Inovio Pharmaceuticals, Inc. H.C. Wainwright 28th Annual Global Investment Conference

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. 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 recent E-file 10-Q and 10-K documents for further details." 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. We have a BLA on file with a target date of October 30th 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. 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.

In this presentation, I'll be touching upon our new partnership with Akeso, Inc. for the evaluation of 5401 in combination with Akeso's bispecific checkpoint inhibitor for the treatment of glioblastoma. 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. To give you a quick overview of our technology, our DNA medicine platform is really focused on producing targeted proteins within the body. We start off by identifying the gene 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 a plasmid, and then we deliver those plasmids to either skin or muscle cells within the body using our proprietary delivery devices called CELLECTRA. 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. These proteins can either drive an immune response or they can be the therapeutic agent themselves. 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. Then the proteins that we are producing can be the therapeutic agent themselves.

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 are producing can be therapeutic proteins to treat diseases with missing or defective proteins that need to be replaced. To move on to our lead candidate, INO-3107, in more detail. RRP is a really difficult disease that really exerts a terrible toll on patients. It is a rare disease, and it is characterized by these small wart-like growths throughout the respiratory tract, but particularly in the larynx and the vocal cords. What this does is it can make it very difficult for a patient to talk, to breathe, to swallow, and it is driven by infection by HPV 6 or 11 viruses.

We think why people get RRP is that there is an insufficient immune response that either fails to prevent infection in the first place or fails to clear that infection, and that is what leads to RRP. It is 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. RRP can be diagnosed at any age. Recurrent and repeated surgery remains the standard of care, and because the surgery really is not addressing the underlying cause of the disease, the virus, these papilloma grow back time after time after each surgery. It really requires, in some cases, hundreds of surgeries over a patient's lifetime to control this disease. 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 cords. What patients are really concerned about are these surgeries, and they are really desperate to reduce the numbers of surgeries that they require to control their disease. We believe that INO-3107 addresses the patient's primary concern, reducing need for surgery to control their disease. INO-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. To move on to where we are in terms of our regulatory submissions, as I mentioned, we are in the late stage of the review. We have 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 CDER, CBER, and the Office of Therapeutic Products leadership. During this meeting, we had the opportunity to present the totality of our data supporting INO-3107's safety and efficacy, as well as our highly differentiated approach in treating RRP and our rationale for Accelerated Approval Program eligibility. We also discussed the current standard of care and the ongoing need for additional therapists. However, in the meeting, FDA did not discuss its preliminary comment that they made in the file acceptance letter regarding Accelerated Approval Program 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.

To tell you a bit about the trials that supported our BLA submission, we conducted two 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. 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 HPV 11-caused disease. What we were looking to do here was to see whether or not treatment with INO-3107 could reduce the numbers of surgeries these patients needed to control their disease. Patients entered into the study by requiring a clinically required surgery to control their disease.

They were then given 4 doses of INO-3107, and we counted every surgery that was required to control their disease after day 0. Any surgeries that were required during the dosing window were counted against our endpoint. In terms of what we were focused on was obviously safety, as this was a phase I/II trial. 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. In the durability and extension trial, what we were looking to see was how those patients did following treatment. They weren't getting any additional treatment. We were able to collect a median of 2.8 years of follow-up of those patients following treatment. These were the trials that generated the data that underpinned our BLA submission.

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. When you look at in terms of a 50%-100% reduction in surgeries prior to the year before, we saw 72% of patients in year 1 met 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. This is the data that we also used to justify eligibility for Accelerated Approval Program. When there's a product that's received a full approval to obtain Accelerated Approval Program, you need to demonstrate two things.

One is a meaningful therapeutic benefit over the existing treatment, and the other point you have to prove is the potential to meet remaining critical unmet need. We believe INO-3107 does exactly that across its efficacy, its safety, and its differentiated MOA. As I mentioned, we don't conduct any dosing or scoping during the treatment window, and we counted every surgery after day zero. 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. 83% of the trial participants from their phase I and phase II trials required 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. A key differentiator for INO-3107 is its ability to treat patients who are not served by existing therapy. In relation to Papzimeos, because 3107 is a DNA medicine, it doesn't have any impact on clinical benefit from pre-existing neutralizing antibodies, unlike viral vectored products like Papzimeos. We were able to show that there was no impact on clinical benefit from immunosuppressive factors within the papilloma microenvironment. In contrast, Papzimeos has reported that an immunosuppressive microenvironment inhibits their efficacy.