Hi, good morning. Welcome to the JP Morgan Healthcare Conference. I know it's the final stretch on a Thursday, so really appreciate you all being here. My name is Raji Gunasekera. I'm with the healthcare investment banking team at JPM. Today, I'm pleased to introduce the team from Cullinan Oncology, and we have their CEO, Nadim Ahmed. I'll hand it over to you. Thank you. Thank you very much. It's a pleasure to be here to share all of the exciting developments going on at Cullinan Oncology. The next slide is my disclaimer slide. At Cullinan Oncology, we take a very unique approach to developing first-in-class and best-in-class programs through what we call a modality-agnostic targeted oncology approach. What that means is, at the start of our discovery process, we identify high-impact cancer targets, and it's only then that we think about the best vehicle to prosecute against those targets. So for us, it's always target first, modality second, rather than the other way around, unlike many other companies, and this means we're not dependent on a singular platform or even a single product. Secondly, we have a very high go, no-go bar across the R&D spectrum as we move molecules forward. We front-load as much experimentation as possible early into the discovery process through what we call thriller or killer experiments. So as the name suggests, when we get a killer result, we quickly terminate the program and reallocate our resources. When we get the thriller result, we look at how can we accelerate this program and increase our investment into this program. And so in this way, we only bring forward the most promising, highly differentiated molecules into the clinic, and our strategy is yielding results. We now have a robust clinical-stage pipeline across targets, across modalities, and across both hematologic indications and solid tumors. We've evolved very quickly in about 18 months from essentially a research-based company to now a development-stage organization, with our ultimate goal of becoming a commercial-stage biotech company, so that we can deliver on our mission to create new standards of care for patients with cancer. And as we've advanced these molecules into the clinic, we have a very exciting 2024 ahead of us, with multiple clinical data readouts across our programs. Starting with CLN-619, this is our anti-MICA/MICB antibody, where we showed single-agent efficacy last year when we presented the initial monotherapy data at ASCO. This year, we'll be presenting combination therapy data for the first time in 2Q 2024, where we combine CLN-619 in combination with pembrolizumab. Based on the early signal we saw with the monotherapy data, we also initiated cohort expansions in both endometrial cancer and cervical cancer, and those data will report out in the first half of 2025. Zipalertinib is our potential best-in-class profile, EGFR exon 20 inhibitor, and for that program, we plan to complete the accrual in the pivotal relapse disease study by the end of 2024. CLN-049 is our first-in-class FLT3 x CD3 T-cell engager, which is currently in a phase I dose-escalation study in relapse refractory AML and high-risk MDS, and we plan to present some data from this program in the second half of 2024. And CLN-418 is our first-in-class B7H4 x 4-1BB bispecific immune activator, and this is another program that's in phase 1 dose escalation in solid tumors, and we plan to present the initial data from this program in the second half of 2024. So we have a very data-rich environment in this year. The other point I'll mention is that we're very well capitalized, so we have a robust cash position with $417 million of cash at the end of 2023, giving us cash runway into the second half of 2026, well beyond the near-term clinical data milestones that I've laid out. For the purposes of this presentation, I'm gonna focus on three programs today, three key programs in our pipeline: CLN-619, our anti-MICA/MICB antibody; zipalertinib, our EGFR exon 20 inhibitor; and CLN-978, which is our CD19 x CD3 T-cell engager, especially in the context of all of the exciting data that we've seen with CD19-directed cell therapy in autoimmune diseases. So let me spend a few minutes talking about CLN-619, our anti-MICA/MICB antibody. As I mentioned, this is the first antibody in the clinic targeting MICA and MICB, and we were very pleased to share single-agent efficacy from ASCO last year. Now, MICA and MICB are ligands for the NKG2D receptor on NK cells and subsets of T cells, such as gamma delta T cells. You can see from this heat map that of all the NKG2 ligands that are out there, MICA and MICB are the most highly expressed across both hematologic malignancies and solid tumors. MICA and MICB is also not expressed on normal healthy cells, so therapies targeted MICA and MICB would be expected to have a broad therapeutic index. MICA and MICB is upregulated in situations where the cells undergo stress, so viral infection, malignant transformation. So when these cells express MICA and MICB, they then send a kill me signal to the immune system via the NKG2D receptors that we find on NK cells and subsets of T cells, and these cells are able to then destroy the cells that are sending this kill me signal through both the innate and adaptive immune system. In the next slide, on the left panel, you can see what happens in the case of cancer cells. So initially, because these cells become stressed, they do upregulate MICA and MICB. However, in the tumor microenvironment, proteases cleave the MICA and MICB off the cell surface, so then these cells once again become invisible and evade the immune system. In the middle panel, you can see how CLN-619 exerts its mechanism of action in multiple ways, again, invoking both the innate and adaptive immune system. So firstly, CLN-619 binds to and stabilizes MICA and MICB on the cell surface, so the immune system now is again able to see these cells. Secondly, CLN-619 also works through ADCC and ADCP by binding to the CD16 receptor on NK cells and subsets of T cells. And finally, CLN-619 also facilitates the direct interaction between MICA, MICB, and NKG2D on these immune cells. You can see on the far right panel how checkpoint inhibition can enhance the effect of CLN-619, because now you're invoking the full repertoire of T cells. Currently, CLN-619 is in a global phase I dose-escalation study, investigating CLN-619, both as monotherapy and in combination with pembrolizumab. As I mentioned, we were pleased to see the initial monotherapy data at ASCO last year, and based on that early signal, we opened up expansion cohorts in both cervical cancer and endometrial cancer as well. The next slide shows a swimmer's plot of the efficacy data, showing activity by dose level. Early on, we were able to start seeing stable disease, starting at the 1 mg per kg dose, and then we started to see objective responses at the 3 mg per kg dose. We saw three objective responses in 22 evaluable patients, one in a patient with parotid gland cancer, that was a complete response, and two objective responses in patients with endometrial cancer. In summary, 10 of the 22 evaluable patients experienced either an objective response or stable disease. Now let me go into the efficacy data in a bit more detail. Interestingly, of the three objective responses we saw, two of these responses were in patients that had progressed on prior checkpoint inhibitor therapy, an important clinical finding. The other interesting aspect of these responses is that the responses that these patients experienced on CLN-619 treatment was better than the responses they experienced on their prior therapies. So, for example, the parotid gland cancer patient had a best prior response on checkpoint inhibition of PR. This patient went on to subsequently experience a complete response on CLN-619 monotherapy. One of the endometrial cancer patients previously had a best response of stable disease, and this was on a combination regimen of checkpoint inhibition plus lenvatinib. The other endometrial cancer patient didn't derive any clinical benefit from her prior therapies. Both of these patients went on to experience a partial response on treatment with CLN-619. We did see an early signal among gynecologic malignancies in this initial data cut of the phase I study. So in addition to the two objective responses in endometrial cancer, three patients with cervical cancer also experienced stable disease, and two patients with ovarian cancer also experienced stable disease. However, we did also see clinical activity beyond the gynecologic tumors. Obviously, we saw a complete response in parotid gland cancer, but there was also a patient with breast cancer and a patient with salivary gland cancer that experienced stable disease. So we're very excited about these data, again, in the monotherapy setting. Now let's take a look at the safety data. The bottom line is the CLN-619 monotherapy data showed that this treatment is well tolerated. We saw no dose-limiting toxicities at any of the dose levels tested. And in fact, most of the adverse events were either grade one or two, and most of them were infusion-related reactions, which is typical for monoclonal antibodies. We did see one grade three laryngeal edema, but that was in a patient who did not receive their protocol-mandated steroid pre-medication. So we feel very good about the safety profile, both for ongoing monotherapy development, but it also makes CLN-619 an ideal combination partner also.... I mentioned we saw a signal in gynecologic malignancies, so let me talk a little bit more about endometrial cancer and how we're thinking about that opportunity in this next slide. Endometrial cancer is a very underdeveloped disease with very few approved or even effective treatments. Every year in the U.S., 66,000 women are diagnosed with endometrial cancer. 25,000 patients receive systemic therapy. The other aspect of endometrial cancer is patients often have multiple comorbidities, so there is indeed a high unmet need, not just for more efficacious treatments, but treatments that are also well-tolerated, which is obviously important in the context of CLN-619. And the clinical landscape is also changing with endometrial cancer. The main approved treatments in endometrial cancer are checkpoint inhibitor-based regimens, and they were originally approved in the relapse setting. Those treatments are now moving up into the frontline setting in combination with the current standard of care, which is platinum-based chemotherapy based on large randomized phase III studies. So as checkpoint inhibitors move up to the frontline setting, this leaves a very large and growing pool of patients in the relapse disease setting for whom there are no effective therapies. For us, this opens up a significant clinical opportunity as well as a commercial opportunity. Even the best treatments in this relapse setting post-PD-1, you see about a 15% response rate. As we think about next steps for CLN-619 in endometrial cancer, given this lack of approved treatments, there's a very clear regulatory pathway here, especially in relapse disease. I mentioned we've already opened up a cohort of monotherapy patients with endometrial cancer, and we're also now planning a combination therapy expansion cohort in combination with checkpoint inhibition. The data from both of these cohorts will be really important to inform our next steps as it pertains to a registration strategy in endometrial cancer for CLN-619. I will add, though, endometrial cancer is the beginning of the story, not the end of the story, given the broad profile we've seen of activity across tumor types. And so in summary, we're very excited about the opportunity with CLN-619, especially given the fact that we've seen single-agent activity, including objective responses. The molecule has shown us a very favorable safety profile, which makes it an ideal combination partner as we think about combination strategies in the future. We've clearly seen clinical benefit across a range of tumor types, including objective responses in patients who have progressed on prior checkpoint inhibitor therapy, an important clinical problem. I mentioned we've seen an early signal in gynecologic malignancies, and so we've opened up expansion cohorts already in endometrial and cervical cancer, and those are ongoing. I also outlined that there's a very clear regulatory path in this disease and a significant commercial opportunity for a drug like CLN-619. Our study is ongoing in both monotherapy and combination therapy, so we'll look for additional signals that will allow us to open up even more expansion cohorts with this important treatment. Again, summarizing and recapping, we'll be presenting the initial combination therapy data for our ongoing phase I study in second quarter of 2024, as well as the follow-up monotherapy data following the initial ASCO data presentation. In terms of the current expansion cohorts, we expect to report those data out in the first half of 2025. Now let me turn to another important program in our pipeline, addressing another significant unmet need, and that's zipalertinib, our EGFR exon 20 inhibitor. The exon 20 patient population makes up a substantial proportion of all mutated EGFR patients with an annual incidence in the U.S. of approximately 3,000-4,000 patients. Now, this is a disease with a really high unmet need, and I'll demonstrate that by the data that's published out there. So even in the frontline setting, patients with exon 20 non-small cell lung cancer, with the standard of care, which is currently platinum doublet chemotherapy, experience a median progression-free survival of only six months. So there's clearly a need for more effective therapies to address this disease. In the next slide, I can outline the profile for zipalertinib. We believe we have a best-in-class profile with this molecule, which bodes well and positions us well relative to the competition. Zipalertinib does have a unique chemical structure, which allows it to target the exon 20 insertion mutation, specifically relative to wild-type EGFR. It also doesn't bind to HER2, so this combination of attributes should portend for a favorable safety profile. In terms of efficacy, in our early phase I/II study, we've shown that zipalertinib is at the top end of efficacy that we've seen with the other approved agents, and we have Breakthrough Therapy Designation for this molecule, which for us is additional external validation of the best-in-class profile that we have with this drug. We are co-developing zipalertinib with our partners at Taiho, with the option to co-commercialize in the future, where we have 50/50 profit share in the U.S. Zipalertinib is currently in two pivotal ongoing studies, both in the frontline setting and in the relapse disease setting. Now let me dig into a little bit more about the clinical profile that we've seen in the initial phase I/II study. So we tested a range of dose levels with zipalertinib and we found the 100 milligram BID dose to give us the best balance of tolerability and efficacy. We saw a 41% objective response rate, which is at the higher end of the current approved agents in this space. We saw a median progression-free survival of 12 months, which again compares favorably with the six to eight months that we see with not only the approved agents, but the other agents that are currently in clinical development. We saw no grade three or greater rash or diarrhea, typical EGFR-related toxicities, and we think this is due to the specificity of the molecule for the exon 20 insertion mutation, and we saw a relatively low rate of dose reductions and dose discontinuation. So 100 milligrams BID is a dose we've taken forward into our pivotal studies. And so we believe zipalertinib has the best overall therapeutic profile, supported by efficacy at the higher end of what we've seen, a differentiated safety profile, combined with the convenience of an oral therapy. We also have, you can see in the next slide, a broad development plan with our partners at Taiho through the REZILIENT suite of studies. So REZILIENT1 is the study we're conducting, our pivotal study in the relapsed disease setting, where we're enrolling patients who have received prior chemotherapy. And we also have a very important cohort that we're enrolling, and that's patients who have received prior chemotherapy and prior exon 20 approved agents, which will be very important data, both from a commercial perspective and from a regulatory package perspective. Our partners at Taiho are conducting the REZILIENT3 study, which is our frontline study, combining zipalertinib plus standard of care versus standard of care. And our partners at Taiho are also exploring zipalertinib in other important patient populations, such as patients with active brain mets, patients with uncommon EGFR mutations, and also, also exploring zipalertinib monotherapy in the frontline setting. Okay, so now let me switch gears to another important program, a clinical stage program, and that is CLN-978, which is our T-cell engager, which targets both CD19 x CD3. We're obviously very excited about all of the developments we've seen with CD19-directed therapies in the autoimmune disease space, and we believe that this is a molecule that could be disruptive in this space. Now, CD19 obviously now has been clinically and commercially validated across B-cell malignancies, both leukemia and lymphoma, and it's also emerging as a very important therapeutic target in autoimmune diseases. T-cell engagers, as a modality, have obviously shown remarkable efficacy across a range of B-cell malignancies, again, including leukemias, lymphomas, multiple myeloma, and in many cases, have shown CAR-T-like efficacy without the issues associated with CAR-T, such as the logistics, practical administration, and some of the safety aspects. Speaking about CLN-978 specifically, this is a molecule that we've engineered to seek out very low levels of CD19 expression, and in vitro, we've already shown very impressive tumor cell kill at very low levels of the antigen expression. CLN-978, as I mentioned, offers off-the-shelf convenience in the form of sub-Q dosing, and we look forward to continuing to advance this molecule. In the next slide, let me go through the structure of CLN-978 very briefly. So as I mentioned, very high-affinity binding for CD19 at extremely low levels of CD19. In fact, at low levels, levels that are so low, sometimes are considered CD19 negative disease. It has a human serum albumin binding domain, which significantly extends the half-life of the molecule, and all components of this antibody are fully human, and so lowering the risk of things like ADAs, et cetera. As I mentioned, in vitro, we've seen robust tumor cell killing at very low levels of CD19 expression, and very importantly, in our non-human primate studies, with one single dose of CLN-978, we were able to see profound and complete B-cell depletion, which is very important as we think about the application of this molecule in autoimmune diseases. As I mentioned, CLN-978 is currently in an ongoing phase 1 dose escalation study in relapse refractory lymphoma. Now, many of you may be aware of obviously the exciting data we've seen of CD19-directed cell therapy in autoimmune diseases, and I'm showing here the original work from the group at the University of Erlangen in Germany, where they were able to show very deep and durable remissions in lupus. And again, they also updated the data at ASH, where they were able to extend these deep and durable remissions into other autoimmune diseases. So obviously, that's got our attention, and is exciting for us. We believe that CD19 for autoimmune diseases is a much better target than CD20, given the breadth of coverage you get across B-cell lineage. And relative to CAR-T or cell therapy, CLN-978 offers a potent off-the-shelf therapy. You don't need lymphodepletion regimens. It's not associated with some of the second primary malignancies that the FDA is reviewing cell therapies for. So we believe this could be a powerful alternative to cell therapies in this space, and as I mentioned, we have an ongoing phase 1 study in lymphoma, but that will also, probably give us additional important data, especially as it pertains to B-cell depletion in patients, which will be important considerations as we think about autoimmune indications. And so this is a very high-priority program for us, and we're very excited to have the opportunity to take an off-the-shelf, potent CD19-directed therapy into the space of autoimmune diseases. And now let me conclude. So today, I covered three key programs in our pipeline. I mentioned we have a strategic approach that takes only the best first-in-class or best-in-class molecules into the clinic, and so we have multiple shots on goal. Not only do we have multiple shots on goal, we have multiple high-quality shots on goal. I mentioned that we have set ourselves up for a very data-rich 2024, going into the first half of 2025, so multiple value creation opportunities based on important clinical data readouts across our portfolio. We have a robust cash position of $470 million of cash at the end of 2023, which gives us runway into the second half of 2026, comfortably beyond the near-term data milestones I mentioned, allowing us to continue to advance our pipeline. 2024 will be a very important and exciting year for Cullinan Therapeutics. And so finally, I'd like to thank JP Morgan for the opportunity to showcase the work of my brilliant colleagues at Cullinan Oncology, and thank you very much for your attention. Happy to take questions. We'll now be taking questions from the audience. We just ask that you wait for the mic so, folks on the webcast will be able to hear you. Thank you. So you're doing a trial combining zipalertinib. Yeah. So you're doing a trial combining zipalertinib plus platinum-based chemo- Yeah ... in the front line. Have you reported any data off zipalertinib in combo with that chemo already? We haven't. Actually, this study does have a safety run-in phase as well, so that we get the data that you're alluding to. The one thing I will add is, you know, what we've seen with Janssen and the PAPILLON study, which was positive, clearly, was that probably the best approach for the frontline setting is to combine with standard of care rather than take the approach of monotherapy TKI, for example. That didn't work with Takeda, right? Because that confirmatory study failed, and some of our competitors are actually repeating that experiment. But when we were designing this study, we heard very clearly from U.S. investigators, you need to combine with standard of care so that you fully optimize patient outcomes. Thank you. Yeah. Any other questions from the audience? All right. I'm actually glad you have this slide up. So you have six programs. How do you expect to advance all of these? Sure. We do have a lot going on, but I can tell you it's a better problem than the opposite problem, where you don't have any assets. And look, just about 18 months ago, the only program we had actually was zipalertinib in the clinic. So the team has done a remarkable job of execution, going from one program in the clinic to now six programs in the clinic. You know, as I mentioned, we're very disciplined about hitting go and no-go criteria. So as I think about your question, zipalertinib is obviously already in the clinic in pivotal studies, right? So that's on its path to regulatory approval and commercialization with our partners at Taiho. CLN-619, I shared the important efficacy data, so in a way, that's already hit our go criteria, and we're looking to how can we exploit that opportunity. Then we have four programs in phase I. So the way we think about it is phase I clinical trials is a relatively low cost base relative to the phase II and phase III studies you need to do afterwards. That's one thing. Secondly, we've seen, especially over the past year or so, that if anything's gonna move the needle, it's clinical data, not preclinical data, right? So for each of these additional four programs, I went through some of the data outlines through 2024 and 2025. We need to complete the experiment, turn the cards over, and then we'll know how many programs we have. So there'll be very clear go, no-go criteria at the end of each of these phase I experiments. If we don't hit our go criteria for one of our phase I programs, we're very good at killing those programs and then thinking about redeploying capital. But the other thing I would add is, look, we're in a business of attrition as you go through the various stages of of development, right? And so while, you know, we have five programs in phase I, I would love every single one to work. You know, the history and the data shows that's probably not likely to be the case, so we would expect some, you know, level of attrition. And then, look, if we do hit more upside potential in terms of clinical data than we expect, well, that drives value in the company, and, you know, again, we have the opportunity for strategic optionality and talking to partners from a strategic opportunity perspective, as well. So that gives us... Just like we did with zipalertinib and Taiho. So for us, I think we feel very good about the programs we have in flight. Yes, the quantity is high, but, you know, when you account for attrition, when you account for, you know, data that you get, we feel we're in a very good place, and in the relatively near term, we're gonna be turning over the data cards for each of these programs, and looking forward to doing that. Speaking of data, could you talk about what we can expect in terms of updates this year, specifically your Q2 update coming out for CLN-619? Sure. Happy to do that. So as a reminder, this is the first time we're presenting the combination therapy data in combination with pembrolizumab. Last year, we presented the monotherapy data. So we'll present updated monotherapy data following what we presented at ASCO. For the combination therapy cohort. We started the dose escalation at a higher dose level since we saw the data in the monotherapy cohort. And so there we'll probably have maybe a couple of dozen patients and probably about 40 patients in the monotherapy arm. And for us, you know, there's always the challenge of how do you interpret combination therapy data, right? And so the things we'll be looking for is, you know, in the combination cohort, are we seeing activity in tumor types where you typically don't expect checkpoint inhibitors to work? Are we seeing activity in patients who have already progressed on prior checkpoint inhibition therapy? So I think we'll have some, we'll have some useful data here, but again, you know, this is the first cut of the data. Thank you. And now, why do you think that CLN-619 is so active in gynecological tumors? And what do you think is the regulatory path or efficacy bar for endometrial cancer? Sure. Yeah, so, you know, we clearly saw an early signal in gynecologic malignancy, so very, very pleased to see that 'cause it allows you to kind of focus your development. At the same time, though, I will point out we did see activity outside gynecologic malignancies. We saw the complete response in the parotid gland cancer patient. We saw prolonged stable disease in a patient with breast cancer. We also saw stable disease in a patient with salivary gland cancer. So we do feel we're at the beginning of the story, but the guidance signal does help us to kind of focus our development. As I mentioned, we've opened up expansion cohorts in endometrial cancer, cervical cancer. You know, we have some theories of why there could be additional activity in gynecologic malignancies. We know, you know, the female reproductive organs has relatively high levels of MICA mRNA expression. We know that. We know the literature shows that estrogen can often upregulate MICB expression, MICA-MICB expression. We also know that, you know, NK cells are often implicated in the physiology of the uterus, both normal pathophysiology and malignant disease as well. So there's some theories. I mean, we don't know for definite yet, but the ongoing study will show us, and of course, our very rich biomarker plans as well. How have recent developments in the EGFR exon 20 space sort of affected the prospects for zipalertinib? Sure. In a way, it's kind of going back to your earlier question as well. So overall, lots of changes in the exon 20 landscape, including some companies have recently dropped their programs. Now, you probably saw that earlier in the week. For us, we think it's a net, net positive for zipalertinib. So why do I say that? Well, as we discussed, the phase III studies design of frontline non-small cell lung cancer follows the design of a positive study that's already out there. And so we think that validates our REZILIENT3 study. And so we feel good about the opportunity in the frontline disease setting. You know, in the relapse disease setting, since the withdrawal of mobocertinib because of a failed confirmatory study, that kind of reaffirms the unmet need in the relapse disease setting. Again, we feel we have a best-in-class profile, so the relapse disease setting is now wide open from both a regulatory and commercial perspective. And then the last point I'll add is, you know, in our pivotal relapse disease study, we are also enrolling that very important cohort of patients who have received prior chemo and prior exon 20 agents, which we think will sufficiently strengthen our regulatory package and support our commercial positioning as well. Got it. And given the CD19 CAR- T developments in autoimmunity, what opportunity you see with your CD19 T cell engager, CLN-978? Yeah, so obviously, we're currently reviewing next steps here. So for us, it's really a case of how to progress, not if to progress. You know, we believe that a T-cell engager approach could be very disruptive in this setting, especially relative to treatments like cell therapy, where again, there's practical considerations, lymphodepletion, some of the safety things that we're seeing with the FDA reviewing the second primary malignancies. So we're very excited about the opportunity to take this molecule, which, by the way, there's only currently two CD19, CD3 T- cell engagers in the clinic versus however many cell therapies, and we heard that from the prior presentation here. So we feel, again, this kind of fulfills our first-in-class, best-in-class opportunity, and we think it could be a significant disruptor in the autoimmune disease space. Definitely something we're looking forward to taking to that setting. Thank you. I think there's a question over there. Yeah. One more question about CLN-081. We know that amivantamab is about to get a full approval for first-line EGFR exon 20, right? And turn this product to a fully approved product for these patients. So do you think there is still a chance for our CLN-081 to get an accelerated approval based on the phase IIb trial? Yes, I do. And, and the reason we feel confident about that still is because we're enrolling that cohort of patients who have received prior chemotherapy and prior exon 20. If we didn't have those dataset, I agree, I think it would be challenging. But we believe that having those two cohorts will give us a very strong regulatory package and potentially fulfill the unmet need for accelerated approval. Okay, thank you. Any other questions from the audience? All right. If not, that concludes this session. Thank you very much to the Cullinan Oncology team, and thank you, Nadim. Thank you, everyone.