Good afternoon, everyone. Welcome to H.C. Wainwright's second annual Cell Therapy Virtual Conference. My name is Arthur He, a senior biotech analyst at the firm. Thank you for joining us to have a conversation with Dr. Kristin Yarema, President and CEO of Poseida Therapeutics. Poseida is a clinical stage biopharmaceutical company focused on developing novel cell and gene therapies to treat cancers and the rare genetic diseases. The company currently has three clinical stage allogeneic CAR-T candidates, and a number of preclinical in vivo gene therapy programs. Notably, Poseida has forged strategic partnerships with both Roche and Astellas. To discuss these programs and to learn about the company's development strategy in 2024 and beyond, I'd like to invite Kristin to this fireside chat. Good afternoon, Kristin. Good afternoon, Arthur, and thank you for the invitation. It's great to be here. Sure, our pleasure. So, first of all, to help set the stage for our audience, Kristin, could you give us an overview of Poseida's pipeline? Absolutely. So, you know, like you said, Arthur, we are really foundationally a platform company working in allogeneic cell therapy and gene therapy, but we're doing that using non-viral approaches. That's really the key that underpins everything. And so the way that Poseida came about was the founders thought, "What type of products are going to be needed to be medically impactful and commercially successful?" And realized very quickly that that product profile was not going to be achievable using the set of genetic engineering tools that were available at the time. So now, having produced those tools, we're now at the stage where the assets, the programs that we developed using those tools, are in the clinic. So like you said, Arthur, we have three clinical stage allogeneic CAR-T. The lead program is P-BCMA-ALLO1. That is in multiple myeloma. It's directed at B-cell maturation antigen. BCMA is a target. Phase 1, and we reported some data in at ASH in December. The second program is P-CD19CD20-ALLO1. This is a fully allogeneic. It carries two complete CARs against CD19 and CD20. That is also in phase 1. Both of those programs are in the partnership with Roche that you mentioned. And then the third program, which is fully owned, is our solid tumor program, P-MUC1C-ALLO1. So that is in a basket study for various epithelial cell tumors, and it's targeted at the C-terminal portion of the mucin 1 protein, which is only exposed in the case of malignancy. So it should be a well-targeted specific approach for solid tumors. So we also have other programs upstream in allogeneic cell therapy in the preclinical and research stage, and then we also have, as you mentioned, gene therapy programs for rare genetic diseases. We have an upcoming R&D day on April 17th, where we will be covering those preclinical programs and technology developments. Oh, thanks, Kristin. So we speak of the technical platform by Poseida. 'Cause we all know that recently the FDA raised the secondary malignancy risk with the currently approved auto CAR-T therapy. I'm just curious, does Poseida technology have the potential to kind of mitigate those kind of risks? Well, in our view, it absolutely does, Arthur. So, you know, as you're aware, FDA found this of sufficient concern that they added a black box warning to the labels of the commercially available autologous CAR-T. And, you know, what seems to be behind that concern are the lentiviral vectors that are used to insert the CAR transgene. So Poseida uses a completely non-viral approach. So, you know, to start with, our cells are allogeneic, so they do have a finite lifespan, but we are not using lentivirus, we are using a transposon-based technology. And in addition, our cells carry an embedded safety switch. It's in every single one of our programs. We can do that because the transposon has a much larger cargo capacity. It's about 30 times higher than what you can get from a viral vector. So we can put all kinds of functionality into our cells, which could include one or more CARs, we use a selectable marker and purification, but also that safety switch, and we know it works very quickly on a timescale of, you know, hours. So should there ever be a concern for a malignancy, and we haven't seen anything that gives us concern, we think, you know, that, we're not going to see that in our programs. But even just for that peace of mind, you know, we can point to that safety switch is always there and very easy to use. That's quite interesting. So yeah, let's dive into some of the early data for the P-BCMA program. I know, this is the first clinical candidate in a collaboration with Roche. Could you highlight the clinical data accumulated today, and tell us more about how your collaboration with Roche ongoing? Yes, absolutely. So, the collaboration with Roche is fantastic, in a word. They're, you know, a joy to work with. They like talking about Poseida, too, and we're very happy. With that, they announced actually we announced that because of the progress in the program, we've been able to accelerate milestones, and Roche has increased the certainty of paying some milestones, including just last year, we got another at the end of the year, another $30 million milestone that was paid at the start of this year. So the collaboration in general is progressing wonderfully well, and I think Exhibit A really has to be the ASH data from the BCMA program. So just to cover that with you, this was an early data cut from the study. The study is ongoing, but in this data cut, we had 11 patients who received adequate lymphodepletion, and this was at a dose of 2 million cells per kilogram. So we looked at these patients in one of two lymphodepletion conditioning regimens, and what we found, starting with the efficacy, was very exciting. So if we pool those two arms, we saw an overall objective response rate of 82%. In fact, 100% of the patients responded if they received anything except Teclistamab, which is a BCMA CD3 bispecific. So it doesn't matter what myeloma therapy you got, if you received anything other than Teclistamab, you responded to BCMA-ALLO1. So that in itself is extremely exciting. But we also saw great depth of responses. So, at the higher of our two lymphodepletions, everybody got a very good partial response or better, and 40% achieved a stringent CR. So that's the kind of responses you want to see in myeloma. What makes it particularly exciting is that this was achieved in a very sick, very refractory patient population. So the median number of prior lines of therapy for our study was seven. If we think about autologous CAR-T studies, you're seeing, you know, maybe five prior lines of therapy. So these patients were extremely, refractory. In addition, 40% of them had actually already failed prior BCMA-targeting agents, and 30% had high-risk cytogenetics. So, the BCMA patients are often excluded from trials. So we're seeing these response rates and depth of responses in, you know, a very, very ill patient population. We were also able to treat all of the patients, so every patient who signed up for our study, we were able to treat with the product, which is a little bit maybe obvious for an off-the-shelf allogeneic CAR-T, but, you know, that's not the case with autologous cell therapies. Patients might progress, they might not manufacture. We're excited about that, and even better, they received the therapy quite quickly. One day after they enrolled in the study, our patients were able, on average, to start their lymphodepletion, and then a median of seven days, one week after starting the study, they received the cells and were treated. That's very different than autologous CAR-T, where patients are waiting many weeks or even months to receive their treatment. So we're really thrilled with the early efficacy that we have seen, but also the safety profile is, you know, again, while early, particularly encouraging. So we saw no dose-limiting toxicities, no graft-versus-host disease, very low rates of cytokine release syndrome and neurotoxicity, so only 21% and 6%, respectively. And it was all, you know, mild to moderate. It was grade two or less and easily resolved. So we did not see the kinds of, you know, severe adverse events that we're seeing with some of the autologous cell therapies. So when you put together the package of, you know, very high response rates and deep responses, you know, an early but very encouraging safety and tolerability profile, and the ability to treat everyone, you know, off the shelf, one week from the time of the treatment decision, you know, we think this is really, an emerging therapy that's, that has, you know, tremendous commercial potential. That's quite encouraging, especially when you can treat all patients if they needed to be treated, right? It's really a big, big thing compared to the autologous CAR-T. So, what's next? I mean, when or what kind of data set we could expect from this program to be updated? Yes. So, you know, we have guided that we will give a data update on that program, actually, all three of our clinical programs, in the second half of this year. So sticking with BCMA, you know, the study has continued to enroll. Obviously, people have seen the ASH data. There's a lot of enthusiasm for the study. It's recruiting very robustly, and we've actually, you know, continued and even expanded things. So by the time of the second half of this year, we should have you know, a nice number of patients and quite a bit of follow-up on these patients, because we began dosing them in June, July of 2023. So I think it's really gonna be something that investors wanna watch out for, and, you know, think about Poseida even in the run-up to that data readout. And it's a catalyst-rich year, because we will have updates also in the second half on the other two programs, too. Well, I'm very much looking forward to that. Let's switch the gear to your own pipeline program, the MUC1-C. First of all, could you tell us a little bit more about the study design of this and highlight the clinical data to date? 'Cause I know the study design is quite a little bit complicated. Yes. Yes, that's one way of looking at it, is that it's complicated. We also like to think that we engineer a lot of, you know, flexibility and optionality into the protocol, too. But sure... So you're right. At its core, it's a typical 3-by-3 type of study design, so typical dose escalation cell therapy study. We begin at a dose level of 750,000, you know, cells per kilogram, and then we can, you know, escalate the dose. But we also are looking at different lymphodepletion regimens, so we've been studying that quite systematically. And it's important to understand that this study is a basket trial design as well. So, you know, MUC1 and MUC1-C, after protein is cleaved in the case of a malignancy, you know, it’s expressed on a number of different epithelial cell tumors. So we've been quite open to recruit patients of different, you know, different tumor types into the study. So we're looking across all of those things: cell dose, lymphodepletion, and tumor type. Gotcha. And, how about the, the data so far? Is there any. Can you give us a little bit, color on that part? Yes. So, the data update that we gave was last at ESMO. This was back in 2022, and it was really just the very first patient cohort, so six patients. Wow. We did see a partial response in a breast cancer patient, and we saw stable disease in a couple other patients, with other tumor types. So that was quite encouraging, even at that low cell dose. So since then, as I mentioned, we've been, you know, looking at cell dose, lymphodepletion regimen, and, as well as tumor type. And while the larger clinical data update will be in the second half of the year, we do have preview coming up at AACR on April 8th, that will look at cellular expansion in the MUC1-C program. Gotcha. So yeah, so very, very concentrated catalyst in the second half. And just a quick follow-up on this MUC1-C program, 'cause I know you guys did a collaboration with Astellas back last summer. Could you highlight the deal for to our audience, and what's the rationale behind that? Yeah, thanks, thanks for the question, Arthur. So yeah, this was in the summer, as you said, and it was really a strategic investment from Astellas. So Astellas, essentially, you know, purchased a small equity stake and gave us some cash. So it was $50 million in total. And for that investment, what they received was a board observer seat for 18 months, and a right of first negotiation on the MUC1-C program. So Astellas, you know, is a company with a strong interest in cell and gene therapy. Their CEO, Okamura-san, has, you know, been very vocal about their interest in advanced technologies, advanced therapies, like cell and gene therapy, and they're a company with a solid tumor heritage. So you can see why they would have, you know, interest in allo cell therapy and the MUC1-C program. But it's important to understand that they haven't licensed it or optioned it. They have a right of first negotiation, which is also time-bound. So it expires in twelve months. I see. So before I jump to the pipeline question for you, I just want to ask you, 'cause we all know the manufacturing is a pain point for the cell therapy sector for this modality. Could you give us more color on Poseida's progress made on the manufacturing part of the story? Absolutely. So at Poseida, we really strive to think about the problem of delivering cell therapies or gene therapies holistically. So what is everything that is required to do that? And that means not just delivering the clinical data, but it also means being able to manufacture as well. So we have been very, you know, mindful to progress the clinical development and the manufacturing in lockstep. So we have our own GMP facility on site. We do not use contract manufacturer at all. All three programs are manufactured in that GMP facility, and that's really fantastic for us because it allows proximity to process development. We take a very standard approach to the process for all of our programs. So if we find a learning, if we optimize a unit operation and find a way to increase yield, for example, on one program, we can very rapidly translate those learnings to the other programs. So, you know, we've been very excited with our progress. We announced with CAR-T back in the summer that we are able to produce up to over 100 doses per batch. And that's at current yield levels, we think we can go even higher than that, but up to 100 doses per batch, depending on what you believe about the cell dose. And we think that's really powerful, because that's in a far smaller facility than autologous cell therapy, much smaller footprint, and, you know, much lighter staffing. So it gives us a tremendous advantage when we think about the cost of goods manufactured. Wow, that's really amazing to look at this manufacturing capacity come out to your site. So, we know right now in the industry, people are moving CAR-T into the autoimmune disease area. Does Poseida also has this kind of plan? Or could you share us a little bit more on that part of strategic thinking internally? Yeah. Thanks, Arthur. So we absolutely are. So what we have said is that we're actively working on this. Let me start by saying, you know, we believe that all the advantages that our platform has in oncology are likely to play equally as well in autoimmune disease. So we think our type of cell, the T stem cell memory cell, you know, that especially in oncology, will be equally so in autoimmune disease. Things like the safety switch, you know, very interesting for autoimmune disease, and then, of course, the ability to just manufacture at scale at a reasonable cost to the patient, you know, populations in autoimmune disease may, in fact, be even larger and more geographically dispersed than in oncology. So, you know, we think that we can absolutely deliver products for autoimmune disease. What we want to make sure that we are doing is doing it in a mindful way, because our programs in oncology, you know, at least keying off of the BCMA data, you know, the approach is working, right? The data looks great. So what we are not doing is we are not being forced by an inability to manufacture or poor clinical data to retreat or find, you know, something else that we need to do, and, "Oh, we'll try autoimmune disease." No, we are looking at this opportunity, and we think it really is a commercial opportunity from a position of strength. So we are going to be strategic. We are thinking very carefully about the right cellular target, the right disease state, and there are many in autoimmune disease, and then the right entry approach. So probably the among the fastest things we could do, smoothest things, would be, you know, to, to collaborate with Roche on some of the programs we are already collaborating on, but we have other options as well. You know, we might be able to do things alone. We might be able to partner with others, and we've gotten a lot of interest. So we're looking at this very carefully. We haven't announced our plans yet, but we have said, you know, this is an area of opportunity, and we're gonna be very strategic about it. Sounds great. I guess we're gonna hear more regarding the autoimmune opportunity in the second half year of, at another R&D Day. So, to wrap up our conversation, Kristin, could you help to summarize your upcoming catalyst as well as the cash position? Absolutely. So, our first catalyst, is potentially right around the corner. We have our first ever gene therapy R&D day on April seventeenth. We mostly focused on cell therapy today, but that will be an opportunity to, you know, hear a strategic update on gene therapy and all the progress on our tools and programs in that arena, so encourage everybody to tune in for that. It will be virtual. Then we have, the three allogeneic cell therapy data updates, all in the second half. There'll be some posters, you know, at the AACR, as I mentioned, in between, but, you know, very big clinical data updates in the second half. And we will also have, as you said, Arthur, a cell therapy R&D day in the second half as well. And then our cash position, what we reported at the end of the year, was $212 million, but that does not include that $30 million payment that I mentioned, that we've recently earned from Roche. So on a go-forward basis, I think $242 million. Sounds great. Yeah. I think we're in a good position, you know, through the into the second half of 2025. A lot of our cost basis is actually now carried by Roche, given the stage of development that we're at for the program. Okay. People may not appreciate that, but that certainly helps our burn a lot. Yeah, that sounds great. So thank you, Kristin, for accepting our invitation and joining us for this conversation. And also thank for our audience tuning in in our today's Fireside Chat. Thank you.