Good morning, and 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 Cullinan Oncology with CEO Nadim Ahmed. Welcome, Nadim. Thanks, Jeff. Good to be here. For those who may not be familiar with Cullinan, can you provide a brief introduction? Sure. At Cullinan Oncology, as the name suggests, we're purely focused on cancer. We have a broad and deep pipeline currently of eight programs in the clinic, and they span a range of hematology and solid tumor indications across a range of different modalities as well. We currently have three programs in the clinic, and by this time next year, we'll have five programs in the clinic. Within each of our programs, we really focus on developing either first in class or best in class assets. That's the kind of strategic approach that we take. We're fortunate to have a pretty robust cash position. At the end of Q2, over $650 million in cash, which gives us a five-year cash runway to and through the end of 2026. We have a leadership team that has great depth in oncology, again, across hematology, solid tumor indications, across different modalities. Functionally, we have expertise in research, development, and commercialization as well now on the leadership team as we build out the leadership team. You know, talking again about the cash, you know, we're looking at ways of how can we accelerate kind of our current pipeline. How can we continue to bring in interesting assets, especially in the current market dislocated conditions. Ultimately our goal is to kind of evolve from, you know, a discovery machine to a late-stage development company and ultimately to become a commercial stage fully integrated biotech company. That's a little bit of background about Cullinan Oncology. Great. Maybe before going to the pipeline, let's talk about Cullinan's approach. You kind of touched upon this, but, you know, you take a pretty unique approach to driving innovation, so maybe if you can talk a little bit about that. Sure. I would say modality agnostic precision oncology is kind of at the heart of our discovery efforts. Our discovery team focuses on identifying high impact targets and then identifying the best way to prosecute against those targets. We do the target first and then the modality rather than the other way around. That's allowed us to build out a very diversified portfolio. If you look at our portfolio, we range from small molecules to biologics to fusion proteins. We're very much driven by the target as opposed to the platform. That means we're not dependent on one specific platform. That's one aspect of it. You know, as well as modality agnostic, we're very agnostic to the source of innovation too. You know, we look to the external environment, external partnerships. We call it innovating without borders. We recognize there's a world outside of our shop where there's excellent innovation taking place, and you can see that reflected in our pipeline. Ultimately our goal is to make sure that we're bringing forward only the most promising oncology assets. We're pretty rigorous in our early-stage discovery efforts through what we call thriller or killer experiments. If it doesn't meet the criteria, we kill it, and if it does meet the criteria, we double down on the investment to progress those molecules. The areas we really target, we have kind of three key criteria for advancing our assets or as we look at business development opportunities. As I mentioned earlier, it has to have the potential at least to either be first in class, or best in class. Assets that either activate the immune system or target key oncogenic drivers. Pre-clinically, at least, we have to see monotherapy activity. We're very disciplined about the way we progress assets and as we bring assets in as well. Again, modality agnostic and also agnostic to the source of innovation. Ultimately, our goal is to create new standards of care for patients with cancer. Now in June, Cullinan announced an agreement where Taiho gets back U.S. rights to CLN-081, and you jointly develop and commercialize in the U.S. Can you talk about that deal and why was now the right time? Sure. I guess this was one of my first projects that I walked through the doors at Taiho Oncology back in October 2021. I asked the team to look at the range of strategic options that we had for CLN-081. Ultimately, for us, a couple of things I've mentioned. You know, one, it was a competitive process. Two, we picked the deal that had the best financial terms and strategic terms for us. As a reminder, we got $275 million upfront, which was obviously cash is king right now, so that's important to us. We get an extra $130 million based on U.S. regulatory milestones on the core indications of front line and second line exon 20 non-small cell lung cancer. Strategically important for us, we get to participate in the 50/50 profits in the U.S., which obviously is an important oncology market. It's a co-development and co-commercialization agreement. The co-development is 50% funding of the U.S. development. We have a strategic option to co-commercialize in the future. Why have an option to co-promote in the U.S.? Why not just get a royalty on U.S. sales? Sure. Great question. I would say a couple of things. One, you know, arguably the U.S. is the most important oncology market in the world. For us, it was really important to be able to participate at a much higher rate through a 50/50 profit share than it was to kind of just set up a royalty stream, right? The 50/50 participation is really important for us. Strategically, I mentioned earlier that our ultimate goal is to become a commercial-stage biotech company, right? Through a 50/50 profit share and co-commercialization agreement, it allows us to build a commercial infrastructure in a very lean and cost-efficient way that can be applied to CLN-081, but also the rest of the pipeline that I spoke about. You know, the overwhelming financial benefits and strategic benefits of the deal, you know, made it quite an easy decision for us to move forward with Taiho Oncology, who by the way, has been a great partner for us When is the deadline for exercising the right to co-promote in the U.S.? Like, what would be the deciding factors for that, and how are you thinking about the sales force that would be needed at Cullinan? Sure. As I mentioned, the co-commercialization is an option. We're gonna make a decision as we get closer to launch. We have plenty of time to think about both the market conditions, the competitive environment, et cetera. Any sort of decision on what that structure would look like, we're gonna defer until we need to make that decision. We have that strategic optionality, which is important for us. Great. Maybe moving on to CLN-049, the FLT3 program. That's a bispecific antibody. Like what are the limitations of current FLT3 inhibitors, and how is 049 potentially better? Sure. Again, as a reminder, I spoke about going with first in class assets or best in class assets. CLN-049 is another example of a first in class asset, the first bispecific antibody to enter the clinic that targets FLT3 in AML patients. The key areas of differentiation are, one, obviously there are approved FLT3 agents in AML currently, at least two commercially approved, and they focus in on the mutant form of FLT3, which is about 20%-30% of patients. The way CLN-049 works, it addresses the extracellular domain of FLT3. Basically it doesn't matter whether it's wild type FLT3 or mutant FLT3. When you put that together, you're talking about 80%-90% plus of patients. It's a much larger addressable pool of patients that we can address with CLN-049. Can you talk about the preclinical data that you have for CLN-049, you know, that gives you confidence in the approach? Sure. For us it was important to look at both wild type and mutant FLT3. Through AML cell line experimentation, we were able to show that, you know, very significant tumor cell lysis across both mutant and wild type FLT3. That was important for us. In terms of potential safety profile, we also showed preclinically that, you know, our antibody only activates T cells in the presence of FLT3. Hopefully, you know, things like CRS, et cetera, it'll make our molecule much more specific. In mice that were leukemia-bearing, we've showed improved survival in those mice with very low doses of CLN-049. And also when we transfected human AML blasts into rodents, we were able to show complete eradication. Our preclinical package is very robust. Now of course we have an ongoing phase 1 study, and so we're obviously looking forward to generating data in that setting. Can you talk about that study and what we should look for in the upcoming clinical update? Sure. As I mentioned, ongoing phase 1 study with dose escalation. We've guided to clinical data available in mid-2023. It is a phase 1 study, so the primary objective is safety. You know, as we get closer to that time, we'll be able to more accurately describe the data set that we'll be sharing. Any sense for, and maybe it's a bit early still, but any sense for, you know, how many patients, the data you might provide in that update, whether, you know, any early glimpses at FC, that kind of thing? Yeah. I would say a couple of things. One, because CLN-049 is a T-cell engager, many of you may be aware, the FDA has been quite cautious with T-cell engagers, right? We have to make sure we do the dose escalation in the right way, and matching the requirements of the FDA. Again, it's primary goal is safety. Again, I'll go back to the guidance of mid-2023. Of course, as accrual happens, and if we can give clearer guidance, we'll do that. But at the moment, that's what we're saying. We'll have an initial clinical data set mid-2023. Okay, great. Well maybe moving on to CLN-619. You know, that targets MICA and MICB. How do tumor cells use those as evasion mechanism? Sure. The interesting thing is, MICA, MICB, we find in various conditions in the human body. Stress cells express MICA, MICB, tumor cells express MICA, MICB. Normally what happens is, when MICA, MICB sits on the cell surface, it's able to invoke immune cells, especially NK cells and subsets of T cells through the NKG2D axis. Those cells come in and those immune cells come in and destroy the stress cell or the tumor cell. The issue with cancer is, you know, cancer is very clever. In the tumor microenvironment, you see, proteases generated. Those proteases then are able to cleave MICA and MICB off the cell surface of tumor cells, which basically renders those cells invisible to the immune system. It's a way that it evades the immune system. We think there's very interesting and unique biology here. CLN-619, by the way, is another example of a first-in-class approach that we're taking. It's the first antibody to enter the clinic targeting MICA and MICB. We're very excited about that opportunity. MICA, MICB is ubiquitously expressed across solid tumors and hematologic indications. We think this could really be a pan-cancer opportunity for us. How does CLN-619 prevent shedding of MICA/B? How do other programs targeting MICA/B differ from CLN-619? Sure. Six one nine, actually, the antibody binds to the site of proteolytic cleavage, as I described, with what happens in the normal tumor microenvironment. It prevents the shedding of MICA, MICB. In a way, it's tagging the tumor cells again to be attacked by NK cells and subset of T cells through the NKG2D axis. That's one main mechanism of working. Those tumor cells, because they have MICA, MICB on the cell surface, they're no longer able to hide from the immune system. That's, you know, a key way it works. Also, six one nine induces ADCC as well, so you're able to use ADCC. With six one nine, we're invoking both the adaptive and the innate immune system, almost a double mechanism of action there. Again, that's why we're both excited by the biology of MICA, MICB, but also the molecule that we've created to kind of address that opportunity, which again, can be pan-cancer. Can you walk us through the preclinical and biomarker data you've collected so far for the asset? Sure. I'd say a couple of things. In the literature, you'll see that soluble levels of MICA, MICB, basically MICA, MICB, that shed in cancer patients portends for poorer survival. That's one point. Number two, when you look across a host of different diseases, you see that the ligand that's most expressed across tumor types is MIC-A, followed closely by MIC-B, which is why we talk about pan-cancer potential opposite of B. We've also shown in xenograft models, you know, significant tumor shrinkage, even at very low doses of CLN-619 as a monotherapy agent. That's been encouraging. In those same models, at the same time as we've seen tumor regression, we've also seen reduction in shed MIC-A and MIC-B as well. The preclinical package is tying up nicely with the hypothesis that I just described, and now we're in phase one in the clinic with six one nine. How is your ongoing trial designed to examine both monotherapy and combination activity? What should we look for in that upcoming data that you just mentioned? Sure. I think, look, one of the advantages of being in a fortunate position of having the robust cash position that we have, is that we're now able to do things in parallel that perhaps we would've done sequentially before. An example of that is with six one nine, where we're doing parallel development of both monotherapy dose escalation as well as combination therapy dose escalation in combination with pembrolizumab. 'Cause we think there's a very strong rationale to both combine MICA, MICB approach as well as checkpoint inhibition. That study is ongoing. You know, again, we're excited at the opportunity to address a range of cancers, both through a monotherapy approach as well as a combination therapy approach. Great. Maybe moving on to CLN-617. Can you just talk about the historical limitations of cytokine delivery, and how does CLN-617 address that? Sure. I mean, one thing we know about cytokines as a historical treatment, you know, IL-2, IL-12, very potent molecules, very efficacious, but unfortunately, when given systemically, we've just seen tremendous toxicity, which has kind of limited widespread use of those agents. With CLN-617, we've developed a fusion protein that combines, for the first time, IL-2 and IL-12, so potent cytokines, to be able to deliver that fusion protein intratumorally. It also has a collagen binding domain, which is important because that will help to keep IL-2 and IL-12 and limit it to stay within the tumor. So we think that's a novel approach, again, a first-in-class approach. We've also seen, preclinically, we've been able to generate both a robust memory T cell response as well as an abscopal effect. The abscopal effect is really important because we wanna be able to go beyond the tumor and reach other sites and other lesions. We're pretty excited about the preclinical data that we're seeing, very robust. We plan to advance CLN-617 into the clinic in the first half of next year. Great. Well, maybe in the last minute or two, are there any other, aspects of the Cullinan pipeline that, you'd like to highlight or, any aspects of the story that you think the street is missing? Yeah. I think, you know, like many companies, we're actually trading a little bit below cash, and so we're in a very funky environment, which many of you know about, right? I would say a couple of things. One, as I described earlier, you know, the fact that we take this modality agnostic precision oncology approach means we have multiple shots on goal and a very diversified pipeline. We're not limited by a singular platform. We have assets that cross the range of cancer, solid tumors, hematology. I think from that perspective, again, very diversified pipeline. As I mentioned earlier, we're very disciplined about only advancing the most promising assets. Very early on, we decide to either thrill or kill. I say I think that's something unique to Cullinan Oncology. We wanna make a big difference to cancer patient outcomes. That's why we only advance the most exciting assets. You know, when I joined the company on October 21, we had one program in the clinic. As of now, we have three programs in the clinic. By this time next year, we'll have five programs in the clinic, all very novel, either first in class, best in class. Combine that with our cash position, that will then allow us to accelerate the pipeline. We're doing lots of things in parallel, as I described. We're still looking externally as well as a source of innovation, as I mentioned earlier. If there's the right asset out there that's a good strategic fit, hopefully at the right price in the current conditions, you know, we have the firepower to bring additional innovation in. With CLN-081, you know, given that we have a co-commercialization arrangement, you know, post-launch, that will continue to bring, you know, an annuity annual revenue into the company to do additional things. I would argue we have one of the most rich and diverse portfolios for a company of our size, but we also have, you know, the cash firepower to do all the things that we wanna do, building out an amazing leadership team, many of whom are in this audience. Ultimately, I think that will help us to deliver the vision of becoming a fully integrated, you know, commercial stage end-to-end biotech company. We're really excited about the opportunity ahead of us. You know, our stock is trading at a great discount right now with such a great pipeline. Yeah, we're just really excited about the opportunity. I hope you can hear that in my voice. Great. Well, let's take off and leave it there. Thanks so much for your time. Appreciate it. Thanks so much, Jeff. Thanks, everyone.