I'm Jennifer Kim, one of the biotech analysts at Cantor, and I'm looking forward to hosting this fireside chat with Poseida Therapeutics. I'm joined by Kristin Yarema, the CEO, and Syed Rizvi, the CMO. Thanks to you both for being here. Kristin, you took the reins as CEO this past January. Syed, you joined even more recently. Maybe to start things off, can you give a quick snapshot of Poseida, how you feel in your roles today, and what you're excited for looking ahead? Yeah, absolutely. Well, you know, thank you, Jennifer. First of all, it's great to be here. Thanks to all of you at Cantor for having us. It is fantastic to be at Poseida. I feel great in my role, and I feel great about our prospects. You know, at Poseida, we're in a period of very, very heavy news flow, you know, starting this month, September, and running right through, right through the end of the year. If you may not be familiar with Poseida, Poseida is, at its root, a platform technology company, but I like to say a platform technology company with assets. Everything that we do in cell therapy and genetic medicines is using a non-viral approach, and in the cell therapy space, we really focus on producing CAR-T, all allogeneic, and using a very particular type of T cell, the CAR-T stem cell memory cell. So, you know, we use a very unique and proprietary genetic engineering toolkit to manipulate cells outside the body that makes those allo CAR-T for us. We also use them in vivo, and that's our earlier, but very exciting genetic medicine side of the business. Okay, so starting on a high level, tell us more about the technology toolkit that you've put together and that fuels your pipeline. Why have you invested so heavily behind this approach, and what are the potential advantages that you see? Yeah, well, like I said, Jennifer, everything that we do at Poseida is non-viral. So think non-viral genetic engineering, and then if you're thinking cell therapy, think allogeneic CAR-T using T stem cell memory cells. And how we're able to do that is using a suite of technologies that Poseida has been working on for a very long time. So we have always been focused on, for gene insertion, a non-viral transposon-based approach. That was very important to our founder. We've been working on it for a long time, and we pair that with other tools, such as our proprietary gene editor called Cas-CLOVER. That system, we've run some experiments head-to-head versus Cas9, which you might be more familiar with from the CRISPR system, and we see that is up to 25-fold higher fidelity. We use this non-viral gene insertion approach and a non-viral high-fidelity gene editor, together with other technologies, such as proprietary manufacturing technologies. We have additives that allow us to grow cells without using cytokines, still in high yield or differentiating the cells, and we have our own lipid nanoparticle groups that also helps us on the genetic medicine side. So the real thing to appreciate about our system, Jennifer, is we've been very planful, very mindful to come up with an entire suite of tools that work together in concert to enable us to deliver these ALLO CAR-Ts or these in vivo genetic medicines. And you know, they're really quite different and quite distinct from the tools that everyone else is using, and proprietary to Poseida. Okay, and like you said, you've positioned yourself as a platform tech company with assets. Mm-hmm. Two of the assets that get a lot of focus these days are through your partnership with Roche. Mm-hmm. I think that's going on two years now. Remind us the terms of that collaboration, how that partnership has advanced, and what has kept Roche engaged? Yeah, sure. So like you said, we've just passed our two-year anniversary with this partnership with Roche. It's one of two major partnerships we have in the area of allogeneic CAR-T, and it's the larger of the two. It is focused in the area of hematologic malignancies, and it's a pretty broad-ranging alliance. So Roche has licensed our lead two programs. I'm sure we'll talk more about those, but the first is a program for multiple myeloma that is called P-BCMA-ALLO1. So it is an allogeneic CAR-T directed against B-cell maturation antigen. This is currently in phase I b. The second clinical program that is in that Roche partnership is P-CD19CD20-ALLO1. So this is an ALLO CAR-T, again, based on that T stem cell memory cell phenotype that carries two full-length CARs, so one against CD19 and one against CD20. You might think about using it in cases of antigen escape with someone who's already been treated with a CD19 CAR-T, for example. They might lose CD19, and you can give them this dual that has both CD19 and CD20, or you could give it upfront in advance of a CD19, and you have coverage of both of those targets. So both of those are programs that have been licensed to Roche. Right now, they're in clinical development. Poseida runs the clinical development through phase I of these programs, but it's a great arrangement because Roche is really funding things, right? It's not requiring a lot of expense on our part at Poseida. There are also additional programs that are further upstream. There are a couple of programs that Roche has an option on, and then we have a research collaboration where Roche can nominate up to six additional targets for other heme malignancy programs. So, you know, I think you can tell this is multifunctional, multi-asset. It's a very deep and extensive relationship that we have with them. What's kept them engaged? Well, I think first and foremost, it's been our execution and our success. So at one of our earnings calls or earnings releases last year, we talked about how, given the speed of progress and the success of our execution, Roche actually accelerated and increased the likelihood of payment of a number of the payments and milestones. So, you know, that is not something that you hear every day from large pharma partners. So, you know, I think that has worked well, and the two companies share a high science mindset and a commitment to creating value for shareholders and meaningful new therapeutic options for patients and physicians. Okay, great. Maybe we can dig into the BCMA program. Can you recap the data you've shown so far, and just thinking about the competitive landscape, where do you think your therapy sort of fits in? Yeah. So when you think about CAR-T, so right now we have a couple of autologous CAR-T on the market. We have no allogeneic CAR-T, right? So I'm going to come back to that point because it's important in terms of, you know, how to think about this in the placement, in, you know, in the market and in, and in the armamentarium. In terms of what we've seen thus far, so we gave a data update at ASH in December of 2023. That was early, but to our minds, very exciting. So we saw in patients receiving adequate lymphodepletion, of which there were 11, an overall pooled response rate of 82%. If we were to look at patients in the arm, what we call the P2 arm, all of those patients achieved a VGPR or above, and 40% achieved a stringent CR. Now, that was an early data set, so we don't have a lot that we can say about, you know, durability of those patients in that time at ASH. It certainly was quite exciting data, particularly when you understand that this was data that we generated in probably the sickest myeloma patient population that had been studied. The median lines of therapy that the patients had received was seven. Most normally we see something like maybe four, maybe five. All of these patients were able to start their therapy the day after enrolling in our study. No waiting weeks or even months for treatment. We were able to treat all of the patients. It was an off-the-shelf ALLO product, so no manufacturing failures, you know, no, patients progressing before they could receive therapy. None of them received any bridging therapy, which normally patients receive something like a triplet therapy in multiple myeloma, and that, frankly, is part of the response rates that we see from auto CAR-T. That's like baked into the response rates. We didn't do that. And then let's talk about safety. So it's always been our thesis that the T-stem cell memory cell-based CAR-T could have a differentiated safety profile, and we think that's what we're seeing. We saw very low rates of CRS and ICANS, and it was all grade two or less. We didn't see any GVHD. We didn't see, you know, even infections were quite rare, even in the arm with the highest lymphodepletion. It was an early snapshot of what we think will be a very exciting product. Where will it fit? Well, and I'm sure Syed will talk about this, as we're looking ahead, but another notable aspect of our study is we are enrolling not only BCMA-naïve patients, but also BCMA-experienced patients, and we're continuing to do that. So right now, today, we really don't have hardly any, and I would say, not great choices to treat patients who failed some kind of BCMA-directed therapy. That's a patient population that's included in our study. That could be a patient population of high unmet need. In fact, just yesterday, we were able to announce that FDA has awarded this program the Regenerative Medicine Advanced Therapy Designation. It's RMAT, for short. If you're not familiar with this, this is like breakthrough designation for cell and gene therapies. And what's really notable is that our RMAT designation matches the inclusion criteria in our trials, so it's for a patient population who've received three or more prior lines of therapy. I think that's important because you will remember that the initial approval for the autologous CAR-Ts or even bispecifics in multiple myeloma was a more restricted patient population, four or more prior lines of therapy. So we are looking at a sicker patient population, but at the same time, FDA is saying, "Hmm, we're going to give you an RMAT designation for a slightly broader patient population than some of these earlier products." So I think that's, you know, I think that's pretty notable. Can you talk more about the RMAT designation? What data did the FDA have access to, to sort of base their decision? Yeah, it's a great question. So you do submit a data package to the FDA. They review it and decide, you know, to whether to award you this designation or not. So to FDA, we provided the ASH data set that I just, you know, explained to you, as well as some additional supporting data. Okay. I do wanna talk about the upcoming presentation- Mm-hmm. where we'll get an updated look. But you also flagged recently that there was a patient case study that you presented at SOHO. This was from your autologous BCMA program, and I'm wondering, can you walk through what that case study showed and how that might translate into the allogeneic program? Yeah, absolutely. And maybe I'll just start to give some context, and Syed can go into the study. So as you mentioned, this was data released at the SOHO conference recently, and it was from an autologous program. Now, you're saying, "But Kristin, you just said everything that you're doing is allogeneic," which is true, but the company did have a couple of autologous programs in the past before making the pivot to allogeneic CAR-T. This was a patient who was in long-term follow-up from our previous autologous BCMA CAR-T. And it's important that we use the same technology in that autologous program that we now use in our allogeneic program. So think of it, same T stem cell memory cell, same tools and genetic engineering approaches, but that was an auto program, and now we've switched to ALLO. So really a very interesting, you know, remarkable case. Syed, maybe you can take us through this. Absolutely, Kristin. So this case was really, really interesting. And why? Because this has never been seen in medical literature. So this patient received their autologous CAR-T about three years ago, and this was a patient who was a relapsed refractory patient and received many, many therapies before receiving the autologous CAR-T. And patient went into a stringent CR, which was maintained for about two years, and then slowly and gradually, patient started to relapse. And patient was given other multiple myeloma therapies. Nothing was really working. And at that point, the physician thought that maybe I'm going to give them the TCE, which is GPRC5D-focused or targeted talquetamab. So they started talquetamab, and the way it's been given to patient is that there's a step-up dosing. Three doses are step-up, and then the final dose, the fourth dose is a full dose. After this patient received one full dose, patient has, you know, drastic, you know, CAR-T enhancement, leukocytosis, that was looked into, what is the phenomenon? And there were various analyses being done to where this is coming from, and it was purely our autologous CAR-T, which was engrafted in a patient, and that actually reactivated and put the patient very quickly again in a stringent CR, and that stringent CR is going on for nine months and counting. Okay. I was gonna ask, is there any chance that it's driven by that single dose? And what is the hypothesis for what's happening there? Yeah, I mean, we certainly don't think so. You know, the investigator does not believe so. You know, one full-strength dose of talquetamab, one week in total, you know, is not likely to put a patient this refractory into a stringent CR for nine months and counting. And I think more strikingly, Jennifer, we could see the CAR-T. So we were able to measure it and measure the level. We saw 685,000 DNA copies, which was really, really reassuring, and it was not a monoclonal, it was polyclonal for our CAR-T. So it was everywhere that we were able to really see. So the way to think about this is, you know, in CAR-T, we use all this like colorful car language, right? Like everything is like some kind of car. So we talk about this as like jump-starting and then steering the car. You know, it was you know, kicked by another antigen target entirely, the GPRC5D T-cell engager, but reactivated our CAR-T, causing it to re-expand and putting this patient back into this, you know, fantastic stringent CR, where the patient is now off of all therapies. Okay. I'm a fan of the car metaphor. So, I mean, I guess we'll see more data very soon. You're presenting updated data from the phase I trial at IMS i n late September. I don't believe we'll get a glimpse of that data until the day of the presentation. Can you set the stage in terms of how fulsome of an update that will be, and what additional data should investors expect? Yeah, thanks. Thanks, Jennifer. So yeah, unfortunately, the abstract is under embargo until the time of the presentation itself. If you're following Poseida, if you have interest in us, that data presentation will be on Friday, September 28, in the evening, East Coast time, and then we will have an investor call the following Saturday morning. It's, you know, the conference is in Rio. It's a time zones and logistics thing. But that is when, you know, we'll have a great look at what this data update is. And it will be a continuation of the phase I study. So this study has been ongoing. We've been looking at patients in these arms of adequate lymphodepletion since June or July of last year, 2023. So we've been recruiting since then. We've added some sites, so we think it should be, you know, a pretty nice, fulsome data update. And I would just remind people of what I said before, which is, you know, our study is, you know, very open. We are enrolling both BCMA-naive patients as well as patients who are BCMA experienced and may have seen other therapies as well. Anything to add there, Syed? I think the point that we should also, you know, keep in mind is the patient population. Because when you think about autologous CAR-Ts, patients have to go through bridging therapy, they have to wait for manufacturing times, which are quite long. But when you talk about allogeneic cell therapy, when a patient comes in and the patient is found eligible, they can start the therapy right away because that CAR-T is available in that hospital's freezer, basically. And our median time to start therapy is just one day. You will see that not only patients who are BCMA naive versus BCMA exposed, but also that those patients who could not wait, who have explosive disease or who need therapy right away, those are the patients who are also coming into allogeneic cell therapy. So you will see the patients are sick, and these are the patients who really need treatment. Okay, and durability of response, obviously a huge focus for allogeneics. How much will we get a sense of durability in that data cut? Yeah, it's a terrific question, Jennifer. And, you know, we, because the abstract remains under embargo, there's not a whole lot that we can say. But, you know, but we can remind people what we talked about at ASH. So that ASH data cut that we released in December was based upon a data set, you know, a data cut in late October, and we started dosing those patients again, you know, in the summertime of 2023. So there will be, you know, some amount of follow-up. Like many oncology studies, this has been a three-by-three dose escalation design. So you enroll a patient per month for some period of time, and then you're able to expand the study. You know, we are going to see a good amount of follow-up on some patients, but certainly, you know, given the rolling nature of the study, we won't have, you know, a long duration of follow-up on all of the patients. I remember at the time of the ASH update, you talked about exploring and finding the right lymphodepletion regimen and- Mm-hmm. I think you said, you were in the ballpark. That's right. How would you describe the progress you've made? As of now, are you still in the ballpark, or what should we expect? Yeah. Yeah, great question, and maybe let me just put a little bit of context around that. So when we talk about a dose and dose finding in cell therapy, we really have to think about three different things. It's a little more complex than if you're doing a small molecule or a monoclonal antibody. So dose really means, what lymphodepletion did you give? How many cells did you give in terms of an absolute number of the cells, and how did you give them? Did you give them in one dose? Did you have a split dose, you know, cycle or something like that? And at Poseida, we have decided that this dosing question is a very important one that needs to be well-studied. Our partner on this program, Roche, feels exactly the same way. You know, big pharma companies are often very focused on getting dose selection right. So we've been very systematic in taking a look. So what you're referring to in the ASH data set, we had found a range, five hundred to a thousand, milligrams per meter squared of Cytoxan plus fludarabine. That all seemed to work. And what we had said at the time was we felt that was in the ballpark, but we were not, we hadn't decided on a final go-ahead dose, and we were gonna continue to iterate that somewhat this year, which is exactly what we have been doing. I would say we have learned a lot about how to properly give these therapies. We had a couple of posters earlier in the year at AACR, where we elaborated some of that, you know, people could take a look at if they have interest, but we've continued, I think, to really make a lot of progress in studying the different aspects of that question. What's the best lymphodepletion? How many cells to give, and how do you give the cells? Is that an answer that we'll see in the IMS update? You know, we will intend this to be a fulsome data update. Those are some of the things that we've been looking at. You know, you'll see in 10 days, but, you know, that's definitely what we've been working on. That sounds good. You also recently noted you've aligned on the phase I b trial design with Roche. What can you tell us about that design, where you at, and sort of the timing for that trial? The timing for that trial is underway. We announced just about a week ago or so that this P-BCMA-ALLO1 program has formally moved into the phase I b expansion phase of the study. That was clearly a joint decision. It was an important decision. You know, that phase typically means you're in the ballpark, you're getting really close to having settled on a dose, and you're just trying to collect a little bit more data to have real confidence in the decision that you've made. made. That triggered another $20 million milestone from Roche to us. You know, just this year we've collected $70 million in milestones there. That part of the study is active. We're very excited about it, and it is ongoing as we speak. Okay, maybe with the time we have left, we can turn to the CD19, CD20 program. That started its phase I more recently. Mm-hmm. And that's your first dual CAR program. Can you talk about sort of the. You've talked about the potential advantages of being able to carry both full-length CARs? Mm-hmm. So, what is the potential differentiation there? Yeah, absolutely. So what Jennifer is referring to is this dual CD19, CD20 program. It's one single CAR-T cell, but when a lot of companies talk about they have a dual CAR-T, what they mean is they have one CAR-That's, you know, in the membrane, and they put a couple different domains on it, a tandem. So you might have a CD19 and then a CD20 or, you know, some other combinations. That is not what we do. We put a full-length CD19 and a full-length CD20 CAR in. That is an option that is open really only to us, and it has to do with the cargo capacity of our transposon technology. If you're using a virus to do your gene insertion, you can't fit that much, you know, nucleic acid into the virus. You need to use a transposon if you want to do this kind of multiplexing functionality in a cell. So that's what we have. This is the first ALLO dual CD19, CD20. Now, why is that important? Well, we touched on this a little bit before, and it has to do with this. This is a program for B-cell malignancies, could also have application in autoimmune disease. There might be multiple targets that you want your CAR-T cell to hit. In lymphoma, we know that up to 40% of all patients who are relapsing or progressing after a CD19 autologous CAR-T, that's happening to them because they've lost the CD19 antigen. So if you have a CD19, CD20, you still have another option. You know, you might be able to pick up whatever residual CD19 there is, but you're also targeting the CD20, which is an antigen that doesn't tend to be lost. But you could also use this therapy ahead of a CD19 autologous CAR-T, and then you have coverage of both targets in the event of potential antigen escape. So, Syed, any additional color to add there? I think that, being the dual CAR-T, I think this is something where the community is extremely interested. They would like to see where they can give more chance to relapsing patients. So definitely more to come. Okay, and since you brought it up, where are you at in terms of considering opportunities outside of oncology, either with this asset or just leveraging your technology? Yeah. Well, we are very excited about the opportunity for cell therapy in autoimmune disease. You know, just very personally, this is something that I've thought about for a long time. You know, a lot of my career has actually been in autoimmune disease as well as oncology, both drug development and commercialization. We're an autoimmune disease family, so, you know, I'm on a board of a patient advocacy group, for example. And the thing about developing drugs in autoimmune disease is it's very different from developing them in oncology. It takes a different approach, it takes a different set of capabilities. It also takes the right technology. So what we have said is that we are working on our strategy. We have great ambitions in autoimmune disease, and we have assets that could be very relevant. We've talked about BCMA, but CD19, CD20 is a great combination. A little bit earlier upstream, we have a BCMA, CD19 dual CAR-T, also could be applicable for autoimmune disease and even some other targets. So we have a rich array of programs that could be really relevant in autoimmune disease. But when we disclose our autoimmune strategy, you know, it's going to be very intentional, and it's coming from a position of strength. So we are very pleased with our results in oncology. We're not looking for a pivot to autoimmune disease. We're looking for a growth extension opportunity, and we feel our platform, which is non-viral, and has other intrinsic, we believe, safety advantages that we've seen play out in our ASH data, also is allogeneic and can be produced at scale. Already we're getting up to over 100 doses per batch from our oncology programs that we manufacture in our own GMP manufacturing facility. Autoimmune disease patient populations can be even much larger than those in oncology, and the patients can be very geographically dispersed. We believe success in autoimmune disease means starting with the right technology, having the capabilities to do the right drug development programs, and being able to manufacture at scale to meet the need of the larger volumes of patients who might someday be looking for these therapies. Okay, I think we've reached the end of our time. Kristin and Syed, thank you again for a great discussion, and I'm looking forward to the data ten days from now. Enjoy the rest of your conference, everyone. Thanks, Jennifer. Thank you.