INOVIO Pharmaceuticals Inc. (NASDAQ: INO), a biotechnology company, has reported its financial results for the first quarter of 2024, alongside updates on clinical trials and future plans.
The company is preparing for the potential approval and commercialization of INO-3107 for recurrent respiratory papillomatosis (RRP), with a Biologics License Application (BLA) expected to be filed in the second half of the year.
INOVIO has also advanced other candidates in its pipeline and strengthened its financial position by raising approximately $33 million through an offering of common stock and pre-funded warrants. The company's cash runway is projected to extend into the third quarter of 2025.
Key Takeaways
- INOVIO is focusing on the approval and commercialization of INO-3107 for RRP treatment.
- A BLA for INO-3107 is planned for submission in the second half of 2024, with FDA alignment on confirmatory trial design.
- INOVIO reported a reduction in total operating spend and a net loss of $30.5 million for Q1 2024.
- The company raised $33 million through an offering and estimates its cash runway to last until Q3 2025.
- Positive Phase 1/2 trial results for INO-3107 indicate a statistically significant reduction in surgeries for RRP patients.
- INOVIO is discussing clinical development efforts with European regulators and plans a multicenter study in North America and Europe.
- The company is also developing INO-3112 for HPV-positive throat cancer in combination with LOQTORZI, aiming to increase event-free survival with a Phase 3 trial.
Company Outlook
- INOVIO is focused on bringing INO-3107 to market as a potential game-changer for RRP patients.
- The company is working on securing a temporary CPT code for administration, selecting a distribution partner, and identifying potential specialty, distribution, and pharmacy partners.
- Clinical data from the DARPA-funded Phase 1 trial evaluating anti-SARS-CoV-2 dMAb candidates is expected in the second half of 2024.
Bearish Highlights
- INOVIO reported a net loss of $30.5 million for the first quarter of 2024.
Bullish Highlights
- The company has successfully reduced its total operating spend.
- INO-3107 has shown promising results, potentially reducing the need for surgeries in RRP patients.
- INOVIO's financial position has been strengthened with the recent capital raise.
Misses
- There were no specific misses reported in the earnings call.
Q&A Highlights
- The company discussed the potential impact of HPV vaccines on RRP, noting a significant effect in countries with high vaccination rates, although vaccination levels have stalled in many high-income countries.
- INOVIO highlighted the positive reception of the selector device for INO-3107 by physicians and patients.
INOVIO continues to make strides in its clinical development programs and remains committed to delivering on the promise of DNA medicine for patients.
With a solid financial footing and promising clinical trial results, the company is poised to pursue its strategic objectives through the remainder of 2024 and beyond.
InvestingPro Insights
INOVIO Pharmaceuticals Inc. (NASDAQ: INO) has shown a remarkable price performance with a 152.44% increase over the last six months, reflecting investor optimism as the company advances its clinical pipeline. Despite the challenges faced by the biotech sector, INOVIO's stock has been buoyed by positive clinical trial results and the potential for its INO-3107 therapy.
InvestingPro data indicates that INOVIO holds a market capitalization of $294.3 million, with a notable price uptick in recent months. The company's revenue for the last twelve months as of Q1 2024 stands at $0.72 million, which is a significant decrease from the previous year. The gross profit margin during the same period is reported at an unusual -11987.65%, underscoring the company's current focus on research and development over profitability.
Here are a couple of InvestingPro Tips for INOVIO:
1. INOVIO is quickly burning through cash, which is a critical factor for investors to consider given the company's current non-profitable status.
2. The company does not pay a dividend to shareholders, which is common for growth-focused biotech companies reinvesting earnings into research and development.
For those interested in deeper analysis, there are an additional 10 InvestingPro Tips available, including insights on the company's cash position relative to its debt, gross profit margins, and earnings revisions by analysts. To explore these further, visit https://www.investing.com/pro/INO and remember to use coupon code PRONEWS24 to get an additional 10% off a yearly or biyearly Pro and Pro+ subscription.
Full transcript - Inovio Pharmaceuticals Inc (NASDAQ:INO) Q1 2024:
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 a listen-only mode. Following the presentation, we will conduct a question-and-answer session. [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.
Thomas Hong: Good afternoon and thank you for joining the INOVIO first quarter 2024 financial results conference call. Joining me on today's call are Dr. Jacque Shea, President and CEO; 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 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 has concluded. I will now turn the call over to INOVIO's President and CEO, Dr. Jacque Shea.
Jacqueline 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 three 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 two 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 3107 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 first potential FDA approved therapy for this devastating disease, and we're now moving to initiate the trial as soon as possible. As you'll 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.
anti: 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 pre-funded 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?
SARS: 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 pre-funded 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?
CoV: 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 pre-funded 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?
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 million through an offering of common stock and pre-funded 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?
Michael Sumner: Thank you very much, Jacque and greetings everyone. As Jacque 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 two 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, 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. So, 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, 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. The paper emphasizes that while researchers saw cumulative risks for patients who had more than five surgeries, 44% of patients who had less than five surgeries had incurred permanent iatrogenic injury. That's 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 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 affecting 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 1/2 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 1/2 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 three surgeries. Further, 28% of the patients required zero surgeries in the year following the first dose. Relative to other Phase 1/2 clinical trials, our protocol required that all surgeries conducted during the dosing window, a 54-day period during which four doses were administered be counted in the overall results. The protocol for our trial also did not include prescribed laryngoscopy and surgery at weeks six 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 candidates clinical and immunological strengths. Based on historical data from other DNA medicines programs which involve re-dosing, we believe we will be able to effectively re-dose 3107 to potentially enhance immune responses for partial and non-responders. We plan on investigating re-dosing strategies to build on the impressive results as shared on the previous slide and plan to submit a re-dosing 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.
anti: In combination, this therapeutic approach is designed to leverage the antigen specific T cells elicited by 3112 and the ability of LOQTORZI to re-engage 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 higher met need within this rapidly growing patient group. 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 paper package for our Phase 3 trial to the FDA in the first quarter and recently received feedback giving us confidence that we can move forward with our Phase 3 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.
PD-1: In combination, this therapeutic approach is designed to leverage the antigen specific T cells elicited by 3112 and the ability of LOQTORZI to re-engage 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 higher met need within this rapidly growing patient group. 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 paper package for our Phase 3 trial to the FDA in the first quarter and recently received feedback giving us confidence that we can move forward with our Phase 3 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.
FANG: 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 2/3 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 non-human primate challenge study to human-titis [ph]. 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-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?
Mark Twyman: 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 and to patients. RRP 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. 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, healthcare 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 advantages of 3107, they were just one part of our foundation for commercial success. As I highlighted last quarter, that foundation also includes a critical understanding of the patient and healthcare provider landscapes and building a deep fence 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 3107, selected a three PL [ph] 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 non-field based ACP inpatient 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 and 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 has many similar characteristics to 3107. Nirogacestat is the first FDA approved treatment for adults with desmoid tumors, a rare disease characterized by noncancerous growth found in connective tissue that, much like papillomas, are rarely fatal, but plays 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 in of itself places significant physical and emotional burden on patients. Approved for marketing by the FDA in late 2023, nirogacestat 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 3107 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 first quarter financial results. Peter?
Peter Kies: 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 Jacque 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 non-cash 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 of 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 Jacque.
Jacqueline Shea: Thanks Peter. I'd now like to open up the call to answer any questions you might have. Operator?
Operator: [Operator Instructions] Your first question is from the line of Hartaj Singh from Oppenheimer. Your line is now open.
Hartaj Singh: Great, thank you. I've 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, Jacque and 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 3 advancing for INO 3112, would you expect the burn to start moving up over the next few quarters? And thank you for the questions.
Hartaj Singh: Hi, Hartaj. Nice to hear from you. So, yes HPV vaccines, 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 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, 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%. 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 three main age peaks. So pediatric RRP tends to peak at around age seven, 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 men, and these are the part of the population that are least likely to have received HPV vaccination. So, taken altogether, whilst I think we are seeing encouraging progress in terms of HPV vaccines, which do protect against infection, with HPV-6 and HPV-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?
Michael Sumner: You hit every major point.
Hartaj Singh: 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?
Peter Kies: Thank you, Jacque. Yes Hartaj. So we did increase our estimated burn this quarter by $4 million. I do expect that to be fairly consistent. But we've given guidance that we have cash into third quarter 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 INO-3112 more and get that launched, we could see some potential increases after that.
Unidentified Analyst: Great. Thank you, Jacque. Thanks, Peter. Thanks, Mike.
Operator: Your next question is from the line of Roy Buchanan from JMP. Your line is now open.
Roy Buchanan: Hey, thanks for taking the questions. Just a few on INO-3107. This one's 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?
Jacqueline Shea: 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?
Michael Sumner: Thank you, Jacque. 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 five PSP device has been used in two Phase 3 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.
Roy Buchanan: 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 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 INO-3112. Thanks.
Jacqueline Shea: Yes. Mike, do you want to talk about the confirmatory trial and what we're thinking about in terms of enrollment timeline?
Michael Sumner: 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 1/2 study across eight clinical sites. Within approximately a year time period, we are going to be expanding beyond the eight 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 or publications at the moment, but we will do so as soon as we know.
Jacqueline Shea: Yes. If I can just add sort of one additional point with regards to the confirmatory study, we just, the FDA have advised us we just need to 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.
Roy Buchanan: Right. Okay. Do they have any requirements on enrollment? Like 10 patients in or anything or not at all?
Michael Sumner: 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.
Roy Buchanan: Got it. Okay and then INO-3112. 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.
Michael Sumner: 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 three. Okay.
Roy Buchanan: Thank you.
Operator: Your next question is from the line of Gregory Renza from RBC Capital Markets. Please go ahead.
Anish Nikhanj: Hi, guys, it's Anish for Greg. Thanks for the color on today's call and for taking our questions. I just wanted to ask on INO-3107 and more on the clinical use side in considering the competitive landscape and with Precigen (NASDAQ:PGEN) utilizing a subcu route of administration, what are you hearing from KOLs, physicians and even patients on the use of the selector device as another relative layer or step for drug administration? And how do you feel this positions INO-3107 in the opportunity ahead? Just in thinking about if it could be better suited for certain clinics, practitioners or even patients. Thanks so much.
Jacqueline Shea: 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 and in two other Phase 3 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 healthcare 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. And we're really not seeing it as a barrier compared to subcu administration. Mark, do you want to talk about it?
Mark Twyman: Yes. I mean, just to be a little bit more specific, your comments were spot on, but we've done primary market research with physicians and they've said exactly what Jacque 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, that's pretty much what's on the conference floor. So, again, the results of 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.
Anish Nikhanj: Great. Thanks so much and look forward to seeing you at our conference this week.
Jacqueline Shea: Yes, look forward to seeing you as well Anish.
Operator: Your next question is from the line of Roger Song with Jefferies. Please go ahead.
Roger Song: Great. Thanks for the update and taking our question, maybe a couple questions related to INO-3107. In a confirmatory study, one is in terms of the control arm treatment option at the site. And I'm just curious how heterogeneous though 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 understanding? You probably alluded one less, one fewer surgery can be clinically needed for those patients. But just curious, want to confirm, what's the power assumption, the effect size assumption you have for the intra-confirmatory study? Thank you.
Jacqueline Shea: Thank you, Roger. So your line's 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 questions?
Roger Song: That's correct. Sorry about the connection here. Yes, those are the questions we ask.
Jacqueline Shea: Great. So, Mike, would you like to talk about the, the sites we've used today, the sites we're thinking of using going forward, and why we think actually having already been in eight sites is actually very helpful for us.
Michael Sumner: And precisely that fact that [Indiscernible] to me. We have conducted the Phase 1/2 study across eight 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. So as we expand beyond the original eight 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 two to one 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 1/2 study, both of those cohorts individually were statistically significant. And we, as part of the study, we also collected three year data for patients coming into that study. And so we really used that data to try and estimate what the placebo effect. And 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 1/2 study and what data we have, that we will. We have an appropriate effect size and statistical sample.
Jacqueline Shea: 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 four per year. And therefore there are a lot of patients who are having less than four 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 INO-3107 into Europe. Mike, anything else you want to add to those aspects?
Michael Sumner: No, I think we've covered all the relevant points.
Jacqueline Shea: Thanks.
Roger Song: Great. Thank you.
Operator: Thank you. Your next question is from the line of Yi Chen from H.C. Wainwright. Please go ahead.
Yi Chen: Thank you for taking my questions. 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? Thank you.
Michael Sumner: No, I think one of the things we were very pleased about was that the data set we saw from our Phase 1/2 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 two surgeries in the previous year and be representative of the true RRP population that's out there.
Jacqueline Shea: And just as a reminder, we enrolled people in the Phase 1/2 study who'd had from between two and eight surgeries the prior year. People had both six and 11 positive disease as well as people with mixed disease. So we really do believe that patient population is representative of the population we want to treat.
Yi Chen: So when you see a broader spectrum of RFP disease, what exactly does that mean for the confirmatory trial?
Michael Sumner: This relates to the fact that we are allowed to recruit patients with two 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 three or more surgeries. And as Jacque 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.
Yi Chen: Okay. So if for the confirmatory trial, there are a lot of two surgeries, patient population road, could that potentially change the readout?
Michael Sumner: 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 1/2 study. I would fully expect we will have that full range that we saw in the previous study, starting at two, but going up to eight and maybe more surgeries, it's difficult to say. But based on the RRP foundation data that they say, they note a median of four 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.
Yi Chen: Okay. Thank you.
Operator: Your next question is from the line of Sudan Loganathan [ph] from Stephens. Please go ahead.
Unidentified Analyst: 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 being on track for INO-3107, is with the, under the accelerated approval pathway is, 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 to, just make sure that you're on track for that, for 2025?
Michael Sumner: I think 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 six month review period once the file has been accepted.
Unidentified Analyst: Great. And then secondly, real quick, in terms of the initiation of the confirmatory trial, with the feedback that the FDA may provide 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 line up between the two.
Michael Sumner: 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.
Jacqueline Shea: And then we will need the full data from the confirmatory trial for full approval.
Unidentified Analyst: Got it. 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 be looking 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?
Jacqueline Shea: 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 1/2 trial, we actually recruited faster than we initially thought recruitment was. The trial was fully enrolled in less than a year.
Unidentified Analyst: Great. Thank you so much. That's all my questions. Thanks for squeezing me in here.
Jacqueline Shea: Nice to talk with you.
Operator: There are no further questions at this time. I would now like to hand the call back to Jacque Shea, president and CEO, for closing remarks. Please go ahead.
Jacqueline Shea: 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.
Operator: Ladies and gentlemen, this concludes today's conference call. Thank you very much for your participation. You may now disconnect.
This article was generated with the support of AI and reviewed by an editor. For more information see our T&C.