Founder Stories: Eric Ostertag, Co-Founder and CEO of Poseida Therapeutics

If you've been listening to The Business of Biotech podcast for a while now, you'll recall that Erin Harris has joined me to co-host a few episodes. Erin's my friend, colleague, and chief editor over at cellandgene.com, and she just recently launched a podcast of her own. It's aptly named Cell and Gene, the podcast, and if you're working in the cell and gene space, you should give it a listen. It's a collection of interviews with the industry and academic leaders moving the space forward, and you can find it at cellandgene.com anywhere you listen to podcasts. Cell and Gene, the podcast. Check it out. You're listening to The Business of Biotech. I'm Matt Piller, and my guest on today's show is a guy who I wrote about back in June and one whose startup story I found quite inspiring, to the point that I wanted to have him on the show to to tell it himself and to share some of the important work that his company is doing in the CAR-T therapies for oncology space. Today, Dr. Eric Ostertag is CEO at Poseida Therapeutics, but the entrepreneurial journey that led him to that position isn't typical of that taken by most biotech founders. He earned his PhD in molecular biology and MD degrees at the University of Pennsylvania, with the distinction of being the first graduate of UPenn's gene therapy program. He served his clinical pathology residency at the Hospital of the University of Pennsylvania before moving on to a transfusion medicine fellowship. His academic career looked promising, but Dr. Ostertag had other notions. Dr. Ostertag, thanks for making some time for us and welcome to the show.

Hi, Matt. Thank you. Great to be back.

Yeah, it's great to see you again. So that's where I want to start, the other notions. I'd like you to share, and this is a story that you've told me, and I know you've told it to a few other folks, but I'd like you to share the story behind the somewhat abrupt transition of your career from academic to biotech founder.

Right. It was a little bit unusual in the sense that I never anticipated going into industry, much less becoming a CEO. I really had my heart set on academic medicine. And as you mentioned, I did my MD, PhD, residency, fellowship, so quite a, quite a long stretch in training at University of Pennsylvania. Everyone, including myself, anticipated I would just go into academia. I had a Nice spot there lined up. But what happened was I was getting increasingly frustrated that some of the technology I worked on as a graduate student was not being licensed by the university. I knew that this was very valuable technology that could be used for gene therapy, and I didn't see any real effort by them to out-license it. So I walked into the tech transfer office one day and met with the director and I said, I think we should start a company. And he was like, okay, great idea. Who's, who's going to run the company? And I said, well, I'll, I'll do it temporarily until we can find another CEO. And he was rather dramatic. He, he put down a $100 bill on the table and he said, uh, there are so many people right now who want to start a company with way more experience than you. I bet if I gave you this technology, I bet you $100 you would, you would fail. But I kind of talked his ear off, and after that, he picked up the $100 bill and he gave us our first license to the technology. Ironically, we don't actually use that technology anymore, but that's kind of how I got the start. And then I wrote a grant, a bunch of money was available for doing the research, and there was at that time no CEO, so I just sort of stepped into that job, and here I am now about 20 years later.

Yeah, yeah. So, I mean, share with me a little bit of the, I guess, experience or feeling of being a young first-time CEO with little experience. And, you know, I can't blame the guy, right? And neither can you. You can't blame the guy for being like, come on, let's— being skeptical, right, about you taking the reins as CEO of this company. What was kind of your mindset at the time heading into it? Was it supreme confidence, or were there a little bit of internal skepticism as well?

Well, honestly, even then, I didn't necessarily expect to do this for a career. I thought I would do it temporarily. And when a company is small, on the one hand, there's less that you need to worry about. There are fewer employees to manage. But on the other hand, you're really starting from scratch. So of course, we had that intellectual property that we got from the University of Pennsylvania, but other than that, we had no employees. We had been that grant, so we had a little bit of money, but we had no equipment, we had no lab space. So I did learn pretty quickly that you have to learn a lot, or at least a bit about all kinds of things, employment law and things I never anticipated learning, but As the company grew, my knowledge grew, and it was really now about 6 years ago that we decided to spin out Poseida from that parent company called Transposagen. By that point, I had been CEO for over a decade. I had grown that company. It was very successful. It was profitable. So I don't think by that point there were any questions about whether I was capable to run Poseida, but Yeah, back in my early to mid-20s, I got a lot of comments like, "Well, you don't have any gray hair, so why am I going to give you any money? You don't know what you're doing." Right.

Yeah, I can imagine. So take us through that progression. You just referenced the time that's elapsed from that day to now. Take us through the progression of PhenoTech to Transposagen to ultimately how you ended up in the CEO's chair at Poseida.

Well, Phoenix Tech was actually a company that one of my mentors had founded, and when I was in this waiting pattern, if you will, for an academic position at UPenn, I was completing my fellowship research and I was basically running his little company also. And what happened was— so this is, this would be simultaneous with early days for Transposagen. And what happened there was, I think the original technology was not going to work, but I saw some potential in another area. And that was actually the foundation of another company that I did found called Vindico, which is focused on nanoparticle technology. And what I realized was long-term in gene therapy, what you would like to do is not just have an integrating technology, and that's what I had developed as a graduate student, something to deliver a therapeutic transgene into the DNA, but ideally you would get rid of what people had been using up until that point to get into a cell, and that is a virus, and the virus has evolved to do that, but there's some downsides to the virus, some toxicity issues. Your body, of course, has also evolved to get rid of virus, so there was a need to do a packaging technology to get rid of this virus, and that's where nanoparticle comes in. So that company focused on the nanoparticle piece of it. Transposagen focused on the gene delivery technology, and then it was after we did a deal with Transposagen and Janssen, J&J, in what's now called the CAR-T space, chimeric antigen receptor T-cell therapy. It's a new type of immuno-oncology therapeutic. After that deal, that really gave me the idea that, okay, we're ready now to combine all of these technologies under one roof. So I founded Poseida, and the gene delivery technology called piggyback went into that. A gene editing technology I invented called Cas-CLOVER went into that. And then we purchased the nanoparticle company. So really, at that point, we had all the tools necessary to do a really new and novel advanced form of gene therapy that doesn't require any viral components.

Yeah, and that's— I mean, quite frankly, when we last spoke, one of the things that was most challenging for me, not coming into the conversation as a scientist or with a science background, was understanding these three platforms that kind of serve as the foundation, sort of the three-point foundation or three-legged stool, if you will, of Poseida. You just mentioned them, the piggyback DNA delivery system, the Cas-CLOVER gene editing system, and the nanoparticle AAV delivery technology. I'd like you to share with us a little bit more about those platforms and perhaps functionally how they work together to serve as the foundation of your company?

Right, so there, those are the three pillars, and there are different types of gene therapy. First of all, you could divide it by cell type, and one broad division is taking what you might call in the body, putting your technologies in the body, that's in vivo gene therapy. And then there is taking cells out of the body, out of the patient, modifying them, and then putting those cells back in, that's ex vivo gene therapy. So, you could divide gene therapy by the cell type. You can also divide gene therapy by the method that you're trying to use to correct the disease. So, for example, with a congenital disease, one that you're born with, you have a bad copy of the gene. So, one way to try to fix that would be to just add the new gene, gene addition. You're not fixing the gene that's in there. You're leaving the bad gene, but you're going in to deliver a new gene, new copy. The other way to do this would be to specifically edit, do almost like a surgical repair of that gene, and that's called gene editing. So, when keeping in mind all of these different methods to perform gene therapy, we really have it all now under one roof, because the nonviral piggyback technology I referred to is really good at gene addition. It can deliver potentially very large genes into the genome, and it can do that safely and at low cost. The gene editing technology, I think a lot of people have heard about CRISPR at this point. The inventor's got the Nobel Prize for that. We have an advanced version of that, which is, it's not CRISPR, but it takes one component from CRISPR the natural CRISPR system. We call that Cas-CLOVER, and it solves the major problem of that form of gene editing. So this is the gene surgery I talked about, making specific mutations in the genome or fixing mutations in the genome that are otherwise bad. And the downside with the CRISPR system is that it can do that, but in the meantime, it will create unwanted what's called off-target mutations. So you can fix the bad mutation, but you can create additional bad mutations. Our CaspLOVER technology has solved that problem. Now, either one of those two technologies for gene addition, piggyback, or for gene editing, CaspLOVER, can be used in any cell type, both in vivo, in the body, or ex vivo. But when you think about it, if you're going to put them in the body because they are not viral technologies, they don't have what's called a capsid, the coat that would go on the outside of a genetic cargo. And without that coat, it can't infect the cell. So you either have to put them inside of a virus, or our preferred method is what I alluded to earlier, put them into a nanoparticle, and that kind of functionally substitutes for that virus coat. So we have what we would call then the gene delivery tools: gene addition, gene editing, and gene delivery. And you can combine those or mix and match those to do just about anything you could think of in gene therapy space.

Is that, in your estimation, is it common to have platforms that enable all three of those functionalities under one roof?

No, it's not, it's not common. You would not see that among most of our competing gene therapy or gene editing companies. They usually have just one or two of those. There are some big pharma companies that accumulate all of those technologies through partnerships, usually with multiple different companies or different academics. So for us to have it all under one hood, one roof, is very unique.

Yeah, I mean, I assume so. That's why I asked. It seems almost audacious for a small, you know, emerging biotech to go after that. What has that meant? Just curious what that's meant for you from a leadership perspective around, you know, supporting all three of those platforms from a personnel standpoint and intellectual property standpoint, and funding. We'll talk a little bit about some of your fundraising success here shortly, but And from a funding perspective, has it been— obviously it's a competitive advantage, but has it been a challenge to sustain or maintain or build?

Well, it is an embarrassment of riches, but it also, as you pointed out, could be construed as grandiose. You could look at that and say, well, you're saying you can do everything in gene therapy. I am saying we can do everything in gene therapy, and I'm saying we have some advantages compared to most of the technologies out there. But what I'm not saying is we will do everything in gene therapy. So we've been very focused on getting a few specific programs into the clinic to establish proof of concept. And we've done that in the cell therapy space with what I referred to earlier, the T-cell therapy, CAR-T. And we've done that with a couple different flavors of the therapy, if you will. Meaning we've shown that we can both target and treat successfully liquid tumor or blood tumors. We've shown that we can target and successfully treat solid tumors, which is pretty much unique for the CAR-T therapies. Most of the other CAR-T companies have not had success in solid tumor. And we've shown that we can do both what's called an autologous therapy, which means if you're, God forbid, sick with a cancer, I could take your cells and modify them, but I can only give them back to you. They're not something I could give to another person with the same cancer. But now we're moving to what's called fully allogeneic, and that means I could take cells from a young, healthy donor and make lots of doses and then give them off the shelf to anyone who has that cancer. And that, that's pretty exciting. That's what we call the holy grail. We've now got this year two separate filings with the FDA, INDs they're called, to get these fully allogeneic therapies in the clinic. So we've kind of been very focused with the CAR-T therapeutics, and now we're moving into some of the other applications like the in vivo liver-directed gene therapies. But even there, we've been very, I think, selective about what we've gone after, and we've chosen diseases that I think we'll have a real wow factor. People say, wow, if you can do this, you can do anything. So we, by doing this very careful, focused, targeted drug development, I think what we are able to do is not spend enormous amounts of money, but yet establish great proof of concept in a lot of different areas. And at that point, we start attracting partners, and that could be big pharma companies that have more bandwidth, have more resources, and then they come in to want to partner on those technologies because frankly, we just can't do it all ourselves, to your point.

The Business of Biotech is brought to you in partnership with SciTeva. Together, we're committed to helping the leaders of new and emerging biopharma companies navigate the financial, organizational, human resources, and regulatory waters you'll encounter on your way from discovery to the clinic and beyond. Check out a host of useful resources for biotech leaders at Cyteva's Emerging Biotech Accelerator at cytevalifesciences.com/emergingbiotech. That's cytevalifesciences.com/emergingbiotech. I'm glad when you referenced the wow factor of the indications you're chasing, you didn't get too specific because you would have been getting— you would have been putting the cart in front of the horse, so to speak. We're going to get to that later. I'm glad you didn't go there. You're going to move ahead. Before we do go there, I want to talk about cost. You just referenced keeping your costs down. It goes without saying that cell and gene therapies are extremely expensive at this point in time. And when we last spoke, we talked a little bit about how your nonviral manufacturing approach contributes to more cost-efficient GMP production. So can you tell us a little bit about that, what, and more generally, what Poseida's plans are to contribute to the industry-wide effort to make these therapies more accessible.

Right, so when you're thinking about making a human therapeutic, you can't just brew it in the lab over a weekend, right? You have very specific regulations about how all the components are made. And this is what you refer to GMP. This is a very expensive process. And when you look at the viral technologies, which again are typically used historically for gene therapy, the viral technologies are very expensive to make, time-consuming. There are a lot of manufacturing issues with them. And that might not make sense to everyone, but it's just a very complicated process to take a virus to eliminate its insides and put in your therapeutic transgene instead, and then manufacture it at high titer in a very safe way. So to further complicate problems, the groups that do this— sometimes you could do this in-house, you might make your own manufacturing facility, but a lot of times you would outsource this to a contract manufacturer or CMO.. And these groups are really with limited capacity right now because, one, gene therapy is exploding. There are many, many gene therapy companies and approaches out there, so high demand for the CMOs. But also, the pandemic actually made this worse, that they are shifting some of their resources towards vaccine production, for example. So, it's been a consistent been a problem over the years where the viral technologies are both expensive, time-consuming, and sometimes there are bottlenecks where you just can't make it. The non-viral technologies are basically just nucleic acids, so they are DNA, they are RNA. These things are easy to make, and again, you could make them in over a weekend in a laboratory, literally in just hours. They're easy to produce, but to produce some GMP takes more time, you know, more stringency, but still much cheaper and much faster than the viral technology. So just as an example, making a single batch of this auto-CAR-T virus probably costs about $50,000 to $60,000 more than a single dose of the GMP auto nonviral technology that we make. And that's a pretty substantial amount of money, right? We're trying to get these costs eventually down to just a few thousand dollars per dose. That would be with the allo, or off-the-shelf CAR-T. So an important component of that is actually the nonviral technology and the nonviral manufacturing.

Awesome. I want to talk about cargo capacity as well. Transgene cargo capacity, the advantage of a cargo capacity that's larger than that offered by typical lentivirus and gamma retrovirus approaches, that is, to CAR-T. So tell us a little bit about your competitive advantage there.

Yeah, there are many advantages of the nonviral technology over viral. We touched on some of them: the lower cost of manufacturing, faster timelines, the safety is actually better. But one that is not as obvious maybe is the cargo capacity. What is cargo capacity? We're talking about how much DNA of the vector, and that determines how much you can deliver to the patient. And so why is that important? Well, some diseases are from— they're derived by a mutation in a gene that is small, and so indeed you could do this pretty easily in a virus. But some have a transgene that would be so big you actually can't treat them. With standard virus therapy, like AAV is one typically used for gene therapy. You can't fit the gene for hemophilia A, that's a bleeding disorder. The gene is called factor VIII. It's just too big to fit into the capsid of the virus. So you can do that with our technology. There are really no limitations in terms of the size, but easily 10, 20 times larger than than the viral cargo capacity. Okay, what about with oncology, immuno-oncology? Even there, cargo capacity is really pretty important because number one, even though you can get your therapeutic transgene that could target, cause a T cell to target a cancer or kill a cancer, you can get that into standard viral technologies. There are other things you would want to put in, but you cannot because of the cargo limitations. Let me give you some examples. One is a safety switch. What if the cells that you put in have some sort of problem and you want to hit the safety switch and remove those cells? You can do that pretty easily with our technology. It's very difficult with, with a viral technology. So those are what I call bells and whistles, things you might want to add to make the product better. And you can only do that if you have cargo capacity. Now, another really interesting application is when you think about targeting a cancer, you need a target. And not too many cancers have a nice clean target. If they did, it would be a lot easier to cure cancer. So, you have to get a little bit creative sometimes, and you might want to target more than one thing on the surface of a cancer cell at the same time. Or you might even want to create what we would call a logic gate. So you would say, okay, only if this cancer cell has target A and target B but not target C, then I want to have my cell kill it. That's really pretty much impossible unless you have a very large cargo capacity. You just can't do that with the viral technologies. You can easily do that with our piggyback technology.

Yep. All right, thanks for that explanation. Now I want to get into some of the indications you guys are targeting, and perhaps you can share some clinical successes, study successes with us on these indications. Your lead candidate, PBCMA-101, correct? That's right. Yep, targets multiple myeloma. Tell us about that. How does the candidate work and where are you as far as clinical journey's concerned.

So multiple myeloma is a predominantly blood cancer. It does go to your bone marrow, but I talked early on about difference between blood cancers and then solid tumors. Blood cancers have been easier to treat generally with CAR-T, and so that was where we started with blood cancer. And here what you're trying to do is kill a cell in your body that has become cancerous, but normally makes your antibodies. So it's a specific cell, and luckily in this case, you do have a pretty clean target. You have a target called BCMA, B-cell maturation antigen. It's basically on all multiple myeloma cells. It's on not many other healthy normal cells. You don't need to worry about killing a normal healthy cell, you're only targeting your cancer cell in this case. So the target is nice. And in the case of BCMA, we took the initial approach I talked about, which is auto, autologous CAR-T, taking cells just from the patient, manufacturing them, putting them back just in that patient. So it's an individualized cell therapy that is BCMA-101. But we've now advanced to the point where we have an allogeneic or off-the-shelf version of that, and that will be going into the clinic this quarter, actually. So later this year, we'll see some data from first patients in this program. And that, that again, I mentioned, I think is, is the holy grail. But even with that being where we want to end, we've learned a lot with the auto program, the BCMA-101, and we have shown some advantages in our technology. One is that Our technology makes a very special cell type in the product called TSCM, or stem cell memory. And this particular cell type can last a long time in the body. And so, unlike some of our competitor products, we're seeing occasionally responses that last years. In some cases, you would unfortunately only see, you know, the cells in the body last a few months, but our product can last for years. And when the product is there, the patient stays in remission. So that's pretty exciting. The other one is safety. So safety with CAR-T is sometimes pretty rough, meaning the patients can get good responses, but they go through some pretty difficult period where they have something called cytokine release syndrome. Sometimes you can see something called neurotoxicity. And not, not with our products BCMA-101, but with some of our competitors, this can even be fatal. So what we found with the high TSCM stem cell memory product, we get much less toxicity. And when I say much less, I mean about 10 times less. We've never had to put a patient into the intensive care unit. We've never had a patient death from the product. And that actually allows us to give the product outpatient. We can simply give the product in the hospital, then they go home, and they really would never need to come back unless they're needing to get a test. That, that's unique in the CAR-T space. Yeah. Um, but when you think about the auto version, it's even better. It's a step past that because it's a lot lower cost to manufacture. That increases the accessibility, and the patient doesn't have to come in and get this expensive and time-consuming manufacturing process. You already have the product there. It's ready for them. You can just give it to them, and that could also be done fully outpatient.

Yep, that's excellent. Also challenging in CAR-T traditionally, historically, has been addressing solid tumors. Now, here again, the last time we spoke, Dr. Ostertag, you told me about some impressive data on your CAR products' effect on solid tumors in a patient with prostate cancer. And, you know, I remember I was struck when we had that conversation. I was struck by the, well, by the story itself. I mean, it's, you know, the way that it was posed to me, it sounded pretty big. It sounded like a big deal. So tell us about that. I'll let you kind of fill us in on that story and the results of that study and maybe qualify just how big a deal is this, not just for Poseida, but for the general industry and its endeavors to leverage CAR T-cell therapy in solid tumors?

Well, it is a big deal. And if you go back to the history of CAR T, there was a child named Emma Whitehead who was the first pediatric patient to get CAR T. This was at my alma mater, University of Pennsylvania. I didn't personally participate in this study, but one of my colleagues did, Carl June. And what happened was this child had failed everything that would be a standard therapy for what's called B-cell ALL and probably didn't have too long to live, was given a single treatment of CAR-T and is now 9 years cancer-free. So she's probably cured. And of course that That was amazing. That means you could potentially cure cancer. Now, not every B-cell ALL patient unfortunately responds like that, but it's proof of concept that you can cure the disease. So you can imagine the entire field was pretty euphoric. There were a lot of different companies started to try to improve upon these results and then start treating other blood indications like BCMA. We were one of the first to do that. But, you know, what about solid tumors? Solid tumors are much more common. Everybody's heard of somebody that, or knows somebody personally that has a breast cancer, ovarian cancer, prostate cancer. These are the big, most common cancers. So there was a lot of hope that CAR-T would immediately show the same kind of positive results against solid tumor. And a few companies tried it and it didn't work. It didn't work at all. So, there were a lot of theories about, okay, what, what went wrong? Why is this not working as well as for blood tumors? And to this day, no one knows exactly. It probably has different explanations for different diseases, but there were different hypotheses for why this wasn't working. Maybe the T cells can't get into the tumor very well, tumor access. Maybe they get there, but they get inactivated. So, there are things called checkpoint inhibitors that when a tumor evolves, it makes it harder for your immune cells, including T cells, to kill those tumors. So, I think in some cases, these are probably correct. There probably are these reasons that make it harder to treat. But when we started developing our very first product, for solid tumor, which is targeting prostate cancer. What we found in the very predictive animal models, which are actually a human cancer inside of a mouse model, so you're using a mouse to grow these human cancer cells, and this is typically not easy to treat, but what we found is we could get complete tumor elimination, and that's without something called armoring. Armoring is to try to get around these problems I just talked about in the solid tumor environment, some way to improve a CAR-T so that it doesn't get affected by, for example, checkpoint inhibitors. And what we found, frankly, this was a little bit of a surprise to us, is we didn't need them. We had made very advanced armoring platforms, but we didn't need them. We were getting 100% tumor elimination even at pretty low doses every time in every animal. So that was like, hmm, maybe it's because the stem cells, this very special stem cell type that we have and other companies don't have, maybe that stem cell can do something special. It can get into the patient, it can make multiple waves of effectors. It works more like what would be called a prodrug. So we decided to just go right into the clinic without armoring. And as we talked last time, we had some really early data there, and it was, quite frankly, it was remarkable. It was something no one had ever seen before with a CAR-T against solid tumor. And I can't really expand upon that yet, but we are going to do a new data cut. In other words, all of the patients we've treated up until a specific point in just 2 weeks. So there's a conference called CAR TCR Summit, and the title of that presentation is TCM product, TCM CAR T with exceptionally deep and durable responses. So you can guess, you know, what the data are going to look like. We're very excited about it. The response that we've seen, I'll just reiterate, is among the best ever seen for a CAR-T product against any solid tumor, not just prostate cancer. So, you know, we do believe that that's because of the platform, and we're quite excited about it.

Yeah, well, congratulations on that. I mean, it's certainly exciting. And just for our listeners' reference, by the time this podcast comes out, that data that Eric just referenced will have been released. So perhaps we can throw a footnote up on where they, you know, where we can kind of check in on that readout. But yeah, I appreciate that. That's, it's exciting news. And I apologize if I partially spilled a few of the beans prior to your—

No, that's great, Matt. And I'll just say then, if this will be shown, you know, after that presentation, that the presentation will be available to the public after we give it. So www.pasita.com is our website.

Awesome. Yeah, thanks for that. So what challenges remain to be solved, or refinements need to be made generally to enable more widespread CAR-T therapies against solid tumors? And you mentioned toxicity and cost, you mentioned the ability for the biologic to actually influence the cell. What other challenges remain to kind of address it on a more industry-wide level?

Well, the first thing you referred to is what we would call accessibility, and CAR-T right now is an experimental therapy. There have been a few approved for blood tumors, but generally when they're given, they're given to a patient at a large academic medical center. And given some of the side effects of our competitor products, they're often given where there's an ICU, intensive care unit, available. And sometimes they even reserve one ahead of time knowing a patient may need to go to the ICU. So with our safety advantage, we think we can solve that problem. We think we can give this outpatient. Patient might be able to come into, for example, outpatient oncology infusion center, get their drug, and then go home and not need to worry about going to an ICU. And then the other part of accessibility you refer to yourself is cost. These are not inexpensive to make. They're very complicated therapeutics. But the solution there, I think, is allogeneic. If you can make an off-the-shelf product and you can make literally hundreds of doses from a single manufacturing run, which is what we are currently seeing, we have a unique technology called a booster molecule that allows us to do this. That drops the cost of manufacturing to sort of the range of more standard oncology therapeutics, like a monoclonal antibody, for example. So those two things combined will make CAR-T very accessible. Then some of the other things we talked about are getting it to work in more and more indications, not just the blood tumors, but all different kinds of solid tumors. And then lastly, I'd say it's getting it to work in a higher percentage of patients. So I talked about some remarkable responses, but it's not every single patient. That has a remarkable response. We need to figure out why not. Let's make it a remarkable response for everyone and let's make it a durable response. So I talked about Emma Whitehead. She's probably cured. She's 9 years cancer-free. Some of the other indications like multiple myeloma, we're out several years for a few of our patients, but some patients relapse. We're really striving to get single treatment cures for our patients.

What's going into that research? Is it a matter of like figuring out biomarkers, genetic response? And I know that you could probably teach a dissertation on that question. I don't expect you to go super, super deep. I'm just curious, you know, when it comes to that patient in the prostate cancer study who, you know, his tumor was eradicated, cases like Emil Whitehead where,, from the outside, the disease may look identical to someone who didn't respond in such an incredibly positive way. So, just give us a little flavor into what sort of research is going into figuring out that why.

That's a great question. Everyone is looking at this. Everyone in the space, academics, industry, are looking at every possible correlation to figure out what makes a good product, what gives a patient a good response. Is it The cell type, is it something in the manufacturing, is it something about the patient? So we've done this looking at patient characteristics, the pre and post manufacturing characteristics, all kinds of biomarkers using very sophisticated molecular, molecular methods. And to a large extent, we don't know. Now I'll tell you one of the very strongest correlates with best responses in the clinic is the percent of these desirable TSCM cells in your product, both pre-manufacturing and post-manufacturing. So we know that the stemness matters. This gives the cell something we call proliferative capacity. It can expand greatly and kill the tumor. It can expand multiple rounds to continue to kill the tumor. So, you know, to me, that should not be a surprise that in a cell therapy, the type of cells that you have in your cell therapy are going to determine how well that product works. But the other thing that we and others are finding to be important is the binder. So I mentioned you have to find a nice clean target on the cell. You also need a good binder to bind that. And what are the characteristics that make a good binder? That's also not totally obvious. It would be great if you just said, I'm going to pick the strongest binder out of 100 possible binders, and that's going to work the best in the clinic. Unfortunately, it doesn't work that way. You have to make CAR molecules out of all of these. You have to test them individually in your most predictive animal models. So I think as a field, we at Poseida and others are learning every day. And it's very exciting. If the first couple patients had a few cures like Emma Whitehead, you can only imagine how fast this is advancing and what it's going to be like in 5 or 10 years. It's very exciting. But to be fair, We don't know all of the things that make a really good product.

Yeah, yeah. Well, you've got, you've certainly got that financial backing to help figure it out. 2020 was a pretty incredible fundraising year for Poseida. You know, despite the challenges that the pandemic brought, you somehow managed to do like $300 million in a Series D and an IPO, correct me if I'm I'm wrong there. How— we're running a bit short on time here. So we can't, you know, can't go too deep on the fundraising strategies that worked in 2020. But just give us a flavor for the strategies you employed in 2020 to have such a successful financial year when obviously it was less than ideal conditions for fundraising.

Yeah, it was a very unusual year. And we, like all of these early-stage biotech companies, require a lot of money to do this research. It's not, it's not a cheap proposition. It's, um, it's, it's especially the auto CAR-T clinical trials are just very expensive. So we had previously done what's called a Series C, and that was $150 million. But then in 2020, the pandemic struck and we knew we were going to need to raise some, some money, we decided to do the public offering approach, which was uncharted waters at that point because we had to do it completely virtual. And we weren't the very first company to get out on a public IPO, on an IPO during the pandemic, but we were one of the earliest biotech companies to do that. So it was an interesting learning experience, and I think actually, there are things about that process that will now not change even after the pandemic, because it was a fairly efficient process. We ended up doing what's called a Series D or crossover round with Fidelity leading that round, and then we went right into an IPO. And between those two rounds, we did raise well over $300 million. So that was great. That's plenty of money to do everything we wanted to do in 2020 and 2021, and even will be enough to get us through most, if not all, of 2022.

Excellent. Well, congratulations on that. Like I said, perseverance, it seems to be, you know, your perseverance, it's— there's a common thread there. It started back in school when you said, hey, you know, we need, we need to make a product out of this and wouldn't take no for an answer. And it continues to drive your company today. So congratulations on the success to date. And it's been a pleasure talking with you, Dr. Ostertag. I enjoyed it last time, and I'm glad you made the time to come on the show. Great.

Well, thank you, Matt. Yeah, it's always fun to have these conversations. Appreciate the invite.

Yeah, I know there's a lot more to talk about. So we'll, we'll get a scheduled part 2. Put together so we can have you back on the show, maybe after that research is published in a few weeks.

Yeah, that would be great.

Cool, thank you. So that's Poseida CEO Dr. Eric Ostertag. I'm Matt Piller, and this is The Business of Biotech. We're produced by Bioprocess Online and supported by Cyteva. Please visit Cyteva's Emerging Biotech Accelerator at cytevalifesciences.com/accelerate. Emerging biotech, then visit us at bioprocessonline.com, where I invite you to sign up for my newsletter. And if you like what you're hearing on this podcast, please subscribe, give us 5 stars. And as always, thanks for listening.