Inovio Pharmaceuticals, Inc.

Good afternoon, ladies and gentlemen, and welcome to the Inovio First Quarter 2025 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. If at any time during this call you require immediate assistance, please press star zero for the operator. This call is being recorded today, Tuesday, May 13, 2025. I would now like to turn the conference over to Jenny Wilson, Director of Communications. Jenny, please go ahead.

Good afternoon, and thank you for joining the Inovio First Quarter 2025 Financial Results Conference Call. Joining me today on today's call are Dr. Jackie Shea, President and Chief Executive Officer, Dr. Mike Sumner, Chief Medical Officer, Peter Keyes, Chief Financial Officer, and Steve Egge, Chief Commercial Officer. Today's call will review our corporate and financial information for the quarter ended March 31, 2025, as well as provide a general business update. Following prepared remarks, we will conduct a question and answer session. 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, 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. Jackie Shea.

Good afternoon, and thank you to everyone for joining today's call. First of all, I am very pleased to say that we remain on track to submit our BLA for INO3107, our lead candidate for treatment of recurrent respiratory papillomatosis, or RRP. As previously stated, our goal is to begin rolling submission in mid-2025, complete the submission in the second half, and receive file acceptance by the end of this year. This would allow for a PDUFA date in mid-2026 if we receive priority review. Our primary focus continues to be the submission of our BLA for 3107. We reported in March that we had resolved the manufacturing issue involving the single-use array component of this Electra device, and we have now moved on to the next step, initiating the device design verification testing, known as DB testing. required for our IND update and BLA submissions. We've also been pursuing targeted opportunities to highlight key data from our completed Phase 1-2 trial. We were delighted to announce the publication of clinical and immunology data from that trial in Nature Communications in February. We also look forward to the publication of the previously announced data on the longer-term clinical effect of 3107. which has been submitted to a peer-reviewed journal. In addition, we've been very active at scientific conferences this spring, which has been integral to our strategic outreach to healthcare providers and key opinion leaders. Mike will provide an update on that shortly. On the commercial readiness front, ongoing market research with physicians, patients, and payers continues to support our belief that 3107 has the potential to be the preferred product for patients and physicians if approved. Steve will provide a brief overview of both market opportunity and insights from our market research with healthcare providers later in the call. And finally, a highlight from our earlier stage pipeline this quarter was the announcement of promising interim results from an ongoing phase one proof of concept trial evaluating DNA encoded monoclonal antibodies or DMAPs. We're excited about the potential of this next generation technology and what it could mean for the future of our DNA medicines pipeline. With that, I'll turn it over to Mike for a brief update on our progress with 3107 and some highlights from our recent presentations. Mike? Thanks, Jackie.

As Jackie noted, we are making steady progress towards our BLA submission goal for INO3107. The manufacturing issue involving the single-use array component of the device has been resolved, and we have begun manufacturing the updated commercial-grade arrays and initiated DV testing, which is a significant component of the device-related BLA modules. As a reminder, we have completed drafting all the non-device modules, including non-clinical and CMC modules, And we'll request to begin the submission of our BLA under the FDA's rolling submission process in mid 2025. In addition, we remain on track to launch our confirmatory trial, targeting more than 20 sites at major US medical centers. While that work is underway, we've leveraged several important opportunities to engage with the RRP community. sharing why we believe 3107 could be the preferred product for patients and doctors who are eager for an alternative to surgery. 3107 offers the potential for a majority of patients to see significant clinical benefit that improves over time, a favorable safety profile, and a patient-centric treatment regimen. This spring, we have presented key clinical and safety data at multiple scientific conferences. including the inaugural National HPV Conference, the first scientific conference in the U.S. to focus solely on HPV research and related diseases. It was an excellent opportunity to connect with experts from across sectors and to broaden awareness of both RRP and the potential benefit of INO3107. This week, Inovio will also be presenting a year two and three durability data at the combined otolaryngology spring meeting, otherwise known as COSM. This is the largest US national meeting for otolaryngologists, the specialist physicians who treat the majority of RRP patients. At these conferences, we've been able to paint a compelling picture of the potential impact of 3107 for the RRP community, for the patients, physicians, and caregivers who know that every single surgery comes with both significant risks and cost. As a reminder, we completed a phase 1-2 open-label trial of ino3107 called RRP001 in patients who required at least two surgeries in the previous year for the removal of HPV6 and HPV11-related papillomas. Every surgery performed after the initial dose was counted against the efficacy endpoint in our trial. where we followed the patients for 12 months. We also conducted a retrospective trial called RRP002, where we collected data on 28 of the original 32 patients to assess the longer-term treatment effect with a medium follow-up of 2.8 years. The key takeaway from these two studies is clear. We saw a statistically significant reduction in surgeries in the first 12 months following treatment. And that clinical benefit continued to improve beyond the initial one year period into the year two and three timeframe. More specifically, in the first year, 72% of patients saw a 50 to 100% reduction in the number of surgeries after starting treatment with 3107. With no additional dosing, this number increased to 86% in the second year. with half of the patients requiring no surgeries at all. Moving on to next steps, we are focused on completing the DV testing and finalizing the device-related aspects of our BLA. As a reminder, this testing is required for both our BLA submission and to update the IND before we can dose patients in our confirmatory trial. Our timeline for the BLA remains the same. We plan to request rolling submission and begin submitting our modules in mid-2025 and complete the full submission in the second half of the year. Our goal is to have FDA acceptance of our complete BLA filing by year end. And if we receive priority review, that could allow for a PDUFA date in mid-2026. After that, we plan to finalize our longer-term treatment strategy. with the goal of maintaining or even improving upon the clinical benefits seen to date and submit a proposed protocol to the FDA to support a supplemental BLA in the future. The ability to maintain or increase the immune response over time by continuing treatment is a key feature of our DNA medicines platform and has been demonstrated in our previous work in other HPV related indications. And finally, as we noted last quarter, deployment of our medical science liaison team is planned for this quarter, and I look forward to providing an update at our next quarterly report. I will now turn it over to our Chief Commercial Officer, Steve Ege, for some insights on the market opportunity for 3107. Steve? Thanks, Mike.

I'd like to spend a few minutes on the significant market opportunity we see for 3107 and why we believe that 3107 could be the product of choice for patients and providers. I'll start by describing the market opportunity. RRP is a rare HPV-related disease that affects around 14,000 people in the U.S. Because HPV vaccination rates are plateauing and because the majority of the adult population remain unvaccinated, risk of RRP remains. HPV experts believe the HPV vaccine is unlikely to have a significant impact on RRP prevalence in adults in the near term or for at least a generation. This disease is characterized by persistent wart-like growths called papilloma in the respiratory tract. There are currently no regulatory-approved therapeutic options available, and the current standard of care is surgery, often multiple surgeries a year. These surgeries have the potential to cause irreversible harm to the vocal cords and surgery does not address the underlying disease so the papillomas can grow back repeatedly. Patients and doctors have expressed time and again the urgent need for a non-surgical treatment option that addresses the underlying cause of the disease. And this is where we see the potential for 3107. In our trial, 3107 provided significant clinical benefit, was well tolerated, and is delivered via a simple patient-centric treatment regimen. After reviewing our data during market research, many laryngologists commented that about 8 out of 10 patients achieved a 50 to 100% reduction in surgeries, meaning the vast majority of patients saw significant benefit from treatment. And this is the data that they found most compelling. and that they believe will be most meaningful to patients. Treatment with 3107 was also well tolerated with the most common adverse events being transient injection site pain and fatigue, and there were no discontinuations. The simplicity of our treatment regimen is also key. Most notably, 3107 does not require scoping and surgeries during the window as part of the treatment regimen, which is vitally important when every single surgery comes with real risk and costs to patients. 3107 can also be administered in the physician's office and does not require a referral to an infusion center, which leaves the physician in control. These and other market insights gathered to date will be critical as we continue to advance our commercial planning. We're currently refining our go-to-market model and planning a further build-out of the commercial organization, and I look forward to providing more updates on our progress next quarter. With that, I'll turn it back to Jackie.

Thanks, Steve. As I mentioned earlier, we're also making important progress with the next generation of DNA medicine with our DNA-encoded monoclonal antibody, or DMAP, technology. This technology leverages the strengths of our DNA medicine platform to create precisely designed DNA plasmids that encode for specific monoclonal antibodies. These plasmids can then be delivered directly into muscle cells in the arm using our Selectra delivery system. The DMAPs are produced within the muscle cells and then secreted into the blood where they circulate within the body. This contrasts with conventional monoclonal antibodies which are manufactured in in vitro systems and then need to be administered through regular infusions or injections. We're researching the potential of this technology in several disease targets and recently announced interim clinical data from an ongoing phase one proof of concept trial evaluating DMAPs for COVID-19. Led by the Wistar Institute in collaboration with AstraZeneca, the University of Pennsylvania, and Inovio, and funded by DARPA and JPO, this trial provided the first clinical proof of concept that DMAPs can be durably and simultaneously produced inside the human body. The data showed long-lasting in vivo antibody production across 72 weeks. No anti-drug antibodies or immune rejection of the DMAPs. And the treatment was well tolerated with no serious adverse events related to treatment. Of note, we saw that the express DMAPs successfully banned the SARS-CoV-2 spike protein receptor binding domain, confirming functional activity. To be clear, this was a proof-of-concept study of our technology, and Novio does not have plans to develop these DMAPs for COVID-19 going forward. Part of this data will be presented at ASG CT this week by our partners at the Wistar Institute, and a manuscript has been submitted to a leading peer-reviewed journal and is currently available in preprint on Research Square. We believe this technology has breakthrough potential and could overcome many of the challenges seen with traditional monoclonal antibody production. Offering rapid manufacturing, low cost of production, temperature-stable storage and distribution, and the ability to redose, DMAP technology could help expand use, reduce cost, and enable access in low-resource settings. And importantly, our DNA-based approach has demonstrated sustained antibody production without generating anti-drug antibodies, making it a potentially promising long-term solution for conditions requiring continuous therapy. We're excited about the potentially broad application we see for this technology, including the potential to leverage the sustained in vivo protein production we have observed to produce other kinds of proteins beyond monoclonal antibodies. For instance, to enable protein replacement therapies and as a potential alternative to gene therapy for some indications. I'll now hand over to our CFO, Peter Keyes, for a brief financial update. Peter?

Thanks, Jackie. Today, I'd like to provide an overview of Anobio's financial results for the first quarter 2025. As Jackie mentioned, we're focusing resources on advancing our lead candidate, 3107, and our other strategic priorities, And I'm pleased to report that we've been able to support significant progress towards those goals while continuing to reduce costs. As you can see here, we've been able to significantly reduce our operating expenses over the past year. This quarter's operating expenses dropped from $31.5 million in the first quarter of 2024 to $25.1 million in the first quarter of 2025. a 20% decrease. Anovio's net loss for the first quarter of 2025 was $19.7 million, or $0.51 per share of basic and dilutive, compared to a net loss of $30.5 million, or $1.31 per share of basic and dilutive, for the first quarter of 2024. We finished the first quarter of 2025 with $68.4 million in cash, cash equivalents, and short-term investments, compared to $94.1 million as of December 31, 2024. We estimate our cash runway to take us into the first quarter of 2026. This projection includes an operational net cash burn estimate of approximately $22 million for the second quarter of 2025. These cash runway projections do not include any further capital raise activities that we may undertake. As a reminder, you can find our full financial statements in this afternoon's press release, as well as in our quarterly report, Form 10-Q, filed with the SEC today. And with that, I'll turn it back over to Jackie.

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

Operator?

Thank you. Ladies and gentlemen, we will now begin the question and answer session. Should you have a question, please press the star followed by the one on your touch-tone phone. You will hear a prompt that your hand has been raised. Should you wish to decline from the polling process, please press the star followed by the number two. If you are using a speakerphone, Please lift the handset before pressing any keys.

One moment, please, for your first question.

Your first question comes from the line of Roy Buchanan from Citizens. Please go ahead.

Hey, thanks for taking the questions. I guess to start, maybe, can you just give any additional detail on the COSM program? presentation coming up in a few days. Are you going to have any data beyond year three, and what else are you going to present other than surgery counts?

Hi, Roy. Nice to hear from you. Mike, do you want to give some further background on our COSM presentation?

Yeah, absolutely. So we'll obviously be focusing on the surgery counts, as obviously every surgery matters to these patients because of the risk and the cost. But we will be able to show a little bit more color around that. Also, as part of having an oral presentation at COSM, you also get to submit the data to laryngoscope. So we will hopefully be having that peer-reviewed publication available soon also, which will again provide additional color.

Yeah, and I think the real importance of COSM is this is really the primary meeting for otolaryngologists. who are the primary treating physicians for RLP. So it really is a good opportunity to get our data in front of the physicians who really matter for RLP patients.

Okay, great. And then a follow-up. Can you remind me how many MSLs you plan to onboard? And I had a question about epidemiology. I mean, as we know, the 14,000 number is a bit older. You guys, and Presagen is saying 27,000, although I'm not sure how they're backing that up. Are you coming up with your own number, or how do you plan to think about the market, and when might we see an updated number if you are? Thanks.

Yeah, both great questions. So maybe we'll take the epi question first of all. So yep, the 14,000 days of active cases here in the U.S. is relatively old data. It's the most commonly cited data by most experts in the field. And we have been conducting our own research to try and get a better handle on that number. And our own research suggests, in common with many rare diseases, that that might be an underestimate. Steve, do you want to add any other comments to that?

Yeah, the only other thing I would add is, and this is common in rare disease, for RRP, there's no diagnostic code, right? So there's no source to go to get kind of a count of the number of patients. So we have done some research and continue to do research looking at procedure codes that are used to conduct RRP procedures. Even that is not particularly straightforward. But based on what we see, we do think the 14,000 is an underrepresentation, but we're continuing to look at this through research. And as we go forward, maybe able to share more. But now, you know, we prefer to just be conservative and quote the 14,000. But again, we do think it's an underrepresentation.

And then that, of course, is the prevalent pool. And on top of that, there are new cases arising every year. And the figures there are about 1.8 per 100,000 new or instant cases a year. So actually, this is, you know, for a rare disease, there is actually a pretty significant pool of patients that need to be addressed. In terms of the MSLs, Mike, do you want to?

I mean, we haven't specifically guided yet as to the size of the MSL team. But, you know, as you've heard Steve mention before, I mean, the actual number of physicians treating RRP is not that large. And so, you know, as we are considering the number of MSLs, it's really about what we think that sort of key opinion leader base will look like. And also considering just the sort of geography of where we can, where we'll have those interactions and to optimize that.

Okay, thank you.

Thank you. Your next question comes from the line of Jay Olson from Oppenheimer. Please go ahead.

Hey, congrats on the progress and thanks for taking the questions. Maybe to start with, as you look ahead to a potential approval for 3107, do you expect to have a surgery sparing claim in the label and how important is the surgery sparing benefit for differentiation from your competitors?

Yeah, that's a great question, Mike. I mean, it's an interesting terminology. I mean, ultimately, I mean, in our discussions with the FDA, I mean, they recognize the clinical benefit is that reduction in surgeries. And so, and obviously, as you look at our phase 1, 2 data, we see a statistically significant reduction in those number of surgeries. How the FDA will actually sort of approach that terminology, I think it is too early to predict, but I think it will lead, you know, all paths lead to a reduction in surgeries.

Okay, great. Thank you. And then since you provided the update on your rolling submission of a BLA, is there any update on your registrational strategy in other geographies outside of the U.S.? ?

Yeah, so just as a reminder, our confirmatory trial is going to be in patients who've had two or more surgeries in the prior year. It's also going to be a placebo-controlled trial, two-to-one randomization. And in discussions with European regulators and with the UK regulators, they've been very clear that they expect to see placebo-controlled data for approval. So as Mike mentioned earlier on in the call, After we've started our confirmatory trial and after our BLA is in, the next thing we're really going to be focusing on is getting in a protocol for continued treatment. That's our next immediate priority. But certainly we've had some good discussions with European regulators and we think we're well aligned with them in terms of the design of any trials required there.

Okay, great. Thank you. And then for your DMAP platform, we understand that you use COVID-19 as a proof of concept. What are you thinking of in terms of your initial indication for the DMAP technology?

Yep. So outside of those indications that have been disclosed through publications, we haven't disclosed the indications we're currently working on. But as you can imagine, with such a broad and versatile technology, we can apply this to monoclonal antibodies. We can also apply this to proteins that are missing or defective in certain indications, such as enzyme replacement therapies. So we'll be providing more details when we have additional data to share there.

Okay, great. We'll look forward to that. Thanks again for taking the questions.

Thank you. Thank you. Your next question comes from Sudan Loganathan from Stevens. Please go ahead.

Hi, everyone. I appreciate the update today and congrats on the continued progress, you know, toward filing for INO 3107. My question, you know, my first question is regarding the priority review for 3107. Could receiving priority review status be in any jeopardy with the potential of another RRP treatment on the market this August or September potentially with, you know, a competitor's therapeutic? or is there anything else outstanding that, you know, is the final steps to actually making sure that the filing is completed and for priority review status?

Yeah. Thanks, Sudan. I mean, from when you look at the sort of guidelines around accelerated approval, I mean, it talks to obviously both the clinical benefit in, you know, most often a rare disease for RRP But it also talks to the difference of the product we're bringing to market. I think we've always felt that based on some of the precision data with potentially their efficacy could be impacted by neutralizing antibodies. or by the papilloma microenvironment, neither of which impact INO3107. We've always felt there is a population that can only be uniquely treated with 3107. So I don't think, you know, if we have to have that discussion with the agency, I think we have a very solid rationale of why 3107 should still be brought to market under the accelerated approval pathway.

Great. Thank you. And my second question really quick is, you know, since your filing is expected to be completed by the year end of 2025, is there any plans to add any more data, you know, to the actual filing or is it already all pencils down when it comes to adding to the data package or the filing package and just now jumping through the hoops of actually getting it submitted?

Yeah, so I mean, obviously one of the reasons we went ahead and performed RRP002 was to strengthen our overall clinical and safety package. But as I mentioned earlier on the call, that's all now integrated. So from a clinical perspective, you know, it really is pencils down and they're ready to go.

But it's an important point. We got breakthrough therapy designation and then our initial discussions with the FDA were just on that initial phase 1, 2, 12-month date. And since then, we've really strengthened the package with very detailed immunology characterization that was published in February in Nature Communications. And then what we think is very exciting is year two and year three durability data where we saw that the clinical benefit that we saw in the first 12-month period continued on into the second 12 months and the third 12-month period and actually improved during the second 12-month period. So I think, you know, we now have a very compelling package to put in front of the FDA.

And that's an excellent point. I mean, as we've said on previous calls, we've actually got a three-year history of these patients. So we really can sort of compare like for like. And, you know, as we talked about on the call, we're seeing a very significant and impressive reduction in surgeries. And that only, I think, becomes more impressive when you look at these patient history. So all of that is now incorporated into our clinical modules.

Great.

I really appreciate all the added detail and looking forward to the, you know, the execution in the second half of this year.

Thank you. Thank you. Your next question comes from the line of Roger Song from Jefferies. Please go ahead.

Great. Thanks for taking our question and then for the update. So two questions from us. One is very interesting for the year two, three durability data from 3107. Given your initial approval, will be based on the current data. How should we think about the pricing as you continue to accumulate the durability data? Second question is related to the confirmatory study and then the commercialization. What's the current thinking about the overall cost for the next steps and then how you will considering partnership or your own to fund the next steps?

Thank you. Great. Thank you.

They're excellent questions. Steve, do you want to comment on our thoughts on pricing for the initial treatment regimen?

Yeah. So we've done quite a bit of research with payers. In fact, we've spoken with payers that represent about 70% of commercial lives in the U.S. We've gone through the data with them, you know, talked about kind of price ranges in the rare disease kind of space. You know, payers felt that that was appropriate given the product, given the benefits. And the analogy that we've shared, and we've mentioned this before, SpringWorks Therapeutics product, Oxivio for desmoid tumors, we think is a good analogy. That product is priced at $360,000 per year. And that's kind of the guidance that we've provided around pricing. And payers seem very open. They think that's appropriate. We haven't commented or kind of guided on kind of pricing in terms of or continued treatment over time or duration. We haven't kind of guided to that. We've really focused on that initial four doses.

In terms of funding, in the U.S., we plan to bring 3107 to market ourselves. In the U.S., we think with the relatively small number of positions that we'll need to reach, we'll be able to do that with a small and efficient field force. XUS, certainly we're very open to partnering to bring 3107 to market XUS.

Got it. Thank you.

Thank you. Your next question comes from the line of Yi Chen from HC Wainwright. Please go ahead.

Thank you for taking my question.

Does the current tariff policy or the most favorite pricing or sales from?

Yeah, and clearly this is a rapidly evolving situation, and I think we, like others, are waiting to see how this plays out. But what I would say at the moment is we're very much focused on our first approval in the U.S. That's where our focus is. So as a first U.S. launch without a product available in another market, that would be something that we wouldn't have to face in those initial launch years. But clearly, this is going to be very important for the entire sector, and we'll be paying close attention to this as it evolves.

Got it. Thank you. Thank you.

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

Hi, this is for Greg. Thanks for taking our question. We were wondering if you were planning on disclosing baseline characteristics for the patients in the confirmatory trial and how might HPV genotype affect these trial results based on the findings you disclosed in your Nature Communications paper? Thanks so much.

Yeah. Apologies. We couldn't hear the first part of your question. Could you repeat that?

We were wondering if you were planning on disclosing the baseline characteristics for the patients in the confirmatory trial related to HPV genotype.

I can't remember the details in there, but we've always talked about the HPV serotypes was actually very representative of what the normal RRP population is. So there were just over 60% were HPV 6, 30% were HPV 11, and then there were some patients who were co-infected. So exactly what you'd expect to see in the normal RRP population. I think that's in the paper somewhere, but it's been a while since I've read it.

So that was the split in our phase one, two trial, Mike. You know, in terms of the confirmatory trial, we're going to try and recruit a patient population that's very representative of the normal RRP patient population, which is, as Mike said, predominantly HPV6. skews male, and so we'll look to try and recruit the appropriate population. It's very similar to our phase 1, 2, which we do think it was representative.

Yeah, I mean, hopefully with, you know, the targeted 100 patients, you know, that will give us a greater chance to once again replicate what the actual RRP population is.

Thanks very much. Thank you.

There are no further questions at this time. I'd like to turn the call back to Jackie Shea for final closing comments. Thank you.

As I've outlined here today, we're making significant progress and remain focused on the catalysts ahead that will help us achieve our primary goal, submitting our BLA for 3107 and being prepared for a swift and efficient commercial launch, if approved. I'm really excited about how 3107 could change the treatment paradigm for RRP and for the patients who could benefit from it. We're moving forward knowing that each day and each surgery matters to patients and our mission.

Thank you for your attention and good evening, everyone.

Thank you. Ladies and gentlemen, this concludes your call for today. We thank you for participating and ask that you please disconnect your lines.