Welcome, everyone. I'm Sanjibita with J.P. Morgan Healthcare, and we are pleased to have with us Taylor Schreiber, M.D., Ph.D., Co-founder and CEO of Shattuck Labs. For logistical purposes, please reserve any questions that you may have till the end of the presentation. With that, I will let Taylor have the stage. Great. Good afternoon, everyone. Thanks to the J.P. Morgan group for the invitation to present at the 2024 Healthcare Conference. These are my forward-looking statements. So the content of today's presentation will focus on our lead clinical asset, we call SL-172154. I'll explain the structure of this compound in the next slide. This is a SIRPα-Fc-CD40 ligand dual-sided fusion protein. And throughout today's presentation, I'll refer to this simply as 154. The structure of 154 is shown in the schematic in the middle of this slide. And on the upper portion of the molecule in orange, we have the extracellular domain of the human SIRPα protein. This is the natural ligand for the CD47 receptor, and in a construct like this, you have six of those domains juxtaposed nearby one another, which provides an avidity characteristic to the molecule binding to the CD47 target. We adjoin those SIRPα domains through an engineered Fc domain to the extracellular domain of CD40 ligand on the lower portion of the molecule shown here in blue. CD40 ligand is a member of the TNF superfamily of co-stimulatory ligands, all of which natively assemble into trimers, and that is what drives the structure of the molecule into the hexamer that's shown in the cartoon. The reason why we arrived at this format for a compound is because all TNF receptors are also trimeric, and if you do not assemble them into a trimer, they will not signal. Over the years, many, many efforts have been made to try to activate CD40 and other TNF receptors with antibody-based compounds, all of which have failed for a mixture of toxicity reasons, but also because when you try to activate a trimeric receptor with a bivalent compound, that leads to bell-shaped dose response curves. So the hypothesis in building this compound, which has now been borne out in the clinic, is that by activating a TNF receptor with a trimer, you would avoid both those toxicities and the bell-shaped dose response curve seen with non-trimeric agonists. The Fc domain of this molecule was engineered to lack any residual Fc gamma receptor binding activity, and that was a design choice that was made because if you build a CD47 blocking agent with an active Fc domain, it will cause hemolytic anemia. That is the reason for discontinuation of some of the prior CD47 targeted agents. The place where CD47 sits in the immuno-oncology axis is at the interface between a cancer cell and a macrophage. And the cancer cell shown in gray on this slide is exemplary of many different tumor cells that upregulate CD47. And what that molecule does is it provides a stiff arm to any nearby macrophages that prevents them from phagocytosing those tumor cells. And so it's appropriately described in the literature as the "don't eat me" signal. But that name is also deliberate, and SL-172154, as you can see in the cartoon, will bind and competitively inhibit the CD47 target on cancer cells. Importantly, that is not enough to entice a macrophage to phagocytose or consume a tumor cell. In order for that to happen, the CD47 signal needs to be blocked, but then that tumor cell target also needs to be decorated with a pro-phagocytic or "eat me" signal. That can come from exposure of those tumor cells to certain chemotherapies that cause immunogenic cell death and upregulation of native pro-phagocytic signals. It can be provided by antibody-drug conjugates, some of which have active Fc domains and also a payload that can cause immunogenic cell death, or it can be provided by traditional tumor antigen-targeted antibodies that have an active Fc domain with ADCC or ADCP function. And so those are the rules of engagement for the axis, and that's the reason why all CD47 inhibitors are being developed in combination with chemotherapy, ADCs, or tumor-targeted antibodies. Where 154 differs from all CD47 inhibitors in development is through inclusion of that CD40 ligand domain on the carboxy terminus of the molecule. The reason for that is that while macrophages are key to initiate an antitumor immune response, macrophages are not the cell type that debulks a tumor. In order for that to happen, those macrophages need to process and present antigens from the cells they consume to T cells. CD40 is a co-stimulatory receptor abundantly expressed by macrophages, and we've published preclinically that when you stimulate those macrophages with CD40, it dramatically enhances their ability to present tumor antigens, which leads to greater tumor rejection in comparison to CD47 inhibitors and greater durability to those responses as well. So this is an overview of our current phase 1A/B clinical program. We have four phase 1b expansion cohorts ongoing today. Two of those are for patients with platinum-resistant ovarian cancer, where one expansion cohort, we're administering 154 in combination with pegylated liposomal doxorubicin. And the second expansion cohort, we're administering 154 in combination with ImmunoGen's recently approved drug mirvetuximab, also known as ELAHERE. In the other two clinical studies, these are for patients with frontline TP53 mutant AML, where we're giving 154 in combination with azacitidine, or in patients with higher risk myelodysplastic syndrome, where 154 is also being administered in a combination with azacitidine. We'll start with a few comments on the platinum-resistant ovarian cancer program. So first of all, ovarian cancer still remains an area of very high unmet medical need. Over 20,000 women are diagnosed per year in the United States, and unfortunately, many of those diagnoses occur when the disease is already quite advanced. The frontline treatment is very commonly a platinum-based regimen, and unfortunately, most patients eventually progress on that platinum regimen and end up with platinum-resistant disease. Ovarian cancer is also one of the tumor types that has very high expression of CD47. It's a tumor type that is not typically responsive to traditional immune checkpoint inhibitors like anti-PD-1 and anti-CTLA-4, and it's a tumor type that's abundantly infiltrated by immunosuppressive macrophages. It's also a tumor type where we had done significant preclinical work to show that approved agents, such as pegylated liposomal doxorubicin and incoming agents, such as ELAHERE, had good activity on their own, but that activity could be potentiated by combining them with 154. And so that's the reason for those two, that indication and those two expansion cohorts. PLD has been approved for a long time. There are two benchmark studies that are worth looking at to know what PLD offers in and of itself to patients with platinum-resistant ovarian cancer. One of those studies was published back in 2011. It's called the AURELIA study, and within that study, there's a subgroup analysis of about 70 patients where the objective response rate to PLD alone was 8%. The second study is a more recent and larger study published by Pfizer. It's called the JAVELIN study. It's about 170 patients that were enrolled, and the objective response rate in that study was 4%. So you can expect the response of PLD to be somewhere in that zone. The label, current label for ELAHERE, is in patients with ovarian cancer that express high amounts of folate receptor alpha. The label currently captures about 40% of patients with platinum-resistant ovarian cancer, and we did work with ImmunoGen starting about three years ago to demonstrate that when you add 154 to ELAHERE, it improves the activity of ELAHERE in ovarian cancer cells that express low and medium amounts of folate receptor alpha. And so the opportunity we're trying to address here is to roughly double the proportion of patients that may benefit from receiving ELAHERE in this setting. We completed the dose escalation study in ovarian cancer last year, moved quickly into both of these expansion cohorts. We have finished enrollment of 20 patients in the PLD cohort last quarter. And enrollment, as you might imagine, in the ELAHERE combo is going quite well. We expect enrollment in that cohort will complete very soon. This is an overview of the phase 1a/b clinical development program. After completing the dose escalation study, we selected 3 milligram per kilogram as the dose to move into combinations. 3 mg per kg was chosen as the appropriate dose for multiple reasons. It was a dose that was well-tolerated. It was a dose, one dose level above where we saw a full receptor occupancy on both CD47 and CD40, and it was a dose at which the pharmacodynamic effects driven by CD40 reached a maximal plateau. And those pharmacodynamic effects included large increases in serum cytokines, including interleukin 12, IP-10, CCL2, CCL3, CCL4, and CCL21. We then took that dose, and, and I should mention, if, if you'd like to see those data, they are available on our website from a poster that was presented at ASCO last year. I mentioned the Pfizer JAVELIN study as one of the benchmark studies for what you'd expect PLD to do alone in a patient population like this. What this chart shows you are the disease characteristics of patients that we enrolled in our study to date in the middle column, and the patients that were enrolled in the JAVELIN study in the right column. You can see that the patients between the two studies are nearly a dead match, with the exception that a higher proportion of the patients we've treated have bulky disease, and a higher proportion of the patients that we've treated have received treatment in the past with bevacizumab. This is the data for the first 11 patients that were enrolled in the study presented last quarter. As of this time, we had three patients that were in partial remission or partial response. One of those was a confirmed partial response, the other two were unconfirmed PRs. I'm pleased to report that those two unconfirmed PRs have since been confirmed. Those patients are continuing on therapy. An initial 27% ORR compares favorably to what you might expect for PLD alone, based on the JAVELIN study of 4%. What we need to see in this study is those, for those responses to be accompanied by greater than 5-month durability. So we'll provide an update on this study, including the full 20-patient cohort, with objective response rates as well as response durability in the middle of this year. We'll now change gears, and I'll give you the update on what is going on with 154 development in both TP53 mutant acute myeloid leukemia, as well as high-risk myelodysplastic syndrome. These are combination studies where 154 is being administered together with azacitidine. Similarly, we completed the monotherapy dose escalation study last year and presented those data in a poster at ASH in December, just about a month ago. 3 mg per kg was chosen as the dose to move into the expansion cohorts for the same reasons that we chose 3 mg per kg as the appropriate dose in ovarian cancer. Those dose expansion cohorts now in frontline TP53 mutant AML and high-risk myelodysplastic syndrome enrolled very quickly. They started in June of last year, and the TP53 mutant AML cohort completed initial enrollment by the end of October. These are the patient characteristics of for the initial cohort of 14 patients. 100% of the patients that were enrolled have multiple TP53 mutations with complex karyotype. This is the worst acting subgroup of AML patients. When you treat these patients with azacitidine, you expect less than 10% to have a true CR. When you treat these patients with azacitidine plus venetoclax, up to 30% or so of patients can go into true CR. The reason that physicians are comfortable using azacitidine alone is because even when you add venetoclax to azacitidine, it does not increase overall survival. In both cases, overall survival is six months, yet by adding azacitidine, those patients experience significantly greater toxicity early in treatment. These are the safety events for the study so far. In the table on the left, you'll see the all causality safety events in greater than 15% of patients. The most common treatment-related adverse events are infusion-related reactions, and this is an expected adverse event given the CD40 ligand immune agonist domain in the compound. We began pre-medicating patients in the dose expansion cohorts with dexamethasone on the day of treatment, and that has led to both a reduction in the frequency and the severity of those IRRs, and they remain highly manageable. The other common adverse events are constitutional in nature and are likely driven by a mixture of the underlying disease and the concomitant medications being given to these patients. In the box on the right, you can see a summary of AEs of special interest. In the past, many CD40 agonist agents have been discontinued due to liver toxicity, which was a common toxicity with CD40 agonist antibodies. We have seen grade 3 AST/ALT elevation in a single patient, and this was a patient who had liver enzyme elevation at baseline. Those AST/ALT levels rose to grade 3 following a single infusion, resolved within 6 days spontaneously and were not accompanied by any evidence of hepatocellular damage. Importantly, that did not recur in the patient as that patient continued on therapy. We also had one grade 5 event of an MI. This was in a patient that was 80 years old with uncontrolled AML. This patient had a previous history of coronary artery disease, had a prior MI, had been stented, had a known arrhythmia, which was being controlled with amiodarone, and then became hypokalemic on study. When you become hypokalemic and you continue using amiodarone, it actually becomes pro-arrhythmogenic. The treating physician said, "Look, this is likely related to this patient's underlying disease, but this is also a phase 1 trial, and I cannot completely exclude that 154 played a role." Importantly, we haven't seen any evidence of hemolytic anemia in this or any other study that we are running. The figure on the left is showing you the kinetics of blast reduction in the patients treated to date. We're very encouraged to see that in every patient where we have a follow-up biopsy, there is a significant reduction in bone marrow blasts. You do not expect 100% of patients to have a reduction in bone marrow blasts with this disease treated with azacitidine alone. To date, 3 out of those 11 patients have achieved CR. If you look at the kinetics of blast reduction, when blasts drop below 5%, that's when a patient can have a CR or CRi. The trajectories of those responses strongly suggest that at the next follow-up, some of these SD patients may also achieve CR or CRi. We're encouraged as well because these data were collected at a time which remains relatively early on study. The median time to CR in a patient population like this, treated with azacitidine and magrolimab, is 3.7 months. Most of these patients remain earlier on their course of therapy. And the other reason we're encouraged by these data is those patients that are showing a kinetic of blast reduction are also achieving peripheral count recovery in neutrophils and platelets. In patients like this, you receive the CBC data about twice a month, but the bone marrow assessments are separated by three-month intervals. Seeing peripheral count recovery tends to be a leading indicator of what you might then see at that next follow-up bone marrow... So seeing an initial 27% CR rate is certainly an encouraging place to begin. In this patient population, because the median overall survival when treated with aza or azaven is six months, we are looking for a duration of response in these patients of greater than six months. I'll now switch over and give you the update on where we are with the high-risk myelodysplastic syndrome study. This was a slightly larger cohort of patients. At the time of the data cutoff, we had 22 patients on study, and we ended up with a very strong bias in these patients toward those that have TP53 mutations. Otherwise, this is a typical higher-risk myelodysplastic syndrome population. About a third of the patients that have been enrolled have secondary MDS in the setting of a prior malignancy. This is the safety data to date, and what you'll see is that the safety profile is very similar to what I just showed you for the AML patients. Infusion-related reactions are the most common adverse event observed in these patients. The rest of the common AEs are constitutional in nature. When we first started the expansion cohorts, we advised the treating physicians to administer dexamethasone on the day of infusion for the first two cycles of therapy. It was then left to their discretion whether they wanted to continue administering dex in cycles three, four, five, six, as patients went on. That ended up being a very helpful setup for the study because there were two patients where the treating physician decided to no longer give dex in cycle three, four, or five, and those two patients did develop a grade three IRR when dex was not given as a premedication in those later cycles. Since that observation, we have changed the study so that we're giving dex with every infusion, and we've not seen a grade three IRR since. These are the blast reductions that we've seen in patients in the first group of 14 patients. Out of that group of 14, nine patients have achieved CR or marrow CR with hematologic improvement. As many of you likely know, in this disease, marrow CR can be achieved when blasts drop below 5%, but marrow CR in the absence of peripheral count recovery is not strongly predictive of an improvement in overall survival. And so that's the reason we're encouraged by seeing peripheral count recovery in 3 out of 4 of these marrow CR patients. Also encouraging is that these two SD patients are also showing count recovery. These were two stable disease patients that came on study with 5% blasts. One of them has achieved almost a 50% reduction in blasts and has bi-lineage recovery in the peripheral blood. The other came on study with 5% blasts and continues in cycle 5, still at 5% blasts. However, that patient has now achieved tri-lineage recovery. That other stable disease patient is the second one shown in the swim lane plot here, and very similar to AML, the bone marrow biopsies in these patients are separated by three-month intervals, and so we certainly hope that those peripheral count recoveries are an indicator of the ability to capture some of these additional patients in CR as the data mature. The expected complete response rate for azacitidine alone in a TP53 mutant AML pop-MDS population is 22%, and that comes from the Aprea study. Out of the patients shown in this table, all but one have TP53 mutation. The other benchmark study that's worth looking at in an all-comer MDS population is the study that Takeda ran with pevonedistat, where azacitidine had a CR rate of about 30% in that case. And so we're looking to provide CR rates well in excess of what's been seen in both of those benchmark studies. And it's also important that we show response durability in this population, and the durability target here is nine months. It's a great start that we have this one patient continuing beyond nine months in a CR. And then you can see in the middle portion of the swim lane plot here, 10 patients continuing on study in responses in that 4-6-month window. And the next update for this study is expected to be presented at EHA, and by that point in time, we will have the full CR rates for all enrolled patients, and it will be very clear whether that middle group of 10 patients are continuing beyond that 9-month duration of response target or not. So we're very encouraged by the data in both TP53 mutant AML and higher-risk myelodysplastic syndrome to date. When we started this study, there were other CD47 inhibitors ahead of us in development, and that is no longer the case because those agents were discontinued due to anemias. And so 154 has a first-to-market opportunity in these indications, and so we're taking several steps today to prepare for registration-directed studies beginning around this time next year. The first thing that we have done already is we have an approved amendment to double the size of the TP53 mutant AML cohort. We expect most of those patients will be enrolled this quarter, and we are also expanding the size of the higher-risk myelodysplastic syndrome cohort and intend to answer the likely question from the agency related to dose optimization with that expansion of the MDS cohort. So in both of those cases, as I mentioned, we are planning to present that next data update at EHA in June, including both full response rates and response durability. Also mid-year, we plan to provide an update on the pegylated liposomal doxorubicin combination in patients with platinum-resistant ovarian cancer. The full cohort was enrolled last quarter, and so by mid-year, we will know both the objective response rates and whether response durability is trending beyond five months in that patient population. The mirvetuximab arm has also enrolled very well, as you might expect. We expect enrollment of the full 70 patients will be completed very shortly, and we are working with both ImmunoGen and AbbVie on the disclosure strategy for mid-year. So it's an exciting time for the company. We're certainly pleased to be beyond those dose escalation studies and be at a point where we're showing efficacy in both heme and solid tumors in these expansion cohorts. We're in a fortunate position to shore up the balance sheet at the end of the year last year, and we are really looking forward to providing the durability data for all of these studies by the middle of this year. And that will tell what the next step in development will be for 154 in both heme and solid tumors. And as I mentioned, we expect that that would include initiation of a pivotal study around this time next year. So appreciate all of your attention. Be happy to answer a few questions and look forward to engaging with you over the course of 2024. What are you most excited for, during 2024? Do you have, upcoming milestones in that checklist, like what excited the most about now? Yeah, so the question, in case folks couldn't hear it, was, what are we most excited about in 2024? You know, these heme studies are two-part victories, and it's great to be starting out with high initial CR rates. But that's not a medically meaningful result in the absence of response durability. And we will know the answer to the duration of response for these trials, you know, over the course of the second quarter. And if we hit on durability, particularly in TP53 mutant AML, that is a rapid path to registration. This is an area of particularly high unmet medical need. Overall survival is six months, and so, you know, I think you'd be in a position to have discussions with the agency with that data in hand about accelerated designs. That could be the part of the program that moves fastest toward approval. But it's unlikely, you know. TP53 mutant AML and MDS are one continuum of the same disease, and showing responses and achieving an early path to approval in one likely portends the same outcome in the other. And all along, there's been a third cohort built into the phase 1b study, which is in TP53 wild type AML. The reason we didn't start that one as early as we started the other two was because that's a azaven combination, where azaven on its own has both a, a pretty high response rate and response duration. And so it would have been harder to decipher the contribution of components of 154 versus the control at this stage in development. Now that we've done that in the TP53 mutant AML and MDS populations, getting that going as well would be a priority this year. Great. Thank you. Maybe another question from me. For the ovarian cancer program, is the response, or action in any way dependent to any underlying, BRCA mutations? It's a good question. We are certainly collecting that information, and we don't have enough data to date to say whether there's a differential response based on the profile of underlying mutations. What I can say is we have a mixture of both in the patients that we've enrolled so far, and so we can look at that as the data mature. All right. Well, thank you all for your attention. Take care.