Inovio Pharmaceuticals, Inc. (NASDAQ: INO) held its Q3 2024 earnings call on November 14, 2024, where CEO Dr. Jacqui Shea and other executives shared updates on the company's DNA medicines platform.
The highlight of the call was the lead product candidate, INO-3107, for treating recurrent respiratory papillomatosis (RRP), which demonstrated an 81% clinical response rate in its Phase 1/2 trial. Inovio is preparing for a Biologics License Application (BLA) submission by mid-2025, following a positive pre-BLA meeting with the FDA.
The company reported a net loss of $25.2 million for Q3 2024 but improved its cash position to $84.8 million. Inovio also addressed a manufacturing issue related to a device component, which is critical for advancing their Phase 3 trial of INO-3112. Executives expressed confidence in INO-3107's market potential, despite competition, and are developing strategies for successful market entry.
Key Takeaways
- INO-3107 showed an 81% overall clinical response rate in Phase 1/2 trial for RRP.
- A Biologics License Application (BLA) submission is targeted for mid-2025.
- Inovio ended Q3 2024 with $84.8 million in cash and no debt.
- The company reported a reduced net loss of $25.2 million for Q3 2024 compared to the previous year.
- Manufacturing issues with a device component need resolution before advancing Phase 3 trial of INO-3112.
- The company is actively preparing for a confirmatory trial for INO-3107 and engaging with European regulators on trial design for INO-3112.
Company Outlook
- Inovio is on track to submit the BLA for INO-3107 by mid-2025.
- The company plans to request a rolling submission and priority review from the FDA.
- Educational materials are being developed for both patients and physicians to facilitate INO-3107's market entry.
Bearish Highlights
- The company reported a net loss for the quarter, although it was an improvement from the previous year.
- Manufacturing challenges related to a device component must be addressed to proceed with the Phase 3 trial of INO-3112.
Bullish Highlights
- Strong immunological data supports the clinical efficacy of INO-3107.
- The company has a clear go-to-market strategy and is preparing to engage with health plans pre-approval.
- Inovio is confident in the distinct profile of INO-3107 compared to the competition.
Misses
- No specific financial performance targets or revenue projections were discussed.
- The resolution of the manufacturing issue remains a critical step before progressing with the Phase 3 trial of INO-3112.
Q&A Highlights
- Executives addressed the competitive landscape, emphasizing INO-3107's differentiation from Precigen (NASDAQ:PGEN)'s product.
- A separate trial for redosing INO-3107 post-commercial launch is planned.
- The company is exploring options to strengthen their balance sheet while advancing other candidates.
InvestingPro Insights
Inovio Pharmaceuticals' recent earnings call paints a picture of a company at a critical juncture, with promising clinical results for INO-3107 but facing financial challenges. InvestingPro data and tips provide additional context to the company's current situation.
According to InvestingPro, Inovio's market capitalization stands at $123.85 million, reflecting the market's current valuation of the company. This relatively small market cap aligns with the company's developmental stage and the challenges it faces.
An InvestingPro Tip highlights that Inovio is "quickly burning through cash," which is consistent with the company's reported net loss and the need to strengthen its balance sheet mentioned in the earnings call. This rapid cash burn is typical for biotech companies in the development phase but underscores the importance of the company's efforts to explore options for financial reinforcement.
Another relevant InvestingPro Tip indicates that Inovio "holds more cash than debt on its balance sheet." This aligns with the company's reported cash position of $84.8 million and no debt, providing some financial flexibility as it moves towards its BLA submission for INO-3107.
The InvestingPro data shows a significant revenue decline, with a -93.85% revenue growth in the last twelve months. This decline is reflected in the earnings call's focus on future potential rather than current financial performance, emphasizing the importance of INO-3107's success for the company's future.
Investors should note that InvestingPro offers 13 additional tips for Inovio Pharmaceuticals, providing a more comprehensive analysis of the company's financial health and market position.
Full transcript - Inovio Pharmaceuticals Inc (NASDAQ:INO) Q3 2024:
Operator: Good afternoon, ladies and gentlemen, and welcome to the Inovio Third Quarter 2024 Financial Results Conference Call. At this time, all lines are in a listen-only mode. Following the presentation, we will conduct a question-and-answer session. [Operator Instructions] This call is being recorded on Thursday, November 14, 2024. I would now like to turn the conference over to Thomas Hong, Manager of Investor Relations. Please go ahead.
Thomas Hong: Good afternoon and thank you for joining the Inovio third quarter 2024 financial results conference call. Joining me on today's call are Dr. Jacqui Shea, President and Chief Executive Officer; Dr. Mike Sumner, Chief Medical (TASE:PMCN) Officer; Peter Kies, Chief Financial Officer; Steve Egge, Chief Commercial Officer; and Dr. Matthew Morrow, VP of Translational Sciences. Today's call will review our corporate and financial information for the quarter ended September 30th, 2024, as well as provide a general business update. Following prepared remarks, we will conduct a question-and-answer segment. During the call, we will be making forward-looking statements regarding future events and the future performance of the company. These events relate to our business plans to develop Inovio's DNA medicines platform, which include clinical and regulatory developments and timing of clinical data readouts and planned regulatory submissions, along with capital resources and strategic matters. All of these statements are based on the beliefs and expectations of management as of today. Actual events or results could differ materially. We refer you to the documents we file from time to time with the SEC, which under the heading risk factors, identify important factors that could cause actual results to differ materially from those expressed by the company verbally, as well as statements made within this afternoon's press release. This call is being webcast live, and a link can be found on our website, ir.inovio.com. And a replay will be made available shortly after this call is concluded. I will now turn the call over to Inovio’s President and CEO, Dr. Jacqui Shea.
Jacqui Shea: Good afternoon, and thank you to everyone for joining today's call. This quarter, we continued to make progress on the key objectives we've been focused on for 2024 to deliver value to stakeholders in the near, mid, and longer term, and most importantly deliver on the promise of DNA medicine for patients. Those objectives include, firstly, advancing our lead product candidate, INO-3107, towards commercialization. Secondly, advancing our pipeline. And thirdly, continuing to strengthen our business overall. Today, I will provide an overview of our progress and then ask my colleagues to provide greater detail. To begin with, we've recently announced important additional immunology data, supporting the proposed mechanism of action for 3107 and its potential to eliminate or reduce the number of surgeries RRP patients have to face. This extensive immunological characterization data, highlighting the ability of 3107 to induce T-cell responses that correspond to the clinical benefit observed in our Phase 1/2 trial has been presented at two scientific conferences, including the International Papillomavirus Conference this week. We have also presented the full safety and efficacy data, demonstrating that 3107 was shown to be well tolerated and have clinical benefit in our Phase 1/2 trial at two recent scientific conferences. We believe the powerful combination of this additional data further highlight the potential for 3107 to become the preferred choice for the broadest number of RRP patients should it be approved. Mike and Steve will provide further details on this later in today's call. Moving on to regulatory matters, in August, we held a positive pre-BLA meeting with the FDA. Since then, we have continued preparing for submission of our BLA targeted in mid-2025. We expect to have all non-device related modules for the BLA completed by the end of this year. You'll recall during our last quarterly call, we announced we had recently identified a manufacturing issue for the single-use component of our device during the testing required for our BLA submission. We believe we have identified the appropriate resolution for this issue and are making good progress in implementation. In summary, we remain confident in our ability to deliver 3107 to the market for patients as an important and new therapeutic option to treat this devastating disease. As this is our primary focus, we are directing the majority of our resources, both people and financial, towards completion of development, BLA submission, and preparing for our potential commercialization of 3107. However, even with 3107 as our primary focus, we are mindful of the significant potential of the rest of our pipeline and have continued to make important progress on several other candidates as well. For INO-3112, we've consulted with European regulators regarding the design of our proposed Phase 3 trial, evaluating 3112 in combination with the PD-1 inhibitor LOQTORZI as a potential treatment for locally advanced HPV16/18 positive high risk oropharyngeal squamous cell carcinoma, also known as throat cancer. We anticipate conducting this trial in North America and Europe. Previous discussions with the FDA have indicated alignment with the proposed trial design. Continuing in oncology for INO-5401, patients continue to be dosed in the GBM-001 trial in newly diagnosed glioblastoma that combines 5401 with Regeneron (NASDAQ:REGN)'s PD-1 checkpoint inhibitor, Libtayo. Regeneron and Inovio have discussed that an appropriate next step for GBM could be a controlled Phase 2 trial. A separate trial evaluating 5401 in patients with the BRCA mutation is ongoing at the Basser Center at the University of Pennsylvania. We also have an upcoming meeting scheduled with the FDA later this quarter to discuss the Phase 2 trial design and development pathway for INO-4201 as a heterologous boost to the FDA licensed Ebola vaccine, Ervebo. From our earlier stage candidates, we expect clinical data from an ongoing Phase 1 study with DNA encoded monoclonal antibodies to be submitted to a peer-reviewed publication by year-end. We believe this will be the first clinical data for DNA-delivered monoclonal antibodies to be reported and illustrates what we believe to be the transformational potential of our DNA medicines platform. Finally, our commitment to financial discipline and strengthening our business is a core component of our strategy for success. While we've made substantial progress on our overall goals, we've done so while continuing to reduce our operating expenses. We closed the third quarter with $84.4 million in cash, cash equivalents, and short-term investments, and with no debt. Now, I'll turn it over to Mike for some additional insights from the new data on 3107. Mike?
Mike Sumner: Thanks, Jacqui. Before I dive into the new data that we have presented at several scientific conferences over the last couple of weeks, I think it's important to review why we're working so hard to bring INO-3107 to patients. RRP is a rare HPV related disease, characterized by small wart-like growths called papillomas, found in the respiratory tract. People with RRP mount an insufficient immune response that's unable to prevent or clear the HP (NYSE:HPQ) infection from their airways, so the papillomas can grow unchecked. The papillomas often cause difficulty speaking or complete voice loss, difficulty swallowing, shortness of breath, or choking episodes. The current standard of care is surgery to clear out the papillomas, but that doesn't address the underlying viral cause of the disease. And the papillomas grow back, setting patients up for an endless cycle of resurgence of symptoms and need for more surgery. Every single surgery presents a risk of permanent vocal cord damage, reinforcing what patients have said time and again, that a reduction of even one surgery would be life changing. That patient experience has been central to our efforts to develop 3107, which we believe has the potential to change the treatment paradigm for RRP. Designed to generate antigen-specific cytotoxic CD8 T cells, targeting both HPV-6 and HPV-11, 3107 is a potential novel, non-surgical treatment option for RRP patients. In our Phase 1/2 clinical trial, we observed a compelling combination of clinical benefit and tolerability across the disease spectrum of severity and including both HPV-6 and HPV-11 driven disease. In addition, we saw the generation of a significant and targeted immune response that was associated with a reduction or elimination of surgeries for these patients. We believe that the growing body of evidence shows that 3107 could be used to treat the vast majority of RRP patients and supports its potential to be the preferred product of choice by patients, healthcare providers, and payers if approved. At the International Society of Vaccines Conference and the Fall Voice Conference this past October, Inovio presented its full safety and efficacy data for the Phase 1/2 trial, which is summarized here. In the trial, the overall clinical response, defined as patients experiencing a decrease in the number of surgical interventions in the year after the initial 3107 administration compared to the prior year was 81% or 26 of the 32 enrolled patients. This number includes 28% that required no surgical intervention during or after the dosing window. These are our complete responders. Further, 44% of patients had a partial response, defined as a reduction of at least 50% in the number of surgeries when compared to the prior year. The overall response rate, calculated by adding our complete responders and partial responders, was 72%, or 23 out of 32 patients. Importantly, in our trial design, we counted every surgery after day zero because every surgery matters to patients. On this slide, you can see our overall safety data. 3107 was well tolerated in the study, with the most common treatment-related adverse events being injection site pain reported in less than a third of patients. Supporting that as [CELLECTRA] (ph) electroporation device was well tolerated by patients and was also easy to use by healthcare providers. Fatigue was the next most frequent reported treatment related AE in just three patients. No treatment related adverse events greater than Grade 2 severity were reported. One of the core strengths of our DNA Medicine Platform is the ability to drive a T-cell response, which is particularly important for treating chronic viral disease. You can see on this slide the proposed mechanism of action for 3107, inducing HPV antigen-specific T-cell responses in the blood, then having those T-cells travel to and infiltrate the papilloma and airway tissue, and ultimately eradicate the HPV infected cells to reduce or eliminate the need for surgery. I'd like to now turn to our new immunology data that we have shared at the recent scientific conferences, including this week at the International Papilloma Virus Conference. To further characterize immune responses to 3107, we analyzed blood and tissue samples from patients in our Phase 1/2 trial. Our goal was to evaluate the individual steps that combine into the proposed mechanism of action that I just presented. We conducted a number of very extensive immunological assessments on blood and tissue samples to, one, confirm the induction, activation, and expansion of cytotoxic T-cells with antigen specificity to HPV-6 and HPV-11. And two, to assess the level and form of immunological change from baseline, including T-cell infiltration and profiling, and the potential impact of the papilloma microenvironment on clinical effect. In short, what we discovered was very compelling. The data demonstrated the ability of 3107 to do exactly what it was designed to do, induce HPV antigen-specific T-cell responses in the blood that infiltrate papilloma and airway tissues and that they are the right kind of T-cells to eradicate HPV-infected cells and ultimately reduce or eliminate the need for surgery. Overall, the key takeaways from this study include five main points. First, INO-3107 generates the right kind of immune responses to fight HPV for the vast majority of RRP patients. In our research, we see generation of HPV-6 and HPV-11 antigen-specific cytotoxic T-cells with responses that are durable out to 52 weeks, indicating a long-lived memory response, which is important for the treatment of a chronic viral disease like RRP. Second, the newly generated T-cells get to where they need to go. Our data shows that T-cells travel from the blood to the papilloma and airway tissue, and the resulting inflammatory and antiviral responses are seen in the tissue. Third, the immune response we have observed is targeted and specific to treatment with INO-3107. We saw expansion of both pre-existing T-cell clones and the emergence of new T-cells in the blood. These new T-cells could not be detected prior to treatment, meaning the majority of T-cells seen in airway tissue at the 52-week time point were emergent clones. The presence of these new T-cells in the tissue corresponds with the clinical benefit we saw in the trial. Fourth, we were also able to show that immune responses in responders are different to those seen in non-responders. While all 32 patients in the trial were seen to generate an immune response in the blood, the kinetics and magnitude of that response differed based on the clinical response seen. We believe we can build on these initial responses in non-responders through the administration of additional doses. And finally, from our evaluations to date, we have looked at elements of the papilloma microenvironment that have been reported in recent scientific literature to impact the potential efficacy of treatment. To date, we have not found evidence that these elements appear to restrict the clinical benefit of 3107. This immunology data is currently under review at a peer-reviewed journal, and we look forward to providing an update on that publication when available. So in summary, I would like to point out why this new data is so important to the potential of INO-3107. First and foremost, we believe the immunology data support the biological mechanism of action of 3107. This data will be an important component of our upcoming BLA submission and other future regulatory filings. The data confirm that 3107 effectively targets HPV-6 and HPV-11, the strains that cause the vast majority of RRP disease. The data confirm that 3107 generates new and expands existing populations of T-cells and activates them to eliminate the underlying cause of the disease. The data also support that 3107 can have clinical benefit across the disease severity spectrum and in both HPV-6 and HPV-11 driven disease. Remember that patients tell us that every surgery matters. So our goal is to be able to treat patients with RRP, regardless of the severity of disease. In short, we believe these data provide compelling evidence that INO-3107, if approved, can be a game changer for RRP patients by reducing their need for repeat surgeries to treat their disease. I'd also like to mention that in addition to this important immunology work, we have also recently completed a retrospective study investigating the long-term durability of clinical response seen in patients treated in our Phase 1/2 study. We anticipate announcing that data by year-end. On that note, I'll now turn it over to our Chief Commercial Officer, Steve Egge, for an update on our commercial efforts. Steve?
Steve Egge: Thanks, Mike. Hello, everyone. At our last quarterly report, I outlined the significant opportunity I see for 3107 based on its compelling product profile. Over the last quarter I've worked closely with our internal team and external consultants to continue to develop and refine our plans for the launch of 3107 if we receive FDA approval. We're making important progress and focused on developing a go-to-market strategy that's rooted in ensuring we meet physician, payer, and most importantly, patient needs. We've conducted a significant amount of market research to develop key insights with stakeholders to ensure we have a deep understanding of the market and the opportunity for 3107. We have repeatedly heard from patients that every single surgery matters and that a reduction in even one surgery makes a meaningful difference in the lives of patients. Because of the potential of a competitive marketplace, I won't go into significant detail, but at a high level, we are making strategic choices in a number of key areas, including pricing and access. From a pricing standpoint, we do expect to price in line with current rare disease pricing, and we've confirmed acceptability of this in feedback from payers that represent the majority of commercial lives in the US. We're also making strategic choices on distribution, physician and patient targeting and segmentation, as well as product positioning to ensure we're well differentiated. We've refined our plan for pathways for product adoption to ensure we provide an optimal customer experience. We did hear from the FDA earlier this month that our proposed brand name for 3107 is acceptable at this time. Of course, the decision of the brand name will be confirmed by the FDA during the BLA process. We're refining our forecasting and gross-to-net assumptions, and we've also developed strategic imperatives for the business to ensure we're focused on what matters most in a successful product launch, And these include metrics on how we'll measure our progress. And finally, we've also planned out -- planned the build-out of the commercial organization, including field teams in 2025. We're planning for a lean and efficient commercial footprint. And as we've communicated previously, we plan to be launch-ready by the end of 2025. I also want to echo Jacqui and Mike. The new data we've shared today supporting our proposed mechanism of action builds on 3107's compelling product profile and strengthens my belief that 3107 can treat a broad range of RRP patients, and that it could be the preferred choice for RRP patients and physicians. I'll now turn it over to our Chief Financial Officer, Peter Kies, for a financial update.
Peter Kies: Thanks, Steve. Today I'd like to provide an overview of Inovio’s financial results for the third quarter of 2024. As Jackie noted at the start of the call, we are primarily focused on advancing INO-3107 and our goal to submit a BLA mid-2025. To support these efforts, we have continued to control our operating expenses. For the third quarter ended September 30, 2024, our total operating expenses dropped 24%, from $35.9 million in the third quarter of 2023, to $27.3 million in the third quarter of 2024. Inovio's net loss for the third quarter of 2024 was $25.2 million, or $0.89 per share, basic and dilutive, compared to a net loss of $33.9 million, or $1.52 per share, basic and dilutive, for the third quarter of 2023. We finished the third quarter of 2024 with $84.8 million in cash, cash equivalents, and short-term investments, compared to $145.3 million as of December 31, 2023. We estimate our cash runway to take us into third quarter 2025. This projection includes an operational net cash burn estimate of approximately $24 million for the fourth quarter of 2024. These cash runway projections do not include any further capital raising activities that Inovio may undertake. As a reminder, you can find our full financial statements in this afternoon's press release as well as in our Form 10-Q filed with the SEC. And with that, I'll turn it back over to Jacqui.
Operator: [Operator Instructions] Your first question comes from the line of Jay Olson from Oppenheimer. Your line is now open.
Jay Olson: Congrats on all the progress with your 3107 BLA filing in the US. Can you talk about any regulatory updates for 3107 outside the US? It sounds like you're making progress in EU and UK. What are the timelines for filing in those markets and any update on Japan, China or other major markets? And then I had a follow-up if I could.
Jacqui Shea: Hi, Jay. Nice to hear from you. Mike, do you want to comment on where we are with our other regulatory filings?
Mike Sumner: Yeah, certainly. So I mean, we have met with the UK and they gave very similar advice to their European colleagues. And that was basically that to gain approval in the European Union and the UK, you're going to need placebo controlled data that needs to be compelling. And so the rationale behind us running a placebo controlled study was not only that we would get an indication of just two surgeries, but also that that data could be used in those markets. But we are going to have to complete that study prior to submitting into Europe. We have not yet reached out to Japan and China, but clearly they do have RRP. We've spoken to AOLs in some of those regions, and so they are areas of interest for us to progress.
Jay Olson: Okay, great. Thank you very much. That's super helpful. And then congrats also on the new immunology data that you presented at AACR and IPVC. Could you share any physician feedback that you may have received on that data and what are physicians ultimately looking for?
Jacqui Shea: Mike, do you want to come in here?
Mike Sumner: Yeah, certainly. So, I mean, firstly, look, I think as I talk to it, it really is compelling data. Matthew Morrow, who's also on this call, is our translational sciences person. He's done a great job of really characterizing the mechanism of action of 3107. And I think as we've talked to clinicians and scientists about that data, they really can see what 3107 is doing from an immunological basis. And I think that just gives them more confidence in the clinical data that we have presented. So I think it just ties in very nicely, and also will tie in very nicely as we submit that BLA to link up the clinical data with what's actually happening from an immunological standpoint.
Jacqui Shea: I think we can also say, Mike, and as evidenced by Professor Steinberg's quotes in our recent press release around the data, generally KOLs in the field have been very impressed with the data when we've shared and discussed it with them. I think for them, this is part of going after the holy grail of having the effective therapeutic option to treat RRP.
Jay Olson: Great. That's super helpful. Congrats again on all the progress. And thanks for taking our questions.
Jacqui Shea: Pleasure.
Operator: Your next question comes from the line of Roy Buchanan from Citizens JMP. Your line is now open.
Roy Buchanan: Hey, thanks also for taking the question. Just, I mean, maybe to start on 3107 as well, can you just give maybe some additional detail on the steps that you're envisioning to resolve the manufacturing issues? Thanks.
Jacqui Shea: Hi, Roy, nice to hear from you. Yeah, so as I outlined on the call, we encountered the issue, the manufacturing issue, earlier on this summer, just ahead of our pre-BLA meeting. And we're going through, and this is an issue with a single use disposable component of our device. We've gone through the steps we need to take to understand the appropriate resolution for that issue and we're making good progress in implementation. And I think that's all I can really say at the moment.
Roy Buchanan: Okay, fair enough. And then I think this, correct me if I'm wrong, but the Phase 3 start for 3112 was also gated by resolving this manufacturing issue. Is that correct? The device is approved, essentially, in Europe, right, with the CE mark. Is it possible that you might be able to start first, the Phase 3 in Europe? And when do you think you might be in position to do that if so?
Jacqui Shea: Yeah, that's a great question, Roy. So yes, for 3112, starting that Phase 3 trial is dependent on resolving this device issue as well. Mike, do you want to talk about our regulatory interactions in Europe around 3112?
Mike Sumner: Yes, so I mean as we've previously said we've got an alignment from the FDA on the design that we proposed for that study. We're in discussions with the EMA, and we're expecting feedback to gain alignment. HPV is a global disease, and in most high-income countries, the incidence of throat cancer continues to rise. So we would very much like to run this study across -- in both regions. So we're anxiously awaiting that feedback and then we can update you on that at the next call.
Roy Buchanan: Okay, great. And maybe I'll jump back in queue, and let other people ask questions.
Operator: Your next question comes from the line of Sudan Loganathan from Stephens. Your line is now open.
Sudan Loganathan: Thank you for taking my question. Quick question on the competitive landscape. I think Precigen’s 2012, how do you differ from that product, and how do you see the competitive landscape panning out?
Jacqui Shea: Yeah, that's a great question. So I'll start off by saying, first of all, we're very confident in the product profile that we see for 3107. And we believe that it has the right profile to be the preferred product of choice for patients and physicians. And the sort of reasons why we believe in that, as Mike discussed earlier on in the call, our ability to drive clinical benefit across the severity of disease, across both HPV-6 and HPV-11. And I think this new immunology basis really gives us a very clear idea of exactly how 3107 is doing that. So 3107 is a DNA medicine. Precigen's product is based around a Gorilla adenovirus. So it's using an adenoviral vector to deliver the gene sequences. And it's difficult to compare the clinical data, because the two trials were conducted in a very different way. So, for 3107, we believe every surgery matters to patients. So we counted every surgery after day zero. And I think in conjunction, Precigen used a somewhat different trial design that allowed scoping and surgery prior to assessment of the efficacy period. So we really took a very different approach. Mike, anything else you want to add to that sort of calls out the differences between those two products? Product candidates?
Mike Sumner: I mean, I think fundamentally, they're very different treatment regimen. While we both have four doses, their treatment regimen at week six and week 12 includes proactive scoping and removal of any papilloma that is visualized. And so if you go back to sort of the message we've heard from patients, every surgery matters. They did see a significant number of surgeries at those week six and week 12 time points. And so we do think that's going to impact how other physicians take up the treatment and also how patients might perceive it.
Sudan Loganathan: Thank you. If I can ask another question. The manufacturing plastic molding, would you consider changing the manufacturer? Is that on the table?
Jacqui Shea: Yes. So I guess your question relates to the manufacturing issue I mentioned earlier relating to the single-use disposable component of the device. And what we're doing here is we've, as I mentioned, we believe we've identified the issue and come up with a proposed resolution path. And we're working very closely with the manufacturer of that injection molded component to implement that resolution. So at the moment, we're not planning on changing manufacturer. We're working very closely with our existing manufacturer to implement that resolution.
Sudan Loganathan: Thank you.
Operator: Your next question comes from the line of Liang Cheng from Jefferies. Your line is now open.
Liang Cheng: Hey, team, thanks for taking our questions. This is Liang Cheng for Roger from Jefferies. So I guess my first question, also about 3107, just wondering any idea about the confirmatory trial, are you still thinking about the same design, or do you envision any implement of redosing in that study? And then also about 3107, the immunology study. So I just wonder, have you looked at the responders versus non-responders? And anything you notice there? Thanks.
Jacqui Shea: Yeah, that's a great question. So we have talked about the design of our confirmatory trial. Mike, do you want to outline that design and why we decided on it?
Mike Sumner: Yeah, absolutely. So in discussions with the agency, they made it very clear if we wanted to have an indication similar to what we used in our Phase 1/2 trial of two surgeries in the preceding year, then the study had to be a placebo controlled study. And so, along with my previous comments with respect to the feedback we've received from Europe, it just made sense to run a randomized study. And we're clearly very confident in the clinical efficacy that we've seen. This isn't going to be a particularly large study about a hundred patients. We're going to have a two-to-one randomization and then follow those patients out. We aren't going to include a redosing element into this study at present. And the rationale for that is, we have had previous patients treated with an HPV-6 only plasmid that have had efficacy out to [500 in] (ph) over 800 days. So in discussion with the agency, they were keen for us to have a longer follow-up than we previously had in our Phase 1/2 study. And that was also the motivation for us to run the retrospective study that we'll hopefully -- well, we will report on by the end of the year. So we really do think you need a longer period of time to characterize the benefit of 3107. That's why we picked that confirmatory study design the way we have.
Jacqui Shea: Thanks, Mike. And I'll just comment briefly on the immunology data, and then I'll ask Matthew to fill in a bit more detail. So yes, absolutely, we looked at responders versus non-responders. And we looked at two sets of samples. The first set of samples were peripheral blood samples that we collected throughout the duration of the trial. And then we also had tissue samples, so samples taken from the airways prior to treatment and then at the 52-week time period. And these were paired tissue samples taken from the same patients and from the same anatomical location. And we saw a difference in the kinds of immune responses that we saw in responders versus non-responders that we believe corresponds with clinical benefit. But, Matthew, do you want to jump in and add some other comments here?
Matthew Morrow: Sure. Good afternoon. So, yes, in addition to what Jacqui has mentioned, the responses within the tissue of the responders is slightly different than that of non-responders with respect to degree of infiltration of T-cells, some of the functionality of those T-cells, and just the overall inflammatory response and interferon alpha and interferon gamma responses that are being observed. And all of these assessments will be further described in the publication that is forthcoming.
Liang Cheng: Thanks, that's very helpful. I guess also for 3112, just wondering for the ongoing conversation with the EU regulators, what's needed before the cloud initiation? Thanks.
Jacqui Shea: Yeah, Mike, do you want to comment on that?
Mike Sumner: Yeah, so I mean, obviously, the purpose of the interaction is to gain alignment with the overall strategic intent of how we've designed 3112. And I think, as we've said previously, we actually used global KOLs in this study design. And so we have a very good representation from Europe. And so we're optimistic that we can gain that alignment. And then just the practical part is we obviously would have to put a clinical trial application into the EMA, so before we started recruiting patients.
Liang Cheng: Got it. Thanks, Mike. That's all for now. Thank you.
Operator: Your next question comes from the line of Yi Chen from H.C. Wainwright. Your line is now open.
Unidentified Analyst: Hi there, this is Eduardo on for Yi. I wanted to thanks for taking the question. I was curious if you could offer a little bit more clarity on the timeline for initiating the confirmatory trial for 3107 and how that fits in with the BLA submission that you already expressed?
Jacqui Shea: Yeah, great question, Eduardo. So as we stated very clearly on the call, we're targeting our BLA submission for mid-2025. We need to start our, FDA have told us that we need to start our confirmatory trial ahead of commencing that BLA submission. And we're expecting to request rolling submission priority review as part of that BLA submission. So what I can tell you today is mid-2025.
Unidentified Analyst: Great.
Mike Sumner: Maybe I'll add a little bit of color around our activities. We -- the FDA said we needed to commence that study and clearly their rationale for that is often sponsors have not been very forthcoming in delivering their confirmatory studies. We, however, are at the opposite end of that spectrum. We have almost all our sites identified. We are contracting with sites. We have active IRB submissions. So we will be in a very good position to demonstrate our commitment of delivering on that confirmatory study to the agency.
Jacqui Shea: Yeah, thank you, Mike. That's a great point. I think we've also really leveraged our experience from our Phase 1/2 study that we conducted in the US, where we worked across eight different clinical trial sites, relief centers that are at the forefront of treating RRP. So I think that experience of working across different sites as well has been very helpful.
Unidentified Analyst: Great. Thanks so much for the clarity there.
Operator: Your next question comes from the line of Gregory Renza from RBC capital markets. Your line is now open.
Unidentified Analyst: Hi team, it's Anish on for Greg. Thanks for taking our questions. On 3107 and the selector device, maybe if you could just remind us the duration of the AE's such as injection site pain and fatigue, how rapidly they were resolved and how this translates to patient and physician expectations when using the selector device. And if you think about the commercial strategy, with Precigen also reporting after the close and suggesting a 2025 launch, how are you thinking about your approach and go-to-market strategy, which could support uptake in the market given the prospects of a competitor already being on the market by the time you would launch. Thanks so much.
Jacqui Shea: Okay. Thanks, Anish. Great questions. So, in terms of 3107, as Mike talked about during the call, in terms of our combined safety data, I think, Mike, you can talk about the adverse event profile that we saw and how quickly they resolved?
Mike Sumner: Yeah, absolutely. So when you look at the population as a whole, we only had 41% of patients report any treatment related adverse event. 10 of those were -- 10 out of the 32 patients reported injection site pain. From a grading perspective, only one of those was Grade 2. The rest, in fact, the rest of the entire treatment-related adverse events were Grade 1 after that. And we have data from other electroporation studies that show that the injection site pain associated with the initial administration really falls off in about a sort of 5,10 minute timeframe. And as part of our rollout of the device is really going to be around explaining what the patient should expect, how the physician should educate the patient on that, because clearly this is a new procedure. So half of it is around the unknown. So as we come to market, we'll very carefully be able to have materials for the patient to know what to expect. And history says that having that level of expectation in place will hopefully further diminish any adverse events associated with electroporation and diminish that injection site pain.
Jacqui Shea: I think it's also very important to note, Mike, is these adverse events are very transient. They resolve very rapidly. And certainly we hear from patients that the treatment is very tolerable, and the healthcare providers tell us that the device is very easy to use. So we think, particularly in a disease like RRP, where it's really having a devastating impact on patients. That the rapid resolution of those AEs is going to be very important. So, Anish, does that answer your questions around the 3107 profile? And then we can maybe go on to the ‘25 launch and go-to-market strategy.
Unidentified Analyst: That would be great, thanks.
Jacqui Shea: Yeah. So, as I discussed earlier on in the call, we believe that 3107 has a compelling product profile that will enable it to become the preferred product of choice for the majority of patients and physicians. And I'll hand over to Steve to expand on this in a bit more detail. But it's also, we've only seen limited data from Precigen to date. We haven't seen the full data package published yet from the second cohort. So I think we'll be very interested to see that data when it's published. And the difference in the two treatment regimens and approaches, I think, are going to be very interesting. I think our duration data that we expect to be able to announce later on this year is also going to be important. So, Steve, do you want to provide your point of view?
Steve Egge: Yeah, so we don't know necessarily that that Precigen will be in the market, before we will. We'll see kind of how things unfold. But regardless, we do plan to have MSLs out of approval, as well as national account managers engaging health plans ahead of approval, which they can do. We think we've got a well differentiated product based on the data that we've seen so far. So that's certainly what we'll be focused on, but we know there's tremendous on that need in the market and the burden around surgeries. As we've talked about, every surgery matters. So as soon as we're able, as soon as we're approved, we will be out there in full force, making the case for 3107.
Unidentified Analyst: Perfect, thank you.
Operator: Your next question comes from the line of Roy Buchanan from the Citizens JMP.
Roy Buchanan: Hey, thanks for taking the call. It was about the redosing and you actually answered most of it, but I guess just thinking you're going to run a separate trial to look at redosing of 3107, correct? Do you plan to run that in conjunction with the confirmatory trial, or is it going to be sequenced after the conclusion of that trial? Thanks.
Jacqui Shea: Yeah, Mike, do you want to talk about that redosing approach?
Mike Sumner: Yeah, absolutely. So we've always thought that the redosing work would be in commercial patients. So we will commence that as sort of as soon as practically possible post launch. And, we are thinking that those complete responders potentially could maintain. And at IPVC this week, there's been a lot of talk around, can you actually eliminate all the HPV infected cells and I think that'll be one of the interesting scientific questions that we can look at through continued dosing. But that work is going to take a while. And we will commence that after commercial launch.
Roy Buchanan: Okay, thank you.
Operator: There are no further questions at this time. I will now turn the call back to Jacqui Shea for closing remarks. Please go ahead.
Jacqui Shea: Thank you. The new immunology data that we've discussed today adds to a growing body of evidence that continues to illustrate the potential of 3107 to truly transform the treatment paradigm for patients who have been living with the devastating effects of RRP. We are mindful of those patients as we remain focused on moving as quickly as possible to meet the key milestones ahead, including publishing the new immunology data, announcing new durability, submitting our BLA, and preparing to be launch-ready at the end of 2025 should we receive approval. At the same time we're advancing other key candidates and evaluating ways to strengthen our balance sheet to support our work going forward. As we wrap up this year, I'm proud of the important progress we've made in just 12 short months, and we plan to keep that momentum going in the year ahead. Thank you for your attention, and good evening, everyone.
Operator: Ladies and gentlemen, this concludes today's conference call. Thank you for your participation. You may now disconnect.
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