INOVIO Pharmaceuticals, Inc. (NASDAQ: INO) has outlined a robust plan for the upcoming years, focusing on the development and potential 2025 launch of its leading product, INO-3107, for the treatment of Recurrent Respiratory Papillomatosis (RRP).
During its fourth-quarter and year-end 2023 financial results conference call, President and CEO Dr. Jacque Shea highlighted the company’s strategic milestones, including the anticipated submission of a Biologics License Application (BLA) in the second half of 2024. The call also addressed financial discipline, market potential for its RRP therapy, and collaboration with Coherus BioSciences on throat cancer treatment.
Key Takeaways
- INOVIO plans to submit a BLA for INO-3107 in H2 2024 and launch the product in 2025.
- Positive Phase 1/2 trial results for INO-3107 show reduced surgeries for RRP patients.
- INOVIO has received Orphan Drug and Breakthrough Therapy designations for INO-3107.
- A clinical collaboration with Coherus BioSciences will evaluate INO-3112 with LOQTORZI for throat cancer.
- The company has a financial runway extending into Q2 2025.
- INOVIO is in discussions with the FDA about a confirmatory trial for accelerated approval.
Company Outlook
- INOVIO is preparing for the potential 2025 launch of INO-3107.
- The company is conducting market analysis and mapping the physician landscape for RRP.
- INOVIO is focused on advancing its therapy for RRP and progressing other pipeline candidates through partnerships and non-dilutive funding.
- There is confidence in the market potential for INO-3107 as a non-surgical treatment option for RRP.
Bearish Highlights
- The company reported decreased operating expenses and a net loss for Q4 2023 and the full year.
Bullish Highlights
- INOVIO's financial position is solid, with a cash runway until Q2 2025.
- The company's DNA medicine platform and pipeline show promise in addressing unmet medical needs.
- The collaboration with Coherus BioSciences aims to expand the use of LOQTORZI in combination with INOVIO's product.
Misses
- No specific details were provided regarding the regulatory pathway for the European Union.
Q&A Highlights
- INOVIO is finalizing trial details with the FDA and anticipates revealing them soon.
- The company is assessing rare disease pricing comparatives for its asset.
- The Phase 3 design for one of the pipeline candidates is in progress.
- Discussions with the FDA are pending to determine the pathway forward for registration studies.
INOVIO Pharmaceuticals has positioned itself as a key player in the DNA medicine space, with a clear focus on delivering innovative treatments for rare diseases. As the company moves toward the submission of its BLA and potential product launch, it remains committed to financial discipline and strategic collaborations to enhance its market presence and address the needs of patients with unmet medical conditions.
InvestingPro Insights
INOVIO Pharmaceuticals, Inc. (NASDAQ: INO) has garnered attention with its ambitious plans for INO-3107 and its strategic partnerships. As investors consider the potential of INOVIO's pipeline, real-time data from InvestingPro provides additional context to the company's financial health and market performance.
InvestingPro Data:
- Market Cap (Adjusted): 224.53M USD, reflecting the company's current valuation in the market.
- Revenue Growth: A significant decrease of -92.22% in revenue over the last twelve months as of Q1 2023, indicating challenges in revenue generation.
- Price Total Return: The stock has seen a strong return over the last three months with a 117.59% increase, suggesting a positive investor sentiment in the short term.
InvestingPro Tips:
- INOVIO holds more cash than debt on its balance sheet, which could provide financial flexibility and support its strategic initiatives.
- Analysts anticipate a sales decline in the current year, which may be a point of consideration for investors looking at the company's future revenue streams.
For investors seeking a deeper analysis, there are additional InvestingPro Tips available at https://www.investing.com/pro/INO, including insights on the company's cash burn rate and profitability forecasts. Utilize coupon code PRONEWS24 to get an extra 10% off a yearly or biyearly Pro and Pro+ subscription, unlocking access to these valuable tips and more. With a total of 13 InvestingPro Tips listed, investors can gain a comprehensive understanding of INOVIO's financial and market position.
Full transcript - Inovio Pharmaceuticals Inc (NASDAQ:INO) Q4 2023:
Operator: Good afternoon, ladies and gentlemen and welcome to the INOVIO Fourth Quarter and Year-End 2023 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 Wednesday, March 06, 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 2023 fourth quarter and full-year 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 and full-year ended December 31, 2023, 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 is 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. The past 12 months have been transformational for INOVIO. Today we are a company planning to submit our first BLA in the second half of this year and preparing for the potential commercial launch of our first product in 2025. If approved, INO-3107 could also become the first non-surgical therapeutic option for patients with RRP and be the first DNA medicine available in the United States. To achieve this transformation, we have prioritized our product pipeline to focus on 3107 and other promising late-stage assets, all with high unmet medical need and strong commercial potential. We remain committed to financial discipline cutting our operating expenses nearly in half compared with 2022 and focused on leveraging the advantages of our platform to deliver on the promise of DNA medicine. In addition to the significant progress made with 3107, our strategic refocus helped drive progress across the pipeline including a new clinical collaboration and supply agreement with Coherus BioSciences to develop INO-3107 in combination with LOQTORZI for throat cancer. We also shared encouraging results for INO-4201 as an Ebola booster vaccine, continue to advance other clinical-stage candidates and made progress with promising preclinical research opportunities for next generation candidates adding to the positive momentum. Looking ahead, several key catalysts will help continue that momentum across our pipeline. In addition to submitting our BLA for 3107 under FDA's accelerated approval program, we plan to initiate a confirmatory trial in the second half of 2024 and will continue preparations for a potential 2025 launch. For our immuno-oncology candidates, we plan to finalize the trial design for evaluation of 3112 in combination with LOQTORZI in patients with throat cancer as well as determine next steps for 5401 in glioblastoma a deadly form of brain cancer. We also expect some key milestones for our infectious disease candidates including discussions with collaborators and potential partners around development plans for INO-4201 as an Ebola booster vaccine in the first half of 2024 and a readout of the first clinical data from the Phase 1 trial evaluating the anti-SARS-CoV-2 dMAbs candidates in the second half of 2024. I'd now like to pass the call over to our CMO, Mike Sumner, who will provide some additional details on our clinical progress over the past year and our goals for the year ahead.
Michael Sumner: Thank you very much, Jacque, and greetings everyone. As Jacque outlined, we have made significant progress across our pipeline over the past year. Thanks to a strong strategic vision that prioritizes promising candidates with strong commercial potential. One of the highlights has been the significant progress of INO-3107 for the treatment of Recurrent Respiratory Papillomatosis or RRP. For those who are not familiar with RRP, it is a devastating rare disease of the respiratory tract caused by HPV-6 and HPV-11. It is characterized by wart-like growth called papillomas that can develop throughout the respiratory tract but primarily affect the larynx and vocal cords. RRP most commonly causes difficulty speaking or complete voice loss, difficulty swallowing, shortness of breath, and choking episodes. In rare cases, papillomas can spread to the lungs or become malignant. Incidents and prevalence of RRP is variable globally and depends on several factors. The most widely cited U.S. epidemiology data published in 1995 estimated that there were 14,000 active cases for both adults and juveniles and about 1.8 new cases per 100,000 adults per year. The only way to remove the papillomas is surgery. But surgery doesn't address the underlying HPV infection, so the papillomas grow back, often forcing patients to have multiple surgeries a year. In the worst cases, that could be 100 of surgeries over a lifetime. This puts an extreme physical and emotional burden on patients, including the threat of permanent vocal cord damage, impacting the patient's ability to speak normally ever again. A recent study found that even patients who have had less than five surgery, face a 50% chance of permanent vocal cord damage. In patients who have had ten or more surgeries, that increases to a 98% chance. From our conversations with patients and healthcare providers, RRP patients are desperate for a non-surgical treatment option. As Kim McClellan, President of the RRP Foundation, reiterated last week at the White House Forum on Rare Diseases, even one less surgery a year would be life changing for patients. This slide shows the very real impact of INO-3107 has had in reducing surgeries for RRP patients in our Phase 1/2 trial. As you can see here, the majority of patients, 81%, saw a reduction in surgery after treatment, with 28% needing no surgeries at all during the year after treatment. As a reminder, we counted all surgeries, including any surgeries performed during the dosing window. We believe 3107 has the potential to completely change the treatment paradigm for patients as a therapeutic adjunct to surgery. As you can see on this updated timeline, we have achieved some major development and regulatory milestones in just over a year. In the first quarter of 2023, we shared positive results from our Phase 1/2 trial, which were later published in a leading peer-reviewed journal read by our future physician customer base. In the second quarter, we received Orphan Drug Designation in the European Union followed by Breakthrough Therapy Designation from the FDA in the fourth quarter. We now have an established path to BLA submission under the FDA's accelerated approval program and announced plans earlier this year to submit a BLA in the second half of 2024. Looking forward, some of the key catalysts on the horizon for INO-3107 include: completing submission of our BLA under the accelerated approval program in the second half of ’24, initiating our confirmatory trial prior to that submission, requesting rolling submission and priority review, which would lead to possible action on our BLA application within six months compared to the usual 10 month review. We will also target publication of our immunological data supporting the mechanism of action of 3107 in the second half of the year. And finally, commercial launch in 2025 if we receive FDA approval. Our Chief Commercial Officer, Mark Twyman, will provide an update on our commercial preparations, and we look forward to accelerating the development of this promising product candidate over the next year and ultimately delivering on the promise of our DNA medicine for RRP patients across the United States. Shifting gears now to another late-stage DNA medicine. I'd like to spend some time talking about INO-3112 and our exciting new clinical collaboration and supply agreement with Coherus BioSciences that we announced earlier this year. This partnership will allow us to evaluate 3112 in combination with LOQTORZI, a PD-1 inhibitor that recently received FDA approval for treatment of nasopharangeal carcinoma. We will be studying this combination therapy as a potential treatment for patients with locoregionally advanced high-risk HPV-16 and HPV-18 positive oropharyngeal squamous cell carcinoma. In combination, this therapeutic approach is designed to leverage the antigen specific T-cells elicited by 3112 and the anti-tumor immunity generated by LOQTORZI to potentially provide improved patient outcomes. Under the terms of the agreement, Coherus will provide LOQTORZI for use in a planned Phase 3 clinical trial and provide support for regulatory interactions. With this collaboration in place, we have submitted our clinical development plans to the FDA and expect to receive feedback in the second quarter. So, what is oropharyngeal squamous cell carcinoma? It's a type of head and neck cancer that occurs in the base of the tongue, tonsils, and/or soft palate, and is most commonly referred to as throat cancer. Throat cancer is typically causally related to high-risk subtypes of HPV, which are responsible for 70% to 80% of all oropharyngeal cancers diagnosed in the United States. They are also associated with tobacco and alcohol use. HPV-positive throat cancer is rapidly increasing in instance among patients in high income countries and has surpassed cervical cancer as the most common HPV-related cancer diagnosed in the U.S. with nearly 20,000 new cases each year. Most throat cancer patients are diagnosed with locoregionally advanced disease, and the current treatment practice is focused on curative options through the use of multi-therapeutic approaches, including surgery and chemo radiotherapy. With this treatment protocol, about 75% of patients do very well as measured by a three year progression free survival. However, those 25% of patients who have their cancer progress face very poor clinical outcomes. Our proposed trial of INO-3112 in combination with LOQTORZI will be in patients who are HPV-16 or HPV-18 positive and exhibit a high-risk of recurrent disease with the goal of preventing disease progression. There are an estimated 3,000 to 4,000 new patients in the U.S. every year, who are deemed to meet these criteria. Based on previous trial data and the growing body of research indicating that DNA medicines are adept at combating HPV-related diseases, there is a strong rationale in combining 3112 with a proven PD-1 inhibitor. Results from a Phase 1/2 trial of 3112 as a single agent treatment in ‘22 HPV-positive head and neck squamous cell carcinoma patients demonstrated T cell responses and infiltration of CD8+ T cells into the tumors. In early ‘23, updated results were also published from a different Phase 1/2 trial of 3112 in combination with AstraZeneca (NASDAQ:AZN)'s PD-L1 checkpoint inhibitor, durvalumab, showing an overall response rate of 28%, which was comprised of four complete responses and four partial responses in 29 evaluable patients. This was accompanied once again by increased peripheral HPV-specific T cells and tumoral CD8+ T cells. The efficacy of this combination of 3112 with durvalumab resulted in a median overall survival of more than 29 months. This compares favorably to immune checkpoint blockade therapy alone, which reports median overall survival of approximately 12 months. This combined data set provides compelling evidence to support our belief in the potential of INO-3112 and LOQTORZI. I will now turn the call over to Mark, to provide an update on our commercialization efforts for INO-3107. Mark?
Mark Twyman: Thanks, Mike, and hello, everyone. I'm pleased to share that our commercial efforts for INO-3107 are well underway as we continue to prepare for potential 2025 launch. While there's still much work to be done, I'm confident in our commercial launch strategy for several important reasons. First, we have made understanding patients and their experiences a top priority every step of the way. To continue building on our understanding of the market, we held an Advisory Board panel in October of last year with adult patients suffering from RRP. They shared their journeys from diagnosis to treatment and provided invaluable insights into the unmet needs of the RRP patient community at large. We've also conducted other Advisory Boards with healthcare providers specializing in the treatment of RRP and with caregivers of juvenile patients. Next, we understand that mapping the physician landscape will be critical to our commercial success. To this end, we have initiated a very comprehensive market analysis of physicians that treat RRP that will allow us to focus on commercialization process for innovative products, particularly for rare diseases. Our collective expertise in putting the plans and essential systems in place for successful launch has been essential to our progress thus far and will help ensure that we stay on track moving forward. And perhaps most importantly, we believe that INO-3107 offers potential compelling clinical and commercial advantages that will serve as an important foundation to our commercial efforts. As you can see here, the FDA has advised that we can use the data from our completed Phase 1/2 trial to submit a BLA under the accelerated approval program. In the trial, INO-3107 was immunogenic and generally well-tolerated and over 80% of patients across the disease severity continuum had a reduction in the number of surgeries compared to the previous year. This data was key in supporting our application for, and subsequent receipt of Breakthrough Therapy Designation from the FDA. From a commercial standpoint, INO-3107 offers several key differentiators. It targets and has shown similar efficacy across both HPV-6 and HPV-11 which cause RRP. Patients in our trial had a range of two to eight surgeries in the prior year with efficacy demonstrated across the range of disease severity. INO-3107 also offers important attributes typical of our DNA medicines platform, including the potential for re-dosing and stability for up to three years at refrigerator temperatures. Administration with CELLECTRA, our proprietary electroporation device was well-tolerated by patients was easy-to-use for healthcare providers in the Phase 1/2 trial consistent with its use in other trials. Also important for the commercialization of INO-3107 is our well-defined commercial scale manufacturing process as well as Orphan Drug Designation in both the U.S. and EU which offer the potential commercial incentives and regulatory mechanisms in those markets. I'll now turn the call back to our CEO, Jacque Shea, for some additional pipeline updates. Jacque?
Jacqueline Shea: Thank you, Mark. Mike has highlighted the important progress we've made with both INO-3107 and INO-3112 and we are focusing the majority of our internal resources on advancing those candidates. However, we have several other late-stage clinical-stage assets and next generation candidates that we plan to advance through partnerships and collaborations across industry, academia and governmental agencies. I'd like to provide a brief update on each of them. Earlier I mentioned the encouraging results we announced in early 2023 from our Phase 1b clinical trial of 4201 as Ebola vaccine booster candidate. More recently, we've received feedback from the FDA and identified a potential development pathway and are now in discussions with collaborators and potential partners to define next steps. INO-5401 has two current disease targets. For glioblastoma, we're in discussions with our partner Regeneron (NASDAQ:REGN) and investigators about next steps and our goal is to have a finalized plan in the first half of 2024. The second target is to prevent cancer or reoccurrence of cancer in adult cancer or non-cancer patients with BRCA1 or BRCA2 mutations. A Phase 1b study is being conducted by the University of Pennsylvania and we look forward to updates as they become available. Our partner ApolloBio is also conducting a Phase 3 trial of VGX-3100 as a therapeutic treatment in cervical HSIL caused by HPV-16 and HPV-18. A Phase 2 trial sponsored by the AIDS Malignancy Consortium is also underway evaluating VGX-3100 in HIV-positive participants with anal HSIL caused by HPV-16 and HPV-18. And there is also exciting work advancing next generation DNA medicine technology including a trial with our collaborators at the Wistar Institute evaluating DNA-launched Nanoparticles or dLNPs. dLNPs are designed to provide high and maintain levels of antibody responses including neutralizing antibodies while continuing to generate T cell responses. The first dLNPs to enter clinical trials INO-6172 is a preventative HIV vaccine candidate in a Phase 1 trial sponsored and funded by NIAID. And finally, we're still on partners from AstraZeneca, the University of Pennsylvania and Indiana University leading Phase 1 trial using our DNA encoded monoclonal antibody or dMAb technology to develop dMAb as both therapeutic and preventative treatments for COVID-19. We're excited about what the future holds for these innovative technologies and look forward to sharing more in the year ahead. I'll now turn the call over to our CFO, Peter Kies, for our fourth quarter and full-year 2023 financial summary. Peter?
Peter Kies: Thank you, Jacque. Today I'd like to provide an overview of INOVIO'S operational highlights and financial condition for the fourth quarter and full-year of 2023. As Jacque, Mike and Mark have noted, we have made significant progress across our pipeline over the past year, advancing key candidates while working successfully to reduce our operational spend after our pipeline reprioritization. As you can see from this slide, we have again reduced our total operating spend dropping from $56.1 million in the fourth quarter of 2022 to $27.5 million in the fourth quarter of 2023, a 51% decrease. Our full-year operating expenses were also nearly cut in half from $277.8 million for 2022 to $144.8 million for 2023. Breaking down operating expenses a bit more, our R&D expenses in the fourth quarter of 2023 totaled $17.3 million compared to $42.1 million for the same period in 2022. Our full-year R&D expenses for 2023 were $86.7 million compared to $187.7 million for the same period in 2022. 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 fourth quarter 2023 were $10.2 million compared to $14 million for the same period in 2022. G&A expenses for the full-year of 2023 were $47.6 million compared to $90.2 million for the same period in 2022. Revenues for the fourth quarter of 2023 were $103,000 compared to $125,000 for the same period in 2022. Revenues for the full-year of 2023 were $832,000 compared to $10.3 million for the same period in 2022. Note that revenues reported for 2022 was associated with the procurement contract with the U.S. Department of Defense for INOVIO's devices and accessories to be used for the delivery of INO-4800, our COVID vaccine candidate, which we have since discontinued. These factors combined to bring our net loss for the fourth quarter of 2023 to $25 million or $1.10 per share basic and dilutive and our net loss for the full-year 2023 to $135.1 million or $6.09 per share basic and dilutive. We finished the fourth quarter of 2023 with $145.3 million in cash, cash equivalents and short-term investments compared to $253 million as of December 31, 2022. INOVIO estimates its cash runway to extend into the second quarter of 2025. This projection includes an operational net cash burn estimate of approximately $26 million for the first quarter of 2024. This amount excludes repayment of $17 million in remaining principal and accrued interest on convertible senior notes that matured on March 1, 2024. Including the repayment, the total net cash burn for the first quarter of 2024 is expected to be approximately $43 million. These cash runway projections do not include any funds that may be raised through and at-the-market program or other capital raise activities. As a reminder, you can find our full financial statements in this afternoon's press release as well as in our Form 10-K filed with the SEC. And with that, I'll turn it back over to Jacque.
Jacqueline Shea: Thanks, Peter. I'd now like to open up the call to answer any questions you might have. Operator?
Operator: Thank you. [Operator Instructions] Your first question comes from the line of Hartaj Singh with Oppenheimer Company. Please go ahead.
Hartaj Singh: Great. Thank you. Thanks for the questions. I have a couple actually, if you don't mind. One is, I know the confirmatory trial has been in discussion with the FDA for a little bit. In fact, I believe you were going to start that sometime last year, early this year, and then the FDA kind of, granted you the accelerated approval process. Can you maybe just give us some color on what that looks like? And especially how long would it take to recruit the evaluation period and roughly when it could read out? And, again, we're not looking for any guidance. And then secondly, we talked to a lot of KOLs, about this in therapy and RRP. They think it should broadly apply to a lot of patients. There's academics, literature that suggests that, cost of surgery is $70,000 to $100,000 per patient per year, but it adds up over time. Just how are you thinking of pricing comps? And so, just any color there or any thoughts there? Again, back to the question.
Jacqueline Shea: Good afternoon, Hartaj. Those are great questions. So, as I think we covered in the call, in our BTD multi-disciplinary meeting that we held with the FDA just before Christmas, we got guidance on a number of different elements that needed to go into our BLA submission and part of that was getting further guidance on the design of that confirmatory trial. So, I'm going to hand over to Mike, to provide a bit more detail there and then perhaps Mark, you can talk about some of the comparatives and thoughts on pricing. So, Mike?
Michael Sumner: Yes. Thanks, Jacque, and hi, Hartaj. With respect to the confirmatory trial, I think we're in the final stages with discussing the details with the agency. So, I'm hoping we will, soon be in a position to, reveal the sort of details around our design and future strategy. You also asked about sort of recruitment and readouts. Until we get the final on the sample size, it's difficult to totally predict how long it's going to take. But, what I can say is, we included eight clinical trial sites in our original Phase 1/2 study. We're certainly going to go broader than that for a confirmatory study. And, I think, we've talked consistently about the patient need and their openness to receive treatment for a non-surgical option. So, I'm really hoping that we'll be able to recruit the subjects pretty quickly. And again, with respect to readout, that's really going to depend on what the final design and sort of length of observation that we're going to need to include. But hopefully, next quarterly call, I'll be able to provide some more color around that.
Jacqueline Shea: Thanks, Mike. And Mark on the pricing comparatives?
Mark Twyman: Yes, sure. Hey, Hartaj, good to talk to you. So, I think what we said previously is that RRP is a rare disease and we would anticipate rare disease pricing for this asset. I think with that said though, there are a number of rare disease analogs, some of which also are positioned as alternatives to surgery that we're assessing as a part of the pricing work that we're doing. And I would say that as we get closer to launch, we'll be in a better position to say more about that.
Hartaj Singh: And Mark, can I just have a quick follow-up on just that? I mean, will you be publishing [pharmacoeconomic] (ph) data also as you get closer to launching or maybe after that on 3107? And, thanks for all the questions.
Mark Twyman: I think, Hartaj, I'm going to direct that question to Mike. Mike, would you like to respond to that?
Michael Sumner: Yes, certainly. I mean, we obviously didn't include too many quality of life, impact on patients in our Phase 1/2 study. I mean, we will we are certainly in the process of assessing how we can document the impact of RRP on patients, and we will most likely include more measures prospectively in our confirmatory study. So, again, we will have I mean, obviously, we will aim to have supporting evidence for the price that we eventually set.
Hartaj Singh: Okay. Thank you, all.
Operator: Next question comes from the line of Roy Buchanan with Citizens. Please go ahead.
Roy Buchanan: Hey, great. I guess, maybe just sticking to 3107 for a second, then I have a few others. But, just when you say commercial scale manufacturing, how many patients do you think you can address in 2025? Do you think you can address the entire population or just what are you thinking for initial penetration?
Jacqueline Shea: Yes. So, Mark, do you want to take that one?
Mark Twyman: Sure. I'll take a whack at that. And if there's some additional comments, feel free to add. I guess the way I respond to that question is, as you would expect, we've done sort of a lot of modeling and we have been working sort of closely with our manufacturing team. And so, we are confident that sort of based on our market projections and our estimates around adoption etcetera that we'll be able to sort of fully meet the demand for 3107.
Jacqueline Shea: Yes. And, if I can just add on the manufacturing side, we had already got to commercial scale, some other product candidates. And, this is a rare disease in terms of dose requirements. The actual numbers of dose requirements is very manageable for us from a manufacturing standpoint. So, I think we're pretty well-positioned from a manufacturing standpoint to be able to build up the launch inventory and be able to support the market need over the first couple of years pretty easily.
Roy Buchanan: Okay. Perfect. And, switching to the pipeline, deeper pipeline a bit. I guess for 3112, anything you could tell us about the design that you submitted for that Phase 3? Do you expect that it can be registrational by itself? And then, the last slide deck you had, eight additional clinical-stage candidates. Can you just help us understand a bit what, I guess, level of development you can do for those candidates given the runway into 2Q '25? I guess, what does that runway assume in terms of what you can develop out of the pipeline beyond 3107? Thanks.
Jacqueline Shea: Yes, that's great. So, Mike, why don't you take the 3112 Phase 3 design and what we're thinking there or not? Then I can talk about the rest of the pipeline candidates.
Michael Sumner: Yes. Thank you. So, as you heard in the call today, we clearly sort of articulated the patient population that we're going after, high-risk patients with local regionally advanced disease. And high-risk really comes down to based on tumor size, local infiltration, local node involvement and also smoking history. So, I think we did a lot of work with KOLs on a global basis to define that population. I mean, as we think of developing this candidate, I mean, based on the well-known safety profile of PD-1 inhibitors and also the well-documented safety profile of our DNA medicines, we certainly feel we can do a registration study. Obviously, that will ultimately be decided by the agency. And, as we've looked to that design, we followed sort of very traditional ways. I mean, obviously, the agency is going to want to understand contribution of components. So, that is clearly an element of the design we've submitted to the agency. And so, we're really waiting to have that discussion with them in Quarter 2 to determine what our actual pathway forward really looks like.
Jacqueline Shea: Thanks, Mike. And just to talk about the rest of the pipeline. As I mentioned on the call, clearly we're focusing the majority of our internal resources on advancing 3107 forward license year and then the launch hopefully next year and then moving 3112 forward. We do have a number of partnerships in place for the other assets in our pipeline and we're going to be leveraging those partnerships and non-dilutive funding mechanisms, grants etcetera to be able to help move those candidates forward. And some of the earlier stage-work particularly the pre-clinical work, we can also move forward ourselves. So, we think we have ways leveraging those partnerships non-dilutive funding mechanisms of moving those candidates forward to generate some meaningful progress as well.
Roy Buchanan: Okay. Thanks for taking the questions.
Operator: Your next question comes from the line of Gregory Renza with RBC Capital Markets. Please go ahead.
Unidentified Analyst: Hi, guys. It's Anish on for Greg. Thanks for taking my questions. Just a couple for me. Firstly, on 3107 and RRP, just on thinking about thinking ahead to market shaping, what's some of the pushback you've gotten to-date when engaging KOLs on getting patients on to a therapy like 3107 versus standard-of-care surgery? And how has that feedback been built into your awareness and education directives? And secondly, a question on 3112. If you could just walk us through how the collaboration with Coherus came to be, the selection of LOQTORZI as a combination candidate among other potential candidates and how you can best leverage the partnership going forward? Thanks again.
Jacqueline Shea: Yes, thanks Anish. They're really great candidates. So, I'm going to ask Mark, to comment on how we're thinking about 3107 and Mike, maybe you'd like to comment on some of the clinical aspects there.
Mark Twyman: Yes. Thanks, Jacque. I guess the first thing I would say from a commercial perspective, I've never been more excited about launching a new product. And, I think it speaks to specific to how I'm going to address your question. We've conducted multiple Advisory Boards with both HPVs that are treating RRP as well as for the patients. We've been closely aligned with listening to what the RRP foundation suggest is important for probably the last three or four years. And one of the things that we've heard is that physicians don't like doing this surgery, right. They're looking for an alternative to surgery. As Mike has alluded to, I mean surgery doesn't address the underlying infection, right. So, in this cycle of surgical procedure after surgical procedure and that's actually surgery that's driving the morbidity. So, they're looking for an option, right. And, this is sort of unlike other launches where you're replacing a surgical alternative in that physicians are welcoming it, right. There's no disincentive for them to use this I know 3107 because the current standard-of-care is wholly inadequate. And similarly from a patient perspective, as Mike mentioned, it's a devastating disease and even with the reduction of sort of one surgery a year could be life changing for them. So, I am really, really confident that everything that we've learned about this marketplace pretends that we're going to have a really successful launch for 3107.
Jacqueline Shea: Thanks, Mark. Mike, do you want to talk about some of those clinical aspects and the need that the patients and the physicians are highlighting?
Michael Sumner: Yes, absolutely. So I mean, as you heard me talk about today, I mean, the latest data that was published by Simon Best from John Hopkins around the ability to cause permanent vocal cord damage is really in the mind of all the sort of RRP surgeons we've spoken to. They recognize that while surgery is hugely beneficial for the patients, they understand that sooner or later, there is going to be damage caused. And so, from a surgical perspective, as Mark said, they really would, they're just as excited as the patients, I think, for looking for a non-surgical treatment for these patients. And I keep going back to sort of having discussions with Kim McClellan. It really is every surgery just impacts a patient's life. And so, you saw on the graph I showed earlier that the tremendous impact we have had on reducing surgical burden in the RRP population. And so once again, I really feel you see that clinical efficacy and you associate it with the safety data we have accomplished or accumulated on 3107 to-date. There really isn't any reason that we've heard from the patients of why they wouldn't want a non-surgical option. So, we're very excited to move this program forward.
Mark Twyman: Hey, Mike. Can I add one other point real quick? One other sort of really important dimension of the patient component of this market is that unlike in other rare diseases and when I was at sort of Genzyme this was the case, we spend a lot of effort identifying patients, right and getting them to originate for therapy. I mean that won't be the case with RRP. I mean these are patients who originate for treatment. And the primary reason is because the impact on voice quality, right. So again, the combination of patients who originate for treatment for RRP, the fact that surgery is inadequate and burden and causes a lot of morbidity and that physicians are looking for alternative really puts us in a good position with 3107.
Jacqueline Shea: I think those are excellent points, Mark. So, moving on to 3112. So, I think maybe if we just take a step back here. For 3112 we saw really encouraging data both as a monotherapy and in combination with durvalumab. And whilst we were disappointed that AstraZeneca decided not to move durvalumab forward in the head and neck space. We were very excited by what we saw in that study and it really goes back to one of the strengths of the platform, our ability to generate these antigen specific cytotoxic CD8 T cells that we know are capable of getting to the tumor. And we know in some of our other HPV, dysplasia programs are capable of clearing HPV precancerous lesions and leading to viral clearance. So, when we wanted to move 3112 forward, we saw a lot of promise for 3112 and we really conducted quite extensive analysis looking for the right PD-1 to using combination. And Mike, maybe now is the point where you might want to jump in and talk about some of the reasons why we're so excited about LOQTORZI.
Michael Sumner: Absolutely. I mean, conducting any clinical partnership, I mean, first of all, is finding a partner that's just excited about the program as you are and the fact that LOQTORZI works with a lot of the same KOLs that will hopefully eventually prescribe 3112, gives them a unique insight into seeing the value of what we see with 3112 and LOQTORZI. And so, as a partner, they're great to work with. They share the enthusiasm for the program. Having a very recent approval with nasopharangeal carcinoma, I think, is they want to also see the use of LOQTORZI expand. And so, so far, everything every interaction we've had with Coherus has been very positive. They bring knowledge of the head and neck space to the table as well. And so, we're just really very encouraged to continue with that partnership and perform the clinical trial.
Unidentified Analyst: Thanks, guys.
Operator: Your next question comes from the line of Roger Song with Jefferies. Please go ahead.
Unidentified Analyst: Hey, good afternoon. This is [Liang Chang] (ph) for Roger. Thank you for taking our questions. So, I guess from us, regarding to the confirmatory study of 3107, could you comment on how thinking about standard-of-care practice among the different sites, how do you see that impact of study results? And how, at this point, what's the powering assumptions that you are thinking about for your confirmatory study? Thank you.
Jacqueline Shea: Yes. Mike, can you take that one?
Michael Sumner: Yes. Absolutely. Thanks, Roger. So, we can't yet obviously talk about the sample size elements. I can certainly address the clinical trial site elements. I mean, we in our Phase 1/2 study, we actually had eight recruiting sites. And, the results, while we only had 32 subjects in the Phase 1/2 study. We didn't analysis. There was certainly no site-to-site variation. So, we believe the results will be very consistent as we look to utilize more sites in our confirmatory study. So, that is certainly not a concern for us. And obviously, as we look to sites using [five PSP] (ph) device, we have a lot of experience from our previous Phase 3 program with 3100. So again, that isn't of any concern to us.
Jacqueline Shea: Mike, maybe I can just add in here. In addition to working with eight sites, we also enroll patients across the disease spectrum and we also enroll patients with both HPV-6 and HPV-11. So, I think in our Phase 1/2 study, we built up a good understanding of that variability within that patient population.
Michael Sumner: Absolutely.
Unidentified Analyst: Thank you. Maybe another question, if I may. So, regarding the 3107 Phase 1/2 data, I know one key difference from the precision study that you included the surgeries right after, including through the treatment window. So, maybe could you remind us what do you see if you do not only include surgeries after the treatment window?
Jacqueline Shea: Yes, that's a great question. I mean we designed this trial because every surgery matters to the patients. That's what we've heard time-after-time from the patients every surgery matters. Mike, do you want to talk about the data because I'm not sure if we've disclosed that yet if it's published.
Michael Sumner: No. We haven't provided any details of that. And I think also if we were going to do a like-to-like comparison, we'd obviously want to include a full 52 weeks after excluding any surgeries from the surgical window. So I mean, we will be looking at collecting that data but that's not going to be available in the short-term.
Unidentified Analyst: Got it. Thank you. That’s it for me.
Operator: [Operator Instructions] Your next question comes from the line of Yi Chen with H.C. Wainwright. Please go ahead.
Yi Chen: Thank you for taking my questions. Could you comment on the typical age range of the RRP patients? What percentage of patient population actually are on Medicare? And how much time do you think it would take to secure Medicare reimbursement following the potential FDA approval in 2025? Thank you.
Jacqueline Shea: Yes. Great question. So, Mike, do you want to talk about the age range and then Mark, maybe you can take the Medicare question?
Michael Sumner: Yeah. Absolutely. So, RRP involves all age groups. And there's actually sort of three peaks to the instance. So, the first one is the pediatric peak, which usually is around the sort of five to seven year old mark. Then there is an earlier adult peak, which obviously follows actual activity onset, and that's usually around the age of 35. And now, what is also developed is a later onset peak, which is usually around the age of 65. So, it really encompasses all age groups. But the vast majority is still, actually not the vast majority, the majority is still around the 35 age group with the elderly population growing rapidly.
Mark Twyman: Hi, it's Mark. Thanks for the question. It's really good question. I think what I've said earlier in my comments is that sort of focus and precision is going to be key for our success and consistent with that particularly as it pertains to kind of what the mix is for these patients private versus Medicare or Medicaid. We're going to get a lot of additional information there from this work that I mentioned earlier. Not only are we going to be assessing sort of the physician landscape, but the analysis all starts from the patient level and we'll be able to sort of identify where claims are being adjudicated whether it's been adjudicated in the private sector or in Medicare or Medicaid. And that will really kind of help us focus our efforts on both the commercial payers that are important, but also to help us understand what our approach needs to be from the perspective of Medicare and Medicaid. There are really kind of three pillars that we're focusing on for commercial launch, distribution and then the market access piece as well as field deployment. So, we're moving as fast as we can. I can't give you a specific timeline for when, only to say that we started early with the objective of making sure that patients both private and in Medicare and Medicaid have access to INO-3107 as quickly as possible.
Yi Chen: Thank you. Could you comment on the regulatory pathway going forward in the European Union?
Jacqueline Shea: Mike?
Michael Sumner: Yes. So, we have, obviously engaged with the European Union. We have not yet disclosed what our strategy is going to be with Europe. I certainly believe there's a pathway forward based on the information we have received, and I think we'll be able to give more details in upcoming calls.
Yi Chen: Okay. Thank you.
Jacqueline Shea: Yes. If I can just add to Mike's answer though. There's a RRP unfortunately like HPV is everywhere. There is a strong, unmet medical need as well in Europe. The standard-of-care may differ slightly from the U.S. So, that's also an important consideration to take into account. But, we'll certainly be trying to provide some more details on that as our discussions with the European regulators progress.
Yi Chen: Okay. Thank you.
Operator: Ladies and gentlemen, there are no further questions at this time. I'll now turn the call back over to Jacque Shea, President and CEO for closing remarks. Please go ahead.
Jacqueline Shea: Thank you. I open this call by highlighting the transformation INOVIO has undergone over the last year. A transformation made possible by our renewed strategic focus on the strengths of our DNA Medicine platform and our aim to become a commercial stage company. We have made more than just progress. We have built a foundation for long-term success that we will continue to build on. And we have advanced DNA medicine for patients around the world that could potentially benefit from its promise. I look forward to sharing more updates on progress with you in the year ahead. With that, thank you again for your attention and have a great evening everyone.
Operator: Ladies and gentlemen, this concludes your conference call for today. We thank you for participating and ask that you please disconnect your lines.
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