All right. Oh, good evening, everyone. Thanks for coming as we look forward to discussing the compelling initial results for CLN-049 that were presented at ASH today, and also look forward to the promise of CLN-049 for patients with AML. So, our disclosure slide. So, as outlined in the slide during this event, management will be making certain forward-looking statements. Please consult the risk factors discussed in our SEC filings for additional uncertainties that may cause the actual results to differ. All right, glad to get that one out of the way. Okay, so, turning to this evening, I'm very pleased to welcome Dr. Jeff Jones, our Chief Medical Officer, and we're especially pleased to welcome Dr. David Sallman from the Moffitt Cancer Center, where he's Associate Member and Myeloid Section Head, also the Research Institute. And now, not only is Dr. Sallman, a leading investigator in our study, he's also a leading researcher in the field of TP53 mutated AML and MDS, which you'll see is very, very important for the content today, so I'm gonna start out by outlining our broad pipeline strategy as a company. Jeff will then recap the results for CLN-049 that were presented today and also talk about immediate next steps for development. Dr. Sallman is gonna cover the current treatment of AML, including the need for more broadly applicable treatments and especially new treatment options for patients with TP53 mutated AML, which is a very poor prognosis disease, and then I'll conclude by outlining our development and regulatory strategy for CLN-049 and also frame the potential commercial opportunity, and then we'll open up the session for Q&A. I will say, Cullinan Therapeutics, we're very excited to be entering a rich catalyst period in 2026, starting from today and enabled by our pipeline strategy. And so now we have a de-risked pipeline of four clinical programs that are either first or best in class. And the reason I say de-risked is because each molecule is addressing a high-impact, clinically validated target. Each molecule has already demonstrated monotherapy efficacy in the clinic, and each program is addressing large market opportunities. And so, for the purposes of this talk, I'm gonna be focusing on two of our T-cell engager programs that we consider high priority. And if you look at our pipeline, the majority of our programs now are T-cell engagers, which is a core capability of our company and, of course, a highly promising treatment modality not only for oncology but also for autoimmune diseases. And so let me start with the onco-immunology side of the business. With CLN-978, our CD19 x CD3 bispecific T-cell engager, we have the opportunity to generate multiple value-creating milestones in the first half of the upcoming year. So, very excited about that. And if we dive deeper into the program with CLN-978, we clearly have a highly differentiated molecule and a best-in-class potential for the treatment of autoimmune diseases as a disease-modifying treatment. From a development perspective, we're leading global studies across multiple autoimmune diseases in RA, lupus, and Sjögren's disease. And we also plan to present the first company-sponsored data with a CD19 T-cell engager as we share our initial data from our RA and lupus studies next year. The other thing I'll add, if you've been attending immunology conferences, is that we now have clear external validation of our approach. Data from both ACR more recently and EULAR this year clearly underscores the importance of T-cell engagers for the treatment of autoimmune diseases, as does the persistent interest by large pharma demonstrated by multiple M&A opportunities and transactions in the space. On the oncology side of the house, with CLN-049, it's our FLT3 x CD3 bispecific T-cell engager, obviously the focus of the program this evening. And there we have a first-in-class opportunity to treat a broad all-comer population of AML patients, which we're very excited about. As we'll discuss this evening, we've already generated compelling clinical data as monotherapy in the relapsed/ refractory AML setting. We also have external validation now from the hematology community with our oral presentation at ASH. We've also been selected for inclusion in the upcoming 2026 Highlights of ASH meeting, so very pleased about that. And the other thing that was very important for us was that we secured Fast Track designation from FDA just last week for CLN-049 for the treatment of relapsed/ refractory AML. So, again, underscoring the clinical promise of CLN-049 for the treatment of AML. Finally, we have, and we're fortunate to have, a very robust cash position with approximately $475 million as of the end of September this year, which gives us runway into 2029 and ample resources to continue to execute our programs and generate multiple near-term and longer-term milestones with our immediate focus on quickly delivering the highly anticipated data from our CLN-978 program in the first half of 2026. So, hopefully, I gave you an outline of our overall pipeline strategy and what we've got going on, especially in the space of T-cell engagers. I'm now gonna turn the program over to Jeff, who's gonna cover and recap CLN-049 results that were presented today. Thanks, Nadim. And before we talk about the clinical results that were presented this morning, I'll take a moment to just talk about CLN-049 itself, since this program has been percolating in stealth for a number of years, and it's an opportunity for us to share a little bit more detail. So, CLN-049 is a T-cell engager, very familiar modality in AML, in hematologic malignancies, but AML has been one of the largest indications for which a T-cell engager has not yet been successful. And we think that's what gives us a first-in-class opportunity for an immunotherapy for AML, but also a first-in-class potential to use the FLT3 target as an antigen for the immune therapy. And so, in this case, CLN-049 is a FLT3-directed T-cell engager, and FLT3 presents several features that give it potential both on the safety side as well as on efficacy. For the safety argument, FLT3 expression is nearly uniform on patients with AML. In the blasts, more than 80% will express FLT3, which is an oncogenic driver in this disease. On the other hand, normal hematopoietic precursors, only small subsets of those express FLT3, as well as small subsets of dendritic cells. So, there's an inherent therapeutic index compared to other targets that have been pursued for T-cell engagers like CD33 and CD123. With respect to efficacy, as I mentioned, FLT3 is expressed as an oncogenic driver on AML cells and thus is less likely to be lost as a target antigen. And FLT3 is also expressed on AML stem cells, which are important to eradicate in order to achieve deep and lasting responses in this disease. Finally, FLT3 is, of course, a well-validated target, but there we're considering the 30% of patients who have intracellular mutations leading to constitutive activation of the kinase domain, but here, by looking at FLT3 and binding to the extracellular domain, we are able to address a very broad population of AML patients, as Nadim shared, more than 80%, we believe, so now I'll dive into what is, as Nadim said, very compelling initial data, and I would just remind you that this data comes from a dose escalation study. Now, expectations for phase I studies continue to increase in oncology, and we're always looking for meaningful efficacy from the first patient treated, so it's very gratifying to know that it was only several dose levels in from where we started at a target dose of 1.5 mcg that we were able to see compelling efficacy as well as we'll share. The dose escalation is depicted on the left hand of this slide. And there you'll see we started at a target dose of 1.5 and ultimately escalated in this dataset at the time of the cutoff in August to a dose of 12 mcg per kg. There was dose escalation, but there was also step-up dosing iteration. We began with a one-step-up dose scheme and ultimately added a second step-up dose to further mitigate CRS-related adverse events, as we'll discuss. But importantly, we iterated on that two-step-up dose scheme to further improve the rates of cytokine release syndrome, allowing us to continue the dose escalation beyond, as I'll mention as we close. The step-up doses were given on days one and four, in the case of a two-step-up dose scheme, with the first target dose given on day eight and continued weekly thereafter. Now, this study enrolled a total of 45 patients by the time of the data cutoff in August, but efficacy data was only available for the first 41. The last four patients treated at the three, six, 12 cohort did not yet have efficacy assessments at the time of the data cutoff. So the denominator for all of the efficacy data will be 41 patients in total. Just again, as we said, FLT3 is uniformly expressed on the majority of patients with AML. So there was no requirement for FLT3 testing. And we think that's an important aspect of this program, that there is no need for testing, as our data suggested. So, in understanding the implications of efficacy, you're always interested to understand the nature of the patients who are enrolled in the trial. And, there have been questions on whether the patients we enrolled were cherry-picked. You wouldn't pick these cherries. These are a pretty representative set of patients with relatively adverse risk AML. You can see there by the ELN classification, more than two-thirds of the patients fell into the adverse category. There in the blue box on the bottom, you can see the higher risk cytogenetic abnormalities that characterize these patients, particularly TP53 mutations, as we'll talk about when Dr. Sallman speaks shortly, that were present in the majority of the patients who were treated at the highest dose that we tested. These were also patients who were very treatment experienced with a median of two lines of prior therapy. Another question that came up this morning is whether or not these patients had a significant burden of disease. You can see that there were a substantial number of patients who did have an excess of 50% blasts in their marrow. This is a dose escalation trial. The first thing that we're always interested in is to characterize safety. In general, this is a very favorable safety profile for a therapy in AML. It is likewise a very favorable safety profile for a T-cell engager. I think it compares favorably with any of the T-cell engagers that are currently approved in non-Hodgkin's lymphoma, ALL, and multiple myeloma with respect to the most commonly reported adverse event here, which was cytokine release syndrome in just over a third of patients, and then another third of patients who experienced an infusion-related reaction. Many of these other adverse events are things that are commonly encountered in patients with refractory AML, and are as much attributable to their disease as to how it's treated. So let's dive in a little bit more to the CRS, since it's of great interest for this modality. So I would begin by saying that nearly all of the CRS events, that is, all but one, were Grade 1 or Grade 2, and were not treatment-limiting in any instance. The onset, as expected for a T-cell engager, was early in treatment, typically after a step-up dose or a first target dose. And there was only one Grade 3 event. You'll see it there, the one in green, in a patient who was treated with only one step-up dose. Once we initiated the two-step-up dosing scheme, the rates declined, and they also decreased in grade. So you can see that in general, there was something of a lift and shift with respect to the likelihood and severity of CRS. Now, what about other cytokine-related adverse events? ICANS is another one that is particularly concerning in T-cell redirecting therapies. And in this case, we saw only two cases of low-grade, Grade 1 ICANS that occurred coincident with cytokine release syndrome. Likewise, transaminitis. We saw elevations of hepatic transaminases in three patients that met criteria for dose-limiting toxicity. But once we initiated a two-step-up dosing scheme, we saw no further, significant elevation of liver transaminases. I will mention that in the cases that we did see, all of the transaminase elevations were reversible. And again, this phenomenon could be mitigated through a second step-up dose. And finally, what has been the most gratifying part of this trial to date are the response data. And again, for a dose escalation trial, this is a very robust set of data. You can see that in the group of 32 patients who were treated at doses of six mcg and above, which appears to be the threshold dose for robust efficacy in AML, eight of those patients have responded. And at the highest dose that we assessed, 12 mcg per kg, among those 16 patients, five patients achieved a complete response or a complete response with incomplete hematologic recovery for a composite CR rate of 31%, which is an endpoint of regulatory importance, as you're aware. But a response is only clinically meaningful if it's durable. And this is data that was not available at the time of the abstract and is new in the presentation. Among those eight patients who achieved a CR or CRh at target doses greater than six mcg per kg, we saw that five of those patients had a response that had extended beyond four months, 16 weeks, and three of those patients had an MRD negative response, all of which was durable beyond 16 weeks, including the one patient at the top of the plot whose response was ongoing beyond 36 weeks. So clinically meaningful rates of response, as well as initial data for durability. And this therapy also allowed two patients to go on to potentially curative therapy, before, with hematopoietic stem cell transplant. So that's where we've been. Where are we going? Well, we have further dose escalated since the time of the data cutoff in August and have completed enrollment to a cohort of patients who are receiving a target dose of 18 and anticipate completing the dose escalation later this year, with a planned enrollment at a 24 mcg dose level. At this point, 53 patients have been enrolled to date. So a pretty substantial group of patients enrolled since we began this phase of the trial, a year ago summer. So very, very exciting to see the way that our investigators are interested in helping us explore this exciting new drug. But we've got more work to do beyond completing the dose escalation, and that's outlined on the right. So here we are planning initial expansion to initiate in Q1 of 2026 with a target completion by the end of the year. Here we'll be expanding into separate patient populations. The first is a group of all-comer patients, with the exception of patients with TP53 mutations. We will be exploring the efficacy of the drug in an all-comer population and also be checking the box necessary to satisfy requirements for dose optimization by expanding at more than one dose in that patient population. In parallel is another important patient population with an exceptionally high unmet need: patients with TP53 mutated AML. Not only are we enrolling patients with relapsed/ refractory disease, but also patients who have not received prior therapy. Frontline patients where the recommendation for most treatment guidelines is to pursue clinical trial. This will be an opportunity to assess a broader population of patients with TP53 mutated AML. Just to summarize, the key points from the presentation and again to emphasize why we are particularly excited about what we have already been able to demonstrate, and that is, again, compelling clinical activity, particularly in the patients who were treated at the highest dose we had assessed, 12 mcg, where the composite CR rate was 31%. The majority of those responses durable beyond 16 weeks. Again, in this relatively older patient population, heavily pretreated, safety is also of great importance, and there it's gratifying as well to see that Grade 3 CRS and other dose-limiting adverse events could be mitigated at the highest target doses when the dose step-up scheme was optimized, and as Nadim shared, we will be proceeding forward under FDA Fast Track designation for further development and are excited that the expansion phase of this trial will be initiated very shortly. And with that, I'll ask Dr. Sallman to share his point of view. Thank you so much for joining us tonight. Perfect. Thanks for that beautiful overview. So it's a really exciting time. I actually should have, you know, searched in my Outlook, my first, you know, conversations with Cullinan is probably four or five years ago. So it just takes such an amount of time. And we're now at the really pivotal time. I'm begging for a slot, you know, on a weekly basis. And for being here tonight, I think I was promised an additional one spot is, you know, on the record from that perspective. That'd be a TP53. Exactly, from that perspective. So, and I wish I'll Dr. Chan, who's in our group, she's actually the PI from the study. She has a lot of experience. I would also look to reach out to her, as well. But we're very, very excited by this program. And we really hope that this is going to be the first really immune therapy in acute myeloid leukemia. And I think there's some far-reaching implications from that perspective. So, you know, acute myeloid leukemia is obviously a very, very challenging disease. I argue the most challenging disease in hematology. And again, we'll talk about TP53 mutation in a moment. The majority of patients are older, and the majority of patients are not necessarily able to go for curative therapies. And even with that, even good and younger patients, still a lot of, you know, over 50% of patients are not alive long term. Again, if you take all of AML, you know, five-year survival, you know, can be as low as 10%. Even despite a lot of novel therapies, outside of really the very good molecular subsets of patients, there's still such an emergent need. Even the patients that have good risk disease, once you relapse or often even have some other factors, you're really not good risk from that perspective. I think at the same time, because we've had such a lack of agents for a long time in AML, actually our MRD technologies and a lot of the translational studies have actually very rapidly advanced. I really think over the course of, you know, even just the next couple of years, MRD is going to be dramatically incorporated more and more. I kind of look at it as sort of your emergent 911 system. You need to do something. And again, having a therapy that you can utilize immediately in order to eradicate it is quite critical, and actually, I think that's going to be a really exciting phase of this program, going forward, so for, you know, just broadly, and I know the room is actually very expert on all the therapies that are out there, I think in newly diagnosed acute myeloid leukemia, where we have really done great core-binding factor, which gemtuzumab, you know, on an intensive chemotherapy backbone, we're curing a vast majority of those patients. But I really argue that a lot of the other subsets, we still have a ways to go. Of course, we have targeted FLT3 agents, particularly gilteritinib, quizartinib. Frontline IC is doing quite well from that perspective. NPM1, of course, the conversations, and I'm very happy to not talk about menin tonight, but is, I do think we're going to increasingly cure more and more, you know, of those patients with frontline combination strategies. p53, and again, we're going to talk a little bit in more detail in a moment, is its own disease. Although we are talking tonight about acute myeloid leukemia, I very strongly argue there is a 0% difference between p53 mutants, MDS, and AML. This is a singular entity, actually already recognized by one classification system. We've had a lot of editorials into the sort of harmonization between ICC and WHO criteria, where as soon as you just have 5% blast or you're a multi-hit p53 patient, this is a singular disease. So although, yes, studies focused on AML, if our TP53 signal continues to show, this is going to have, you know, in the United States, instant adoption across MDS, independent of what the label will show. Again, targeted mutations are really exciting, but at the very most, including even IDH, you know, mutant FLT3, NPM1, KMT2A, at the very most, we're talking about half of patients. So that's still half that have essentially nothing in the salvage setting. And of course, all these patients with targeted mutations, once you fail a venetoclax-based therapy, which was a majority, as Jeff presented just a moment ago, these patients do dismal independent if they have something to target or not. Again, in relapsed/ refractory, we essentially have targeted agents that are now here. Again, we're still talking about composite CR/CRh rates that have led to approval around that 20%-23%. So far, we're seeing, you know, close to, you know, one-third and actually a much worse subgroup of patients. And again, a lot of this is really optimizing now into the frontline. That's really the pharmaceutical race across these good subsets. But again, what are we doing for the adverse subsets is obviously a critical question. Now, as far as what is risk, this is obviously continuing to be updated. I think the ELN 2022, which is here, is quite nice. I would just caveat that this is really specific to intensive chemotherapy. So we now have also ELN 2024, which is actually quite quite simplistic. Essentially, if you don't have NPM1 or IDH mutations, you're essentially intermediate or adverse, from that perspective. Again, you can see the survivals, even in favorable. I don't know if we necessarily say it's so great if, you know, unfortunately, you know, too, you know, half of patients are still not having long-term survival. Of course, part of this is enriched in the fact that, you know, a lot of these patients are you know older elderly from that perspective. You know, just to highlight poor and adverse, again, the most important category, and I like the bold here, is TP53 mutant disease. A lot of the other things, for example, monosomal karyotype, complex karyotype, minus five, seven, 17, this is just TP53. These could essentially all be rolled up in that singular one. Most of the other ones are extremely rare changes with the exception of the secondary type mutations, which although as adverse is really sort of a hybrid, I would consider between intermediate and adverse. Just one thing to say at TP53, if you look at every academic center in the U.S. right now, about one-third of patients coming in our doors are TP53 mutant. So we can overnight accrue these cohorts. The world is sort of desperate. And this is with a population incidence of TP53, you know, probably somewhere closer to 8%-10%. But because of this, and if you look at every trial presented at this Congress across elderly AML, why are there so many TP53 mutants? Because these are the patients that we're seeing and why we so urgently need a change in the paradigm. And the world has come together to, you know, universally, we've now run a pivotal frontline phase III, a pivotal frontline, you know, in both AML and MDS. So we can do this, actually quite easily from that perspective. So I've talked a little bit about this. Again, 12-13, I'd probably say 8-10, but again, in real life and across every center across the world, again, we're often talking up to 30% of patients. There are some subgroups that are enriched, particularly therapy-related, where this can be up to 40% of patients. And with the increasing, you know, of all of these novel therapies in solid tumors as well as IO therapies, actually, this is going to probably continue to increase. Where actually the incidence of p53 may start to be, let's say, closer to 15%. A big, big challenge, actually, one of the plenaries we're here with is, you know, how can we prevent maybe p53 clonal hematopoiesis from progressing, this sort of CDK4/6 plenary that was given yesterday from that perspective. The challenge with TP53 is not, you know, response rates are often okay in the frontline setting, but the survival is dismal. What's nice about the signal for TP53 mutant disease, I mean, for good or for bad, is if you have TP53 mutant AML as frontline, independent, if you are an 18-year-old marathon runner, the survival is six months. That is the median survival. It doesn't matter how old you are, how fit you are from that perspective, which is why, again, even in frontline, which I think is really an exciting and bold move by the company, I think is a really interesting, you know, consideration. Unfortunately, once these patients relapse, we're often talking survival more weeks to months. That's why when I highlight a case in a moment, I think you really have to put that into context. Again, this is in a salvage setting where, again, we're talking weeks to months for a majority of these patients. So this is just a singular case. Actually, I had a number of personal patients on the trial that have really done beautifully. And as, you know, Jeff really nicely highlighted, this is not cherry-picked populations. This is the very worst group in salvage setting with severe, you know, cytopenias, infectious risk, bleeding, et cetera. So this is a 70-year-old patient with TP53 mutant AML. You could see just by complex karyotype, this is automatically your multi-hit or biallelic. I know there's a lot of discussion. It's just that, you know, rare, low risk. So complex karyotype equals bad, independent of any other, feature from a TP53 perspective. Again, this patient was treated actually pretty aggressively. Would I have treated this patient exactly this way? This was not my personal patient. I don't know. But essentially [the patient] got a, you know, a novel combination. Actually, the way I treat p53 is at every step from day one throughout their course in therapy is to try to do something different than normal. So this was a novel combination of CPX-351 plus venetoclax, got sort of a partial remission, which is a sort of unicorn in the setting of AML response criteria, but nonetheless was ultimately bridged to a stem cell transplant in January of 2023. Now, what we do, and actually we had a nice abstract here at ASH. Actually, we do universal essentially HMA maintenance. Actually, we pitched a pivotal trial. We'll see if this happens within CIBMTR. This patient actually did really quite well. I mean, this is actually quite good survival for a multi-hit p53 patient that's bridged to transplant, but, you know, ultimately, unfortunately, did relapse, so this patient enrolled on the trial. What's nice with this therapy is responses almost always are quite rapid, so you can see the patient did achieve blast clearance and was actually MRD negative by flow cytometry. I think we've learned and we're still learning actually a lot, kind of the kinetics of response. So a lot of times we kind of see this emptying of the bone marrow, but fortunately a relatively rapid recovery. So if we only had MLFS and that was all the response that we see, I would not be excited at all, you know, in this patient group because patients, particularly with p53, need count recovery. You can see relatively rapidly within two months had CRh. CRh is an amazing response for any relapsed AML patient. This patient further improved to a full CR, which is a very rare event in TP53 mutant patients that relapsed and had a six-month, you know, optimal response in complete remission before the patient optimally relapsed. Again, you know, some of us can count on one hand across studies the number of patients that achieve this type of, this type of response. This just shows the bone marrow biopsy. I'm not a pathologist, but maybe I can fool some people in the room, essentially looking at the top. So these, you know, things that have a very large purple nucleus that looks a little bit more pale are blasts, which is what the arrows are helping us out for. Bone marrow is essentially, you know, relatively hypercellular for, this patient's age. You can see at just one month, you know, essentially all of these blasts are gone. That bottom left picture is really just peripheral blood, which if the bone marrow gets more empty, you see, you can see all the clear white globules essentially as fat, and there's really no blasts, which is kind of some endothelial and a little bit of other cells. Again, these blasts are eradicated quite rapidly. Another way to look at it is for CD34, which in general stains the majority of blasts. So essentially anything that's brown is positive. You can see clearly that at the, you know, one-month mark, all of these blasts are gone. There's no brown. The little brown that you see again is staining endothelial, which do express CD34. So again, we've actually enrolled a decent number of patients. Not like this is a singular example. And again, a 50% CR/CRh has never, ever been seen in the setting of TP53 mutants, you know, salvage therapy. Again, this is with monotherapy with IO. And again, these we have several patients that are having very durable responses. Actually, I would take any CR/CRh, CRi as extremely meaningful. And I wouldn't say MLFS is never valuable, particularly in younger patients. And remember, I have 18-year-olds that have TP53 mutant disease. If we can achieve this and give them a chance for curative therapy, with stem cell transplant, I think is extremely, extremely meaningful. Again, there is nothing really competitive on earth as far in this disease, particularly when we're talking about the salvage setting. And again, we're really, really excited for this next phase. I think what I really, really like is the fact that we're rightly looking at TP53 cohort. We're looking at the other cohort. I think we're going to hear about the developmental strategies in a moment, and I'm, you know, so excited once he releases all of the expansion slots because I have about a list of 20 patients at any one time. And actually up to half of those patients are TP53. But I'm excited about both cohorts. I don't think we should solely be thinking about TP53. Again, any relapsed/ refractory patient has very poor outcomes independent of baseline molecular features. And again, I really hope that this can be the first approved, you know, T-cell engaging type therapy that we'll have in the field of AML. It's been desperately looked at and worked hard by many in the field across multiple technologies. So thank you. I'll be happy to answer questions a little later. Oh, thank you so much, Dr. Sallman. Before Nadim takes over, I'll just state tonight I had reason to reminisce that, during this week, 19 years ago, I began my career as a hematologist attending on a hematology service that was all acute leukemia, during ASH while the whole faculty evacuated, which is the short straw of academic medicine. It's very gratifying to see the progress in AML. It's a reminder that we really rely on people like Dr. Sallman, your patients and their families in order to execute these studies and learn important things to help patients. Thank you very much for your point of view, for your participation in the trial. Nadim, I think you'll share a bit of the strategic context. Yep. Thanks, Jeff. Thanks for Dr. Sallman. appreciate a great talk. Look, one of the things about drug development is when you've got investigators that are fighting for slots on your study, that's a really, really good sign that you have something special, and I think we feel that we have something really special here, so look, let me put our results in some framework around context. You heard a little bit from Dr. Sallman about the current targeted therapies, and so this table shows in recent years all the approvals for these targeted agents in relapsed/ refractory AML, and I'll point out, sorry, I'll point out three key observations. The first thing, all of these drugs received accelerated approval with single-arm studies of approximately 100 patients. All of these drugs were approved for a relatively small biomarker-driven subset of patients, including the recently approved menin inhibitors. Third, these approvals have really kind of set the reference benchmark for approval in the relapsed/ refractory AML setting, which we believe to be a CR/CRh rate of around 20%-30%, as Dr. Sallman mentioned, and a response duration of four to six months, a fairly modest hurdle or benchmark for success. You heard from both Jeff and Dr. Sallman, we've delivered promising clinical data in a broad range of AML patients, including patients with TP53 AML. And so in many ways, we've actually already met the bar for regulatory success. So that's one thing. And secondly, I think our data now have really opened up the opportunity for a very clear development and regulatory pathway for CLN-049. Now let me talk a little bit about the commercial opportunity. So if you look at the table I just presented, all of these recently approved therapies are addressing relatively small subsets of patients. So in other words, we have a very fragmented relapsed/ refractory AML patient population. In contrast to CLN-049, we have a therapy that can be applied to a broad group of general AML patients. And so with CLN-049, we really have the opportunity to both disrupt and defragment the treatment of AML patients, which opens up a sizable patient population. Dr. Sallman presented the incidence of AML. So just again to remind you, every year in the U.S., 22,000 patients are diagnosed with AML. And unfortunately, many of those patients, the vast majority will relapse following initial therapy. Now that does create a relatively large relapsed/ refractory pool of patients, which is representative of about a $1 billion plus opportunity. When you then expand into the frontline setting with a larger patient pool, increased treatment duration, the commercial value significantly increases and opens up a multi-billion-dollar opportunity for CLN-049. The other thing I'll mention, the combination of the unmet need, the opportunity for CLN-049 to address a broad group of AML patients and our internal hematology expertise, which more specifically includes deep experience in the development and commercialization of AML drugs, means we have the opportunity to really rapidly execute the development plan for CLN-049. Jeff alluded to the development plan earlier. And as I mentioned again, in this disease, we have a very clear development and regulatory pathway for success with a two-pronged approach. So for relapsed/ refractory AML, it's a monotherapy approach. Starting in 2026, we plan to complete the execution of both dose expansion dose optimization cohorts, which will give us a recommended phase II dose to then initiate a pivotal single-arm study for accelerated approval. At the same time, and in parallel, we're also developing CLN-049 in the frontline setting with a combinatorial approach. In 2026, we plan to initiate a phase I/II study of CLN-049 in combination with standard frontline treatments. The data from that study will allow us to initiate a confirmatory phase III study, which will also expand the label to the frontline setting. Look, I will tell you, we're very excited to execute this program so that we can deliver a new treatment option for patients with AML. Let me now summarize and bring home the kind of key messages, right? So for CLN-049, we've clearly seen compelling efficacy as a monotherapy in relapsed/ refractory disease. We've also seen promising initial durability data and very encouraging efficacy in the TP53 mutated patients combined with a favorable safety profile. I spoke earlier about why context matters. And in this case, to see this remarkable clinical profile while we're still dose escalating is really something special. Based on its mechanism of action, all three of us highlighted that CLN-049 can address a broad all-comer patient population of AML patients without the need for biomarker testing. Another key point of differentiation versus current therapies. And as I said earlier, the efficacy data we've generated to date already meets the benchmark for regulatory approval and also opens up a very clear development and regulatory pathway for CLN-049, including accelerated approval with a single-arm study. The combination of our fast track status and our internal deep expertise in hematology will allow us to rapidly develop CLN-049, and in terms of the commercial opportunity with CLN-049, with the relapsed/ refractory AML segment alone, we have an opportunity north of $1 billion. Expanding into the frontline setting opens up a multi-billion-dollar opportunity for CLN-049, so now let me open up the session for Q&A and thank you very much for your attention. Questions. Thanks for that and congrats on the data. It's Marc Frahm from TD Cowen. Maybe for Dr. Sallman, you really elegantly talked about the true unmet need in the TP53 positive, but can you maybe just talk through a little bit of the unmet need on the other side of the bar on the TP53 negatives and what you would be encouraged by as the experience gets bigger on that side of the setting as well. And then maybe for the company as well, just in AML, I mean, certainly relapsed/ refractory first line, like you laid out, but another big opportunity often is the maintenance setting. Just what's the, is there a plan there at all? And maybe this is also a little bit for Dr. Sallman, it's just the AE profile you're seeing, how amenable that may or may not be to that setting. Maybe I'll start off with the company part of the question. So I think for us, you know, we really want to focus right now on the very clean development strategy that will rapidly get us accelerated approval. And I think there it includes the relapsed/ refractory setting from monotherapy approach, the combinatorial approach, frontline setting. I think in between that mark, there's lots of different opportunities. And I'll certainly let Dr. Sallman answer your question about the targeted patients. But one way we're thinking about the product profile here is, you know, in the very worst case, you would pick up the non-targeted therapy patient population, but that's not how we're thinking about this. So one way you could look at it is, you know, we've seen approximately 30% CR/CRh rate. In the targeted patient populations with the targeted agents, we're not seeing a 60% CR/CRh rate, right? If you're a conservative treater, the provocative question would be, why would you need to biomarker test if you're getting the same results with a general treatment? However, I think the more provocative question is, what can you do with combination therapy? Can you push that 30% in an IDH2 or an NPM1 patient to 40%, 50%, 60%? There, I think that's a very intriguing opportunity, but I'd love to get your clinical perspective. Yeah, yeah. I would say maybe just briefly about the tolerability. The agent, you know, I think it's sometimes difficult looking at AE tables and what do things mean from that perspective. You know, fortunately, actually this hasn't been just specific to this program, but like neurotoxicity is extremely rare for whatever reason across, you know, the myeloid portfolio. Really, it only occurs in the setting of high fever and sort of like delusional issues in that setting. So you could have a Grade 1 CRS, but with some neurotoxicity, as again that we've seen. What we, you know, incorporated and with dexamethasone premed essentially eliminates. I've had zero recurrence issues, you know, from that perspective. And again, these are very well tolerated. Also, the duration of the CRS is often very short-lived. So this is not like they're in the ICU refractory. Again, there was only a singular Grade 3 throughout the event. So it's actually been very easy to get, again, multiple patients, you know, clearly elderly and frail, staying outpatients, you know, from that perspective and doing very well. So the tolerability has been very clean from that perspective. I think one thing I'd say, you know, in the development of relapsed/ refractory AML, you know, one big challenge with one out of three patients coming into all the big centers at p53 is like, like what do you do with that approach? We have all these patients, everybody's eager, you know, again, sometimes, you know, again, up to 50% of patients. What's nice is this, it's not that there's something necessarily unique about p53 mutant versus wild type, although I think translationally there's a lot of work, you know, to be done. It's that these patients are doing just as well as the wild type, which we actually rarely see across studies. I think to your point, there's still a huge patient population. You know, all of the secondary type patients have nothing that is targetable. So again, these are splicing epigenetic factors from that perspective. And again, status post, you know, HMA venetoclax or other therapy, they really don't have anything else. And even in the good risk, again, there is still a lot of patients. You know, I already talked about the expansion of the MDS in the US. This will happen instantaneously in the p53 perspective. And I think what's nice with this sort of ICC, usually it's MDS hoping for, you know, some AML therapies, but I think in this setting, like what's the difference between a 10%-19% blast secondary type MDS patients? There's not. If anything, these are the very best patients to think about, you know, novel IO therapy. So I think there's going to, there would be a lot of extrapolation across the 20% blast barrier. I think frontline combination approaches, I completely agree. It's the right direction to go. They're very complicated, right? Even with, you know, response rates of near 100% across menin portfolio, you know, if people are betting, are these trials going to be positive? It's a very interesting question. This is with a response rate as up to 100% because there's just a lot of challenges. Where I see this type of therapy being really exciting is again, response rates are high, but a lot of patients still will have some level of MRD. So as soon as I had this agent, if I had an HMA venetoclax, IC chemo, whatever from that perspective, they have any level of MRD, this is exactly when I want to apply it. One, the tox risk is essentially 0% in that setting. And again, this is the whole goal of therapy. Whether or not they bridge to transplant or not, I think this could be independent of fitness from that perspective. But there's a, if we can get this, you know, over the line with this, you know, again, very relatively easy single-arm perspective, the expansion, at least the U.S. markets would be great. Agreed. And I think Mark probably, I think what you're alluding to, to Dr. Sallman is that for the MRD patients, it's more of a consolidation type approach, right? Than necessary maintenance. Yeah. Exactly. Whether or not you need to put all the drugs, as Mark Levis likes to say, and mix it, or again, we can have a little bit more of a strategic approach, you know, which may help from a toxicity perspective. Again, I love, you know, running the frontline, you know, trial from that perspective, but I think there'll be a lot of art to how to expand it once we have, you know, the science really starts once a drug is approved. Matt Phipps, but thanks for all the info. For the company, when you're thinking about this dose and step- up and everything, how much do you think the first dose matters for trying to really get early control of the blast? You know, you're really only tested kind of one and one half so far, just moving up. So do you think that can get you more efficacy or is it trying to get to that higher target dose? I'm not sure how much, you know, you're really able to look at changes in between these doses as you're doing some of this initial step- up work. There's certainly many instances where you sort of experience a kinetic failure where the kinetics of the disease outpace your ability to escalate. I think this is what you're referring to, to like to escalate to a therapeutic dose. That's why we did some of the iteration that we did. It's important that the first dose actually be sufficient to have a pharmacodynamic effect with respect to T-cell activation that you can assess through modest, but you know, not clinically significant cytokine production. If you haven't achieved that, then your step- up dose is probably not effective. I think what we've seen is that the 3/6 scheme is allowing us to escalate beyond where we saw really compelling efficacy. So I'm not concerned that we're at risk for the kind of kinetic issue with the step- up scheme. And then sorry if I missed it on the potential pivotal accelerated approval path. Is that just in TP53 mutants as the first step or that's all comers? No, that would be the going in approach would be all comers. Now, it would be great to see activity in the TP53 patients. I think that opens up a whole nother opportunity too. Guys, Robert Driscoll from Wedbush. Maybe just, did you guys see a correlation with FLT3 expression at all or is that something you're not looking at? We didn't talk about that tonight, but in the presentation, you'll have seen that there is no correlation with FLT3 expression. You know, T- cell engagers are particularly efficient, somewhat differentiated from CAR-T in being efficient at very low levels of antigen expression. So here, using conventional flow methods, we didn't detect any difference between responders and non-responders, which is a great thing if it does open up a very broad opportunity as we've discussed. And maybe I missed it on some of the swimmer plots, but did you guys treat after transplant in any of the patients that did go through? There were patients who were included who had relapsed after transplant, but we did not continue the drug beyond transplant. No. And I think just to comment on that, it's an interesting group because a lot of patients will have mixed chimeras and it's actually the functionality of the T- cells may be better. Actually, if you look across CAR-T programs, which we have done a lot with not necessarily amazing success, actually a majority of the responses in CAR-T and AML have been in the post-transplant relapse, at least with autologous products. So, you know, I think it's a huge unmet need that has nothing. And again, because we have great technology, you know, actually an interesting trial I would love to pitch, you know, let's say, you know, post-approval is for TP53, like because we're already essentially doing maintenance. Again, that was our abstract, but like why not at day 42 or something do this? There's already discussions around prophylactic DLI. We need to be very aggressive with anything to augment GVL. So that would actually be something I would love, you know, to pitch. And we'll mark tonight as the first night it was mentioned from that perspective. I think you just pitched it. I think there's a question here. Justin Zelin on for Julian, BTIG. My first question is, what do you attribute your beneficial CRS profile to relative to other approaches here? Is it something with the dose schema or the modality itself? And I'll ask a follow-up. Yeah, so it's a good question. I mean, certainly preclinically, this molecular format performed best. There were attempts to try the same binders using different formats, and this one won empirically. I think there is something that we're still looking to understand about structure- function relationships with respect to toxicity, and it probably depends on that specific antigen that's being targeted. I also think that there's something unique about FLT3. Its expression is relatively low as compared to something like CD19 on B- lineage cells or BCMA on plasma cells, and that may also be beneficial. Yeah, I think to piggyback, because we've done a lot both with CD33 and CD123, and I think the fact that there's such broad expression throughout hematopoiesis has been a major issue. CD123, and again, excited about some of the data here at ASH, you know, from that perspective. Also has endothelial expression and the sort of whatever you want to call it, capillary leak syndrome versus edema tox has been an issue across multiple, you know, technologies. So I think that, you know, is a unique difference, you know, with FLT3 as far as not broad expression across all of hematopoiesis and even, you know, antigen sink, et cetera, are some challenges from that perspective. Great. And I was just curious on how you'd expect the data to evolve in earlier lines where you might have higher immune cell fitness in patients. And is the goal here to be a bridge for transplant, or do you think that this can ultimately have durable activity in patients? Maybe you take that one. Yeah, that's kind of a softball, but yeah, I mean, yeah, I think anytime we can move things in earlier lines of therapy, I think exactly right, you know, from T- cell fitness, it should definitely be better. I would be shocked if, you know, we're not moving, you know, metrics between the sort of 10%-20% as we move into, you know, earlier lines of therapy. Again, that sort of consolidated MRD eradication approach is something that I think would also be very exciting from that perspective. We actually do have, do you want to describe the ongoing study we have in MRD? Yeah, so we didn't talk about it tonight, but in parallel with the study, we have a second study ongoing in Europe where we are utilizing CLN-049 as consolidation therapy to eradicate MRD in patients who are in CR with persisting MRD after induction or reinduction. And that study is ongoing in parallel. So we are interested in this. You know, MRD is still a challenging endpoint from a regulatory standpoint, but from a clinical standpoint, it's very meaningful. Without it, you're not going to have a durable response. Even in the next like year or two, for instance, I collaborate with Stephen Chung at UT Southwestern, and he does actually a very cheap CD34 selection, and we're getting up to like 90% MRD calling, you know, from that perspective. Hopefully the paper will be out shortly, but it's been presented before. There was a time when MRD was not accepted in myeloma, right? But it is now by the agency. So I think these things evolve over time if you can show the data. This is David Dai from UBS. A couple of questions from me. One is, is there any correlation between the onset of CRS and complete response? There's no apparent association that we've identified in the data- to- date. It's a short answer. Great. And then just on the three Grade 4 transaminitis, I'm just curious, you know, what's the reason behind it, you know, and how confident, you know, now that you have gone through mitigation strategies and the step-up dose, how confident are you that you won't be to see transaminitis happen again? Yeah, so I think our hypothesis is that it's like cytokine related. It only occurred in the context of higher grade CRS. And in all instances, you know, there was no hepatic dysfunction. This was clearly just, it looked more like a cytokine- driven acute liver injury sort of pattern. And so when we have better managed CRS, we haven't seen it recur. Yeah, I would say across, you know, like we have a very large, you know, CAR-T service as well as actually a bispecific service, you know, at our group. We see this not infrequently across approved. Fortunately, I don't think I've ever seen across any technology like the fatal liver event afterwards, but especially early, you can get this, you know, significant transaminitis in a rare subset of patients that is rapidly reversible. I have a patient currently screening for a trial, and he went to Grade 3 without actually therapy. So some of these AML patients in general, whether or not it's extramedullary disease or et cetera, and a lot of comment issues with azoles and other medications, you know, we see these LFT things, but again, without the actual liver failure events, it's clinically irrelevant. Hey, Brad Canino, with Guggenheim. Kind of difficult to ask a hard question on the data because as you've shown the dose escalation, you're already meeting the bar. So maybe let me try a regulatory one. Okay. Because the precedents that you put up there, they're all targeted therapies, right? And they've gotten full approvals on single-arm trials, really based on palliative care thinking from the FDA. And I'm wondering, is there a chance that the FDA looks at an immunotherapy and asks for a higher bar on OS? And I know between Nadim and Jeff, you've sat through a lot of AML regulatory discussion. What would you say about that potential risk? Yeah, let me ask. Let's see if we say the same thing. So the first thing I would say is, you know, when we're thinking about accelerated approval, then it isn't the longer-term outcomes like EFS, PFS, or overall survival, right? It's really focused in on the kind of some form of composite CR rate, whether it's CRc, CRh. I think there, the fact that we're seeing so far, and again, remember, we're still in dose escalation. So, you know, we've got room to go. The fact that we're seeing, and that was a comment I made earlier, the fact that we're seeing approximately 30%, but we're not seeing 60% of the targeted therapies. You know, our view is that that reference benchmark should still apply to a broader group of patients. And that's kind of how we're thinking about it. Yeah, I mean, I think the reference benchmark is a measure of clinical benefit. And so I think if you, we started, Dr. Sallman emphasized that roughly 50% of AML patients, particularly if they've relapsed, they don't have anything and they don't have a targetable mutation. So there, I think the unmet need is just as high. I think the benchmark for clinically relevant outcomes is the same, which is a meaningful rate of response that is durable. And there isn't an expectation of demonstrating, and technically, outside of a randomized controlled trial, you can't demonstrate a survival advantage. So the agency is indifferent to survival, at least in terms of, you know, making label claims. I still think it's influential and sometimes in thinking, but it's not something that enters into the specific regulatory discussion. Yeah, usually when it becomes challenging, Brad, is when you're seeing something, you know, kind of spectacular in that targeted group of patients, right? So if you think of lung cancer and you think about ALK and those other things, right? Checkpoint inhibitors contraindicated. But here, we're kind of seeing similar activity across the broad group. And I think what we would want to do in our expansion cohort is to be able to report out on patients with IDH1, IDH2, and show the same results. So I think, unfortunately, because of the poor prognosis of the disease, the bar is quite modest. And I think we're excited about the opportunity to bring this forward. Yeah, and I think regardless of modality, I mean, historically, there are instances where the agency has shown great latitude, where companies have demonstrated robust relapsed/ refractory data, and it's led to frontline approvals. And that's in other types of leukemia, but in a very high, you know, high unmet need population, if the efficacy is compelling, it's difficult to say that patients should have failed some sort of inferior therapy before progressing to something that's more efficacious than a frontline therapy. Okay. Our time's up, I guess. So, very subtle team we have. And I still wasn't getting it. Very subtle. Yeah. So look, in closing, the thing I would say is with CLN-049, we're at the very beginning of transforming outcomes in patients with AML, with a therapy that's broadly applicable to a broad segment of AML patients, as we just discussed, independent of the cytogenetic risk factors and mutational status. So that's why we're super excited about this. And when you think about the promise of CLN-049 for AML patients, together with the promise of CLN-978 for patients of autoimmune diseases, I would say Cullinan Therapeutics is really poised to deliver a very exciting and catalyst-rich period in 2026. So thanks again for coming. We look forward to updating you in the future. Thanks, everyone. Thank you.