Inovio Pharmaceuticals, Inc. (INO) Q4 2025 Earnings Report, Transcript and Summary

Good afternoon, ladies and gentlemen, and welcome to the Inovio Fourth Quarter and Full Year 2025 Financial Results Conference Call. [Operator Instructions] This call is being recorded on Thursday, March 12, 2026. I would now like to turn the call over to Jennie Wilson. Please go ahead.

Good afternoon, and thank you for joining the Inovio Fourth Quarter and Full Year 2025 Financial Results Conference Call. Joining me on today's call are Dr. Jacqui Shea, President and Chief Executive Officer; Dr. Mike Sumner, Chief Medical Officer; Steve Egge, Chief Commercial Officer; and Peter Kies, Chief Financial Officer. Today's call will review our corporate and financial information for the quarter and year ended December 31, 2025, 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 and planned regulatory submissions, our interactions with the FDA regarding our BLA for INO-3107, including our yet to be scheduled meeting with the FDA to discuss eligibility for the accelerated approval program. The potential benefits of INO-3107, along with capital resources including the sufficiency of our cash resources, our expectations regarding competition, the size and growth of the potential market for INO-3107, if approved, and our ability to serve those markets. The rate and degree of market acceptance of INO-3107 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. Jacqui Shea.

Good afternoon, and thank you to everyone for joining today's call. These are very exciting times for Inovio with our first BLA for INO-3107 as a potential treatment for adults with recurrent respiratory papillomatosis or RRP, currently being reviewed by the FDA. In late December last year, we were pleased to announce that the FDA accepted our BLA review under the accelerated approval program. The FDA granted a standard 10-month review with a Prescription Drug User Fee Act or PDUFA target date set for October 30 of this year. While the BLA was accepted under the accelerated approval program, in the file acceptance letter, the FDA noted as a potential review issue, its preliminary conclusion that the company has not provided adequate information to justify eligibility for the accelerated approval program. This preliminary conclusion was made during the initial 60-day filing review period and was the first time a potential issue with respect to eligibility have been raised. As Mike will explain later in the presentation, we strongly believe that INO-3107 does fulfill the criteria for review under the accelerated approval program, by meeting an unmet medical need and providing a meaningful therapeutic benefit over existing treatment. The FDA has agreed to meet with us, we have provided additional documentation, and we're waiting for them to provide a meeting date. In the meantime, we are continuing to advance our commercial preparations, focusing on optimizing and expanding our resources towards our October PDUFA date. To achieve this, Inovio has taken steps to further conserve its financial resources, rescoping projects and activities and eliminating roles that don't directly support our primary goal for advancing INO-3107 towards U.S. approval. These efforts have enabled the extension of our estimated cash runway into the fourth quarter of this year. While the majority of our resources are directed to advancing our lead candidates towards approval, we are continuing to leverage the power of partnerships to advance other promising candidates in our pipeline. We have recently announced an exciting opportunity to build on our research in glioblastoma through an innovative Phase II adaptive platform trial sponsored by the Dana-Farber Cancer Institute, where we'll collaborate with Akeso to evaluate INO-5412 in combination with their novel PD-1, CTLA-4 bispecific antibody checkpoint inhibitor. Like our lead program, INO-3107, this program utilizes the antigen-specific cytotoxic T cell generating ability of our DNA medicines platform, but in this instance, to target cancer cells. We have also continued to advance some of our earlier-stage next-generation DNA medicine candidates, which I'll touch on later in this presentation. I look forward to advancing these programs in tandem with our top priority for 2026, achieving FDA approval of our first product and bringing INO-3107 to patients. Now I'll turn it over to Mike for some additional insights on our regulatory progress with 3107. Mike?

Thanks, Jacqui. As Jacqui outlined, we have made significant progress with our BLA as outlined on this slide, including the acceptance of our file for review under the accelerated approval program, with a PDUFA date of October 30, 2026. We believe our BLA makes a strong argument outlining how INO-3107 meets an unmet medical need and provides a meaningful therapeutic benefit over existing treatments, thus fulfilling the accelerated approval program criteria. Our next step is to discuss this with the FDA. In preparation for this meeting, they had requested that we complete an assessment aid, which we submitted in February. In this document, we reiterate and expand on our rationale for accelerated approval review. It is important to note that while we wait to meet with the FDA, the BLA is under active review, and we have been responding to routine requests for information. In addition, we submitted an updated protocol for our confirmatory trial to the IND and are awaiting feedback from the agency regarding finalizing the study design. I'd like to take a moment to focus on why we believe 3107 meets the accelerated approval criteria. Following the unexpected full approval of PAPZIMEOS in August last year, the regulatory landscape changed with respect to the requirements for eligibility. Based on published FDA guidance, when there's an already approved product, eligibility for accelerated approval depends on a candidate's ability to provide a meaningful therapeutic benefit over existing treatments and its ability to meet a remaining critical unmet need among patients. We believe that 3107 meets both of those criteria based on demonstrated efficacy and improved safety profile that does not include required surgery during the dosing window and a differentiated mechanism of action that provides the ability to treat patients who are not able to be served by existing therapy. Getting into more detail. In our trial, the majority of patients experienced fewer surgeries after treatment with 3107, with most experiencing a 50% to 100% reduction compared to the year before treatment. That clinical benefit continued to improve in the second 12-month period post treatment with half of the patients requiring 0 surgeries during that time. Efficacy was achieved without the vast majority of patients requiring surgery during the dosing window, a key differentiating advantage of the 3107 safety profile. Remember, in our Phase I/II trial, our protocol counted every surgery conducted after day 0. In contrast, surgeries conducted during the 12-week treatment window in the PAPZIMEOS trial were not counted against the efficacy end point, and 72% of the reported complete responders in the single-site Phase I/II trial had at least 1 surgery during the 12-week dosing window. To maintain what is referred to as minimal residual disease, or MRD, a protocol that is required for the efficacy of that product and is included in the label. Additionally, 3107 offers a differentiated mechanism of action, which provides the ability to treat patients who are not served by existing therapy, and thus address an unmet need in the RRP treatment landscape. PAPZIMEOS utilizes a gorilla adenoviral vector, and it is well established in the scientific literature that efficacy of adenoviral vectors may be impacted by preexisting neutralizing antibodies as they have been shown to limit the immune response that patients with these antibodies can generate. In addition, several immune factors relating to the papilloma microenvironment were identified by the investigators as being linked to the lack of efficacy for PAPZIMEOS. In contrast, ad data published in Nature Communications shows that efficacy of INO-3107 is not impacted by the papilloma microenvironment. We look forward to discussing our rationale for review under accelerated approval with the FDA. And with that, I will now turn it over to Steve for a brief commercial update. Steve?

Thanks, Mike. The burden of RRP on patients is significant, and there's an urgent need for treatment options that reduce the need for repeated surgery. RRP is characterized by chronic wart-like growth called papilloma, to grow in the respiratory tract and can cause difficulty speaking, swallowing and breathing. Surgery is still the standard of care and patients have numerous surgeries, sometimes hundreds of surgeries in the most severe cases throughout their lifetime. Every surgery matters to patients because the risk is well established. Every surgery carries the risk of permanent damage to the vocal cords and airways, and the cost of surgery can have a significant impact as well. Traveling hundreds of miles for specialized RRP care, missing work and social functions while preparing for or recovering from surgery, the anxiety and frustration of impaired voice quality making it difficult to communicate, and the psychological trauma of undergoing repeated surgeries. This is why we're committed to delivering on the potential of 3107 for RRP patients. And that potential has been validated in market research, which supports our belief that this product is approved to become the preferred treatment based on its efficacy, tolerability and simple treatment regimen. I shared these insights previously, but I think they bear repeating. Physicians we engaged in market research were most interested in the fact that the vast majority of patients by 50% to 100% reduction in surgery from 3107 and for many of them, that clinical benefit continued to improve over time. Physicians were similarly impressed with the tolerability data, which shows that 3107 was generally well tolerated, limiting the impact on patients return to daily life. This is important considering the treatment protocol includes 4 doses over a relatively short period of time. And in terms of the treatment regimen itself, 3107 takes into account concern of both physicians and RRP patients. It can be administered in the physician's office without an ultra cold chain requirement. The device is simple to use and importantly, there's no requirement for surgeries to maintain minimal residual disease during the treatment window. This is a key area of differentiation from Precigen's gorilla adenoviral based therapy, which, as Mike noted, requires scoping and surgery during the treatment window to maintain minimal residual disease. Precigen's data publication indicates that these surgeries are required to mitigate the effect of the immunosuppressive papilloma microenvironment to maximize the chance of clinical benefit from the product. We believe this key difference makes 3107 a more patient-centric approach to treating RRP. I will also mention that the recently published RRP foundation position statement on the management of adults with RRP now recommends immunotherapy as first-line treatment for RRP and notes that 3107 if approved, would also be included as a first-line treatment option. I would also like to share just a few updates on our ongoing commercial launch preparations. Over the past year, we've executed critical market research, which informed strategic choices on launch preparations for 3107. We completed targeting segmentation of product positioning work and developed our pricing strategy. On the operational front, we've selected key commercial partners, including our third-party logistics provider, specialty distributor, specialty pharmacy, patient services hub and our agency of record. We are also finalizing our go-to-market model and planning the build-out of our commercial organization. I look forward to providing further updates on our progress next quarter. I'll now turn it back over to Jacqui for a pipeline update.

Thanks, Steve. While we remain steadfastly focused on INO-3107, in the past few quarters, we've also provided some important updates on how we're continuing to advance our DNA medicine platform. That includes promising Phase I proof-of-concept dMAb data published in Nature Medicine in October of last year, which demonstrated the technology's ability to durably and tolerably produce monoclonal antibodies, a complex protein within the human body for up to 72 weeks without generating antidrug antibodies. Additional data presented this year has now demonstrated consistent production of dMAbs out to 96 weeks. Our DPROT technology builds on this research, aiming to enable additional types of complex proteins being made within the body. Preclinical work evaluating the potential to expand into in vivo production of other types of therapeutic proteins, which presented at the World Federation of Hemophilia Global Forum last November, including our first data on Factor VIII production. We see great potential for this DPROT technology to treat multiple diseases and are actively seeking partnerships to advance additional rare disease targets into clinical evaluation. We also announced an exciting opportunity to build on our research in glioblastoma, or GBM, the most common and deadly brain cancer, through an innovative Phase II adaptive platform trial sponsored by the Dana-Farber Cancer Institute. In this trial, we will partner with Akeso to evaluate INO-5412 in combination with cadonilimab, their first-in-class PD-1, CTLA-4 bispecific antibody checkpoint inhibitor. The trial is planned to initiate in the second half of this year. INO-5412 is composed of INO-5401, which encodes for 3 tumor-associated antigens. And then INO-9012, which encodes for IL-12 and immune stimulants. When combined with a checkpoint blockade, this targeted DNA immunotherapy has the potential to overcome the limitations for immune checkpoint therapy alone by stimulating a T cell-based immune response against the tumor antigen, and driving T cell infiltration into the GBM tumor micro environment. Combining 5412 with Akeso's novel checkpoint modality represents an important evolution of our research in GBM, building on our previous data showing the potential to improve patient outcomes and highlights our ongoing commitment to advancing innovative treatments for rare diseases with significant unmet need. We are looking forward to collaborating with these 2 trailblazing partners and leveraging a unique opportunity to efficiently advance another promising late-stage candidate. Now I'll turn it over to our CFO, Peter Kies, to give financial update. Peter?

Thanks, Jacqui. Today, I'd like to provide an overview of Inovio's financial results for the fourth quarter and full year of 2025. As Jacqui noted, our primary goal is to advance INO-3107 towards approval, and we remain focused on directing resources and extending our cash runway towards a potential launch date in 2026. With the October PDUFA date in mind, we have further prioritized programs and resources, including recently reducing head count by approximately 15% and have focused on continuing to reduce spending to extend our cash runway. We now estimate our cash runway to take us into fourth quarter 2026. This projection includes an operational net cash burn estimate of approximately $22 million for the first quarter of 2026. Historically, our first quarter operational net cash burn runs higher than other quarters. These cash runway projections do not include any further capital raising activities that we may undertake. We finished the fourth quarter of 2025 with $58.5 million in cash, cash equivalents and short-term investments compared to $94.1 million as of December 31, 2024. Turning to our results for 2025. Our total operating expenses dropped from $20.5 million in the fourth quarter of 2024 to $17.5 million in the fourth quarter of 2025. Our full year operating -- operational expenses decreased 23% from $112.6 million in 2024 to $86.9 million in 2025. Inovio reported a net income for the fourth quarter of 2025 of $3.8 million or $0.06 per share and a dilutive net loss per share of $0.26. Our total net loss for the full year of 2025 was $84.9 million or $1.81 per share basic and dilutive. The net income for the fourth quarter 2025 was primarily driven by $21.2 million noncash gain on fair value adjustment related to our warrant liability as the fair value of the warrants fluctuates with our share price and other market inputs, the adjustment can result in significant variability in our reported net income or loss. As a reminder, you can find our full financial statements in this afternoon's press release as well as in our annual report Form 10-K filed with the SEC today. And with that, I'll turn it back over to Jacqui.

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

[Operator Instructions] And we have our first question from Ted Tenthoff with Piper Sandler.

Great. I wanted to first start just with respect to the conversations with the FDA upcoming regarding accelerated approval. Are there any additional data that you would need to submit? Or what other factors will go into that conversation for potentially transitioning the review to accelerate our approval?

Thanks, Ted. Great question. So there's no new clinical data. However, we have already submitted new documentation to the FDA in the form of an assessment aid, which we submitted in February. So we are now waiting for the FDA to get back to us regarding the date of the meeting. Mike, anything you want to add to that?

Yes. The only thing I'd add, Ted, is we utilize that document to sort of reiterate what we put in our original BLA submission and really expand on our rationale for accelerated approval review. So we're -- as I mentioned, we're looking forward to having those discussions with the agency.

We have our next question from Jay Olson with Oppenheimer.

Thanks for providing this update and taking our questions. We had a couple of questions. I guess maybe to start with, if you do eventually gain alignment with the FDA on a priority review, how would a 6-month priority review timeline impacts your ability to launch? And any launch preparations that you have underway. If you could just talk about that, that would be great. And then we have 1 follow-up, please.

Thanks, Jay. Nice to hear from you. So our focus at the moment is really on ensuring we have align with FDA for review under the accelerated program. We're not really focused on priority review at this stage. However, having said that, we are well advanced in our commercial preparations. And I'll ask Steve to make any comments here.

Yes. So as I mentioned in the prepared remarks, I mean, we've done a lot of market research with physicians, with patients, with payers. So we feel like we know the market opportunity quite well. We've built kind of our strategies around that. We've got our commercial partners kind of onboard or selected. And we will be prepared to get out of the gate really, really quickly, should we get approved. So I think we're doing everything that we need to, to be prepared and to move very quickly once the FDA makes a decision.

Okay. Great. And then if we could follow up on the publication in Nature Communications and The Laryngoscope. Can you just talk about any feedback that you got from KOLs and patients and how you might anticipate that feedback to translate into the uptake trajectory upon approval?

Yes. Great question, Jay. So as we mentioned on the call, we do believe that we have the preferred product profile in this space, and that's based across efficacy, tolerability in a very patient-centric treatment regimen. And when we have conducted research and with research conducted by third-party providers, both patients and physicians really appreciated and preferred the product profile for 3107. And what was really interesting to them was the fact that the majority of patients see a significant reduction in the numbers of surgeries. So 72% of patients see a 50% to 100% reduction in the first year following treatments, and that improves up to 86% in the second year with 50% of patients in the second year, requiring no surgeries at all. So a very strong efficacy profile. With regards to tolerability, the fact that we don't require these minimal residual disease surgeries during the treatment window is very well received. And for the competitor product, over 70% of the patients required surgery during their treatment window, requiring one or more surgeries during that treatment window. Actually -- sorry, that number was actually 83%, and it was 72% of their complete responders. So as you can see, the competitive product -- patients receiving competitive products in their trial actually required a lot of surgery during the dosing [ period ]. And the fact that INO-3107 doesn't require these surgeries maintain minimal residual disease is very attractive. And then as I think Steve mentioned, it's our ability to administer 3107 in the doctor's office, and the simple patient-centric treatment regimen, again, is very attractive to patients. Steve, anything else you want to add to that?

No, I think you covered it. I mean the research has shown really repeatedly a lot of evidence that we have the potential to be the preferred product in this space.

We have our next question from Sudan Loganathan with Stephens.

This is Kesav on for Sudan, and congrats on wrapping up the quarter. Just a quick one. So as you engage with the third-party logistics and commercial partners ahead of launch, are you specifically using those partners to incorporate learnings from the PAPZIMEOS rollout to inform your distribution strategy, site activation plannings, reimbursement approach and overall launch execution for 3107?

Sure. So yes, I mean, obviously, we would -- we're watching carefully what our competitors doing and learning from that. I don't know that they're necessarily the same commercial partners that Precigen is using but they have very deep broad experience in the rare disease space. So we're learning from that as well. So I would say the more general rare disease experience, but also Precigen's experience as well to do everything that we can -- to ensure that we're kind of very well prepared from a launch standpoint.

And if I can add, there were some key differences for 3107 to PAPZIMEOS. We don't require any ultra-cold chain also -- so we don't have those logistical issues setting up an ultra-cold chain. And also as we don't require these minimal residual disease surgeries during the treatment window, physicians don't have to plan for scoping and possibly doing surgery as well, which obviously makes the treatment regimen very attractive to physicians and to patients.

Our next question is from Roger Song with Jefferies.

This is Nabeel on for Roger. I had a question on the Akeso partnership. If you could just kind of walk us through that biological rationale of the dual PD-1, CTLA-4 blockade. How does that sort of add on top of the T cell priming that you've shown before with 5412 and GBM?

Yes, great question. So in the previous study, we combined 5401 plus IL-12 plus a PD-1 inhibitor from Regeneron called Libtayo. And what we saw in that study was encouraging data where we saw beneficial patient outcomes linked to the immune responses against the antigens that were encoded within 5401. So by partnering with Akeso in this innovative trial, what we're hoping is that the CTL4 element in addition to the PD-1 inhibition by providing an additional pathway for checkpoint inhibition will allow those immune responses against the tumor-associated antigens to provide additional benefit. So we're excited to be partnering with Akeso and excited to get the study underway. Mike, anything else you would like to add?

The only point, I mean it's well established that there is significant synergism between CTLA-4 and PD-1. So as Jacqui said, we think it will be a very nice combination to 5412.

Yes. That's exciting. A follow-up on that. I think inside, historically, you guys emphasized the O6-methylguanine methyltransferase the unmethylated group. Any idea, this is like early, but in terms of subgroups, like does the methylation status influence any expectations for like the immunotherapy responsiveness?

Yes. So it is a prior trial. We saw benefits in both methylated and unmethylated groups. So we were very encouraged by that data. Sorry, Mike, you wanted to say something?

I was going to say exactly the same. But the INSIGhT trial is actually in the unmethylated population. So while it's very sad for the patients that will lead to a quicker readout as they have a poorer prognosis.

We have our next question from Yi Chan with H.C. Wainwright.

This is [ Katie ] on for Yi. Taking a look at your pipeline, if 3107 is approved, what are your plans to move forward with 3112? Are you guys planning to reinvest internally or seek partnership for that type of program?

Yes. Great question. So for those of you who are not familiar, 3112 is our program in HPV-16 and HPV-18 positive head and neck cancer, oropharyngeal squamous cell carcinoma. And there, we announced a partnership with Coherus for their PD-1 inhibitor, Loqtorzi, which is approved in nasopharyngeal carcinoma. We're looking to start a Phase III trial. However, at the moment, the vast majority of our resources are going towards moving 3107 forward. So should -- should 3107 be approved later on this year and we have sufficient financial resources available, then we'll be looking to move forward with the other candidates in our pipeline. But we're very excited by our later stage candidates, which are predominantly focused on T cell mechanisms. So 3107, 5401, 3112, are all focused on driving T cell responses, either against viral antigens or against cancer antigens. And then we also have our earlier stage pipeline around our DPROT and our dMAb candidates, where we're looking to move those candidates into the clinic through partnerships. So partnerships are going to be very important to us in terms of how we see our pipeline developing going forward.

Thank you. We have no further questions. I will now turn the call over to Jacqui Shea for closing remarks.

Thank you. As we've outlined here today, our strategic focus for the months ahead is clear, advancing the BLA review for 3107 and optimizing our resources to extend our cash runway towards our October 30 PDUFA date. At the same time, we'll continue driving progress across our pipeline where possible, leveraging partnership opportunities and the potential of our platform in GBM, hemophilia and other rare diseases. As I close today, I'd like to reiterate our belief that 3107 can address the unmet needs of RRP patients. Patients who have faced the risks and burdens of their disease were far too long. We're moving forward committed to making sure that every patient can find relief from repeated surgery that they deserve. Thank you for your attention, and good evening, everyone.

And thank you, ladies and gentlemen. This concludes our conference call. We thank you for your participation. You may now disconnect.