Inovio Pharmaceuticals Inc

NASDAQ:INO

Earnings Call Analysis

Inovio Q3 2023: Pipeline Progress and Fiscal Discipline

In Q3 2023, Inovio highlighted its DNA medicines platform progress, notably INO-3107 for recurring respiratory papillomatosis (RRP). It has been well-tolerated in trials, has no need for frozen storage, and may be re-administered overtime to boost immune response. Financially, Inovio emphasizes fiscal discipline, reducing Q3 operational expenses by 20% to $35.9m (43% after adjusting for a onetime impairment charge), and reports a net loss of $33.9m or $0.13 per share. With $167.5m in cash reserves and a $26m cash burn estimate for Q4, Inovio expects its funds to last into Q2 2025.

Inovio's Leap Towards its First DNA Medicine Offering

Inovio Pharmaceuticals has taken a significant stride in the third quarter of 2023 towards pioneering DNA medicine in the U.S. market. Their lead candidate INO-3107, aimed at treating Recurrent Respiratory Papillomatosis (RRP), has received both Breakthrough Therapy designation and the green light from the FDA to file for Accelerated Approval. This pathway eliminates the need for a Phase III trial before the submission of a Biological License Application (BLA), potentially accelerating time-to-market. Inovio eyes this as an opportunity to intensify its interaction with the FDA, request a priority review, and capitalize on submitting portions of the BLA on a rolling basis.

INO-3107's Development: Racing Against Time

Inovio highlighted the swift pace of INO-3107's development: taking the candidate from proof of concept to BLA-ready in three years. Granted orphan drug status by the FDA and the European Commission, the candidate stands to benefit from the FDA's push to expedite rare disease therapies. INO-3107 has showcased effectiveness in reducing the frequency of surgeries required for RRP patients, a key factor in the FDA's decision to facilitate its Accelerated Approval Program for the candidate.

Inovio's Commercial Readiness and the Path to the BLA

Inovio has been intensively preparing for INO-3107's market entry, underpinned by existing data points and device use strategies from prior engagements with the FDA. With a strategy alignment meeting with the FDA pivotal for confirming the protocol for necessary confirmatory trials, Inovio is setting the stage for a successful BLA filing that is supported by strategic planning and robust data.

Charting the Path for Effective Commercialization

Inovio's commercial strategy for INO-3107 in the RRP space is focused on efficiency and efficacy, targeting about 300 to 400 laryngologists with a specialty sales force and early groundwork for distribution and payer discussions. With plans to leverage in-house capabilities where feasible and outsource judiciously, Inovio aims to stay financially disciplined as it provides further guidance on cash runway into 2024 after more definitive timelines are established post-FDA discussions.

Preparing for Future Treatment Options

Inovio acknowledges the feasibility of re-dosing INO-3107, a trait inherent to its DNA medicines platform, although this has not yet occurred in clinical trials. Future strategies might incorporate this approach based on clinical outcomes and regulatory labels. The company intends to work closely with payers to ensure that the value proposition of INO-3107 aligns with treatment flexibility for clinicians, ensuring optimal patient care and satisfaction for both physicians and payers.

Inovio's Long-term Vision and Focus

Inovio's pursuit of INO-3107 represents more than an isolated success—it's part of a broader corporate strategy aimed at achieving long-term triumphs in the DNA medicine space. With a diversified pipeline, proprietary technology, and a focus on operational excellence and financial discipline, Inovio is prepared for the development and potential commercialization of INO-3107. The team is energized by the possible impacts their work could have on patients worldwide, embarking on the many tasks ahead with a collective motivation.

Earnings Call Transcript 2023-Q3

[Operator]

Good afternoon, ladies and gentlemen, and welcome to the Inovio Third Quarter 2020 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. (Operator Instructions). This call is being recorded on Thursday, November 9, 2023. And I would now like to turn the conference over to Mr. Thomas Hong. Thank you. Please go ahead.

[Thomas Hong, executive]

Good afternoon and thank you for joining the Inovio 2023 Third Quarter Conference Call. Joining me on today's call are Dr. Jackie Shea, President and CEO, Dr. Michael Sumner, Chief Medical Officer, Mr. Mark Twyman, Chief Commercial Officer, and Mr. Peter Kies, Chief Financial Officer. Today's call will review our corporate and financial information for the quarter ended September 30, 2023, as well as provide a development progress update for our DNA medicines platform.Following prepared remarks, we will conduct a question-and-answer segment. During the call, we will 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, 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.

[Jacqueline Shea, executive]

Good afternoon and thank you to everyone for joining today's call. Over the last few months, I'm delighted to say that we've made significant progress advancing our lead candidate, INO-3107 for the treatment of recurrent respiratory papillomatosis or RRP. After two very important regulatory developments, we are closer than ever to delivering on the promise of DNA medicines to patients and bringing the first DNA medicine to market in the United States. Specifically, in the third quarter of 2023, the FDA granted breakthrough therapy designation to INO-3107 based on clinical evidence indicating that it may demonstrate substantial improvement over existing therapies for RRP.A couple of weeks following that breakthrough therapy designation, we received feedback from the FDA that data from our completed Phase I/II trial of 3107 could be used to support submission of a biological license application or BLA for review on the FDA's Accelerated Approval Program. Our Chief Medical Officer, Mike Sumner, will provide more context shortly, but this news means that we no longer need to complete a Phase III trial before BLA submission and will ultimately allow for a potentially much faster development pathway. We will, however, be required to initiate a confirmatory trial and satisfy all other FDA filing requirements prior to BLA submission as is usual for the accelerated approval pathway. To achieve that, our team has already submitted a request for an initial comprehensive multidisciplinary breakthrough therapy meeting to the FDA for the fourth quarter. This meeting will help further align our plans with the FDA and determine the timing for critical deliverables associated with our BLA submission.As we make progress on this new expedited pathway, we have every intention to utilize the opportunity to increase communication with the FDA and other advantages offered by breakthrough therapy designation, such as requesting a rolling submission of completed sections of our BLA and a priority review of the fully submitted BLA.As a result of this new time line, we have accelerated our commercialization strategy to be prepared to launch 3107 should it be approved. Led by Mark Twyman, our Chief Commercial Officer, whom you'll hear from shortly, our commercial team has extensive experience bringing products to market, including innovative new technologies and products in the rare disease space. Mark will spend a few moments today talking about his team's current efforts to expedite building a number of critical capabilities and establishing pathways for commercial success, such as creating the value proposition for 3107, putting in place an optimized distribution model, developing payer, specialty pharmacy and pharmacy benefit management strategies to ensure favorable access and preparing to stand up a field organization.Mark and his commercial leadership team brings decades of combined biopharmaceutical experience from such companies as Sanofi Genzyme, Merck, CSL Behring and MedImmune. They've been personally involved in nearly every aspect of successfully commercializing products from sales and marketing to distribution, market access and government affairs. I am really pleased with the progress of this team as they worked hand in glove with leaders from across the company to optimize the launch plans for our lead candidate.In addition to the regulatory achievements and commercial readiness efforts I've described, we've worked very hard over the past 18 months or so to restructure our corporate organization with the goal of meeting our current focused pipeline needs and reducing spending, while at the same time, retaining and building the expertise critical to implement our plans for our late-stage pipeline.After many difficult months and quarters, I'm pleased to see the collective efforts of our dedicated and experienced cross-functional team make a real difference. With that, I'd like to turn it over to our Chief Medical Officer, Dr. Mike Sumner, to provide a brief overview of the regulatory and development progress we've achieved for 3107, the next steps on our accelerated development time line and other key preparations to support the BLA submission and, if approved, to bring this candidate to market. Mike?

[Michael Sumner, executive]

Thank you very much, Jackie, and greetings evening, everyone. As Jackie has mentioned, we have made substantial progress with our lead candidate, INO-3107. To provide a little perspective on how fast this candidate has been advancing through development, we've created this time line. We started our Phase I/II trial in 2020, the same year the FDA granted orphan drug status. After announcing positive final results from the trial earlier this year, the European Commission granted orphan drug status in May, followed by the FDA's Breakthrough Therapy designation in September.Shortly thereafter, we received important feedback that data from our completed Phase I/II trial could support submission of a BLA for review under the FDA's Accelerated Approval Program. To take a candid from proof of concept to working on in filing a BLA in the span of three years is lightning speed and speaks to the hard work and collaboration of the broader Inovio team. Looking ahead, the opportunity to file our BLA under the Accelerated Approval Program assures that our team will need to continue to run fast and hard.I'd like to speak briefly as to why we have been granted the opportunity to submit a BLA for 3107 under the FDA's Accelerated Approval Program. First, keep in mind that the FDA instituted its Accelerated Approval Program to allow for early approval of drugs that treat serious conditions and fill an unmet medical need. Additionally, they have recently issued a press release identifying their desire to utilize this program to further accelerate the development of rare disease therapies. In general, to qualify, a drug candidate must address a serious or life-threatening condition with consideration for the severity, rarity or prevalence of the condition and available treatment options.For those who are not familiar with RRP, and I must include myself in this category before coming to Inovio last year, it's a debilitating and rare disease caused primarily by HPV-6 and/or HPV11. RRP is characterized by the development of small wart-like growth or papillomas in the upper respiratory tract. While these papillomas are generally benign, they can cause severe life-threatening airway obstruction and respiratory complications. The majority of patients with RRP need to undergo multiple surgeries year after year to remove the recurring papillomas. This has a significant impact on quality of life, coupled with the potential for long-term impact on vocal cords, which can limit the patient's ability to speak effectively. We are pleased that the FDA has now recognized the impact this devastating disease has on patients' lives and awareness that in large part is due to the persistent efforts of the RRP Foundation; a patient advocacy organization that has been working tirelessly to raise the need for better and less invasive treatments.This links was another characteristic required to qualify for the Accelerated Approval Program, which is that a drug candidate must provide a meaningful advantage over other available therapies. In this instance, the standard of care for RRP, as I mentioned, is repeat surgeries to remove the papillomas from the throat and vocal cords. I'm pleased to say that in our completed Phase I/II study, 81% of patients experienced a reduction in the number of surgeries in the year after treatment versus the year prior to treatment. This included nine patients representing 28% of patients in the study who did not require any surgeries following treatment initiation.Further, our immunology data provides a potential mechanism of action, which supports the clinical evidence, which I will highlight next. This slide helps illustrate the scope and impact of the immune response in a natural patient who had undergone six surgeries a year prior to the trial, followed by zero surgeries during the trial. The graph on the left here depict the CD8 T cell response observed in this patient before and after completion of dosing. As you can see, this patient experienced a strong induction of HPV-specific CD8 T cells that have markers of cellular activation and a positive for granzymes and perforin, which are known to be key mediators of eliminating virally infected cells by killer T cells.The data in both graphs indicate that 3107 expanded these critically important cells in impressive fashion with the most highly active killer T cells, which are those showing expression of all three activation markers, exhibiting close to a tenfold increase in frequency. It is these types of cells that we believe are key contributors to reduction in the need for surgery exemplified in photos on the right-hand side of the slide. These are images of the same patients vocal cords before and after treatment with 3107. Again, this patient went from having six surgeries in the year prior to treatment to zero surgeries in the 12 months following the first dose. As you can imagine that level of reduction in surgeries had an incredible impact on the patient, but it's important to highlight that RRP patients and their health care providers have indicated time and again that a reduction of even 1 surgery would provide significant improvement in quality of life.One important note about our trial design, while our treatment involved four doses over nine weeks, what we call the treatment window, we counted any surgery conducted after the first dose. We did not wait until after all four doses were administered to start counting surgeries. The rationale behind this is important. As I stated above, patients care about every single surgery, regardless of when it happens, whether it happens during the treatment window or not because each and every surgery impacts that patient's life. These results add to the growing body of evidence that our DNA medicine candidate are well-tolerated immunogenic and particularly adept at promoting viral clearance and lesion regression in HPV-related diseases.From a regulatory standpoint, we now have several key objectives ahead. We have submitted our request for an initial comprehensive multidisciplinary breakthrough therapy meeting and have asked the FDA for it to take place in the fourth quarter of this year. At that meeting, we will discuss key elements of our planned future submission for an accelerated approval review, including required immunology data, key CMC plans, including process performance qualification or PPQ strategy, alignment on questions about our s-electric delivery device and other clinical strategy sets. The outcome of this meeting will be instructive to the time line of critical deliverables for the BLA submission.Shortly thereafter, we plan to submit a protocol for our confirmatory trial to the FDA, drawing on our previous alignment with the agency on study design. Under accelerated approval, a confirmatory study is always required to verify the anticipated clinical benefit of a candidate, and we have been requested to initiate this trial prior to BLA submission. Throughout the process of submitting our BLA under the Accelerated Approval Program, we will utilize the benefits of our breakthrough therapy designation status, which affords priority access to the FDA's guidance and advice to try to quickly resolve any outstanding questions. We also plan to take advantage of the opportunity to submit under the FDA's rolling review program and plan to request a priority review once the BLA is fully submitted, which has the potential to further accelerate the product development time line.Rolling review allows for a company to submit completed sections of a BLA for a review by the FDA generally over a 3-month window rather than waiting until every section is completed to submit. Under priority review, the FDA aims to take an action on the application within six months compared to ten months under standard review. It's important to recognize that achieving an approval of our BLA requires a team with expertise across an array of functions. We are fortunate to be working with such an incredible team of experts who bring with them years of price success in advancing innovative medicines through approval to commercialization with the ultimate goal of benefiting patients.Every one of the functions I've listed here on the slide is critical. But just to give you a sense of the work one important area has underway and medical affairs function is focused on developing and implementing plans for scientific engagement, medical communications and field operations. The work done by medical affairs is an important juncture between those who work to develop medicines and our partners in commercial who make sure the patients can ultimately receive them.With that, I'll now turn the call over to our Chief Commercial Officer, Mark Twyman, for some important updates on how our commercial team is working to ensure just that. Mark?

[Mark Twyman, executive]

Thanks, Mike. Before I jump into the specifics of our commercial strategy, I'd just like to say that it's a pleasure to have the opportunity to speak with you all today and how excited I am about the prospects for INO-3107. While this is my first time on a quarterly financial call for Inovio, I have been with the company for about six years, and as Jackie mentioned earlier, I've been involved in the commercialization of biopharmaceutical products for many years for both small and large companies, as has my team.We are extremely excited to begin implementing many of the plans we have been working on to benefit patients who are in desperate need of options to improve their quality of life. Let's take a few minutes to discuss what we believe are five key areas to achieve success in the launch of an orphan drug. The first is to create a long-term commercial strategy by starting early and continuously updating based on end market data. It is also important to build up the required resources as early as possible before regulatory approval is granted. As I mentioned, I've been at Inovio for several years, helping the company prepare to bring DNA medicines to market. We now have the opportunity to leverage existing cross-functional capabilities for the development and potential launch of INO-3107.The next key element to a successful launch of an orphan drug is demonstrating the value of your product to all stakeholders. This value proposition has to be provided in the context of any competition and it must leverage trial data in real-world evidence.Next, a company that successfully launches a biopharmaceutical product must ensure that patients have a voice in their care and the options offered. This is accomplished by involving patients and patient organizations early in the development process. As Mike mentioned, the RRP Foundation has done a wonderful job in advocating for patients with RRP over the years, sharing their experiences with regulators and policymakers alike. We are proud to consult with them on our shared goal to help patients suffering from this debilitating and serious disease.The fourth key element is to take an active role in disease education with a detailed stakeholder activity plan. This includes sending medical liaisons into the field early and creating innovative sales roles such as patient-centric field reps. And last, but probably most importantly, is to get the supply chain up to speed as quickly as possible. This includes determining the appropriate distribution strategy model for INO-3107, identifying and selecting supply chain partners and really understanding the last mile logistics for the product, a complete manufacturer-to-patient solution.It's important to note that INO-3107 does not require ultra cold or frozen storage or thawing prior to injection and is refrigerator stable at 2 to 8 degrees Celsius, which will be key factors for both distribution and administration. I'm pleased to report that for INO-3107, many of the key areas for success I just outlined are underway or being addressed. For example, we are actively engaging external partners and service providers and have started implementing plans for product distribution and logistics, payer engagement and reimbursement, specialty pharmacy identification, patient and provider awareness and education, customer service programs and other sales and marketing activities. It is also worth noting, we believe that INO-3107 will be considered by payers to be a specialty pharmacy product, not a buy-and-bill product, consistent with many other orphan disease treatments.We are also continuing to deepen our understanding of RRP as a disease, the treatment paradigm in the United States and the impact of both the disease and the current surgical treatment regimen on patients. We have taken extra care to really understand the needs of patients, doctors, caretakers and advocates to inform our path forward.Here is a high-level snapshot of what we understand so far. RRP is a chronic, rare disease caused by HPV 6 and HPV 11. The current standard of care surgery with many patients facing a lifetime of repeated surgeries as their only option. Incidents and prevalence of RRP is variable globally and depends on several factors. The most widely cited U.S. epidemiology data estimated that there were 14,000 active cases and about 1.8 per 100,000 new cases in adults each year. Our recent publication site set on average, patients with RRP undergo about four surgeries per year. These surgeries and surrounding care for a tremendous financial burden on patients and the health care system.Based on ongoing market research, we believe that laryngologists are the primary health care providers treating patients separate from this condition that they are comfortable administering drugs and utilizing new tools and devices. In our discussions with them, they have expressed particular interest in finding a more effective nonsurgical treatment option for their RRP patients. We estimate that about 300 to 400 laryngologists in the U.S. conduct the majority of our RP surgical procedures. We are currently in the process of validating those estimates and geographically mapping their practice locations to support final decisions about the size and alignment of our field-based sales team for INO-3107.Key opinion leaders estimate that approximately one-half of all laryngologists practice in academic institutions. In recent discussions with RRP patients, we heard that many of them prefer to be treated at these regional academic centers. As I've outlined today, we are considering every detail that could impact patients, health care providers and ultimately, our commercial strategy as we work to potentially bring INO-3107 to market. We will continue drawing on the strength of the Inovio team across functions and working with seasoned partners to meet the demands of this accelerated time line and deliver on the promise of DNA medicine.I'll now turn the call back to our CEO, Jackie Shea, for a pipeline update. Jackie?

[Jacqueline Shea, executive]

Thank you, Mark. Before I cover some additional updates from our pipeline, I'd like to take a moment to reiterate some of the key takeaways from what you've heard today from Mike and Mark, which highlight why we believe in the commercial potential of 3107 and its ability to potentially transform the treatment paradigm for RRP. In our completed Phase I/II trial, 3107 was able to generate antigen-specific T cell responses against both HPV 6 and 11, a result that was observed in patients across the spectrum of disease severity. We also saw a reduction in surgery in HPV 6 and 11 positive patients, again, across the spectrum of disease severity.3107 was well tolerated by participants in the trial, resulting in mostly low-grade treatment-emergent adverse effects, such as injection site pain and fatigue. Unlike other T cell generating platforms, 3107 and DNA medicines in general, don't cause an antibacterial response, which means that 3107 could potentially be readministered over time to boost immune response if needed. Because RRP is a chronic viral disease that can lead to persistently occurring symptoms, re-administration may be an important factor in extending efficacy over a lifetime. And we anticipate exploring that opportunity further if 3107 is approved.Thinking further down the line to potential use in market, it's important to reiterate the point that Mark made earlier, 3107 is a refrigerator stable at 2 to 8 degrees Celsius, does not require frozen or ultra-cold storage and will be packaged in a single-use vile, all of which will be key factors in distribution of administration.We see INO-3107 as an exemplar of the larger potential of our DNA medicines platform, and we remain dedicated to driving progress across our pipeline to unlock that potential for patients across the globe. We believe that this is achievable in a three-step process. As you can see on this slide, in the near term, Inovio is focused on optimizing the opportunity for 3107 as a potential treatment for RRP patients. In the midterm, Inovio is working to advance eight other clinical stage candidates targeting HPV-related diseases, cancers and infectious diseases.For the longer term, Inovio is developing next-generation DNA medicine technology, including DNA-encoded monoclonal antibodies or DMAbs targeting COVID-19 as well as DNA-launched nanoparticles or DLNPs, targeting infectious disease targets and cancer vaccines that have various disease targets.This slide provides greater detail on our pipeline. Obviously, 3107 is closest to market, but we also had several key candidates that we're working to advance. In particular, we're finalizing the study report and data analysis on INO-5401 for treatment of newly diagnosed glioblastoma and continue to support treatment for some patients on the trial. We're currently in discussions about next steps with KOLs and our partner, Regeneron.In an excellent example of the versatility of our DNA medicine candidates, INO-5401 is also being studied in a Phase Ib investigator-sponsored trial by the University of Pennsylvania's Basser center. Researchers there are evaluating 5401 in patients with BRCA1 or BRCA2 gene mutations. This vaccine candidate may have the potential to prevent breast cancer for people with those mutations. The research was recently featured on the -- today show, highlighting both the potential of DNA medicine and the power of partnerships to help accelerate progress for patients.We aim to continue building strategic partnerships like this one to drive medical progress for patients, innovation and ultimately, shareholder value. We also remain encouraged by the final data reported earlier this year from the study of INO-3112 in head and neck cancer in combination with the PD-L1 checkpoint inhibitor. We are continuing discussions to find a potential PD-1 checkpoint partner to advance this promising candidate. I believe there is a significant opportunity to be explored for 3112 in combination with a proven PD-1 checkpoint inhibitor.On the infectious disease side, earlier this year, we announced positive data from a Phase I study for INO-4201 as a potential Ebola vaccine booster. We're continuing discussions with our partners for that program to determine next steps and evaluating potential funding opportunities. We also have some exciting next-generation DNA medicines in early clinical development. For instance, our DMAbs and DLMPs and also candidates in preclinical development. We believe these next-generation candidates built on the strength of our DNA medicines platform with significant potential advantages over other platforms.I'll now turn the call over to our CFO, Peter Kies, for our third quarter 2023 financial summary. Peter?

[Peter Kies, executive]

Thank you, Jackie. Today, I'd like to provide an overview of Inovio's operational highlights and financial condition for the third quarter of 2023. As Jackie noted and as required in today's economic environment, Inovio is committed to financial discipline as we advance our pipeline. To achieve our longer-term goals, our strategy over the past 18 months has been to reprioritize our pipeline, reshape our organization and scale our operational spend.As you can see from this slide, we have succeeded in bringing our operational spend down for both the third quarter and the nine-month period ended September 30, 2023, compared to the same period in 2022. For the third quarter 2023, operational expenses dropped 20% to $35.9 million from $44.9 million compared to the same period in 2022. The third quarter included a onetime noncash charge for goodwill impairment that totaled $10.5 million. Excluding that onetime charge, our operational expenses for the third quarter would have declined 43% from the same period or same quarter in 2022.For the first nine months of 2023, we cut our operating expenses nearly in half, dropping to $117.3 million from $221.8 million in the first nine months of 2022. Breaking down total operating expenses a bit more. For the third quarter, our R&D expenses totaled $15.5 million in 2023 compared to $33.1 million for the same period in 2022. The decrease in R&D expenses was primarily the result of lower drug manufacturing, clinical trial expenses and outside services related to INO-4800 and other COVID-19 studies and lower employee and consulting compensation, including stock-based compensation, among other variances.G&A expenses for the third quarter 2023 were $9.9 million compared to $11.9 million for the same period in 2022. Revenues for the third quarter of 2023 were $388,000 compared to $9.2 million for the same period in 2022. The revenue reported for the 2022 third quarter was associated with a procurement contract with the U.S. Department of Defense for Inovio's device and accessories to be used for delivery of INO-4800, which we have since discontinued. These factors combine to bring our net loss for the third quarter of 2023 to $33.9 million or $0.13 per share, basic and dilutive.Excluding previously mentioned onetime noncash charge for goodwill impairment, our loss would have been $0.09 per share basic and dilutive. For the 2022 third quarter, our net loss of $37.8 million or $0.15 per share basic and dilutive. We finished the third quarter of 2023 with $167.5 million in CAS, cash equivalents and short-term investments compared to $253 million as of December 31, 2022.Following feedback from the FDA on the Accelerated Approval pathway for INO-3107, we now estimate that our funds should support operations into second quarter of 2025. This projection includes a cash burn estimate of approximately $26 million for the fourth quarter of 2023. These projections do not include any funds that may be raised through our existing at-the-market program or other capital raise activities. 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.

[Jacqueline Shea, executive]

Thanks, Peter. I'd now like to open up the call to answer any questions you might have. Operator?

[Operator]

Thank you. Ladies and gentlemen, we will now begin the question-and-answer session. (Operator Instructions). One moment, please, for your first question. Your first question comes from the line of Roger Song from Jefferies.

[Jiale Song, analyst]

Great. Congrats for all the progress. Maybe just focusing on the RRP program. The first question is related to the BLA filing in the Phase III confirmatory study design. Can you just let us know what is the outstanding items for the filing in the confirmatory study design? And any current guidance around the timing of the BLA filing and the potential approval?

[Jacqueline Shea, executive]

Thanks, Roger. It's nice to hear voice. So, as we mentioned during the call, the news on accelerated approval pathway is relatively new. We just heard in September. So, over the past few weeks, we've really been working to accelerate our time lines. We put together quite a detailed package to be considered by the FDA under the upcoming meeting. And I'll hand over to Mike to provide a few more details there. But what we're really hoping to achieve in that meeting is to get some alignment with the FDA as to some of the content that needs to go into that submission package as well as some further discussion on the design of the confirmatory study. Mike?

[Michael Sumner, executive]

Yes. Thank you, Jackie. I think you hit some of the highlights. I mean, obviously, since we heard the news in September, I think we've made tremendous progress as a team. We've really mapped out every single function and what we need to do to get to our BLA. In terms of the input we need from the FDA, I mean, obviously, we have a strategy. We need to get the FDA to agree to that strategy. But we're pulling on significant data points that we've had. I mean, we've already gone through our PPQ strategy for 3100. We've used our s-electric device in our Phase III program. We've had several interactions with the agency on what we need to do for the device. We know, again, from a confirmatory study that what we want to propose, and we've had significant input of what we believe is going to be acceptable to the agency. And so, we need alignment on that protocol as we do need to start that study prior to filing our BLA.But overall, I think we're -- based on all the interactions we've had on our platform and specifically around RRP, we're in a very good place. And now it's really just going through the process of aligning strategy with the agency so we can move rapidly forward.

[Jiale Song, analyst]

Great. Maybe just a quick question around the commercial infrastructure. With the current runway into second quarter 2025, how should we think about the overall commercialization cost post approval for assuming the approval for the RRP?

[Jacqueline Shea, executive]

Yes. That's a really great question, Roger. Before I ask Mark to jump in there, I think really this upcoming discussion with the agency will really help us be more definitive on the time lines. I think Mark can talk a bit about this in a bit more detail. But I think one of the encouraging things for us as a relatively small biotech company is that this is a rare disease. We believe that there are a reasonable number of core points for a company of our size to take on. We have in-house manufacturing for our device that we think can meet our device manufacturing needs. And we have well-established relationships with our drug manufacturing CMO to manufacture the drug. So, Mark, maybe you can talk a bit more about how we're thinking about going to market for 3107.

[Mark Twyman, executive]

Thanks, Jackie. Great question. I think that exactly really hit the nail on the head when she was talking about this laryngology space and for RRP and being a perfect fit for Inovio. I mean if we think about the field sales organization, we're thinking now that there are roughly between 300 and 400 laryngologists that are performing the majority of the RRP surgeries in the U.S. And we really think that a small specialty sales force can officially address the needs for both patients and physicians. But I think the other sort of component, and it sort of speaks to the experience that we have in the organization in commercializing products, we're getting an early start. It's not just about the sales organization, but it's about everything you're doing behind that from the perspective of your distribution strategy, the early conversations you need to have with payers and PBMs, specialty sort of pharmacy. So that's all work that's been started. And I think what is emerging is that we've identified the key work streams. We've begun to identify the key partners that we need to have on board. And I feel really good about where we are right now and being able to leverage this accelerated approval.

[Jacqueline Shea, executive]

Thanks, Mark. And Roger to answer your question about cost. So, we are planning to operate a lean and efficient model. So, where it makes sense for us to do things in-house, we'll do them in-house. Where it makes sense to leverage our people's capabilities such as the contract sales force and potentially defer expense there, we'll be doing that. So, I think we'll be able to provide a bit more guidance in terms of our phasing of our cash runway over 2024 once we've had that discussion with the FDA.

[Operator]

Thank you. (Operator Instructions). Your next question comes from the line of Yi Chen from H.C. Wainwright.

[Yi Chen, analyst]

Could you tell us whether any patient in the clinical trial has been re-dosed with INO-3107. And in the real-world setting, commercially speaking, do you think laryngologists will have the flexibility of those choosing to do -- how often a particular patient should be dosed with 3107 or that could be limited by payers to, let's say, just once every year.

[Jacqueline Shea, executive]

So, I'll hand over to Mike maybe for talking about the initial clinical question on the completed Phase I/II trial. And then Mark, maybe you and Mike together can address the next question.

[Michael Sumner, executive]

So, I mean, starting off, obviously, one of the real benefits of the DNA medicines platform is there's no anti-vector response, and we believe redosing is capable. In fact, we know redosing is capable from many of our oncology programs. At present, we have not re-dosed any of the patients from the Phase I/II study. But as we come to think about those patients, maybe, we obviously saw some patients with complete response. We saw a significant number of patients with a very good partial response with a 50% reduction in their surgeries. And then unfortunately, there were a few patients who [didn't] have such great response on me. I keep all those three buckets separate from a clinical strategy. But we certainly want to, in the future, sort of examine how we can continue to build on the excellent clinical efficacy we've seen to date. But I would say, obviously, any -- until that's in our label, it would all be off-label. And so, it will be down to the clinicians to decide what they want to do with their patients.

[Mark Twyman, executive]

Yes, I think what I would add to that, Mike, is the question we'll let payers decide. I think that what I know is that -- we have a very strong value proposition for INR 3107. I think we can all kind of look at the results to date from a clinical perspective and know that we have a real potential to address this unmet medical need, both from a patient perspective, it still unsettles me to know that some of these patients experienced hundreds of surgeries over a lifetime. And that comes with significant cost burden and just how they go about living their daily lives. But on -- but the other sort of point is that physicians aren't satisfied. I mean these surgeons are used to sort of treating and resolving an issue that their patient might have. And that's just not the case with RRP and hence, the name recurrent respiratory papillomatosis.And I know from having a number of discussions with some of the key KOLs and physicians that are doing a large number of surgeries that they are really looking forward to having this option. And it's really kind of our job, and it's the job we've already started, to make sure that there's alignment with what the payers -- how the payers sort of value INO-3107 and the fact that physicians are looking for a new option for treating RRP. So, I'm feeling really good about where we are, but we'll have to get to the finish line.

[Yi Chen, analyst]

Will redosing be part of the Phase III trial?

[Michael Sumner, executive]

We're still in discussions with the agency regarding that and haven't really put the details out there, but it's certainly -- as I said, it's certainly something that we are thinking about.

[Operator]

(Operator Instructions). There are no further questions at this time, please continue.

[Jacqueline Shea, executive]

Thank you. The significant progress we have made in advancing INO-3107 over the past few months, means that we are moving closer to providing a potentially life-changing nonsurgical treatment option to patients suffering from RRP. I remain incredibly grateful to the patients, patient advocates, trial investigators and our dedicated team here at Inovio that has enabled us to achieve this. I am confident that our experienced team is prepared for the next critical steps of development and potential commercialization for INO-3107. And thanks to the corporate strategy we've been implementing over the past year, I'm also confident that Inovio now has the key drivers in place for broader long-term success. We have a diversified pipeline focused on candidates with scientific and clinical promise, achievable pathways to market and strong commercial potential. We have our proprietary DNA medicines platform and technology, along with a history of strong partnerships to accelerate progress and innovation. And we have the benefit of an incredibly experienced team focused on financial discipline, operational excellence and motivated by the patients who could someday benefit from the power of DNA medicine.There is much work to be done, but I speak for the entire Inovio team when I say that we are energized by what the future could hold for DNA medicine and patients around the world. With that, thank you again for your attention. Have a great evening, every month.

[Operator]

Thank you. Ladies and gentlemen, that does conclude our conference for today. Thank you all for participating. You may all disconnect.