Inovio Pharmaceuticals - Earnings Call - Q4 2024

Executive Summary

• Q4 2024 showed disciplined cost control and smaller losses: total operating expenses fell to $20.5M and net loss improved to $19.4M ($0.65 per share), with minimal revenue of $0.117M.
• The company resolved the single-use array issue for its CELLECTRA device, plans to complete FDA-required design verification (DV) tests in 1H 2025, start a rolling BLA submission for INO-3107 in mid-2025, and target FDA acceptance of the submission by year-end.
• Long-term durability data strengthened INO-3107’s profile: complete responses rose to 50% in year 2 (54% in year 3), with mean surgeries dropping from 4.1 pre-treatment to 1.7 (year 1) and 0.9 (year 2).
• Cash runway extended into Q1 2026; Q1 2025 net cash burn guided at ~$27M, supporting operations through key regulatory milestones (excludes additional capital raises).
• Wall Street consensus (S&P Global) for Q4 2024 EPS/revenue was unavailable at query time; we cannot assess beat/miss versus estimates [SPGI error].

What Went Well and What Went Wrong

• What Went Well

  • Device remediation on CELLECTRA’s single-use array completed; DV testing slated for 1H 2025, keeping mid-2025 rolling BLA timeline intact. “We have resolved the previously announced manufacturing issue… and completed drafting of all non-device BLA modules”.
  • INO-3107 durability data improved markedly: CR 50% by end of year 2 and 54% in year 3; ORR maintenance 95% (year 2) and 86% (year 3).
  • DMAb Phase 1 PoC showed durable in vivo antibody production through 72 weeks and no anti-drug antibodies, broadening platform optionality.

• What Went Wrong

  • Revenue remains immaterial ($0.117M in Q4), limiting margin analysis; company is pre-commercial and reliant on financing and partners.
  • Cash declined year-over-year ($94.1M cash, cash equivalents and short-term investments at Dec 31, 2024 vs. $145.3M in 2023), reflecting spend ahead of BLA and trial starts.
  • Estimates comparison unavailable: S&P Global consensus data could not be retrieved at query time, reducing visibility on Street expectations and near-term sentiment [SPGI error].

Transcript

Operator (participant)

Good afternoon, ladies and gentlemen, and welcome to the INOVIO Pharmaceuticals Fourth Quarter 2024 Financial Results Conference Call. At this time, all lines are in 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 Tuesday, March 18, 2025, and I would now like to turn the conference over to Ms. Jennie Wilson. Thank you. Please go ahead.

Jennie Willson (Company Representative)

Good afternoon, and thank you for joining the INOVIO Fourth Quarter 2024 Financial Results Conference Call. Joining me on today's call will be Dr. Jacquie Shea, President and Chief Executive Officer; Dr. Mike Sumner, Chief Medical Officer; Peter Kies, Chief Financial Officer; and Steve Egge, Chief Commercial Officer. Today's call will review our corporate and financial information for the quarter and year ended December 31, 2024, as well as provide a general business update. 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 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. Jacquie Shea.

Jacqueline Shea (President and CEO)

Good afternoon, and thank you to everyone for joining today's call. After significant progress in 2024, we remain focused on transforming INOVIO into a commercial-stage company and delivering on the promise of DNA medicines for patients and shareholders alike. To achieve that goal, our work this year will be driven by three main strategic priorities: submitting our BLA for INO-3107, our lead candidate for recurrent respiratory papillomatosis, advancing our commercial plan and preparing for a fast and efficient launch, and leveraging the strengths of our platform to drive progress across our diversified pipeline. Advancing INO-3107 is our primary focus, and I am very pleased to report that we have resolved the previously announced manufacturing issue involving the single-use array component of the CELLECTRA device.

Our next step is to perform the FDA-required [design] verification testing, known as DV testing, for the combined handset and single-use array required for our IND and BLA submissions. We now plan to begin submitting our BLA under the FDA's rolling submission process, as well as commencing our confirmatory trial and requesting priority review in mid-2025. With this timeline, we anticipate being able to complete rolling submission in the second half of the year to enable the FDA to accept our BLA filing before the end of the year. Most importantly, we remain confident that if approved, 3107 could be the preferred non-surgical treatment for RRP for both patients and their physicians, a position that is strengthened by the year-two and year-three clinical data announced in December and the detailed immunology data we published in February.

Mike will provide more detail later in the call, but in our retrospective trial of INO-3107, patients showed continued improvement in reduction in surgery after year one, with 50% meeting criteria for complete response in the second 12-month period or year two, meaning they were surgery-free. Overall, the mean number of surgeries across the patient population continued to decrease into year three. The ongoing efficacy was observed. It is also supported by the immunology data published in Nature Communications, demonstrating the ability of INO-3107 to drive an antiviral immune response in airway tissue, though correlated with a reduced or eliminated need for surgery. We also published the full safety and efficacy data set for the completed Phase 1/2 trial, which showed that the administration of INO-3107 was well tolerated.

In summary, INO-3107 offers significant and durable clinical benefit, tolerability, and a simple, patient-centric dosing regimen that does not require scoping or surgery during the dosing window, all of which we believe could be compelling advantages once on the market. While our immediate focus is on advancing INO-3107, I'm also pleased to provide an important update from our work on next-generation DNA medicines. Together with our partners, we recently announced top-line interim results from an ongoing Phase I trial with our DNA-encoded monoclonal antibody technology, which we call DMAb. This proof-of-concept trial involved two DMAbs targeting SARS-CoV-2 and showed that they can be durably and simultaneously produced in humans at biologically relevant levels.

We believe this technology has the potential to overcome some of the biggest challenges with traditional recombinant monoclonal antibodies and could also transform treatments for a broad range of diseases by enabling long-term in vivo production of therapeutic antibodies or other proteins. Now, I'll turn it over to Mike for some additional insights on our progress and new data on INO-3107. Mike.

Mike Sumner (CMO)

Thank you, Jacquie. As Jacquie mentioned, we have made tremendous progress towards our primary goal, submitting our BLA for 3107. We have now completed the drafting of all non-device modules, including non-clinical, clinical, and CMC modules. After extensive testing and internal quality sign-off, we have resolved the previously announced manufacturing issue involving the single-use array component of the CELLECTRA device. To resolve the issue, our device team strengthened key components, reduced stress on breakage areas, and refined the production process for the plastic-molded part of the array. We have tested the new array under similar testing conditions to when the issue was first identified and have not been able to reproduce the breakage, which gives us great confidence that the modifications have resolved the issue.

We began manufacturing our new commercial-grade arrays, which will now be utilized in the design verification testing, so we can move forward to completing our IND and BLA submissions. In addition, the full Phase 1/2 clinical data and accompanying detailed immunology data were recently published in Nature Communications. These data further support the T-cell mechanism of action for INO-3107, which underpins the efficacy results we've seen. We also announced some very exciting clinical durability data, showing that patients treated with INO-3107 continue to show further reduction in the need for surgery to manage their disease in the second and third year. This data will be the subject of an oral presentation at the Combined Otolaryngology Spring Meeting to be held in New Orleans this May, one of the most frequented meetings by our target physicians treating RRP. We've also made important progress in preparing for our Phase III confirmatory trial.

As a reminder, this will be a randomized placebo-controlled trial enrolling patients with two or more surgeries in the prior year, conducted at approximately 20 sites at major U.S. medical centers. This progress to date will enable us to enroll in a timely manner following submission of our updated IND. I'd like to spend some time now discussing the new data, as it paints a compelling product profile that strengthens our belief that INO-3107 could be the preferred product for RRP patients and their physicians. As a reminder, we completed a Phase I/2 open-label trial of 3107 in patients who required at least two surgeries in the previous year for the removal of HPV 6 and 11-related papillomas.

It's important to note that based on our understanding of the risk and cost to the patient of every single surgery, every surgery performed after day zero was counted against the efficacy endpoint in our trial, where we followed the patients for 12 months. We then conducted RRP 002, a retrospective trial in which we were able to collect data on 28 of the original 32 patients to assess the longer-term treatment effect with a median follow-up of 2.8 years. RRP is a chronic, often lifelong disease, and duration of efficacy is clearly important. Here we dive into the 002 data, looking at the longer-term efficacy results we observed in the trial. We were very pleased to see that patients continued to show improvement into years two and three following their initial dosing regimen.

In fact, the complete response rate increased to 50% for the second 12-month period when evaluated at the end of year two. We also saw the overall response rate, that is, the number of patients that had 50%-100% fewer surgeries compared to their pre-treatment baseline, increased from 72% in the first 12-month treatment period, or year one, to 86% for the second 12-month period, or year two. When you look at this in terms of the average or mean number of surgeries this patient group faced, it reduced by more than half from a mean of 4.1 surgeries per year prior to treatment to a mean of 1.7 surgeries at the end of year one, and then reduced further by the end of year two to a mean of 0.9 surgeries.

Across the population of patients treated with INO-3107, this is a reduction of greater than 75% following the initial treatment regimen alone. However, one of the core strengths of our DNA Medicines platform is the ability to administer additional doses to continue to drive and amplify strong T-cell-based immune responses without having to worry about the impact of an anti-vector response. Looking again at the mean surgeries per year across the population, we saw a significant decrease in the year following treatment and then a further decrease in the second 12-month period, or year two. Into year three, the improvement seems to be holding steady, and what we would like to be able to do is consider a longer-term treatment strategy that supports both the maintenance of that complete or partial response and potentially extending clinical improvement, including the potential for non-responders to mount a clinical response.

We have published data from a similar DNA medicine that targeted the E6 and E7 antigens of HPV 16 and 18 that demonstrated we were able to augment the CD8 T-cell responses with a single additional dose, given after completion of the primary treatment course when compared to predose levels. This further increase in cytotoxic T-cells supports the potential of extending the duration and improving upon the already excellent clinical response that we have seen to date. Every surgery matters to patients, and our vision for INO-3107 is to further minimize or eliminate future surgeries for all RRP patients. As I said earlier, the immunology data we've recently published becomes important here as it underpins the mechanism of action of INO-3107 and how we believe treatment is providing the favorable efficacy results we observed.

First, in our analysis, we found that all the patients were generating the right kind of antiviral immune responses to fight HPV, specifically antigen-specific cytotoxic T-cells. We saw that these T-cells really got where they needed to go, traveling from the blood into the airway and papilloma tissue. Once they were in the airway tissues, they created an antiviral immune response, which we believe is responsible for reducing or eliminating the need for surgery by eradicating HPV-infected cells. I would also like to note that while other investigators have suggested that multiple factors such as high viral loads or neutrophil infiltration in the papilloma microenvironment can be barriers to immunotherapy treatment of RRP, we didn't see any such factors impacting the efficacy we observed in the trial.

While all patients were generating the right kind of immune response, in our non-responders, this response was not as large and tended to decrease faster than in our responders, which again is why we believe continued treatment may improve clinical outcomes in these patients. Overall, our immunology data provide a clear demonstration of the mechanism of action behind INO-3107, showing that it is doing exactly what is needed to treat the underlying HPV infection that causes RRP. To wrap up, I want to provide some additional detail on our next steps for INO-3107. Now that we have resolved the array issue, we have commenced the manufacturing of the new arrays, which we will subsequently age condition and utilize in the conduct of the FDA-required design verification, or DV testing process, which we anticipate will be completed in the first half of this year.

This testing is required to update the IND before we can dose patients in our confirmatory trial and is also part of the last remaining module of our BLA package we need to complete. We plan to request rolling submission and priority review of our BLA, and if FDA agrees, we will begin submitting our modules in mid-2025 and complete the full submission three to four months later, with the goal of having the FDA accept our complete BLA for filing by the end of the year. Once the entire BLA is submitted, we plan to finalize our long-term dosing study strategy and submit a proposed protocol to the FDA to support a supplemental BLA in the future.

We also look forward to commencing onboarding of our field medical science liaison team and presenting this exciting data package at several upcoming conferences this spring, including the U.S.-based National HPV Conference, the European ALS Congress, and COSM, among others listed on the slide. With that, I will now turn it over to our Chief Commercial Officer, Steve Egge, for an update on our commercial efforts. Steve?

Steven Egge (Chief Commercial Officer)

Thanks, Mike. I'd like to build on the INO-3107 data Mike shared by reviewing why our work on RRP is so important, what the market looks like, why INO-3107 could be the product of choice for patients and providers, and what we're doing to prepare for potential commercialization. For those new to our work, RRP is a rare HPV-related disease that affects around 14,000 people in the U.S. It's characterized by wart-like growths called papilloma that grow in the respiratory tract and can cause difficulty speaking, swallowing, and breathing, and repeated surgery is the standard of care today. Every one of these surgeries matters to patients because every surgery poses a risk of irreversible damage to the vocal cords and carries costs, including the financial expense, but more importantly, the significant time and stress of preparing for and recovering from each surgery.

Patients and their providers want a non-surgical option for RRP that addresses the underlying disease and that ultimately helps them avoid additional surgeries. We designed 3107 with the patient experience in mind, and we believe it has the potential to become the preferred treatment option for RRP based on the efficacy and tolerability results we've observed to date, as well as the simple patient-centric treatment regimen. As Mike discussed, not only did we observe favorable efficacy results in patients treated with INO-3107, we saw continued improvement into the second 12-month period, or year two, for both complete and overall response rates. INO-3107 was well tolerated in the trial, and there were no discontinuations. Finally, INO-3107 offers a simple patient-centric treatment regimen that does not require additional, potentially unnecessary scoping and procedures during the treatment window.

Finally, INO-3107 offers office-based administration without the need for referral, a preference that many physicians shared with us in market research. We have shared a few other insights on this slide from that research, reinforcing our belief in the strength of INO-3107's product profile. One laryngologist told us the complete response rate of 50% is good, but a 50%-100% reduction in surgeries in eight out of 10 patients is the most compelling. When laryngologists review our data, they quickly move to think about how they would describe the product to their patients, and they indicate they like being able to say the vast majority of patients see significant benefit from treatment. Likewise, both the tolerability profile and simple patient-focused treatment regimen were very well received by laryngologists who are currently treating RRP patients. Moving on, I would like to share just a few updates on our commercial launch preparations.

Since last quarter, we've made significant progress, including developing our distribution channel strategy and identifying channel partners, developing our initial pricing strategy, and completing targeting, segmentation, and product positioning work to establish positive differentiation. We're currently developing our go-to-market model and planning a further build-out of the commercial organization. Given the RRP market is highly concentrated, with the majority of RRP patients treated by relatively few laryngologists, we believe we will need a small and efficient field force footprint. There's still a lot of work ahead, but I'm energized by what we've built so far and look forward to providing an update on our progress next quarter. With that, I will turn it back to Jacquie.

Jacqueline Shea (President and CEO)

Thanks, Steve. While INO-3107 is at the forefront of our work, we are excited about the opportunities to leverage the strengths of our platform across the pipeline, including what we see as the next generation of DNA medicine technology. Harnessing the power of in vivo protein production and enabling the body to generate its own disease-fighting tools is a key strength of our DNA medicine platform, and our DMAb technology leverages that strength in a novel way. Using our proprietary gene sequence optimization technology, we can create precisely designed DNA plasmids that encode for specific monoclonal antibodies. These plasmids, or circular DNA, can then be delivered directly into muscle cells in the arm using our CELLECTRA delivery system.

The heavy and light chain proteins that make up the DMAbs are produced and then assembled into functional antibodies within the muscle cells and are then secreted into the blood where they can circulate within the body. This contrasts with conventional monoclonal antibodies, which are manufactured in in vitro systems and then need to be administered through regular infusion or injection. We recently announced top-line interim clinical data from an ongoing P proof of concept trial evaluating DMAbs for COVID-19. Led by the Wistar Institute in collaboration with AstraZeneca, the University of Pennsylvania, and INOVIO, and funded by DARPA and JPO, this trial has provided the first clinical proof of concept that DMAbs can be durably and simultaneously produced inside the human body. Specifically, we saw long-lasting in vivo antibody production, with DMAb levels remaining stable for 72 weeks in all participants who have reached that time point.

No antidrug antibodies or immune rejection of the DMAbs was detected across approximately 1,000 blood samples, unlike other gene-based antibody delivery approaches. Treatment was well tolerated, with the most common side effects being mild temporary injection site reactions such as pain and redness, and no serious adverse events related to study drug. We saw that the expressed DMAbs successfully bound the SARS-CoV-2 spike protein receptor binding domain, confirming functional activity through week 72. I also just want to point out that the panel on the right-hand side of the slide shows the representative data from one dose-level cohort from the trial. The consortium plans to present this important clinical data in the first half of the year at various scientific conferences and has submitted a manuscript to a leading peer-reviewed journal, which is currently available in preprint on Research Square.

We believe this technology could have the potential to be a breakthrough that could overcome many of the challenges seen with traditional monoclonal antibody production. With rapid manufacturing, low cost of production, temperature-stable storage and distribution, and the ability to redose, DMAb technology could help expand use, reduce costs, and enable access in low-resource settings. Importantly, unlike other delivery platforms, our DNA-based approach has demonstrated sustained antibody production without generating antidrug antibodies, making it a potentially promising long-term solution for conditions requiring continuous therapeutic protein delivery. We see broad potential for this technology, and we and our partners at Wistar have been investigating the feasibility of DMAbs across multiple disease targets, mostly in a preclinical setting, from flu to HIV to cancers and to the most recent clinical trial targeting COVID-19.

I believe this is an excellent example of how we have been able to work through partnerships with non-dilutive funding to advance our DNA medicines platform. We look forward to continuing working with our partners to complete the current Phase I trial and on future research, where we plan to explore a number of these broader applications of our technology for long-term therapeutic protein delivery. Moving on to the rest of our pipeline, you'll see here that we have two other novel technologies in the preclinical stage. DNA-launched nanoparticles, or dLNP candidates, addressing infectious diseases. Following on from my comments on DMAbs, DNA-encoded protein replacement candidates, or dProts, addressing various disease targets where disease is caused by missing or defective proteins. These fall into that next-generation category of our technology, and we're very excited about what the future holds for these novel approaches.

With regards to our later-stage pipeline, we're leveraging the opportunity to build on our extensive experience in HPV-related diseases and advancing plans for a Phase III trial to evaluate INO-3112 in combination with the FDA-approved PD-1 inhibitor, LOQTORZI, as a treatment for locally originally advanced, high-risk HPV 16 and 18 positive throat cancer. With the trial planned across both North America and Europe, we've discussed the trial design with FDA and most recently received some initial feedback from the European regulators on the trial design. We believe our current design will be sufficient to address those comments, and our next steps include finalizing the trial protocol and completing manufacture of the candidate. We're also advancing discussions on the design for a Phase II trial of INO-5401 in newly diagnosed glioblastoma, and we look forward to advancing this and other promising candidates through collaborations and other potential strategic opportunities.

I will now turn it over to our Chief Financial Officer, Peter Kies, for a financial update. Peter?

Peter Kies (CFO)

Thanks, Jacquie. Today, I'd like to provide an overview of INOVIO's financial results for the fourth quarter and full year of 2024. As Jacquie noted at the start of our call, our primary goal is advancing INO-3107, being ready to begin the submission of our BLA in mid-2025, and ensuring that we have the resources to support this critical work. To that effect, we raised more than $72 million in gross proceeds from two equity offerings in April and December of 2024, and from equity sales from our ATM. We also continue to decrease operational spending, with our total operating expenses dropping from $27.5 million in the fourth quarter of 2023 to $20.5 million in the fourth quarter of 2024. Our full-year operational expenses decreased 22% from $144.8 million in 2023 to $112.6 million in 2024.

INOVIO's net loss for the fourth quarter of 2024 was $19.4 million, or $0.65 per share basic and dilutive, and our total net loss for the full year of 2024 was $107.3 million, or $3.95 per share basic and dilutive. We finished the fourth quarter of 2024 with $94.1 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 the first quarter of 2026. This projection includes an operational net cash burn estimate of approximately $27 million for the first quarter of 2025. Historically, our first quarter operational net cash burn runs higher than other quarters. These cash projections, this cash runway projections, do not include any further capital raise activity that INOVIO may undertake.

As a result, you can find our full financial statements in this afternoon's press release, as well as in our Form 10-K filed with the SEC. With that, I'll turn it back over to Jacquie.

Jacqueline Shea (President and CEO)

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

Operator (participant)

Thank you. Ladies and gentlemen, we will now begin the question and answer session. Should you have a question, please press star followed by the one on your telephone keypad. Should you wish to cancel your request, please press star followed by the two. If you are using a speakerphone, please lift the handset before pressing any keys. One moment, please, for your first question. Thank you. Your first question comes from the line of Roy Buchanan from Citizens. Please go ahead.

Roy Buchanan (Analyst)

Hey, thanks for taking the question. Glad to hear you're on track with INO-3107. I had some, I guess, some details. Let's start with INO-3107. The BLA submission request, do you need to meet with the FDA, or do you just request that in writing? If you need to meet, have you requested that meeting?

Jacqueline Shea (President and CEO)

Yeah, good question, Roy. Mike, do you want to take that?

Mike Sumner (CMO)

Yeah, happily. We actually held a pre-BLA meeting with the FDA prior to the single-use array breakage that we found and have now resolved. At that time, we actually had very good alignment with all the remaining modules. As soon as we complete the device modules, our BLA will be complete. As we talked about today, we plan to hopefully start rolling submission in the middle of this year as all the other remaining modules are complete.

Roy Buchanan (Analyst)

Okay.

Jacqueline Shea (President and CEO)

Mike, that's just a request. Yeah, we don't need to have another meeting.

Mike Sumner (CMO)

No, no more meeting, but we do need to request the rolling submission.

Roy Buchanan (Analyst)

Yeah, got it. Okay. For the stability test, is that, maybe you said, sorry, I missed it, is that a single test, or do you need to repeat a whole battery of tests? Are you doing that yourself, or is it a third party who conducts the test?

Jacqueline Shea (President and CEO)

Yeah, that's a great question, Roy. We need to repeat a number of the tests required for device verification or DV testing, where we're testing the array in combination with the handset. We need to repeat a number of those different tests. We use an external testing house to do that. We previously worked extensively with this testing house. They're great partners, but we do need to do that externally. There's also some external certification that's required as part of this process that goes into our BLA as well. Mike, anything to add there?

Mike Sumner (CMO)

No, I think you've covered all the major points.

Roy Buchanan (Analyst)

Okay, great. Maybe on the DMAb, I thought the data in the publication is pretty compelling, clearly differentiated from mRNA, even self-amplifying RNAs in terms of durability. I did not see anything in the publication about half-life. Seems like it is clearly longer than even the extended half-life antibodies that you are expressing. Do you have any sense of what the half-life from the DNA constructs themselves might be in people?

Jacqueline Shea (President and CEO)

Yeah, I'm not sure if we've released all of that data yet, Roy, as part of the publication. What we do have in the publication are some details of some modifications we've made for these particular monoclonals to extend half-life. Happy to follow up with you after the call on the specific details of those.

Roy Buchanan (Analyst)

Okay, great. Jacquie, I know you mentioned some other wide range of potential applications for the technology, and the publication mentions GLP-1, for example. Do you have anything you can disclose today about potential programs over the next 24 months or so? Thanks.

Jacqueline Shea (President and CEO)

Yeah, I think first of all, I would say we were really excited to see that the level of functional antibody production that we saw over such a long time period and the fact that we did not see any antidrug antibodies at all coming up. We were really excited about that. On today's call, we shared with you a broad range of other targets that we previously worked on and are working on, and we hope to provide further updates on those targets in due course. We are really excited by the power of this technology, and the level that we are producing these antibodies at at the moment is biologically relevant and spans the levels needed for a wide range of targets. We are really excited by this.

Roy Buchanan (Analyst)

Yep. Okay, sounds good. Thank you.

Jacqueline Shea (President and CEO)

Thanks, Roy.

Operator (participant)

Thank you. Your next question comes from the line of Jay Olson from Oppenheimer. Please go ahead.

Jay Olson (Analyst)

Oh, hey, congrats on resolving the manufacturing issues with the CELLECTRA device, and thank you for providing this update. We had a question about the timeline for testing and validation of the new manufacturing process and how long it takes for validation before including the new manufacturing information in your filing package.

Jacqueline Shea (President and CEO)

Yeah, sure, Jay. First of all, I'm just really thrilled and delighted that we fixed the snap frame part, the single-use array component of the device that broke. The process did take a little longer than we initially expected, as we needed to make some design changes to the part, which also required us to improve the actual molding process. Now that we've got this behind us, we've started manufacturing the new arrays, and we plan to start device verification testing very soon. We anticipate we're going to complete all of that in the first half of this year. As Mike said earlier on in the call, once this process is near completion, we'll reach out to the FDA and request rolling submission of the BLA since we have all of the other modules completed and ready for submission.

Once that's granted, we expect to begin submitting the modules in mid-year and anticipate being able to complete the submission three to four months later, with the expectation that FDA will accept our full BLA for review prior to the end of the year.

Jay Olson (Analyst)

Okay, great. Thank you so much for that detailed explanation. Maybe just one follow-up question. Do you need to initiate the confirmatory study before the BLA submission?

Jacqueline Shea (President and CEO)

We do need to initiate the confirmatory trial before the BLA submission, but we've made really good progress in terms of doing that. Mike, do you want to jump in here?

Mike Sumner (CMO)

Yeah, absolutely. I mean, we've previously talked that we have identified the majority of the sites. We've actually advanced contracts and actually have IRB approvals at several sites. The whole reason the FDA usually asks you to commence that trial is so that they can feel confident that you are going to meet the commitment to complete the study. We'll be very easily able to demonstrate to the FDA the seriousness we're approaching the study and the fact that we want to complete enrollment and the study as quickly as possible.

Jay Olson (Analyst)

Great. That's fantastic news. Thanks again for taking the questions, and congrats on all the progress.

Jacqueline Shea (President and CEO)

Thanks, Jay.

Operator (participant)

Thank you. Your next question comes from the line of Sudan Loganathan from Stephens. Please go ahead.

Sudan Loganathan (Managing Director)

Hi, good afternoon, and thank you for giving this update and congrats again on the great progress here with this CELLECTRA device and resolving those issues. My question is on that topic. Just curious to hear your take on, aside from the initiation of the confirmatory trial needed to submit for the BLA, is there anything else holding you back from just starting to submit the non-device component modules of the BLA now and starting the rolling process that way versus waiting a few more months to start submitting everything?

Jacqueline Shea (President and CEO)

Yeah, that's a really good question, Sudan. We have, as we said, we have all of the other modules ready to go. FDA normally, once you've started rolling submission, FDA normally likes you to submit all of your modules in a three to four-month time frame. It is a discussion that we can have with the FDA as to when we can start rolling submission. I think the important thing is that we start our DV testing, have made good progress on the DV testing before we set that end timeline for when we're going to deliver all of the modules to the BLA. I think the guidance that we're providing at the moment is that we're going to start rolling submission mid-year, and we expect to complete that within three to four months.

Obviously, we're going to try and accelerate things as much as possible. Every day matters to our occupations, and we're very conscious of that.

Steven Egge (Chief Commercial Officer)

Got it. No, thank you for that. Just to hopefully jog my memory better, was the DV testing where the initial breakage of the CELLECTRA device component was discovered previously, or did you get to the DV testing point last time before?

Jacqueline Shea (President and CEO)

Yeah, I mean, last time we were pretty far through our DV testing when I believe we identified the issue with the single-use array. Mike, do you want to add any detail there?

Mike Sumner (CMO)

Yeah. I mean, we identified the issue following the age conditioning. We have actually, as part of the progress that we made and how we developed this, already aged some of the arrays in a similar manner and actually performed the testing. We really are confident that we've resolved the issue. We do, however, have to actually repeat the formal aging and the formal testing once we have actually signed off the fix, which we have done, and we've started manufacturing those sort of commercial-grade arrays. We do not expect to see any issues going forward with the array.

Sudan Loganathan (Managing Director)

Got it. Thank you. Just really quick, one last one. Just given the context for the RRP patients, often require multiple surgeries per year, and the substantial healthcare costs and risks associated with that, as you know. Has there been any health economist or payer research conducted yet on the potential pricing or the advantages of therapeutics such as INO-3107 that would in savings for the healthcare providers or the healthcare facilities and the system in general? Is that something that could come maybe after approval once we kind of get a better idea of pricing? Just kind of curious if anything has been done on your end on that.

Jacqueline Shea (President and CEO)

Yeah. Steve, do you want to take that one?

Steven Egge (Chief Commercial Officer)

Yeah, sure. Thanks for the question. We've done a fair amount of research with payers where we reviewed the product profile, reviewed budget impact models, and talked to them about kind of price ranges. This is rare disease. We do expect rare disease pricing. What we've shared is that could be a pretty big range, anywhere from $200,000-$2 million a year. One analogy that we look at that's pretty close, like we've referenced it before, the OGSIVEO from SpringWorks Therapeutics. It's a product for desmoid tumors, kind of the first medical therapy. The standard of care kind of prior to that launching was repeated surgeries. They're in the price range of $360,000 per year. That's kind of a price that we've referenced.

The feedback that we've gotten from payers is that that kind of rare disease pricing range is very acceptable to them. We don't expect any issues kind of with rare disease pricing, if that helps.

Sudan Loganathan (Managing Director)

Yeah, that's great. Thank you again for all the answers here, and congrats again on all the progress, and looking forward to the progress going forward.

Jacqueline Shea (President and CEO)

Thank you.

Operator (participant)

Thank you. Your next question comes from the line of Yi Chen from H.C. Wainwright. Please go ahead.

Yi Chen (Managing Director and Senior Healthcare Analyst)

Hi, thank you for taking my question. Regarding the utility of the DMAb technology, particularly in terms of the Phase I proof of concept trial evaluating DMAb targeting COVID-19, could you tell us how durable is the in vivo antibody production? In future clinical trials, in case the produced antibody has some undesirable effects, is there a way that you can turn off the antibody production? Thank you.

Jacqueline Shea (President and CEO)

Yeah. Hi, Yi. Those are both great questions. In terms of how durable the antibody production is, I mean, as I think you saw on the slide we presented, and if you take a look at the preprint as well, we're now out to 72 weeks, and we're not seeing any drop in terms of the levels that we're seeing secreted into the serum. Our production seems to be holding up over 72 weeks. We think that's really excellent durability. In terms of future clinical trials, I mean, we're excited by what this technology could mean across a wide range of targets. There are either inducible or repressible promoters that you could use to turn off the genes or turn on the genes to be able to control expression.

I think initially we'll be focused on targets that are already in the right therapeutic range and where there's less concern about potentially turning off those antibodies. I think those will be the targets that we focus on initially.

Yi Chen (Managing Director and Senior Healthcare Analyst)

In terms of the location of the antibody production, is it primarily produced in certain parts of the body, or it's produced throughout the body?

Jacqueline Shea (President and CEO)

Yeah. Again, great question. We're administering our DMAbs into the deltoid muscle in the arm. The DMAbs are actually produced within the myocytes, within the muscle cells. They're produced as heavy and light chain proteins, which then self-assemble and are secreted into the bloodstream from the myocytes. It's actually production in these muscle cells, which are pretty long-lived cells, the myocytes.

Yi Chen (Managing Director and Senior Healthcare Analyst)

Okay. Got it. Thank you.

Operator (participant)

Thank you. Your next question comes from the line of Gregory Renza from RBC Capital Markets. Please go ahead.

Anish Nikhanj (Analyst)

Hi guys. It's Anish Nikhanj for Greg. Congrats on the progress this quarter, and thanks for taking our questions. Just a couple from us. As you think about taking INO-3107 commercial in the future, potentially, what are your going assumptions for labeling, and what particular points would you like to see that could play to the strengths of your program, both on its own merits and even over competitors? Thanks so much.

Jacqueline Shea (President and CEO)

Yeah. Great question, Anish. I mean, first and foremost, I think we're really confident in the very strong product profile that we're seeing with INO-3107. We've observed great and durable efficacy. The treatment's been very tolerable. Then we've designed really INO-3107 with the patient in mind. We have a very patient-centric treatment regimen. We don't require any scoping or any surgery during the dosing window. We're able to administer the treatment in the doctor's office, so there's no need for them to go to, for instance, an infusion center to receive the product. We think that product profile is really, really compelling. I think obviously we're still very close to filing our BLA, and I think we can't really comment at the moment about the potential label implications.

I think the data that we've generated in this patient population who previously had two or more surgeries is really compelling. Mike, anything you want to add there?

Mike Sumner (CMO)

Yeah. I mean, when you have these discussions with the agency, your label is always a negotiation. Ultimately, it is about sharing the risk-benefit ratio for the physician and for the patient. I think as you heard today, I mean, we're able to now really demonstrate the durable clinical effect of INO-3107. I would hope we'll be able to discuss that with the agency and get that taken into account because RRP is not a disease that's defined by a 12-month period. It's a chronic viral infection, and these patients have multiple surgeries. I think it'll be an interesting discussion that we'll have with the agency in the future.

Anish Nikhanj (Analyst)

Great. Thank you so much.

Operator (participant)

Thank you. Your next question comes from the line of Roger Song from Jefferies. Please go ahead.

Liang Cheng (Analyst)

Hey, team. Thank you for taking our questions. This is Liang Cheng for Roger. Just two questions from us regarding RRP and the INO-3107. First one, really great to see the durability data of the INO-3107 up to two years, three years. Just wondering, how should we think about the re-dosing commercially if you think about the durability and increased response there? Second, as we think about the treatment of RRP disease, how should we think about in the longer term the epidemiology and addressable market there? Thank you.

Jacqueline Shea (President and CEO)

Thanks. I caught your first question about the re-dosing strategy. I'm sorry, I didn't quite catch your second question. Could you repeat that?

Liang Cheng (Analyst)

Yes. As we now have those INO-3107 and those new treatments for RRP, do we expect lower epidemiology, decreasing epidemiology over time, and how should we think about the addressable market there?

Jacqueline Shea (President and CEO)

Yeah. Great question. Okay. Mike, do you want to take the re-dosing, and then I'll take the epi question?

Mike Sumner (CMO)

Yeah, absolutely. I mean, as we said in today's call, we're actually still deciding on the re-dosing strategy. I think as we looked to our sort of excellent efficacy, it did make us think about how we could design the clinical trial to get a future labeling change. I think we're also sort of in the position now that we started off this process looking at it very much from a sort of regulatory lens of complete remission, partial remission, etc. Really, that isn't how the physicians look at this. They look at this at a totality of the surgeries that these patients have. We want to, as we think about this strategy, see how we can reduce the surgeries to hopefully zero and how we can maintain that excellent clinical response that we've seen.

I mean, hopefully, we'll have some more details in upcoming calls. At the moment, we really are still thinking about how best to accomplish the goals, knowing exactly what our platform is capable of doing with the re-dosing and being able to boost that CD8 response that we've seen with AMD3100 in the past.

Jacqueline Shea (President and CEO)

Yeah. I think that's a really excellent point. With our DNA Medicines platform, we're able to re-dose from a previous product, VGX-3100. We've shown that we can boost the existing T-cell responses by going in with a single dose later. We're really confident that we can continue to maintain the immune response that's associated with clinical benefits, potentially augment the immune response. We're very excited by what that means for potential long-term treatment for RRP. As Mike said, this is a chronic, often lifelong disease. Being able to provide durable clinical benefits is really incredibly important. In terms of the epidemiology, what we're seeing is in most developed countries where the vaccination rates are around sort of 50% or 60%, we're still seeing large numbers of RRP cases in adults, which don't seem to be affected by the vaccination rates yet.

The level of cases in adults seems to be holding pretty steady. If you think about the epidemiology of RRP, you see a peak of disease cases around age five to seven, another peak in the age sort of 30 group, and then another peak in the late 50s, early 60s. Currently, in the U.S., for instance, vaccination for HPV is only around 50% in males, a low 60% in females. A large proportion of the adult population, I think it's been estimated at around 70%, is not protected against HPV 6 and 11. It's also not entirely clear how long the vaccine protective effects remain as well. Unfortunately, I think it looks as though RRP is going to be with us for several generations to come.

Where we are seeing a decrease in the number of patients and the impact of vaccination is in pediatric RRP, where the number of pediatric cases are declining. We are not seeing any impact on cases in the adult population. In fact, we think this is actually an underdiagnosed disease in the adult population.

Liang Cheng (Analyst)

Got it. Very helpful. Thank you, Jacquie and Mike.

Jacqueline Shea (President and CEO)

Thank you.

Operator (participant)

Thank you. Thank you. There are no further questions at this time. I will now hand the call back to Ms. Jacqueline Shea for any closing remarks.

Jacqueline Shea (President and CEO)

Thank you. As we've outlined here today, we are moving into 2025 with very focused strategic priorities. First and foremost is completing the next steps necessary for submitting our BLA for INO-3107. At the same time, we'll be continuing to advance our commercial readiness plan so we can hit the ground running and use our compelling product profile to its full advantage. Finally, we'll continue driving progress across our pipeline, advancing promising programs like INO-3112 and leveraging potential partnership opportunities. This includes building on the breakthrough potential of our DMAb program and other next-gen DNA medicine technologies. I'll close today by noting that the inspiration for all of this work continues to be the patients around the world who could benefit from the power and potential of DNA medicine. For those suffering from RRP in particular, we are strongly motivated by the understanding that every day and every surgery matters.

Thank you for your attention, and good evening, everyone.

Operator (participant)

Thank you. That concludes our conference for today. Thank you all for participating. You may now disconnect.