Great. Good afternoon, everyone. I'm Andy Berens, Senior Biotech Analyst at Leerink Partners. Welcome to day two, the end of the day, Annual Healthcare Conference in Miami. We're very excited to have with us Cullinan Therapeutics. We have the CEO, Nadim, and CMO, Jeff. Thank you, gentlemen, for joining us. Thanks for the invite. Thanks, Andy. Great. Why don't we start with a brief overview of Cullinan? Sure, yeah. I think what I would say is 2026 is a really exciting year for the company. Actually, potentially a defining year since we have so many milestones across our programs, but especially for our two high-priority T-cell engager programs. That's CLN-978, our CD19xCD3 T-cell engager in autoimmune diseases, and CLN-049, which is our FLT3xCD3 T-cell engager in AML. Focusing on CLN-978 first. There I think we have a potential best-in-class molecule for autoimmune diseases, and a comprehensive development program across a range of high and large market opportunities. There we have a molecule that we believe is best in class, highly differentiated from the other CD19 T-cell engagers, especially in the areas of very high affinity binding for CD19. We also have small molecular size, which could be important for tissue penetration, combined with the convenience of subcutaneous administration. That's a program where we have ongoing studies in three high-value indications, lupus, RA, and Sjögren's disease, and we plan to present the first company-sponsored data for a CD19 T-cell engager throughout 2026. More specifically, in Q2, we have the initial clinical data from SLE and RA. In Q3, we have the initial multi-dose data from RA, and then in Q4, we have the initial data from our Sjögren's disease study. Very excited about that program. You know, it's an area that's of high strategic interest too. You saw the recent acquisition by Lilly of Orna Therapeutics. This B-cell depletion space remains highly interesting. On the oncology side, I mentioned CLN-049, our FLT3xCD3 bispecific T-cell engager. There we have a first-in-class opportunity to take an immunotherapeutic approach to a broad group of AML patients. That allows us to unlock a significant commercial opportunity. At ASH, we showed compelling monotherapy efficacy data with the molecule that's in line with the reference benchmarks for regulatory approval. Very excited about that program. Just before ASH, we received Fast Track designation from the FDA. This year we're gonna utilize that Fast Track designation and select a recommended phase II dose this year so that we can then move on to a pivotal study in relapsed refractory disease. At the same time, in parallel, we're also pursuing frontline development, and that's in combination with Venetoclax. By the end of this year, we're planning to initiate a phase I/II study in combination with Venetoclax in the frontline setting. The other couple of things I would add, today, we announced that we completed our NDA submission for zipalertinib, so that's a great milestone for the company to get our first NDA under our belt. And Taiho has also guided to completing the frontline study. They've completed recruitment, and we'll have top-line data by the end of this year. Velinotamig, our BCMA x CD3 program in autoimmune diseases, we've guided to data in Q4 this year. A very busy year for the company, as I said. Finally, I'd say we have very robust balance sheets. We reported at the end of the year, last year, over $430 million in cash, which gives us runway into 2029. That allows us to continue to advance all these programs, but especially CLN-978 and CLN-049. We're very excited about 2026. Wow. Yeah, very busy, exciting year for you guys. For sure. Yeah. I think the data at ASH last year we thought they were very strong and kinda surprised us that it wasn't really a focus for a lot of people. Yeah until the data got turned over. Why don't we go into each of these programs individually? For CLN-978, you know, there's been a lot of data from cell therapies about using the immune system, T cells to modulate the immune system. Can you walk us through the strength of the data and why you're confident about the TCE approach? There's been some TCE data too. Yeah. I think, Andy, when you really think about it, the most compelling observation is that across a broad swath of autoimmune diseases, deep B-cell depletion, so sort of subtotal B-cell depletion, can affect an immune reset, and the clinical correlate of that biomarker observation is a treatment-free remission in diseases where patients have typically required ongoing therapy of some kind. Even when they could spare steroids, they needed to stay on something. That's been really remarkable. Data has emerged over the last two years that suggest as we initially thought when we pivoted our own CD19 T-cell engager into autoimmune development. Accumulating data that is showing that you can achieve that same depth of B-cell depletion and that same treatment-free response with a T-cell engager against various B-cell targets. That's been CD20, CD19, and BCMA. We still think that among those targets, CD19 offers the best chance for achieving that immune reset with the least side effects as compared to BCMA, higher likelihood of achieving that through the breadth of B-cell depletion versus CD20. We think we're well-positioned to achieve some first-in-class data for a sponsored CD19 T-cell engager that we'll share in Q2 of this year. Okay. Why would CD19 be a better approach than BCMA and CD20? For diseases where B-cell depletion is the aim, CD19 is more broadly expressed than CD20. We think if you're really trying to effectively carpet bomb the B-cell compartment, you're more likely to achieve that with CD19 versus CD20. In diseases that are really driven by B-cells versus plasma cell-derived autoantibodies, and there are many of those, particularly in rheumatology, CD19 allows you to deplete B-cells, but spares long-lived plasma cells. With that, you will spare your humoral memory immune response. There won't be a need for immunoglobulin supplementation to prevent infection in periods of hypogammaglobulinemia, and you won't need to revaccinate patients, because they won't have lost their humoral memory immune response to prior vaccination. In diseases that are really driven by autoantibodies produced by long-lived plasma cells, that extra supportive care burden, that extra risk for infection, we think is offset by potential for increased clinical benefit. Okay. A lot of the data, the early data for sure was from some of the cell therapies. Sure From the Schett group. Can you talk a little bit about what they showed and what we've learned from cell therapy? Yeah. I think there are a couple of things and one is that really in diseases that you know many of the therapies are perhaps T-cell directed, like lupus, for instance, many patients receive mycophenolate, particularly for lupus nephritis, and yet B-cell depletion can achieve these dramatic treatment-free responses that appear to be quite durable in many patients, some now extending beyond three and four years. SLE is one of the places where the initial data from academic experiments in China and in the Schett group have been replicated with multiple different CAR T constructs. Now we've seen similar phenomenon in diseases like systemic sclerosis, Sjögren's disease, inflammatory myositis, being probably the most prominent. One of the more remarkable findings is that in some of these diseases, autoantibodies actually persist. In those cases, they appear to be more markers of immune dysregulation than directly pathogenic, sort of suggesting again that B-cell depletion is in those diseases enough without having to affect long-lived plasma cells. Okay. In terms of the durability that they've seen, you said there have been cases of several years? Yeah, there have been cases of several years. I think even the very first patient that was reported was from China, and I believe that patient's response is extending now beyond four years. Okay. In terms of comparing what you see with cell therapy versus TCEs, what have we seen in terms of durability? Yeah the level of the response? Yeah. Part of that, you know, question is somewhat confounded because in many cases, patients have probably been treated with suboptimal doses or exposures of the T-cell engager. In places where patients have been dosed closer to, you know, a true B-cell depleting dose, and this is primarily with BCMA and teclistamab, there have been patients who have achieved treatment-free responses. The durability, you know, the last sort of landmark was at six months, and in the series of 10 patients from Erlangen, eight of the 10 patients were in ongoing remission at 6 months. The ultimate durability of response has yet to be reported. Just draw a distinction between what you would expect or need to see from a CAR T-cell product versus a TCE. For a CAR T, that comes with the risk of chemotherapy, the cost and logistical hurdles of CAR T. That has to kind of be a one and done. Contemplating repeat treatment with CAR T is very hard. With a T-cell engager, patients could be redosed at relapse, for instance. The benchmark for success there could be as short as six months, if the safety's good. Okay. You do have the, like you said, the option to retreat. Retreat. You don't. The durability is nice, but it's not as imperative. Less imperative. As it is with CAR T. Okay. When we talk about the competitive landscape, obviously this created a lot of excitement in the financial community as well as the medical community and the pharma community. How many different companies now are pursuing similar approaches to reprogram the immune system? Yeah. I think it's important to, like the way we think about it, we think about what really is our competitive set. You probably have three buckets. One is, CAR T, the other is T-cell engagers, and then the third is monoclonal antibodies. I think the way we're thinking about CLN-978 and the positioning of CLN-978 is that we can deliver the potency of T-cell redirecting therapies, but with the convenience and accessibility of antibody treatment. For us, really, our competitive set is other CD19 T-cell engagers. I think Jeff very well articulated why we think CD19 is the optimal target. Yep Especially for rheumatology diseases. In that specific subset category of other CD19 T-cell engagers, I think some of the molecules or companies that we're following most closely, probably Roche. I mean, they presented the CD20 mosunetuzumab data last year at EULAR. They have a CD19. We haven't seen the data yet, so we'll see when those data come out. You know, we plan to present the first company-sponsored data for a CD19 T-cell engager in Q2 of this year, so very pleased with the execution that, you know, Jeff and his team have been driving. Some of the others tend to be a little bit further behind. Whether it's Novartis, Merck with the program they picked up from Curon, GSK, they're a little bit further behind. At the same time, you know, we feel that we also have a differentiated molecule. We have very high binding affinity for CD19. Okay. We have a small molecular size, so half the size of these antibody backbone-driven treatments, which could be important for tissue penetration, combined with the convenience of subcutaneous administration. I think from a executional perspective and a molecular perspective, I think we feel very good about where we're positioned at the moment. Ultimately, though, we would wanna move up earlier in the treatment sequence, and that is to displace monoclonal antibodies. Because today, and we hear this from rheumatologists all the time, with monoclonal antibodies, they have to add them on top of chronic immunosuppressive therapy. With these T-cell redirecting approaches, you're able to have patients come off that chronic background therapy so that you can get a true treatment-free remission. It's clear from the data now that, you know, T-cell engagers are generally more potent than monoclonal antibodies because you're getting direct cell kill that is T-cell mediated versus some of the indirect mechanisms like ADCC, et cetera. You can deliver that without the need for background chronic immunosuppressive therapy. Very excited about the opportunity we have for CLN-978, and obviously we have a catalyst rich year, again, emphasizing that we plan to present the first company-sponsored data for a CD19 T-cell engager in autoimmune diseases. The sub-Q delivery, how many other of the TCs are being formulated for subcutaneous delivery? I think the majority are, you know, even if they were initially developed IV, are trying or planning to move that way because I think, you know, the kinetics of subcutaneous delivery are much more favorable respect to the risk for CRS. Anytime it's feasible, that's probably the first best approach. Plus, if you're thinking about downstream, when these enter the clinic, patient throughput, patient convenience, it's all gonna be easier with subcutaneous administration. I'd say that's the general trend. Okay. How feasible is it to think about this being an outpatient, self-administered regimen? Outpatient, yes. Self-administered would take really remarkable safety. Anytime there's a risk, I mean, right now we still expect that there'll probably be still some risk for cytokine release syndrome in, you know, some patients. I think that still means that this is something that is likely to be administered in a clinic setting rather than at home. You know, it's really gonna depend on the safety observations. Most programs, you know, starting out, if they're in sponsored development in Europe or the U.S., there's still an expectation that patients be hospitalized until you have a greater sense of the safety profile with greater patients, greater numbers of patients in the safety set. I do think in oncology, low-grade malignancies like follicular lymphoma are treated with T-cell engagers in the outpatient setting routinely now. I do think that's feasible, but self-administration at home, that's harder to imagine at this point. Yeah, I would add to what Jeff said. I think, you know, this is another clear and distinct advantage of T-cell engagers. Ultimately, our goal is to make these outpatient administered therapies. That's much harder to do with some of these complex modalities where you have to go, for example, to a CAR T-certified center. We wanna deliver the treatment where the patients are. Okay. Like with a nurse, a home health nurse? Yeah, exactly. Okay. I think there is a lot of flexibility. I think given the potency of these molecules, to echo what Jeff said, I'm not sure you wanna be doing this as a patient self-administration. Okay. The trial protocol, what does it require for administration now? Yeah. Right now it's 48 hours of in-hospital monitoring post-dose for a step-up dose and the first target dose. That's, you know, kind of by regulatory expectation until you have sufficient safety observations to justify something different. For when we get to repeat dosing, any repeat beyond the first target dose can be administered on an outpatient basis. Okay. It's just during the step-up scheme that patients require monitoring in hospital. At least at this phase of development. Ultimately, the plan is to make it fully outpatient. Right. Okay. That's just standard protocol? It's standard. If you see a lot of CRS or ICANS, what is the? You would still have to monitor the patients for the multiple doses or? Um, yeah, so there's- The dose selection is important there, right? Yeah, there's first it's the dose selection. We're starting with a single ascending dose. Yeah. There we're looking for a dose that's B-cell depleting not only in the peripheral blood, but also at the tissue level that has a safety profile that we think is acceptable, for further development. Here that means no Grade 3 CRS, likely no ICANS, and you know, predominantly Grade 1 CRS with low rates of manageable Grade 2 CRS. Anything beyond that is probably not, probably needs more work before moving into a repeat dosing scenario. Okay. In other words, let's say a target dose, you saw an unacceptable rate of adverse events. That might mean that you have to modify the step-up scheme to facilitate administration of that dose. Go to a lower dose. Go to a lower dose. I see. Okay. Why don't we talk about what you've seen before? The drug's been in patients. Yeah A few patients with NHL. What did you see there? What are we gonna see with this first update, how many patients? Yeah. It's good that you bring that up because that's really sort of anchors the discussion around the doses we're exploring in our autoimmune program. Eddie's alluding to a first-in-human study that we conducted in B-cell non-Hodgkin's lymphoma. We only treated three patients in that study, but the observations clinically and pharmacologically were very compelling. At a starting dose of 30 micrograms, we saw that in one of three patients treated, we achieved a complete response to therapy in a patient with refractory mantle cell lymphoma who had relapsed following transplant, autologous stem cell transplant. Very compelling to see clinical efficacy at the starting dose of a T-cell engager trial. That came with a very favorable safety profile, no higher than Grade 1 CRS. Quite remarkable. There were two other patients that were treated there, no higher than Grade 1 CRS. One of those patients experienced prolonged stable disease through 17 administrations of the drug. In terms of the biomarker observations of relevance to our autoimmune program, in two of the three patients, there were measurable B-cells at baseline. Both of those had greater than 95% reduction of B-cells in the peripheral blood following a single 30-microgram dose of 978. If you pivot now and think about, well, how does that translate to what we're doing in autoimmune disease? We are planning to dose escalate to at least the 30-microgram dose in our autoimmune program since efficacy in autoimmune studies has typically been close to an efficacious dose in a malignancy, particularly lymphoma. We're starting only two dose levels below. We're starting at a 10-microgram dose, and once that's cleared for safety, utilizing it to as a step-up dose to higher potentially therapeutic doses. This part of the trial is effectively a single ascending dose study, but we are incorporating step-up dosing to further mitigate the risk of CRS in a patient population where higher Grade CRS is not acceptable. Okay. How many patients are we expecting to see in lupus? So at the time of the- All right. JP Morgan meeting in January, we stated that we were enrolling patients to the 30-microgram target dose level of both the SLE and RA studies, and we expect to have completed that for safety evaluation before presentation in Q2. That means a minimum of nine patients of SLE data, seven patients of RA, likely more since we have the capacity to continue dose escalation if there's therapeutic index, and we may backfill at various doses of interest to increase the PK/PD set for modeling. Okay. It's my recollection that originally some of the data were expected last year, but because of the entry criteria, it was slow to enroll. In the lupus trial, you made some changes. How did that affect the enrollment substantially? It's been dramatic. We have increased the pool of patients available for screening, but we have significantly reduced the screen failure rate by about 50% improvement in the screen failure rate as compared to where we were in the second half of last year. It's been. We've continued to activate sites globally as well. Altogether, I'd say we've made up for lost time. Okay. Well, congratulations on that. That's exciting. It's always good. Yeah. You know, particularly when you're sitting next to your boss. No, one point I would make that Jeff made around the kind of dose escalation, I think it's really important. When you do dose escalation for T-cell engagers, it's very tricky. We kinda have the oncology and T-cell engager experience prior to doing this because you're solving for several things. You're solving for what is the right target dose, you're also solving for how do I get to that target dose safely? The way to do that really is in a systematic way through a company-sponsored study, not through IITs or compassionate use. This is why when you look at the datasets that are out there, particularly for T-cell engagers, a lot of it has been generated by, you know, academic groups, sometimes undershooting the dose, sometimes overshooting the dose. This does mean at the beginning, you kinda take your time to do it the right way, but by doing it in that rigorous way allows you to accelerate development from phase II and beyond. Yeah. That's really important for these modalities. Yeah. It sounds like the FDA is very, very aware of that. Yep. They are. Yeah. Okay. We only have a few minutes left. I do wanna cover. AML? Yeah, I think so. I think let's go to AML. Okay. I think it was a very exciting data set and, you know, it's obviously people were focused on your INI program, but all of a sudden the AML data came out and it looked really better than all the other classes that we've seen in similar settings. Can you give us just an overview and put it in perspective with some of the alternative therapies that are in development? All right. The three-minute summary. Andy's alluding to a program. We have a T-cell engager FLT3xCD3, and we presented initial data from the dose escalation in 45 patients at ASH this year. We showed- Last year. Last year. Yeah. Still feels like 2025. We presented data on 45 patients and showed favorable safety with pretty compelling efficacy. At doses of six micrograms and above, we saw that there was pretty consistent likelihood of achieving a complete response to therapy. We reported that at a dose, target dose of 12 micrograms per kilogram, we saw a 31% composite CR rate, CR plus CRh, which compares favorably with anything that has been approved in the relapsed refractory AML setting in the last 10 years. I'd emphasize that the majority of those drugs, all of them actually, have been approved for molecularly targeted subsets of AML. In this case, we're using FLT3, the extracellular domain, as a hook for immunotherapy. Here, that leaves us at an 80+% addressable patient population in AML, where FLT3 is an oncogenic driver regardless of kinase domain mutations. This drug is amenable to treating both wild type and FLT3 mutated patients. This was achieved with safety no higher than 35% overall, all Grade CRS. Only one case of Grade 3 CRS in a patient who received only one step-up dose. With two step-up doses, we could achieve a better safety profile, Grade 1, Grade 2 CRS, and lower rates of other cytokine-related adverse events, but with efficacy that would meet a benchmark for approval if replicated in a larger group of patients. Yeah. I think the other thing that, we were also very excited about, and including the KOL who was with us at our event, is the activity we saw in TP53 patients, right? That's right. In those patients, you know, there's nothing approved. The likelihood of response to any available therapy is very limited. The overall survival in that patient subgroup is only six months beyond diagnosis. There we saw pretty equivalent response rates in patients with or without TP53 mutations. Numerically, they were actually higher in TP53 patients, but I'd say, qualitatively the response rate's the same. Which means, you know, a significant opportunity in a very difficult to treat subset. In our initial plans for expansion, given the high medical need and the lack of a standard of care in the front line, we'll actually be able to treat patients with previously untreated TP53 mutated AML as well as relapsed refractory patients. The other thing I would add, this, there's a very clear development and regulatory pathway here. You have the opportunity to get an approval in relapsed refractory disease with a single arm study of about 100 patients as long as you show CR/CRh rate 20%-30%, durability of four-six months. For us, we're excited about identifying that recommended phase II dose this year so that we can start our pivotal study. In parallel, we also plan to start by the end of this year a frontline combination study, a phase I, phase II with venetoclax azacitidine, which would then allow us to do a randomized phase III study to get frontline approval. One phase II study, one phase III study to get relapsed and frontline setting and really unlock a significant multi-billion-dollar commercial opportunity. Right. Okay. The next updates, I assume could be at ASH or EHA. What will we see at ASH? We've said second half of this year. There we'll be presenting updated data from the dose escalation phase. At ASH last year, we said that we would continue the dose escalation through a couple of additional dose levels, since we did not yet believe we had exhausted the exposure response relationship. We'll present data from the further dose escalation, as well as longer follow-up for responding patients since durability of response is of keen interest to stakeholders and important for our future development potential. Great. Well, it is a big year for you guys. It is. A lot of cards to turn over. Appreciate it. Thanks, Andy. Thanks so much. Thanks, everyone. Thank you.