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

Good morning, and welcome to the H.C. Wainwright 27th Annual Global Investment Conference. I'm Katherine Degen, an associate with the firm, and I'll be moderating today's session. It's my pleasure to welcome the CEO of Inovio, Jacqueline Shea, and I look forward to your talk.

Thank you, Katherine. It's a pleasure to be here today, and I'm excited to be telling you about some of the work that we've been doing here at Inovio. So before I move into the presentation proper, this is just to let you know that I'll be making forward-looking statements during this presentation, and I refer you to our most recently filed Form 10-Q 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. We have a deep pipeline of both therapeutic and vaccine candidates with multiple potential near and midterm catalysts coming up. Our lead program is INO-3107 for the potential treatment of recurrent respiratory papillomatosis or RRP, which is a rare HPV-related disease. FDA has granted us breakthrough therapy and orphan drug designations, and we're following the accelerated approval pathway. We expect to complete our BLA submission in the second half of this year with the goal of FDA accepting the file by year-end. And we believe that 3107 has the potential to become the preferred first-line treatment over the current standard of care, which is repeated surgery and a recently FDA-approved therapy based on our positively differentiated product profile. To note, we believe the recent approval in the space is good news for 3107 as it indicates FDA support for expediting rare disease treatments and open us to new therapeutic technologies. It's also positive validation of the broader indication and the high unmet medical need within the RRP community for new therapeutic options. We've established commercial scale manufacturing for our DNA plasmids, and we assemble our devices in-house. We also have some exciting next-generation technology at earlier stage development, and these include our DNA-encoded monoclonal antibody and our DNA-encoded protein technology. And we believe these technologies are poised to further unlock the potential of our DNA medicine technology. And I'll be talking a bit more about this work later on in the presentation. Our goals across the near, mid and longer term with our next-generation therapies are shown on this slide. In the near term, we really focused most of our efforts and resources on delivering 3107 to patients. To reiterate, our top priority for this year is our BLA submission, and we recently announced that FDA has agreed to our rolling submission time line. Our goal is to complete this submission in the second half of this year with file acceptance by year-end. And if approved, 3107 will be the first DNA medicine approved in the U.S. Following on behind 3107, we have 8 additional clinical stage candidates, including other HPV-related candidates, cancer candidates and our new clinical stage dMAb program. And I'll be touching a bit more on our next-generation pipeline as we go through the presentation. So how do our DNA medicines work? DNA medicines are really founded upon the principle of in vivo protein production, which is teaching the body to make its own disease-fighting tools. So we start off by identifying either antigens or proteins that we want to produce within the body across -- and these can be across various target indications, including HPV and cancer, infectious diseases or protein replacement diseases. We then optimize those gene sequences using our proprietary algorithms and insert them into circular molecules of DNA called plasmids. We're able to manufacture these plasmids at commercial scale using typical E. Coli fermentation technologies, and then we can deliver them to either skin or muscle cells using our proprietary delivery devices called CELLECTRA. Once the plasmids are in the cell, they use the cell's own machinery to produce proteins. And these proteins can either stimulate an immune response as in the case of HPV or cancer, where we're looking to drive a cellular or T cell response, particularly an antigen-specific cytotoxic T cell, which can destroy HPV-infected cells or cancer cells or in the case of our infectious disease indications, we're looking to drive both an antibody and a T cell response to prevent disease or the protein that we're producing in the cells can be the therapeutic agent itself as in the case of our monoclonal antibody technology or therapeutic proteins to address protein replacement diseases. So moving on to our lead candidate, 3107 for RRP. We believe this could be a potentially transformational therapy and is currently progressing under the FDA's accelerated approval pathway. So to tell you a bit more about RRP, as I mentioned, this is an HPV-related disease. It's caused by infection with either HPV-6 or HPV-11. And RRP is characterized by the growth of small wart-like growth or papillomas in the respiratory tract. They can form anywhere in the airways, but they primarily affect the larynx and the vocal cord. And these papillomas can cause difficulty speaking and deterioration of the voice is normally the first symptoms. They can lead to complete voice loss, difficulty swallowing and can lead to shortness of breath or choking episodes. In some cases, RRP can spread to the lungs. And under those circumstances, unfortunately, there's a higher risk of malignancy, which can have pretty bad outcomes. And the current standard of care is surgery, repeated surgery. And the papillomas grow back time after time. The key is in the name, recurrent since the underlying infection with HPV remains. So why do some patients get RRP? We believe this is because they mount an insufficient immune response that fails to prevent and clear the HPV-6 and HPV-11 infection that leads to RRP. And patients and their physicians are really looking for a therapeutic alternative that addresses the underlying cause of RRP, the virus and eliminates the surgery. So repeated surgery is very tough on patients. Some patients require hundreds of surgeries over their lifetime. And every surgery matters to patients because every surgery comes at both the risk, the risk of a potential irreversible damage to their vocal cords, bleeding or infection and the cost, the impact to their quality of life as well as financial costs. So every surgery really does matter to patients. So I'll now tell you a bit about our Phase I/II trial and our durability extension trial that led us to be awarded breakthrough therapy designation and access to the accelerated approval pathway. We designed both 3107 and our trial really with patient needs in mind. And FDA recognizes that a reduction of a single surgery is clinically meaningful. So our 001 trial was an open-label trial. We enrolled 32 patients, gave them 4 doses of 3107 over a 9-week time period. And we enrolled patients who had required at least 2 surgical interventions in the prior year for removal of HPV-6 or HPV-11 papilloma. Up to 14 days before the first dose, patients had a clinically meaningful surgery to remove their RRP tissue. And then any surgery after day 0 during the dosing window or during the follow-up period was counted against the efficacy endpoint. Our efficacy, our prospectively designed efficacy endpoint was the change in number of surgical interventions pre versus post treatment. And it was the data coming out from the 001 trial that led to us being awarded breakthrough therapy designation and access to the accelerated approval pathway. And FDA regard data from this trial as substantial evidence of effectiveness under the accelerated approval pathway. We were very pleased with the data that we saw coming out of 001, and we wanted to understand how the patients did in longer-term follow-up. So we conducted 002, which was a retrospective look-back trial to look at the durability of the reduction in surgery that we saw during 001. We were able to enroll 28 of the original 32 patients, and we had a median follow-up in this trial of 2.8 years. Now before I go into the data in a bit more detail, I think the key things to really take away from our data is that in 001, we showed a statistically significant reduction in surgery from a median of 4 prior to treatment down to 1 at the end of 12 months. And in the follow-up trial, what we saw was that this reduction of surgery continued to improve into the second year and was maintained into the third year. So to go into the data in a little more detail. This is the data from our 001 trial. And as you can see, just to remind you, we saw a statistically significant reduction in surgery when comparing the year prior to treatment to the year following treatment. And when we go back and look at what FDA considers clinically meaningful, which is a reduction of one surgery, we saw 81% of the patients in this trial demonstrated at least a reduction of one surgery. When you look at a more stringent readout in terms of a 50% or greater reduction in surgery or an ORR rate, an overall rate of response rate, we saw 72% of patients in the first year had an ORR, so a reduction of 50% or more. And 28% of these patients required absolutely no surgeries after day 0. So we're surgery-free. So moving on to the second year data. As you can see in the second year data, we saw a further reduction in surgery. So we went from a mean number of surgeries in the first year of 1.7 to a further reduction of 0.9 by the end of the second year. So what this means is compared to the year prior to treatment, where the mean number of surgeries was 4.1 by the end of the second year -- in the second 12-month period, we've seen a reduction of over 75% of surgeries compared to the year prior to treatment. And this is without any additional dosing. So we're really pleased by what we saw in terms of these excellent clinical results. And then looking at the data in a slightly different way here. What we're looking at here is the mean number of surgeries per year. So 4.1 surgeries in the pretreatment year, 1.7 at the end of year, 1 at the end of the first 12-month period, a reduction down to 0.9 at the end of the second year. And we see that this rate seems to be holding up into the third year. In the third year, we have a median follow-up of 0.8 years. So this isn't a full year for the third year data. But this brings us on to one of the key advantages of our DNA medicine technology. DNA medicines are able to be redosed and to continue to stimulate a T cell response, unlike some other T cell generating modalities. And we think that longer-term therapy could potentially offer the potential for both maintaining the excellent clinical response we've seen to date as well as the potential for further extending clinical improvement. So -- and we think this is very important for a chronic viral disease, which can often be lifelong. So just to recap the progress that we've made towards our BLA goal. This year, we completed our device design verification testing, which was the final piece of work that we needed to do ahead of submitting our BLA. FDA agreed to our rolling submission time line, and we're on track to submit our BLA in the second half of this year with the goal of receiving file acceptance by year-end. We've made good progress on our confirmatory trial preparations. We're currently updating our IND application for the trial initiation, and we're targeting conducting this trial at 20-plus sites across major U.S. medical centers. And we published the data from RRP-001 in Nature Communications in February this year, the retrospective duration study in the laryngoscope and the Nature Communications paper also describes in detail the immunology work that we've done to really characterize our T cell mechanism of action, where what we saw was that our T cell responses correlated with clinical benefit. We're going to be presenting this data at other conferences coming up in the second half of this year. So let's talk about the commercial opportunity for 3107. We see a really significant commercial opportunity here for a nonsurgical therapy for RRP. As I've mentioned, the current standard of care repeated surgery has the potential to cause irreparable harm to patients' vocal cords, and it doesn't address the underlying cause of the disease, the viral infection. And work and research conducted at Johns Hopkins has shown that by the time patients have had about 10 surgeries, most of them have suffered irreversible damage to their vocal cords. So limiting the number of surgeries really is important to preserve patients' voices and their quality of life. Whilst RRP is a rare disease, it's not that rare. There are an estimated 14,000 patients in the U.S., about 1.8 per 100,000 new cases annually, similar estimates across Europe. And based on work that we've conducted with Inovio on claims database analysis, we believe that this could be an underestimate. HPV experts have pointed out that HPV vaccination is unlikely to have a significant impact on the rates of RRP prevalence in adults in the near term since the majority of the adult population remains unvaccinated. And we believe 3107 has the potential to become the preferred product in this space as well as its potential for continued treatment. Work that we've conducted with payers has also supported the potential for rare disease pricing for therapeutics to address RRP. So why do we think we have the preferred product profile potentially in this space? This is really built across 3 pillars: efficacy, tolerability and a simple patient-centric treatment approach. On the efficacy side, we saw a very encouraging overall response rate, so a 50% to 100% reduction in surgeries, 72% in year 1, 86% in year 2 with complete responses. So these are patients who required no surgeries, and we counted every surgery after day 0, 28% in year 1, 50% in year 2. And when we've conducted blinded market research and talked to physicians and shown them this profile, what they tell us is they regard the complete response rate is good. But what they're more excited about is that 50% to 100% reduction in surgeries in 8 out of 10 patients. That's what they find the most compelling because what it means for their patients is that the vast majority of them are going to see significant benefit from treatment. 3107 was also very well tolerated and physicians find this tolerability profile attractive as well, particularly for patients who've undergone numerous surgeries, the tolerability profile looks very good. And this suggests that patients can go back to work, which is important, especially when patients receive multiple doses over a relatively short time frame. And 3107 can be administered in the doctor's office, which leads the doctor in control. Our delivery device has been found to be very easy to use by health care providers. And importantly, there's no requirement for scoping or minimal residual disease surgeries during the dosing window. And again, physicians find this simple patient-focused treatment regimen very attractive. So we're well underway in terms of preparing for launch. Work that we've conducted has confirmed that about 300 to 400 laryngologists who are the specialist physicians who treat RRP patients treat the majority of RRP patients in the U.S. As I said, we're well underway in terms of our launch preparations. We've developed our distribution and channel strategy and our channel partners. And we are now finalizing our go-to-market model and planning further build-out of the commercial organization. And the fact that this is such a focused market means that we'll be able to use a very small and efficient field force to effectively serve this market. So turning now to our pipeline. We have a pipeline of other candidates following on behind 3107 that will address high unmet medical needs as well as some exciting technology in early-stage development, transitioning from preclinical development into early-stage clinical development. And moving on to one of those candidates now, I'd like to turn to our dMAb candidates, where we recently announced data from a Phase I trial as part of a preprint and which we expect to be published in a top-tier peer review journal in the coming weeks. And what we were doing in this trial was we were encoding 2 separate monoclonal antibodies on our DNA plasmids, administering them with our proprietary in vivo delivery devices and then producing these monoclonal antibodies within the patient cells where they were then assembled and then secreted into the blood where they were able to circulate around the body. And what we saw in this trial was a durable and consistent production of monoclonal antibodies, which were stable out to 72 weeks in all patients reaching that time point. Very importantly, we saw no antidrug antibodies against the monoclonals in all of the blood samples that we tested from the study. The treatment was very well tolerated. Most common side effects were mild temporary injection site reactions. We saw no serious adverse events related to study drug. And very importantly, the monoclonal antibodies continue to be functional throughout the entire 72 weeks. And this was a collaboration with Wistar Institute, the University of Pennsylvania and AstraZeneca with funding from DARPA and JPO. So we think our dMAb technology has the potential to address challenges of conventional monoclonal antibodies. And through this clinical proof of concept, we think we can also apply our technology to produce proteins for other indications such as monoclonal antibodies to address other indications as well as therapeutic proteins to address enzyme replacement diseases. We're very excited about this technology, and we're in active discussions with partners about potential collaboration opportunities. So to wrap up, this has been a very exciting year for Inovio to date. We're very excited about the second half and completing our BLA submission for 3107, and we'll be out talking about our work at a number of conferences. And this will include our 3107 work as well as some of our earlier-stage technology as well. Thank you very much for your attention, and have a great day. Thanks.

Thank you so much for that talk, and thank you for being here.