INO - NASDAQ

Good afternoon, ladies and gentlemen, and welcome to the Inovio First Quarter 2024 Financial Results Conference Call. [Operator Instructions] This call is being recorded on Monday, May 13, 2024. I would now like to turn the conference over to Thomas Hong, Manager of Investor Relations. Please go ahead.

Good afternoon, and thank you for joining the Inovio First Quarter 2024 Financial Results Conference Call. Joining me on today's call are Dr. Jacqui Shea, President and Chief Executive Officer; Dr. Michael Sumner, Chief Medical Officer; Mark Twyman, Chief Commercial Officer; and Peter Kies, Chief Financial Officer. Today's call will review our corporate and financial information for the quarter ended March 31, 2024, as well as provide a general business update. Following prepared remarks, we will conduct a question-and-answer segments. During the call, we'll 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 has concluded. I will now turn the call over to Inovio's President and CEO, Dr. Jacqui Shea.

Good afternoon, and thank you to everyone for joining today's call. To begin with today, I'd like to discuss our key objectives for 2024. Mike, Mark and Peter will go into greater detail throughout this presentation but I feel it's important to emphasize the recent progress we've made in the 3 main areas that are driving our business forward. Firstly, preparing for the potential approval and commercialization of our first product, INO-3107, which is being developed for the treatment of recurrent respiratory papillomatosis. Secondly, advancing other promising candidates in our pipeline, particularly INO-3112, and thirdly, strengthening our business as a whole. Over the last 2 years, our strategic focus on these areas has been instrumental in ensuring that we are using our time and resources efficiently to work toward a [indiscernible] to deliver on the promise of DNA medicines to patients. Of utmost importance, we remain on track to file our BLA for 3107 in the second half of this year under the FDA's accelerated proof pathway. And we believe we have alignment with the FDA on our proposed confirmatory trial design based on recent feedback. Our team is energized by the opportunity to deliver the first potential FDA-approved therapy for this devastating disease and we're now moving to initiate the trial as soon as possible. As you will hear from Mark, we have also been advancing our commercial plans for 3107, establishing key relationships and putting the building blocks of a successful commercial launch strategy into place. In parallel, our clinical and R&D teams have continued to advance other promising candidates across the pipeline, focusing on later-stage assets with high unmet medical need and strong commercial potential. We believe we have reached alignment with the FDA on the Phase III trial design for 3112 in combination with Loqtorzi for throat cancer. And we'll focus next on discussing those plans with European regulators. Following feedback from the FDA, we also expect to submit plans for a Phase II/III study with INO-4201 as an Ebola vaccine booster in this quarter and look forward to a readout of the first clinical data from the Phase I trial evaluating the anti-SARS-CoV-2 dMAb candidates in the second half of this year. Finally, we've continued to strengthen our business, adding key personnel, managing our resources and strategically strengthening our financial position to support our key objectives. Of particular note, we recently raised approximately $33 million through an offering of common stock and prefunded warrants in April. We remain committed to financial discipline and operational excellence to achieve milestones, which I believe will continue to be critical to our future success. I'd now like to pass the call over to our CMO, Mike Sumner, who will provide some additional details on 3107 and our other clinical progress across the pipeline. Mike?

Thank you very much, Jacqui, and greetings, everyone. As Jacqui mentioned, we are all focused on advancing INO-3107 and excited by the potential to help deliver on the promise of DNA medicine for RRP patients. I'm pleased to share that we remain on target to submit our BLA seeking accelerated approval for 3107 in the second half of 2024. I'm also pleased to inform you that the FDA has advised us that they had no additional comments on our proposed confirmatory trial design. So we are working to initiate the trial as soon as possible. The trial will be randomized and placebo-controlled involving approximately 100 patients with a history of 2 or more surgeries in the prior year with a treatment option for the placebo arm at trial end. The trial is strategically designed to focus on evaluating clinical benefit in reducing surgical interventions for the majority of RRP patients. We believe this approach targets a broader spectrum of RRP disease while also supporting expansion into the global marketplace. This is based on feedback we have received from European regulators indicating that they will require a randomized placebo-controlled study for licensure. But perhaps most importantly, we believe our approach reflects what we've heard time and again matters most, reducing the number of surgeries patients face. That translates into reduced risk of permanent vocal cord damage and a significant improvement in quality of life. Our plans for this year also include the submission of new immunological data for 3107 to both peer-reviewed publications and key conferences. I look forward to sharing more details on this important work in the year ahead. But I can tell you that it supports what we believe to be one of the most important characteristics of 3107. And that it reduces the need for surgery in patients by teaching their immune systems to mount an effective response to the underlying HPV infection. Specifically, the team has found that treatment with 3107 induces strong immune responses in the airway tissues of patients who are clinically responding to treatment. The types of immune activity we are seeing in these patients are diverse and include activation of antiviral pathways and engagement of both innate and adaptive cells of the immune system. For moving on to how we think 3107 and our focus on reduction in surgery could make an impact on patient outcomes. I think this quote from a recent paper co-authored by Dr. Simon Best, allowing oncologist that specializes in treating RRP and also an investigator on our completed trial, captures the burden that this disease puts on RRP patients, and the real risks they face every time they go in for surgery. The paper emphasizes that while researchers saw cumulative risk for patients who had more than 5 surgeries, 44% of patients who had less than 5 surgeries had incurred permanent iatrogenic injury. As an injury caused by the surgery itself, not the underlying disease. More simply put, the cumulative risk for injury increases with every surgery but ultimately, any one surgery could cause permanent damage. Consider them that many patients have hundreds of surgeries over their lifetime. With 3107 we aim to prevent further surgeries before that cumulative risk becomes dangerously high. So let's recall what RRP is as a disease, how it's caused and what drives patients to seek medical treatment? We'll also address why we continue to believe 3107 could be useful for the broadest number of patients. First off, as we've spoken about extensively, RRP is a disease caused by infection with specific strains of the human papillomavirus, HPV-6 and HPV-11 in the majority of patients. The main symptom of the disease that drives patients to seek treatment as adults is the development of papillomas in the airway, especially in the throat and on vocal cords. These papillomas can cause difficulty speaking and breathing, substantially affect a person's quality of life. 3107 has been shown to have the ability to generate antigen-specific T cells with lytic potential targeting both HPV-6 and HPV-11, which may eradicate HPV infected cells. Next, what we know about HPV is that it is a very common virus that affects nearly everyone at some point in their lives. Most people have the ability to fight off HPV infections, often without even symptom development. But those who go on to develop RRP have immune systems that are unable to create an adequate defense. For these individuals, we believe 3107 has the potential to teach their immune system to mount a response that will help it fight back against the virus and prevent the development of papillomas. This is an excellent example of the benefits of our platform technology. In short, we have designed our proprietary delivery device CELLECTRA to optimally deliver DNA medicines to the body cells without use of chemical adjuvants, lipid nanoparticles or viral vectors and without the adverse effects that can be associated with those delivery methods. This results in our DNA medicines teaching the immune system to react in an effective way to protect or treat the patient. Finally, the current standard of care for RRP is surgery, which, as I mentioned earlier, can cause greater permanent damage to the vocal cords than the underlying disease itself. Data from our completed Phase I/II trial showed treatment with 3107 resulted in a statistically significant reduction in the number of surgeries in that trial. Treatment with 3107 was observed to be well tolerated with the most common adverse events being injection site reactions. As a reminder, this slide shows the results from our Phase I/II trial. As you can see here, 81% of patients experienced a reduction in the number of surgeries versus the prior year and improvement was seen in patients with a wide range of disease severity with a median decrease of 3 surgeries. Further, 28% of the patients required 0 surgeries in the year following the first dose. Relative to other Phase I/II clinical trials, our protocol required that all surgeries conducted during the dosing window, a 54-day period, during which 4 doses were administered be counted in the overall results. The protocol for a trial also did not include prescribed laryngoscopy and surgery at week 6 and 12 to maintain minimal residual disease during the treatment window. As we look to the future development opportunities for INO-3107, we plan to capitalize on the product's candidates' clinical and immunological strengths. Based on historical data from other DNA medicines programs, which involve redosing, we believe we will be able to effectively redose 3107 to potentially enhance immune responses for partial and nonresponders. We plan on investigating redosing strategies to build on the impressive results I shared on the previous slide and plan to submit a redosing trial design to the FDA in the third quarter. We are also continuing our conversations with regulators in Europe to help frame clinical development efforts for ex-U.S. markets, which we believe will be expedited by utilizing a placebo-controlled study design for our U.S. confirmatory trial. Our strategy in Europe is supported by the orphan drug designation granted by the European Commission last year, and the previously granted CE Mark for our CELLECTRA device, which indicates that it meets certain European health and safety requirements. Turning now to another lead stage candidate. I'd like to provide some important updates on INO-3112. As you may recall, we announced a clinical collaboration and supply agreement with Coherus BioSciences in the first quarter of this year to investigate 3112 as a potential treatment for HPV-16 and 18 related local regionally advanced high-risk throat cancer when used in combination with Loqtorzi, an anti-PD-1 monoclonal antibody recently approved for the treatment of nasopharyngeal carcinoma. In combination, this therapeutic approach is designed to leverage the antigen-specific T cells elicited by 3112, and the ability of Loqtorzi to reengage T cells to boost the immune response against cancer cells. We're excited about the potential for this novel combination therapy and believe it could meet the high unmet need within this rapidly growing patient group. The incidence of HPV-positive throw cancer is on the rise in high-income countries and has surpassed cervical cancer as the most common HPV-related cancer diagnosed in the United States. We previously submitted a study package for our Phase III trial to the FDA in the first quarter and recently received feedback giving us confidence that we can move forward with our Phase III trial to evaluate the ability of 3112 in combination with Loqtorzi, with the aim of increasing event-free survival. Our goal is to conduct a multicenter study in North America and Europe, and our next steps are to discuss the trial design with European regulators. We are also continuing to drive progress with some of our earlier-stage candidates, including INO-4201, which is being studied as a heterologous boost to the FDA licensed the Ebola vaccine, Ervebo. We recently generated some encouraging new antibody response data from our previously reported Phase I study by utilizing the FANG assay. This assay, which is often used in this disease space and more accurately allows us to benchmark our data against other primary vaccines on the market indicates that 4201 elicits a strong antibody response, comparable to the Ervebo primary vaccination. We are planning on publishing this data in a peer-reviewed journal and based on productive feedback from the FDA and discussions with KOLs and collaborators. We are moving forward and aim to submit our revised protocol for the Phase II/III clinical trial with 4201 this quarter. We are aiming to conduct the trial in tandem with a nonhuman primate study to allow immunobridging of protective antibody levels in the nonhuman primate challenge study to human titers. And finally, from our work on next-generation DNA medicines, we look forward to sharing a readout of the first clinical data from the DARPA-funded Phase I trial evaluating the anti-SARS CoV-2 dMAb candidates in the second half of 2024. For those not familiar with this innovative technology, we're using our core DNA medicines platform to evolve traditional monoclonal antibody therapeutics by encoding the DNA sequence for a specific monoclonal antibody in a DNA plasmid. We believe our dMAb technology has transformative potential enabling functional monoclonal antibodies to be directly produced within the body. With that, I'll turn the call over to Mark to provide an update on our commercialization efforts for 3107. Mark?

Thanks, Mike, and hello, everyone. I'd like to start today by taking a moment to highlight what's really driving our efforts to bring 3107 to market patients. RRP patients are desperate for a treatment that will provide relief from the physical and emotional burdens of surgery, and we are focused on bringing a potentially game-changing treatment option to market for them. Listening to patients allows us to continue to act our understanding of their journey and the impact of the disease has in their lives to enable us to best serve them. The quotes listed on this slide come from actual patients we've spoken to about RRP and how it has affected them. I can tell you that is the case with all rare diseases, for those living with RRP, the impact is real, and can be life altering to the point that they can't work in their desired profession or enjoy their friends and family like they used to. I would like to thank the patients, health care providers and patient advocacy groups who are assisting us in ensuring that we develop 3107 to best meet patient needs. While Mike laid out what we see as the clinical advantage of 3107, they are just 1 part of our foundation for commercial success. As I highlighted last quarter, that foundation also includes a critical understanding of the patient and health care provider landscapes and building a defense of expertise on our commercial team. At a strategic level, for some time now, we can clear on what the key strategic drivers of commercial success will be and have made significant progress to date against each of them. As examples, we've secured a temporary CPT code for administration of 3107 selected its 3PL partner and have identified potential specialty distribution and pharmacy partners that we believe can best support our intended channel strategy. Based on a comprehensive claims database analysis, we are in the final phase of locking down our geographic field footprint and ACP payer deployment strategy, and supporting nonfield-based ACP and patient engagement strategies. We also plan to submit the proposed brand name for 3107 to the agency for review in the near term. We're moving fast but remain grounded in a very thoughtful, methodical approach that I believe will carry us forward successfully. With the potential to be the first therapeutic treatment for RRP in the first DNA medicine approved in the U.S., 3107 could be groundbreaking from a scientific perspective. But a product like the recently approved nirogacestat serves an important reminder of why treatment options for rare diseases like RRP are necessary. Nirogacestat that has many similar characteristics to 3107. Nirogacestat is the first FDA-approved treatment for adults with desmoid tumors, a rare disease characterized by noncancerous gross found in connective tissue that much like papillomas are rarely fatal, replacing incredible physical and emotional burden on patients, reducing their quality of life. Like RRP, the standard of care for desmoid tumors is surgery, which doesn't address the underlying disease or eliminate the probability of recurrence and of itself places a significant physical and emotional burden on patients. Approved for marketing by the FDA in late 2023, nirogacestat offers industrially needed nonsurgical treatment option to patients who might otherwise face the risk of damage to local soft tissues in joints, very much in the same way that we hoped 3107 to prevent the need for surgery for RRP patients. I'll now turn the call over to our Chief Financial Officer, Peter Kies, for an overview of our first quarter financial results. Peter?

Thank you, Mark. Today, I'd like to provide an overview of Inovio's operational highlights and financial condition for the first quarter of 2024. As Jacqui noted earlier, we continue to strengthen our financial position while working to advance 3107 and other promising candidates. We are pleased to announce a completed offering of common stock and prefunded warrants in April 2024 with net proceeds from the offering of approximately $33.2 million after deducting underwriter discounts and commissions and operating expenses. These additional funds will help support our commercialization efforts for 3107 and support progress across our pipelines. We have again reduced our total operating spend, dropping from $44.1 million in the first quarter of 2023 to $31.5 million in the first quarter of 2024, a 29% decrease. Breaking down our operational spend further, our R&D expenses in the first quarter of 2024, totaled $20.9 million compared to $30.2 million for the same period in 2023. The year-over-year decrease in R&D expenses was primarily the result of lower drug manufacturing, clinical trial expenses, outside services and expensed inventory related to INO-4800 and other COVID-19 studies and lower employee and consultant compensation, including stock-based compensation, among other variances. G&A expenses for the first quarter of 2024 were $10.6 million compared to $13.9 million for the same period in 2023. The decrease in G&A expenses was primarily related to a decrease in employee compensation, including noncash employee and consultant stock-based compensation and a decrease in other legal expenses, among other variances. Inovio's net loss for the quarter was $30.5 million or $1.31 per share basic and dilutive compared to a net loss of $40.6 million or $1.89 per share basic and dilutive for the first quarter 2023. During the quarter, we paid the remaining balance of our convertible notes of $16.9 million and have no further debt. We finished the quarter of 2024 with $105.6 million in cash, cash equivalents and short-term investments compared to $45.3 million as of December 31, 2023. Inovio estimates its cash runway, including the net proceeds of $33.2 million raised in April 2024 to extend into the third quarter of 2025. This projection includes an operational net cash burn estimate of approximately $30 million for the second 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 today with the SEC. Now with that, I'll turn the call back over to Jacqui.

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

[Operator Instructions] Your first question is from the line of Hartaj Singh from Oppenheimer.

I got a couple of questions, one broad and one just kind of specific to the P&L. Just on the broad question, we've had some investors kind of ask us what the effect of HPV vaccines. I know they've been around for a while, Jacqui, Mark. But I guess, Australia, they published a 2020 perspective saying that RRP rates have been going down there. So can you just give us your thoughts there on how you view HPV vaccines in the context of RRP? And then secondly, just on OpEx burn. Peter, if you can just give us an idea that with the Phase IIIs advancing for 31 -- for INO-3112, would you expect the burn to start moving up over the next few quarters?

Hartaj, nice to hear from you. So yes, HPV vaccine, very important -- very important question here. So HPV vaccines were launched in 2006 and 2009. First of all, targeting girls and then moving into boys as well. And what we've seen is that the HPV vaccine are certainly starting to have an impact on pediatric levels of RRP in countries that have achieved very high vaccination rates. So countries like Australia, for instance, that you mentioned where they have seen a significant impact and reduction in RRP. But I think an important thing to note is HPV vaccination levels have really stalled in many high-income countries. So for instance, in the U.S., HPV vaccination rates are in the low 60% for girls and women, and slightly lower than that for boys and man in the sort of high 50%. So there's a significant proportion of the population that remains unvaccinated and therefore, unprotected against RRP. And another very critical point to bear in mind is the fact that RRP has 3 main age peaks. So pediatric RRP tends to peak at around age 7. And then there's a peak in adulthood in the 30s and then a further peak in the early 60s. And for people in those sort of peak adult age groups, many of those people have not yet been vaccinated or were not vaccinated or were not eligible for vaccination given the relatively recent rollout of the HPV vaccines. And then lastly, RRP is a disease that disproportionately affects boys and mens. And these are the part of the population that are least likely to have received HPV vaccination. So taken all together, whilst I think we are seeing encouraging progress in terms of HPV vaccines, which do protect against infection with HPV 6 and 11, providing some protection in the juvenile population, we're still not really seeing that come through yet into the adult population. So unfortunately, RRP is going to be with us for decades to come. Mike, anything you'd like to add to that?

No, you hit every major point.

Okay. And then moving on to your question around OpEx burn. We are -- as Mike mentioned during the call, our next step for 3112 will be to conduct discussions with the European regulators because we're looking to conduct this trial in both North America and Europe. And it's going to take us a little bit of time to go through those interactions. But I'll hand over to Peter, and he can provide some further color on the financials. Peter?

Thank you, Jacqui. Yes, Hartaj. So we did increase our estimated burn this quarter by $4 million. I do expect that to be fairly consistent. And we've given guidance that we have cash into third quarter of 2025. So a lot of that's related to that increase right now is related to our commercial -- accelerating our commercial activities after our fundraising but once we dive into 3112 more and get that launched, we could see some potential increases after that.

Your next question is from the line of Roy Buchanan from JMP.

I just a few on 3107, is one pretty naive but just what are the device aspects of the BLA? What do you need to do to get that submitted in terms of the device itself?

Yes. Great question, Roy. So as people may be aware, INO-3107 in the U.S. is regulated as a combination product. So that means we need to submit on both the drug component as well as the device component. And I'll hand over to Mike to talk about our regulatory interactions around this combination with the FDA. Mike?

Thank you, Jacqui. So I mean, obviously, devices are living, breathing element. And so basically, our file is really updating, making sure we are aligned with all the latest regulations that relate to the device. But I would remind you that the 5 PSP device has been used in 2 Phase III studies before. We have significant experience with it. So we have a very good idea of how it performs in the clinical setting. So really, it's just updating the device to bring it up to meet all the current standards for the BLA.

Okay. Great. And then I know this is hard to say until you actually start enrolling it. But can you just give us any kind of sense on how long it might take to enroll the confirmatory trial? And then for the immunology presentation you mentioned in the second half, can you point us to any conferences we should be particularly looking at? And then I have one on 3112.

Yes. Mike, do you want to talk about the confirmatory trial and what we're thinking about in terms of enrollment time line?

Certainly. So I mean, we had said on the call today that we're targeting approximately 100 patients we were able to recruit the 32 patients in the Phase I/II study across 8 clinical sites within approximately a year time period. We are going to be expanding beyond the 8 clinical sites significantly. So we're targeting roughly around the same recruitment period because, obviously, we're hoping that there'll be a commercial product available, so we want to recognize that patients will be wanting to access that as soon as possible. With regards to the immunology, we haven't indicated what conferences we're going to target all publications at the moment but we will do so as soon as we know.

Yes. If I can just add sort of one additional point. With regards to the confirmatory study, we just -- the FDAs have advisers. We just need to start that study before we can submit our BLA. So whilst we'll be looking to complete that study as quickly as possible, we just need to start it before we can -- we submit that BLA.

Right. Okay. Do they have any requirements on enrollment, like 10 patients in or anything or not at all?

No, they have not given us any targets I mean as you can expect, we believe it is to make sure that we are meeting our obligation of performing that confirmatory study, and we will definitely be able to demonstrate that to the FDA.

Got it. Okay. And 3112, you may have answered this but have you reached out to the EU regulators and schedule the meeting? Or just any sense on timing for that?

We have not reached out yet. We will be -- now that we have had our meeting with the FDA and got alignment and have a pathway forward, we aim to get that submission in as fast as possible. So I would imagine it will be sometime during quarter 3.

Your next question is from the line of Gregory Renza from RBC Capital Markets.

It's Anish on for Greg. I just wanted to ask on 3107 and more on the clinical use side, in considering the competitive landscape and with Precigen utilizing a subcu route of administration, what are you hearing from KOLs physicians and even patients on the use of the CELLECTRA device as another relative layer or step for drug administration? And how do you feel this positions to 3107 and the opportunity ahead, just been thinking about if it could be better suited for certain clinics, practitioners or even patients.

Yes, that's a great question. So for people who are not familiar with our devices, as Mike mentioned earlier on in the call, this is a device that we've used previously in 2 other Phase III studies. We've used the device in clinical trials, and I believe more than 30 countries now. And what we uniformly hear back from physicians and patients is that the device is very administration of DNA medicines by the device is very tolerable for patients and it's quick and easy to use for health care providers. So we really see the device as an important part of our delivery and that it's enabling targeted and localized uptake of our DNA medicines. And so we see it as a core component of that. we're really not seeing it as a barrier compared to subcu administration. Mark, do you want to talk about it?

Yes. Just to be a little bit more specific your comments were spot on, that we've done primary market research with physicians, and they've said exactly what Jacqui said. The device is not an obstacle. It's easy to use. In fact, laryngologists are device physicians, right? They use devices sort of every day, if you go to one of their conferences, it's pretty much what's on the conference floor. So again, the results of the -- and the input from the market research suggests that it won't be an obstacle for use either in their practice should they decide to use the device in their practice or in the OR. So we're pretty confident about that.

Your next question is from the line of Roger Song from Jefferies.

May be a couple of questions related to 3107 and the confirmatory studies. One is in terms of the control arm trim option at the site by end. I'm just curious how heterogeneous we're talking about here, particularly as you expand this trial into global clinical side? And also for the 100 patients in the sample size, what is the powering assumption there, particularly related to the effect size, how much reduction you are powering for the study to show? I understand that you probably alluded on less on fewer surgery can be clinically need for those patients. But just curious I want to confirm what's the power assumption and effect size and assumption you have for the confirmatory study?

So your line is not terribly clear but I think what we heard you asking was around the sample size and the powering for the confirmatory trial. What we're thinking of there and also around the clinical trial sites, how heterogeneous they are and what the potential implications of that could be for a global rollout. Does that capture your question?

That's correct. Sorry about the connection here. Yes, those are the questions I was asking.

Great. So Mike, would you like to talk about the sites we've used to date, the sites we're thinking of using going forward and why we think actually having already been in 8 sites is actually very helpful for us.

Yes. And precisely that fact, I mean, we have conducted the Phase I/II study across 8 academic sites primarily. And we obviously looked from an analysis point of view to see if there was any variability from site to site, and we did not see that. As you can imagine in the United States RRP based on sort of sites that are able to do clinical trial or academic in nature. So as we expand beyond the original 8 sites, we really do not expect to see any impact from the site characteristics. And we are aiming to perform this study within the United States at this stage. As you mentioned, we have spent some time with European KOLs. The disease while is treated surgically, they don't necessarily have access to the same surgical equipment. So we've kept that level of heterogeneity in mind as we've designed both the study and our planned rollout. With respect to the effect size, we obviously haven't detailed that but what I will say is that we will be using a 2:1 randomization because we want to limit the number of patients that do not receive active treatment. If you remember, as we released both cohorts from the Phase I/II study, both of those cohorts individually were statistically significant. And we -- as part of the study, we also collected 3-year data for patients coming into that study. And so we really use that data to try and estimate what the placebo effect. And we've gone -- we've got a very nice safety margin, we believe, in terms of how we've powered the study. So we're very confident based on what we've seen in our Phase I/II study and what data we have that we will -- we have an appropriate effect size and statistical example.

Yes. if I can just add here, Mike, one of the reasons why we've gone down this path of conducting a placebo-controlled componentry trial, there are a couple of sort of real key reason underpinning this. First of all is the median number of surgeries for RRP patients is approximately 4 per year. And therefore, there are a lot of patients who are having less than 4 surgeries a year. And so it's important for us to be able to address that population of RRP patients as well, ideally before they start experiencing significant damage to their vocal cords. And then also in our discussions with the European regulators, they've also made it very clear that they see the path forward in Europe as potentially requiring a placebo-controlled trial. So we think conducting a placebo-controlled trial in the U.S. will be very helpful as we start to think about how we move 3107 into Europe. Mike, anything else you want to add to those aspects?

No, I think we've covered all the relevant points.

Your next question is from the line of Yi Chen from H.C. Wainright.

With respect to the target patient population in the confirmatory trial, what percentage of those patients do you expect to be different from the existing -- the completed trial? And do you expect that to alter the -- potentially alter the efficacy readout in the future?

No. I think one of the things we were very pleased about was that data set we saw from our Phase I/II was highly representative of the RRP population and the inclusion exclusion criteria are not changing on any significant points. So we would hope again that we will have a population of greater than 2 surgeries in the previous year and the representative of the true RRP population that's out there.

And just as a reminder, we enrolled people in the Phase I/II study who had from between 2 and 8 surgeries the prior year. People have had both 6 and 11 positive disease as well as people with mixed disease. So we really do believe that, that patient population is representative of the population we want to treat.

So when you see a broader spectrum of RRP disease, what exactly does that mean for the confirmatory trial?

This relates to the fact that we are allowed to recruit patients with 2 surgeries. The FDA made it very clear to us that if we wanted to do a single-arm study, we could only go down to 3 or more surgeries. And as Jacqui mentioned earlier in the call, that isn't fully representative of the RRP population. So that was one of the driving forces behind us picking a placebo-controlled design.

Okay. So if you -- for the comfort trial, there are a lot of 2 surgeries patient population in the world, could that potentially change the readout?

I don't think we have any reason to believe that the population we recruit will be any different than what we saw in the Phase I/II study. I would fully expect we will have that full range that we saw in the previous study, starting at 2, but going up to 8 and maybe more surgeries. It's difficult to say. But based on the RRP foundation data that they say they note a median of 4 surgeries a year in this patient population, which was exactly what we had as we expand their clinical trial sites, I'm sure they treat a very similar population.

Your next question is from the line of Sudan Loganathan from Stephens.

Just wanted to ask really quickly, just in terms of the BLA submission being on track for INO-3107, is with the -- under the accelerated approval pathway, would there be the ability if not for the accelerated approval pathway? Is there still a chance to get under regular approval processes in the market by 2025? Or is there any assurances from the FDA regulators that you can get just to make sure that you're on track for that for 2025?

So I mean, as part of our pre-BLA meeting with the agency, we will obviously request priority review, which is one of the advantages of breakthrough designation based on everything the FDA has said to us about their recognition of the significant impact on these patients' quality of life. We are very hopeful that we will get granted priority review, which would substantially contract the review period. So obviously, I can't talk on behalf of the FDA but we are on track to submit our BLA in the second half of this year. So with priority review, we would hope that would mean a 6-month review period once the file has been accepted.

Great. And then secondly, real quick. In terms of the initiation of the confirmatory trial, with the feedback that FDA may provide with -- for that trial, is any of the outcomes of that trial going to be necessary or needed for like a full approval or any part of the approval process kind of going forward with the prior year review? Or just how is the timing going to kind of line up between the two?

Yes. So with respect to the BLA filing under the accelerated approval process, none of the confirmatory study data will be required. The only thing the FDA have asked us to do is commence that trial. And based on our previous work with CROs, we are already engaging with clinical trial sites to get that process moving as fast as possible. So we do not anticipate that, that will hold up our filing.

And then we will need the full data from the confirmatory trial for full approval.

Got you. And is there like any guidance on like how -- when you could expect to have full data for the confirmatory trial? Or is it -- could we look back at the trial so far and how long it's taken to get data to extrapolate to how long it may be also to get that final confirmatory trial data?

Yes. So as Mike said, we will be making further details about the trial available when we've started the trial. We are looking to try and get this trial started as soon as possible. And as Mike said, we're looking to recruit around 100 patients. We're going to expand the number of clinical sites that we're going across. And we'll look to try and recruit the participants as quickly as possible. For the Phase I/II trial, we actually recruited faster than we initially thought and recruitment was -- the trial was fully enrolled in this year.

There are no further questions at this time. I would now like to hand the call back to Jacqui Shea, President and CEO, for closing remarks. Please go ahead.

Thank you. As I outlined at the opening of this call, we have set an ambitious agenda for the year but with a strengthened balance sheet and a strategic focus on the BLA submission and other important catalysts ahead we are continuing to deliver on our key objectives. And with our commitment to deliver on the promise of DNA medicine for patients in mind, we're committed to keep the momentum going. With that, thank you again for your attention. Have a good evening, everyone. Good night.