Inovio Pharmaceuticals, Inc. (NASDAQ:INO) Jefferies Healthcare Conference 2023 June 9, 2023 8:00 PM ET
Company Participants
Jacqueline Shea – President & CEO
Michael Sumner – CMO
Conference Call Participants
Roger Song – Jefferies
Roger Song
Welcome, everyone, for last day, day three, 2023, Jeffrey’s Healthcare Conference. My name is Roger Song. One of the Senior Analyst cover Biotech, Semi Cap Biotech here. Our next printing company is Inovio. With us today is CEO, Jackie; and CMO, Michael. How are you?
Michael Sumner
Good. Thank you.
Jacqueline Shea
You’re welcome.
Question-and-Answer Session
Q – Roger Song
Thank you. All right. Maybe you get the star, maybe Jackie what are your updated animated pitch for Inovio, particular for those people, maybe new to the story? Thank you.
Jacqueline Shea
Yeah. Thanks, Roger, and it’s nice to see you in person. So Inovio is a clinical stage biotech company developing DNA medicines to help treat to protect people from HPV-related diseases, cancer and infectious diseases. Our technology, DNA medicines is based around nucleic acids. And we use precisely designed plasmids or circles of DNA to encode targeted genes of interest to drive protein expression within the patient’s own cells.
In this way, we can generate immune responses that can help fight HPV-related diseases in cancer and protect against infectious diseases. We’re also able to generate therapeutic proteins such as monoclonal antibodies or proteins that can be used to replace missing or defective proteins within the body.
When it comes to our pipeline, our lead programs are HPV-related, so these are VGX-3100, which we’re developing for dysplasia or precancers of the genital tract, and INO-3107, which we’re developing for recurrent respiratory papillomatosis or RRP, which is caused by HPV6 and 11 mainly and is a rare disease of the respiratory tract.
We also have a number of other pre-clinical and clinical candidates in development across HPV-related diseases, cancer and infectious diseases. I think it’s important to note that our DNA medicines are delivered by our proprietary smart device, which is called CELLECTRA.
Roger Song
Awesome. Great. Okay. Maybe we just spend most of the time on your lead program engine HPV-related. And then, if we have time, we’ll talk a little bit about the other, earlier pipeline. Maybe we start from 3107 RRP that you have — more recent today, you have some data. I feel pretty impressed by this surgery reduction or the surgery free rate. And maybe just remind us, what are the key data points you feel pretty supportive of the potentially pivotal kind of path forward and maybe also talk a little bit about why the biomarker and the safety also supporting? Thank you.
Jacqueline Shea
Thanks, Roger. So maybe I’ll start off by sort of explaining why we’re so excited about the INO-3107 data and why RRP is an important disease, and then maybe Mike you can dive into some of the more specifics. So RRP is a rare disease. We recently received orphan drug designation for INO-3107 within Europe. You already have orphan drug designation for 3107 in the U.S., but it’s a really nasty disease with very high unmet medical need.
If you can — RRP is caused by HPV6 and 11, it causes growths of warts or papillomas in the respiratory tract and voice box. And in adults, the main symptoms are really hoarseness of voice, difficulty talking, occasionally difficulty of breathing. In children, I mean children’s airways are really, really small. I mean, they can be like this little diamond in my fingers. So you can imagine if you’ve got warts and papillomas growing in that airway, it’s very easy to obstruct breathing.
And it’s a really, really debilitating disease that it really affects patients’ lives because they have to schedule our lives around surgery. The only really effective treatment is just repeated surgeries and some patients have hundreds of surgeries over their lifetime. So really strong unmet medical need. And when we talk to patients and when we talk to physicians, what they’re really telling us and what they’re telling us it really matters to them is to reduce the numbers of surgery, even one less surgery would be valuable to them.
So Mike, do you want to talk a bit about the data?
Michael Sumner
Yeah. No, happily. So, I mean, we’re really hoping that 3107 can change the treatment paradigm for these patients. And when I look at the results, I mean, firstly, starting with the safety, it was primarily a safety study, we looked at 32 patients. And one of the hallmarks of DNA medicines is it’s well tolerated. It has a good safety profile. And we certainly saw that in the Phase 1/2 study. And really, the only treatment emergent adverse event of note was related to the administration.
From an immunological side, we saw antigen specific, memory cells helper Cytotoxic T cells and we think that led to the excellent efficacy that we saw. So out of the 32 patients, 26 of them saw a reduction in surgery and we measured efficacy by comparing the number of surgeries after the commencement of treatment to the previous year. And so out of those 26 patients that saw a reduction, the overall population had a median number of surgeries of four and we saw a reduction, median reduction of three surgeries.
And we actually saw nine patients require no surgical intervention following the start of treatment. So taking that totality of the data, we’re really delighted to move this program forward.
Roger Song
Excellent. Yeah. You reported multiple Phase 1/2 data pretty supportive and since you are moving into the pivotal stage, maybe just remind us of what have been discussed — discussing with the FDA in terms of the potential pivotal study design.
Michael Sumner
Absolutely. So we’re in active discussions with the FDA and the European authorities. And one of the hallmarks of this disease really is variability within the patient over time. And there are also no surgical guidelines. So what we’ve got concurrence with the agency is to run a pivotal randomized control Phase 3 study, which will actually account for that variability, so we’re happy with that design. We think it’s going to answer the scientific questions and support the data we’ve seen. And also, we’re moving forward with under that proposition to do that.
Roger Song
Yeah. Probably you’re not going to be able you give too much specifics before you finalize the design. But one of the key thing in my mind regarding this pivotal design is the criteria for the surgery reduction or surgery free because across sites, across country, different, investigator, they may have a different kind of a way to decide when or if it will do the surgery. How do you think about this? You know, help us to understand when you try to design this end point, what are the key considerations and how to harmonize across different investigators? Thank you.
Michael Sumner
Actually, that’s one of the questions we’re still discussing with the agency. As you can imagine, we spend a lot of time with key opinion leaders discussing that very thing. One of the things for adults is primarily affects the voice. And so there are some measurements around voice quality that we can look at and we have worked on other criteria so that we believe we can standardize across sites and across countries.
Roger Song
Okay. Look forward to it. And then, so I think, Jackie, you mentioned those patients pretty debilitating and they may even went through — they even go through the 100 surgery, which is pretty surprising. And then so, what will be considered as a clinically meaningful for surgery reduction as you power your study, assuming you have a standardized criteria for the surgery.
Jacqueline Shea
So Mike, you want to…
Michael Sumner
Yeah. So I mean, you speak to the patients and you hear from them. And I think, Jackie mentioned this. I mean, to them, just one surgery reduction is meaningful and it was actually — there’s actually some data, I think, coming out from Simon Best that really shows that you don’t know which surgery could be the one that could cause long damage in these patients. So any surgical reduction is important.
I mean as you can — as you heard me say earlier, we saw a median decrease of three surgeries. So we think we can certainly deliver a rare disease study based on a sample size that is certainly less than the three we saw. So when you, it’s always a balance between what you can do from an efficacy point of view and also making sure we have an adequate safety population.
Roger Song
Yeah. Good. And then so do you have any guidance when you will start this pivotal trial we get (ph) based on the conversation you’re having with the agencies?
Michael Sumner
We haven’t announced yet. We’re still as you can imagine, it’s a number one priority for us to address the final questions that we have with the agency. We have engaged with a CRO and we’re looking for sites on a global basis, so we can really reduce the time from finalizing the protocol with all the final FDA comments and getting the first patient into the study.
Roger Song
Okay. All right. And then, Jackie, you mentioned this is a rare disease, but also affect pretty broad population in terms of the impact. So how should we think about the market opportunity for RRP given you don’t have too many other company doing this indication, but we do have one, right? So at least I know in the public domain. But, just help us to understand the market size and how do you think about this RRP market?
Jacqueline Shea
Yeah. Thanks, Roger. So it is a rare disease. So that sort of the best data really around the prevalence and the instance comes from a task force that was led by Craig [indiscernible] and they estimated that there are about 14,000 active cases in the U.S. about 1.8 – hundred thousand (ph) new cases in adults. The prevalence in children is a little lower than that. HPV is a worldwide disease. Wherever you have HPV you’re going to have a RRP.
When we think about, as we mentioned, we do have orphan drug designation in both the U.S. and EU. And when I think about the potential market, I think this very high unmet medical need, a reasonable number of patients, plus the RRP foundation estimated that the average cost just of treatment per patient in the U.S. is about $72,000 a few years ago. So I think when you take all of these things together you can see that there’s actually a quite an attractive market there.
Roger Song
Got it. And you talk about the incidents versus the prevalence. Do you have any, further granularity in terms of which the population of the RRP maybe need this type of the therapeutics given, maybe they require more surgery or they just hire may need more likely to get a novel therapy like 3107?
Jacqueline Shea
Yeah. That’s a great question. I think when you talk to RRP patients and their physicians, having to lead your life, manage your life around scheduling surgeries is really challenging. The recovery after surgery as well takes time. For children, it’s a very, very difficult disease. So I think any therapies that provide a meaningful reduction in surgery would certainly receive, I think, good uptake and be welcomed by the community. So I think that’s we’re really driving for. Effective therapies that are safe that can be used over long periods of time, potentially because it’s a chronic disease and reliably reduces the numbers of surgeries.
Roger Song
Okay. All right? Good. Maybe we move on from 3107 to 3100. You have actually two Phase 3 data already reported. And maybe just let us know what is the next step for 3100, seems, based on the public disclosure, you want to try to combine those three, two or Phase 3 radars to discuss with the FDA in terms of the next pivotal study design.
Michael Sumner
Yeah. So yes, as you say, we have REVEAL 1 and REVEAL 2 both looking at VGX-3100 in cervical HSIL. And the primary endpoint in those studies was looking for absence of virus and regression of the lesion. And so when we read out REVEAL 1, we narrowly missed the primary endpoint and that really what got us started looking for the biomarker.
And based on the biomarker, we selected from REVEAL 1, we saw the biomarker was actually present in about a third of the population and we saw the overall efficacy being at 66%. So with that, we approached the agency and decided to change the primary population for the readout for REVEAL 2 for that biomarker selected population.
And then, as you — we read out the results early — earlier this year and we missed narrowly in the biomarker population. And that was really because of two things, we saw a lower frequency of the biomarker. And we also saw reduced efficacy in that population. However, we did hit on the — all comers population and we saw viral clearance that we were very pleased of at 37%.
So now looking at those results, we’re really trying to understand why we saw a reduced frequency and why we saw the lower efficacy. So looking at the clinical parameters of those patients. And we hope to be able to talk to those results sometime in quarter three. We were always in the position that the FDA had said to us we changed to the biomarker selected population for the primary endpoint that we would need to run one or two additional studies but we really need to understand that biomarker from REVEAL 2 before we can decide a path forward.
Roger Song
Okay. So what would you to release for the biomarker data in 3Q outside of where we already know, and also, I believe you’re thinking about maybe enhance the current — the biomarker strategy. What could be the potential methods you will or means you will enhance the biomarker?
Michael Sumner
To be honest, we haven’t seen all the results yet, so I don’t know how we’d be able to adopt a sort of different biomarker strategy to be able to give us the results that we were originally looking for. I think for us as an organization, you’ve heard me talk about, we actually have several late stage assets. 3100 is also we’ve studied in anal HSIL. We also have 3112 in HPV-related head and neck cancers and we have 5401 in GBM. So we’re really looking at all these assets as we decide what’s the best near term asset to bring to market.
Roger Song
All right, okay. Then we talk about those other pipelines. So for anal, so what are the data you have seen? You think, okay, maybe that’s very interesting and that will be the next step for the anal?
Jacqueline Shea
Yeah. So maybe I’ll provide a bit of background, Mike, and maybe you can talk about some of the data. So as you mentioned, Roger, we’re developing VGX-3100 for a number of different indications across the genital tract. And what we’ve really seen across all indications are tissue regression, so regression of the abnormal tissue and lesions and also viral clearance, which has been very encouraging. I think as Mike talked about it, it really comes down to the mechanism of action of DNA medicines driving that T-cell response.
So when you look at anal dysplasia as you find that the majority over 90% of cancers that go on to occur after anal dysplasia, our HPV positive, HPV is 16 or 18 positive. So there’s a very strong link there. So clearly, clearing the virus, getting tissue regression is an important step. When we think about incidents, anal dysplasia is an incredibly under diagnosed in the disease both in the U.S. and then more globally, it’s estimated that there are some way between [indiscernible] and 1.1 million cases of anal dysplasia in the U.S. and a similar number in Europe, so really a high unmet medical need there.
So Mike, do you want to talk about the data?
Michael Sumner
Absolutely. So we really have two studies. We released the Phase 2 results back in ‘21 where we actually saw 50% of patients at week 36 have no evidence of HPV16 and 18 HSIL (ph). And we’re also working and supporting the AIDS malignancy consortium with a study that’s looking at HIV positive individuals and treating in a [indiscernible]. I think really what changed our sort of mind, obviously, the significant prevalence that Jackie just talked to.
But the ANCA results, which showed that is changing the treatment paradigm for anal HSIL. And the fact that active treatment of the anal HSIL has actually been shown to reduce progression to carcinoma. So we do believe that we’re very — we’ve seen excellent results with respect to viral clearance across all our HPV portfolio. So we do believe that using 3100 in anal HSIL should hopefully lead to the same benefits that they saw in the ANCA study.
Roger Song
Okay. Any timeline you want to provide some guidance?
Michael Sumner
No. I think again, as I said, we’re looking at all our assets and really deciding what we feel is the most promising.
Roger Song
Okay. And then quickly GBM, why you’re — I believe you have to partner with Regeneron to do the combination for GBM. So how’s the, conversation with your partner going, and what should we expect for the next?
Michael Sumner
Yeah. So as you know, GBM is a devastating diagnosis and it occurs in about 15,000 patients on an annual basis. We released the results at ASCO last year 52-patient study, we looked at median overall survival in methylated and unmethylated patients and compared to historical controls. We did see an improvement in both those populations. We actually do still have a few patients ongoing in the study.
And in talking to Regeneron and Doctor Reid and who was a principal investigator for the study. I think we’re all very encouraged by what we saw. So we’re really discussing what mechanisms we can to continue there and get further evidence of supporting the efficacy of 5401.
Roger Song
Okay. Given you have this DNA platform, so you have a lot of the pipeline. Maybe just the last couple minutes, what are the other earlier pipeline, COVID, HIV, Ebola, as you said, you are trying to decide, prioritize which one in the portfolio strategy, how you’re going to think about those earlier pipeline versus the pipeline we discussed a little bit more advanced stage.
Jacqueline Shea
That’s a great question, Roger. So Mike, why don’t you take Ebola, and then I’ll talk about COVID and HIV. Thank you.
Michael Sumner
Yeah. So we released a study for a Phase 1 study for Ebola funded by DARPA and we saw — we had 36 patients treated who’d previously been received the Merck of ERVEBO vaccine. All 36 patients showed a significant response with respect to with neutralizing and binding antibodies. And a pretty fast response we saw at week two that was sustained out to week 24. There’s no currently approved booster for Ebola in the United States. So we certainly are encouraged by those results and we’ll continue to develop the program and also look for partnership to take that forward.
Jacqueline Shea
I think that’s a really good point, Mike. When we look at our infectious disease programs as well as some of our other programs, for instance, the GBM program, we really see the power of partnership. We were working with a number of partners on the Ebola study. For COVID, we have discontinued our own internal efforts to develop INO-4800 as a preventative COVID vaccine, mainly because of the shifts that have occurred in the COVID vaccine market. But we still have partners who are continuing development by INO-4800, Advaccine in China and also the WHO INO-4800 is part of the ongoing solidarity study.
Then on the HIV side, again very much partnerships, so Inovio is working as part of a consortium on two Phase 1 vaccine trials. That are being conducted by NIAID in partnership with the HVT or the HIV vaccine trials network. And these Phase 1 studies are looking at two different candidates. One of the candidates we’re particularly excited about because it’s a next generation basically infectious disease, iteration of our DNA medicines platform its DNA launched nanoparticles, and we’re very excited to see what that study is going to show.
So I think a number of shots on goal in terms of the infectious disease platform and we are further evolving our technology to improve upon immune responses or to really capitalize on something immune responses such as the T-cell response where we’re particularly strong.
Roger Song
Excellent. Okay. Maybe just lastly, remind us what’s your cash position, what’s the wrong way, anything else that we haven’t discussed, but you want to sure, you missed there kind of get the message?
Jacqueline Shea
Thanks, Roger. So at the end of quarter one, we had approximately $224 million left of cash. We put out a forecast of about $33 million spend for the second quarter. And we have runway into about the first quarter of 2025. I think the key message I’d like to leave everybody with is we have some exciting late stage candidates based around are developments for HPV-related diseases as well as a number of exciting both pre-clinical and clinical candidates of cancer and infectious diseases. We’ll be out talking about the data, the exciting data we’ve been generating over the past year at various meetings and conferences. And we look forward to sharing with all stakeholders which candidates we’re going to be advancing in the near future.
Roger Song
Excellent. Thank you, Jackie. Thank you, Michael.
Michael Sumner
Thank you.
Jacqueline Shea
Thank you.
Roger Song
Thank you, everyone.
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