Okay, I think we are live. Good morning, everyone. My name is Yatin Suneja. I am one of the biotech analysts here at Guggenheim. Welcome to our SMID Cap Therapeutics, or Biotech conference. Our next presenting company today is Cullinan Therapeutics from the company. We have a few executives here in the room. With me, I have Nadim Ahmed, who is the Chief Executive Officer. We also have Jeff Jones, who's the Chief Medical Officer. Nadim, I'm going to hand it over to you. Why don't you make some opening comment, tell us a little bit about Cullinan, what are some of the upcoming milestones that we and investors should be focused on, and then we'll go into sort of the fireside session. Sounds good. First, thanks for the invite. Great to be here. I would make several remarks. So one of the first things I would say is we're a Biopharma company that's dedicated to creating new standards of care for patients. And so we're really into therapies that are going to make a big difference for patients. We've strategically built a pipeline of now five clinical stage assets that either address key drivers of disease or harness the immune system to remove disease cells from the body. And if you look at our pipeline, it encompasses a wide range of modalities, all with the opportunity to be either first in class or best in class. So that's the first thing I'd say strategically, how we do discovery and development. 2024 was a really big year for us. It was when we decided to expand beyond oncology and R&D into immunology. A lot of it was driven by the potential of CLN-978, our CD19, CD3 T-cell engager, and the opportunity in autoimmune diseases. As we thought about that strategic decision, there were several factors that came to our mind. One was, if you look at our pipeline of oncology products, most of our molecules actually harness the immune system in one way or another. Secondly, in recent years, the biology of oncology and immunology has continued to converge. If you think about cancer and autoimmune disease, cancer is often driven by a suppression of the immune system. Autoimmune diseases are often driven by an overactive immune system. In a way, we're a company that's in the business of restoring balance to the immune system. Entering into immunology was a very natural adjacency for us and an excellent strategic fit. So I started talking about CLN-978, which obviously we're very excited about. So that's a molecule that is an off-the-shelf potential disease-modifying regimen that can be applied to a broad range of autoimmune diseases. And 2024 was really a year of execution of that program for us, which culminated in clearing an IND towards the end of the year. And I will point out that we are the first and only company that has, with a CD19 development stage CD19 T- cell engager, that has cleared an IND in the U.S. If you look at the larger pharma companies, they're all running their studies ex-U.S. So that was tremendous execution by Jeff and his team. And obviously, that gives us a leadership advantage. And that IND that we cleared, it was for a global study in lupus or SLE. From that study, we've guided to initial data at the end of 2024. At the same time, we're also planning to initiate a study in rheumatoid arthritis, or RA. For that study, we're collaborating with the group in Erlangen, Georg Schett and his colleagues that originally came out with the CAR-T data in lupus, as well as the Gemelli University Hospital in Rome. These are two groups that have actually pioneered the role of T-cell engagers in autoimmune diseases. We're excited about that collaboration. We've guided to initiating the RA study in Q2 of this year. That's kind of where we are with immunology. On the oncology side, I think we believe we have a very differentiated pipeline that can address a range of cancers. For example, at ASCO last year, we presented data from CLN-619, which is our monoclonal antibody targeting the novel MICA, MICB pathway. And there we were able to show responses in patients that are typically unresponsive to checkpoint inhibitors, especially in lung cancer. And so we currently have expansion cohorts of that program in endometrial cancer, cervical cancer, as well as lung cancer. And we also have a study in multiple myeloma ongoing in relapsed refractory disease. That's CLN-619. Very recently, just over a week ago, we announced for our program zipalertinib, which is our EGFR exon 20 tyrosine kinase inhibitor, that we met the primary endpoint of overall response rate in our pivotal Phase 2B study in exon 20 relapsed non-small cell lung cancer. So we're planning to submit those data and present them at a medical conference mid-year this year. And then, pending FDA discussions with our partners at Taiho, we're planning our first NDA submission for our company. So we're excited about that milestone. And so immunology, oncology pipeline continues to move forward. And a couple of other things I would add are that at the end of September last year, we reported approximately $640 million in cash. So that gives us runway into 2028. And so I would summarize by saying we have a catalyst-rich year ahead of us with multiple shots on goal across immunology and oncology. We have the resources to continue to unlock the full potential of CLN-978 in autoimmune diseases and advance our oncology pipeline. You're all aware of the macro headwinds in the market. And so we're trading at below cash currently in terms of enterprise value. So we're getting no credit for our pipeline. We believe that the combination of these factors makes it a compelling value proposition for investors to invest in our company now, ahead of what promises to be a transformational year for Cullinan Therapeutics. Very good, Nadim. Thank you so much for setting that stage. We're going to discuss all these programs that you have. But just one high-level question. Could you maybe perhaps put in perspective some of the preclinical, translational, clinical data that we have seen on the TCE front that is driving the buzz around development of TCEs across many autoimmune diseases? Like why we didn't see it earlier? Because CD19, for example, is a very known target, right? It was just never very well developed for autoimmune. So what's driving that? And then we'll go into your programs. Sure. Yeah, let me start and then Jeff, please feel free to chime in. I think one of the things is anytime you see academic data come out, people want to be sure and they want to validate the data. And so I think the first foray into that space after Georg Schett and his colleagues did the pioneering work were people wanting to replicate the data to say, look, is this really what we think it is? And so I think that's where kind of a lot of companies that were developing, especially CD19 CAR T in cancer indications, pivoted to autoimmune diseases. So I think that was the first thing. And then I think people started thinking, well, the application of autologous CAR T, how are we going to be able to address autoimmune diseases where benefit-risk can be very different to oncology? And I'm somebody who worked on cell therapy for five years before I came to Cullinan. So I understand the transformational nature in hematology-oncology, but the risk-benefit is very different in autoimmune diseases. So I think then people, including us, by the way, started thinking, well, look, we can come up with a modality that can be delivered off the shelf, still a potential disease-modifying regimen, favorable safety profile, and then has all the convenience of an antibody treatment that can be delivered in the community rather than having to take patients to these CAR T-certified centers. And so I think it was a natural kind of start with replicating the data that you first saw with CAR T. Okay, what is the opportunity beyond CAR T? And I think ACR was really interesting. When you listen to some of the KOL teleconferences after ACR, one notable academic rheumatologist said, look, I went into ACR thinking about CAR T. I left ACR with T cell engagers on my mind. And so our view is that CAR T has provided a very powerful proof of concept, but a gateway to T cell engagers in these diseases because of all the issues we discussed. But Jeff, please. No, I don't think it's a whole lot different. So if you would have talked to us at this time last year, we were making this argument that CAR T had shown that very profound but transient B cell depletion could alter the course of not only SLE, but perhaps a much broader group of autoimmune diseases. But it was very challenging, even given the commercial uptake of CAR T, where it's potentially curative in oncology, to think about autologous CAR T as a scalable product addressing the unmet need across a very heterogeneous, very large patient population. Something dramatic would have to happen in our healthcare system to make that feasible. So I think the promise of a T- cell engager to be able to provide T- cell redirecting therapy, an order of magnitude more potent than the monoclonal antibody mechanism of action, but in a format that is potentially deliverable in community settings, outpatient settings, not unlike the way the T- cell engagers are given now in many oncologic settings, is what really captured people's interest. People can understand it as a product with immediate clinical applicability in a way that CAR T remains challenging. Got it. Very good. So let's go into your program. So 978, what are the features of 978 that makes it potentially best in class? And if you can sort of just also talk about structurally how it might be similar or different to Blincyto. Yeah. So I mean, Blincyto is the first T-cell engager approved. A CD19 T-cell engager has several shortcomings, most importantly of which is a very brief elimination half-life that requires continuous IV administration in order to deliver the drug. So other companies have thought about ways around solving for that by utilizing antibody formats. Many of those molecules are much larger than CLN-978, about three times larger. And there is some potential advantage of a smaller molecular format like 978 with 65 kilodalton potentiating intratissue penetration. There are some other aspects, though. Unlike blinatumomab, 978 is a fully human molecule. It is half-life extended through the addition of an antibody domain binding to human serum albumin, but in other respects has a BiTE-like structure in that the binding arms to CD19 and CD3 are comprised of single-chain variable fragments. Among the drugs that are in active development, it is relatively unique. There is another roughly similar BiTE-like format under development at iTab Med, but that drug still is handicapped by a short half-life and does require frequent administration even by the subcutaneous route. Probably the thing that I think is most unique is that we dialed in high affinity binding for CD19 and established preclinically and then subsequently in our now terminated non-Hodgkin's lymphoma project that there was a therapeutic index between robust- B -cell killing and cytokine production. By increasing the affinity for CD19, maintaining roughly medium-level affinity for CD3, we established a cytokine window that we think translates into an improved safety profile clinically. Again, we saw this in our preclinical studies in cynomolgus monkeys and then replicated those findings in the clinical study. Dialing down CD3, the detune CD3 approach has some potential challenges. That is the mechanism of action of a T- cell engager. So it's basically, I think in many clinical situations that hasn't shown differentiation, when you dose the molecule to actually achieve comparable efficacy, you tend to dose at a point where you overcome the detuned aspect of CD3 attenuation. Got it. With regard to, so it's a sub-Q and off-the-shelf, right? Eventually, how do you envision the treatment paradigm or administration to be similar to Rituxan or could be completely outpatient administration? Yeah, I think, going back to the CAR-T example, the most profound insight there is that deep but transient B-cell depletion could translate into prolonged therapeutic effect. A year, two years now, some patients with SLE have been followed without requirement for ongoing immune suppression. I think if you think about the first approximation would be to consider ways of delivering a T-cell engager to achieve a similar therapeutic effect with a defined duration of therapy. One thing about a T-cell engager unlike a CAR-T is that there is flexibility to retreat at the time of recurrence of symptoms. This would be a different paradigm versus rituximab in many instances where the plan, say, in a disease like MS, is for continuous maintenance therapy. At least with a T-cell engager, you have that flexibility. With a CAR T, it's hard to see how repeat dosing is either clinically or fiscally feasible. Got it. Very good. So then going into the SLE program that you have, could you just walk us through the study design? I understand there are two parts to it, part A and part B. How is the enrollment going? What is the difference between A& B? And when exactly and what type of data you envision to produce? Yeah, so let me start that one, so part A is the dose escalation phase and really the primary objective of the study, and that's to identify a safe target dose, and then our secondary endpoints include things like PK/PD parameters, B-cell kinetics, clinical activity. And so once we identify the correct target dose in part A, we'll use part B to address the question that Jeff raised, is what is the right schedule? Is it one dose and you're done? Is it two or three doses over a period of time? So we'll be able to address dose in part A and then schedule in part B, and as it pertains to your question about recruitment, as I mentioned, we cleared the IND towards the end of last year, so the team's very focused on activating as many sites as possible, it's a global study. We're expanding our site footprint in the U.S., Australia, and now Europe so we can rapidly accrue as many patients as possible. At the same time, we're having very productive conversations with investigators who are very excited about the possibility of exploring a potent disease-modifying regimen, but as an off-the-shelf therapy in their patients with autoimmune disease, especially in rheumatology. An example is the Lupus Research Alliance and Lupus Therapeutics who lead what's called the LuCIN Network. This is a network of experts in lupus who partner with the industry to run studies with the most promising treatments in lupus. And then the other part of your question around recruitment, I think as we head into Q4 this year where we plan to disclose the initial data, I think given the increasing competitive intensity in this space, I think we're going to be very thoughtful about how and when we provide other study updates. So we aren't enabling others given that we have a leadership position here, especially since CLN-978 is the only game in town currently in the U.S. from a clinical trial perspective. What type of SLE patients are you enrolling, and what is the FDA view on the type of patient that you could? Are you also willing to, or are you also enrolling LN patients, nephritis patients? Yeah, sure. It's a great question. So first, there are approved drugs for SLE. And while they are suboptimal with respect to efficacy, they are approved. So there is some expectation in a first in essentially first in disease, first in human study in SLE that patients will have exhausted at least some available therapies. So these will be treatment experienced patients who have likely been exposed or treated with more than at least two standard of care agents. The patients will have to have moderate to severe disease. This is roughly comparable to the patient population that's been treated in CAR T trials. And that will include patients who have lupus nephritis, but not patients with severe lupus nephritis. The ones who are rapidly progressing towards needing renal transplant dialysis, those patients are probably not sufficiently stable to be ideal for an early phase clinical trial. But I think our focus is to try to be inclusive of different organ system manifestations so that we can address a broad population of SLE patients and hasten accrual. Got it. Jeff, you mentioned a couple of times about this transient depletion of B-cell. Is there an ideal duration of B-cell depletion to ensure optimal efficacy? Yeah, theoretically, it's hard to say. I have heard Georg Schett say that very deep or subtotal B cell depletion for as long as a day, two days, may be sufficient. But that's something that's very hard to measure. I think it's more conjecture at this point, hypothesis rather than data-driven. But I think as studies continue to be conducted, as we see more data accruing about B cell depletion at the tissue level, we'll have a better understanding. Got it. I think he talks about valleys. Georg Schett talks about valleys, how you do the depletion. So in terms of the readout that comes out later this year, I understand the part A is more safety finding, but you do have part B where you could optimize the regimen. So when you produce the data, should we be focusing on safety? Are there particular endpoints like SLEDAI or proteinuria that we should be focused on, or it's just trying to understand how we think about the data? Yeah, great question. So I think if you look at the objectives of the study, right, so the primary objective, given that it's a Phase 1 dose escalation study, is establishing the safe dose. But we do in our secondary objectives include clinical activity measures like PK/PD dynamics, B cell kinetics, clinical activity, which includes some of the things you mentioned like impact on SLEDAI score, can you reduce autoantibody production, are you getting treatment-free remissions. So part A, we will be able to explore some of that. So ideally, we want to see both safety and activity from the study. Got it. And two more questions here on just this program. With regard to the TCEs, what is your view about this drug-free remission that we hear from either the CAR T players or physicians? Is there a potential that TCE sort of can achieve that? Yeah, I think so. I mean, that's been our contention since we undertook the strategic pivot this time last year, and I think at that point, we did it in the absence of any data. Without diving into too many details, there have now been published case reports or case series across a number of autoimmune diseases using both BCMA and CD19 targeted TCEs that have shown that this can happen, that patients can achieve this, so it's not theoretical anymore. It's demonstrated. I think those projects so far are hampered by the fact that they are one-off experiments. They're not rigorously designed clinical trials, and I say that the results at the end of the day establish proof of concept, but also establish that there needs to be some dose and schedule optimization. Yeah, I would add to what Jeff said. If you think of the two indications that we're pursuing, we do now have clinical data of CD19 T cell engager in RA, remember the paper from last year, and now more recently ACR in lupus. So in many ways, we view these as somewhat clinically de-risked indications. Got it. For your RA program, how should we think about the patient population? Is it going to be similar to the paper that read out last time? And then when should we expect data? Yeah, the first one's easy. We haven't yet guided to availability of the data only to initiation of the trial in Q2 of this year. We remain focused on that. With respect to the first question, it's not unlike the SLE patient population. There are a lot of drugs available for RA, but the sad fact is that many patients ultimately sequence through them. And so in this study, we'll be focused on what has been called difficult to treat RA, patients who would have failed multiple disease-modifying agents but have persistence of their disease. It's actually a pretty sizable population here in the US. It's at least 60-some thousand patients, which as compared to lymphoma, I think Nadim, you say it's all of lymphoma, B cell lymphoma in terms of the size of the patient population. Okay, got it. Then in terms of the choice of the target, obviously CD19, any thoughts about BCMA? Is that something of a plan? I'm just curious how the pipeline is going to shape up over time. Your thoughts on the targets? Yeah, so I think there has been some data showing we've sort of alluded to some activity of BCMA, but in those papers, B cells are also depleted. So it's hard to distinguish whether there's added benefit of plasma cell depletion. Theoretically, there could be some disorders that are better or differentially treated with BCMA. I think it's still a hypothesis to be demonstrated with data. What we do know is that CD19 is likely to be active across a large group, particularly one like 978 that is able to target the plasma cell compartments where CD19 is expressed in low copy numbers. And we do know that BCMA will come with substantial infection liabilities. So to develop a BCMA asset, you would have to decide that it has incremental efficacy that justifies the additional need for immunoglobulin prophylaxis, antimicrobial prophylaxis, and likely revaccination for common illnesses. Yeah, I would add the differentiation, the way we view it, is based on both the combination of the target, and we think CD19 is the optimal target, and the modality where we believe T cell engagers are the better modality, and as Jeff said, if you had to pick one target that covers the breadth of the B cell continuum, it is CD19. Okay, just quickly in the last few seconds on the oncology side, so you will be presenting more data at an upcoming medical meeting. Tell us what we should be looking at, what is making you excited on that program? For Zipalertinib, I presume. Yes. Yeah, so sure. We completed a pivotal trial in exon 20 insertion mutation patients who had experienced prior treatment with chemotherapy, as well as the now fully approved drug amivantamab in two parallel cohorts of patients. And we've shown previously that zipalertinib has robust clinical activity in both of those patient groups. But this will be data from our pivotal phase 2B study, which we have guided to presentation in Q2 of this year. And as Nadim shared, the upshot that we hope to submit for a new drug application in the second half of this year after regulatory discussions. Very good. I think that's all the time we have. Thank you, gentlemen, for your time.