All right. Good morning, everyone. Welcome to H.C. Wainwright 26th Annual Global Investment Conference. My name is Arthur He, a Senior Biotech Analyst at H.C. Wainwright. Thanks for joining us for have a conversation with the management of Poseida Therapeutics. A little bit about Poseida. Poseida is a clinical stage biopharmaceutical company focused on developing novel cell and gene therapies to treat cancers and rare genetic disease. Joining me here are Dr. Kristin Yarema, President and Chief Executive Officer, and Dr. Syed Rizvi, Chief Medical Officer. Welcome. Thanks, Arthur. Thank you. So Kristin, to help the audience who are not so familiar with Poseida, could you give us an overview about Poseida and its unique non-viral approach to cell and gene therapy? Yeah, of course, so first of all, thank you, Arthur, for having us here today. We're very happy to be here and Poseida, at its core, is really a platform technology-based company, though I like to say a platform technology company with real assets, and everything that we do is non-viral. Poseida has a quite unique and totally proprietary toolkit of genetic engineering tools. We have a unique approach to gene insertion, to gene editing, and also a whole suite of manufacturing technologies, and we have been working on these tools for a very long time. We have two sides of the business. We have a completely allogeneic cell therapy business, and then we also have a genetic medicines business, where we use those same tools to do in vivo gene editing and gene insertion, again, non-viral. We also have several partnerships that are well along. On our ALLO cell therapy side, we have a very extensive partnership with Roche in the area of heme malignancies. That partnership has just passed its second birthday, and we have two of our three clinical stage assets in that partnership. We also have a newer partnership with Astellas, which is in the area of solid tumors, which is also very exciting. Sure. Thanks, Kristin. So I guess in the technology platform-wise, could you help us better understand how different are the piggyBac and the Cas-CLOVER you guys have. Mm-hmm Compared to other methods used for the CAR-T manufacturing, and what are the key advantages they can offer? Right. So what Arthur has just referred to are, you know, two of our set of technologies. So our gene insertion technique, we use a transposon technology. That's what's called piggyBac, and then we have our own proprietary gene editor, Cas-CLOVER, which we have run in experimental bake-offs versus Cas9, and we know that it's twenty, twenty-five times higher fidelity than Cas9. So those are two of the central tools, and the great beauty of using this toolkit is that it enables us to produce allogeneic CAR-T that are not only using a non-viral technology, but they are uniquely rich in CAR-T stem cell memory cells. So if you remember nothing else about Poseida from this morning, remember that what we do in cell therapy is allogeneic CAR-T, but allogeneic CAR-T that are uniquely rich in T stem cell memory cells. That is a very different type of CAR-T than what you see anywhere else in the field, whether it's auto or allo, because in order to get a CAR-T stem cell memory cell, you need to use a non-viral technology. You simply can't do it with a viral vector. And why does that matter? Well, what we've seen over the years and as the literature has really grown in this area, we have seen that the more stemness you have in your CAR-T product, the greater the depth and durability of your clinical responses. So we've seen the whole field shifts. Poseida, from the very beginning, has been talking about stemness and T stem cell memory cell. But over the intervening years, we've seen more and more companies try to increase the percent or the amount of stemness in their product, and to some extent, they've been able to do that. But no one has been able to get to the kind of CAR-T stem cell memory type that we have. We've seen others get maybe more central memory, other types of memory, but in order to get CAR-T stem cell memory cell, you need to use the transposon, not a viral vector, and that's really unique to Poseida. Yeah. Thanks, Kristin. And, you mentioned about the partnership before. Mm-hmm. I just want you to highlight the ongoing partnership with both Roche and Astellas to our audience. Yeah. So we have really built our business model on the strength of partnerships, and this has been very successful for Poseida, especially at a time when, you know, our current investors don't wanna be diluted, the capital markets are very difficult. So think of it as we really run our operations off of non-dilutive funding. So we've just looked back, and over the last three years, we have collected $400 million through partnerships and various payments associated with the partnerships. So right now, we have these two partnerships in ALLO cell therapy. We're still looking for some interesting partnerships on the genetic medicine side. The Roche partnership is the larger of the two. It is in the area of heme malignancies, and it has a couple of programs that are in the clinics. We have two state-of-the-art phase I programs, our lead program, which is for multiple myeloma and against the BCMA target. That data, that program will have data in just a couple weeks. We also have another program, which is a dual CAR-T, so two full-length CARs against CD19 and CD20 that we're looking at for lymphoma and B-cell malignancies. There are also additional programs where Roche has an option, and there is a research collaboration component, too, so it's really quite a wide-ranging and ongoing partnership. It's very strong. If you follow us at all or if you follow Roche, you'll see that Roche talks about Poseida a lot, even these earlier stage programs, and so we're very happy to have such a strong partner in Roche. The Astellas partnership is newer. It's actually the second investment that Astellas has made in Poseida. So, last fall, almost just about a year ago, they put a strategic investment into the company, so, you know, made an equity investment and got some limited rights, including a board observer seat that's time-bound, but that wasn't really a partnership. But then they built on that more recently, this past spring, and now our two companies are in a collaboration in the area of solid tumors, where we bring together Poseida's platform, so we produce the CAR-T cell for them. There's a short list of targets, and we've selected the first target, and then we pair that with the technology that Astellas has to produce convertible CARs. So this program will have up to two targets in it, and it's fantastic. You know, we know these companies have known each other for a while. It's really going in a very productive direction, but it also preserves a huge amount of space in the solid tumor arena for Poseida to develop wholly owned internal programs. So those are our two current collaborations. Awesome. Syed, I know you just joined the company little bit of time, a while ago. So I'm just curious, could you tell us what attract you to here, yeah, maybe based on your previous experience? Yeah. Thank you so much, Arthur. I must say that it's a great question, first of all. So previously, I have spent more than 20 years in oncology drug development. Previously, I worked with companies like Merck, Novartis, Celgene, Legend Biotech. I've spent about eight years in cell therapy, have been associated with approval of three auto CAR-Ts, including Abecma, Breyanzi, and Carvykti, also work on allogeneic therapies. What really have attracted me to Poseida is really the technology. When I saw the data, which was presented last ASH, that was extremely unique, because that allogeneic CAR-T is really acting like a autologous CAR-T, where patients are getting help. We have, you know, squeaky clean safety. You have great responses. I also felt that company is doing their own clinical manufacturing, which is a huge undertaking, but that's really, really a winning strategy, because I feel that many, many companies out there in cell therapy space really struggle with that approach, especially when they are working with external partners who would manufacture on their behalf or contract manufacturing facilities. And then above all, you know, working with people like Kristin, who have, you know, great vision and, you know, great pharma background, and who can see, you know, how the product should be developed and what the commercialization look like. So those are some of my reasons to come to Poseida. Thanks. No, I say, I have to say welcome. So let's take a little bit dive into the pipeline, Kristin. So could you please highlight the data you guys already accumulated for the BCMA program? It's great, yeah. Yeah, absolutely. So we reported really our first dataset at last ASH, okay? This was a dataset where we had 11 patients receiving lymphodepletion that worked well. I'll let you know, Syed, go into the details about it, but what I think people really want to know is we are on the brink of providing a data update, which will be much more extensive regarding that trial. So we will be at the International Myeloma Conference later this month, presenting on the 27th of September, and that will be quite a fulsome data update. We had hoped that the abstracts would actually be available already, but they have remained under embargo. But, we're really looking forward to that, to that conference, and that will build upon the data that Syed will talk to us about right now. Thank you, Kristin. So this presentation that Kristin is talking about in a few weeks at the International Myeloma Society Annual Congress is going to be an oral presentation, so we are really looking forward to it. The data that we presented at ASH was really you know quite convincing, because we saw an overall response rate of about 82%. If you look at patients who are BCMA naive, the response rate was 100%. Safety was squeaky clean. We did not see any GvHD. We did not see any Grade 3 CRS or ICANS. Safety profile overall was very, very expected, where you would see cytopenias, but we saw cytopenias you know getting recovered very quickly. So all in all, we feel that the safety and the efficacy that we are seeing in a preliminary fashion right now is really on the right track, and we are looking forward to, you know, gather more data and then share with you, all of you. So let me just, you know, provide a little context and color to that. So, you know, it's very unusual that people in this space are running trials that are including both BCMA-naïve and BCMA-experienced patients. And we have done that since the beginning. We've continued to do that, and like Syed said, you know, what we felt was very encouraging about the ASH data was we saw very high response rates in both BCMA-naïve and BCMA-experienced patients. And right now, we really don't have anything, you know, available to meet the needs of BCMA-experienced patients. So that's a story that we're following very closely. We put a little bit more data out at AACR this past spring, with some case reports looking kind of a double-click on some of these BCMA-experienced patients. But you know, that's certainly something that is very much of interest. And Syed mentioned the safety profile. Well, in this very, very ill patient population, so they received in the ASH data a median of seven therapies previously, we saw no CRS or ICANS above Grade 2. The rates were very low, 21%, 6%. We didn't see any parkinsonism, and I think it's important for people to remember and realize we didn't give those patients any bridging therapy at all. So normally, when we think about data in multiple myeloma, you're not seeing data presented that's for the entire intent to treat patient population, patients are progressing, patient cells are not manufacturing. We treated everyone. They started their therapy the next day after enrollment. They didn't receive any bridging therapy, and they didn't receive any prophylaxis, so not prophylactic tocilizumab, not prophylactic antivirals. All we're giving is Tylenol and Benadryl. And so we are seeing really high response rates. We know everyone is interested in durability. We are as well, but it was an early data set that just simply didn't have much maturity to it. But we're seeing these very, very high response rates with good depth of response in an extremely ill patient population, and those response rates are not being artificially amplified by bridging therapies or other things given, you know, as a concomitant therapy. So, you know, I think it's really an excellent time for potential investors to take a closer look at Poseida as we're heading into this IMS data update, and we've actually given guidance that we will be giving data updates for every program in our portfolio before the end of the year. So we have an unusually rich news flow coming from now straight through the end of the year. Cool. I'm looking forward to that, so let's switch gear a little bit to your second program the MUC1-C. It's your own, fully owned program. Could you tell us first how these candidate targeted MUC1-C is differentiated from the other drug candidate also target the same target? Right. So what Arthur is referring to is our second of the three clinical stage programs. This is in the solid tumor space, and it is wholly owned by Poseida. The target is MUC1-C, which is a. So the MUC1 is a dimer. It cleaves in the context of cancer and exposes the C-terminal domain. So it's a very selective target in solid tumors, which is quite difficult to find, so that's why we selected the tumor. This study is a basket study looking at a number of different epithelial cell malignancies. And, Syed, you know, where are we with this program? Yeah. So in this study, we are enrolling patients who are with breast cancer, CRC, ovarian cancer, that type of thing. It's a three plus three design, very classic in terms of really looking for those findings, so that is underway. We have seen one thing that what we saw on the heme side, that probably because of allogeneic, you have to give a bigger punch in terms of lymphodepletion. Mm. So we have shared some data that just going with 300 Cytoxan may not work, so we may have to think about going to a higher dose of Cytoxan. So that's what we are going to be using here in this study, and study is coming along in terms of moving forward. Yeah. Solid tumor patients in their patient journeys see different kinds of treatments than patients with liquid tumors. And, you know, without getting into the details of those, they tend to be less lymphodepleting. And so we've looked at that more systematically than anyone else and have taken from that experience the learning, just as Syed says, in the solid tumor setting, we probably need to go to a little bit higher lymphodepletion in order to make enough space or niche for the CAR-T cells to expand and be ready to be active, taking on the tumor. So, for the upcoming update, data update. Mm-hmm. What kind of data set we could expect from this study? Right. So we haven't given a guidance on the number of patients or anything like that, but what we have said is that we will give a clinical data update before the end of the year. Okay, cool. Thanks. So and for the dual CAR program, should we also expect some data by the end of this year? Yes. So this is now the third of our phase I programs, and the dual CAR, that's our B-cell or lymphoma, malignancy or lymphoma program. It's the second program. This is also partnered with Roche, who have for a very long time been the world leaders in lymphoma, right? So, you know, this program has got people who know the space, really working on it. And what's unique about it is it carries two full-length CARs. It carries a full-length CAR against CD19 and a full-length CAR against CD20. That's something else that's only available if you use the transposon technology and not a viral vector technology, so other companies can't do this. It's a very interesting combination of targets because in the cancer space, you could think about using this product for patients who were refractory to an anti-CD19 agent or auto CAR-T, because we know that losing CD19 is a frequent reason for patient relapse. But you could also use it ahead, earlier in the patient experience, and then you would be covered against, you know, both CD19 and CD20 as targets. So this program is also in phase I dose escalation, and we will be giving a clinical data update on this program before the end of the year as well. Sure. And, you also plan to have a R&D day focused on cell therapy? That's right. O n November 14th, right? Yes. So what's the main topic we could expect from that event? I think there are going to be many topics. We did an R&D day on our genetic medicines business back in April, and we decided this year we just have too much data. We needed to do two different R&D days. The cell therapy R&D day is the one coming up in November. We will certainly touch on all three of the clinical programs that we just talked about. But in addition, I think it's gonna be a great opportunity for people to really understand what we have in our earlier stage pipeline in our technology development, where we have really been making great advances that I think are gonna be quite applicable to cracking the solid tumor problem, if we can say that. And we also have a number of earlier stage assets that are Poseida's own, that we really haven't talked about, and that will be a great opportunity to do so. We've also said for a long time that we're working on a strategy for cell therapy in autoimmune disease, but we haven't disclosed what it is, and that we would talk about that when the time was right. So that might be something else that people would hear about at that time. Sure. I'm looking forward to that. So I know we kind of focused the most part of the conversation on the cell therapy side, but I know the gene therapy is another set of the franchise you guys have. What's the strategy there, and could you give us a kind of outlook for what Poseida is going to do with those, that portfolio? Absolutely. So, you know, let's come back to the point about the tools and the technologies. So Poseida really has, you know, this unique transposon technology and Cas-CLOVER. We also have a lipid nanoparticle group. So we have these tools that we can use, manipulating cells outside the body. That gives us the allo CAR-T, but we can also deliver them through lipid nanoparticles inside the body for a fully non-viral approach to gene editing or gene insertion and gene therapy. So that is what we are doing. Those programs are a little bit earlier, but they are moving. We have a gene-editing program in hereditary angioedema, and we have a Factor VIII program for hemophilia A, and we have guided one or more INDs by 2025, by the end of 2025. So these programs are advancing very nicely. We've just been awarded an INTERACT program, INTERACT meeting by FDA for the factor VIII program. And if you're familiar with that construct, not every company gets an INTERACT meeting. It's a sign that the agency really wants to talk to you to ensure that your program is on the rails and able to move quickly into the clinic. So I think there's a lot of excitement. You know, let's be honest, the gene therapy space, you know, has been a difficult one, from a commercial perspective, particularly for these viral therapies. But I think we, and you know, in the community, and certainly FDA is looking ahead to non-viral approaches that might really be able to effectively treat patients for some of these diseases. So. Again, if you remember just a couple things about Poseida on the cell therapy side, it's allo CAR-T, and it's T stem cell memory cell-based CAR-T, and then on the genetic medicine side, it is non-viral, and Poseida has proprietary, unique tools and a delivery system to deliver them, that we think are really differentiating and moving ahead quickly. Yeah. Thanks, Kristin. So I guess for the sake of time, so to close our conversation, could you remind us what's the major catalyst in the next twelve months, as well as your cash position? Yes, absolutely. So like I said, we have a lot of news coming, even before the end of the year, so we will see data updates on all three of these programs. You know, we have more to come. There'll be more to come into 2025, but we haven't given specific guidance there, yet. But, you know, look to our R&D day to potentially hear more. In terms of our cash position, we've given current guidance that our runway is, well into the second half of 2025, but we're only counting cash in hand and some payments that, you know, we have very clear line of sight to. There are many more potential payments that would extend our cash runway, some of which we will hear about in quite the near future. So back to those partnerships, we haven't really counted... Roche doesn't like to talk about forward-looking milestones and payments that haven't been decided upon yet, but there's a very real possibility that we would be able to update that cash guidance in the near future. Sure. So, thank you, Kristin, and thank you, Poseida, for coming down to talk to our audience. Thank you. Thank you, Arthur.