Good afternoon, everyone. My name is Kelly Shi, one of the biotech equity analysts at Jefferies. Thank you for attending our virtual healthcare conference. We are very pleased to have Mr. Paul Hastings, President and CEO from Nkarta Therapeutics join us today. He also brings his big team, Kanya, Ralph, Nadir, James, and Greg. To start off, Paul, could you introduce your team and also the company for those who are less familiar with the Nkarta story? Yes. Thank you, Kelly, for inviting us, and we're thrilled to be here. The beauty of Zoom is you have the whole team, so you can ask whatever questions you'd like, Kelly, and we will be happy to give you multiple points of view on that one question you ask. The team here, you have James, our CSO, Chief Scientific Officer, Kanya Rajangam is our Chief Medical Officer, Nadir Mahmood is our Chief Financial and Business Officer, and Ralph Brandenberger is our Senior VP of Tech Ops, running all of manufacturing process development. As everybody knows, the process is the product in cell therapy. Greg Mann, who is our VP of Corporate Communications and Investor Relations. Myself, CEO, Paul Hastings. Happy to be here. Did you want me to introduce the company too, Kelly, is that what you asked, or just the team? Yes, at a high level, for the audience who join us for the first time and are not familiar with your story. Absolutely. Greg, why don't you go to slide three? Let me just say at the outset that we're laser-focused on engineering CAR-NK cell therapy for cancer. The beauty of the NK cell is it's part of the innate immune system. They're short-lived cells. They tend to go in, they tend to attack the tumor, and they tend to leave. Like an antibody or a chemotherapeutic agent, these are cells that you can give multiple times, and they don't have the long-acting activity of the adaptive immune system, which is still a good activity to have, but the NK cell is a short-lived cell, so it has the benefit of being able to dose like an antibody. All of our programs, from our NKG2D-targeted NK cell to our CD19-targeted NK cell, CD70, are designed to be allogeneic, for off-the-shelf use. They have the broadest possible access ultimately, where you can cryopreserve these cells, put them in vials, freeze them, thaw them, give them at the patient's therapeutic site. Could be in an infusion center, could be in a hospital setting, could be in a community-based setting. That potential for outpatient administration is something that is very unique and very exquisite to the NK cell. Much easy cell type to give in an outpatient administration in the community oncology center. We're starting with donor-derived cells. There's a lot of talk out there about platforms. I have to tell you, if someone asked me as a patient, do I want to start with a real NK cell that gets expanded as a real NK cell in large numbers with a relatively modest cost of manufacturing so that you have the flexibility to multiple dose and to have real NK cells that haven't been altered, that's the way I would go. A healthy donor-derived platform and a next-generation healthy donor-derived platform, being an allogeneic off-the-shelf cryopreserved in-vial product, is one that we really want to focus on, and that's where we start. We design our cells with donor-derived cells. We use a proprietary expansion technology that our founder, Dario Campana, came up with, K562 cell line. We achieve a very attractive cost of manufacturing, around $2,000 a dose for a cryopreserved product in a vial at peak. That's a conservative estimate, between 500 and 700 doses per healthy donor. We also have the potential to have a universal donor as time goes on. We've got a lot of the advantages of any other platform, the ability to gene engineer. We recently did a deal with CRISPR, so we can do that as well, and do everything that any other platform can do, but with a natural killer cell to start with. We have two co-lead programs, 101, which is our NKG2D-based CAR-NK cell therapeutic. NKG2D is a natural receptor on the NK cell, so actually turbocharging the NK cell with additional NKG2D ought to take what's in the literature with unengineered NK cells in a disease like AML, and really help to get that kind of effect, that kind of CR rate longer term in a more controlled setting. We expect to have data in a handful of patients by the end of this year for the NKG2D program in AML and MDS. Our NKX019 program, the IND was recently cleared, and we expect to be dosing patients in the second half of this year, and we expect to have data in 2022. We'll give more guidance on that as soon as we get closer to FPI or first patient in for the 019 program. Two co-lead programs that will ultimately read out in the early part of 2023. Both together and the capital we raised in our IPO will take us into the second half of 2023. Proof of concept for two co-lead programs in the timeframe of our capital raise, and where that will take us. Our platform is strongly differentiated. We start and finish with real natural killer cells. I cannot emphasize that enough. We're not differentiating from stem cells. We're starting with natural killer cells. Donor source is important, and we start with a high volume of cells. The manufacturing is rapid. We're not putting cells through rounds and rounds of manipulation that can add complexity, cost, and genetic variability. We're starting with a real NK cell. We're expanding over 14 days, not 45, and we're coming up with a very attractive cost to manufacture. We have an integrated platform with all the components in place, expansion, proprietary stimulatory cells, engineering for persistence with a proprietary membrane-bound IL-15, Proprietary targeting like our CD19, as well as cryopreservation. As you know, these cells don't like to be frozen. They don't like to be thawed. We've been able to do that, freeze them, thaw them, put them in a vial, ship them, thaw them, give them to patients in an outpatient-based setting. All of that is integrated into our platform, and we just recently added the deal with CRISPR, so we can now add genomic engineering with CRISPR to our already very robust platform. At the end of the day, while much is made of the cell source in the NK field, it's the final product that drives efficacy. When there's clinical data, that's what's going to matter and not the starting material. A lot of questions we hear about platform differentiation will be settled by clinical data, and we're well on our way to showing that, both with 101 as well as 019. That's an introduction to the company, Kelly. Great. It's very informative, clearly 2021 is a big year for Nkarta. Before we dive into our pipeline and for details, maybe I have one high-level question for you to share your insight for the cell therapy space. What do you think about CAR NK versus CAR T? What's the advantage and the disadvantage? Also, in terms of the stage of development for NK cell space or CAR NK, could you actually share some comments on that relative to the stage of CAR T? What kind of new development innovation going to come in next three to five years in NK space? There's a lot to unpack there, but Greg, why don't you go to the slide that James can talk about the differences between NK versus T. James, do you want to grab that one? Sure. I'll comment first that we're big fans of T cells and CAR T cells, as well as CAR NK, and we have a program that we'll be collaborating with CRISPR on that combines the two modalities together. Ultimately, I think the cell types have different strengths. From a manufacturing point of view, it's much easier, I believe, to expand very large numbers of NK cells, as well as to engineer them. They are somewhat safer in their application. They should be, because they don't have that sort of wild expansion that T cells exhibit. They're naturally suited to allogeneic use without editing, because they don't cause GvHD. You don't need to worry about the variant targeting of the T cell receptor. We see advantages to combining the two modalities. They support one another. They're complementary to one another. In terms of indications, I'm sure we'll see that there's spaces where NK cells are naturally better suited than in other spaces where T cells are. Was this the slide you wanted me to speak to, Paul? No, I think I wanted you to go to the T cell versus NK cell. Yeah. I guess the only other point I would make about them, we know that NK cells on a cell-per-cell basis are highly cytotoxic, and they recognize many different determinants that are overexpressed on tumor cells. What we've observed is that even against cell types that are expressing very low levels of the target ligand, say very low levels of CD19, NK cells retain their cytotoxic capability in settings where T cells will tend to lose their potency because they can no longer see their target antigen. Again, even without our engineering, NK cells will recognize and kill target tumor cells in solid tumor settings. That's likely to be a really important factor. I'm not sure this is a slide that illustrates that, but we have data speaking to that point, and I think it's generally understood of NK cells as well. Great and thank you. Since you are on this slide, maybe I can add on another question regarding another company actually working on iPSC-derived NK cells, then you're working on donor-derived NK cells. I think one difference standing out is the variation of the NK cell population. My question here is, for the manufacturing process, you actually expand the NK cells from individual donor, alternatively, you actually pool the cells from different donors, to gain better homogeneity. Which way you think is better? First, what is your manufacturing process? Secondly, maybe make a comparison between these two approaches. Right. James is going to answer that with this slide. Thank you, James. I have to apologize. The slide I was referring to is no longer in this deck, so James did a great job answering the question without the slide. We've kind of moved on between the comparison with NKs and Ts, but I think this question is a really important one. James, why don't you go through this slide of the differences, and then Ralph can talk about our 14-day expansion and our manufacturing process after you do that, if that's okay. Yeah. Again, I think this is illustrating differences between cell sources, and you were asking specifically about variability in the final product. I think it's important to bear in mind with cell products in general, a lot of that variability will be driven by your process. We found that our expansion and engineering process tends to focus the phenotypes of the cells to a great extent, so that from donor to donor, final product cells exhibit more similarity than difference. That's partly because it's a very rapid process. We're not keeping them in culture for an extended period of time. We're driving the expansion and the activation very strongly and very consistently in every donor. We have a very, I would say, for this field, a very simple and straightforward process. By contrast with iPSCs, for instance, it's typically over a six to seven-week process with multiple steps of differentiation. It's hard to maintain complete control of a cell product over that period of time and hard to keep costs under control. Final point I guess I would make is you asked about deriving the cells from a single donor rather than a pool. We use single donors, and at this point, that's supported by all the regulatory guidelines as well, where pooling of donors is really kind of a high bar, and it's discouraged by regulatory agencies. Let me just add a little bit to that, Kelly. When anybody refers to first generation and second generation platforms, first generation human-derived platform is generally referring to the autologous T cell platform. We are not that first generation. We're a next generation platform with allogeneic off-the-shelf CAR NK. Ralph, with that, do you want to answer Kelly's question about our manufacturing process and walk people through that? Totally happy to do that. Just to remind everybody is that all our product candidates are being designed as off-the-shelf therapies, and that our eventual manufacturing process at commercial scale is going to deliver hundreds of doses from a single healthy donor. Our starting material, as we've already discussed, are bona fide NK cells from adult healthy donors. We start with real NK cells at the beginning of the process, and the two critical components of our expansion technology are proprietary. The stimulatory cell line, as well as the transductions with the membrane-bound IL-15, both of which are required and activate the NK cells, induce them to grow, and are important for the assistance of the cells. Another key component of the manufacturing platform is, of course, cryopreservation. We have been able to come up with a cryopreservation process that results in functional cells straight out of the vial. At the clinical site, there is no further processing or culture of the cells required other than to basically thaw and dilute the cells for administration. We can show both in vitro and vivo experiments that the cells out of cryopreservation maintain their potency and are really straight out of the vial. If you go to the next slide, I think I want to talk a little bit about the potential for expansion. As you can see in our roughly two-week manufacturing process, we can get several thousand-fold of expansion of the NK cells. If you take that together with the high number of the 700 million NK cells we get from a single donation, that enables this manufacturing platform where we think we can get greater than or 500+ doses from a single manufacturing run at 1 billion cells per dose. That's another advantage, for example, of cord blood cells where the starting material from cord blood is about 100-fold less NK cells compared to adult healthy donors. This potential for large expansion then also drives down the cost of manufacturing. We believe we can get to that $2,000 per dose from a cost manufacturing perspective. Ralph, you could go longer than the 14 days as well and expand further, right? This is a relatively conservative approach, but one that we're really comfortable with at the moment. Yeah, that is correct. We can continue to expand these cells beyond that time. Also from one donor, per Ralph, you actually can generate enough doses for one phase III trial. He felt better if he actually said two more trials. I can also do I can also do phase III. Thank you for saying that, Kelly. Yes. It's a very accurate and timely manufacturing process from a healthy donor. I see. I can see the advantage. I think we went through the good information regarding your technology and the manufacturing process. Now we can switch the topic to your lead asset NKX101. Maybe start with the NKX101. Could you talk more about the rationale to select the NKG2D and also why prioritize the human malignancies AML and MDS as the first two indications, given that NKG2D actually has very broad expression across hematology, including solid tumors? Right. That's a great point. Why don't you go to the pipeline slide, Greg? That way Kelly can ask more questions on the pipeline. Kanya, if you'd like to walk through a little bit the rationale behind AML, MDS first, and then solid tumors, because both of those are in the pipeline. Yeah, happy to, Paul. One of the biggest rationale for us with looking at NKX101 in relapsed/refractory AML as our first human indication comes from clinical literature using non-engineered NK cells in these patients. I believe we have a slide on that as well. What we did is that's relevant to NKX101 because NKG2D is the main activating receptor on a natural unengineered NK cell or naked NK cell. We've always done, I shouldn't say all, what we've done is taken it, added it to a CAR and a membrane-bound IL-15. This table on the right directly answers the question of why we chose relapsed/refractory AML. When you look at the clinical experience with non-engineered NK cells, when folks across variety of small, single center academic trials, they have noticed a response of between 20%-50% of complete remissions with varying degrees of hematologic recovery in patients with these malignancies. That's the main rationale that drove us to evaluating NKX101 in AML as our first trial. As you rightly pointed out, these ligands are upregulated across a variety of different tumor types, as shown on the table on the left here. It is our intention, as clinical data supports it, to expand our development program into other indications as well. Kelly, just to be clear, NKG2D has the potential in multiple indications, both heme and solid tumor in its current form. We're real excited about this molecule. NKG2D being the natural receptor on the NK cell makes absolute good sense to use this as the first program of the two co-lead programs going forward, along with our CD19 program. Very interesting. Could you also introduce to us, regarding the phase I trial design and where you're at, and what will be the next data readout? Kanya? Yeah. Our phase I trial design is summarized on the slide. There's a lot of information, so I'll walk you through quickly from the top to the bottom. It's a multicenter phase I study with the primary goal of finding safety DLTs and also looking at efficacy, of course. We think of our study treatment as multi-dose in a cycle, and there's an option to give multiple cycles as well. In a cycle, there's lymphodepletion, the standard low intensity CAR T like lymphodepletion, followed by multiple doses of NKX101. We are evaluating two regimens in parallel of NKX101, one given on day 0, seven, and 14, another on day 0 and seven. The rationale for both of these regimens is driven by, again, from literature, which shows that when you use a regimen like this with cyclophosphamide and fludarabine-based lymphodepletion, there's a two-to-three week window where the host immune system is suppressed. These being allogeneic cells, we want them to be given during that window and they can go in and hopefully achieve deep tumor control, hence the multiple doses. There is an efficacy assessment on day 28, and based on protocol pre-specified criteria, there is the option to continue to get additional cycles to try and deepen the response. Right. The idea of giving the two-dose regimen is to give more cells up front and two doses versus them spread out over three doses to see if there might be a different impact. We've seen in the literature, we've heard that by giving a loading dose of these NK cells, it may have an impact on the efficacy of the product. We're going to see that now with this new amendment. Great. Makes sense. Even though you call it a multi-dosing cycle, it's actually only composed of two approaches, one, two doses, one for three doses. I'm just curious if you see the disease progression, are you going to actually offer additional doses beyond the third dose? Kanya? Yes. We think of this as one cycle. Depending on any response on day 28, there is the ability to give another identical cycle, lymphodepletion and multiple doses as well beyond cycle one. Each time there's an assessment of is there blast reduction in the case of AML or lymphoma regression in the case of NKX019, as well as safety criteria being met to get additional cycles. Okay. The decision point is actually after you see disease progression, probably, not actually before. I want to clarify. Right. To get a second cycle, it's to deepen a response. Those patients who already have some evidence of activity, a partial reduction, for example, or some decrease in blast, they can get an additional cycle to deepen the response. Okay. Got it. Thank you. This is very helpful. Switch to second beta asset NKX019. It targets a very well-known CD19. My question here is, given there are already three CD19 CAR T in a commercial place, what's the rationale actually to work on this target and what's the trial design? Let me just start with if you can create an allogeneic off-the-shelf CAR NK cell, cryopreserved in a vial that can be given multiple times with proprietary bits on the technology, like our CD19, like our membrane-bound IL-15, we believe there are advantages of the CAR NK cell as in terms of other CAR NK cells, but also in terms of T cells. It just provides another option of giving a shorter lived cell multiple times without having that longer term expansion of the T cells. We think that the space is ripe for CAR T CD19 programs as well as CAR NK CD19 programs. I think when you look at the CAR NK landscape, is there room for more than one player with a CD19? Absolutely. There's more than one big pharma company interested in CD19. There's more than one autologous CD19 company interested in allogeneic off-the-shelf CD19 cells. There's a lot of opportunities for the CD19 program, and it's a target that everybody knows has proof of concept, both clinically and from a manufacturing point of view. We've got a great program with some great proprietary technology around it in a cryopreserved vial, ready for shipment, ready for thaw, and ready for injecting in patients. Is there anything anyone wants to add to that? Kelly Shi, one additional piece to add to that is while I think we've seen tremendous progress in the allogeneic CAR T space, I think as we think about moving from the specialized centers that currently administer autologous T cells and try and move more into the community outpatient setting, I think there's a spectrum of sort of opportunities there. We might still be with the allogeneic CAR Ts kind of moving from specialized center inpatient to outpatient, but maybe not quite to community settings. The safety profile and benefits of an NK cell platform, I think, are going to move the paradigm dramatically towards that true community setting. I think the patient access that enables with the safety, the manufacturing cost, and the ability to multiple dose, you're starting to think more like you're dosing an antibody rather than a cell therapy. I think it's that paradigm shift that the NK cell enables. Makes a lot of sense. The NK cell has the flexibility. The very last question is, for the next 6 to 12 months, what will be the key milestones and the big events for investors to pay attention? Also, what are the key learnings since the company was established in NK space? Great. Why don't you go to that next slide, Greg? As you can see, we've guided to a handful of patients in the NKX101 trial. The AML/MDS trial. We'll have a handful of patients of data by the end of this year. That's what we've guided to. The protocol amendment that Kanya just went through with the regimen B will only enhance our ability to get there by the end of this year. We haven't said where we might present the data. It could be at a medical meeting, it might just be a presentation. But where we have the patients and we have a couple of cohorts and maybe a dose response, we're going to talk about those data. That's one key milestone coming up. The IND for CD19 was cleared recently, and the first patient will be in the second half of this year. We'll have, as Nadir, I think, mentioned earlier, data in the 2022 timeframe, interim data. Final data on both programs will happen in the first half of 2023 for proof of concept for both of our programs and the proceeds from our IPO right now we've guided will take us to the second half of 2023. Proof of concept data from the two co-lead programs. Additionally, we'll file an IND amendment for a solid tumor indication for NKX101. That's hepatocellular carcinoma, cholangiocarcinoma, and colorectal carcinoma isolated from the liver with a local regional approach. You get as many cells as possible into a solid tumor for proof of concept. We'll bridge into a systemic type of administration. That's another milestone that's coming up real soon. The CD70 program is coming up as well, and that's attached to a very major milestone that we recently did, which was an awesome deal with CRISPR Therapeutics, which Nadir just did. This is a multi-gene editing genome engineering deal that we did with CRISPR, where we're taking the benefits of our technology together with the benefits of their technology in a very equal partnership, contributing equal to the cost as well as the profits of the CD70 program and the NK+T program, and another third program to be determined later. That is part of our pipeline now and that collaboration with CRISPR, where we're using their experience with their CD70 CAR T cell and their clinical experience with our CD70 CAR-NK cell, as well as their T cell component along with our NK component in the NK+T program. We're really excited about that deal. I wish we had another 10 minutes for Nadir to take you through that deal because it's really exciting. For the next time. Finally, the manufacturing. We put that on the pipeline slide because it's important you own your own manufacturing. The process is the product. We've completed a roughly 3,000 square foot clinical GMP facility that's making our NKX019 clinical supplies and will make our NKX101 clinical supplies. Now we're planning on a commercial facility, which is here on the bottom of this chart, which will enable the launch of our products, where we will own our process and own our manufacture. Those are the milestones. What have we learned from the beginning of the company? Own your own manufacturing is one of the most important things, particularly in light of what we went through with COVID. The best thing to do is have control of your manufacturing, have your own people who are responsible for the process development and implementation of your process, be involved in the manufacture of your process, have it nearby. That's our intention for our commercial facility. That's one big thing. The other is to pick indications for your lead molecules and to have a balance of that sort of novel target on a novel platform with a well-known target that has clinical proof of concept on a novel platform. To use natural killer cells as the starting material, to expand natural killer cells into more natural killer cells, so that what you're giving patients is a natural killer cell engineered for targeting and persistence, and cryopreserved in a vial so you can deliver that product to a patient in the community as well as a hospital-based setting. Great. A lot ongoing, and it's a very exciting moment. We are running over time, and we have to wrap up our session here. Thanks again for Nkarta team joining us today, and we're looking forward to the next milestone. Thanks everyone online for attending our session. Thank you. Thanks, Kelly Shi.