Inovio Pharmaceuticals, Inc.

Good afternoon, ladies and gentlemen, and welcome to the Inovio Third Quarter 2024 Financial Results Conference Call. At this time, all lines are in a listen-only mode. Following the presentation, we will conduct a question-and-answer session. If at any time during this call you require immediate assistance, please press star zero for the operator. This call is being recorded on Thursday, November 14, 2024. I would now like to turn the conference over to Thomas Hong, Manager of Investor Relations. Please go ahead.

Good afternoon, and thank you for joining the Inovio Third Quarter 2024 Financial Results Conference Call. Joining me on today's call are Dr. Jackie Shea, President and Chief Executive Officer, Dr. Mike Sumner, Chief Medical Officer, Peter Keys, Chief Financial Officer, Steve Egge, Chief Commercial Officer, and Dr. Matthew Morrow, VP of Translational Sciences. Today's call will review our corporate and financial information for the quarter ended September 30th, 2024, as well as provide a general business update. Following prepared remarks, we will conduct a question and answer segment. During the call, we'll be making forward-looking statements regarding future events and the future performance of the company. These events relate to our business plans to develop Inovio's DNA medicines platform, which include clinical and regulatory developments, and timing of clinical data readouts and planned regulatory submissions, along with capital resources and strategic matters. All of these statements are based on the beliefs and expectations of management as of today. Actual events or results could differ materially. We refer you to the documents we file from time to time with the SEC, which under the heading Risk Factors, identify important factors that could cause actual results to differ materially from those expressed by the company verbally as well as statements made within this afternoon's press release. This call is being webcast live, and a link can be found on our website, ir.inovio.com, and a replay will be made available shortly after this call is concluded. I will now turn the call over to Inovio's President and CEO, Dr. Jackie Shea.

Good afternoon, and thank you to everyone for joining today's call. This quarter, We continue to make progress on the key objectives we've been focused on for 2024 to deliver value to stakeholders in the near, mid, and longer term, and most importantly, deliver on the promise of DNA medicine for patients. Those objectives include, firstly, advancing our lead product candidate, INO3107, towards commercialization. Secondly, advancing our pipeline, And thirdly, continuing to strengthen our business overall. Today, I will provide an overview of our progress and then ask my colleagues to provide greater detail. To begin with, we've recently announced important additional immunology data supporting the proposed mechanism of action for 3107 and its potential to eliminate or reduce the number of surgeries RRP patients have to face. This extensive immunological characterization data, highlighting the ability of 3107 to induce T-cell responses that correspond to the clinical benefit observed in our Phase I-II trial, has been presented at two scientific conferences, including the International Papillomavirus Conference this week. We have also presented the full safety and efficacy data, demonstrating that 3107 was shown to be well-tolerated and have clinical benefit, in our Phase 1-2 trial at two recent scientific conferences. We believe the powerful combination of this additional data further highlight the potential for 3107 to become the preferred choice for the broadest number of RRP patients, should it be approved. Mike and Steve will provide further details on this later in today's call. Moving on to regulatory matters, In August, we held a positive pre-BLA meeting with the FDA. Since then, we have continued preparing for submission of our BLA, targeted in mid-2025. We expect to have all non-device-related modules for the BLA completed by the end of this year. You'll recall during our last quarterly call, we announced we had recently identified a manufacturing issue for the single-use component of our devices. during the testing required for our BLA submission. We believe we have identified the appropriate resolution for this issue and are making good progress in implementation. In summary, we remain confident in our ability to deliver 3107 to the market for patients as an important and new therapeutic option to treat this devastating disease. As this is our primary focus, we are directing the majority of our resources, both people and financial, towards completion of development, BLA submission, and preparing for our potential commercialization of 3107. However, even with 3107 as our primary focus, we are mindful of the significant potential of the rest of our pipeline and have continued to make important progress on several other candidates as well. For INO3112, we've consulted with European regulators regarding the design of our proposed BASE-3 trial, evaluating 3112 in combination with the PD-1 inhibitor Loctorsi as a potential treatment for locally advanced HPV 16 and 18 positive high-risk oropharyngeal squamous cell carcinoma, also known as throat cancer. We anticipate conducting this trial in North America and Europe. Previous discussions with the FDA have indicated alignment with the proposed trial design. Continuing in oncology for INO5401, patients continue to be dosed in the GBM001 trial in newly diagnosed pleoblastoma that combines 5401 with Regeneron's PD-1 checkpoint inhibitor, Libteo. Regeneron and Inovio have discussed that an appropriate next step for GBM could be a controlled Phase II trial. A separate trial evaluating 5401 in patients with the BRCA mutation is ongoing at the Bassa Center at the University of Pennsylvania. We also have an upcoming meeting scheduled with the FDA later this quarter to discuss the Phase II trial design and development pathway for ino4201 as a heterologous boost to the FDA-licensed Ebola vaccine, Avibo. From our earlier stage candidates, we expect clinical data from an ongoing phase one study with DNA-encoded monoclonal antibodies to be submitted to a peer-reviewed publication by year-end. We believe this will be the first clinical data for DNA-delivered monoclonal antibodies to be reported and illustrates what we believe to be the transformational potential of our DNA medicines platform. Finally, Our commitment to financial discipline and strengthening our business is a core component of our strategy for success. While we've made substantial progress on our overall goals, we've done so while continuing to reduce our operating expenses. We closed the third quarter with $84.4 million in cash, cash equivalents and short-term investments, and with no debt. Now, I'll turn it over to Mike for some additional insights from the new data on 3107. Mike?

Thanks, Jackie. Before I dive into the new data that we have presented at several scientific conferences over the last couple of weeks, I think it's important to review why we're working so hard to bring INO3107 to patients. RRP is a rare HIV-related disease characterized by small wart-like growths called papillomas found in the respiratory tract. People with RRP mount an insufficient immune response that's unable to prevent or clear the HP infection from their airways, so the papillomas can grow unchecked. The papillomas often cause difficulty speaking or complete voice loss, difficulty swallowing, shortness of breath, or choking episodes. The current standard of care is surgery to clear out the papillomas, but that doesn't address the underlying viral cause of the disease. and the papillomas grow back, setting patients up for an endless cycle of resurgence of symptoms and need for more surgery. Every single surgery presents a risk of permanent vocal cord damage, reinforcing what patients have said time and again, that a reduction of even one surgery would be life-changing. That patient experience has been central to our efforts to develop 3107. which we believe has the potential to change the treatment paradigm for RRP. Designed to generate antigen-specific cytotoxic CD8 T cells, targeting both HPV6 and HPV11, 3107 is a potential novel, non-surgical treatment option for RRP patients. In our Phase I-II clinical trial, we observed a compelling combination of clinical benefit and tolerability. across the disease spectrum of severity and including both HPV6 and 11 driven disease. In addition, we saw the generation of a significant and targeted immune response that was associated with a reduction or elimination of surgeries for these patients. We believe that the growing body of evidence shows that 3107 could be used to treat the vast majority of RRP patients. and supports its potential to be the preferred product of choice by patients, healthcare providers, and payers if approved. At the International Society of Vaccines Conference and the Full Voice Conference this past October, Inovio presented its full safety and efficacy data for the Phase 1-2 trial, which is summarized here. In the trial, the overall clinical response defined as patients experiencing a decrease in the number of surgical interventions in the year after the initial 3107 administration compared to the prior year was 81% or 26 of the 32 enrolled patients. This number includes 28% that required no surgical intervention during or after the dosing window. These are our complete responders. Further, 44% of patients had a partial response, defined as a reduction of at least 50% in the number of surgeries when compared to the prior year. The overall response rate calculated by adding our complete responders and partial responders was 72%, or 23 out of 32 patients. Importantly, in our trial design, we counted every surgery after day zero, because every surgery matters to patients. On this slide, you can see our overall safety data. 3107 was well tolerated in the study, with the most common treatment-related adverse events being injection site pain reported in less than a third of patients. supporting that our Selectra electroporation device was well tolerated by patients and was also easy to use by healthcare providers. Fatigue was the next most frequent reported treatment-related AE in just three patients. No treatment-related adverse events greater than grade two severity were reported. One of the core strengths of our DNA medicine platform is the ability to drive a T cell response. which is particularly important for treating chronic viral disease. You can see on this slide the proposed mechanism of action for 3107, inducing HPV antigen-specific T cell responses in the blood, then having those T cells travel to and infiltrate the papilloma and airway tissue, and ultimately eradicate the HPV-infected cells to reduce or eliminate the need for surgery. I'd like to now turn to our new immunology data that we have shared at the recent scientific conferences, including this week at the International Papillomavirus Conference. To further characterize immune responses to 3107, we analyzed blood and tissue samples from patients in our Phase I-II trial. Our goal was to evaluate the individual steps that combine into the proposed mechanism of action that I just presented. We conducted a number of very extensive immunological assessments on blood and tissue samples to one, confirm the induction, activation, and expansion of cytotoxic T cells with antigen specificity to HPV6 and 11. And two, to assess the level and form of immunological change from baseline, including T cell infiltration and profiling. and the potential impact of the papilloma microenvironment on clinical effect. In short, what we discovered was very compelling. The data demonstrated the ability of 3107 to do exactly what it was designed to do, induce HPV antigen-specific T cell responses in the blood that infiltrate papilloma and airway tissues, and that they are the right kind of T cells to eradicate HPV-infected cells and ultimately reduce or eliminate the need for surgery. Overall, the key takeaways from this study include five main points. First, INO3107 generates the right kind of immune responses to fight HPV for the vast majority of RRP patients. In our research, we see generation of HPV6 and 11 antigen-specific cytotoxic T cells with responses that are durable out to 52 weeks, indicating a long-lived memory response, which is important for the treatment of a chronic viral disease like RRP. Second, the newly generated T cells get to where they need to go. Our data shows that T cells travel from the blood to the papilloma and airway tissue, and the resulting inflammatory and antiviral responses are seen in the tissue. Third, the immune response we have observed is targeted and specific to treatment with INO3107. We saw expansion of both preexisting T cell clones and the emergence of new T cells in the blood. These new T cells could not be detected prior to treatment, meaning the majority of T cells seen in airway tissue at the 52-week time point were emergent clones. The presence of these new T cells in the tissue corresponds with the clinical benefit we saw in the trial. Fourth, we were also able to show that immune responses in responders are different to those seen in non-responders. While all 32 patients in the trial were seen to generate an immune response in the blood, the kinetics and magnitude of that response differed based on the clinical response seen. We believe we can build on these initial responses in non-responders through the administration of additional doses. And finally, from our evaluations to date, we have looked at elements of the papilloma microenvironment that have been reported in recent scientific literature to impact the potential efficacy of treatment. To date, we have not found evidence that these elements appear to restrict the clinical benefit of 3107. This immunology data is currently under review at a peer-reviewed journal, and we look forward to providing an update on that publication when available. So in summary, I would like to point out why this new data is so important to the potential of INO3107. First and foremost, we believe the immunology data support the biological mechanism of action of 3107. This data will be an important component of our upcoming BLA submission and other future regulatory filings. The data confirm that 3107 effectively targets HPV6 and HPV11 the strains that cause the vast majority of RRP disease. The data confirmed that 3107 generates new and expands existing populations of T cells and activates them to eliminate the underlying cause of the disease. The data also support that 3107 can have clinical benefit across the disease severity spectrum and in both HPV 6 and 11 driven disease. Remember that patients tell us that every surgery matters, so our goal is to be able to treat patients with RRP regardless of the severity of disease. In short, we believe these data provide compelling evidence that INO3107, if approved, can be a game changer for RRP patients by reducing their need for repeat surgeries to treat their disease. I'd also like to mention that in addition to this important immunology work, we have also recently completed a retrospective study investigating the long-term durability of clinical response seen in patients treated in our Phase 1-2 study. We anticipate announcing that data by year end. On that note, I'll now turn it over to our Chief Commercial Officer, Steve Egge, for an update on our commercial efforts. Steve?

Thanks Mike. Hello everyone. At our last quarterly report, I outlined the significant opportunity I see for 3107 based on its compelling product profile. Over the last quarter, I've worked closely with our internal team and external consultants to continue to develop and refine our plans for the launch of 3107 if we receive FDA approval. We're making important progress and focused on developing a go-to-market strategy that's rooted in ensuring we meet physician, payer, and most importantly, patient needs. We've conducted a significant amount of market research to develop key insights with stakeholders to ensure we have a deep understanding of the market and the opportunity for 3107. We have repeatedly heard from patients that every single surgery matters and that a reduction in even one surgery makes a meaningful difference in the lives of patients. Because of the potential of a competitive marketplace, I won't go into significant detail, but at a high level, we are making strategic choices in a number of key areas, including pricing and access. From a pricing standpoint, we do expect to price in line with current rare disease pricing. and we've confirmed acceptability of this in feedback from payers that represent the majority of commercial lives in the U.S. We're also making strategic choices on distribution, physician and patient targeting and segmentation, as well as product positioning to ensure we're well differentiated. We've refined our plan for pathways for product adoption to ensure we provide an optimal customer experience. We did hear from the FDA earlier this month that our proposed brand name for 3107 is acceptable at this time. Of course, the decision of the brand name will be confirmed by the FDA during the BLA process. We're refining our forecasting and gross to net assumptions, and we've also developed strategic imperatives for the business to ensure we're focused on what matters most in a successful product launch, and these include metrics on how we'll measure our progress. And finally, we've also planned the build out of the commercial organization, including field teams in 2025. We're planning for a lean and efficient commercial footprint. And as we've communicated previously, we plan to be launch ready by the end of 2025. I also want to echo Jackie and Mike. The new data we've shared today supporting our proposed mechanism of action builds on 3107's compelling product profile and strengthens my belief that 3107 can treat a broad range of RRP patients and that it could be the preferred choice for RRP patients and physicians. I'll now turn it over to our Chief Financial Officer, Peter Keys, for a financial update.

Thanks, Steve. Today I'd like to provide an overview of Inovio's financial results for the third quarter of 2024. As Jackie noted at the start of the call, we are primarily focused on advancing INO 3107 and our goal to submit a BLA mid 2025. To support these efforts, we have continued to control our operating expenses. For the third quarter ended September 30th, 2024, our total operating expenses dropped 24% from 35.9 million in the third quarter of 2023 to 27.3 million in the third quarter of 2024. Anobio's net loss for the third quarter of 2024 was 25.2 million, or 89 cents per share, basic and dilutive, compared to a net loss of 33.9 million, or $1.52 per share, basic and dilutive, for the third quarter of 2023. We finished the third quarter of 2024 with $84.8 million in cash, cash equivalents, and short-term investments, compared to $145.3 million as of December 31, 2023. We estimate our cash runway to take us into third quarter 2025. This projection includes an operational net cash burn estimate of approximately $24 million for the fourth quarter of 2024. These cash runway projections do not include any further capital-raising activities that Inovio may undertake. As a reminder, you can find our full financial statements in this afternoon's press release, as well as in our Form 10-Q filed with the SEC. And with that, I'll turn it back over to Jackie.