Inovio Pharmaceuticals, Inc. (INO) 2023 RBC Capital Markets Global Healthcare Conference (Transcript)

Inovio Pharmaceuticals, Inc. (NASDAQ:INO) 2023 RBC Capital Markets Global Healthcare Conference May 16, 2023 4:05 PM ET

Company Participants

Greg Renza - Biotechnology Equity Research Analyst, RBC

Conference Call Participants

Jacqueline Shea - President & CEO

Greg Renza

Great. So welcome back to the 2023 RBC Global Healthcare Conference. My name is Greg Renza, I'm one of the biotechnology equity research analyst here at RBC and we're pleased now to be joined by Inovio Pharmaceuticals and representing the company is the President and CEO, Jacqueline Shea. Jacqueline, it's great to see you. Thanks for joining us.

Jacqueline Shea

It's nice to see you as well in person Greg and it's been a nice conference. So thank you for having me.

Greg Renza

That's great. Great to see you at many virtual interactions, especially over the last several years. Inovio has been top of mind over the years as well, but a lot has changed and you're there along the way. So maybe for those who are not just unfamiliar with the Inovio story, but maybe just revisiting it and getting up to speed, just provide us with an intro to the company and maybe an update on where you are.

Jacqueline Shea

Thanks Greg. So Inovio is a biotech company that's developing DNA medicine. We're developing product candidates across infectious diseases, HPV-related diseases and cancer. We deliver our DNA medicines with a unique proprietary delivery device, CELECTRA and we're currently a late-stage clinical development company with late-stage assets, particularly in the HPV focus space.

So when I look at our pipeline probably top of mind our, INO-3107 candidates for our recurrent respiratory papillomatosis, which is a rare disease caused by HPV 6 and 11 subtypes and also our VGX-3100 program, which has just wrapped up the second of two Phase 3 studies and we're developing VGX-3100 for a number of different HPV-related pre-cancers across cervical dysplasia, anal dysplasia and vulvar dysplasia. So that could be a sort of snapshot of our late-stage pipeline.

Question-and-Answer Session

Q - Greg Renza

Yeah. It's great to see 3107 really come to center stage with some of the recent data and really what is an indication where treatments are needed and surgical avoidance is important. Maybe for those who aren't familiar with RRP, just walk us through some of that disease pathophysiology, that progression over patient lives and really the current standards of care and management.

Jacqueline Shea

Yeah, pleasure. So as I mentioned, RRP or recurrent respiratory papillomycosis, it's a rare disease. It's caused by HPV or human papillomavirus subtype 6 and 11. And, the way the disease, it's a really nasty disease and the way this disease manifests is that you get the growth of these wart-like papillomas in the throat and in the airway.

In rare cases, these papillomas can spread down into the lungs and in very rare cases, they can become malignant and become cancerous. RRP is a disease that can occur at any age. It can occur in young children where they're normally infected during transition through the birth canal. But it can occur at any age. You see sort of peaks, I would say, in sort of early childhood between about two and seven. You see another peak in adolescence and then you see some more peaks in sort of late 20s and into early 30s.

The current standard of care is surgery. There's really no other way of dealing with these wart-like growth. And for people who suffer from RRP, for an adult, the principal manifestation is really a nasty impact on voice quality. People can become very hoarse. They can have repeated coughing. And if the papilloma growth becomes very aggressive, then it can restrict their breathing as well. So huge, huge impact on their quality of life.

For kids, if you think about a child's airway, it's tiny. So it's like the size of a diamond between your fingers. So as you can imagine, if you've got papillomas growing in a child's airway, one of the primary impacts is ability to breathe, which is obviously very concerning for the child and the child's caregivers as well. So really nasty disease.

Most people or the average number of surgeries seems to be about four surgeries a year, but some people require hundreds of surgeries over their lifetime. And repeated surgery can lead to scarring of the vocal cords, impacting voice quality again and in some cases, unfortunately, it leads to tracheostomy. So really, really unpleasant disease.

Greg Renza

And as a rare disease, as an orphan indication, just walk us through some of the epidemiology in the U.S., even how we're thinking about it in other geographies.

Jacqueline Shea

Yeah. So in the U.S., it's estimated that there are about 14,000 cases of prevalence. Estimates of disease, of incidence disease, these range between about one to 400,000 and unfortunately, HPV is everywhere. So it's a global disease. And we would estimate similar levels of prevalence elsewhere.

Greg Renza

Okay. And to that, just the rationale of 3107 in this indication and from there, maybe we can just talk about the data that you've generated, the two cohorts, and the path forward.

Jacqueline Shea

Yeah. So we reported out data from our two cohorts of our Phase 1-2 study. The first cohort we reported out in October last year. That was with our standard needle as part of our CELLECTRA delivery device. The second cohort, further 11 patients, we reported out this year, in February this year. And that was with a slightly different needle as part of our delivery device.

We saw very similar data across both cohorts. When you look at the combined data set between Cohort 1 and Cohort 2, so across 32 patients, we saw just over 81% of patients experienced a reduction in surgery in the year following treatment with INO-3107 compared to the year prior. The median reduction of surgeries was three surgeries. For entry into the trial, patients had to have had a minimum two surgeries in the prior year.

And for about 28% of patients, they saw no surgery at all during the year after treatment with INO-3107. So we're really encouraged by that data. I think it builds upon Inovio's experience over the past decade, really, in terms of therapeutic vaccination for HPV-related diseases.

Greg Renza

And maybe help us contextualize just the concept of surgical reduction. I think it's very easy to get caught up on percentages, but how compelling is just -- not just avoiding all surgeries altogether, but minimizing or producing even one surgery? What impact does that represent as it translates to a patient's quality of life and even the cost of care?

Jacqueline Shea

Yeah. Great question. So when we talk to patients and their physicians and their caregivers, what they tell us is reduction in surgery is the primary thing that they're concerned about. Going in for surgery is traumatic for children. Going in for repeated surgeries is even more traumatic, as you can imagine. It's a huge burden on adult patients. They have to have time to schedule a surgery and time to recover. It takes a while for their voice to come back after the surgery. So it's a tremendous burden on them.

When we look at, the approximate cost, I think the RRP Foundation, which is a patient advocacy organization, estimated a couple of years ago that the average cost for surgery was about $72,000 a year. But that doesn't take into account some of the other health economic outputs, time off work, etcetera, etcetera.

Greg Renza

And of course, what also matters is what the regulatory bodies think. So clinical meaningfulness also establishing regulatory gradients. So what can you tell us about the latest on FDA engagement thus far? You mentioned combining the data packages or the cohorts, I should say. And really, the concept here is to establish a path forward for nearest term approval. What's the latest on the feedback?

Jacqueline Shea

Yes, we submitted our data to the FDA, the combined Phase 1-2 data. And we've been in discussions with the FDA over the design of the Phase 3 trial. And I'm pleased to say that we seem to have alignment and a framework as to what the next study looks like. There is some heterogeneity in the disease course for RRP. So it will be a placebo-controlled study. And reduction in surgeries, we think is an important endpoint. And we seem to have alignment with the FDA there.

Greg Renza

Okay, great. And how meaningful is it to have others across the landscape also going after RRP? Certainly, PRGN 2012, currently in Phase 2. How is Inovio's asset 3107 positioned in accordance to the landscape?

Jacqueline Shea

Yeah, so I would say, this is, as I've talked about, this is a really horrible disease. There's a desperate need for new therapeutic non-surgical options. I think the progress that Inovio is making this space is certainly encouraging others to look at that space. I don't particularly want to comment on Preston's program. I'm much more focused on our development path.

We've wrapped up our Phase 2 study now. We're really focused on the Phase 3 program and trying to get what could potentially be a really important therapeutic available to those patients as soon as possible.

Greg Renza

Great. And to that, as Inovio scales to meet the responsibilities of a Phase 3, just talk to us a bit about your resourcing, the capabilities that have been in place for you, of course, on the drug, also the device side to deliver a larger scale trial.

Jacqueline Shea

Yeah. So, again, great question. So, Inovio has had a track record of successfully running Phase 3 trials. We ran REVEAL 1, REVEAL 2. Both of those were successfully conducted Phase 3 trials. So, we've had experience of taking our device into Phase 3 and conducting those studies.

I think, what's important to remember also about the upcoming Phase 3 trial is we think it's going to be very important to look at the sort of total treatment effect. So, look at the impact on reduction surgery from Phase 0, really, throughout the entire trial.

Greg Renza

Great. And you mentioned your experience with Reveal 1, Reveal 2. Maybe just remind us of those studies that had readouts, as you're alluding to. Some results that had been open to interpretation. Some came in unexpected. Others, not so in the expected fashion. Maybe just remind us of where you stand with those data packages.

Jacqueline Shea

Yeah. So, VGX-3100 is a similar product candidate in some ways to INO-3107. But with VGX-3100, we're targeting HPV16 and 18. We don't have IL-12 in this product candidate. So, it's just encoding the E6 and E7 antigens of HPV16 and HPV18. And our Reveal 1 and Reveal 2 studies, they were very similar Phase 3 studies in women who had cervical dysplasia.

So, SYN2, SYN3, pretty high-grade dysplasia. And what we were looking at there in the primary endpoint was both absence of HPV16 and HPV18 following treatment, and also regression of that high-grade dysplasia or lesion. So, combined endpoint there. So, in Reveal 1, in the intent-to-treat population, we just missed the primary. However, in the modified intent-to-treat population, where we were looking at people who received all four doses, we did meet the primary.

When we digested that data, we decided to move analysis of Reveal 2, which had been completely mulled at that time, to really focus the primary endpoint on a biomarker-enriched population. And here, we were using a microRNA biomarker that we'd identified from looking at the results from Reveal 1, and prospectively applying it to Reveal 2, which had already recruited, but before we had unblinded Reveal 2. And what we were hoping to show was that in this biomarker-selected population, that we had an enrichment for the primary endpoint.

When that data read out at the beginning of this year, what we were able to show was that we did meet the primary endpoint in the all-comers population. Unfortunately, we didn't meet it in the biomarker-enriched population. We missed it there. And actually, we saw less biomarker-positive women than we were expecting to see based on Reveal 1. So, we're currently digging down into that biomarker data, and we'll be, hopefully be able to share more details about that data in quarter three this year with people.

What I would say, though, is what was very encouraging from both Reveal 1 and Reveal 2 is that we saw consistent clearance of virus, clearance of HPV virus, and we saw consistent tissue regression. And I think that's very similar to what we're seeing also in the RRP space.

Greg Renza

Great. You mentioned Vin and Ane at the top as well as other potential avenues with trials underway. What's the status with the vulvar and anal indications?

Jacqueline Shea

Yeah. So, for vulvar and anal indications, we've completed Phase 2 studies of our own. In the anal indication in HIV-negative people, we saw approximately 50% of people clear the virus and clear virus-related anal H-cell lesions, which was very encouraging.

For Vin, we saw a slightly lower effect. That's a bit of a tougher disease to treat. We currently have an HIV-positive study being conducted by the AIDS Malignancy Consortium in HIV-positive people, and we're expecting a readout from, an interim readout from that study over the sort of coming time period. That study is being conducted, as I mentioned, by the AIDS Malignancy Consortium. So, we'll be waiting to hear the data from them.

Greg Renza

And just remind us of the relative market sizes for Vin and Ane, and maybe as they compare to Sin and Cervical.

Jacqueline Shea

Yeah. Well, obviously, Sin and Cervical is a huge market, hundreds of thousands of women, unfortunately, each year just in the U.S. are diagnosed with Sin 2 and 3. So, a huge unmet medical need there. For anal H-cell, actually, that's a very undiagnosed indication at the moment. It's estimated somewhere between 210,000 to over a million people in the U.S. are currently suffering from anal H-cell.

There aren't really good effective treatments there for anal H-cell either. Surgery is the main treatment there. So, a non-surgical alternative for anal H-cell, I think, would also be very attractive to both patient and physician.

Greg Renza

That's helpful. And maybe just closing with other activities in your pipeline and I think one of the marks you've left on Inovio is really establishing that focus. So, maybe I'll pitch it to you as far as other pipeline opportunities under development that you're finding of interest that you think investors should be worth watching. And with our familiarity with 5401, of course, 3112. And I know that there are others that could prompt intrigue from you. Which ones are you most excited about?

Jacqueline Shea

Yeah. Well, I'm excited in the anal oncology space with 5401, which is a drug candidate for nearly diagnosed glioblastoma, which is a very deadly brain cancer. We recently conducted a Phase 1, 2 study there. We're just wrapping up that phase 2 study currently. And that was conducted in partnership with Regeneron, who were supplying their PD-1 inhibitor, Libtayo. That was an open-label study.

We saw promising potential clinical benefits in that study with encouraging progression-free survival at six months and good potential improvement in median overall survival as well. So, we're excited by that data. We think that candidate's worthy of moving forward. And we're in discussion with Regeneron and KOLs, including the lead PI of our study, Dr. Dave Reardon, about the right next steps there.

So, 3112, that's an asset that was returned from AstraZeneca to us. This is a candidate that's been developed for HPV-related cancers rather than precancers. So, similar to VGX, 3100 is in some ways, but also has IL-12 there, really focusing on HPV 16 and HPV 18 cancers, which drive the majority of HPV-related head and neck, cervical, and some other cancers. So, we're excited by that asset.

The phase 2 study run by AstraZeneca reported back an ORR of about 27%. We saw four partial, four complete response there. And there, we're really looking to find the right PD-1 inhibitor to combine with 3112 and take into that next study.

Also, sort of talking about the power of partnerships, we have early-stage technologies and studies that are being conducted mainly by our external partners. For instance, we have a collaboration with the Wistar Institute for a study that's being conducted by NIAID, which is delivery of a DNA-launched nanoparticle vaccine for HIV, which I would say is the next generation on of our vaccine technology.

We have a collaboration with, funded by DARPA, over development of an Ebola booster vaccine. And then, we have also DNA-encoded monoclonal antibodies, again, programs that are being funded externally and conducted in partnership. So, I think what those partnerships really enable us to do is to help us evolve the technology, really advance what the technology can do, but that it doesn't dilute down the resources that we're able to bring fair on our late-stage clinical assets, which is for Inovio is really focusing our resources.

Greg Renza

Great. I think that's a great place to leave it. Really appreciate your time. I look forward to following the progress, and great to see you.

Jacqueline Shea

Great to see you too, Greg, and thank you very much for your time. Thank you, everyone.