Everybody again for joining us, Citizens JMP Life Sciences Conference. My name is Roy Buchanan, I'm a biotech research analyst, and we're happy to have Inovio Pharmaceuticals here with us. So we've got Jackie Shea, she's the Chief Executive Officer. So certainly exciting time at Inovio. Earnings call yesterday, if anybody listened, a lot going on. So maybe first, Jackie, just give us a, you know, quick background of the company for people not familiar, what the technology is, and what it, what it does, and maybe talk a bit about how you joined, why you joined, and- Yeah. Sure. So thanks very much for having us. So Inovio is a clinical-stage biotechnology company. We're focused on developing and commercializing DNA medicines in the areas of HPV-related diseases, oncology, and infectious diseases. We deliver our DNA medicines using a proprietary delivery device called CELLECTRA. And we're very focused at the moment in terms of developing our lead program, INO-3107, where we're looking to file our BLA in the second half of the year. And following on behind 3107, we have a deep pipeline of other late-stage assets, as well as some earlier-stage assets following on. So one of the reasons why I joined Inovio was I was incredibly excited by the platform. DNA medicines have been around for a very long while, same as mRNA medicines. What really attracted me to Inovio was that, I felt that Inovio had solved the delivery problem for DNA medicines, in the same way that lipid nanoparticles had solved the delivery problem for the mRNA medicines. Inovio had also produced some really compelling data in the field of HPV-related diseases coming out of its phase I and phase II studies, as well as in oncology. That's really what brought me to the company. I was very excited by the platform. Okay, great. All right, thank you. And just maybe an aside, but you can't use an LNP for DNA, right? You need to get in the nucleus, and- That, that's right, and that's why we use in vivo electroporation. Right. Okay, great. All right. Got that out of the way. Let's talk about 3107, INO-3107 first. That's the hot topic of the moment. You know, as you said, submitting the BLA by the end of the year. We think it's got an extremely high likelihood of getting approved, but maybe first, let's talk about the indication, what the unmet need is, what's out there now, and yeah. Yeah. So RRP, recurrent respiratory papillomatosis, it's a rare disease. It's an HPV-related disease. It's caused by HPV, 6 and 11, and it, the key is really in its name, recurrent. So what happens is infection, chronic infection with HPV 6 or 11, causes the growth of wart-like structures or papillomas in the airways, and particularly on the vocal cords. And these papillomas can make it extremely difficult to talk, can make it difficult to breathe, even swallow. If you can imagine your vocal cords, these are very fine, delicate tissues. They need to vibrate hundreds of times a second to be able to talk. So if you've got wart-like growths on those vocal cords, it can really impact your voice and quality of life. Current treatment is recurrent surgery, repeated surgery, to basically shave off these wart-like structures, and unfortunately, the surgery itself can lead to permanent damage of the vocal cords. So it's a really devastating disease. In rare cases, it can spread from the throat into the trachea and into the lungs, and in about 2% of cases, it can become malignant and fatal. Right. Can you remind me, what the... There's a rate of patients getting a certain number of surgeries, having permanent damage just from the surgery alone. Yeah, so- You said it on the- Yeah, so that's a really important consideration. So this was data that was published by Simon Best and some of his collaborators. And they showed that in, I think in about 40% of patients or 44% of patients who'd had 5 surgeries or less, 44% of those patients had had permanent damage to their vocal cords. And I think the key message really is here, you know, surgeons do their very best to perform these surgeries in a way that preserves the vocal cords. But ultimately, any one surgery at any point can lead to damage of the vocal cords, and obviously, the more surgeries you have, the higher the risk is. So you know, surgery really isn't the solution. It's not eradicating the underlying virus, and it's really just, you know, enabling people to talk and breathe. Yeah. And another thing I think highlights the unmet need is, a lot of patients get, Gardasil, which is shown again and again to not work therapeutically. They get Avastin, and the data is extremely weak, but they still, physicians are giving these patients anything just on the hope that it, that it might work. Absolutely. I mean, there's a real, real need for a therapeutic alternative to surgery. Yeah. Okay, great. So and you have an agreement from the FDA, just announced yesterday, the pivotal confirmatory trial. Maybe just tell us about that and about your interactions with the agency. Why you, I guess, decided to go with the placebo-controlled trial, did you have an option to do a single-arm trial? Precigen says they're gonna address, you know, a single-arm trial, use a single-arm trial. Just how did that play out? Yeah. So, after we completed our phase I/II trial last year, we were awarded breakthrough designation by the FDA. The FDA then approached us after we'd received breakthrough designation to tell us that our clinical data from that completed phase I/II trial on 32 patients was sufficient to file for accelerated approval. The breakthrough designation's been extremely helpful in being able to have regular interaction with the FDA about the path forward, including the components of our BLA submission, and also the design of the confirmatory trial. We chose to do a placebo-controlled trial following discussions with both the FDA and the European regulators, because we really want to use 3107 in the broadest number of patients. So our phase I/II trial was in patients who'd had between 2-8 surgeries in the prior year, had either 6, 11, or a mix of 6 and 11 infection. We'd also worked across 8 clinical sites previously in that phase I/II trial as well. So to continue to develop 3107 for patients with 2-8 surgeries in the prior year, the FDA told us it needed to be a placebo-controlled trial. We have talked with the patient advocacy organization for RRP patients, the RRP Foundation, about this, we've talked to the FDA about this, and we're gonna be using a 2-to-1 randomization to minimize the number of placebo patients in that trial, and then we're gonna be offering them active drug at the end of that trial. But the placebo structure is, you know, at the end of the day, it's the gold standard, and it's to allow us to go down to patients who've had two or more surgeries in the prior year. Okay, great. Are you going to... So the phase I/II had a surgery at entry, is that gonna be the case for the confirmatory trial, too? Yeah. So pretty much apart from the placebo control element, the design is exactly the same. So patients have a surgery, they then receive treatment with INO-3107, and then in our phase I/II trial, we counted all surgeries after day zero towards our efficacy endpoint. In the confirmatory trial, we're gonna be doing the same thing. We're gonna be looking for a reduction of surgery. Okay. And the, it's four doses, correct? It's the same? That's right. So our regimen is a four-dose regimen, given over a nine-week time period. Okay. You also mentioned looking at re-dosing, for patients that might recur. Of course, there will be some. How do you plan to explore that, and what's the plan for it? Yeah. So one of the key advantages of our DNA medicines platform is the ability to go in and re-dose. Unlike viral vector platforms, we don't have any concerns about anti-vector immunity. We don't have to do any heterologous boosts or swap in other viral vectors to deal with that. So we're initially going to be really focusing on those patients that either didn't respond, so we had 19% of patients that didn't respond, or on those patients who had a partial response. Just as a reminder, we saw 28% of patients in our phase I/II trial who required no surgeries at all after day zero. Okay. Maybe it's too early, but, the label, do you, do you expect anything like patients with 2-8 surgeries or anything like that? And then which age groups are you gonna look at, and how... You've mentioned some buckets, I guess, where this disease is more prevalent, some young patients- Mm-hmm. older patients. Do you have plans to address specific age cohorts or? Yeah, another great question. So, our initial trial was conducted in patients with 2-8 surgeries. We were enrolling adults, so people of 18 years and older. And when you look at the RRP disease epidemiology, you get a peak in the 30s, you get a peak in the early 60s, and in the pediatric population, you get a peak at around age 7. So, we haven't evaluated 3107 yet in pediatrics. Obviously, as part of our European development plans, we'll need to provide a PIP, a Pediatric Investigational Plan, et cetera. But at the moment, we're really focused on adults, getting that accelerated approval for 3107, this adult population, and then moving on to adults in the European population. Okay, great. Okay, no expectations on the label yet? Well, I think you know, that's gonna be a review issue. Okay. Our data was 2-8 in the phase I/II study. Got it. Okay, and then commercialization, I guess, what do you expect to be prepared to do? Maybe I assume priority review, given the Breakthrough Designation, so maybe mid next year, get approved. What are you gonna be able to do at that point? What are your plans for commercialization? Yeah. So as a rare disease, obviously, education of the patients and physicians is gonna be absolutely key. We believe that the majority of RRP patients in the U.S. are treated by between 300-400 laryngologists. Many of these are located in academic centers. So that means that we will need a relatively small field force. We're thinking about, specialty, distribution channels. We're thinking about a contract sales force, to really reach those physicians. But as I mentioned, you know, education is obviously going to be key, for this rare disease space, and really working with the physicians and the patients and patient advocacy organizations, to understand how best to get the product to patients. ... Okay. And then how do you envision the, what's the model for the device? Are you gonna sell the physician the device, and then they buy the vaccine, and is that kind of maybe a draw for the physician to bring patients in, that they've got this? Yeah, so we'll probably be loaning the devices to the physicians- Okay. And then the purchase component will be the drug itself, plus the sterile, disposable use nozzle, that's used for administration. But, you know, we're envisaging a loaner basis for the device itself, because that can be reused many times. Okay, great. All right, let's talk a bit about, I think your next most advanced candidate, 3112. It's also for a human papillomavirus-driven indication, oropharyngeal carcinoma or throat cancer. So is that really identical to 3107, but just targeting a different HPV strain? And then you've got positive feedback from the agency on the phase III, so maybe just discuss the plans there. Yeah, great. So 3112 is very similar to 3107, only this time targeting high-risk HPV, so HPV 16 and 18. Again, we have a plasmid encoding IL-12 included as part of the formulation, which acts as a general immune stimulant. And what we're really doing here again is driving antigen-specific cytotoxic T cells that go after HPV-infected cells. So, we've previously evaluated 3112 in the recurrent metastatic space. That was in combination with AstraZeneca's PD-L1 inhibitor, durvalumab. And we came up with some very encouraging data, where we saw an ORR of about just under 29%. But very encouragingly, we saw an extension of the median overall survival up to just under 30 months, which is compared to about 1 year with just checkpoint inhibitor therapy alone. So we were very encouraged by the data that came out of that trial, where we were able to show that we were able to generate these Cytotoxic T cells in the periphery, that then tracked the tumor sites. So we're making the right kind of cells, and they're getting to where they need to be to have clinical effect. For this next Phase III trial, and we've just announced we've had feedback from the FDA, which enables us to believe that we'll be able to move forward with our Phase III trial. We're going to... Our next step there is to go and talk to the European regulators, because we want to conduct that trial both in North America and Europe. In that trial, what we're going to be doing is, we're gonna be going into the locally advanced setting, so an earlier setting. Most people with HPV-positive head, HPV-positive throat cancer are diagnosed with locally advanced disease, and there's a subsection of this population, about, between 25% and 30%, who are high risk because of their smoking history, nodal involvement, and there are also some other biomarkers that can really narrow down that high-risk, population. Now, most people, outside of this high-risk population do pretty well, but generally, this high-risk population, if they're going to reoccur, they reoccur within two years. So, our phase III trial is designed to look at event-free survival, and we'll be looking at the combination of LOQTORZI, which was recently approved for nasopharyngeal carcinoma here in the U.S., combined with INO-3112. I'm really excited by what we think this combination could do in this disease space. Okay. And it's gonna be versus LOQTORZI alone, or what's the plan on that? Yeah. So, we haven't released those kinds of details yet. Okay. We're, you know, really excited by this combination. They have to talk to the EMA and- Yeah. Okay. We need to have those discussions, so far. Okay, great. Do you think those can happen this year, that the- Yeah. Okay. Absolutely. Okay. All right. Okay, great. Maybe talk a bit about the dMAb program. So this is another DNA-based program, not a vaccine, but you're expressing antibodies- ... from electroporated cells. So, yeah, maybe just describe that technology briefly and where you're at with that. Yeah. So, our DNA medicines platform is all about in vivo protein expression. So, for our therapeutic indications, the proteins we're expressing have been driving those therapeutic immune responses. But the proteins that we're producing themselves can also be the therapeutic. So, in the case of our dMAb program, or DNA encoded monoclonal antibodies, what we're doing is encoding monoclonal antibodies within the plasmids. We're then delivering them to muscle cells, and then the plasmids are transcribed, translated, and the monoclonals themselves self-assemble and then are secreted into the bloodstream. So, this phase I trial has been funded by DARPA. It's being conducted in collaboration with AstraZeneca, the Wistar Institute, University of Pennsylvania, and some other academic collaborators. And what we're looking to do here is encode the monoclonal antibodies, they're part of AstraZeneca's licensed COVID product, Evusheld, on DNA plasmids. have those plasmids expressed within the cells and then detect functional antibody at potentially therapeutic levels in the bloodstream, and we'll be publishing that data from the first cohorts, later on this year. That's a phase I dose-finding and safety study. ... Okay, peer-reviewed publication or a presentation? We're definitely aiming for a peer-reviewed publication, and we'll be out talking about the data as well. Yep. Okay. Okay, so the goal there, so Evusheld is not really relevant anymore, right? But it's to get proof of concept, and then you can, Absolutely. These are extremely well-characterized antibodies. Right. And so being able to demonstrate that we can deliver them at therapeutic levels and that they're functional, I think is gonna be very important. Okay. And your manufacturing is equivalent to mRNA technologies or faster, or how does it compare to? Yeah, so plasmids are DNA plasmids are produced in through E. coli fermentation, just grown up the normal way that you would produce plasmids in the lab, but at a much larger scale, then purified out and resuspended in salt water. Very stable. mRNA is more of an enzymatic reaction. Right. Okay. All right, and I want to ask about the Ebola virus booster, 4201. You just had some updates on that also. And you described a little bit on the earnings call, an assay, I think it was FANG, is that correct? Maybe you can just tell us a little bit more about what that is and what your plans are with that candidate. Yeah. So, beginning of last year, we announced some initial antibody data coming out from that phase I trial. And in this trial, what we were doing was we were taking our Ebola booster vaccine candidate, INO-4201, and boosting healthcare providers who'd previously received the licensed Ebola vaccine, Ervebo. One of the issues with the Ervebo is it's not licensed for boosting, and it's a viral vector candidate. So, this trial was really, you know, leveraging one of the strengths of our platform, which is the ability to go in and boost, particularly heterologous boosting. And what we were looking to do here was show that we could boost patients back up to protective levels. The FANG assay is, it's quite a challenging assay to do because you need access to controls, et cetera, which are quite difficult to obtain. We were able, after our initial data, to access the FANG assay, get that running, and then show that patients who'd received our booster vaccine had actually been boosted up to levels higher than those recorded for the initial primary vaccination. Very encouraged by that. Mm-hmm. We've been in discussions with the FDA about the next steps in the development path for INO-4201. We're planning to submit a study design for a Phase II/III trial in parallel with NHP studies to allow immunobridging. Right. That's the next step for that program. Okay. Are you gonna fund those yourself, conduct those yourself? What's the plan for... Yeah. Yeah. I mean, for Ebola, it's really a global health product or so, you know, emergency preparedness product, and that's something we really look to develop with partners. We've been working very closely with a number of partners in this space. Okay, great. All right, and maybe just really quickly, just, a couple HIV programs still ongoing, I think. I don't know much about those, but just where, where... Give us an update where those are at, what the plans are. Yeah. So, we, we've got a couple of phase I studies, which are being conducted in collaboration with the Wistar Institute and funded and run at NIH study sites. And those are one of those studies is actually evaluating one of our next-generation technologies. So, this is DNA-launched nanoparticle vaccines. So, what we're able to do here is encode within our DNA plasmids a nanoparticle-like scaffolding structure, and then also co-express an antigen, which then joins onto that nanoparticle structure. And those dLNPs are able to produce much higher levels of binding and neutralizing antibody. So, we're very excited by that technology and looking forward to that data. Okay. And Wistar is driving that or-? Wistar are the prime on that grant, yes. Okay. But you can apply this technology potentially more broadly once you- Exactly, yeah. Okay. Okay, great. All right, and maybe one last question. Updated cash on the earnings call, how far does that get you in terms of program stage? Where does that get you, INO-3107? Yeah. So, we announced at the end of the first quarter, we had about $105 million in cash, and then in April, we also completed a direct offering, which brought in another $33.2 million. We're currently projecting our cash runway will take us into the third quarter of 2025. Okay, so right, potentially the start of commercialization and- I think that's gonna depend how quickly we get through the regulatory process. Right. Of course. Okay, all right. Any questions from the audience? Anybody have anything? Okay.