Inovio Pharmaceuticals Q1 2024 Earnings Call Transcript

Quartr
Provided by Quartr
May 13, 2024

There are 12 speakers on the call.

Operator

Good afternoon, ladies and gentlemen, and welcome to the Inovio First Quarter 2024 Financial Results Conference Call. At this time, all lines are in listen only mode. Following the presentation, we will conduct a question and answer session. This call is being recorded on Monday, May 13, 2024. I would now like to turn the conference over to Thomas Hung, Manager of Investor Relations.

Operator

Please go ahead.

Speaker 1

Good afternoon, and thank you for joining the Inovio Q1 2024 Financial Results Conference Call. Joining me on today's call are Doctor. Jackie Hsieh, President and Chief Executive Officer Doctor. Michael Sumner, Chief Medical Officer Mark Twyman, Chief Commercial Officer and Peter Keyes, 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.

Speaker 1

Following prepared remarks, we will conduct a question and answer segment. During the call, we will be 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.

Speaker 1

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

Speaker 2

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-three thousand one hundred and seven, which is being developed for the treatment of recurrent respiratory papillomatosis. Secondly, advancing other promising candidates in our pipeline, particularly INO-three thousand one hundred and twelve and thirdly, strengthening our business as a whole.

Speaker 2

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 common goal to deliver on the promise of DNA medicines to patients. Of utmost importance, we remain on track to file our BLA for 3,107 in the second half of this year under the FDA's accelerated approval 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 1st potential FDA approved therapy for this devastating disease. And we're now moving to initiate the trial as soon as possible.

Speaker 2

As you'll hear from Mark, we have also been advancing our commercial plans for 3,107, establishing key relationships and putting the building blocks of a successful commercial launch strategy into place. In parallel, our clinical and R and 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 3,112 in combination with LOCKTORC 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 twothree study with INO-four thousand two hundred and one as an Ebola vaccine booster in this quarter and look forward to a readout of the first clinical data from the Phase 1 trial evaluating the anti SARS CoV-two dMAb candidates in the second half of this year.

Speaker 2

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 $33,000,000 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 3,107 and our other clinical progress across the pipeline.

Speaker 3

Mike? Thank you very much, Jackie, and greetings everyone. As Jackie mentioned, we are all focused on advancing INO-three thousand one hundred and seven 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 3,107 in the second half of twenty twenty four. 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.

Speaker 3

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.

Speaker 3

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 3,107 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 3,107 that it reduces the need for surgery in patients by teaching their immune systems to mount an effective response to the underlying HPV infection.

Speaker 3

Specifically, the team has found that treatment with 3,107 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. So moving on to how we think 3,107 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 Doctor. Simon Best, a laryngologist 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.

Speaker 3

The paper emphasizes that while researchers saw cumulative risks 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 then that many patients have hundreds of surgeries over their lifetime. With 3,107, we aim to prevent further surgeries before that cumulative risk becomes dangerously high.

Speaker 3

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 3,107 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-six and HPV-eleven 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 affecting a person's quality of life.

Speaker 3

3,107 has been shown to have the ability to generate antigen specific T cells with lytic potential targeting both HBV-six and HBV-eleven, which may eradicate HBV infected cells. Next, what we know about HBV 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 HBV 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 3,107 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.

Speaker 3

This is an excellent example of the benefits of our platform technology. In short, we have designed our proprietary delivery device, Selectra, 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 onetwo trial showed treatment with 3,107 resulted in a statistically significant reduction in the number of surgeries in that trial.

Speaker 3

Treatment with 3,107 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 onetwo 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 onetwo 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.

Speaker 3

The protocol for our trial also did not include prescribed laryngoscopy and surgery at week 612 to maintain minimal residual disease during the treatment window. As we look to the future development opportunities for IMO-three thousand one hundred and seven, 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 3,107 to potentially enhance immune responses for partial and non responders. 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 3rd quarter. We are also continuing our conversations with regulators in Europe to help frame clinical development efforts for ex U.

Speaker 3

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.

Speaker 3

Turning now to another late stage candidate. I'd like to provide some important updates on INO-three thousand one hundred and twelve. As you may recall, we announced a clinical collaboration and supply agreement with Coherus Biosciences in the Q1 of this year to investigate 3,112 as a potential treatment for HPV-sixteen and 18 related local regionally advanced high risk throat cancer when used in combination with LOBTARZI, an anti PD-one monoclonal antibody recently approved for the treatment of nasopharyngeal carcinoma. In combination, this therapeutic approach is designed to leverage the antigen specific T cells listed by 3,112 and the ability of LOCKTORZI 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.

Speaker 3

The incidence of HPV positive throat 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 3 trial to the FDA in the Q1 and recently received feedback giving us confidence that we can move forward with our Phase 3 trial to evaluate the ability of 3,112 in combination with LOPTORZY 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-four thousand two hundred and one, which is being studied as a heterologous boost to the FDA licensed Ebola vaccine of EVO. We recently generated some encouraging new antibody response data from our previously reported Phase 1 study by utilizing the FANG assay.

Speaker 3

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 4,201 elicits a strong antibody response comparable to the AVEVO 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 twothree clinical trial with 4,201 this quarter. We are aiming to conduct the trial in tandem with a non human primate study to allow immuno bridging of protective antibody levels in the non human 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 1 trial evaluating the anti SARS CoV-two dMAb candidates in the second half of twenty twenty four. 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.

Speaker 3

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 3,107. Mark?

Speaker 4

Thanks, Mike, and hello, everyone. Like to start today by taking a moment to highlight what's really driving our efforts to bring 3,107 to market, the patients. RFP patients are desperate for 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 add to our understanding of their journey and the impact the disease has on their lives to enable us to best serve them.

Speaker 4

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 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, healthcare providers and patient advocacy groups for assisting us in ensuring that we develop 3,107 to best meet patient needs. While Mike laid out what we see as the clinical advantage of 3,107, they were just one part of our foundation for commercial success.

Speaker 4

As I highlighted last quarter, that foundation also includes a critical understanding of the patient and health care provider landscapes and building a deep sense of expertise on our commercial team. At a strategic level, for some time now, we've been 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 3,107, selected a 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 in HCP payer deployment strategy and supporting non field based HCP and patient engagement strategies. We also plan to submit the proposed brand name for 3,107 to the agency for review in the near term.

Speaker 4

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 1st therapeutic treatment for RRP and the 1st DNA medicine approved in the U. S, 3,107 could be groundbreaking from a scientific perspective. But a product like the recently approved niragastat serves an important reminder of why treatment options for rare diseases like RRP are necessary. Niragastat has many similar characteristics to 3,107.

Speaker 4

Niragastat is the 1st FDA approved treatment for adults with desmoid tumors, a rare disease characterized by non cancerous growth found in connective tissue that much like papillomas are rarely fatal but place an 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 place a significant physical and emotional burden on patients. Approved for marketing by the FDA in late 2023, niragastat offers a desperately needed non surgical treatment option to patients who might otherwise face the risk of damage to local soft tissue and joints, very much in the same way that we hope 3,107 will 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 Q1 financial results. Peter?

Speaker 5

Thank you, Mark. Today, I'd like to provide an overview of Inovio's operational highlights and financial condition for the Q1 of 2024. As Jackie noted earlier, we continue to strengthen our financial position while working to advance 3,107 and other promising candidates. We are pleased to announce a completed offering of common stock and pre funded warrants in April 2024 with net proceeds from the offering of approximately $33,200,000 after deducting underwriter discounts and commissions and operating expenses. These additional funds will help support our commercialization efforts for 3,107 and support progress across our pipelines.

Speaker 5

We have again reduced our total operating spend, dropping from $44,100,000 in the Q1 of 2023 to $31,500,000 in the Q1 of 2024, a 29% decrease. Breaking down our operational spend further, our R and D expenses in the Q1 of 2024 totaled $20,900,000 compared to $30,200,000 for the same period in 2023. The year over year decrease in R and D expenses was primarily the result of lower drug manufacturing, clinical trial expenses, outside services and expensed inventory related to INO-four thousand eight hundred and other COVID-nineteen studies and lower employee and consultant compensation including stock based compensation among other variances. G and A expenses for the Q1 of 2024 were $10,600,000 compared to $13,900,000 for the same period in 2023. The decrease in G and A expenses was primarily related to a decrease in in employee compensation, including non cash employee and consultant stock based compensation and a decrease in other legal expenses among other variances.

Speaker 5

Inovio's net loss for the quarter was 30,500,000 dollars or $1.31 per share basic and dilutive compared to a net loss of 40,600,000 dollars or $1.89 per share basic and dilutive for the Q1 2023. During the quarter, we paid the remaining balance of our convertible notes of $16,900,000 and have no further debt. We finished the quarter of 2024 with $105,600,000 in cash, cash equivalents and short term investments compared to $45,300,000 as of December 31, 2023. Inovio estimates its cash runway including the net proceeds of $33,200,000 raised in April 2024 to extend into the Q3 of 2025. This projection includes an operational net cash burn estimate of approximately $30,000,000 for the Q2 of 2024.

Speaker 5

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 Jackie.

Speaker 2

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

Operator

Your first question is from the line of Hartaj Singh from Oppenheimer. Your line is now

Speaker 6

open. Great. Thank you. I got a couple of questions, one broad and one just kind of specific to the P and L. Just on the broad question, we've had some investors kind of ask us what the effect of HPV vaccines.

Speaker 6

I know they've been around for a while, Jackie, 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 an idea that would be Phase 3 advancing for hundred and twelve, would you expect the burn to start moving up over the next few quarters? And thank you for the question.

Speaker 2

Hi, Hartaj. Nice to hear from you. So yes, HPV vaccines very important, very important question here. So, HPV vaccines were launched in 2,000 and 6, 2009. First of all, targeting girls and then moving into boys as well.

Speaker 2

And what we've seen is that the HPV vaccines 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 men in the sort of high 50%.

Speaker 2

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 vaccine.

Speaker 2

And then lastly, RRP is a disease that disproportionately affects boys and men. And these are the proportion 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.

Speaker 2

Mike, anything you'd like to add to that?

Speaker 3

You hit every major point.

Speaker 2

And then moving on to your question around OpEx burn. We are as Mike mentioned during the call, our next step for 3,112 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?

Speaker 5

Thank you, Jackie. Yes, Hartaj. So we did increase our estimated burn this quarter by $4,000,000 I do expect that to be fairly consistent. And we've given guidance that we have cash ended Q3 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.

Speaker 5

But once we dive into 3,112 more and get that launched, we could see some potential increases after that.

Speaker 6

Great. Thank you, Jackie. Thanks, Peter. Thanks, Mike.

Operator

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

Speaker 7

Hey, thanks for taking the questions. I guess a few on 3,107. This one is pretty nice, 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 INO-three thousand one

Speaker 8

hundred

Speaker 2

and seven in the U. S. Is regulated as a combination INO-three thousand one hundred and seven in the U. S. Is regulated as a combination product.

Speaker 2

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?

Speaker 3

Thank you, Jackie. So I mean, obviously devices are living, breathing element. And so basically our file is really updating, making sure we're 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 3 studies before. We have significant experience with it.

Speaker 3

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.

Speaker 7

Okay, great. And then I know this is hard to say until you actually start enrolling it, but you just give us any kind of sense on how long it might take to enroll the confirmatory trial? And then for the immunology presentations 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 3,112. Thanks.

Speaker 2

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

Speaker 3

Yes, 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 onetwo 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 are targeting roughly around the same recruitment period, because obviously we're hoping that there'll be a commercial product available.

Speaker 3

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 or publications at the moment, but we will do so as soon as we know. Okay. Go ahead.

Speaker 9

Sorry. Go

Speaker 2

ahead. Yes. If I can just add sort of one additional point. With regards to the confirmatory study, we just the FDA has advised us 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 submit that BLA.

Speaker 7

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

Speaker 3

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.

Speaker 7

Got it. Okay. And then 3,112, you may have answered this, but have you reached out to the EU regulators and scheduled a meeting or just any sense on timing for that? Thank you.

Speaker 3

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 there'll be sometime during quarter 3.

Speaker 4

Okay. Thank you.

Operator

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

Speaker 10

Hi, guys. It's Anish on for Greg. Thanks for the color on today's call and for taking our questions. I just wanted to ask on 3,107 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 Selectra device as another relative layer or step for drug administration?

Speaker 10

And how do you feel this positions 3,107 in the opportunity ahead just been thinking about if it could be better suited for certain clinics, practitioners or even patients? Thanks so much.

Speaker 2

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 3 studies. We've used the device in clinical trials in, 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.

Speaker 2

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. And we're really not seeing it as a barrier compared to subcu administration. Mark, do you want to talk about it?

Speaker 4

Yes. I mean 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 Jackie said, their 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.

Speaker 4

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.

Speaker 10

Great. Thanks so much and look forward to seeing you at our conference this week.

Speaker 2

Yes. Look forward to seeing you as well, Anish.

Operator

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

Speaker 11

Great. Thanks for the update and taking our question. Maybe a couple of questions related to 3,107 in the confirmatory study. One is in terms of the control arm treatment option at the end, I'm just curious how heterogeneous we are talking about here, particularly as you expand this trial into global clinical sites? 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, understand that you probably alluded one fewer surgery can be clinically needed for those patients.

Speaker 11

Just curious, want to confirm what's the power assumption, the effect size and assumption you have for the confirmatory study? Thank you.

Speaker 2

Okay. Thank you, Roger. 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 and 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?

Speaker 11

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

Speaker 2

Great. So Mike, would you like to talk about the sites we've used today, 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.

Speaker 3

Yes. And precisely that fact, I mean, we have conducted the Phase onetwo study across 8 academic sites primarily. And we obviously looked from 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.

Speaker 3

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.

Speaker 3

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 to 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 onetwo 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.

Speaker 3

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 onetwo study and what data we have that we will we have an appropriate effect size and statistical sample.

Speaker 2

Yes. And if I can just add here Mike, one of the reasons why we've gone down this path of conducting a placebo controlled confirmatory trial is there are a couple of sort of real key reasons 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.

Speaker 2

And then also in 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 3,107 into Europe. Mike, anything else you want to add to those aspects?

Speaker 3

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

Speaker 2

Thanks.

Speaker 11

Great. Thank you.

Operator

Your next question is from the line of Yi Chen from H. C. Wainwright. Please go ahead.

Speaker 9

Thank you for taking my questions. With respect to the target patient population in the CONFIRM 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?

Speaker 6

Thank you.

Speaker 3

No, I think one of the things we were very pleased about was that the data set we saw from our Phase onetwo 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 be representative of the true RRP population that's out there.

Speaker 2

And just as a reminder, we enrolled people in the Phase onetwo study who'd had from between 2 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.

Speaker 9

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

Speaker 3

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 Jackie 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.

Speaker 9

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

Speaker 3

Yes. 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 III 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 hit. And as we expand our clinical trial sites, I'm sure they treat a very similar population.

Operator

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

Speaker 8

Yes. Thank you for taking my questions. Sorry, I'm hopping on a little late. Just wanted to ask really quickly just in terms of the BLA submission be on track for INO-three thousand one hundred and seven. 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 market by 2025?

Speaker 8

Or is there any assurances from the FDA regulators that you can get to just make sure that you're on track for that for 2025?

Speaker 3

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 that 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.

Speaker 8

Great. And then secondly, real quick, in terms of the initiation of the confirmatory trial, with the feedback that the 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 priority review? Or just how is the timing going to kind of line up between the 2?

Speaker 3

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're 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.

Speaker 2

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

Speaker 8

Got you. And is there like any guidance on like how when you could expect to have the 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 confirmed KJAR data?

Speaker 2

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.

Speaker 2

For the Phase III trial, we actually recruited faster than we initially thought and recruitment was the trial was fully enrolled in less than a year.

Speaker 8

Great. Thank you so much. That's all my questions. Thanks for squeezing me in here.

Speaker 2

Nice to talk with you.

Operator

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

Speaker 2

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

Speaker 2

Have a good evening everyone. Good

Operator

night. Ladies and gentlemen, this concludes today's conference call.

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Earnings Conference Call
Inovio Pharmaceuticals Q1 2024
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