Welcome to the Morgan Stanley Global Healthcare Conference. I'm Jeff Hung, one of the biotech analysts. For important disclosures, please see the Morgan Stanley Research Disclosure website at www.morganstanley.com/researchdisclosures. If you have any questions, please reach out to your Morgan Stanley sales representative. For this session, we have Nadim Ahmed, CEO of Cullinan Oncology. Welcome, Nadim. Hey, good to be here, Jeff. For those who may not be as familiar with Cullinan, can you provide a brief introduction? Sure, yeah. So we're a company that takes a very unique approach to the discovery process, which we call modality-agnostic targeted oncology. So that means we start the discovery process by identifying high-impact cancer targets and then deciding on the right vehicle to prosecute those targets. So in other words, for us, it's target first, modality second, not the other way around, which you see with many of our peers. So that means as a company, we're not contingent or dependent on a singular platform or even a singular product. So that's one thing. Secondly, we have a very high bar in terms of go, no-go criteria. So we front load as much experimentation as possible, as early as possible, through what we call thriller or killer experiments. So if we get the killer result, as the name suggests, we kill the program, move on, reallocate our resources. If we get the thriller result, then we think about how can we accelerate this program? How can we increase the investment? And so by doing this, we make sure that we only take the most promising, highly differentiated molecules into the clinic, so that we can deliver on our mission to create new standards of care for patients with cancer. So that's kind of the theoretical construct, and I would offer two proof points to say this is working. So if you look at our pipeline today, we have a very diversified pipeline, across targets, across modalities, across solid tumor and hematology. All programs have the potential to be first or best in their class, which is important for us. And also, you know, in about 18 months, we've gone from one program in the clinic to this year, six programs in the clinic, which is a remarkable execution by the team. As we have evolved from a research-based company to now a development stage organization, and ultimately, our goal of becoming a commercial stage biotech company. And then the final point I'd add, we're very fortunate to have a very robust cash position, which gives us a runway into 2026, and the opportunity to create multiple value creation milestones over that period of time. Great. Thanks. Maybe let's start with zipalertinib, which is partnered with Taiho. How is that differentiated from competing treatments, and how does it fit into the treatment landscape? Sure. Look, the first thing I would say is that exon 20 non-small cell lung cancer is still a disease with very high unmet need. So if you look at even in the frontline setting, today, platinum chemotherapy, which is a standard of care, produces a median progression-free survival of 5-6 months. Checkpoint inhibitors don't seem to work in exon 20 disease or EGFR disease broadly. And then coming back to your question, Jeff, you know, we have 2 agents already approved in the relapse setting, but we feel that there's still plenty of room for opportunity based on the observed clinical profile of those agents. So if you think about a drug like, amivantamab, which is a good drug for the disease, you know, you have, an IV therapy, prolonged infusion times. We still see some of the wild type EGFR-related toxicities. We see a high rate of infusion reactions, almost two-thirds of patients. So we think there's opportunity there for us. With mobocertinib, you see quite a high rate of wild type EGFR-related toxicities like rash and diarrhea. And so when you look at the clinical profile of zipalertinib, which we still believe has the potential to be best in class, we have a response rate of 41% that we saw in the Phase 1/2a study, which is at the upper end of the response rate we see with currently approved agents. We have a median progression-free survival of 12 months, which is favorable to the 7-8 months we've seen with the currently approved agents. We've shown activity in prior exon 20 treated agents, which I think is important for us. In terms of the safety profile, again, all at the 100 mg BID dose, we don't see the typical, grade three and above, wild-type EGFR-related toxicities, like rash and diarrhea. So I would say in summary, we have we have an efficacious molecule at the upper end of efficacy that we see with current approved agents, a favorable safety profile, all combined with the convenience of an oral therapy. Now, last month, you and Taiho announced the start of the Phase 3 combination study. Can you just talk about the study and what you need to see for the study to be considered a success? Sure. So the study is a randomized study, starting with a lead-in safety phase, comparing the combination of zipalertinib plus chemotherapy-based treatment versus chemotherapy alone, and the primary endpoint is progression-free survival. You know, earlier I said in the upfront setting, today, with platinum-based chemotherapy, we're seeing a median progression-free survival of 5-6 months at best with most series. As I mentioned, with zipalertinib in the second-line plus setting, we've seen a progression-free survival benefit of 12 months, median progression-free survival. So we feel pretty confident that the combination of zipalertinib plus chemotherapy has the opportunity to have a significant improvement over chemotherapy alone, and we look forward to execution and ultimate reporting out of that study. For your Phase 2 B study, can you just remind us of, like, how enrollment is going in that study? Sure. So our our pivotal relapse study started at the end of Q4 2022. Enrollment continues, and the study design actually is very similar to the approved agents, amivantamab, mobocertinib, where we have about a 100-patient study, primary endpoint of overall response rate, duration of response, single-arm study, aiming for accelerated approval. As I said, enrollment continues, and so we feel pretty good about where we are with that study, and we look forward to reporting out those results. Great! Let's shift to CLN-619. Can you just remind us the mechanistic rationale behind targeting MICA/MICB as a pan-cancer approach? Sure. So MIC-A and MIC-B are both ligands for the NKG2D receptor that you find on NK cells and subsets of T cells. In a normal situation, you don't see the upregulation of MICA/MICB on normal cells. However, when cells undergo stress conditions, like viral infections, like malignant transformation, you see an upregulation of MICA/MICB. What happens then is that those cells send a kill me signal to the immune system, so that then NK cells and subsets of T cells can come and destroy those cells. What happens in the situation of cancer is that proteases in the tumor microenvironment actually cleave MIC-A and MIC-B off the cell surface. So that's a way that the tumor can evade the immune mechanism again. What CLN-619 does, it binds to and stabilizes MIC-A and MIC-B on the cell surface of those tumor cells, which then become visible to the immune system again and get flagged for destruction. It works in multiple ways. Through binding to the CD16 receptor on NKG2D cells, we see ADCC, ADCP. CLN-619 also enhances direct interaction between NKG2D, as well as the MICA/MIC-B interaction. You see that CLN-619 actually activates both the innate and adaptive immune system. For us, that bodes well from a development perspective in both monotherapy, combination therapy. The other thing that's exciting about this program is that, you know, it has the opportunity to have pan-cancer potential, since MIC-A and MIC-B are ubiquitously expressed across a range of solid tumors and hematologic tumors. Great. Now, at ASCO, you reported initial data. Can you just remind us what you saw? Sure. So we have an ongoing Phase 1 dose escalation study, investigating CLN-619 as monotherapy and in combination with pembrolizumab. So at ASCO, we were excited to report the monotherapy portion of that study, where we saw single agent activity. So we saw three objective responses starting at the 3 mg per kg dose of CLN-619. So we saw a complete response in a patient with parotid gland cancer, and we saw two confirmed objective partial responses in endometrial cancer patients. So that got us excited about the program, and two of those three responses are in patients who had progressed on previous checkpoint inhibitor therapy. All of those responses were ongoing at the time of data cutoff, so that was, you know, very interesting for us. The other thing I'd say about the responses that we observed are that each of these responses on CLN-619 were better than the response that these patients experienced on their prior therapies. So, for example, the complete response we saw in the parotid gland cancer patient, that patient had experienced the best response of partial response on prior checkpoint inhibitor therapy, but consequently experienced complete response subsequently on CLN-619. With the 2 endometrial cancer patients, one of those patients experienced the best response of stable disease on a combination regimen of checkpoint inhibition and lenvatinib. The other endometrial cancer patient, she didn't experience any sort of benefit on her 5 prior therapies. Both of those patients experienced a partial response on CLN-619, which for us was very exciting. The other thing that was interesting about this dataset is we did start to see a pattern of gynecologic malignancy activity. So in addition to the 2 endometrial cancer responses, we saw prolonged stable disease, 3 of those in ovarian, in cervical cancer patients, 2 in ovarian cancer patients. So there was an early signal of gynecologic malignancy activity, but it wasn't limited to that. So we also saw a prolonged stable disease in a breast cancer patient, in a patient with salivary gland cancer. So it just showed that 619 has the opportunity to work across a range of different tumor types. And so obviously, we're very excited about the data that we saw at ASCO. What should we expect to see in the initial combination data, and, and do you have a sense for when that might be? Sure. So the thing to point out there is, you know, we took this parallel development path for monotherapy and combination therapy. However, the combination therapy arm was staggered because we had to establish some safety of monotherapy first before we could start the combination therapy. So those data will be forthcoming, we haven't disclosed when yet, but it will be at a future medical meeting. You talked about this parallel, you know, structure, but I guess, how are you thinking about the future development of 619? Sure. So, post ASCO, based on the monotherapy signal that we saw, we already declared monotherapy expansion cohorts in both cervical cancer and endometrial cancer. So other expansion cohorts will follow based on the signal we see, both in the monotherapy arm as well as the combination therapy arm. So I think there's plenty of opportunity there. And then, Jeff, if I take just one example of endometrial cancer, there we have a situation where we have a very clear regulatory path. And what I mean by that is, in endometrial cancer, currently, checkpoint inhibitors are the only approved therapy in the relapse setting. Those agents now, for example, the recent approval of dostarlimab in combination chemotherapy, are moving up into the upfront setting. So that leaves a very large and growing pool of relapse patients for which CLN-619 could enter a very clear regulatory pathway. So you have the potential to gain accelerated approval with a single arm approach, and that would unlock a significant clinical and commercial opportunity for us. But that's just one example of what we've seen early that can lead to a very clear path for regulatory approval and commercialization. Great. Let's move to CLN-049. You know, what are the limitations of current FLT3 inhibitors, and how is 049 differentiated? Sure. So the first thing I would say is, look, now FLT3 is both a clinically and commercially validated target with now 3 tyrosine kinase inhibitors approved in that setting. The other point I would make is where CLN-049 is different to the tyrosine kinase inhibitors. Remember, they target only the mutant form of FLT3, which is about 30% of patients. With CLN-049, because it binds the extracellular domain of FLT3, it means basically it's agnostic to mutational status. So we can target both wild type and mutant FLT3, which opens up about 80%+ of patients, so a much bigger patient pool. Also, as a T cell engager, you know, compared to, some of the agents in development that target CD33, CD123, for us, FLT3 is a target that has a potentially broader therapeutic index because it's relatively highly expressed in blast cells compared to normal myeloid cells, for example. So, so that would be another, aspect. And then, in addition to blast cells, FLT3 is also expressed in pluripotent stem cells, so we have a potential for improved durability of response. And then, as I mentioned earlier, we, you know, the tyrosine kinase inhibitors and T cell engagers are very different mechanism of action. So tyrosine kinase inhibitors target the FLT3 signaling pathway, whereas CLN-049 actually harnesses the power of T cells, a more potent approach, which we think, again, can enhance durability of response. Great. And how are you thinking about the potential opportunity in AML? Sure. So AML is a disease in the US, about 20,000 patients are diagnosed every year with this disease. And really, until today, the only curative form of therapy is, you know, allograft with high-dose therapy. The problem is, these are elderly patients, so actually, probably 75% upwards of patients actually are not eligible to receive this very intense curative approach. And so as you think about that, you know, that makes a challenge in terms of curative drugs for the future. And when you look at the more recently approved drugs, they tend to target subsets of patients. So it's become a very fragmented disease, IDH1, IDH2, mutant FLT3, menin. So there's clearly a need for an agent that's more broadly applicable and that can induce durable responses, and I think that's where we see there's an opportunity for CLN-049. Now, you're currently running the first-in-human study. Can you just talk about the initial safety data, that you've seen for-? Sure, of course. Look, we were pleased to have an abstract at the European Hematology Association this year of the initial safety data from the CLN-049 ongoing study. Look, we started out with a single ascending dose study, where we saw, you know, some cytokine release, as well as low-grade CRS, which we thought was a good marker of the postulated mechanism of action. We then, after completing the single ascending dose study, quickly pivoted to the multi-ascending dose study, which we started in December 2022. And there, we also switched from IV therapy to sub-Q therapy, which seems to be the trend among T cell engagers now, as you look across heme indications, just because it can reduce the risk for CRS. So that study is actively ongoing, and we look forward to sharing those data in the future. Okay, good. Maybe shifting to CLN-418. You've licensed rights from Harbour BioMed in February. So how's 418 differentiated? Sure. So, CLN-418 is a first-in-class clinical-stage bispecific immune activator. It binds with high affinity to B7H4 because the dual binding arms it has. It also, because it's B7H4 and 4-1BB, it conditionally activates 4-1BB. So only when you bind both B7H4, which is a tumor-associated antigen, and 4-1BB, so that you're localizing activity into the tumor itself, which should then portend for a broader therapeutic index in terms of both efficacy and safety. It also has a silenced Fc domain, which means we don't see non-specific T cell activation. And so our view is that this is an agent that has potential to be a pan-cancer opportunity, and, you know, we are currently conducting a Phase 1 dose-escalation study and guide it to data in 2024. So far on that data, like, what should we expect to see in those results? Sure. So, yeah, again, this is a Phase 1 dose-escalation study, so primarily, the initial data is gonna be focused on safety. Of course, we are collecting, you know, response data, et cetera, but, the primary objective of Phase 1 dose-escalation study is the safety, so that would be our first data set. You recently started Phase 1 for CLN-978. Can you just talk about the rationale for 978 and CD19 as a target? Sure. So CD19 is another target, which I'm sure you're familiar with, is that it's been both commercially and clinically validated now with both conjugated and unconjugated CD19 antibodies, as well as CAR T therapies in the marketplace now. The CD19 antibodies, either conjugated or unconjugated, don't seem to be very effective in that setting. Of course, CAR T therapy has been effective. CLN-978 is a drug that targets both CD19 and CD3. It has a human serum albumin binding domain for prolonged half-life, and it's also shown to have very high affinity for the target antigen CD19. So we see it binding in very low level expression settings, which we think is particularly attractive. And why do I say that? Well, there's at least two opportunities that we can think of in the lymphoma space. So given the potency of T-cell engagers, it has the opportunity to deliver CAR T-like efficacy, but as an off-the-shelf therapy. So that's one attractive opportunity for us. Given its very high binding affinity to very low levels of antigen expression, we also think there's a role in the post-CAR T setting, as CAR T therapy is now moving, for example, to the second-line setting in diffuse large B-cell disease. CD19 loss is often a resistance mechanism. So even in that post-CAR T setting, there's a clear patient segment where we think this drug has the opportunity to work. And then the other thing I'll add is that, you know, CD19 in the last couple of years has become a very hot target in autoimmune diseases. And so when you look at CD19 approaches in autoimmune diseases like lupus, for example, it's all been CAR T therapy. Well, you know, the advantages of a CD19 T-cell engager are clear and obvious relative to a CAR T therapy, especially in the context of an autoimmune setting. So that's another reason we're excited about that molecule. Can you talk about the Phase 1 for CLN-978, and then what should investors watch for in the initial data? Sure. So we just started dosing in our Phase 1 dose escalation study, looking at a range of relapsed refractory B-cell or non-Hodgkin's lymphoma subtypes. So since we only started dosing, you know, about a couple of weeks ago, it's a little bit early to talk about the data per se, but, you know, we're obviously excited about that program. Okay, great. And then CLN-617 is about to enter the clinic. What excites you about this program, and how is CLN-617 differentiated from other approaches? Sure. So, the reason we're excited about CLN-617 is, you know, it's taking 2 very potent cytokines in IL-2, IL-12, putting it into a fusion protein. We also have a collagen binding domain, which should retain the cytokines within the tumor, which is really important from a safety perspective, and we're doing this all through intra-tumoral injection. So we think that this is an exciting program. You know, our preclinical data package was very robust. It showed clear abscopal activity that you want to see, so that we saw activity in non-injected distal tumor sites. We also saw a T-cell memory effect induced, which prevented regrowth of tumor. We also saw activity in PD refractory tumor models. And so look, this is a program that cleared an IND at the beginning of this year, and we look forward to dosing patients by the end of this year in our first Phase 1 study. Maybe one last question is, what, if anything, do you think that investors maybe most misunderstand, about the Cullinan story? Sure. So, yeah, I spoke about our strategy, which is differentiated, and I think we are seeing the fruits of that strategy with a number of programs now in the clinic. Secondly, CLN-619, I think, is a very exciting and important molecule. We've seen monotherapy activity in Phase 1, which is pretty uncommon. Like, if you think about some of the excitement around LAG-3 TIGIT at this past ASCO, those specific agents didn't show any objective responses in Phase 1. So we were very pleased to see that single agent activity. We look forward to updating both the monotherapy data, combination therapy data. So I think that, for us, is clearly a very important program now, and we're starting to see where we have clear regulatory commercial paths. So that'd be one. You know, as I mentioned earlier, in 18 months, we've gone from 1 program in the clinic to 6 programs in the clinic. I think by having 6 programs in the clinic, which seems a lot for a company our size, but it also gives us strategic optionality. You know, as we turn those data cards over in the coming months, it also provides strategic optionality for us to decide which of the programs that do we want to continue to develop ourselves and which of those do we want to partner. And so that strategic optionality, I think, is underappreciated by investors. I think investors look at, "Wow, 6 programs, how are they going to do all this by themselves?" But that's not how we think. I mean, the way we've in-licensed in the past, we've taken in important molecules, but it, it's a two-way opportunity. And so I think having the opportunity to decide what you do in terms of six clinical programs actually gives us tremendous strategic optionality and to drive further value creation, whether it's internally at Cullinan Oncology or externally with partners. Great. Thanks so much for your time, Nadim. Appreciate it, Jeff. Thanks a lot. Thanks, everyone.