My name is Benjamin Burnett, Biotech Analyst here at Stifel. Pleased to have Poseida Therapeutics' CEO, Kristin Yarema. Thank you for being here. Thanks, Ben. I think the format's going to be a slide presentation, and if there's room at the end, we'll ask some questions. That sounds great. Great. Yeah, thanks, Ben. It's great to be here. Okay, so I'm here to tell everyone about Poseida Therapeutics today. We have some usual forward-looking statements. Am I okay here? Or can I go up a bit? You can go up, yeah. Yeah, okay. Being a vertically challenged person, I'm going to try to get a little bit more of a vantage point here. That's great, so Poseida, at its core, is a platform technology company. I know that has been somewhat out of vogue these days, but I always like to say we are a platform technology company with assets, and we really have two sides of our business. So we have a proprietary genetic engineering toolkit that I'll tell you more about. We use that to manipulate cells outside the body, and that creates our allogeneic CAR-T business. That's a side of the business that's more advanced, and we have two great partnerships, one with Roche in the area of hematologic malignancies and one with Astellas in solid tumors, then we also use those same tools inside the body to do in vivo genetic medicines. We've also been named a Most Loved Workplace, and we're recognized by BioSpace. So we have great people at Poseida as well. So, as I mentioned, Poseida has invested over many years in developing and creating a proprietary set of genetic engineering tools and enabling technologies that underpins everything that we do. So, to edit genes, we use our gene editor called Cas-CLOVER. This editor uses two guide RNAs, and so in tests that we've run head-to-head versus Cas9, which some of you may be familiar with from CRISPR, we see our system is 25-fold higher fidelity. We also do not use a viral technology for gene insertion. We use a non-viral transposon technology that has a number of advantages we'll talk about, and that allows us to insert our genes. We also do the gene insertion and gene editing together in one single step. We also have a lot of ancillary technologies that we have developed over the years. We have a vast IP estate covering all of this, and those enabling technologies range from booster molecules that we use to increase cell yields in production in our allo CAR-T to lipid nanoparticle technologies where we have IP on entire families of lipids that are used for formulations for in vivo genetic medicines, so like I said, one toolkit, and we use it. It's very flexible, very versatile. We use it outside the body to manipulate cells for allogeneic CAR-T, as well as inside the body to produce fully non-viral genetic medicines. On our cell therapy business, we do all of our manufacturing ourselves, which we think is a great advantage. We're very proud of this. You're taking a look right now at our own facility. It's right on site at our headquarters in La Jolla, California. And what you can see is it's about one-tenth of the size for comparable output to an autologous cell therapy company. So you can imagine that this has great advantages in terms of production costs and COGS. In fact, right now, we are getting up to over 100 doses of cells yield from a single allogeneic healthy donor, one single batch, one donor, one single batch. So we have far lower labor costs and operating costs, and it also allows us to really have very tight connection between our process development group and our manufacturing. We're producing clinical-grade product, GMP product, for all three of our clinical stage programs in this facility. And ultimately, we're targeting biologic-like COGS for our cell therapy products, which we think will be really important to unlocking the full cell therapy opportunity. In our cell therapy business, we're really fortunate to have two terrific partnerships. So the more advanced of the two, and the larger of the two, is with Roche. That's in the area of heme malignancies. In that partnership, we have two programs that are in phase one clinical studies, including our lead program, P-BCMA-ALLO1 for multiple myeloma. And we also have a partnership, it's actually the second deal that we've done with Astellas, that is in the area of solid tumors. That program is for two targets that have been nominated but not disclosed, and these are for convertible CAR technologies. So Poseida supplies the cell chassis for the CAR-T, and Astellas provides two interchangeable MicAbodies that engage the target antigens on the tumor. So altogether, this partnership model has been really fantastic for Poseida in many ways. It allows us to advance the assets that will be meaningful therapies for patients. It has been great validation of our approach and our technology, and it has also enabled us to really fund operations of the company at a time that has been quite challenging in general and for cell and gene therapy companies in particular, and you can see at the bottom of the slide here, just over the past three years, we've collected over $400 million in various partnership payments and milestones through this model, and we're just very happy to work with both of these companies. This is a quick look at our overall pipeline. You can see it is very full. In blue, you see our allogeneic CAR-T. At the bottom in gold are our genetic medicines, so let me just give you a quick run-through for these different programs. So our lead, most advanced program, which is right now in Phase 1B, is P-BCMA-ALLO1 for multiple myeloma. That program is partnered with Roche, and I will share some data that we presented at the International Myeloma Society this past September for that program with you in just a moment. We also have P-BCMA-ALLO1, sorry, P-CD19CD20-ALLO1, which is in development for B- cell malignancies. We also have a program that is wholly owned by Poseida. This is at the IND enabling stage, P-BCMACD19-ALLO1 for multiple myeloma, lymphoma, and autoimmune diseases. And then we have some earlier stage programs as well, including the Astellas programs. In the solid tumor space, we have a Phase I MUC1-C program for a basket of epithelial malignancies, all expressing MUC1-C. We have a prostate cancer program as well that is also wholly owned by Poseida. Our genetic medicines programs are earlier, but we have a non-viral gene editing program for hereditary angioedema that uses the Cas-CLOVER gene editor I mentioned. And then we are also using our transposon technology for non-viral gene insertion of the Factor VIII protein, or Factor VIII gene, leading to expression of the Factor VIII protein for hemophilia A. So let's take a closer look at the allogeneic CAR-T side of our business. If you take away only one thing from this presentation, I'd like to leave you with this. Why do we think Poseida has the ability to open and succeed against the allogeneic CAR-T opportunity, which has been really a struggle for many companies? It's because we engineer in differentiation at the cellular level. This slide gives an overview of four things that we think a company really needs to succeed at in order to do well in allogeneic CAR-T. Starting at the top, we believe you must start with the right cell type. For us, this is the T stem cell memory cell. So think of our CAR-T as CAR-T stem cell memory cell products. Why are we focused on that? It's because stemness has been shown to correlate with depth and durability of response in CAR-T. The T stem cell memory cell has also been theorized to have an intrinsically better safety profile, and we believe we are seeing that in our data as well. Importantly, you cannot create a CAR-T stem cell memory cell by using viral technology. You have to use the transposon. It preferentially inserts genes into naive and T stem cell memory cells. To do that, you need the second of these four areas, which is your gene insertion technique. As I mentioned, we do not use virus and never have in our CAR-T. We use transposon technology. In addition to delivering that T stem cell memory phenotype, the transposon is also very useful because it has a larger cargo capacity than viral vector, about 30-fold higher. And that enables us to engineer a lot of functionality into our CAR-T cells. For example, we can put in multiple CARs, and several of our programs that I just shared with you have multiple independent CARs. At our R&D day last Thursday, we introduced a CAR-TCR platform where we can put in an independent CAR and a TCR. All of our programs also incorporate an embedded safety switch, as well as a selectable marker that we use in purification to ensure that our products are essentially 100% CAR-carrying T cells. So transposon, in our mind, is the way to go. If you're going to do allo, you also have to have an answer for gene editing, though. And this is where our Cas-CLOVER gene editor, which is proprietary to Poseida, we feel is very powerful. In addition to being high fidelity, as I mentioned before, it also is able to edit resting T cells. We don't add any cytokines or activate the cells. This enables us to do gene insertion and gene editing in one single step and to preserve that T stem cell memory phenotype all the way through our production process. Lastly, why allo? It should be faster, it should be more convenient, but it also should be cheaper in terms of its production cost. If you're going to do allo, you need to ask, what is a company's scalable manufacturing capability? I shared with you our own GMP facility, and as I said, we are getting up to over 100 doses from a single healthy donor, single batch of product, and we have proven this capability across multiple programs. Let's take a look at P-BCMA-ALLO1. This is our lead program for multiple myeloma. If you're following the CAR-T space, you're probably well aware of CAR-T as well as bispecifics and multiple myeloma. I would just remind you, multiple myeloma remains an incurable disease. It's among the more prevalent of the blood cancers and always has been and continues to be a very large market opportunity. The problem is that today's auto CAR-T can really only serve a minority of the patients who could benefit from the transformational power of cell therapy. We think P-BCMA-ALLO1 is going to change the game on that. This therapy has been recognized with the RMAT designation by FDA. It's actually very favorable. It's for three or more previous lines of therapy, triple-class refractory, which is actually a wider population than the original auto CAR-T approvals. And we have a novel binder that we use in it. This program is currently enrolling in Phase 1B in conjunction with Roche. This is a slide from our IMS presentation in September of this year. We wanted to show the contrast between the typical autologous CAR-T patient journey and what we're seeing in the clinic with P-BCMA-ALLO1. So if you follow autologous CAR-T, you know that from the time of the treatment decision, what we call the bridging part of this, to observed response in the clinic is going to be numerous weeks or more likely months, given the time for manufacturing, quality release, apheresis, shipping, all of that. For our patients on our trial, we are able to treat them, start their treatment the day after they enroll in the study. They receive the cells within one week, and from the first two arms, A and B of our study that we were able to report on in September, we saw confirmed response in the clinic three and a half weeks from the time that the patient enrolled. We think this is really game-changing in terms of what it means to patients and physicians who really want to begin treatment and get control of the tumor as quickly as possible. Here's a quick summary of the data that we showed. To give this some context, and I'm going to go into a little bit more into this in just a minute, our study enrolled not just BCMA naive patients, but also patients who were very high risk and had received a lot of other therapies, including previous BCMA and GPRC5D therapies. Actually, 62% of the patients had received one or more of those therapies. Nevertheless, we saw really great response rates. In arm C, which is one of the two arms that we're taking forward in the 1B study, we saw an overall 91% response rate. Look at these bars to the left, to the right, rather. It really doesn't matter what the patient had received prior to P-BCMA-ALLO1. BCMA naive 100% response rate. If they had received prior BCMA, 86% response rate. BCMA and GPRC5D, still 86% response rate. We're very happy with the depth of the responses, given that this was a very early data cut where the average follow-up was under three and a half months. It means we can't really comment on durability yet at this time. We have to wait for that data to mature, but we're very happy with these response rates. We are equally happy with the safety profile that we're seeing with these therapies. We feel this is differentiated versus auto CAR-T and bispecific T-cell engagers. We saw no GVHD, no DLTs, no Parkinson's-like symptoms or cranial neuropathies. We also saw low rates of CRS and neurotoxicity, all Grade 2 or less. With this fully non-viral approach, we did not see and do not expect to see secondary primary malignancies. We also did not give patients any bridging therapy or prophylaxis with tocilizumab or steroids. The data that you're seeing is really the pure performance of this auto CAR-T product. We think that that amounts to a superior patient experience. We were able to treat 100% of the patients who enrolled on our studies. This is an off-the-shelf product, manufactured in advance, stored in the freezer of the medical clinic to treat the patient. We treated a number of patients in the outpatient setting, and we believe the safety profile really sets this up to be an outpatient product and potentially a product that could be used in community centers. Of course, there's no waiting. It's available on demand from inventory with no apheresis, no bridging therapy, no wait time for that three and a half weeks from treatment decision to observed response in the clinic. How does that compare to other therapies and where is the place for this product in the myeloma armamentarium? I'm going to show you a couple of slides that are cross-trial comparisons versus published data. We did not run head-to-head studies. I want to be very clear about that. If we just take a look at the published data from the package inserts, this is the auto CAR-Ts, and you see safety on the left and efficacy on the right. If you look at the safety, I think you can see it's readily apparent that the rates of adverse events are lower. Again, no prophylaxis with Tocilizumab or steroids. And then look at the efficacy on the right side. So if you correct the response rates for Abecma and Cavykti to the intent to treat patient population, okay, so we've accounted for all patients who were enrolled, you can see our response rate is very favorable compared to those therapies. Looking at Carvykti, the SCR and CR rates are a little bit lower, but I would remind you that this was a very early data cut, and we expect responses to deepen over time. Moreover, the data for Abecma and Carvykti is in 100% BCMA naive patients, and our patients, 62% of them were BCMA and/or GPRC5D refractory. We also hear from our investigators that even the BCMA naive patients that we're seeing are different from those patients with rapidly proliferating disease and are patients who would not be candidates for autologous CAR-T. If we look at the bispecifics, a similar story. So if you look at the safety profile, we see lower rates of CRS, similar on ICANS, and infections at first blush might appear similar, but what's not listed here are the grade of the infections. And the grade of infections that we've seen is much lower than the infections for bispecifics. And I think if you're following this topic in the community, you'll be aware that these serious late infections are of concern to investigators. And then on the efficacy side, again, we're very, very pleased and believe that this compares favorably. So we have some further pipeline data updates planned for the second half. We will have a poster at ASH on our P-CD19, CD-20 program. We will have clinical data that will be preclinical. We'll have clinical data in 2025. We will also have a fulsome clinical data update on our MUC1-C solid tumor program at ESMO IO. I'd also like to tell you a little bit about P-BCMA-CD19-ALLO1. This is the newest entry into our portfolio. It is wholly owned by Poseida, and it is an allo CAR-T carrying full-length BCMA as well as full-length CD19 CARs. We intend to advance this for a range of autoimmune diseases as well as myeloma and lymphoma. It's an IND-enabling stage currently. We're very excited about this asset and intend to move it as quickly as possible. Just last Thursday, we started to show some very preliminary data that we've been generating using this product. What you're looking at here is the performance to ablate B cells with some samples of PBMCs from patients with various autoimmune diseases. This is just—these are just some samples. We've looked at others, and we've chosen them because they are different autoimmune diseases that have a range of different B cells and T cell involvement. You can see that we're seeing very nice performance, even at an effector target ratio one to one, and then stepping it up further to, I think it's five to one is what we put on this chart. Yes. Okay, turning quickly to our genetic medicine side. Again, this is non-viral genetic medicine. We have two active programs. Our gene editing program is P-KLKB1-101 for hereditary angioedema. This program uses Cas-CLOVER in lipid nanoparticles to directly gene edit the KLKB1 gene for hereditary angioedema. It's in NHP studies right now. On the gene insertion side, we have P-FVIII-101 for hemophilia A. These are both rare diseases. I think this community is probably familiar with them. Both have been looked at by other types of genetic medicines approaches, but we think non-viral is a great way to go here. And let me share just a little bit of data with you from the Factor VIII program in particular. So we have gene therapy for Factor VIII. It has not been particularly commercially successful. We feel that is not because there is not a market waiting to happen for the right type of genetic medicine approach, but rather that that product just has not reached the market yet. So what we're looking at here is this is from a mouse model. And the challenge with today's approaches, gene therapy approaches to hemophilia A, has been lack of durability. We've heard a lot of reasons why. So we've even heard from investigators, "Oh, well, it's the problem with the Factor VIII gene. It's so large. The cells don't like to make it. They kind of conk out." We think the answer instead is that today what we are using are non-inserting, non-stably inserting technologies, and so you're seeing dilution and episomal loss over time. Regardless, what we see in our data is very nice, very stable production of Factor VIII all the way out to 13 months, which is about as long as you can monitor it in a mouse, and we see clotting efficacy that we believe is at physiological levels. What's really interesting about this program is it also incorporates a version of the safety switch that I talked to you about on the auto CAR-T side. In this setting, we would use it as a modulating switch that would allow us to titrate the efficacy up and down to meet the patient need, so this is really an eye chart. I'm not going to walk us through the whole thing, but I think it makes a visual impact that things are really happening at a very, very rapid pace at Poseida. The left side of this slide is where we feel we were at the start of 2024. We had great partnerships. We had three clinical programs, two of which were enrolling. We were early preclinical work in the genetic medicines area, and as we conclude the year, we have shown what we think is really very provocative, very encouraging data with our cell therapy programs and have made a great deal of progress on the genetic medicine side as well, and we have enriched our portfolio with assets, more assets that are wholly owned by Poseida. So with that, I'd like to just say we feel we are really well positioned for efficient value creation and overall leadership in allogeneic CAR-T and non-viral genetic medicines. We have a vast IP estate on our toolbox and how we apply it. And we're well capitalized into early 2026 with potentially more milestones and funding events that we have not accounted for. So with that, Ben, should we take a few questions? Yeah, absolutely. Thank you for that. 30 questions. Go ahead. And maybe I'll start. So there's some great data on multiple myeloma that you showed. I think we're all familiar with the modified intent to treat data from CARVYKTI and so forth, but you showed us the ITT data, which is fascinating. And I think you also talked about the potential to kind of go into the community, get this into the hands of community oncologists, which is, I think, maybe easier to kind of wrap your heads around with an allo product than maybe something that's autologous. But talk about just the path forward. What is the regulatory path forward? If the next update kind of goes as planned and the data continued to evolve as you hope, what is sort of the next step to get this approved? Yeah, absolutely. Like I said, we are in phase 1B, which is a trial that Roche is completely funding, by the way. So at this point in time, Roche is carrying all the costs for both the myeloma program as well as the CD19, CD20 program. So it's in Phase 1B. That's a two-arm study. We are looking at the ARMC regimen that I talked about as well as a higher dose of cells. We don't know that we'll need that, but we certainly have the room and the safety profile, so we're exploring that. That trial we believe will complete quite quickly. It's an auto product, so we don't have to wait for the manufacturer of cells for every patient that's enrolled in the trial. So think typical Phase 1B size. We have an RMAT designation on the program. So we're engaging with FDA. We expect that they will be pretty clear with us on their expectations for a pivotal study. And so we hope to be entering that pivotal study in the very near future. And we think with the data that we've shown, which the FDA did not see all that data in making their RMAT designation, we're going to be really well positioned for a very smooth and rapid path to approval. Great. Okay. We're getting real-time data from ACR, this rheumatology meeting, where there's a lot of CAR-T data being presented there. We saw some allogeneic data this morning. Over the summer, there's a Chinese study that released some allogeneic CAR-T data. So I want to kind of go back to one of the slides where you talked about with your, I believe it was your BCMA CD19 allogeneic product, and you showed some samples where you're depleting B cells. Why is CD19 BCMA, why is that the right approach? And then do you have a sense as to when Poseida will be ready to kind of talk about the specific path and the autoimmune indications that you'll go into? Yeah, absolutely. And thanks for asking about that, Ben. We are really excited to enter autoimmune disease because we feel that the advantages that our platform has demonstrated in the oncology setting will play at least as well in the autoimmune space. So specifically, an allogeneic product, we have that embedded safety switch, so we can kind of, and we know our cells are more persistent, so we can kind of play it either way. We can either let the cells run if we conclude that you would like some persistence in autoimmune disease, or if all we want is a hard, fast reset of the immune system, we could also infuse the cells and then switch them off very rapidly. And we're a non-viral approach. I used to run autoimmune businesses, and we were always getting questions about secondary malignancies from all kinds of immunosuppressants. I think the intrinsic safety profile of our T stem cell memory cells, along with the fact that they're auto and that embedded safety switch is going to be very appealing, along with our ability to manufacture at scale. The patient populations in these autoimmune diseases are much larger than in the oncology space. You really, and we have different pricing anchors too, right? And it's all outpatient. You really want a platform like ours to capture that opportunity. That's the platform. Why BCMACD19 as the asset that we're particularly moving forward rapidly? What that combination of targets does, and I think we saw really exciting data emerge from an auto program using those two targets, it gives you end-to-end coverage of the B cell spectrum. You have every lineage of B cells all the way up to and including the plasma cells and plasma blasts, which you can't get with the CD19. Those cells have been implicated in some autoimmune diseases in particular, such as multiple sclerosis, which would be an example. We think that it could have applicability for quite a number of autoimmune diseases. It also might be appealing for multiple myeloma as well, because with that CD19, that gives you the ability to potentially target progenitor cells, which are CD19 expressing, but not yet BCMA expressing. It may really be a workhorse for many, many different diseases. How are we moving it forward? It is an IND-enabling stage right now. We have wanted to really make sure we were good and ready before kind of bringing this program onto the stage. We have a short list of diseases that we're working on prioritizing, and we look forward to, in the near future, explaining what that will be. We've guided one or more INDs in 2025. Okay. Fantastic. And just one last very quick question. So I thought you did a great job kind of showing what the progress was made by Poseida over 2024. Next year, as we look forward, what are kind of the key moments that we should be focused on? Yeah, absolutely. So certainly the next data update on P-BCMA-ALLO1, right? So the RMAT data will be maturing. We will have that. The 1B study is underway. So I think 2025 will be a very important year for that program. We also have CD19, CD20 right on its heels. We'll have a data update on MUC1C this year. And as I said, I think we've guided that we will have INDs for assets like P-BCMACD19 in 2025 as well. In the meantime, we expect to continue collecting milestones and moving forward with our partnerships. So, yeah. Okay. Well, great. Thank you so much. Thank you, Ben. It's been great to be here. Thank you. Thank you.