Inovio Pharmaceuticals, Inc. (INO) Oppenheimer 33rd Annual Healthcare Conference (Transcript)

Inovio Pharmaceuticals, Inc. (NASDAQ:INO) Oppenheimer 33rd Annual Healthcare Conference Call March 13, 2023 10:40 AM ET

Company Participants

Jacqueline Shea - President and Chief Executive Officer

Conference Call Participants

Hartaj Singh - Oppenheimer

Hartaj Singh

Great, thank you. Thanks always to the operators for making this so easy. Hey, everybody. I apologize for the little delay here. I just had a lack of a better term a brain fart. And we have Jacqueline Shea here with us with Inovio, representing the company and giving us an update. We listened to the company’s fourth quarter call recently, caught up with the company afterwards. So, really looking forward to getting a quick update from Jacque. Jacque, maybe the best way to start would be if you could kind of give us a State of the Union, where Inovio is at for about 3 to 5 minutes and then we can jump into the fireside chat.

Jacqueline Shea

That sounds great, Hartaj and thanks for the invite this morning. It’s nice to see you again. So, Inovio is a company that’s developing DNA medicines. And we do this by designing precisely designed DNA plasmids and then we deliver them with our smart device called CELLECTRA. And we are developing DNA medicines against cancers, HPV-related diseases and also some infectious diseases. So, we have some pipeline candidates that we have recently reported data across our HPV-related diseases, so for VGX-3100 against cervical dysplasia or HSIL for INO-3107, which is our product candidate against recurrent respiratory papillomatosis, or RRP.

Then on our immunooncology side, we have a candidate called INO-5401, against glioblastoma that we have been evaluating in glioblastoma in combination with Regeneron’s PD-1 inhibitor, Libtayo. And we also have a candidate called INO-3112, which was previously licensed out to AstraZeneca was returned to us last year. And we have been evaluating that candidate in HPV-related head and neck cancer together with AstraZeneca.

With regards to infectious diseases, most – our most recent reported data was around INO-4201, which is a candidate that we are developing as a booster candidate against the Ebola licensed vaccine produced by Merck called ERVEBO. So those are the candidates that are currently in play that we have really reported recent data on. And we are also evaluating VGX-3100 in some other – in some other indications as well, such as anal HSIL and vulvar HSIL. But those are our core candidates currently within our pipeline.

Question-and-Answer Session

Q - Hartaj Singh

Jacque, before we jump into the pipeline, specifically, one of the tasks you have had is sort of coming in getting the company focus, we are in a new world for biotech. And I think my personal opinion is that Joseph left a very large, almost fully integrated company for the employees at Inovio. And you are sort of helping it focus more, how are you approaching that from a pipeline perspective, what’s the – with you and your team, what’s the kind of framework you are utilizing to help you understand which projects you want to carry forward and which ones maybe you want to put to the side for the moment?

Jacqueline Shea

That’s a really great question, Hartaj. And one of the strengths of the DNA medicines platform is that we can do so many different things. But for a company of our size, it’s really important that we focus our resources, both our financial resources and our people resources on those candidates that have the best chances of clinical success, a clear regulatory path and have really promising commercial potential. So that’s what we have really been doing over the past few months. We have had to make some difficult decisions to reduce down in size post discontinuation of some of our infectious disease programs, our heterologous boost COVID vaccine program, our laser immerse infectious disease vaccines as well. And so what we have done is really focus on what are the core skills, capabilities, expertise that we need to maintain in-house to really drive forward our core programs around HPV-related diseases, immunooncology and infectious diseases. And to make those choices, we have really been data-driven. We have really looked to see you know, Inovio has generated a lot of data over the past few years, we have had a lot of recent readouts. And what we have really been doing is we have been looking at the data and seeing where do we really have that clinical sweet spot? Where do we see a clear regulatory path? Where is that – there a promising market and that’s how we are making our choices as to what we choose to do next. I think a really important thing to bear in mind with DNA medicines are, they generate a balanced immune response. We get antibody responses. We also get cellular responses. But I would say a real strength of our platform are our CD8 or killer T-cell responses. And I think that’s really what’s enabled us to demonstrate viral clearance, tissue regression, in a number of our HPV-related indications. It’s also what we think is underpinning the promising data for INO-5401 in GBM, the promising data that’s been generated with INO-3112 in head and neck cancer. So it’s those – it’s those killer CD8 T-cells that are antigen-specific that I think really underpin our mechanism of action across those indications.

Hartaj Singh

Yes. And that’s great to hear, Jacque. I mean, we have kind of noticed that ourselves, not to say that Inovio wasn’t like that before, but there definitely seems to be a little bit more focus on the clinical data and what’s it going to take forward? One other question I would just have for you is before moving to the specific projects, again, we sometimes get pushback from investors about the term DNA medicines, Inovio was kind of in the hot and heavy chase with many other companies for COVID-19 vaccine. I think you are very smart to put that to the side to conserve resources. It’s a very competitive space. But what’s the one takeaway? Other than the potential commercial advisor for DNA vaccine, or DNA medicines, what from a clinical data and I think you mentioned this balanced immune response. But could you just dig into that, what is do you think relative to mRNA and other modalities is the greatest strength you have seen from all the data, translational data you have seen and clinical data for your DNA medicines platform?

Jacqueline Shea

Yes. So, that was a great question. I see a number of different strengths. I think the killer CD8 T-cells that we are able to generate, I mean, that’s clearly in experiments that we have performed, we see a clear difference between us and the RNA platforms in terms of the amount and type of CD8 T-cells responses that we are able to generate. So, I think that was a very important differentiator. I think another really important differentiator is with our delivery system, we do not need lipid nanoparticles to deliver our DNA medicines. And I think one advantage of that is we have a favorable safety and tolerability profile, we really only see Grade 1, Grade 2 events so favorable safety and tolerability. And I think that’s again is a bit of a differentiator against the mRNA different vaccine candidates. And then finally I would say, like mRNA vaccines, we are able to do repeat administrations without having to worry about anti-vector immunity. One big plus for DNA medicines are because DNA is inherently a more stable molecule, we are pretty thermostable as well. We are able to have room temperature stability for about a year, able to store 2 to 8 for up to 5 years. So it’s a different profile to mRNA. We are able to be very fast. I mean, once we have the sequence of our target antigen, we are able to design our plasmids and move really remarkably quickly through our platform manufacturing process and bring those candidates into the clinic. So very rapid process.

Hartaj Singh

Yes. And sorry, Jacque, one of the things if you can just touch upon is just on your mode of delivery, what are the advantages in your mode of delivery that potentially provide your approach?

Jacqueline Shea

Yes. So we use a proprietary smart delivery device called CELLECTRA, which uses a process called electroporation, which is a series of very rapid electrical pulses. And what that does is that opens up channels, very small channels in the cell membrane and that enables the plasmids to enter into the cell more effectively than if you didn’t use electroporation. So, it enhances uptake. And what that means is, we need less number of doses. So, shorter dosing regimens than other technologies that are using DNA plasmids, but don’t have the electroporation element.

Hartaj Singh

And Jacque just so that on that, I mean, you did have a Department of Defense contract there, right, which actually really helped you develop that mode of delivery?

Jacqueline Shea

That’s right. So we were really pleased to have the support of the Department of Defense, JPO, in particular, who enabled us to develop a high volume CELLECTRA delivery device, which we call 3PSP, which is for intradermal delivery and we use that for our prophylactic vaccine programs. So for instance, I know INO-4201 our Ebola booster candidate is delivered intradermally. In contrast, we have a CELECTRA 5PSP device, which we use for intramuscular delivery. And we have been using that across our HPV-related programs like VGX-3100, INO-3107 and our immunooncology candidates as well, so two different flavors of delivery device, one for ID, one for intramuscular.

Hartaj Singh

Yes. No, that’s great, Jacque. I mean, I know that we are neutral on you, but what we get excited about is the integrated approach, your ability to go from target to clinic, but you already have a developed delivery device that has a lot of – has had a lot of R&D behind it. And we will talk about your partners also a little bit later that you have – I was going to say, it’s – I didn’t realize that it was time for dinner, Jacque, no, I am teasing. The – maybe we can just talk most clearly first of all, with the HSIL program, right. So REVEAL1 and REVEAL2 you have kind of shown to us, I know it’s early days. When you aggregated the data, you seem to show statistical significance. And there have been some drugs approved on aggregated data and different diseases, not many, but there have been an IPF, if I remember correctly, there was one drug now owned by Roche that was approved on an aggregated database. What are your thoughts looking forward on your aggregated data or just your HSIL data? In your conversation with regulators, how do you see yourself approaching them and what potential do you think is there?

Jacqueline Shea

Yes, that’s a really great question, Hartaj. So for people who maybe new to the program, so we conducted two studies with VGX-3100 against cervical HSIL or cervical dysplasia, so VGX-3100 encodes contains plasmids, which encode for HPV E6 and E7 proteins for HPV types 16 and 18, which are the major causes of cervical cancer. And what we were doing in these two trials that REVEAL 1 and REVEAL 2 both about 200 patients randomized, 2 to 1 active to placebo blinded studies, was in REVEAL 1 we were looking to see whether or not VGX-3100 could achieve both tissue regression. So regress the CIN2 or CIN3 precancerous lesion and achieve viral clearance. And then in REVEAL 2, we decided to check – based on the data that we saw coming out of REVEAL 1 and discussions with the FDA, we decided to switch the primary population to a biomarker-selected population, so again, same endpoint looking for tissue regression and viral clearance. And what we saw in REVEAL 1 was we had a narrow miss there. So we just missed statistical significance in the intent-to-treat population. So everybody basically enrolled in the study. If you looked at the modified intent-to-treat population, so that’s all a valuable subjects, we actually hit statistical significance. So when we got that data from – after discussions with the FDA, we decided to amend the design of REVEAL 2 and focus on a biomarker-selected population. And the reason we did that was we wanted to have a way of ensuring that we could identify those women who were most likely to benefit from treatment with VGX-3100. And in discussions with the FDA, they were very clear with us. That would make changing the endpoints, the biomarker-selected population would make that study an exploratory study would no longer be a pivotal study. And in the recent data that we read out from REVEAL 2 just a couple of weeks ago, what we saw was that we just missed statistical significance in the biomarker and selected population. We did however hit statistical significance, but tissue regression and viral clearance in REVEAL – in the all-comers population in REVEAL 2.

And I think the thing that really encourages us is when we look at the combined dataset across, REVEAL 1 and REVEAL 2 we hit statistical significance in both biomarker-selected and all-comers population. If we just look at the REVEAL 2 data, if we see really nice evidence of viral clearance. So in REVEAL 2, we saw 37.3% of patients cleared the virus versus about 8.7% in the placebo group. And if that’s really the mechanism of action we are going for – we are looking for viral clearance, which in turn drives tissue regression. And we think that’s really down to our ability to elicit those antigen-specific killer T-cells. So we think the data now that we have been generating across HPV-related diseases, across cervical HSIL, anal HSIL, and now, INO-3107 and RRP really demonstrates DNA medicines’ ability to generate those antigen-specific killer T cells that are able to clear that virus.

Hartaj Singh

Jacque, that’s very, very helpful. I guess is the next step here with the VGX-3100 that to have a discussion with the regulators, is there a potential for them to maybe look at the aggregate data in a pre-BLA sort of meeting in type B or would you really have to just run another study in this indication before you can get to that stage?

Jacqueline Shea

So, as I mentioned, this is very recent data for us. We are still digging down into that dataset. We are looking to really understand the biomarker population what we saw. We saw a higher prevalence of the biomarker in the REVEAL 1 population versus the REVEAL 2 population. We are really looking to dig into that dataset and see what it’s telling us dig into the immunology, see what that’s telling us? And then we will craft a regulatory strategy and we will go back and have a discussion with FDA to see if they concur and what the path forward is. So, news to come in the coming months, it’s going to take us a bit of time to dig through this very recent dataset.

Hartaj Singh

Yes, no, that helps a lot. And I hate to be the pushy Wall Street analyst, but we had to do a little bit. Maybe just go to the RRP program, if you can just kind of update us on the data that you provided at the fourth quarter call and we can go from there?

Jacqueline Shea

Yes, to me, INO-3107 is a really exciting program. As I mentioned, Inovio has been working in the HPV-related space for a while. This is our second study in RRP. 3107 contains plasmids, which encodes for the E6 and the E7 antigens of HPV 6 and 11, which are the HPV types that cause the majority of RRP. And before I go into the data, I just like to talk a bit about RRP because now that it’s a rare disease, not everybody knows about it. So RRP or recurrent respiratory papillomatosis is a really awful disease. The virus basically drives wart-like growths in the respiratory tract or the airways. In adults, these are primarily on the vocal cords and it makes it very difficult to talk. In kids, because they have such small airways, these wart-like growths can make it difficult for them to breathe as well as making it difficult for them to talk. And really the only intervention at the moment is surgery, go again and either lasering away or cutting away these papillomas and unfortunately, because you are not clearing the virus, these papillomas keep growing back, and for many people that involves having multiple surgeries a year. ROP can be – can occur at any age, it can occur in kids, in midlife, in older adults. In fact, you see sort of peak incidents in around age 7 years around age 35 years, around age 64 years. So, you see those peaks of disease occurring. And as I mentioned, it’s a rare disease, we estimate that there are about one to four cases per 100,000 people. So, what we were excited to see in with INO-3107 was, first of all, I think it’s very important to talk about the endpoint here. So, what really matters to patients is having less surgery, even one less surgery is really important to patients. So, what we were looking at with in this Phase 1/2 study that we conducted in 32 patients was the ability of 3107 to lessen the number of surgeries required. So, we took patients who had had two or more surgeries in the previous year. And then we have administered INO-3107, four doses of INO-3107. And we followed them for 12 months to see what their requirement for surgeries would be. And I think it’s really important to note that we count surgeries from day zero. So, from the first time that we are administering INO-1307, before the immune response even has a chance to be fully formed and to be optimized, we are counting surgeries, because that’s what patients have told us is important. And what we saw was, over those 32 patients, we saw 81%, or 26 out of 32 showed a reduction in surgeries compared to the prior year. And we think that that’s really promising data. We saw a very favorable safety and tolerability profile, mainly Grade 1 adverse events. And we are encouraged by the immune responses we are seeing where we are seeing those CD8 T-cells being generated and circulating in the periphery. So, we announced the sort of data pretty recently for the second cohort, where we were evaluating an exploratory side port needle. We saw very similar data between both the cohort A using standard needle, and cohort B using this exploratory needle. And we will be using the standard needle going forward in our next study. So, we are currently in discussions with the FDA around the design of the next study. And we hope to start off Phase 3 later on this year. And we are looking to recruit that study globally. So, we will be looking to recruit patients outside of the U.S., as well as within the U.S.

Hartaj Singh

Yes. No, thank you. That helps. Just when you were describing RRP, it’s just such a difficult disease. One question I have, and we don’t have a lot of time remaining. We will go a little bit over Jacqueline, just because I know I joined late, if folks are okay with that. But, just one question I would have is that, surgery has always been a high bar for therapeutic to go up against. We have covered a couple of companies where they went up against surgery, one was in, slowly growing prostate cancer, HCC. And the natural history did not mimic what happened in the placebo arm. So, just what are your thoughts there? What will regulators look for? I know surgery is awful for adults and for children, but just from a clinical trials perspective, how to think about that?

Jacqueline Shea

Yes. So, I mean clearly having surgery as an endpoint, we are going to have to very carefully define how and when that surgery occurs, and that’s part of the discussion with the regulators. But I think it’s also important to bear in mind that RRP is a chronic disease. By and large, the percentage of RRP cases that go on and become malignant and cause cancer are relatively small. And so what you are really looking to do here is, is to lessen that that burden of surgical intervention. So, we see a therapy with a good or a favorable safety and tolerability profile, that’s able to reduce down those number of surgeries, really has a very positive risk benefit profile. So, you are right, going up against surgery, particularly in oncology can be very difficult. But I think for RRP it’s, we are listening to the patients and what they need, and they want this surgery.

Hartaj Singh

And Jacqueline, to that point, does, in your conversations with KOLs, I know the regulators don’t think this way, but is – I mean I know, it totally makes sense that people don’t want to have surgery, but what are KOLs thoughts, because they are the ones doing the surgery? I mean at the end of the day, they are pretty good at it, they have got machines installed, etcetera, etcetera. But how do your KOLs think about, therapeutic for this disease versus surgery?

Jacqueline Shea

Yes. So, we have talked with KOLs extensively, both in the U.S. and ex-U.S. and what we have heard from KOLs, has been very similar to the patients as well. They want less surgery. I mean surgery can cause scarring on vocal cords. It’s not the best solution for their patients. It’s what’s available at the moment. But it’s not the best solution and they want the best for their patients as well. So, a non-surgical alternative that would reduce a therapeutic alternative that would reduce the need for surgery is really what they are interested in as well. And the investigators that have taken part in our study, again, have been very clear on the need for reducing the amount of surgery.

Hartaj Singh

Fantastic. And then Jacqueline, maybe you can just touch on the other programs. I know we just got a couple of minutes here. We usually like the GBM program, with Regeneron, probably Regeneron. But maybe you can just talk about if that one, which one comes to top of mind for you, if you can just mention to us?

Jacqueline Shea

Yes. So, our GBM program in which we have been evaluating INO-5401 with Regeneron’s PD-1 inhibitor, Libtayo, we had some really promising data there. So, this was the Phase 1/2 to study of 52 patients. And what we saw was median overall survival in the unmethylated cohort or cohort A of about 17.9 months, which compares historical controls of about 14.6 months to 16 months. And then in the cohort B or methylated group, which normally do a bit better, we saw a median overall survival of 32.5 months, which compares to historical controls of 23 months to 25 months. And where we are at the moment is we are talking with our partner Regeneron around the next steps for that program, what the clinical trial design would look like, what would be the best alternative for patients, how can we optimize the dosing regimen, the immune responses, etcetera. We were very pleased to see in that initial study some promising CD8 immune responses, which in some cases seem to correlate with potentially improved overall survival. And that’s clearly an exciting signal that we are interested in following up. We do believe that INO-5401 is worthy of further evaluation. 3112, we are very excited about 3112 as well. Its HPV-related head/neck cancer, potential indications in other HPV related cancers. We saw a promising ORR of 27.6% for complete responders, for partial responders when you used – when 3112 was used in combination with durvalumab. And we think that’s promising as well. So, we are excited. We are in discussion with a number of potential companies who are developing or have licensed PD1s. And we think the combination of a PD1 to take the brakes off the immune system, combined with our ability to drive generation of CD8 antigen targets, CD8 responses could really be quite promising in that space. So, one point I would like to clarify is in 3112, 5401, we are seeing some promising data, but clearly we need to do bigger studies to move those candidates forward.

Hartaj Singh

Well, Jacqueline, we just we ran over a little bit, but I really appreciate your patience with us and investors’ patience. I apologize for being late earlier, it won’t happen the next time. I really look forward to continuing updates, Jacqueline.

Jacqueline Shea

Pleasure talking with you Hartaj, as always, have a great day.

Hartaj Singh

As always same here.

Jacqueline Shea

Thank you.

Hartaj Singh

Best of luck.