ahead. That patient actually progressed fairly early in the disease, before the patient had received many doses. So it's hard to know, Gil, hard to know what led to that progression. Okay. And maybe kind of a final one, you know, given the unmet need and given the cytogenetics of these populations of patients, is there a potential, you know, faster registration move here, even with cohort expansions? Thank you. Yes, this has come up from our investigators as well. If this, you know, if this trend continues and we see duration of response, we do, we hope to take, you know, discuss this with the agency. So we are waiting for more mature data, and we hope to discuss the data with the agency. Thank you for taking all our questions. Great, thank you for the questions, Gil. This concludes the Q&A session for the call. At this time, I would like to turn the call back over to Taylor Schreiber, Chief Executive Officer of Shattuck Labs, for closing remarks. Thank you, operator. Thank you all for joining the Shattuck Labs investor conference call to discuss our initial clinical trial data from the Phase 1a/b dose expansion cohorts in frontline TP53-mutant AML and higher-risk MDS, and review of the dose escalation data from ASH 2023. We appreciate your continued interest in Shattuck, and we look forward to updating you on our milestones in the year ahead. Thank you.