Hello, everyone. I'm Jay Olson, one of the biotech analysts at Oppenheimer, and it's a pleasure to welcome you to Oppenheimer's 35th Annual Healthcare Conference and our discussion with Inovio. It's a pleasure to introduce Jacqueline Shea, CEO and President. Thank you so much for joining us here today, Jacqueline. I'll turn it over to you.
Thank you so much, Jay. It's a pleasure to talk with everyone today about our DNA Medicines platform and pipeline, and the potentially transformational year that we have coming up with our planned submission of our first BLA later on this year. Before I start, I'd like to advise you that during this presentation, I'll be making some forward-looking statements, and I refer you to our most recent 10-K and 10-Q filings for further details. To start off with an overview of the company, we're a clinical stage biotech. We're focused on developing and commercializing DNA medicines to treat and protect people from HPV-related diseases, cancer, and infectious diseases. Our DNA Medicines platform technology enables the design and delivery of both therapeutics and vaccines that enable the patient's own body to produce disease-fighting tools. Our lead program is INO-3107 to treat recurrent respiratory papillomatosis, also known as RRP.
This is a rare disease of the respiratory tract caused by HPV types 6 and 11, and we've received breakthrough therapy designation and orphan drug designation from the FDA. We're looking to file and submit our BLA mid this year under FDA's accelerated approval program. Last year, we announced that we'd experienced a CMC issue with our device, and I'm pleased to say we're well on the path to resolving that device manufacturing issue. Following on behind 3107, we have a deep pipeline of other therapeutic and vaccine candidates providing multiple near and midterm catalysts. In terms of manufacturing, we've established commercial scale manufacturing for the DNA component of our product, our plasmids, at external contract manufacturers, and we do our device manufacturing in-house ourselves.
At the end of the third quarter last year, we had approximately $84 million in cash, no debt on the balance sheet, and we then completed a public offering of $30 million in December last year. How do our DNA medicines work? We start off by identifying target genes in, for instance, HPV and cancer, infectious diseases, or even protein replacement diseases. We then use our proprietary algorithms to optimize the sequence of those genes for expression within the body, and then we clone those optimized sequences into a circular molecule of DNA called a plasmid. We're then able to produce those plasmids at commercial scale using traditional biotechnology production methods, and then we use our proprietary delivery devices called Selectra to deliver those plasmids to either skin or muscle cells within the body.
Now, our Selectra device is a very important component of our technology because it really enhances and enables the cells to take up those DNA plasmids. Once those DNA plasmids are in the body, the host cell machinery then produces the proteins that are encoded by those DNA plasmids, and those in vivo produced proteins can then go on to either generate an immune response. In the case of HPV or cancer, what we're looking to see is a strong T cell response. In the case of infectious diseases, we're looking to see either binding and neutralizing antibodies plus T cells, or the proteins that are being produced in the body themselves can be the therapeutic agent, as in the case of monoclonal antibodies or potentially therapeutic proteins.
As you can see, our technology is all about driving this in vivo protein production of targeted proteins within the body. We're adopting a multi-pronged strategy to really unlock the promise of our DNA medicines platform and this very versatile technology. In the near term, it's all about getting 3107 to the market, and we're targeting mid 2025 for our BLA submission. As I mentioned, this is under FDA's accelerated approval pathway, and we plan to request rolling submission and priority review. If approved, 3107 could be the first DNA medicine available in the US, and we believe that the clinical and other data that we've generated to date really shows the potential for 3107 to be the preferred product by both patients and providers.
This is based on the very significant clinical benefit that we've demonstrated, including duration of that clinical benefit into years two and three post-dosing. It's a very well-tolerated therapy, and also we have a very simple treatment regimen that doesn't require any surgeries during the dosing window. Moving on to the candidates following on behind 3107, next up is 3112, where we're planning a phase three trial in combination with a PD-1 inhibitor. Here, this is also an HPV-related candidate, but this time we're going after high-risk HPV-related throat cancer. Following on behind 3112, we have other clinical candidates across a range of indications for HPV-related diseases, oncology, and infectious diseases. We have some earlier stage clinical technology. We're looking forward to reporting the first clinical data for our DMAB program this year.
We see this as a proof of concept generally for our ability to deliver monoclonal antibodies or potentially therapeutic proteins within the body. DNA launched nanoparticle vaccine technology, which is our next generation vaccine technology designed to drive higher antibody responses, and then some early stage work in cancer as well. Very importantly, our lead candidates all target significant unmet medical needs with strong commercial potential. For 3107, whilst RRP is a rare disease, it's not that rare. We estimate that there are about 14,000 active cases in the US, with a new incidence each year of about 1.8 per 100,000 of new cases. Repeated surgery is the current standard of care, and you know, it's really a very challenging prospect for those patients, as I'll go into more detail later. As I mentioned, it's a chronic disease caused by HPV 6 and 11.
For 3112, this is one of the most rapidly increasing cancers in developed countries. Currently, 20,000 new cases a year in the U.S., projected to go up to 30,000 new cases a year by the end of the decade. It's more common in men. This time, it's driven by high-risk HPV types, so HPV 16 and 18, and it recently surpassed cervical cancer as the most common HPV-related cancer in the US. For 5401, glioblastoma is the indication where that's the lead indication here. I'm sure most people are aware glioblastoma is one of the most common and deadly brain cancers. Very poor five-year survival rate, and unfortunately, treatment really hasn't improved much over the past decade. This gives you a quick overview of our pipeline. Today, I'm predominantly going to be focusing on our later stage candidates, 3107 and then 3112.
To do a bit of a deeper dive now onto 3107, we really see this as a potentially transformational therapy and alternative to surgery under FDA's accelerated approval pathway. What is RRP? RRP is a rare disease. It is characterized by small wart-like growths in the respiratory tract. You can see some pictures here of the papillomas in the larynx and the vocal cords. These papillomas can form anywhere in the respiratory tract, but they primarily affect the larynx and the vocal cords. These papillomas, as you can imagine, cause great difficulty speaking. They can even lead to complete voice loss, difficulty swallowing, shortness of breath, and choking episodes. In rare cases, RRP can spread to the lungs or become malignant and be fatal. What we believe underpins RRP is really an insufficient immune response.
Most people are able to clear HPV 6 and HPV 11 from their body. However, for some patients, their immune response isn't able to do this. RRP affects both adults and children. There are three kind of peaks of incidence around age seven, in the mid-30s, and then in the early 60s. There are about 14,000 active cases here in the US. Repeated surgery is the current standard of care, and the key is really in the name recurrent. These papillomas grow back time after time because the underlying infection with HPV still remains. It's very hard to cut a virus out with a scalpel. On average, RRP patients have four surgeries a year, and severe RRP may require hundreds of surgeries over a lifetime.
Surgery can irreversibly damage vocal cords, and by the time patients have had 10 surgeries or so, most patients have experienced irreparable damage to their vocal cords. This is really why every surgery matters to RRP patients, and this is really what's underpinned our development approach with 3107. What we're looking to do with 3107 is reduce the number of these very difficult surgeries that patients have to go through. Each surgery is painful. It requires voice rest afterwards, and it's very disruptive to the patient's life. There is this cumulative risk of permanent damage to the vocal cords and losing their voice. Here you can see an overview of our phase one to clinical trial that led to breakthrough therapy designation, and the FDA advised us the data from the phase one to was sufficient to file our BLA under the accelerated approval program.
INO-3107 targets the E6 and E7 oncogenes of HPV 6 and 11, and it's these oncogenes that are really driving the cellular proliferation that lead to these wart-like growths in the respiratory tract. We enrolled 32 patients in the phase one to. These patients had to have had at least two surgeries in the prior year. We administered four doses of INO-3107 over a nine-week time period, and then we followed those patients for a year, and we recorded every surgery after day zero because every surgery matters to patients. All patients in the study had either HPV 6 or 11 or a combination of those two types. In terms of the endpoints, our efficacy endpoint was a change in the number of surgical interventions from the year after treatment with INO-3107 compared to the year prior.
We also obviously looked, as a phase one to trial, we also looked at safety of 3107, and we also assessed symptoms. As this original phase one to trial was not designed for long-term follow-up, we subsequently conducted a retrospective study of patients in that trial and collected data in year across the whole of year two following treatment and in year three. We were able to consent 28 of the original 32 patients into this retrospective study. We lost four to follow-up. The median follow-up for the patients on this trial was 2.8 years. You can see we have almost three years' worth of data. We were really delighted by the data that we saw coming out of the phase one to trial. This waterfall plot shows you the data for the year one after treatment.
What we were very pleased to see, bearing in mind that every surgery matters to patients, is that over 81% experienced a reduction of at least one surgery compared to the prior year. When we take a more oncology-focused look at this and think about complete responders, these are patients who required no surgery, or partial responders who had at least a 50% reduction in surgery, we saw a very pleasing overall response rate of 72%, with 28% of those patients being complete responders and requiring no surgery. By far, the majority of patients here are seeing a reduction in surgery, and many of them, as measured by ORR, are seeing a very significant reduction in surgery. This data was published today in Nature Communications alongside some immunology data that I'll be talking about later on in the presentation.
As we move on to 002 and the retrospective study, what we saw was that the reduction in surgeries continued to improve after year one. In year two, we saw 50% of patients actually required no surgery in year two versus 28% in year one. We also saw an increase in terms of the partial responders, so those patients who required, who saw a 50% reduction compared to the year prior to treatment. We were very pleased to see this improvement between years one and year two. When you look at this in terms of number of surgeries, when we started out the trial in the year prior to treatment, the patients in this population had a mean number of surgeries of 4.1. In year one, this has gone down by more than half to 1.7 across the whole population.
In year three, it's further decreased again. We are very pleased to see this continued improvement over time. Moving on to the immunology, which really underpins the mechanism of action for INO-3107, what we saw in the characterization of the immune response of the patients in the study was that we were generating the right kind of immune responses, so cytotoxic T cells, antigen specific to the E6 and E7 oncogenes across all of the patients. We saw that these T cells really got where they needed to go. They traveled from the blood into the papilloma and the airway tissue. Once they were in the airway tissues, they create an antiviral immune response. It is this antiviral immune response that we believe is responsible for reducing or eliminating the need for surgery by eradicating virally infected cells.
Very importantly, immune responses in clinical responders were very different to those in non-responders. Also, when we looked at the papilloma microenvironment, other investigators have suggested that high viral load or cytokine levels or neutrophil infiltration can be barriers to immunotherapy and RRP. We did not see any factors in the papilloma microenvironment impacting the clinical benefit of INO-3107. We were very pleased to see that. What does this mean going forward? We see a core strength of our DNA Medicines platform among other T cell generating platforms, such as viral vectors, as the ability to redose repeatedly and continue to drive strong immune responses. Going back to looking at the mean surgeries per year across the population, as we saw, we saw a very good decrease between the year prior to treatment to year one, and then a further decrease into year two.
In year three, the improvement seems to be holding pretty steady. What we would like to be able to do is consider a redosing strategy that allows the potential for maintenance of that complete response or partial response, and even potentially further clinical improvement, and the potential for non-responders to get into response. We are very interested in evaluating potential redosing regimens. Next steps for 3107 is resolution of the device manufacturing issue, which was an issue, a very low level of breakage of a plastic component of the single-use array. It was a plastic molded component that was breaking at low level. We think we are well on track on resolving this issue, and we are due to complete our internal OQPQ sign-off of this fix by the end of February.
We'll then need to complete the required BLA testing on the entire device in conjunction with this new revised array component. In terms of regulatory next steps, we'll need to submit an amendment to our IND to initiate the confirmatory trial, which is going to be a placebo-controlled trial, again enrolling patients with two or more surgeries in the prior year. We plan to submit our BLA mid this year. We're going to request rolling submission and priority review. After that submission is in, we're going to be submitting a redosing study designed to the FDA. As I've explained to you, we see some real significant clinical benefit in terms of our efficacy and tolerability profile. I think it's important to mention we conducted this trial over eight different clinical sites.
We have strong immunology data that supports our mechanism of action, in addition to a very tolerable profile and a strong efficacy profile where the efficacy improved over from year one to year two and seemed to be maintained into year three. We think this translates to some real commercial advantages. INO-3107 demonstrated a similar rate of efficacy against both HPV 6 and HPV 11. HPV 11 causes about a third of RRP, tends to be more severe disease. Very important to have efficacy against HPV 11. Our DNA Medicines platform is able to be redosed to continue to stimulate the immune response. Unlike viral vectors, we do not need to worry about any pre-existing immunity within the population or generating immunity that would prevent redosing. INO-3107 is also a very simple treatment that can be delivered in the doctor's office.
We don't require any scoping or surgeries as part of the treatment regimen. It is a very tolerable regimen for patients. The administration via Selectra is very well tolerated by patients and was found to be very easy to use by healthcare providers. We've used our Selectra devices in thousands of patients across more than 20 countries and have a great deal of clinical experience with Selectra. DNA Medicines are very stable, so they can be stored in the fridge for up to three years. As I mentioned, we're going to be conducting a confirmatory trial, again aiming for patients who have had two or more surgeries in the prior year. We're going to conduct a placebo-controlled study because we believe, based on discussions with European and other regulators, this trial design will be more suitable for global registration.
I think also just to briefly touch on the market opportunity, whilst INO-3107 is a rare disease, there are still a substantial number of patients with about 14,000 active patients each year, plus the new incidence population coming in each year of about 1.8 per 100,000. We've also conducted, as a rare disease, we're also anticipating rare disease pricing. We've conducted research with payers who cover the majority of commercial lives here in the US. They've indicated that rare disease pricing is both appropriate and acceptable. As a rare disease as well, we believe that we'll need a relatively small commercial footprint to be able to really serve this market well. We're planning further build-out of the commercial organization in 2025 to be able to launch this product.
Moving on from 3107, I'd now like to touch on 3112, which is also an HPV-related candidate. This is where we're really building on our experience in HPV-related diseases. For 3112, what we're looking to do here is conduct a phase three combination trial of 3112 in combination with LOQTORZI, which is a proven anti-PD-1 inhibitor licensed for treatment of nasopharyngeal carcinoma here in the US. We're looking to conduct this phase three trial in local, regionally advanced, high-risk HPV 16 and 18 oropharyngeal squamous cell carcinoma patients, also known as throat cancer. To tell you a bit more about throat cancer, most throat cancer patients are diagnosed with local, regionally advanced disease. Current treatment is aimed with curative intent, multimodal, including surgery and chemoradiotherapy. Outcomes are generally pretty good. Three-year probability of progression-free survival is good, about 70-75% of patients.
However, there's this subset of patients, these high-risk patients, who pretty much at diagnosis the physicians know are going to reoccur, either based on high viral loads or number of prior pack years of smoking or the size and location of their nodal involvement. The physicians know these patients are going to reoccur. Unfortunately, when the disease does reoccur, the clinical outcomes are really pretty poor, even with the addition of immune checkpoint blockade therapies, so PD-1s, et cetera. For patients who do reoccur, survival is less than a year on average. We estimate currently that there are about 3,000-4,000 new patients each year that fall into this high-risk category. Really, all the physicians are able to do for these patients at the moment is watchful waiting. Our proposed phase three trial is really focusing on these high-risk patients.
We're planning to conduct the trial across both North America and Europe. We've previously discussed the trial design with FDA. We've most recently had some feedback from the European regulators on the trial design. Before I wrap up, I'd like to just briefly comment on some of our early stage programs. We're looking forward to reporting our first clinical data from our DMAB program. This is where we're producing monoclonals within the body, driven off of DNA plasmids. These monoclonals are produced in the muscle cells, assembled, and then secreted into the blood. We really see this as proof of concept for monoclonals, not just against infectious diseases, but monoclonals in general. We believe the technology can also be applied to protein replacement diseases. This is a collaboration with the Wistar Institute, AstraZeneca, the University of Pennsylvania, and has been funded by DARPA.
Exciting new platform data coming out this year on our DMAB programs. Finally, I'd like to leave you with the key catalysts coming up across our lead programs, 3107 and 3112, and the exciting new data around DMAB. We're very excited by what the year holds for Inovio in 2025. I'd like to thank you very much for your time and attention.
Thank you, Jackie. Really appreciate the update on all the impressive progress you're making. We do have a couple of minutes left for questions. I guess maybe one question is if you could just walk us through sort of the gating factors to getting your BLA submission for 3107. Especially, you've put together a lot of really impressive recent updates with your three-year durability data, the immunology data that you just published. Is that all going into your filing?
I guess, what are the next steps for submitting your BLA?
Yeah, that's a great question, Jay. Our original breakthrough therapy designation and FDA called us up and actually told us the data was good enough to submit under accelerated approval program was just on that phase one two data for just the first year. We will, of course, be submitting the year two and the year three as part of our BLA filing. In terms of next steps and also the very promising immunology data underpinning the mechanism of action that we recently published today. All of that's going to be part of our BLA package. In terms of next steps, we've completed all of the non-device modules of our BLA. We're really just focused now on wrapping up that testing on fixing the device issue.
Then we'll be ready to submit our amendment to our IND to start the confirmatory trial and then start submission of our BLA. That is really what we're focused on executing really well on over the next few months.
Great. We'll look forward to that. Maybe just one last question about the competitive landscape. Really appreciate your patient-centric approach to every surgery matters. I think that really is going to resonate with your target patient population. It is also a very strong competitive advantage. There is a competitor that I think submitted a BLA recently. Can you just talk about how you think the competitive landscape will shake out and what the key competitive advantages are for 3107?
Yeah, I think for 3107, it's really the very strong efficacy data that we presented.
Where our efficacy continues to, on clinical benefit, continues to improve into year two and into year three. We also have a very simple treatment regimen. We do not require any scoping or surgeries during the dosing window. We count every surgery after day zero because, as you say, every surgery matters to patients. We have a very simple treatment regimen. The treatments also are able to be given in the doctor's office. They are not going to have to go to another site potentially to receive therapy. We have a very favorable tolerability profile. We have very few systemic events, very few systemic adverse events, and the majority of our adverse events resolve very quickly.
I think, based on the efficacy profile that we see, the simplicity of the treatment regimen and the very favorable tolerability profile, we think 3107 is really well positioned to be the product of choice for both patients and physicians.
Excellent. Likewise, we're looking forward to your BLA submission. With that, we'll wrap things up. I want to thank you for a super informative and comprehensive presentation today. It's been great catching up with you and learning about all the impressive progress you're making on behalf of patients. Thank you so much, Jackie.
Thank you, Jay. Been a pleasure.