Great. Thank you, operator, for, again, always making this so seamless and easy for us all. We have now Jacqueline Shea, the President and CEO of Inovio, a company we've been covering for a while now, and we recently upgraded, on the back of some really compelling data they present in RRP and conversations they've had with regulators. This is a company that could have their first approved product, sometime, hopefully, next year. Jackie will give us a quick update for about 3 to 5 minutes, on the state affairs at Inovio, and then after that we'll jump into our fireside chat. With that, please, Jackie, take it away.
Hey, thank you very much, Hartaj, for having us. Delighted to be here today to tell you a bit about Inovio and the really fantastic progress we've made over the past 12 months or so. I'll start off by saying, over the past 12 months we've really made some great progress on 3107. T hat has also come off the back of some work that we've really been doing to reshape Inovio. So I became CEO in May 2022. Since then, what I've really been looking at is prioritizing our late stage pipeline. Making sure that we're really focusing our efforts on those late stage programs, that have, meet higher medical needs, have good commercial potential, and have, appropriate pathways to market. So focusing on those late stage, candidates.
I've also been looking at the structure of the organization, looking at our cash burn, and over the past year or so we've reduced down our OpEx spend by about 50% compared to last year. I think it's very important that we're really investing our resources where they're most needed. I've also been building up the team at Inovio. As you mentioned, we're close to filing our first BLA in the second half of this year, hopefully. And it's going to be really important to have the right team in place, a team with great depth of expertise and experience in taking innovative and rare disease products to market. So our focus as a team over the past year has really been on this. And then we've seen some really great progress on 3107, as you mentioned. FDA awarded us breakthrough designation.
Agreed that our completed phase 1/2 data was sufficient to file under the accelerated approval pathway. We had a really good meeting with the FDA just before Christmas to align on the key aspects of our BLA package. We announced early this year in January that we're going to be filing, targeting filing our BLA in the second half of this year. Clearly, a lot of focus and energy in the company is going into our program 3107. But as you mentioned, we also have a diversified pipeline. Inovio is a company that's really focused on developing and commercializing DNA medicines. Everything we do in Inovio is around our DNA medicines platform. We're developing DNA medicines across three main areas: HPV-related diseases, cancer, and infectious disease. Behind 3107, we have quite a diverse pipeline of some later stage assets.
These include 3112. We also put out some news at the beginning of the year about a partnership with Coherus and potentially moving that 3112 asset into a phase 3 study. Then we have some other later stage assets as well. 5401 in oncology, 4201 as an Ebola booster vaccine candidate, VGX-3100 in anal HSIL, that we're also moving towards later stage development. Then finally, we've got some exciting earlier stage technology that's just coming into the clinic. So these are our dMAb technology, where we're encoding monoclonals within our DNA plasmids. And that enables the body to produce monoclonals in vivo through in vivo protein production. And we're also have a next generation vaccine technology called DNA launch nanoparticle vaccines. And those candidates are just entering to the clinic as well.
So when I look at Inovio and our platform, I see these near-term catalysts for 3107 and 3112. A diverse pipeline coming on behind it, and then longer term, this this new transformational technology around the dMAbs and the dLNP technology.
Jackie, that that is fantastic, a really nice synopsis. You're right, I'd actually flaked a little bit, that you had started in May of 2022. It seems like you've been there much longer for all of the major changes that have happened. I personally, I believe that Joseph took the company, you know, a long ways, and you had to come back and kind of rejigger it and fine-tune it and, get a little bit more fit, from an OpEx perspective. Which is all you've done. Excuse me. You know, we've got, we'll talk about 3107 a little bit, then the pipeline. We've actually got quite a few questions online, we leave about 10, 15 minutes towards the end to go through these questions.
But maybe on 3107, the main thing is it seems like there's a really high unmet need in RRP, Jackie, and that, we spoke to a company that we don't cover, Precigen yesterday and the CEO there, and they've got a different approach. T hey're probably going after patients that are much later stage in terms of the number of surgeries they've had. But can you just talk a little bit about the market size there? I t seems that just from the preliminary indications, both from how what's the size of the patient population, which patients could you go after, assuming you get approval in 2025? T hen after that, maybe we might talk about some pricing comps that you think are, you know, the appropriate ones.
Yeah, they're all great questions, Hartaj. So let's start off with a little bit of background about recurrent respiratory papillomatosis, because it's a rare disease and not everybody's familiar with it. So RRP, the key is really in the recurrent. This is an HPV-related disease. So HPV 6 and 11 subtypes cause these benign wart-like growths in the vocal cords and in the throat. And with recurrent really tells you what's going on here. These, at the moment, the only standard of care is surgery. So these warts, these benign warts are removed by surgery, but they grow back and they grow back time after time after time. And the vocal cords are really delicate structures. I mean, the way they generate your voice is by vibrating thousands of times a second.
So you can see that having growths on those vocal cords really impacts your ability to speak. People's voice can get reduced down to a whisper. It can become really hoarse. So that's the major symptom. It's really those voice impacts. When these benign papillomas or wart-like growths get too big, they can also start occluding the airway. They can spread from the voice box into the throat, and also down into the lungs. And in very rare cases, unfortunately, RRP can progress to cancer. And under those circumstances, it's almost unique, almost always fatal. So really, really nasty disease, and surgery is really the only standard of care at the moment. Many of these patients can have hundreds of surgeries over their lifetime. So really devastating disease.
I think I think the other really important thing to bear in mind is the surgeries of themselves cause damage. So, you know, what we're hearing from the KOLs is, you know, after about maybe four or five surgeries, the surgeries themselves can start taking a toll on the vocal cords, start damaging the voice themselves. So that's, you know, really, really challenging. It's a rare disease, but it's not that rare. There are about 14,000 estimated active cases in the US, about 1.8 per 100,000 new cases a year. So in the adult population, that's just under 5,000 new cases a year. So rare, but not that rare.
And then just from that point of view, Jackie, I believe you've got almost a brand spanking new chief commercial officer, kind of like that very nice car you drive off the lot. H e's been doing a lot of work looking at the market. Could you give any thoughts there, any preliminary, ideas as to what is this, from a patient perspective, the accessible patient, what's the what this could look like, assuming approval next year?
Yeah, so Mark, so our Chief Commercial Officer is Mark Twyman, and he brings a great deal of expertise to Inovio from prior companies and being involved in multiple launches across rare disease as well as non-rare disease products. He's actually been with Inovio for quite a while. He predates my arrival at Inovio. So he really understands our technology well. And I think coming back to, I think one of your earlier questions around the patients and the patients that were involved in our phase 1-2 trial. So we enrolled patients from who had had from 2 surgeries in the prior year up to 8 surgeries in the prior year. So we were really spanning the whole spectrum of RRP disease.
The average number of surgeries, I think, has been estimated about 4 surgeries a year for people who have active RRP. So we were looking at people at the relatively mild end of the spectrum, as well as people who had more aggressive disease. And what we were able to show was we were able to show efficacy in terms of reduction of surgeries across that spectrum. And we were also able to show reduction in surgeries in patients who had both HPV-6 and HPV-11.
So in terms of what we're hearing from patients, what we're hearing from caregivers in terms of what's important to them is really this reduction in surgery. And in our phase 1/2 trial, we were able to show that 80% of participants in that trial demonstrated that reduction in surgery. With about 28% of patients having no surgeries whatsoever after day zero. So because we know surgeries are what matters to patients, we counted all surgeries from day zero, even during the nine-week initial dosing regimen.
Jackie, just in terms of, well, we met in San Francisco and you gave us an update there about a month ago, on your interactions with the FDA. Can you just walk us through what not the specifics of interaction with the FDA, but what was the feedback and then what should be the steps, step by step we should look forward to essentially over the next 6-9 months, until you potentially your BLA is complete?
Our discussions with the FDA before Christmas, we're really focused on making sure we had good alignment on all of the components that need to go into our BLA submission. And I think we're well aligned there. We also talked about the design of the confirmatory trial that we'll need to conduct before we file our BLA. So those were the main elements of our discussion. So what I think you can expect to see during 2024 for 3107 is in the second half of the year we'll be starting that confirmatory trial. We'll be submitting our BLA.
W e will also hopefully be publishing some of the immunology data relating to that completed phase 1/2 study at some point this year as well. So that's really what we have in store for 3107. And then, of course, you know, all of the commercialization activities, all of the other activities that you would be expecting to be going on in the background to prepare for launch.
Please, t ell your Chief Commercial Officer, I'm sorry, I referred to him as a brand spanking new car. He might not be a brand spanking new car. No, I'm not going to go there. W e'll look forward to more and more updates on the marketing side. I know previously you had mentioned that you would, you were thinking of like a rolling BLA, right? But this would be not a rolling BLA e ssentially, you would just file the BLA in the second half of the year. But do all of the activities ahead of time for that, correct?
Yeah, so we will be discussing with the FDA the potential for a rolling submission. We'll discuss with them the potential for priority review. But clearly you have to apply for those things. They're not a given. But we will certainly be taking advantage of any mechanisms to try and accelerate the potential launch of 3107.
Jackie, one last question here, which is that what's the status of the device that you're going to be using? Then n ext year, how would you use that? Would you be basically selling the device to hospitals and then just providing the drug, or how would that work?
Yeah, great question. So we're going to be using our CELLECTRA 5PSP device. This is a device that we previously used in two phase three studies for VGX-3100 in cervical dysplasia. It's also a device that has received CE marking in Europe. So in the US, INO-3107 is regulated as a combination product. So both the device and INO-3107 will be approved together. And as such, we'll be supplying them to potential healthcare providers, potential hospitals as a package. We haven't disclosed details of that yet. But very much, you know, thinking about this as a combination product. And making sure that we can really make the product available as rapidly as possible.
Jackie, what would be the cost of goods sold look like? Will the cost of goods sold essentially be the drug cost of goods sold, or will that also be include the device sales that are part of that? But that the device sale would just be a one-off, right, at least in the beginning.
Yeah, so we're looking at various different business models, Hartaj, to really optimize uptake of 3107. So when we have more detail to share about that, we'll be making small comments. But I think it's still a bit early at this far out from launch to be talking about some of the specifics around that.
That's fair. That's very fair. Great. Maybe then Jackie, before we get to the questions we're getting online, just maybe talk a little bit about the kind of the programs following 3107. And from the point of view, which are the key programs or key catalysts this year that we should look forward to?
Yeah, really important, Hartaj. So 3112, we're very excited about 3112. We announced our collaboration with Coherus earlier on this year. We're targeting HPV positive throat cancer. Coherus's PD-1 called LOQTORZI has recently been approved and has been launched for nasopharyngeal carcinomas who are a related indication in, by the FDA earlier on this year. So we think the combination of 3112 where we're really generating these antigen-specific T cells that are able to identify, HPV-infected, cells that are driving the cancer. In combination with a PD-1 with demonstrated efficacy in a related space, it's going to be, really exciting. So we think the combination of these antigen-positive T cells along with the anti-tumor immunity, from the PD-1 could really be exciting in this space.
T here's a t the moment these patients, many of them are on watchful waiting. There's not really a good treatment alternative for them. So we're very excited by the potential of what INO-3112 could do in this space. Also looking at some of the other candidates that we've got following on behind. So INO-5401, we've been wrapping up our phase 2 study in GBM. We're in discussions with our partner Regeneron about the next steps for that candidate. That candidate is also being evaluated in a BRCA-positive breast cancer study. That's an investigator-sponsored study, so independent from Inovio. And then we also have some other assets following on behind. So we have VGX-3100 in anal HSIL. We'll be in discussions with regulators about moving that candidate on to next steps.
It's currently in a phase 2 study in an HIV-positive population for HPV-related anal dysplasia. So hopefully there will be some announcements coming out around VGX-3100. And then for 4201, which is our Ebola booster candidate, we're going to be interacting with the regulators and with potential partners on the next steps for those candidates. So over over the coming year, I think you'll see some, some interesting milestones around 3107. Around filing our first BLA. And then some significant milestones around the the following candidates as well. Our plans for starting 3112 and then moving some of the other later-stage candidates forward as well.
By the way, for me personally, I'm really looking forward to data on your dMAb program. I mean, the ability for your plasmids to generate, create antibodies, basically use the human manufacturing system as an antibody manufacturing system and confer potentially passive immunity. We've seen Moderna do that with chikungunya, about 3, 4, maybe 5 years ago in one of the R&D presentations. So it'll be great to see what, what Inovio can do with its DNA plasmids technology. You know, maybe we'll just go here to and kind of approach this as like Final Jeopardy, kind of like Fast and Furious, Jackie, with some of these questions. We've got quite a few. One is, are you planning on running a redosing trial on 3107? Will this be an arm of the confirmatory trial or a separate trial after the confirmatory?
That's a really important question. RRP is a chronic viral disease. I t's very difficult to demonstrate clearance of the virus. We think that there's a real opportunity for redosing to maintain responses for those people who are having no surgeries. To improve responses for those people who are having a reduction in surgery. So we think there are real opportunities for redosing. But at the moment, we're just very focused on getting everything we need together for filing that BLA submission, making sure that we're making 3107 available to patients as soon as possible. And then we'll be providing further updates on our dosing strategy in due course.
Yep. No, I like that. Keep it simple. Get knock on wood, get approved, and then keep moving forward. Can you talk a little bit about the durability of treatment of 3107 after 12 months? Are the reduced surgeries lasting?
Yeah, again, you know, a really important question. So our phase 1/2 study was designed with a 12-month follow-up period. We did see duration of effect over that 12-month period. In a prior study with a different candidate that was just addressing HPV-6, we saw duration for, I think, 2 and 3 years in a relatively small number of patients. So following up on that duration of protection again is going to be very important. Again, it's something that we're discussing with the FDA as to how we demonstrate that in our confirmatory trial.
Yeah. Got it, Jackie. Then, one more question that, you know, tackles specifically the patients who are complete responders. Have they remained surgery-free after the 12-month mark? And can you just remind us how many were these so-called complete responders, Jackie?
Yeah, so it was about 28% of the 32 patients had no surgery after day zero. As I mentioned in that phase 1/2 study, we only had 12 months of follow-up. So, that duration of response was over that 12-month of follow-up. We are discussing with the FDA as to what additional data we can generate, for longer duration of protection studies.
Yeah. No, that's already pretty good. After 12 months, you're seeing almost a third of patients not have any surgeries. I mean, these we've talked to KOLs, Jackie, and it's they just reiterate to us over and over again how badly they need therapeutic, modalities in this area. This was a question that might be more better related for Peter, but I don't know if you've got any thoughts. T here were a question on why the reverse stock split, was done earlier this year. Why not wait a little bit closer to, I guess, April 29th? I guess that would have been your some kind of an important date. Just any thoughts there, Jackie?
Yeah, so we did the reverse stock split really to get back into compliance with NASDAQ. I think this is a step that multiple companies have had to take. We did it when we felt the time was right. E arlier on this year, we felt it was the right window to do it. So pleased to say we're back in compliance now and the stock price seems to be holding up well at the split level we selected.
Yep. No, I agree on that one. T here is a question on just the vocal cord effect, that there is low blood supply going to the vocal cords. And it seems your approach 3107 is good in terms of trying to keep the vocal cords intact aside from these warts that, you know, are appearing. Just any thoughts there? I know that seems to be early kind of stuff, but any work Inovio has done there?
Yeah, so I think this really goes back to Inovio's deep history in working in the HPV-related space. I mean, we've conducted studies across multiple HPV-related indications. So in cervical dysplasia, anal dysplasia, vulvar dysplasia, HPV positive head and neck cancer. And what we've been able to show in those earlier studies is not only are we able to generate these antigen-specific T cells, but in the case of head and neck cancer and the case of cervical dysplasia, we're able to show that those CD8 T cells get to where they're needed. So they get to the sites of the HPV-infected cells.
In some of those studies, we've been able to also show lesion regression, which is quite difficult and challenging to do as well. So I think we're comfortable in the immune response that we're generating. We're confident that it's specific. That it's the right kind of T cell response. And that it's really getting where it needs to be to be effective.
Got it, Jackie. The other question is, I mean I know what the answer to this is, but what's your expected time frame to get a product to market?
We'll be submitting our BLA in the second half of this year. I know 3107 will be our first product to market. I think once we've heard back from the FDA and we have a PDUFA date, we'll be in a better position to talk a bit more about our launch timing.
Yeah. I'm just going to go a little bit to we're getting some better questions, so we'll keep this Final Jeopardy, Jackie. Any discussions on interest from a larger pharmaceutical company purchasing Inovio?
Inovio has always had a strong history of partnerships. We've worked with some well-known large pharma companies. We continue to talk with potential partners about potential partnerships to move our pipeline forward. We think with 3107, this is the right kind of size of market for Inovio to be able to address itself in the US We think it's a great first launch experience for Inovio. But at the end of the day, we're really looking at how we drive our DNA medicines platform forward, how we bring the resources to bear to be able to do that. So we're quite pragmatic in looking at the potential pathways to do that.
Yeah. What are the expected costs to complete a confirmatory study and manufacture 3107 for the expected public demand?
Yeah, so let's talk about the manufacturing piece first of all. So, in terms of manufacturing, we have in-house manufacturing for our device. So we can scale up or scale down quite easily. In terms of the drug manufacturer for launch, this is a rare disease product. And actually, you know, quite a lot of the material coming out potentially from our PPQ runs could potentially be used to supply that early launch, market. So I think we're going to be in good shape, for that launch.
Yeah, anything afoot for 3107 in Europe?
So in Europe, we have Orphan Drug Designation. We have been talking with the European regulators about a potential path forward there. But really, we're really focusing our efforts and our cash at the moment in terms of driving 3107 towards license here in the US, but c ertainly RRP, there's a lot of RRP disease in Europe, very high on medical need. And we're already engaging with the European regulators there.
A couple of questions on that 28% of patients that were surgery-free. One is an interesting question. It is that were these patients disease-free? So they don't require surgery over the 12 months, but did you measure disease within these patients, Jackie?
Yeah, so there are various different ways to potentially measure disease. So we were scoring them in terms of their, the disease in their throat and in their vocal cords. And we were able to show quite a substantial reduction in terms of that site disease score. And we have previously presented that data, I think, at the ABEA meeting last year. I think some of that's actually in our publication as well.
Got it. And then the 28% of patients with no surgeries. For those patients, how what was the average number of surgeries, that they had before entering into the trial?
So the patients, I don't remember the exact number of surgeries, but what I can tell you is the patients who had no surgeries; they ranged from patients who had had 2 surgeries in the prior year through to patients who had had 6 surgeries in the prior year. So across that range.
Got it. And then Asia partnership for 3100, any updates there, Jackie?
Yeah, so our partner in China, which is Apollo, is conducting their phase three study of VGX-3100 in cervical dysplasia. We understand that trial's going well. But announcements on that study come from Apollo. So I think that's all I can say at the moment.
Yep. And then just, 4800, is that still progressing or is that one of the projects that you kind of put to the side?
Yeah, so with 4800, I think, we had to make the difficult decision to discontinue that program internally. We have provided 4800 to the WHO for an inclusion within their Solidarity study. And, the WHO will be making any announcements on progress on that study. But we discontinued internal efforts, because I think it was pretty clear that there was a diminishing market opportunity for new entrants into the COVID vaccine space.
Jackie, we got more questions coming in, but we're at the end of our time, so we will have to. Actually, I'm going to save these questions, and then just ask them at another time when we either chat, and then we can also publish our thoughts on them and stuff. But to all of the audience members, thank you so very much for asking really good questions. I think they were great. And like I said, we'll save these and we'll keep on asking them, and publishing on them going forward. But, Jackie, thank you so much for joining us here and giving us your update.
Yeah, thank you so much, Hartaj. It's been a pleasure. It's an exciting time for Inovio, so I'm pleased to answer questions when we get the opportunity.
Absolutely. Same here. We're really looking forward to keeping the conversation going, Jackie. Thanks, and our best to the team.
Thank you.
All right. Take care.