Inovio Pharmaceuticals, Inc. ($INO)

Welcome everyone to Jefferies 2026 Global Healthcare Conference. My name is Roger Song covering [indiscernible] Biotech. It is my pleasure to introduce our next company, Inovio, CEO, Jacqui Shea, and then she will do a company overview, and then we will have Q&A towards the end. Thank you.

Thanks, Roger. Yes, thanks for the opportunity to present today. It's great to be at the conference. So moving on, for those of you who are not familiar with the Inovio story, I'd like to provide a quick overview of the company and our lead asset, I know [ 31 is 7 ] in which is in development for treatment of recurrent respiratory papilomatosis or RRP. This is just our standard forward-looking statements disclaimer slide that during this presentation, I'll be making forward-looking statements, and I refer you to our most recently filed 10-K for further details. So to give you a quick overview of the company, Inovio is a clinical stage biotech company. We're really focused on developing -- sorry, I can't really see the slides on the monitor. Can someone switch the monitor into a bigger view because I can't really see them? No. Okay. I'll just work off this main screen then. So we're focused on developing and commercializing DNA medicines to treat -- that's better, thank you -- to treat and protect people from HPV-related diseases, cancer and infectious diseases. Our lead program for treatment of RRP, [ 3107 ]. Our BLA is currently under review with FDA with a PDUFA target date of October 30, 2026. RRP is a rare HPV-related disease. And even not though there is an improved product on the market, there remains a high unmet need and a significant market opportunity. The 3107 is being granted orphan drug and breakthrough therapy designations in the U.S. has orphan drug designation within the EU. And during our file acceptance letter, FDA noted preliminary comment in the letter regarding eligibility of 3107 for review under the accelerated approval program that we're looking to resolve with them and that they promised us an informal meeting to discuss. We have established our commercial scale manufacturing for our DNA component of our combination product, our plasmids, at external contract manufacturers, and we manufacture our devices in-house. Following on behind 3107, we have a deep clinical pipeline with multiple potential near and midterm catalysts. So how do DNA medicines work? So to tell you a bit about the mechanism of action, we start by identifying the protein that we either want to generate an immune response against or that we want to use to replace a missing or defective protein or to produce a monoclonal antibody. We then use our proprietary algorithms to optimize that gene sequence. We insert that sequence into a circular molecule of DNA called the plasmid. And then we've administered the plasmid into either the skin or muscle cells using our proprietary delivery devices called [ CELLECTRA]. They use a process called in vivo [ electroporation ], which are very short transient pulses of electrical energy that allowed the plasmids to enter the cells. Once within the cells, the plasmid's drive protein production, and then that protein can either drive an immune response, either T cells or antibody or the proteins that are produced and secreted themselves can be the therapeutic agent. So DNA medicines are particularly good at driving T cell responses which is very good for targeting treatment of cancers or viral infections. As part of the proteins that we produce, we've shown that we're able to produce DNA-encoded monoclonal antibodies, which are assembled within the cells and then are secreted into the circulation. And we can achieve therapeutic levels of these transgene encoded proteins. So moving on to 3107, our lead candidate. As I mentioned, our BLA has been accepted by FDA for review under the accelerated approval program, and we have a PDUFA date coming up in October 30 of this year. RRP is rare disease causes the small wart-like growth saw papilloma throughout the respiratory tract, but primarily on the vocal chords, where it really impacts the patient's ability to speak or talk, can inhibit the ability to breathe. The papilloma can also grow down into the lungs and can also become elegant, in which case, the prognosis is very poor. It's caused by HPV 6 and 11 serotypes primarily. It's a rare disease, but not that rare, about 14,000 cases in the U.S., about 1,800,000 new cases each year and repeated surgery is still a standard of care. And every surgery comes with a significant cost and risk to the patient. The risk is permanent damage to the vocal chords or scarring of the airway. And there's the potential for irreversible damage with every surgery. The cost is obviously the impact of quality on life, financial, constant recovery from surgery. Some of these patients have had hundreds of surgeries over their lifetime. And 3107 was really designed with this need to reduce surgery in mind. It's designed to generate an antigen-specific T cell response against HPV 6 and HPV 11 and eradicate HPV impacted cells and thus target the underlying cause of RRP. So what really matters to patients? What really matters to patients with their disease is this constant process of surgery. And the cumulative risk of surgery for injury increases after every single surgery. And ultimately, it only takes one surgery to cause permanent damage. By the time patients have had 5 or 10 surgeries, almost all of them have permanent damage to their airway or to their vocal cords. So when we started to develop [ AR-3107], we really took the patient needs in mind. So our treatment regimen requires 4 doses given over a period of 9 weeks. And we counted every surgery after day 0 because every surgery matters to patients and our efficacy endpoint was reduction in surgery. The competitor product, [ Papsimias], which was approved last year in contrast is really a drug surgery combination. They also give 4 doses but over a longer time period. and they conduct cleanup surgeries at doses 3 and 4. So any visible papilloma that they see, they remove doses at the time period of doses 3 and 4. And they only start counting surgeries after the treatment regimen has completed. So they start counting surgeries at week 12. So these are very different treatment approaches. Our approach is really focused on minimizing surgery for all patients. So as I mentioned, in our [ pile ] acceptance letter, FDA commented on a potential review issue that we may not be eligible for review under the accelerated approval pathway. FDA have agreed to have an informal meeting to discuss this, and we have submitted an assessment aid to support that and we're waiting for FDA to schedule that meeting. We very strongly believe that 3107 does meet the FDA criteria for review on the accelerated approval pathway because it provides a meaningful therapeutic benefit over existing treatments, and it has a potential to meet the remaining critical unmet need for patients. And this is what the FDA guidance specify. So on the efficacy side, we were very pleased with the efficacy we saw. We saw 72% of patients had a 50% to 100% reduction in the number of surgeries compared to the prior year. This went increased to 86% in year 2 and 28% of patients in year 1 and 50% of patients in year 2 required no surgeries a hard to control their disease. We also have an enhanced safety profile compared to the improved product because we don't require these additional surgeries during the dosing window. And in the approved product, over 80% of their patients require these surgeries during the dosing window, including over 70% of their complete responders. So there are patients who remind no surgery after treatment. So it's really a very different profile. So moving on to also how we're different to the [ papsemius ] program and our ability to treat patients that are not served by existing therapy. We don't see any impact because we were a DNA medicine that's delivered via electroporation, we don't use any viral vectors, and we see no impact from neutralizing antibody, therefore, against biofactors. We also have shown that we see no impact from an immunosuppressive papilloma microenvironment on 3107 efficacy. So as you can see, we're very different to the approved product. And market research that we conducted continues to support that we believe that we have the preferred product profile in this area. This is based on efficacy, tolerability and a simple patient-focused treatment regimen. As I mentioned, our efficacy improves over time. We're very well tolerated. Most of our [ IAs ] are associated with injection site pain, which then very rapidly resolved. We don't need an ultra cold chain, 3107 is able to be given in the doctor's office. And very importantly, there's no requirement for the scoping or surgeries during the dosing window. And we've worked throughout this program. We've worked very closely with the RRPF, so the recurrent respiratory [ papalomatosis ] Foundation, which is the patient advocacy organization for RRP patients and they also continue to be very supportive of our efforts. They continue to see an unmet need even with an existing product on the market because there really are patients for whom the approved product just isn't meeting their needs. So moving on now to our development pipeline. We have a number of other candidates in development with multiple near- and midterm catalysts. To give you a quick overview of our pipeline. As you can see, we have [ VGX-3100 ] in Phase III and our partner in China, [ ApolloBio ], just reported positive top line data for that Phase III trial and that, that trial met its primary endpoint. We also have some other HPV-related candidates as well as some cancer-related candidates in Phase II which I'll talk about in a bit more detail in a moment. And then as I mentioned, our very promising depot candidates currently in the preclinical space. So to turn to [ 5412 ], briefly, [ 5412 ] is our candidate for glioblastoma, one of the most deadly and aggressive forms of brain cancer, one of the most common forms as well. very poor prognosis. We had conducted a previous study in glioblastoma, where we had shown some promising data in terms of the ability to extend median overall survival in both methylated and unmethylated patient groups. And what we are planning to do now in this trial that is sponsored by the [ Dana Farber Cancer Institute ] is to combine 5412, which is driving T cell responses against tumor-associated antigens, which are increased in glioblastoma tissue is combine that with a dual checkpoint inhibitor from a [indiscernible] and look to see if we can see an extension in median overall survival. And we're looking to start that trial after we have had our PDUFA data on 3107. Then turning to our [ dMAb ] and our [ DPO ] programs. Last year, we published some really groundbreaking data in Nature Medicine, showing that we were able to produce 2 different monoclonal antibodies, driven off DNA plasmids within the same patients. These monoclonal antibodies were produced at therapeutic levels, were functional and were produced at stable levels up to 96 weeks. And this is really the first time any group has been able to show production of monoclonal antibodies like this. Now monoclonal antibodies are, of course, just a form of complex protein. And we can apply this technology to other candidates in our pipeline, such as our [ DPO ] candidates for missing or defective proteins. So our initial program was in the hemophilia A where we were looking to produce [indiscernible]. In our preclinical data, we were able to demonstrate that [indiscernible] can be effectively produced assembled within the muscle cells and then secreted into the circulation. And treated mice very importantly, showed reduced bleeding time and blood loss in a hemophilia model. We also have preclinical programs in [ Fabry ] disease in hypophosphatasia, are also working up some other rare disease targets and are currently seeking partnerships to advance these programs more rapidly. So to summarize, in the near term, our focus is really on our upcoming PDUFA date and 3107 and working to deliver 3107 to patients. Midterm, really focusing on advancing our diversified clinical pipeline. And then we're also very excited by our next-generation DNA candidates, particularly [ pro ] candidates and they're looking to generate some partnerships to move these along more rapidly. Thank you very much for your time.

Thank you, Jacqui. And then we're also joined by [indiscernible] Chief Medical Officer, here. Maybe Jacqui, honestly, the real most important question is how is the regulatory kind of review process looking like, we were quite surprised and then how confusing the language is when you got the acceptance letter. So it is accelerated approval path but they also say you're not eligible for this. So you are still -- maybe just walk us through right now what's the state of our in terms of the review process looking like? And then I know you say you are requesting informal meeting to confirm your eligibility for the accelerated approval? And then what's the key topics you want to bring up to that meeting? And then what's the potential outcome from that?

Yes. All great questions. So as you mentioned, we submitted BLA after rolling submission under the accelerated approval program and FDA has accepted our BLA. In the file acceptance letter, they noted a preliminary conclusion, which could be a potential review issue that we had not provided sufficient data to justify eligibility for review under the accelerated approval program. Now we strongly disagree with that. We have requested a meeting with the FDA to discuss eligibility for review under the accelerated approval program. And FDA has agreed to an informal meeting. We've also completed an assessment aid, which we submitted to them, and we're waiting for that meeting to discuss it with them. In the meanwhile, the review is proceeding as normal. And we're really very comfortable with how the review is proceeding. We've had our mid-cycle review, had no new issues raised. We're looking forward to our late cycle review meeting, which will be in the third quarter. And we expect to have had all of the various inspections that are required as part of the BLA process, also completed ahead of that late-cycle review meeting. So generally, we're very happy with how that review is going. We are continuing to encourage FDA, of course, to schedule the informal meeting to discuss the review pathway. And really for eligibility under the accelerated approval pathway, there needs to be a continued unmet need, which there very clearly is. The approved product doesn't work for all patients and also can't work in some patients, so patients who have neutralizing antibodies against the vector or who have an immunosuppressive [indiscernible] microenvironment. So we're going to be really talking about why we believe that there continues to exist an unmet need and why we think 3107 provides a meaningful therapeutic benefit over the approved product. And that's really across the efficacy, the tolerability. We're not requiring these additional surgeries during the dosing window. So we have a very differentiated safety profile. And also, we have a differentiated mechanism of action where we don't use a viral vector for delivery. We're including different transgenes. We're not impacted by the papilloma microenvironment. So very clearly, very different products.

Yes. I think I agree. A lot of the point you brought up is pretty compelling to qualify the accelerated approval and we'll see how the FDA agree with that. Okay. And then we are kind of experiencing or observing all the changes happening within FDA. So what have you been experiencing in terms of the review team and leadership? And then do you think this accelerated approval eligibility will be impacted by any of those changes on the top?

Yes. Since I mentioned, we've been very happy generally with how our review has been progressing. Clearly, we still need to get this informal meeting to discuss the review pathway in place. And we really can't comment at this time on changes in leadership. There have clearly been a lot of changes over the past few months. And we're encouraged by the signs that we're seeing from the new leadership. And we look forward to collaboratively working with them on the review of 3107.

Okay. Got it. And then another component of the review is you are filed under accelerated approval, which means you are -- you will need to do a confirmatory study to get a full approval. How is that part going and then what -- how this will fit into the whole process right now?

Yes, great questions. So we have submitted an amendment to our IND for our confirmatory trial. We have about 20 clinical sites up and ready to start that confirmatory trial. Once FDA gets back to us on the protocol. But until FDA gets back to us on the protocol, I don't think I can really comment on the design of the trial.

And then do you expect any surprise there or any incremental comments so far from the FDA or it's still kind of an ongoing discussion?

Yes. It's still an ongoing discussion, and we're waiting for their feedback on the protocol.

Got it. And then in terms of the timing of the [ STAR ] and the enrollment of the confirmatory study versus your PDUFA day, so how you should think about it substantially underway or in you enroll one patient or something like that?

Yes. Well, FDA are clearly looking for a commitment to get your complementary trial moving in an appropriate way. And I think we'll be able to demonstrate that we have -- we've taken all of the steps necessary to do that. FDA ultimately have discretion as to what stage your complementary trial needs to be at, at the time of approval.

Got it. Okay. Good. And then move forward, you get accelerated approval, happy result. And then moving to the commercial stage. One is how you think of the pricing strategy over there. You do have another approved drug in similar population, but not entirely the same.

Yes. So obviously, we're thinking rare disease pricing is appropriate. We've conducted market research, which has validated that assumption. We'll be talking about our pricing a bit closer to approval.

Got it. And then do you think you want to launch the drug? It's often drug and then not [ your ] by yourself or you want to seek a partner?

Yes. So we're planning to launch the drug ourselves in the U.S. We'll probably use a contract sales organization. We have the other elements of that we're going to require to commercialize such as the 3PL, our patient hub, our specialty distributor, specialty pharmacy. So we have all of our partners lined up, and we're really waiting for our PDUFA date. Ex U.S., we're really looking to partnerships to commercialize.

Got it. Okay. Makes sense. And then to the extent you can comment on how the first approved RRP drug on the market and how they perform and what you can learn from them in terms of the commercial dynamic and then the ramp-up look like.

Yes. So we're obviously very closely watching the [indiscernible] launch and seeing what we can take away from that launch and how we can -- how that can benefit our launch. I think what we're seeing is encouraging uptake. I think that's because there's a very high unmet need amongst RRP patients. And we continue to believe that we have the preferred product profile. And I think there are plenty of examples, particularly in the rare disease space, of a fast follower coming on to market with a better product profile that can rapidly capture market share. So we're excited by the market opportunity for 3107.

Yes. Based on your feedback from your adviser and then the cognition, you've been interacted. Do you think they are ready to adopt your drug versus others? And then how they think about in terms of the patient readiness and then how the ramp-up is going to look like. It's a rare disease, but I think with even better drug, they do they -- do you think they will be more ready to use the drug?

Yes. So when we've conducted market research, what both physicians and patients really like is the fact that 8 out of 10 patients really see a marked improvement in terms of reduction in surgery compared to the pretreatment period. So for a patient taking 3107, they have a very good chance of seeing a significant reduction. So that's very appealing to them. The fact that they don't require additional surgeries or scoping during the dosing window is very appealing to them. And then the fact that 3107 can be given in the doctor's office and the physician doesn't have to worry about could my patient have neutralizing antibody against the vector? Could the papilloma microenvironment be inhibiting efficacy as for the approved product? That really doesn't apply to 3107. So it's a much more straightforward decision. Patients can expect to see a good reduction in surgery. They're not going to have to undergo the scoping and surgeries and they're not going to have to worry about factors that may mean that they're not a good candidate for 3107.

And how do you think about the durability going to play into the decision here and also the potential label? I understand it's pretty long lasting for a lot of patients. And then will this become -- at some point, they need to read those. If that's the case, how the label is going to be looking like and how the payer is going to decide to reimburse that.

Happy to. So I mean, as you saw, Jacqui present, we saw 72% of patients 50% or greater reduction. That actually increased to 86% in the second year. When you look at the complete responders, i.e., 0 surgeries after the first dose. We saw 7 of those continue that into the second year. So the vast majority of patients are seeing a significant reduction that is durable. And as you mentioned, one of the benefits of our DNA medicine platform is the fact that we can redose. So following approval, we do plan to do a continued treatment protocol. And obviously, we hope to certainly be able to maintain that excellent response we saw with the initial treatment. But obviously, also hope for further improvement with continued treatment.

Yes. And with regard to your comment about payers and how they would view continued treatment, I mean, clearly, the current approved product is quite an expensive drug. It's marketed at about $115,000 per dose. And I think really what payers are looking for is they're looking for long-term durable control of disease. And if that requires additional doses to do that, then that's in the patient's best interest. So I think from our discussions with payers, they've been open to continue treatment if it's really delivering results.

Got it. And then the -- in terms of the durability, those patients, if they are durable and then it will become interesting dynamic if they continue to responding and then you're waiting for them to do potentially relapse and then you can do the redose? And then how the time [indiscernible] certainty will play into the decision for payers to cover this.

I mean, we're dealing with a chronic viral infection here. So I mean, we're not eradicating the virus in most of these patients. So it actually, I think, makes much more sense to have a well-laid-out treatment protocol for these patients so that we can. So we're not necessarily waiting for them to relapse and we have a treatment protocol that hopefully eventually can eradicate the underlying viral infection.

Okay. So you're not waiting them to relapse to do the results. Maybe I ask another question is, how are you going to test this redose regimen? It's in your confirmatory study or you can just follow those patients you already treated and then see any signal you can start to retreat them? That's maybe a more fair question.

Yes. So I mean, we -- as you heard Jacqui mentioned, we haven't aligned on yet what our confirmatory protocol will look like. We'll obviously use all opportunities we can to show the evidence of 3107's ability to redose. But we have also seen that ability with previous plasmid in HPV targeting 1618. So we're very confident of what 3107 will be able to deliver.

Got it. And then interesting, we just saw the news, the current drug that they filed for or get accepted for the [indiscernible] designation. How does that impact your regulatory approval and then also commercial?

Yes. Great question, Roger. So the approved product just received orphan drug exclusivity. And what that means is that you can't basically bring the same drug for the same indication to market. 3107 is very clearly different to [indiscernible]. We're not delivered via a viral vector. We encode different transgenes. We're a different product. So 3107 isn't impacted by the orphan drug exclusivity, and it doesn't impact our regulatory pathway.

Excellent. All right. Time's up, and thank you so much, Jacqui and [indiscernible]. And thank you, everyone, for watching and listening.

Thank you.