Inovio Pharmaceuticals Q4 2024 Earnings Call Transcript

Quartr
Provided by Quartr
March 18, 2025

There are 12 speakers on the call.

Operator

Good afternoon, ladies and gentlemen, and welcome to the Inovio Pharmaceuticals Fourth Quarter twenty twenty four Financial Results Conference Call. This call is being recorded on Tuesday, 03/18/2025. And I would now like to turn the conference over to Ms. Jenny Wilson. Thank you.

Operator

Please go ahead.

Speaker 1

Good afternoon, and thank you for joining the Inovio fourth quarter twenty twenty four financial results conference call. Joining me on today's call will be Doctor. Jackie Hsieh, President and Chief Executive Officer Doctor. Mike Sumner, Chief Medical Officer Peter Keyes, Chief Financial Officer and Steve Ege, Chief Commercial Officer. Today's call will review our corporate and financial information for the quarter and year ended 12/31/2024, as well as provide a general business update.

Speaker 1

Following prepared remarks, we will conduct a question and answer segment. During the call, we will be making forward looking statements regarding future events and the future performance of the company. These events relate to our business plans to develop Inovio's DNA Medicines platform, which include clinical and regulatory developments and timing of clinical data readouts and planned regulatory submissions, along with capital resources and strategic matters. All of these statements are based on the beliefs and expectations of management as of today. Actual events or results could differ materially.

Speaker 1

We refer you to the documents we file from time to time with the SEC, which under the heading Risk Factors identify important factors that could cause actual results to differ materially from those expressed by the company, verbally as well as statements made within this afternoon's press release. This call is being webcast live and a link can be found on our website, ir.inovio.com, and a replay will be made available shortly after this call is concluded. I will now turn the call over to Inovio's President and CEO, Doctor. Jackie Hsieh.

Speaker 2

Good afternoon, and thank you to everyone for joining today's call. After significant progress in 2024, we remain focused on transforming Inovio into a commercial stage company and delivering on the promise of DNA medicines for patients and shareholders alike. To achieve that goal, our work this year will be driven by three main strategic priorities: submitting our BLA for INO-three thousand one hundred and seven, our lead candidate for recurrent respiratory papillomastosis advancing our commercial plan and preparing for a fast and efficient launch and leveraging the strength of our platform to drive progress across our diversified pipeline. Advancing 03/2007 is our primary focus and I'm very pleased to report that we have resolved the previously announced manufacturing issues involving the single use array component of the Selexa device. Our next step is to perform the FDA required spiase verification testing known as DB testing for the combined handset and single use array required for our IND and BLA submission.

Speaker 2

We now plan to begin submitting our BLA on the FDA's rolling submission process as well as commencing our confirmatory trial and requesting priority review in mid-twenty twenty five. 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. Most importantly, we remain confident that if approved, 03/2007 could be the preferred non surgical treatment for RRP for both patients and their physicians, a position that is strengthened by the year two and year three clinical data announced in December and the detailed immunology data we published in February. Mike will provide more detail later in the call, but in our retrospective trial of March and '7, patients showed continued improvement in reduction in surgery after year one with fifty percent meeting criteria for complete response in the second twelve 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 2

The ongoing efficacy was observed is also supported by the immunology data published in Nature Communications demonstrating the ability of 3,107 to drive an antiviral immune response in airway tissue that correlated with a reduced or eliminated need for surgery. We also published the full safety and efficacy data set for the completed Phase onetwo trial, which shows that the administration of three thousand one hundred and seven was well tolerated. In summary, three thousand one hundred and seven 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, all of which we believe could be compelling advantages once on the market. While our immediate focus is on advancing three thousand one hundred and seven, I'm also pleased to provide some important update from our work on next generation DNA medicines. Together with our partners, we recently announced top line interim results from an ongoing Phase one trial with our DNA encoded monoclonal antibody technology, which we call dMAb.

Speaker 2

This proof of concept trial involved two dMAb's targeting SARS CoV-two 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 broad range of diseases by enabling long term in vivo production of therapeutic antibodies or other proteins. Now I'll turn it over to Mike for some additional insights on our progress and new data on 03/2007. Mike?

Speaker 3

Thank you, Jackie. As Jackie mentioned, we have made tremendous progress towards our primary goal, submitting our BLA for 03/2007. 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.

Speaker 3

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. We began manufacturing our new commercial grade arrays, which will now be utilized in the design verification testing, so we can move forward to completing our IND and BLA submissions. In addition, the full Phase onetwo clinical data and accompanying detailed immunology data were recently published in Nature Communications. These data further support the T cell mechanism of action for 03/2007, which underpins the efficacy results we've seen. We also announced some very exciting clinical durability data showing that patients treated with three thousand one hundred and seven continue to show further reduction in the need for surgery to manage their disease in the second and third year.

Speaker 3

This data will be the subject of an oral presentation at the combined otolaryngology spring meeting to be held in New Orleans this May, '1 of the most frequented meetings by our target physicians treating RRP. We've also made important progress in preparing for our Phase three 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.

Speaker 3

This progress to date will enable us to enroll in a timely manner following submission of our updated IND. I'd like to spend some time now discussing the new data as it paints a compelling product profile that strengthens our belief that 3,107 could be the preferred product for RRP patients and their physicians. As a reminder, we completed a Phase onetwo open label trial of three thousand one hundred and seven in patients who required at least two surgeries in the previous year for the removal of the HPV six eleven 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 twelve months. We then conducted RRP-two, a retrospective trial in which we were able to collect data on twenty eight of the original thirty two patients to assess the longer term treatment effect with a median follow-up of two point eight years.

Speaker 3

RRP is a chronic often lifelong disease and duration of efficacy is clearly important. Here we dive into the two 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 fifty percent for the second twelve month period when evaluated at the end of year two. We also saw the overall response rate that is the number of patients that had fifty percent to one hundred percent fewer surgeries compared to their pre treatment baseline increased from seventy two percent in the first twelve month treatment period or year one to eighty six percent for the second twelve month period or year two.

Speaker 3

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 one point seven surgeries at the end of year one and then reduced further by the end of year two to a mean of zero point nine surgeries. Across the population of patients treated with three thousand one hundred and seven, this is a reduction of greater than seventy five percent following the initial treatment regimen alone. However, one of the core strengths of our DNA medicines platform is the ability to administer additional doses to continue to drive and amplify strong T cell based immune responses without having to worry about the impact of an anti vector response. Looking again at the mean surgeries per year across the population, we saw a significant decrease in the year following treatment and then a further decrease in the second twelve month period or year two. Into year three, the improvement seems to be holding steady.

Speaker 3

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 sixteen and eighteen 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. Every surgery matters to patients and our vision for INO three thousand one hundred and seven 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 three thousand one hundred and seven and how we believe treatment is providing the favorable efficacy results we observed.

Speaker 3

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

Speaker 3

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, 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 HBV infection that causes RRP. To wrap up, I want to provide some additional detail on our next steps for 03/2007. Now that we have resolved the array issue, we have commenced 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.

Speaker 3

We plan to request rolling submission and priority review of our BLA. And if FDA agrees, we will begin submitting our modules in mid-twenty twenty five and complete the full submission three to four months later with the goal of having the FDA accept our complete BLA for filing by the end of the year. Once the entire BLA is submitted, we plan to finalize our long term dosing study strategy and submit a proposed protocol to the FDA to support a supplemental BLA in the future. We also look forward to commencing onboarding of our field medical science liaison team and presenting this exciting data package at several upcoming conferences this spring, including The U. S.

Speaker 3

Based National HPV Conference, the European ALS Congress and COSM among others listed on the slide. With that, I will now turn over to our Chief Commercial Officer, Steve Agee for an update on our commercial efforts. Steve?

Speaker 4

Thanks, Mike. I'd like to build on the 3,107 data Mike shared by reviewing why our work on RRP RRP is so important, what the market looks like, why 3,107

Speaker 2

could be

Speaker 4

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 fourteen thousand people in The U. S. It's characterized by work like growth called papilloma to 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.

Speaker 4

Patients and their providers want a nonsurgical option for RRP that addresses the underlying disease and that ultimately helps them avoid additional surgeries. We designed 3,107 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 do we observe favorable efficacy results in patients treated with three thousand one hundred and seven, we saw continued improvement into the second twelve month period or year two for both complete and overall response rates. Three thousand one hundred and seven was well tolerated in the trial and there were no discontinuation. And finally, three thousand one hundred and seven offers a simple patient centric treatment regimen that does not require additional potentially unnecessary scoping and procedures during the treatment window.

Speaker 4

And finally, three thousand one hundred and seven offers office based administration without the need for 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 three thousand one hundred and seven's product profile. One laryngologist told us the complete response rate of fifty percent is good, but a fifty percent to one hundred percent reduction in surgeries in eight out of ten patients is the most compelling. When laryngologists review our data, they quickly move to think about how they would describe the product to their patients. And they indicate they like being able to say the vast majority of patients see significant benefit from treatment.

Speaker 4

Likewise, both the tolerability profile and simple patient focused treatment regimen were very well received by laryngologists who are currently treating RRP patients. Moving on, I'd like to share just a few updates on our commercial launch preparations. Since last quarter, we've made significant progress, including developing our distribution channel strategy and identifying channel partners, developing our initial pricing strategy and completing targeting, segmentation and product positioning work to establish positive differentiation. We're currently developing our go to market model and planning a further build out of the commercial organization. Given the RRP market is highly concentrated with the majority of RRP patients treated by relatively few laryngologists, we believe we will need a small and efficient field force footprint.

Speaker 4

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.

Speaker 2

Thanks, Steve. While three thousand one hundred and seven is at the forefront of our work, we are excited about the opportunities to leverage the strengths of our platform across the pipeline, including what we see as the next generation of DNA medicine technology. And enabling the body to generate its own disease fighting tools is a key strength of our DNA medicine platform and our dMAb technology leverages that strength in another way. Using our proprietary gene sequence optimization technology, we can create precisely designed DNA plasmids that encode for specific monoclonal antibodies. These plasmids also called the DNA can then be delivered directly into muscle cells in the arm using our selection delivery system.

Speaker 2

The heavy and light chain proteins that make up the dMAb 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 one proof of concept trial evaluating dMAbs for COVID-nineteen led by the WithStar Institute in collaboration with AstraZeneca, the University of Pennsylvania and Inovio and funded by DARPA and JPO, this trial has provided the first clinical proof of concept that dMabs can be durably and simultaneously produced inside the human body. Specifically, we saw long lasting in vivo antibody production with dmAb levels remaining stable for seventy two weeks in all participants who have reached that time point. No antidrug antibodies or immune rejection of the dmAb was detected across approximately 1,000 blood samples, unlike other gene based antibody delivery approaches.

Speaker 2

And 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. And we saw that the Xpressi maps successfully balanced the SARS CoV-two spike protein resexor binding domain confirming functional activity through week seventy two. 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 review journal, which is currently available in preprints on Research Square. We believe this technology could have the potential to be a breakthrough that could overcome many of the challenges seen with traditional monoclonal antibody production.

Speaker 2

With rapid manufacturing, low cost of production, temperature stable storage and distribution and the ability to redose, CMAP technology could help expand use, reduce costs and enable access in low resource settings. Importantly, unlike other delivery platforms, our DNA based approach has demonstrated sustained antibody production without generating antidrug antibodies, making it a potentially promising long term solution for conditions requiring continuous therapeutic protein delivery. We see broad potential for this technology and we and our partners at Whistler have been investigating the feasibility of dMAb across multiple disease targets, mostly in a preclinical setting from flu to HIV to cancers and to the most recent clinical trial targeting COVID-nineteen. 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 medicines platform. We look forward to continuing working with our partners to complete the current Phase one 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.

Speaker 2

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 dMAb, DNA encoded protein replacement candidate or deprops, 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. 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 three trial to evaluate INO-three thousand one hundred and twelve in combination with the FDA approved PD-one inhibitor LOCKTORCY as a treatment for locorutinib advanced high risk HBV16 and eighteen positive throat cancer. With the trial planned across both North America and Europe, we've discussed the trial design with FDA and most recently received some initial feedback from the European regulators on the trial design.

Speaker 2

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. We're also advancing discussions on the design for a Phase two 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. I will now turn it over to our Chief Financial Officer, Peter Keyes for a financial update. Peter?

Speaker 5

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 03/2007, being ready to begin the submission of our BLA in mid-twenty twenty five and ensuring that we have the resources to support this critical work. To that effect, we raised more than $72,000,000 in gross proceeds from two equity offerings in April and December of twenty twenty four and from equity sales from our ATM. We also continue to decrease operational spending with our total operating expenses dropping from $27,500,000 in fourth quarter of twenty twenty three to $20,500,000 in the fourth quarter of twenty twenty five.

Speaker 5

Our full year operational expenses decreased 22% from $144,800,000 in 2023 to $112,600,000 in 2024. Inovio's net loss for the fourth quarter of twenty twenty four was $19,400,000 or $0.65 per share basic and dilutive and our total net loss for the full year of 2024 was $107,300,000 or $3.95 per share basic and dilutive. We finished the fourth quarter of twenty twenty four with $94,100,000 in cash, cash equivalents and short term investments compared to $145,300,000 dollars as of 12/31/2023. We estimate our cash runway to take us into the first quarter of twenty twenty six. This projection includes an operational net cash burn estimate of approximately $27,000,000 for the first quarter of twenty twenty five.

Speaker 5

Historically, our first quarter operational net cash burn runs higher than other quarters. These cash projections this cash runway projections do not include any further capital raise activity that Inovio may undertake. As a result, you can find our full financial statements in this afternoon's press release as well as in our Form 10 K filed with the SEC. And with that, I'll turn it back over to Jackie.

Speaker 2

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

Operator

Thank you. Thank you. And your first question comes from the line of Roy Buchanan from Citizens. Please go ahead.

Speaker 6

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 03/2007. 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?

Speaker 2

Yes. Good question, Lloyd. Mike, do you want to take that?

Speaker 3

Yes, 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 we 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 next of this year as all the other remaining modules are complete.

Speaker 2

Okay. That's just a request. Yes, we don't need to have another meeting.

Speaker 3

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

Speaker 6

Yes, Got it. Okay. And then, so for the stability test, is that maybe you said, sorry, I missed it, but 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 the test?

Speaker 2

Yes, that's a great question, Moi. 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. So we previously worked extensively with the testing house.

Speaker 2

They're great partners, but we do need to do that externally. And then it'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?

Speaker 3

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

Speaker 6

Okay, great. Then maybe on the dMAb, I thought that data in the publication is pretty compelling, clearly differentiated from mRNA even self amplifying RNAs in terms of durability. But I didn't see anything in the publication about half life. It 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?

Speaker 2

Yes. I'm not sure if we've released all of that data yet. Roy, it's part of the publication. What we do have in the publication is some details of specific details of those.

Speaker 6

Okay, great. And then Jackie, I know you mentioned some other wide range of potential applications for the technology and the publication mentions GLP-one, for example. Do you have any anything you can disclose today about potential programs over the next twenty four months or so? Thanks.

Speaker 2

Yes. 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 antidrug antibodies at all coming up. So we were really excited about that. On today's call, we shared with you a broad range of other targets that we previously worked on and are working on, and we hope to provide further updates on those targets in due course. 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.

Speaker 2

So we're really excited by that.

Speaker 6

Yes. Okay. Sounds good. Thank you.

Speaker 2

Thanks, Ryan.

Operator

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

Speaker 7

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

Speaker 2

Yes, sure, Jay. 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 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.

Speaker 2

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

Speaker 7

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 2

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. And Mike, do you want to jump in here?

Speaker 3

Yes, 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 ask 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.

Speaker 7

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

Speaker 2

Thanks, Jay.

Operator

Thank you. And your next question comes from the line of Sidon Lueganera from Stephens. Please go ahead.

Speaker 8

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

Speaker 2

Yes, 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 timeframe. But it is a discussion that we can have with the FDA as to when we can start rolling submission. And I think the important thing is that we start our DB testing, have made good progress on the DB testing before we set that end timeline for when we're going to deliver all of the modules to the BLA.

Speaker 2

So I think the guidance that we're providing at the moment is that we are going to start filing 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 RUP patients and we're very conscious of that.

Speaker 8

Got it. No, thank you for that. And quickly just to hopefully jog my memory better, was the DV testing where the initial the breakage of the selector device component was discovered previously? Or did, yes, were you able to get to the DV testing point last time before?

Speaker 2

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

Speaker 3

Yes. So I mean, we identified the issue following the age conditioning. And we have actually with the as part of the progress that we made and how we develop 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.

Speaker 3

But we do not expect to see any issues going forward with the array.

Speaker 8

Got it. Thank you. And just really quick one last one. Just given the context for the RRP patients often require multiple surgeries per year and the substantial health care costs and risks associated with that as you know. Has there been any health economist or payer research conducted yet on the potential pricing or the advantages of therapeutics such as 3,107 that would in savings for the healthcare providers and or the healthcare facilities and the system in general?

Speaker 8

Or is that something that could come maybe after approval once we kind of get a better idea of pricing? Just kind of curious what if that's anything has been done on your end on that?

Speaker 2

Yes. Steve, do you want to take that one? Yes, sure.

Speaker 4

So thanks for the question. So we've done a fair amount of research with payers where we reviewed product profile, reviewed budget impact models and talked to them about kind of price ranges. This is rare disease. We do expect rare disease pricing. So kind of what we've shared is that could be a pretty big range anywhere from $200,000 to $2,000,000 a year.

Speaker 4

But one analogy that we look at that's pretty close, like we've referenced it before, the OXYVIO 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 reference. And the feedback that we've gotten from payers is that that kind of rare disease pricing ranges is very acceptable to them.

Speaker 4

So we don't expect any issues kind of with rare disease pricing if that helps.

Speaker 8

Yes, 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 progress going forward.

Operator

Thank you. Thank you. And your next question comes from the line of Yi Chen from H. C. Wainwright.

Operator

Please go ahead.

Speaker 9

Hi. Thank you for taking my questions. Regarding the utility of the DMAF technology, particularly in terms of the Phase one proof of concept trial evaluating dMAb causing COVID-nineteen. Could you tell us how durable is the in vivo antibody production? And in future clinical trials, in case the produced antibody has some undesirable effects, is there a way that you can turn off the antibody production?

Speaker 9

Thank you.

Speaker 2

Yes. Hi Yi, those are 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 for seventy two 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 seventy two weeks. So we think that's really excellent durability.

Speaker 2

And then 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 promosas 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 therapeutic range and where there's less concern about potentially turning off turning off those antibodies. So I think those will be the targets that we focus on initially.

Speaker 9

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?

Speaker 2

Yes. Again, great question. So we're administering our dMAb into the deltoid muscle in the arm. And the dMAb are actually produced within the myocytes within the muscle cells. They're produced as heavy and light chain proteins, which then are self assembled and then are secreted into the bloodstream from the myocytes.

Speaker 2

So it's actually production in these muscle cells, which are pretty long lived cells, the myocytes.

Speaker 9

Okay, got it. Thank you.

Operator

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

Speaker 10

Hi guys. It's Anish 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 03/2007 Commercial in the future potentially, what are your going assumption for labeling?

Speaker 10

And what particular points would you like to see that could play to the strengths of your programs, both on its own merits and even over competitors? Thanks so much.

Speaker 2

Yes, great question, Manish. 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 we've observed great and durable efficacy. The treatment has been very tolerable. And then it's we've designed really 3,107 with the patients in mind. So we have a very patient centric treatment regimen.

Speaker 2

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, to go for instance to an infusion center to receive the product. So we think that product profile is really, really compelling. I think, 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.

Speaker 2

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

Speaker 3

Yes. I mean, when you have these discussions with 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 twelve month period. It's a chronic viral infection and these patients have multiple surgeries.

Speaker 3

So I think it'll be an interesting discussion that we'll have with the agency in the future.

Speaker 10

Great. Thank you so much.

Operator

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

Speaker 11

Hey, Tim. Thank you for taking our question. This is Leon Cheng for Roger. So just two questions from us regarding RRP and the 3,107. The first one, really great to see the durability data of the 3,107 up to two years, three years.

Speaker 11

So just wondering, how should we think about the redosing commercially, if you think about the durability and increased response there? And second, as we think about the treatment of RP disease, so how should we think about in a longer term the epidemiology and addressable market there?

Speaker 9

Thank you.

Speaker 2

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

Speaker 11

Yes. So as we have now have those 3,107 and those treatment new treatment for RRP. So do we expect lower epidemiology, like decreasing epidemiology over time? And how should we think about the addressable market there?

Speaker 2

Yes, great question. Okay. Mike, do you want to take the readout, Vic, and then I'll take the epi question?

Speaker 3

Yes, absolutely. So I mean, as we said in today's call, we're actually still deciding on the redosing strategy. I think as we looked to our sort of excellent efficacy, It did make us think about how we could design the clinical trial to get a future labeling change. I think we're also sort of in the position now that we started off this process looking at it very much from a sort of regulatory lens of complete remission, partial remission, etcetera. But really that isn't how the physicians look at this.

Speaker 3

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 three thousand one hundred in the past?

Speaker 2

Yes, I think that's a really excellent point. With our DNA medicines platform, we're able to redose from a previous product, BGX-three thousand one hundred. 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 immune response. And so we're very excited by what that means for potential long term treatment for RRP.

Speaker 2

And as Mike said, this is a chronic often like some disease. So being able to provide durable clinical benefits really incredibly important. In terms of the epidemiology, what we're seeing is in most developed countries where the vaccination rates are around sort of fifty percent or sixty percent, 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 five to seven, another peak in the age sort of 30 group and then another peak in the late 50s, early 60s.

Speaker 2

And currently in The U. S, for instance, vaccination for HPV is only around fifty percent in males, below sixty percent in females. So a large proportion of the adult population, I think it's been estimated that around seventy percent is not protected against HB6 and eleven. And it's also not entirely clear how long 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.

Speaker 2

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. And in fact, we think this is actually an under diagnosed disease in the adult population.

Speaker 11

Got it. Very helpful. Thank you. Jacqueline Hsieh, and Mike.

Speaker 2

Thank

Operator

you. And there are no further questions at this time. I will now hand the call back to Ms. Jacqueline Hsieh for any closing remarks.

Speaker 2

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 03/2007. 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 commenting programs like 03/2012 and leveraging potential partnership opportunities.

Speaker 2

This includes building on the breakthrough potential of our dMAb program and other next gen DNA medicine technology. 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 medicines. For those suffering from RRP in particular, we strongly motivate it by the understanding that every day and every surgery matters. Thank you for your attention and good evening everyone.

Operator

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

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Earnings Conference Call
Inovio Pharmaceuticals Q4 2024
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