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spk05: Good day, and welcome to the Inovio First Quarter 2023 Financial Results Conference Call. All participants will be in a listen-only mode for the duration of the call, and should you need any assistance today, please signal a conference specialist by pressing the star key followed by zero. After today's presentation, there will be an opportunity to ask questions. To ask a question, you may press star, then one on your telephone keypad. And to withdraw a question, please press star, then two. Please also note that this event is being recorded today. I would now like to turn the conference over to Thomas Hong, Manager of Investor Relations. Please go ahead.
spk00: Good afternoon, and thank you for joining the Inovio 2023 First Quarter Conference Call. Joining me on today's call are Dr. Jackie Shea, President and CEO, Dr. Michael Sumner, Chief Medical Officer, and Mr. Peter Keyes, Chief Financial Officer. We also have other members of Inovio's leadership here with us today, who will be part of our Q&A session. Today's call will review our corporate and financial information for the quarter ended March 31st, 2023, as well as provide a development progress update for our DNA medicines platform. Following prepared remarks, we will conduct a question and answer segment. During the call, we will be making forward-looking statements regarding future events and the future performance of the company. These events relate to our business plans to develop Inovio's DNA medicines platform, which include clinical and regulatory developments and timing of clinical data readouts, along with capital resources and strategic matters. All of these statements are based on the beliefs and expectations of management as of today. Actual events or results could differ materially. We refer you to the documents we file from time to time with the SEC, which under the heading Risk Factors, identify important factors that could cause actual results to differ materially from those expressed by the company verbally, as well as statements made within this afternoon's press release. This call is being webcast live, and a link can be found on our website, ir.inovio.com, and a replay will be made available shortly after this call is concluded. I will now turn the call over to Inovio's President and CEO, Dr. Jackie Shea.
spk02: Good afternoon, and thank you to everyone for joining today's call. In the first quarter of 2023, we made solid progress with several key pipeline candidates. Notably, we made important headway in the development of INO3107, our product candidate for recurrent respiratory papillomatosis, or RRP. Our Chief Medical Officer, Dr. Mike Sumner, will provide more detail about our overall progress for this product candidate. But in short, since our last investor call, we received the initial feedback from the FDA on our proposed Phase 3 plans, leading us to believe we have an achievable framework for a Phase 3 trial for INO3107. We also announced that the European Committee for Orphan Medicinal Products issued a positive opinion on our application for orphan drug designation for INO3107, with the European Commission's final decision expected in May. These regulatory developments come on the heels of positive data from the second cohort of our Phase 1-2 trial for INO3107 shared in February, and additional combined data on the safety and immunogenicity of INO3107 that was presented by lead investigator Dr. Ted Mao at ABEA, a premier ENT meeting in Boston just last week. This data shows that INO3107 has the ability to elicit a robust immune response and has the potential to provide clinical benefit to patients who otherwise face a lifetime of disruptive surgeries. The data presented was accepted for publication by the Laryngoscope, one of the key journals read by physicians who care for RRP patients in APROS. In the first quarter, we also announced encouraging data from our Phase I trial with INO4201 as an Ebola booster for Avibo, which not only showed the potential of INO4201 as an important tool in extending protection against the Ebola virus, but also demonstrated the versatility of our platform and the ability of DNA medicines to elicit potentially protective immune responses across multiple indications. Additional safety and immunological data shared last month by lead investigator Dr. Angela Huntner at the 33rd European Congress of Clinical Microbiology and Infectious Diseases, or ECMID, provided more insight on the potential ability of INO4201 to generate robust immune responses and extend protection against Ebola. Mike will also share more details on that data. On our last earnings call in March, we announced top-line results for REVEAL-2, the second Phase III trial for VGX3100 as a treatment for cervical, high-grade squamous intraepithelial lesions or cervical H-cells. As we shared at that time, the trial results did not meet the primary endpoint in the biomarker-selected population, but did show statistical significance in the all-comers population. Since then, we've continued to analyze the data to better understand the biomarker population. Our goal is to share the results of this analysis with you in the third quarter of 2023. We continue to believe that the data from Reveal 2 which showed VGX3100's ability to promote viral clearance, highlights this drug candidate's potential to address the underlying cause of the disease, the HPV virus, which could make it an effective treatment option for additional indications, particularly anal H-cell. On INO5401, our collaboration with Regeneron continues. and as we wrap up the phase two study for this product candidate in glioblastoma. We still have patients on study that we are continuing to provide drug for, and we are evaluating next steps for this candidate, which we believe is worthy of further evaluation. While we've been making headway on the clinical front, we've also been able to maintain our financial position as we continue to expect our cash runway to take us into the first quarter of 2025. We will continue to ensure our strategic focus and financial discipline as we work to build on our important progress to date. An essential part of our strategy is ensuring that we have the resources and talent in place to advance our product candidates quickly and efficiently. This quarter, we welcome Dr. Cheryl Elder Senior Vice President of Regulatory Affairs to Inovio. She joins a seasoned product development team to oversee regulatory strategy and company interaction with global regulatory authorities. With over 30 years of experience leading cross-functional teams in drug development in multiple therapeutic areas, Dr. Elder has a successful track record of driving regulatory strategies within both small and multinational biotechnology companies, including Hoffman LaRoche and, most recently, Novartis Pharmaceuticals. I am confident we will benefit from her expertise as we seek to implement efficient regulatory strategies for key candidates across our pipeline. With that, I'd like to turn it over to our Chief Medical Officer, Dr. Mike Sumner, to provide some important clinical highlights.
spk03: Mike? Thank you very much, Jackie, and greetings, everyone. I'd like to start today with INO3107, our product candidate for RRP, and the development progress we've made since our last quarterly call. As Jackie alluded to, one of the most important developments for this project has been the productive interactions we've had so far with the FDA, which have helped shape the design for our Phase III trial. One of the challenges of studying the treatment effect of any drug candidate in RRP patients is that the disease can be variable among patients over time, and there are no standardized guidelines for surgical intervention. With these parameters in mind, we are preparing to conduct a randomized placebo-controlled phase three trial. We believe this trial format reflects the constructive feedback we received from the FDA and provides a clearer path forward to assess both the safety and efficacy of INO3107. We still have some additional trial details to work out with the agency before we can officially start our phase three trial, including questions related to our Selectra 5 PSP delivery device, which we are working to address. As a reminder, this device was previously successfully used in two phase three trials, Reveal 1 and Reveal 2. As we address these details, we have moved forward with engaging a clinical research organization and are actively identifying global sites as we continue to make the appropriate preparations to conduct this important, innovative, pivotal trial. Meanwhile, I'm pleased to report that we've shared the full results from our Phase 1-2 trial at different scientific and medical conferences over the last several weeks, including having our lead investigator, Dr. Ted Mao, present at the ABEA program at COSM in Boston last Friday. Dr. Mao's presentation included more detailed safety, immunological, and demographic data, which I would like to share with you today. This slide shows at a glance the impact 3107 had on the number of surgeries for the patients who were involved in our trial. I'm really pleased to summarize that 26 out of 32 patients, or 81%, experienced a decrease in surgical interventions in the year after treatment commenced versus the prior year, including 9 or 28% of patients that required no surgical intervention during that year. Patients experienced a median decrease of three surgeries in the year following treatment in comparison to the year prior to baseline. As a reminder, any surgery performed following day zero, including during the dosing window, was counted against the efficacy endpoint. As a reminder, RRP patients, as well as their physicians and advocates, have expressed that a reduction in surgeries is the most important outcome to them and that a reduction of even one surgery is a meaningful difference. In terms of demographics of the patients involved in the trial, The median age was 47 years with an age range of 25 to 82. The median number of surgeries in the year prior to dosing was four with a range of two to eight. This slide shows 3107's overall safety profile. An important hallmark of DNA medicines in general is favorable tolerability and safety. and INO3107 behaved as expected on that front in our Phase I-II trial. You can see here the most frequently reported treatment emergent adverse events being related to administration, either injection site pain or procedural pain. Treatment emergent AEs observed in the trial were generally low-grade, most of which were Grade I. Four of the 32 patients experienced a Grade III treatment emergent AE, but none were deemed related to INO3107. Two serious adverse events were reported during the trial, but again, both were deemed unrelated to 3107. There were no treatment emergent AEs leading to treatment discontinuation, and all subjects who participated in the trial received all four treatments. Next, I'd like to highlight data from the staging assessment scores. Staging assessment scores include both a subjective functional assessment of clinical parameters as well as an anatomic assessment of disease distribution, essentially assessing total disease burden. The combination of the scores measures an individual's clinical course and response to the therapy over time. There is also data supporting that the anatomic burden of RRP, as assessed by the RRP staging system, correlates well with voice-related quality of life for the patients, which is the most frequently reported symptom in adult patients. As you can see on the slide, there were improvements in the total assessment score based on the combined data for all the patients in the trial. As a reminder of what that actually looks like for a patient, I'd like to share a slide we showed at our last quarterly call. For me, it's a powerful of the clinical benefit of INO3107 and how it could potentially provide patients suffering from this terrible disease relief. Next, I'd like to share some highlights on the cellular and immune response we saw in this trial. Treatment-induced cellular responses against both HPV6 and 11, inducing both activated CD4 and activated lytic CD8 T-cells. We believe this type of cytotoxic CD8 T cell response may be important in clearing HPV-infected cells. T cell responses were also observed at week 52, which was 43 weeks after final treatment with INO3107, indicating a persistent cellular memory response. Additional analyses are also ongoing to determine a possible relationship between specific CD4 and CD8 phenotypes and clinical outcomes. This will be important as we look at ways to further improve clinical outcomes, including studying the likely duration of treatment effect and the requirement for repeat dosing. In summary, I'd like to highlight the conclusions Dr. Mao made during his presentation. Investigators noted that the data suggests that INO3107 administered with intramuscular electroporation was well tolerated with a favorable safety profile. In addition, it also appears to provide clinical benefit to adult patients with RRP and together supports further investigation of INO3107 in a phase three trial. Moving to the next slide, we recently received a positive opinion from the European Committee for Orphan Medicinal Products on our application for orphan drug designation for 3107. The European Commission will now review that opinion and make their final decision, which is expected later this month. Orphan designation in the EU would provide Inovio important benefits such as reduced fees for regulatory activities and 10 years of protection from market competition once approved. Furthermore, we recognize the considerable burden RRP places on the pediatric population and believe 3107 could also provide clinical benefit to these patients. We therefore plan to move forward in both the U.S. and the European Union with a proposal of how to approach pediatric development. At the recent International Papillomavirus Conference in Washington, D.C. that I attended, I was once again reminded of the considerable impact RRP has on patients and their caregivers' lives. As an organization, we are keeping that in mind every single day as we work to move INO3107 forward for patients around the world. Staying on our HPV franchise, I also wanted to provide some updates on VGX3100. a product candidate focusing on high-grade squamous epithelial lesions or H-cell. On our last earnings call, we announced results from our REVEAL-2 study, which was conducted in patients with cervical H-cell. At that time, we shared that the trial did not achieve statistical significance in the biomarker positive population. However, the study did achieve statistical significance in the all-comers population. Looking across the totality of data we've collected for 3100 in HPV-related diseases, we remain encouraged by the viral clearance data in various studies, including Reveal 2, where we saw viral clearance of 37% in the treated group versus 9% in the placebo group. To get a better handle on the biomarker data, we have been analyzing the results, highlighting two main areas. Firstly, a determination of why some biomarker positive subjects did not respond to treatment with a focus of looking at clinical characteristics such as stage of disease, infection with other HPV types, clinical site location, age, and smoking status. Secondly, we are looking to understand why some patients who exhibited a clinical response were not biomarker positive. For this, we plan to investigate the microRNA dataset in more detail. We expect to be able to provide you further insights into this analysis in the third quarter of 23. This biomark analysis is vital from a competitive standpoint, as VGX3100 must compete with LEAP, or the loop electrosurgical excision procedure, a well-established standard of care in the U.S. for cervical H-cells. being able to demonstrate a similar risk-benefit profile is going to be important in future regulatory discussions for that indication. VTX3100 has, however, also been studied in other indications, including anal H-CIL. As a reminder, in December 2020, we announced results of our open-label single-arm Phase II trial for anal H-CIL in which we saw that 50% or 11 out of 22 participants had no evidence of HPV1618 positive H-cell at week 36. In addition, Inovio is supporting an ongoing externally sponsored run study by the AIDS Malignancy Consortium, examining the potential of 3100 in HIV positive individuals with anal H-cell. Anal H-cell is mostly caused by HPV 1618 infections, and if left untreated, may progress to anal cancer. HPV is detected in over 91% of anal cancers, and HPV 1618 account for approximately 80% of HPV genotypes detected. In the U.S. alone, estimates of HPV 1618-related anal H-cell prevalence range from 210,000 to 1.1 million, with similar prevalence figures estimated in the European Union. While watchful waiting has historically been a common clinical practice for anal HCL, greater attention is now being paid to proactive treatment options. Recent results from the NIH and NCI-funded Anal Cancer HCL Outcomes Research, or ANCA study, in HIV-positive patients showed that treatment of anal H-cell is superior in the prevention of progression to cancer. At present, treatment of this condition is usually surgical. That includes radiofrequency ablation, resections, or laser therapy. However, ablation, which is the most common treatment currently, does not clear the underlying HPV infection, and recurrence rates are high, up to 49% one year after treatment. This leads us to believe anal H-CIL is a disease with significant unmet need that could potentially be met with a therapeutic candidate like VGX3100. The viral clearance data I mentioned earlier from our two Phase III cervical H-CIL studies, as well as our Phase II data, provide additional confidence regarding the potential of 3100 to treat the underlying cause of the majority of anal H-CIL cases. Based on positive feedback from key opinion leaders, we have started discussions with both the FDA and regulators in the European Union to determine the path forward for this indication. Now I would like to switch gears to INO4201, a DNA booster vaccine targeting Zaire Ebola virus. As Jackie mentioned recently, Dr. Angela Hutmer, lead investigator of the Phase 1B trial, for INO4201 presented new safety and immunological data at the 33rd European Congress of Clinical Microbiology and Infectious Diseases. The trial showed that the single dose of INO4201 along with intradermal electroporation was well tolerated and immunogenic compared to placebo in a cohort of healthy volunteers primed with Avibo. As you can see on this slide, both binding and neutralizing antibody titers rose significantly after the boost in 100% of subjects, with binding antibody titers rising significantly at each time point measured, peaking at week two. Likewise, neutralizing antibody titers demonstrated a similar profile. On this next slide, you can see a noteworthy engagement of T cells. Specifically, we observed an increased production of Th1 cytokines looking at interferon gamma IL-12 TNF alpha from CD4 and CD8 positive T cells following the INO4201 boost. Given the increasing attention on the role that cellular immunity may play in protecting against severe disease and its potential for aiding the durability of protection, In infectious diseases such as SARS-CoV-2, we believe having a strong cellular response profile in addition to the humoral response is a value and a potential booster for Ebola. Finally, memory marker phenotyping suggests the cytokine production was generated predominantly from central memory CD4-positive T-cells and effector memory CD8-positive T-cells. most likely indicative of persistent protection against Ebola. The data presented suggests that a booster dose of INO4201 has the potential to extend protection against the Zaire Ebola strain and could be an important tool in future Ebola virus disease prevention, a threat that does not seem to be waning. As you can see, outbreaks have continued to pop up across the African continent consistently since 1976. And as the past few years have shown, a globalized world only increases the potential for these outbreaks to jump borders. After consultation with external experts, we believe we are now in a position to share our proposed development pathway with regulatory agencies. and have set a goal for alignment our next steps by year end. The latest work with 4201 is an excellent example of the real power of partnerships. Spearheaded by GuardRx, sponsored by Geneva University Hospitals, and funded by the US Defense Advanced Research Projects Agency, or DARPA, this collaboration shows how partnerships can amplify the potential of Inovio's platform. providing opportunities to innovate, explore indications that could improve human health, and ultimately advance our DNA medicines. We have several other externally sponsored programs in the pipeline at various stages of development, including the Phase II trial for anal HCL in HIV positive, sponsored by the AIDS Malignancy Consortium that I previously mentioned, as well as candidates in two Phase I HIV trials sponsored by the National Institute of Allergy and Infectious Diseases. We also have a DARPA-funded collaboration with the Wistar Institute, University of Pennsylvania, Indiana University, and AstraZeneca to develop anti-SARS-CoV-2-specific DMABs, or DNA-encoded monoclonal antibodies. We look forward to sharing updates from our partners as they're made available to us. and we'll continue to explore additional partnership opportunities that align with our strategic vision. With that, I'll now turn the call over to our CFO, Peter Keyes, for our first quarter 23 financial summary. Peter?
spk04: Thank you, Michael. What I'd like to provide today is an overview of Inovio's financial condition for the first quarter of 2023. As Jackie and Mike have discussed with you here today, Anobio is focused on advancing the most promising candidates in our pipeline as quickly as possible. Part of this effort has included making sure we have enough cash runway to support those research efforts. As you can see on this slide, I've highlighted how our operating expenses have declined over the last year. In the first quarter of 2023, our total operating expenses were $44.1 million, which is down 39% from the first quarter in 2022, as well as down 21% from the fourth quarter of 2022. Breaking down total operating expenses a bit more, We see that research and development expenses for the first quarter of 2023 were $30.2 million compared to $56 million for the same period in 2022, a 46% reduction quarter over quarter. The decrease in R&D expenses was primarily the result of lower drug manufacturing, clinical trial expenses, and outside services related to INO 4800, as well as lower expenses, expense inventory and outside services related to our Selectra 3P SP device and array automation project, among other variances. General and administrative expenses for the first quarter of 2023 were $13.9 million, versus $16 million for the same period in 2022, which is a 13% drop. The decrease was primarily due to lower non-cash stock-based compensation, insurance, and other outside services offset by higher legal expense. Our revenues for the first quarter of 2023 were $115,000, which is down from 199,000 in the same period in 2022. These factors combine to bring our net loss for the first quarter of 2023 to 40.6 million, down 49% from 79.1 million, which was our net loss for the prior period, prior year. On a per-sure basis, both basic and dilutive, our net loss for the first quarter of 2023 was 16 cents, down from 36 cents for the 2022 period. We finished the first quarter of 2023 with $223.8 million in cash, cash equivalents, and short-term investments, compared to $253 million as of December 31st Looking forward, we are maintaining our prior projections of our cash runway taking us into the first quarter of 2025. This includes our cash burn estimate for the second quarter of 2023 of approximately $33 million. These projections do not include any funds that may be raised through our existing ATM at-the-market offering program. or other capital raise activities. As a reminder, you can find our full financial statements in this afternoon's press release, as well as in our Form 10-K filed with the SEC. And with that, I'll turn it back over to Jackie.
spk02: Thank you, Peter. I'd now like to open up the call to answer any questions you might have. Operator?
spk05: We will now begin the question and answer session. To ask a question, you may press star, then one on your telephone keypad. If you're using a speakerphone, please pick up your handset before pressing the keys. And to withdraw a question, please press star, then two. At this time, we will take our first question, which will come from Greg Renza with RBC Capital Markets. Please go ahead with your question.
spk01: Hi guys, it's Anishan for Greg. Great to hear about the continued progress this quarter and thanks for taking my questions. Just on 3107 and the newly presented combined cohort one and cohort two data, how should we be thinking about the degree of heterogeneity between the cohort in terms of baseline characteristics, just to get a sense of how well they meld together? And maybe secondly, if you have a sense on the data package and its composition that you present to regulators on the path ahead. Appreciate your time and thanks again.
spk02: Yeah, thanks. Those are really great questions. And before I ask Mike to respond in more detail, I'd just like to say again how encouraged we are by this combined data set and our interactions with the FDA to date. You know, we do believe that we have a workable framework going forward for our phase three clinical trial design. And we're very encouraged by the potential I know 3107 has to really be a therapeutic option for patients suffering from RRP. So with that, I'll turn it over to Mike to comment on some of the more specific items you asked about. Mike?
spk03: Yeah, thank you. So starting off with the heterogeneity between the two groups, I mean, overall we felt that the two cohorts were very similar in terms of baseline characteristics as well as clinical response, and obviously the safety profile was similar also. So we didn't really... really feel when we put the data set together that we needed to treat cohort one differently from cohort two. And as you saw from a sort of range of surgeries, we saw a range from two to eight. And we saw a same decrease, median decrease in surgeries in both cohorts. So we were actually very pleased from that because it's always nice to get a second set of study results that reinforce the primary results that we've seen. So with respect to the data package, obviously, it consisted of the results that we've talked about to date, as well as the full phase three study outline. And as I talked to, I mean, the two main elements that we wanted to address that we knew were of concern to the agency was the variability in disease among patients over time. And really the only way that you can do that is through a randomized placebo-controlled trial. And so that's where we ended up, but it was actually where we expected to end up when we started discussions with the agency. Does that answer your question?
spk01: Yeah, that was really helpful. Really appreciate the time, and congrats on the progress again.
spk08: Thank you. Again, if you have a question, you may press star, then one, to join the queue.
spk05: Our next question will come from Harthash Singh with Oppenheimer. Please go ahead with your question.
spk06: Great. Thank you, and thanks for the couple of questions. You know, one is just going back to that RP question that I was just asked, but thinking about the phase three, how many patients are you thinking about the trial could be. And, you know, should we just assume that the patients will have at least those two surgical interventions? And just give us a sense of the market, you know, if the market, I mean, the total sort of patient sizing for this, if it's possible. And I just had one follow-up question on, you know, HSIL after this. Thank you.
spk02: So thanks very much, Hataj. I think those are great questions. So I'm going to ask Mike to take the Phase 3 questions that you asked, and then I'll comment a bit about the market size. So, Mike? Okay.
spk03: So as we haven't obviously disclosed the final sample size for the Phase 3 study, but to give you some parameters of sort of how to think about it, At the end of the day, we were not expecting to see a statistically significant result in either cohort. This was a phase one, two exploratory study. And I think the fact that we did see that statistical significance just points to the size of the clinical effect that we're seeing in both those cohorts. So when we actually looked at the sample size, we could actually get away with probably a way too to smaller sample size. And so, you know, we also realize that you have to balance that with making sure you have an adequate safety database with the agency. So, you know, if you run the numbers, don't expect it to be the smallest number that you could get away with. But it is certainly a very manageable sample size for a Phase III program.
spk02: Thanks, Mike. And, Satosh, to talk a bit about the potential market size, in the U.S., I think current epi figures estimate that there may be around 14,000 patients with active RRP, probably a similar number in Europe. As you know, HPV, unfortunately, is everywhere, so there are RRP patients globally. I think an estimate from the RRP Foundation a few years back estimated an average cost of treatment for a patient in the U.S. to be at about $72,000 per annum. So as you can see just by doing the math, that pretty quickly gets to some pretty big numbers that are being spent currently on RRP treatment. We would expect appropriate treatment rare disease pricing for this. And we believe that there is a significant high unmet medical need that could be addressed by therapeutic options for RRP and as an alternative to surgery. So we think that there is an appropriate market here.
spk06: Yeah, no, that's great. Thank you for all the color. And then, you know, just on NLHSIL, I know it's been a while since you presented the data. And, you know, how much sort of insight and confidence have you gotten from Reveal 1, Reveal 2 in these forms of cancers and the biomarker data to kind of give you a good line of sight into the next step? And, you know, what would that be? Would that be a Phase 2, strictly a Phase 2-3? And so thanks for the question.
spk02: Okay. So, again, before I ask Mike to jump in here, perhaps what I can say is, you know, whilst these are separate indications, we have been really encouraged by the data that we've seen now for BGX3100 across multiple studies, multiple indications in terms of its ability to generate cytotoxic T cells, and also the levels of viral clearance that we've seen and tissue regression. So we're really encouraged by the totality of the data as a whole. Also seen very encouraging safety and tolerability profiles across those studies. So, Mike, do you want to expand a bit more on sort of what we're thinking around anal H cell?
spk03: Yeah, no, thank you, Jackie. I mean, obviously, we started at the point that Jackie has just talked to. We're seeing very consistent viral clearance of HPV-infected cells And we actually saw very promising results from the anal HC Phase II results. So, you know, while I can't talk to the specifics of the program we've put in, you know, we do believe, you know, now that ANCA has led the way in terms of how anal HCL patients should be treated, We believe we have a good place for VGX3100 in the treatment paradigm of these patients and think that we're confident that we would see a similar effect of VGX3100 on clearing those HPV-infected cells. It is As in all of these things, it is a discussion with the agencies, and we're just in the process of having that.
spk06: Mike, thank you so much. And then, Jackie, just one very quick follow-up. You know, the numbers you cited on RRP, the 72,000 per annum on average, about how long do these patients tolerate these surgeries before sort of, I guess, progressing or dropping off or whatever is the next step after that?
spk02: Yeah, again, a really great question, Hartaj. I mean, unfortunately, RRP can be a lifelong disease. People who have their first occurrence of RRP as children can suffer from repeated issues throughout their lives. It really is a chronic disease. You can also get RRP occurring for the first time in adulthood. and even in older adults as well. Once you have RRP, as Mike said, the disease course can be variable, but many people have RRP for decades, and really I think what we're looking for here is a treatment that's going to be appropriate for people who are suffering from a chronic disease, So a treatment that's really going to be suitable across their lifetime. So, Mike, do you want to add to that?
spk03: Yeah, no, I mean, I think from the number of surgeries, I mean, because of the lifelong nature of the condition, I mean, there are several patients out there with, you know, having hundreds of surgeries. I mean, it really is, you know, just drives it home to you that, the impact RRP has on these patient lives when you start getting out there in the community. So, you know, I think we will, you know, I think to your previous question, I mean, we didn't see any reason to veer away from two surgeries in the year being a reasonable indicator of, you know, a need to intervene and hopefully change the course of these patients' diseases.
spk08: Great, thank you, thank you for all the questions. And our next question will come from Yi Chen with HC Wainwright.
spk05: Please go ahead with your question.
spk07: Thank you for taking my question. Could you give us some additional color on FDA's primary concern regarding the design of the phase three trial for 3107?
spk03: I mean, first of all, I'll say it wasn't a primary concern. These are just routine questions that we have as part of the review. So, I mean, we talked about that they concurred with our design of a Phase III study being randomized placebo-controlled trial. We have, because there are no surgical criteria, we're, you know, we're paving a way forward in RRP clinical development. So we have some questions around how we can agree what those surgical criteria are. And then the device questions were just part of the review of a combination product, which occurs when you submit a protocol for Phase III development.
spk07: Do you think FDA will require any modification to the injection device?
spk03: I mean, I don't believe. I mean, when you look at our EP history, we've administered EP to over 18,000 patients. That's obviously intradermal and intramuscular. I think we've established the EP parameters. I don't believe there'll be changes. certainly any changes to the administration profile of electroporation.
spk02: Yeah, and maybe I can just jump in here as well, Mike. You know, we have previously used this device in two other previous Phase III studies, both Reveal 1 and Reveal 2. And as Mike mentioned, we think these questions are part of the normal review of a proposed Phase III study.
spk07: Once you start the phase three trial, will that increase the quarterly cash burn?
spk04: Hi, this is Peter Keyes. That's built in currently right now, and we feel like we have sufficient funds to complete the trial, but we are still working through everything with the feedback from the FDA.
spk08: Okay, thank you. And that concludes our question and answer session.
spk05: I would like to turn the conference back over to Dr. Jackie Shea for any closing remarks.
spk02: Thank you for your questions and for joining us today. Inovio has made important headway in the clinical development of our key candidates in the first few months of this year, and we will continue to work hard to build on that progress in the months to come. We plan to present and publish our work at leading medical conferences and journals, as well as share additional regulatory and development updates from our key candidates as they become available. We will continue to work with our partners and collaborators to advance our pipeline, as well as look for new and creative ways to develop our DNA medicines. I look forward to sharing updates on our additional progress at our next quarterly report as we drive toward delivering on the promise of DNA medicines for patients globally. With that, thank you again for your attention. Have a great evening, everyone.
spk08: The conference has now concluded. Thank you very much for attending today's presentation. You may now disconnect your lines.
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