Inovio Pharmaceuticals, Inc. (INO) Earnings Call Transcript & Summary

Hello, everyone, and thank you for joining us today. It's my pleasure to introduce Dr. Jacqueline Shea, President and CEO of Inovio Pharmaceuticals. Jacqui has more than 25 years of experience across the life sciences and biotech industries and has led Inovio since 2022. Prior to becoming CEO, she has served as the company's Chief Operating Officer and earlier in her career, held leadership roles at Aeras and Emergent BioSolutions with much of her work focused on the development of vaccines and therapies for infectious diseases. She holds a PhD from the National Institute for Medical Research in the U.K. and currently serves on the Board of Trustees of the Sabin Vaccine Institute. Jacqui, thanks very much for coming today and joining us, and I'll turn it over to you.

Thank you. It's a pleasure to be here today and tell you about some of the exciting work that we're doing here at Inovio. So before I move into the presentation in full, this is just a standard slide that says during the presentation, I'll be making forward-looking statements, and I refer you to our most recently filed 10-Q and 10-K documents for further details. So to provide you a quick overview of Inovio, we're a clinical stage biotech company. We're focused on developing and commercializing DNA medicines to treat and protect people from HPV-related diseases, cancer and infectious diseases. Our lead program, INO-3107 for the treatment of Recurrent Respiratory Papillomatosis or RRP, is currently being reviewed by FDA under the accelerated approval program. So we have a BLA on file with a target date of October 30 this year. RRP is a rare HPV-related disease with significant unmet need, and we believe a significant commercial market opportunity. We've been granted both Orphan Drug and Breakthrough Therapy Designations by the FDA, and we have Orphan Drug Designation in the EU. The FDA review is advancing. We're currently in the late stages of the review, and I'll be discussing our regulatory progress in further detail later on in the presentation. And as we approach our PDUFA date, our commercial preparations are also ramping up. And we believe that we have an opportunity for 3107 to become the new standard of care for RRP with an improved risk-benefit profile over existing treatments. Following on behind 3107, we have a deep clinical pipeline with multiple near- and midterm catalysts, and in this presentation, I'll be touching upon our new partnership with Akeso for the evaluation of 5401 in combination with Akeso's bispecific checkpoint inhibitor for the treatment of glioblastoma. And also the positive data that's recently been reported by our partner, ApolloBio, in China from their pivotal Phase III trial of VGX-3100 for the treatment of cervical dysplasia. In terms of cash, we have a cash runway into late first quarter next year through the potential launch of 3107. So to give you a quick overview of our technology, our DNA medicine platform is really focused on producing targeted proteins within the body. And we start off by identifying the genes for the target protein that we want to produce. We then use our proprietary algorithms to really optimize that gene sequence. We insert the optimized gene sequence into a circular molecule of DNA called the plasmid. And then we deliver those plasmids to either skin or muscle cells within the body using our proprietary delivery devices called CELLECTRA. So once the DNA plasmids are within the nucleus of the cell, the DNA is transcribed to RNA. The RNA is then used to produce proteins and then the proteins are released from the cell. And these proteins can either drive an immune response or they can be the therapeutic agent themselves. So in terms of driving an immune response, we can drive antigen-specific cytotoxic T cells and we use this primarily to treat virally mediated diseases or oncology indications. We can also produce both antibodies and T cells, and these are primarily for our infectious disease indications. And then the proteins that we are producing can be the therapeutic agent themselves. So we can use our DNA medicines technology to produce monoclonal antibodies directly within the body to either prevent or treat disease or the proteins that we're producing can be therapeutic proteins to treat diseases with missing -- or defective proteins that need to be replaced. So to move on to our lead candidate 3107 in more detail. RRP is a really difficult disease that really exerts a terrible toll on patients. It's a rare disease, and it's characterized by these small wart-like growth throughout the respiratory tract, particularly in the larynx and the vocal cords. And what this does is it can make it very difficult for a patient to talk, to breathe, to swallow. And it's driven by infection by HPV-6 or 11 viruses. And we think why people get RRP is that there's an insufficient immune response that prevent either fails to prevent infection in the first place or fails to clear that infection. And that's what leads to RRP. It's a rare disease, but not that rare. It affects an estimated 14,000 people in the U.S. with about 1.8 per 100,000 new cases in adults annually. And RRP can be diagnosed at any age. Recurrent and repeated surgery remains the standard of care. And because the surgery really isn't really -- isn't addressing the underlying cause of the disease, the virus, these papillomas grow back time after time after each surgery. So it really requires, in some cases, hundreds of surgeries over a patient's lifetime to control this disease. And every surgery takes a toll on patients. Every surgery entails both significant risk to the patient as well as emotional financial physical costs and every surgery comes with the potential for irreversible damage to the vocal cord. What patients are really concerned about are these surgeries, and they're really desperate to reduce the numbers of surgeries that they require to control their disease. And we believe that 3107 addresses the patient's primary concern, reducing need for surgery to control their disease. And 3107 was designed to generate an antigen-specific T cell response against both HPV-6 and 11, which are the targets underlying the cause of RRP. So to move on to where we are in terms of our regulatory submissions. We're in -- as I mentioned, we're in the late stage of the review. We've completed our late-cycle review meeting and all of our scheduled FDA inspections. We also held an informal clinical meeting with FDA in July following the recent change in both CBER and the Office of Therapeutic Products Leadership. And during this meeting, we had the opportunity to present the totality of our data supporting 3107 safety and efficacy as well as our highly differentiated approach in treating RRP and our rationale for accelerated approval eligibility. We also discussed the current standard of care and the ongoing need for additional therapies. However, in the meeting, FDA did not discuss its preliminary comment that they made in the file acceptance letter regarding accelerated approval eligibility. They did, however, indicate that their feedback on the design of the confirmatory trial would be forthcoming. Our next scheduled interactions with the FDA are going to be our label negotiations anticipated in September this year. So to tell you a bit about the trials that supported our BLA submission, we conducted 2 trials, RRP-001, which was a Phase I/II study and then a follow-up study called RRP-002, where we were following up the same patients and looking to see how they did after RRP-001 completed. So with RRP-001, we evaluated patients who had 2 or more surgeries required to control their disease in the prior year. These were patients who had HPV-6 or 11 caused disease. And what we were looking to do here was to see whether or not treatment with 3107 could reduce the number of surgeries these patients needed to control their disease. So patients entered into the study by requiring a clinically required surgery to control their disease. They were given 4 doses of 3107. And we counted every surgery that was required to control their disease after day 0. So every -- any surgeries that were required during the dosing window were counted against our endpoint. And in terms of what we were focused on was obviously safety as this was a Phase I/II trial. And in terms of our efficacy endpoint, what we were looking for was the change in number of surgical interventions in the 12 months prior to treatment versus the 12 months afterwards. And then in the durability and extension trial, what we were looking to see was how those patients did following treatment. So they weren't getting any additional treatment. And we were able to collect a median of 2.8 years of follow-up for those patients following treatment. So this is the data that -- these were the trials that generated the data that underpins our BLA submission. So when we look at what we saw coming out of the trial, we were very pleased to see what we saw as promising clinical benefit. So when you look at in terms of the 50% to 100% reduction in surgeries prior to the year before, we saw 72% of patients in year 1 at this endpoint, and this improved to 86% in year 2. In terms of patients that required no surgery at all after day 0, this was 28% in the first 12 months and improved to 50% in the second 12 months. And this is the data that we also use to justify eligibility for accelerated approval. And when there's a product that's received a full approval to obtain accelerated approval, you need to demonstrate 2 things. One is a meaningful therapeutic benefit over the existing treatment. And the other point we have to prove is the potential to meet remaining critical unmet need. And we believe INO-3107 does exactly that across its efficacy, its safety and its differentiated MOA. So as I mentioned, we don't conduct any dosing or scoping during the treatment window, and we counted every surgery after day 0. In contrast, the approved product requires what they call minimal residual disease surgeries during the dosing window. So prior to doses 3 and 4 to maintain minimal residual disease during treatment. And 83% of the trial participants from their Phase I and Phase II trials require these MRD surgeries during the dosing window. Surgery also remains the current standard of care. The vast majority of RRP patients are still receiving surgery to treat their disease. And PAPZIMEOS to date has reported treating about 200 patients as of the second quarter of this year. And a key differentiator for INO-3107 is its ability to treat patients who are not served by existing therapy. So in relation to PAPZIMEOS, because we're -- because 3107 is a DNA medicine, it doesn't have any impact on clinical benefit from pre-existing neutralizing antibodies unlike viral vector products like PAPZIMEOS. And it doesn't -- and we were able to show that there was no impact on clinical benefit from immunosuppressive factors within the papilloma microenvironment. And in contrast, PAPZIMEOS has reported that an immunosuppressive microenvironment inhibits their efficacy. So as you can see across efficacy, safety and a differentiated mechanism of action, we believe that we provide meaningful therapeutic benefit over existing treatments as well as the potential to meet the remaining critical unmet need. And I'm very pleased to say that we've had the support of the RRPF Foundation. So that's the Recurrent Respiratory Papillomatosis Foundation, who are the patient advocates for RRP patients. And they continue to highlight the need for new innovative therapies to treat RRP. And they explain that every surgery matters to every patient, every patient matters to the RRP community and every patient deserves treatment that works for them. We started off our program working very closely with the RRP Foundation, and we're delighted to have their support as we move through our regulatory process. So this slide just really provides why we believe that 3107 delivers what patients and health care providers want most from a therapy to treat RRP. First of all, patients are really focused on reducing these numbers of debilitating surgeries that they require to control their disease. And as we walk through the data, 3107 does that. It doesn't require additional exposure to surgery during the treatment window to maintain minimal residual disease. And there's no potential impact on clinical benefit from either the pre-existing neutralizing antibodies or immunosuppressive papilloma microenvironment that may impact the efficacy of approved products. Because we're not doing those minimal residual disease surgeries, it minimizes the recovery days needed during treatment. And unlike the approved therapy, we don't require a specialized ultracold chain. So that means that 3107 is easier to use across multiple different clinical settings. So we believe there's a real opportunity to establish 3107 as the new standard of care in RRP. And to do this, we plan to leverage experienced field teams in conjunction with the contract sales organization. We'll be developing a targeted marketing campaign in conjunction with our agency of record, and we'll be using a patient hub to provide strong patient support services. Together, we're aiming to drive health care provider and patient preference for 3107 based on our differentiated product profile. We aim to establish broad access among payers and hospital systems, and we aim to grow the market by educating patients and caregivers about the potential product profile of INO-3107. So following on behind 3107, we have some late-stage candidates that I'll briefly just touch upon. As you can see from our pipeline, most of our later-stage candidates are focused either on HPV-related diseases or oncology indications. We also have some very promising earlier-stage technology, which are our DMAb and our DPROT protein candidates, and I'll talk briefly about those as well. So in terms of our later-stage candidates, we were very pleased with the announcement earlier on this year, that our partner in China, ApolloBio, their pivotal Phase III trial of VGX-3100 for cervical dysplasia met its primary endpoint. And ApolloBio are planning to use this clinical data to potentially file for approval within China and related territories. What this means for Inovio is obviously the potential for regulatory and sales-based milestone payments as well as a royalty payment should VGX-3100 be approved in China. And we also believe that this data further validates our DNA medicines platform in HPV-related disease. Moving on to oncology indications. Earlier on this year, we announced a partnership with Akeso. And in this partnership, what we're looking to do is to combine 5412 in combination with Akeso's bispecific checkpoint inhibitor and see if this novel combination improves survival rates and delays disease progression in glioblastoma patients. And glioblastoma, as I'm sure you're aware, is one of the most deadly and common brain cancers, which unfortunately has a very poor 5-year survival rate and for which there really haven't been new treatments over the past decade. This also involves a partnership with the Dana-Farber Cancer Institute, and we plan to evaluate this combination regimen as part of the Dana-Farber Cancer Institute's INSIGhT trial, where they're the sponsor. So we're very excited about this program. Moving on to those earlier-stage platforms in terms of our DMAb technology, and this is where we're producing monoclonal antibodies in the body. We were able to show in a Phase I human trial as a proof of concept that we were able to produce 2 different monoclonal antibodies against SARS-CoV-2 that we could produce them at potentially therapeutic levels out to 96 weeks and that the production level of the antibody was stable in the blood throughout out to 96 weeks. Very importantly, we didn't see any antidrug antibodies being raised against these antibodies. And these antibodies were functional. We were also able to increase the level of antibody that we were able to see in the circulation by redosing. And we saw that the treatment was very well tolerated with the most common side effects just being injection site reactions. So we were really excited to see this data. And we're now taking the same technology and also applying it to other proteins, for instance, for missing or defective protein diseases. And it really is building on our DMAb technology. And what we're aiming to do by producing these proteins is to address the shortcomings of conventional therapeutic protein or enzyme replacement therapies where patients are having to receive regular injections or infusions of these proteins or have gene therapy to try and correct the underlying defect. In terms of the protein -- in terms of the preclinical programs that we presented on, we presented very promising preclinical data on Hemophilia A at recent conferences as well as announced our work in Fabry disease and hypophosphatasia. And we're currently seeking partnerships to advance these exciting programs as well as other rare disease targets. So in summary, we're really focused on working to deliver INO-3107 to patients as we approach our PDUFA target PDUFA date of October 30. Following on behind, we're advancing our diversified clinical pipeline and with most of our resources focused on 3107, we're primarily doing this through partnerships. And then we have some very exciting technology coming through in terms of our DMAb and our DPROT candidates. And again, we're seeking partnerships to advance these programs. So thank you very much for your attention.

Jacqui, thank you. With INO-3107 approaching its October 30 PDUFA date, there's clearly a lot happening at Inovio over the next few months. It was also great to get a sense of how the program fits the broader DNA medicines platform and the opportunities you're pursuing across the pipeline. Once again, we really appreciate the update and your time with us today. Thanks.

Thank you. It's been a pleasure.