Q4 2024 Inovio Pharmaceuticals Inc Earnings Call

Operator: 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.

Good afternoon, ladies and gentlemen, and welcome to the <unk> Pharmaceuticals first quarter 2020 for 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 you flip it at times. During this call you require immediate assistance. Please press star zero for the offer.

Operator: This call is being recorded on Tuesday, March 18, 2025.

This call is being recorded and Justine much each in 2025 and I would now like to turn the conference over to MS. Jenny Wilson. Thank you. Please go ahead.

Operator: And I would now like to turn the conference over to Ms. Jenny Wilson. Thank you. Please go ahead.

Jenny Wilson: Good afternoon and thank you for joining the Inovio fourth quarter 2024 financial results conference. Thank you for joining me on today's call.

Speaker Change: Good afternoon, and thank you for joining via Nobel fourth quarter 2024 financial results Conference call.

Joining me on today's call.

Jenny Wilson: It will be Dr. Jackie Shea, President and Chief Executive Officer, Dr. Mike Sumner, Chief Medical Officer, Peter Kies, Chief Financial Officer, and Steve Egge, Chief Commercial Officer.

Jackie Shea: It will be Jackie Dr. Jackie Shea, President and Chief Executive Officer, Dr. Mike Submerge Heath Medical Officer, Peter Keyes, Chief Financial Officer, and Steve <unk>, Chief Commercial officer.

Jenny Wilson: Today's call will review our corporate and financial information for the quarter and year ended December 31st, 2024, as well as provide a general business update. Following prepared remarks, we will conduct a question and answer session. 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.

Jackie Shea: Todays call well review, our corporate and financial information for the quarter and year ended December 31, 2024, as well, let's provide a general business update following prepared remarks, we will conduct a question and answer segment.

Jackie Shea: 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 and nobody is DNA medicines platform, which include clinical and regulatory developments and timing of clinical data Readouts and planned regulatory submission along with capital resources and strategic matters.

Jackie Shea: 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.

Jenny Wilson: Actual events or results could differ materially.

Jenny Wilson: 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.

Speaker Change: The statements made within this afternoon's press release this call is being webcast live and a link can be found on our website IR <unk> com and a replay will be made available. Shortly after this call has concluded I will now turn the call over to <unk>, President and CEO, Dr. Jackie Shay.

Jenny Wilson: 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.

Jacqueline Shea: I will now turn the call over to Inovio's President and CEO, Dr. Jackie Shephard. 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 medicine 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 INO3107, our lead candidate for recurrent respiratory papillomasosis. 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.

Jackie Shea: Good afternoon, and thank you to everyone for joining today's call.

Jackie Shea: After significant progress in 2024, we remain focused on transforming and Nokia.

Jackie Shea: <unk> stage company.

Jackie Shea: It brings on the permanent CMA medicines for patients and shareholders alike.

Jackie Shea: To achieve that goal this.

Jackie Shea: This year will be driven by three main strategic priorities.

Jackie Shea: Messing up your leg, Brian do you want a seven our lead candidate for recurrent respiratory papillomatosis.

Jackie Shea: Advancing our commercial plan and preparing for a full and efficient launch.

Jackie Shea: Leveraging the strengths of the bolt platform to drive quick rest of Copa diversified pipeline.

Jacqueline Shea: Advancing 3107 is our primary focus, and I am very pleased to report that we have resolved the previously announced manufacturing issues involving the single-use array component of this lecture device. Our next step is to perform the FDA-required spike verification testing, known as db testing, for the combined handsets and single-use array required for our IMD 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 filings before the end of the year.

Jackie Shea: Advancing 30 more than 70 as our primary focus.

Jackie Shea: And I am very pleased to report that we have resolved the previously announced manufacturing issue involving the single use the rate component of the selected device.

Jackie Shea: Our next step is to perform the FDA required spikes verification testing.

Jackie Shea: Testing for the combined.

Speaker Change: I think we used the rate required for BLA submission.

We now plan to begin submitting a BLA <unk> rolling submission process.

Speaker Change: Well, it's commencing a confirmatory trial and requesting priority review in mid 2025.

Speaker Change: With this timeline, we anticipate being able to complete rolling submission in the second half with the year to enable the FDA to accept BLA filing before the end of the year.

Jacqueline Shea: 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 2 and Year 3 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 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.

Speaker Change: Most importantly, we remain confident that if approved <unk> could be the preferred non surgical treatment RFP for both patients and physicians.

Speaker Change: Our position is strengthened by the year, two and year three clinical data.

Speaker Change: In December.

Speaker Change: On the detailed immunology data we published in February.

Speaker Change: Mike will provide more detail later in the call, but so not retrospective trial of 31, seven patient showed continued improvements and reduction surgery Alky, Iran with 50% meeting criteria for complete response, and the second 12 month period or two meaning they would surgery.

Speaker Change: Great.

Speaker Change: Overall, the main number of surgeries across the patient population continues to decrease in tier three.

Jacqueline Shea: The ongoing efficacy was observed. The research observed is also supported by the immunology data published in Nature Communications, demonstrating the ability of 3107 to drive an antiviral immune response in airway tissue, so 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 shows that the administration of 3107 was well-tolerated. In summary, 3107 offers significant and durable clinical benefits, tolerability, and a simple patient-centric dosing regimen that does not require scoping or surgery during the dosing window.

Speaker Change: The ongoing efficacy was observed.

Speaker Change: It's also supported by the immunology data published in nature communications, demonstrating the ability of 37 to drive an antiviral immune response and highway tissue.

Speaker Change: Correlated with a reduce or eliminate the need for surgery.

Speaker Change: We also published the full safety and efficacy data set but the completed phase one two trial, which showed that kidman illustration of 31 seven was well tolerated.

In summary third.

Speaker Change: If you wanted to seven significant and durable clinical benefits tolerable.

Speaker Change: Colorability simple.

Speaker Change: Simple patient centric.

Speaker Change: Enrichment that does not require open heart surgery during the dosing window.

Jacqueline Shea: all of which we believe could be compelling advantages once on the market.

Speaker Change: All of which we believe could be compelling advanced chip.

Speaker Change: The markets.

Jacqueline Shea: While our immediate focus is on advancing 3107, I'm also pleased to provide an important update from our work on next-generation DNA medicine. Together with our partners, we recently announced top-line interim results from an ongoing Phase 1 trial with our DNA-encoded monoclonal antibody technology, which we call DMACC. This proof-of-concept trial involved two D-mabs 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 treatment for a broad range of diseases by enabling long-term in vivo production of therapeutic antibodies or other proteins.

Speaker Change: While our immediate focus is on advancing 30 wanted seven I'm also pleased to provide an important update from our work on next generation DNA medicines.

Speaker Change: Together with our partners, we recently announced top line interim results from an ongoing phase one trial without the United coated monoclonal antibody technology, which we call demos.

Speaker Change: This proof of concept trial and both <unk>.

Speaker Change: And showed that they can be durably and simultaneously producing human opponent.

Speaker Change: Pre relevant levels.

Speaker Change: We believe this technology.

Speaker Change: Has the potential to overcome some of the biggest challenges with traditional recombinant monoclonal antibodies.

Speaker Change: And could also transform treatment for broad range of diseases by enabling long term in vivo production of therapeutic antibodies or other proteins.

Michael Sumner: Now I'll turn it over to Mike for some additional insights on our progress and new data on 3107. Mike?

Mike: Now I'll turn it over to Mike for some additional insights on our progress our new data from 31 seven.

Speaker Change: Mike.

Michael Sumner: Thank you, Jackie. As Jackie 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. And after extensive testing and internal quality sign-off, we have resolved the previously announced manufacturing issue involving the single-use array component of the selector 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.

Mike: Thank you Jackie as Jackie mentioned, we have made tremendous progress towards our primary goal submitting a BLA for <unk> 107.

Mike: We have now completed the drafting of all non device modules, including non clinical clinical and CMC modules.

Mike: After extensive testing and internal quality sign off we have resolved the previously announced manufacturing issue involving the single use array component of the select your device.

Mike: To resolve the issue and device to strengthen key components would you stress on breakage areas and refine the production process. So the plastic molding part of the array.

Mike: We have tested the new array under similar testing to 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.

Michael Sumner: 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 submission. In addition, the full Phase I-II clinical data and accompanying detailed immunology data were recently published in Nature Communications. These data further support the T cell mechanism of action for 3107, which underpins the efficacy results we've seen. We also announced some very exciting clinical durability data, showing that patients treated with 3107 continue to show further reduction in the need for surgery to manage their disease in the second and third year.

Mike: We began manufacturing our new commercial grade raise which will now be utilized in the design verification testing.

Mike: So we can move forward to completing our R&D and BLA submissions.

Mike: In addition, the full phase one two clinical data and accompanying detailed immunology data were recently published in nature Communications.

Mike: These data further support the T cell mechanism of action for $31, seven which underpins the efficacy results we've seen.

Mike: We also announced some very exciting clinical durability data showing that patients treated with $31 seven continue to show further reduction in the need for surgery to manage their disease in the second and third year.

Michael Sumner: 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 3 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.

Mike: This data will be the subject of an oral presentation at the combined otolaryngology spring meeting to be held in New Orleans. This may.

Mike: One of the most frequented meetings by our target physicians treating RFP.

Mike: We've also made important progress in preparing for our phase III confirmatory trial.

Mike: As a reminder, this will be a randomized placebo controlled trial enrolling patients with two or more surgeries in the prior year.

Mike: Inducted at approximately 20 sites at major U S medical centers.

Mike: This progress to date will enable us to enroll in the timely manner following submission of our updated R&D.

Michael Sumner: I'd like to spend some time now discussing the new data as it paints a compelling product profile that strengthens our belief that 3107 could be the preferred product for RRP patients and their physicians. As a reminder, we completed a Phase 1-2 open-label trial of 3107 in patients who required at least two surgeries in the previous year for the removal of HPV611-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.

Mike: I'd like to spend some time now discussing the new data as it paints a compelling product profile that strengthens our belief that 30 107 could be the preferred product for our LP patients and their physicians.

Mike: As a reminder, we completed our phase one two open label trial of 30 107 in patients who required at least two surgeries in the previous year for the removal of HPV, six and 11 related <unk>.

Mike: It is important to note that based on our understanding of the risk and cost to the patient of every single surgery.

Mike: Every surgery performed after days Aero was counted against the efficacy endpoint in that trial, where we followed the patients for 12 months.

Michael Sumner: We then conducted RRP002, 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 medium 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 continue 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.

Mike: We then conducted RFP zero zero to 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 two eight years.

Mike: <unk> is a chronic often lifelong disease and duration of efficacy is clearly important.

Mike: Before we dive into the 002 data looking at the longer term efficacy results, we observed in the trial.

Mike: We were very pleased to see that patients continue to show improvement into years, two and three following their initial dosing regimen. In fact, the complete response rate increased to 50%. So the second 12 month period when evaluated at the end of year two.

Michael Sumner: We also saw the overall response rate, that is, the number of patients that had 50 to 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.

Mike: We also saw the overall response rate that is the number of patients so that 50% to 100% fewer surgeries compared to their pretreatment baseline increased from 72% in the first 12 month treatment period or year, 1% to 86% for the second 12 month period or year two.

Mike: Sure.

Mike: 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 one surgeries per year prior to treatment to a mean of $1 seven surgeries at the end of year one.

Mike: And then reduce further by the end of year two to a mean of 0.9 surgeries.

Michael Sumner: Across the population of patients treated with 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 response. without having to worry about the impact of an anti-vector source. 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.

Mike: Across the population of patients treated with $31 seven.

Mike: This is a reduction of greater than 75% following the initial treatment regimen alone.

Mike: However, one of the core strengths of our DNA medicines platform is the ability to administer additional doses to continue to drive and amplifies strong T cell based immune responses without having to worry about the impact of an anti vector response.

Mike: 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.

Michael Sumner: 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 pre-dose 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.

Mike: It's 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.

Mike: We have published data from a similar DNA medicine targeted the Essex and <unk> seven antigens of HPV 16 and 18.

Mike: That demonstrated we were able to augment the CDA T cell responses with a single additional dose.

Mike: Given after completion of the primary treatment costs, when compared to pre dose levels.

Mike: This further increase in cytotoxic T cells supports the potential of extending the duration and improving upon the already excellent clinical response that we've seen to date.

Michael Sumner: Every surgery matters to patients and our vision for INO3107 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 3107 and how we believe treatment is providing the favorable efficacy results we observe. 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. And then we saw that these T-cells really got where they needed to go, traveling from the blood into the airway and papillomatician.

Mike: Every surgery matters to patients and our vision for INR 30, 107 is to further minimize or eliminate future surgeries for all our RP patients.

Mike: As I said earlier, the immunology data, we've recently published becomes important here as well.

Mike: It underpins the mechanisms of action of 30, 107, and how we believe treatment is providing the favorable efficacy results we observed.

Mike: First in our analysis, we found that all of the patients were generating the right kind of antiviral immune responses to fight HPV, specifically antigen specific cytotoxic T cells.

Mike: And then we saw that these T cells really got where they needed to go travelling from the blood into the airway and papilloma tissue.

Michael Sumner: 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. 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 wasn't as large and tended to decrease faster than in our responders.

Mike: 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 HBV infected cells.

Mike: I would also like to note the while other investigators have suggested the multiple factors such as high viral loads or neutrophil infiltration in the papilloma microenvironment can be barriers to immunotherapy treatment of RFP, we didn't see any such factors impacting the efficacy we observed in the <unk>.

Mike: Sean.

Mike: Well all patients with generating the right kind of immune response.

Mike: Non responders. This response wasn't as large intended to decrease faster turn in our responders.

Michael Sumner: 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 INO3107. showing that it is doing exactly what is needed to treat the underlying HPV infection that causes RRP.

Mike: Which again is why we believe continued treatment may improve clinical outcomes in these patients.

Mike: Overall, our immunology data provide a clear demonstration of the mechanism of action behind IL 30 107.

Mike: Showing that it is doing exactly what is needed to treat the underlying HBV infection that causes RFP.

Michael Sumner: To wrap up, I want to provide some additional detail on our next steps for 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.

Mike: To wrap up I want to provide some additional detail on our next steps for $31 seven.

Mike: 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 TV testing process, which.

Mike: Which we anticipate will be completed in the first half of this year.

Mike: This testing is required to update the R&D before we can dose patients in a confirmatory trial and is also part of the last remaining module of the BLA package, we need to complete.

Michael Sumner: 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 plan to request Rolling submission and priority review of our BLA and if FDA agrees, we will begin submitting modules in mid 2025.

Mike: And complete the full submission three to four months later with the goal of having the FTA, except a complete BLA for filing by the end of the year.

Mike: Once the entire BLA is submitted we plan to finalize our long term dosing studies strategy and submit our proposed protocol to the FDA to support a supplemental BLA in the future.

Steve Egge: 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 US-based National HPV Conference, the European ALS Congress, and COSM, among others listed on the slide.

Mike: We also look forward to commencing on boarding 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 AOS Congress and Carlson among others listed on this slide.

Steve Egge: With that, I will now turn it over to our Chief Commercial Officer, Steve Egge, for an update on our commercial efforts. Steve. Thanks, Mike.

Mike: With that I will now hand over to our Chief commercial officer, Steve <unk> for an update on our commercial efforts Steve.

Steve: Thanks, Mike I'd like to build on the 30 107 data Mike shared by reviewing wire work on our RP is so important.

Steve Egge: I'd like to build on the 3107 data Mike shared by reviewing why our work on RRP is so important, what the market looks like, why 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. 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.

Steve: What the market looks like why 30 107 could be the product of choice for patients and providers and what we're doing to prepare for potential commercialization.

Steve: For those new to our work our RP is a rare HPV related disease that affects around 14000 people in the U S. It's characterized by worked like growth called papilloma the grow in the respiratory tract and can cause difficulty speaking.

Steve: Boeing and breathing and repeated surgery as the standard of care today.

Steve: Every one of these surgeries matters to patients.

Steve: Because every surgery poses a risk of irreversible damage to the vocal cords and carrier costs, including the financial expense, but more importantly, the significant time and stressed with preparing for and recovering from each surgery.

Steve Egge: Patients and their providers want a non-surgical option for RRP that addresses the underlying disease and that ultimately helps them avoid additional. 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 3107s, we saw continued improvement into the second 12-month period, or year two, for both complete and overall responses. 3107 was well-tolerated in the trial, and there were no discontinuations.

Steve: <unk> and their providers when a non surgical option for RP that addresses the underlying disease and then ultimately helps them avoid additional surgeries.

Steve: We designed <unk> seven with the patient experience in mind, and we believe it has the potential to become the preferred treatment option for RFP based on the efficacy and Tolerability of results, we've observed to date as well as the simple patient centric treatment regimen.

Steve: As Mike discussed not only do we observe favorable efficacy results in patients treated with 31, 7%. We saw continued improvement into the second 12 months period or a year or two for both complete and overall response rate 30, 107 was well tolerated in the trial and there were no discontinuation and finally <unk>.

Steve Egge: And finally, 3107 offers a simple, patient-centric treatment regimen that does not require additional, potentially unnecessary scoping and procedures during the treatment window. And finally, 3107 offers office-based administration without the need for a referral, a preference that many physicians shared with us in market research. We've shared a few other insights on this slide from that research reinforcing our belief in the strength of 3107's product. One laryngologist told us the complete response rate of 50% is good, but a 50 to 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.

Steve: 107 offers a simple patient centric treatment regimen that does not require additional potentially unnecessary scoping.

Steve: And procedures during the treatment window.

Steve: And finally.

Steve: Turning 107 offers office based administration without the need for referral of preference that many physicians shared with us.

Steve: Research we've shared a few other insights on this slide from that research reinforcing our belief in the strength of $31 <unk> product profile one their oncologist told us the complete response rate of 50% is good but a 50% to 100% reduction in surgeries in eight out of 10 patients is the most compelling.

Steve: And I will just review our data they quickly moved 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.

Steve Egge: And they indicate they like being able to say the vast majority of patients see significant benefit from. Likewise, both the tolerability profile and simple patient-focused treatment regimen were very well received by laryngology.

Steve: A significant benefit from treatment.

Steve: Likewise, both the Tolerability profile and simple patient focused treatment regimen were very well received by Laryngologist.

Steve Egge: who are currently treating our.

Steve: We're currently treating our RP patients.

Steve Egge: Moving on, I'd like to share just a few updates on our commercial launch preparation. 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.

Steve: Moving on I'd like to share just a few updates on our commercial launch preparations.

Steve: Since last quarter, we've made significant progress, including developing our distribution channel strategy and identifying channel partners.

Steve: <unk>, our initial pricing strategy and completing targeting.

Steve: Segmentation and product positioning work to establish positive differentiation for.

Steve: We're currently developing our go to market model in planning a further buildout of the commercial organization.

Steve Egge: 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. 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.

Steve: Given the RFP market is highly concentrated with the majority of our RP patients treated by relatively few laryngologist. We believe we will need a small and efficient field force footprint.

Steve: 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 Jackie.

Jacqueline Shea: With that, I will turn it back to Jeff. Thanks, Steve. While 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 is the next generation of DNA medicine. Managing 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 DMAD 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.

Jackie: Thanks, Steve.

Speaker Change: <unk> is at the forefront of work we are excited about the opportunities to leverage the strength of our platform across the pipeline, including what we see as the next generation of <unk> technology.

Speaker Change: The other thing the power I think EBIT protein production in an amazing ability to generate earnings with these pricing tool is a key strength about DNA medicines platform and our bema technology leverage neutral.

Speaker Change: In the novel way.

Speaker Change: Using our proprietary gene sequence optimization technology.

We can create precisely defined DNA plasmid.

Speaker Change: For specific monoclonal antibodies.

Jacqueline Shea: These plasmids, also called the DNA, can then be delivered directly into muscle cells in the arm using our selection delivery system. The heavy and light chain proteins that make up the DMAPs 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 Phase 1 proof-of-concept trial evaluating DMAPs for COVID-19.

Speaker Change: These plasmids both cycles with DNA can then be delivered directly into muscle cells.

Speaker Change: Using our flex delivery system.

Speaker Change: The heavy and light chain proteins that make up the demos are produced and then some.

Speaker Change: Both into functional antibodies within the muscle cells.

Speaker Change: Secreted into the plus.

Speaker Change: Circulate within the body.

Speaker Change: This contrasts with conventional monoclonal antibodies, which are manufactured in in vitro system, and then need to be administered three regular infusion or injection.

Speaker Change: We recently announced.

Speaker Change: Top line interim clinical data from an ongoing phase one proof of concept trial evaluating theme ups the COVID-19.

Jacqueline Shea: 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 DMAPs 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 anti-drug antibodies or immune rejection of the DMAP was detected across approximately a thousand 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 drugs.

Speaker Change: Led by the Western Institute in collaboration with Astrazeneca, The University of Pennsylvania, and the Nokia and.

Speaker Change: Despite the current GPO.

Speaker Change: This trial has provided the first clinical proof of concept the team apps can be durably and simultaneously produced inside the human body.

Speaker Change: Specifically, we saw long lasting in vivo antibody production with demos levels remaining stable for 72 weeks and all participants who have reached that time point.

Speaker Change: No antidrug antibody for immune rejection of the team up with detected across approximately a thousand blood samples.

Speaker Change: Like other gene based antipathy delivery approaches.

Speaker Change: And treatment was well tolerated with the most common side effects being mode temporary injection site reactions such as payment method.

Speaker Change: Serious adverse events related to study drug.

Jacqueline Shea: And we saw that the Express DMAPs successfully balanced 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 its 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 pre-print on ResearchSquare. 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.

Speaker Change: And we saw that express <unk> success pretty balanced itself could be two spike protein receptor binding domain.

Speaker Change: Functional activity three week 72.

Speaker Change: I will take just one clean up the panel on the right hand side of the slide shows the represents with data from one dose level cohorts from the trial.

Speaker Change: The consortium presented its important clinical data in the first half of the year.

Barry: Barry assigned the conferences.

Barry: <unk> submitted a manuscript when leading peer review journal, which is currently available in pre prints on research Gwen.

Speaker Change: We believe this technology could have the potential to be a breakthrough that could have become many of the challenges seen with traditional monoclonal antibody production.

Jacqueline Shea: With rapid manufacturing, low cost of production, temperature-stable storage and distribution, and the ability to redose, DMAP 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 anti-drug 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 DMAPs 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.

Barry: With rapid manufacturing low cost production temperature stable storage and distribution.

Speaker Change: The ability to re dose.

Speaker Change: <unk> technology could help expand mute reduce costs and enable access in low resource settings.

Speaker Change: Importantly, unlike other delivery platforms.

Speaker Change: DNA based approach that has demonstrated sustained antibody production without generating antidrug antibody, making.

Speaker Change: Making it potentially promising long term solution for conditions, requiring continuous therapeutic proteins delivery.

Speaker Change: We see broad potential for this technology.

Speaker Change: In a partnership with Athena.

Speaker Change: Have been investigating the pizza delivery of FEMA.

Speaker Change: Multiples for these target mostly in our preclinical testing concludes the HIV AIDS the cancer and so the most recent clinical trial targeting COVID-19.

Jacqueline Shea: I believe this is an excellent example of how we've been able to work through partnerships with non-dilutive funding to advance our DNA medicine platform. We look forward to continuing working with our partners to complete the current Phase 1 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.

Nick: I believe this is Nick.

Nick: Excellent example of how we've been able to work through partnerships with non dilutive funding to advance our DNA medicines platform.

Nick: We look forward to continuing working with our partner to complete the current phase one trial and on future research, where we plan to explore a number of these broader application technology.

Nick: Long term therapeutic proteins delivery.

Jacqueline Shea: 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 nanoparticle, or CLMP, candidates addressing infectious diseases. And following on from my comments on DMAPs, DNA-encoded protein replacement candidates, or DPROPs, addressing various disease targets where disease is caused by missing or defective protein. These fall into that next-generation category of our technology, and we're very excited about what the future holds for these novel approaches.

Nick: Moving on to the rest of our pipeline you'll see here that we have to offer novel technologies as a preclinical stage.

Speaker Change: CNA launched nanoparticle OFC LNP candidates addressing infectious diseases.

Nick: Following on from my comment from Demob.

Nick: On a inherited pricing replacement candidate.

Nick: April addressing various disease target rare diseases caused by mid single digit types of proteins.

Nick: These fall into that next generation category about technology.

Nick: Very excited about what the future holds these novel approach.

Jacqueline Shea: 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 3 trial to evaluate INO3112 in combination with the FDA-approved CD1 inhibitor Loctorazine as a treatment for locoregionally advanced. I risk HPV 16 and 18 positive throat cancer. with a trial plan for 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 sign will be sufficient to address those comments and our next steps include finalizing the trial protocol and completing manufacture of the candidate.

Nick: 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 31 12.

Nick: Combination with the FDA approved PD, one inhibitor <unk> as a treatment for local reaching a pump.

Nick: High risk HPV 16, 18 positive cancer.

Nick: With the Toronto plans across both North America and Europe.

Nick: Please discuss the trial design with FDA and most recently received some initial feedback from the European regulators on the trial at the time.

Nick: We believe our current sign will be sufficient to address the comment.

Nick: Next steps include finalizing the trial protocol and completing manufacturer the candidate.

Jacqueline Shea: We're also advancing discussions on the design for a Phase II trial of INO5401, a newly diagnosed glioblastoma. And we look forward to advancing this and other promising candidates through collaboration and other potential strategic opportunities.

Nick: We're also Thompson discussion from the design for a phase III trial of INR 54 to one in newly diagnosed glioblastoma.

Nick: And we look forward to advancing fit and other promising candidates from collaborations and other potential strategic opportunities.

Peter Kies: I will now turn it over to our Chief Financial Officer, Peter Kies, for a financial update. Thanks, Jackie. Today, I'd like to provide an overview of Inovio's financial results for the fourth quarter and full year of 2024. As Jackie 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 the success of our company.

Speaker Change: I will now turn it over to our Chief Financial Officer, Peter Keith.

Peter Keith: Financial update Peter.

Nick: Peter.

Nick: Thanks, Jackie today I'd like to provide an overview of <unk> financial results for the fourth quarter and full year of 2024.

Nick: As Jack noted at the start of our call. Our primary goal is advancing I don't know 30 107.

Nick: Being ready to begin the submission of our BLA in mid 2025, and then certain.

Peter Kies: Thank you. 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 ATMs. 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 2025. 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.

Nick: That we have the resources to support this critical work.

Nick: To that effect, we raised more than $72 million in gross proceeds from two equity offerings in April and December of 2024.

Nick: From equity sales from our ATM.

Nick: We also continue to decrease operational spending with our total operating expenses dropping from 27 5 million in fourth quarter of 2000 $23 million to $25 million in the fourth quarter of 2025.

Our full year operational expenses decreased 22%.

Nick: From $144 8 million in 2023 to $112 6 million in 2024.

Nick: <unk> net loss for the fourth quarter of 2024 was $19 4 million or <unk> 65 per share basic and dilutive.

Peter Kies: and our total net loss for the full year of 2024 was $107.3 million or $3.95 per share of BASIC and DLUTO. 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.

Nick: And our total net loss for the full year of 2024 was $107 3 million or $3 95 per share basic and dilutive.

Nick: We finished the fourth quarter of 2024 with $94 1 million in cash cash equivalents and short term investments compared to $145 3 million.

Nick: As of December 31, 2023.

We estimate our cash runway takes us into the first quarter of 2026.

Nick: This projection includes an operational net cash burn estimate of approximately $27 million.

Nick: For the first quarter of 2025.

Nick: Historically, our first quarter operational net cash.

Nick: Byrne runs higher than other quarters. These.

Nick: These cash projections this cash runway projections do not include any further capital raise activities.

Nick: <unk> may undertake.

Peter Kies: 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 FCC.

Nick: As a result, you can find our full financial statements in this afternoon's press release as well as in our Form 10-K.

Peter Kies: And with that, I'll turn it back over to Jack. Thanks, Peter.

Nick: File with the SEC.

Jacky: With that I'll turn it back over to Jacky.

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

Operator: I'd now like to open up the call to answer any questions you might have. Operator? Thank you.

Jacky: Operator.

Speaker Change: Thank you ladies and gentlemen, we will now begin the question and answer session should you have a question. Please press star followed by one on your telephone keypad and should you wish to cancel your request. Please press star followed by the two.

Operator: Ladies and gentlemen, we will now begin the question and answer session. Should you have a question, please press star followed by the 1 on your telephone keypad. And should you wish to cancel your request, please press star followed by the 2. If you are using a speakerphone, just lift the handset before pressing any keys. One moment please for your first question. Thank you.

Speaker Change: If you're using a speaker phone please lift the handset before pressing any Keith one moment. Please for your first question.

Speaker Change: Thank you and your first question comes from the line of Ryan Kennon from citizens. Please go ahead.

Roy Buchanan: And your first question comes from the line of Roy Buchanan from Citizens. Please go ahead. Hey, thanks for taking the questions. Glad to hear you're on track with 3107. Had some, I guess, some details. Let's start with 3107.

Speaker Change: Hey, Thanks for taking the question I was glad to hear you're on track with 31 seven.

Speaker Change: Had some I guess some details let's start with $31 seven so.

Michael Sumner: So the BLA submission request, do you need to meet with the FDA or do you just request that in writing? And if you need to meet, have you requested that meeting? Yeah, good question, Roy. Mike, do you want to take that? Yeah, happily. So we actually held a pre-BLA meeting with the FDA prior to the single-use array breakage that we found and have now resolved. And at that time, we actually had very good alignment with all the remaining modules. And so as soon as we complete the device modules, our BLA will be complete. And 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.

Speaker Change: The BLA submission request you'd need to meet with the FDA.

Speaker Change: Or do you just request that in writing and if you need to meet have you requested that meeting.

Speaker Change: Yes, good question, Mike two months to take that.

Speaker Change: Yeah happily.

Speaker Change: So we actually held a pre BLA meeting with the FDA prior to the single use array.

Speaker Change: Breakage that we found and have now resolved.

Speaker Change: And at that time, we actually had very good alignment with all the remaining modules.

Speaker Change: And so we as soon as we complete the device modules.

Speaker Change: BLA will be complete and as we talked about today, we plan to hopefully start rolling submission in the middle of next of this year.

Speaker Change: As all the other remaining modules.

Speaker Change: <unk>.

Michael Sumner: Okay, great, that's a request. Yeah, we don't need to have another meeting. And no, no more meeting, but we do need to request a rolling. Yeah, got it. Okay.

Speaker Change: Okay.

Speaker Change: Our request yeah, we don't have another meeting.

Speaker Change: And no no more meeting, but we do need to request a rolling submission.

Speaker Change: Got it Okay and then.

Michael Sumner: And then, um, so for the stability test, is that maybe said, sorry, I missed it. Is that a single test? Or do you need to repeat a whole battery of tests? And are you doing that yourself? Or is it a third party who conducts? Yeah, that's a great question, Moit. So, we need to repeat a number of the tests required for device verification or DB testing, where we're testing the array in combination with the handset. So, we need to repeat a number of those different tests. And we use an external testing house to do that.

Speaker Change: So for the stability of the cash does that maybe he said sorry I missed it.

Speaker Change: Is that a single test or do you need to repeat a whole battery of tests and are you doing that yourself or is that a third party to conduct some tests.

Speaker Change: Yes, that's a great question, so we need to repeat the number of the tests required for device verification with TB testing.

Speaker Change: Where we're testing here right combination with the handset so we need to repeat the number of different tests and we used an external testing how to do that.

Michael Sumner: So, we've previously worked extensively with this testing house. They're great partners, but we do need to do that externally. And 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? No, I think you've covered all the major points. Okay, great.

Speaker Change: So we previously worked extensively with the testing.

Speaker Change: Great column.

Speaker Change: But we do need to do that externally and there is also some external certification that's required as part of this process the case and swap BLA as well.

Speaker Change: Mike anything to add there.

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

Speaker Change: Okay great.

Roy Buchanan: Then maybe on the DMAB, I thought the data in the publication is pretty compelling, you know, clearly differentiated from mRNA, even self-amplifying RNAs in terms of durability.

Speaker Change: And then maybe on the demob I thought the scale.

Speaker Change: The publication is.

Speaker Change: Pretty compelling clearly differentiated from mrna even self amplifying.

Speaker Change: Rnase in terms of durability.

Michael Sumner: But I didn't see anything in the publication about half-life. Seems like it's clearly longer than even the extended half-life antibodies that you're expressing. Do you have any sense of what the half-life from the DNA constructs themselves might be in people? 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 is some details of some modifications we've made for these particular monoclonals to extend half-life. So happy to follow up with you after the call on the specific details of those. Okay, great.

Speaker Change: Did you see anything on the publication about half life.

It seems like it's clearly longer than even the extended half life antibody is that youre expressing.

Speaker Change: Do you have any sense of what the half life from.

Speaker Change: From the DNA constructs themselves might be and people.

Speaker Change: Yeah, I'm not sure if we believe that safety yet Brian as part of the application.

Speaker Change: What we do happen to publication of some details modifications. We've made to these particular monoclonal to extend half life.

Speaker Change: Happy to follow up with you after the call on specific details.

Speaker Change: Okay, Great and then Jack I know you mentioned some.

Jacqueline Shea: And then Jackie, I know you mentioned some, you know, other, you know, a wide range of potential applications for the technology and the publication mentions GLIP-1, for example, do you have any Anything you can disclose today about potential programs over the next 24 months or so. 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 didn't see any anti-drug antibodies at all coming up. So, we were really excited about that.

Speaker Change: Other.

Speaker Change: A wide range of potential apt.

Speaker Change: Applications for the technology and the publication mentioned as quick one for example, do you have any.

Speaker Change: Anything you can disclose today about potential.

Speaker Change: Programs over the next 24 months or so thanks.

Speaker Change: Yeah, I think first of all I would say we were really excited to see the level of functional antibody production that we saw over such a long time period and the fact that we didn't see any antidrug antibodies to claw coming up.

Speaker Change: We're really excited about that on today's call we shared with you a broad.

Jacqueline Shea: On today's call, we shared with you, you know, 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. But we're really excited by the power of this technology, and the level that we're producing these antibodies at, at the moment, is biologically relevant and spans the levels needed for a wide range of targets. So, we're really excited by that. Yep. Okay. Sounds good. Thank you.

Speaker Change: Broad range of other targets that we previously fallen are.

Speaker Change: Working on and we hope to provide further updates from those pockets and <unk>.

Speaker Change: But we're really excited by the power of this technology and the level that we're producing antibodies as at the moment.

Speaker Change: Logically relevant from the levels needed for wide range of targets.

Speaker Change: Really excited by that.

Speaker Change: Yeah, Okay sounds good thank you.

Speaker Change: Thanks Ryan.

Speaker Change: Thank you and your next question comes from the line of Jay Olson from Oppenheimer. Please go ahead.

Jay Olson: And your next question comes on the line of Jay Olson from Oppenheimer. Please go ahead. Oh, hey, congrats on resolving the manufacturing issues with the select 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. Yes, sure, Jay.

Jay Olson: Oh, Hey, congrats on resolving the manufacturing issues with the selectors device and thank you for providing this update.

Speaker Change: We had a question about the timeline for testing and validation of the new manufacturing process and how long it takes for.

Speaker Change: For validation before including the new manufacturing information in your filing package.

Jay Olson: Yes sure Jay.

Michael Sumner: So, 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, and 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.

Speaker Change: First of all I'm just.

Jay Olson: Really thrilled and delighted that we fixed the snap train path.

Speaker Change: The single use the rate component of the device that broke.

Speaker Change: They take a little longer than we initially expected we needed to make some design changes to the park.

Speaker Change: Which also required us to improve the actual molding process.

Speaker Change: Now that we've got this behind US we started manufacturing the new right.

Speaker Change: We plan starts fights verification testing very soon.

Speaker Change: We anticipate to complete all of that in the first half of this year.

Speaker Change: As Mike said earlier on in the call. Once this process is near completion.

Speaker Change: Reach out to the FDA and request rolling submission of the BLA.

Speaker Change: We have all of the other module completed and ready for submission.

Michael Sumner: And then 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. Okay, great, thank you so much for that detailed explanation and maybe... One follow-up question. Do you need to initiate the confirmatory study before the BLA? So 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?

Speaker Change: And then bump.

Speaker Change: Once.

Speaker Change: Granted we expect to begin submitting the module and mid tier.

Speaker Change: Anticipate being able to complete the submission three to four months later.

Speaker Change: The expectation that FDA BLA.

Speaker Change: BLA for review prior.

Speaker Change: Prior to the end of the year.

Speaker Change: Okay, great. Thank you so much for that detailed explanation and maybe just one follow up question do you need to initiate the confirmatory study before the BLA submission.

Speaker Change: So 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 Q1 jump in here.

Michael Sumner: Yeah, absolutely. So, 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. So, 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.

Mike: Yeah, absolutely. So I mean, where we've previously talked that we have identified the majority of the sites we've actually.

Mike: Advanced contracts and actually have IRB approvals at several sites.

Mike: As a whole.

Mike: The reason the FDA, usually ask you to commence that trial is so that they can feel confident youre going to meet the commitment to complete the study we will be we will be very easily able to demonstrate to the FDA as a seriousness. We're approaching the study and the fact that we want.

Mike: To complete enrollment.

Mike: The study as quickly as possible.

Jay Olson: Great, that's fantastic news. Thanks again for taking the questions, and congrats on all the. Thank you.

Speaker Change: Great. That's fantastic news, thanks, again for taking the questions and congrats on all the progress.

Speaker Change: Thanks Jay.

Speaker Change: Thank you and your next question comes from the line of Sudan, Luca Nanna from Stephens. Please go ahead.

Sudan Loganathan: And your next question comes from the line of Sudan Loganathan from Stevens. Please go ahead. Hi, good afternoon and thank you for giving this update and congrats again on the great progress here with this Electra device and resolving those issues. My question, you know, is on that topic.

Luca Nanna: Hi, good afternoon, and thank you for giving this update and congrats again on the great progress here with this electronic device in resolving those issues.

Speaker Change: My question.

Speaker Change: <unk> is on that topic.

Sudan Loganathan: 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, you know, waiting a few more months to start submitting everything? Yeah, that's a really good question, Sudan. So, 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 like you to submit all of your modules in a three to four month time frame, but it is a discussion that we can have with the FDA as to when we can start rolling submission.

Speaker Change: Just curious to hear your take on.

Speaker Change: Aside from the.

Speaker Change: The initiation of the confirmatory trial needed to submit the BLA is there anything else holding you back from just starting to submit the non device component modules.

Speaker Change: Of the BLA now and starting to royalty process that.

Speaker Change: Way versus.

Speaker Change: Waiting a few more months.

Speaker Change: <unk> submitting everything.

Speaker Change: Yes.

Speaker Change: A really good question.

Speaker Change: So we have.

Speaker Change: We said we have all of the other modules ready to go.

Speaker Change: FDA normally once he started rolling submission FDA normally like CUSIP, Mr. Lithium molecules in a three to four month timeframe that statistic discussion that we can have with the FDA.

Speaker Change: When when we can start earning submission.

Michael Sumner: And 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. So, I think, you know, 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. But obviously, we're going to try and accelerate things as much as possible. Everyday matters to our RP patients, and we're very conscious of that. Got it.

Speaker Change: I think important thing is that we saw.

Speaker Change: Our TV testing.

Speaker Change: Good progress on the TV testing before we set up and timeline for.

Speaker Change: When we came to the accrual of the module of the BLA.

Speaker Change: I think.

Speaker Change: The guidance that we're providing at the moment is that we think the stockpiling submission midyear and we expect to complete that within three to four months, but albeit Steve we're going to try and accelerate things as much as possible everyday method to RP patients, we're very conscious of that.

Speaker Change: Got it no thank you for that and and quicker.

Michael Sumner: No, thank you for that. And quickly, just to hopefully jog my memory better, was the DV testing where the initial, you know, the breakage of the, of the selector device component was discovered previously? Or, or did, yeah, were you able to get to the DV testing point last time, you know, before? Yeah, I mean, last time we were pretty far through our TB testing when I believe we identified the issue with the single-use array. Mike, do you want to add any detail on that? Yeah, so I mean, we identified the issue following the age conditioning.

Speaker Change: Quickly just.

Speaker Change: Jose Jogged my memory better was the Dv testing where the initial.

Speaker Change: The breakage of the.

The way to a device component was discovered previously or or yes.

Speaker Change: Were you able to get to the TV testing point last time.

Speaker Change: Before.

Speaker Change: Yes, I mean last time, we were pretty thoughtful about TV testing by night sleep, we identified the.

Speaker Change: Issue with the single used array, Mike do you want to add any T cell.

Speaker Change: Yeah. So I mean, we identified the issue following the H conditioning.

Michael Sumner: And we have actually, with the, as part of the progress that we made, and how we developed this, we actually have already aged some of the arrays in similar manner and actually performed the testing. So we really are confident that we will, 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. But we do not expect to see any issues going forward with the array. Got it.

Speaker Change: And we have actually with the.

Speaker Change: As part of the progress we've made in how we.

Speaker Change: To develop this we actually have already aged.

Speaker Change: Some of the arrays in similar manner and actually perform the testing.

Speaker Change: So we really are confident that we will.

Speaker Change: Resolve the issue we do however have to actually repeat the.

Speaker Change: Formal aging and the formal testing once we have actually signed off the fix which we have done and we have started manufacturing those sort of commercial greater race.

Speaker Change: But we do not expect to see any issues going forward with theory.

Speaker Change: Got it thank you and just really quick one last one.

Michael Sumner: Thank you.

Sudan Loganathan: And just really quick, one last one. You know, just given the context for the RRP patients often require multiple surgeries per year and the substantial health care costs and risks, you know, associated with that, as you know, has there been any health economists or payer research conducted yet, you know, on the potential pricing or the, you know, the advantages of therapeutic such as 3107 that would, you know, in savings for the health care, you know, providers and or the health care facilities and the system in general? Or is that something that could come maybe after approval once we kind of get a better idea of pricing?

Speaker Change: Just given the context for the RP patients often require multiple surgeries per year and the substantial healthcare cost and risk associated with that as you know.

Speaker Change: Has there been any health economists are payer research.

Speaker Change: Conducted yet.

Speaker Change: On the.

Speaker Change: The potential pricing or the <unk>.

Speaker Change: Advantages of it.

Speaker Change: Theyre predicts such as 30 107.

Savings for the health care providers.

Speaker Change: Providers.

Speaker Change: Care facilities in the system in general or is that something that could come maybe after approval. Once once we kind of get a better idea of pricing just kind of curious what if anything has been done on your end.

Steve Egge: Just kind of curious what, you know, if that's anything has been done on your end on that. Yeah, Steve, do you want to take that one? Yeah, sure. So, thanks for the question. So, we've done a fair amount of research with payers where we reviewed the product profile, reviewed, you know, budget impact models and talked to them about kind of price ranges. You know, this is rare disease. We do expect rare disease pricing. So, kind of, you know, what we've shared is, you know, that could be a pretty big range, anywhere from $200,000 to, you know, $2 million a year.

Speaker Change: On that.

Steve: Yes, Steve do you want to take that one yeah sure. So thanks for the question so.

Steve: Done a fair amount of research with payers, where we reviewed the product profile for <unk>.

Steve: Budget impact models and <unk>.

Steve: After them about kind of price ranges.

Steve: Is rare disease, we do expect rare disease pricing so kind of.

Steve: What we've shared is that could be a pretty big range anywhere from $202 million a year.

Steve Egge: But one analogy that we look at that's pretty close, like we've referenced it before, the Oxivio 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. And the feedback that we've gotten from payers is that, you know, that kind of rare disease pricing range is very acceptable to them. So, we don't expect any issues, kind of, with rare disease pricing, if that helps.

Steve: But one analogy that we look at that's pretty close that we've referenced it before the auction the auction spring works therapeutics.

Steve: It's a product for desmoid tumors kind of the first medical therapy that the standard of care kind of prior to that launching was repeated surgeries.

Steve: The price range of 360000 per year, that's kind of a price that we've referenced in the feedback that we've gotten from payers is that.

Steve: That kind of rare disease pricing ranges is very acceptable to them. So we don't expect any issues kind of with rare disease pricing if that helps.

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

Speaker Change: Yeah. That's great. Thank you. Thank you again for all the answers here and congrats again on all the progress and looking forward to the.

Steve: Progress going forward.

Steve: Thank you.

Yi Chen: And your next question comes in the line of Yi Chen from HC Wainwright. Please go ahead. Hi, thank you for taking my question. Regarding the utility of the DBAP technology, particularly terms of the phase one proof of concept trial evaluating DMAP targeting COVID-19. Could you tell us how durable is the in vivo antigen? And in future clinical trials, in case the produced antibody has some... undesirable effects. Is there a way that you can turn off the internet?

Speaker Change: Thank you and your next question comes from the line of <unk> Chen from H C. Wainwright. Please go ahead.

Speaker Change: Alright, Thank you for taking my questions regarding the <unk>.

Speaker Change: The.

Speaker Change: Utility of the <unk> technology, particularly.

Speaker Change: Terms of the phase one proof of concept trial evaluating <unk> targeting COVID-19 could you tell us.

Speaker Change: How durable is.

Speaker Change: Evo anti body production in future.

Speaker Change: Clinical trials in case, the produce the entire body.

Speaker Change: Some.

Speaker Change: Undesirable effect is there a way that you can turn off the table.

Speaker Change: Thank you.

Yi Chen: Yeah, hi Yi, both great questions. So, 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. So, our production seems to be holding up over 72 weeks. So, we think that's really excellent durability.

Speaker Change: Yeah I E.

Speaker Change: That's great question.

Speaker Change: <unk> antibody production is.

Speaker Change: In Q4.

Speaker Change: On this slide we presented at <unk>.

Speaker Change: If you take a look at the pre prints as well, we're now up to 72 weeks and we're not seeing any drop in some leather.

Speaker Change: The level that we're seeing.

Speaker Change: To create within the therapy. So all production seems to be holding up at 72 weeks.

Speaker Change: So we think thats really excellent tolerability.

Yi Chen: And 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. But I think initially we'll be focused on targets that were already in the right range and where there's less concern about potentially turning off those antibodies. So I think those will be the targets that we focus on initially.

Speaker Change: And then in terms of.

Speaker Change: Clinical trials.

Speaker Change: We're excited by what this technology.

Speaker Change: Could mean across a wide range of targets.

Speaker Change: Our either in <unk> or a principal promote that you could use to turn off the <unk>.

Speaker Change: Then on the team to be able to control the expression, but I think initially we'll be focused on.

Speaker Change: Targets were.

Speaker Change: Already in the right therapeutic range, and where there's less concern about potentially setting up.

Speaker Change: Turning off the answer you got it so I think those will be at the targets that we apply for common necessarily.

Yi Chen: And 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? Yeah, again, great question. So we're administering our DMAPs into the deltoid muscle in the arm. And the DMAPs are actually produced within the myocytes, within the muscle cells. They're produced as heavy light chain proteins, which then are self-assembled and then are secreted into the bloodstream from the myocytes. So it's actually production in these muscle cells, which are pretty long-lived cells, the myocytes. Thank you.

Speaker Change: And in terms of the location of the anti body protection as a problem where they produce in certain parts of the body.

Speaker Change: It's produced throughout the body.

Speaker Change: Yes, again, great question.

Speaker Change: Right now our team up in.

Speaker Change: Into the deltoid muscle in yellow.

Speaker Change: On the team up there actually produced within the mine sites, but then the muscle cells.

Speaker Change: Could you use the heavy and light chain protein, which then self assemble and then I'll secreted into the bloodstream from the mine site.

Speaker Change: C production needs in these muscle cells, which are pretty long live now.

Speaker Change: And then last night.

Speaker Change: Okay. Good thank you.

Speaker Change: Thank you and your next question comes from the line of Gregory Windsor.

Anish Nikhanj: And your next question comes from the line of Gregory Rensa from RBC Capital Markets. Please go ahead. Hi guys, it's Anish on for Greg. Congrats on the progress this quarter. And thanks for taking our questions.

Speaker Change: We see capital markets. Please go ahead.

Hi, guys its a niche on for Greg Congrats on the progress this quarter and thanks for taking our questions. Just a couple from US as you think about taking $31 seven commercial in the future potentially what are you what are your going assumption for labeling and what particular points would you like to see that could play to the strengths of your programs both on its own.

Anish Nikhanj: Just a couple from us as you think about taking 3107 commercial in the future, potentially, what are you 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. Yeah, great question, Anish. I mean, first and foremost, I think we're really, really confident in the very strong product profile that we're seeing with INO3107 with, you know, we've observed great and durable efficacy. The treatment's been very tolerable. And then it's, you know, we've designed really 3107 with the patient in mind.

Speaker Change: Merit and even over competitors. Thanks, so much.

Speaker Change: Yes, great questions.

Speaker Change: First and foremost I think really well.

Speaker Change: Really competence and the very strong product profile that we're seeing with INR 31, 7%.

Speaker Change: Yes.

Speaker Change: Yes.

Great.

Speaker Change: Couple of efficacy.

Speaker Change: The treatments being very tolerable and then.

Speaker Change: We've designed really 37 with the patients in mind that we have a very patient centric treatment regimen, we didn't acquire any.

Jacqueline Shea: So we have a very patient 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 you know to go for instance to an infusion center to receive the product. So we think that product profile is really really compelling. I think you know obviously we're still very close to filing our BLA and so I think we can't really comment at the moment about the potential label implications, but I think you know the data that we've generated in this patient population who previously had two or more surgeries.

Speaker Change: Pain, or any saturate nature and the dosing window.

Speaker Change: Paul to administer the treatment and the Doctor Buffett.

Speaker Change: Need for them.

Speaker Change: Go ahead Sue.

Speaker Change: To get to it.

Speaker Change: For instance to an infusion center to receive the product. So we think that product profile, it's really really compelling I think obviously with Phil.

Speaker Change: Very close to filing a BLA.

Speaker Change: So I think we can't really comment at the moment.

Speaker Change: The potential label application.

Speaker Change: I think it's safe that we've generated in this patient population, who previously had to a more surgery is really compelling.

Michael Sumner: It's really compelling.

Michael Sumner: Mike, anything you want to add there? Yeah, I mean, when you have these discussions with the agency, your label is always a negotiation. But ultimately, it is about sharing the risk-benefit ratio for the physician and for the patient. And I think as you heard today, I mean, we're able to now really demonstrate the durable clinical effect of INO3107. And 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.

Speaker Change: Mike kind of thing Newman's worker.

Speaker Change: Yes.

Speaker Change: When you have these discussions with the agency you label is always a negotiation, but ultimately it is about.

Speaker Change: Sharing the risk benefit.

Speaker Change: The ratio for the physician and for the patient and I think as you heard today I mean, we able to now really demonstrate the durable clinical effect of INR 30 107.

Speaker Change: And I would hope we will be able to discuss that with the agency and get that taken into account because RFP as noted diseases defined by a 12 month period is a chronic viral infection. In these patients have multiple surgeries. So I think he will be an interesting discussion that we'll have with the agency in the future.

Roger Song: So I think it'll be an interesting discussion that we'll have with the agency in the future. Great, thank you so much. Thank you.

Speaker Change: Sure.

Speaker Change: Okay.

Speaker Change: Great. Thank you so much.

Speaker Change: Thank you and your next question comes from the line of Roger song from Jefferies. Please go ahead.

Liang Cheng: And your next question comes from the line of Roger Song from Jeffries. Please go ahead. Hey, team. Thank you for taking our question. This is Liang Cheng for Roger. So, two questions from us regarding, you know, RRP and the 3107. First one, you know, really great to see the durability data of the 3107, you know, up to two years, three years. So, just wondering, how should we think about re-dosing commercially, you know, if you think about the durability and increased, you know, response there? And second, you know, as we, you know, think about the treatment of RRP disease, so how should we think about, you know, in the longer term, the epidemiology and addressable market there?

Speaker Change: Thank you and thank you for taking our question. This is downtown for Roger.

Speaker Change: So just two questions from us regarding our P&L, starting while seven.

Speaker Change: First one.

Speaker Change: Really great to see the durability data of the starting one or southern.

Speaker Change: Up to two years three years, so just wondering.

Speaker Change: How should we think about the re dosing commercially.

Speaker Change: Do you think about the durability and increased.

Speaker Change: Response there.

Speaker Change: Second.

Speaker Change: As we think about the treatment of RP disease. So how should we think about.

Speaker Change: Longer term, the epidemiology and addressable market there.

Liang Cheng: Thank you. Thanks. I caught your first question about the redosing strategy. I'm sorry, I didn't quite catch your second question. Could you repeat that? Yes, so, you know, as we now have, you know, those 3107 and those treatment, new treatment for RRP, so do we expect a lower epidemiology, decreasing epidemiology over time? And how should we think about the addressable market there? Yeah. Great question.

Speaker Change: Thank you.

Speaker Change: Yes.

Speaker Change: 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.

Speaker Change: Yes so.

Speaker Change: As we have now have.

Speaker Change: 31, 7%.

Speaker Change: We will strengthen new treatment for RP, So do we expect.

Lower epidemiology.

Speaker Change: Epidemiology overtime, and possibly think about the addressable market there.

Speaker Change: Yes, Great question, Okay, Mike do you want to take the readout, taking them ill take the IP question.

Michael Sumner: Mike, do you want to take the redose thing and then I'll take the epi question? Yeah, absolutely. So, I mean, as we said, in today's call, we're actually still deciding on the redosing strategy. I think as we look to a 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, et cetera. But really that isn't how the physicians look at this.

Speaker Change: Yeah, absolutely so.

Speaker Change: As we said in today's call, we're actually still deciding on the re dosing strategy I think as we looked to address.

Speaker Change: Excellent efficacy.

Speaker Change: 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.

We started off this process looking at it very much from a sort of regulatory lens of complete remission partial remission et cetera, but really that isn't how the physicians look at this they look at this at a totality of the surgeries that these patients have and so we want.

Jacqueline Shea: They look at this at a totality of the surgeries that these patients have. And so 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. So I mean, hopefully we'll have some more details in upcoming calls. But 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 redosing and being able to boost that CD8 response that we've seen with 3100 in the past.

Two as we think about this strategy.

Speaker Change: We'll see how we can reduce the surgeries to yeah.

To hopefully zero.

Speaker Change: And how we can maintain that excellent clinical response that we've seen.

Speaker Change: Hopefully, we'll have some more details in upcoming calls.

Speaker Change: But at the moment, we really are still 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 CD eight response that we've seen with 3100 in the past.

Speaker Change: Okay.

Jacqueline Shea: Yeah, I think that's a really excellent point. You know, with our DNA medicines platform, we're able to redose from a previous product, BGX3100. We've shown that we can boost the existing T cell responses by going in with a single dose later. So, we're really confident that we can continue to maintain the immune response that's associated with clinical benefit, potentially augment the immune response. And so, we're very excited by what that means for potential long-term treatment for RRP. And as Mike said, this is a chronic, often lifelong disease. So, being able to provide durable clinical benefits is really incredibly important.

Speaker Change: Yeah.

Speaker Change: I think that's a really excellent point.

Speaker Change: DNA medicines platform, we're able to re dose.

Speaker Change: From a previous product BJ 3100, we've shown that we can place the existing T cell responses by going in a single slide.

Speaker Change: We're really confident that we can continue to maintain.

Speaker Change: Immune response associated with clinical benefit.

Speaker Change: Potentially.

Speaker Change: You mean.

Speaker Change: And so we're very very excited by what that means for potential long term treatment for pain.

Speaker Change: As Mike said this is a chronic cough the microphone to C. So.

Speaker Change: April provide durable clinical benefits really incredibly important.

Jacqueline Shea: 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. And if you think about the epidemiology of RRP, you see a peak of disease cases around age 5 to 7, another peak in the age sort of 30 group, and then another peak in the late 50s, early 60s. And currently in the US, for instance, vaccination for HPV is only around 50% in males, below 60% in females.

Speaker Change: In terms of the X genealogy.

Speaker Change: Thing is.

Speaker Change: In most developed countries.

Speaker Change: The vaccination rates.

Speaker Change: Around sort of 50 or 60.

Speaker Change: We are still seeing large numbers of.

Speaker Change: Oral PK study in adults.

Speaker Change: <unk> seems to be impacted by the passion vaccination.

Speaker Change: Yes.

Speaker Change: The level of cases, not all seem to be holding pretty steady and if you think about the epidemiology of eight <unk>.

Speaker Change: It peaked disease cases around H pipes seven another peak in the H sort of 30 group.

Speaker Change: And then another peak in late 15 early 16.

Speaker Change: Currently and in the U S for instance.

Speaker Change: Taxation friendship HPV, if any around 50% E mails.

Jacqueline Shea: So a large proportion of the adult population, I think it's been estimated that around 70% is not protected against HPV 6 and 11. And it's also not entirely clear how long the vaccine, the vaccine protective effects remain as well. So, 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. But we're not seeing any impact on cases in the adult population.

Speaker Change: 60% female so a large proportion of Seattle population I think it's been estimated at around 70% is not protected against HPV, six and 11 and Influencer.

Speaker Change: Not entirely clear how long the vaccine.

Speaker Change: Protective effects for maintenance as well.

Speaker Change: So unfortunately, I think it looks as though RFP, it's going to be with the subgroup generations to come.

Speaker Change: We are seeing a decrease in the number of patients and the impact vaccination.

Speaker Change: In pediatric are up eight.

Speaker Change: The number of pediatric cases, all declining.

Speaker Change: But we're not seeing any impact on it.

Jacqueline Shea: And in fact, we think this is actually an underdiagnosed disease in the adult population.

Speaker Change: Population.

Speaker Change: In fact, we think this is actually an answer.

Speaker Change: To date in the adult population.

Operator: Very helpful. Thank you, Jackie and Mike. Thank you. Thank you, and there are no further questions at this time.

Speaker Change: Got it very helpful. Thank you Jackie and Mack.

Speaker Change: Thank you. Thank you.

Speaker Change: Thank you and 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: I will now hand the call back to Ms. Jacqueline Shea for any closing remarks. 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 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. And finally, we'll continue driving progress across our pipeline, advancing promising programs like 3112 and leveraging potential partnership opportunities. This includes building on the breakthrough potential of our DMAP program and other next-gen DNA medicine technology.

Jacqueline Shea: Thank you.

Speaker Change: We've outlined here today, we are moving into 2025 with very focused strategic priorities.

Speaker Change: First and foremost is completing the next steps necessary for submitting a BLA for 31 seven at the same time, we will be continuing to advance our commercial readiness plan that we can hit the ground running and use our compelling product.

Speaker Change: Paul to its full advantage.

Speaker Change: And finally, we'll continue driving progress across our pipeline advancing commenting programs like 31, small and leveraging potential partnership opportunities.

Speaker Change: This includes building on the breakthrough potential about the map program and the other Nextgen DNA Medicine technology.

Jacqueline Shea: 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're strongly motivated by the understanding that every day and every surgery matters. Thank you for your attention and good evening everyone. Thank you. And that concludes our conference for today. Thank you all for participating. You may now disconnect.

Speaker Change: 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 RFP in particular with strongly motivated by the understanding that every day and hopefully surgery masses.

Speaker Change: Thank you for your attention and good evening everyone.

Speaker Change: Thank you and that concludes our <unk>.

Speaker Change: Conference for today. Thank you all for participating you may now disconnect.