Inovio Pharmaceuticals, Inc. (INO) Earnings Call Transcript & Summary

Good morning, everyone, and welcome to day 2 of the BofA Virtual Vegas Health Care Conference. My name is Aspen Mori. I am an associate on the large-cap biopharma team. And I'm joined today by my team, Alex Hammond. And we're lucky to be speaking today to Inovio's CEO, Joseph Kim. Joseph, how are you doing today?

Great to be here. Thank you, Aspen.

Great. So I'm thinking today, we'll kind of try and run through as many programs as Inovio has in the clinic right now. But maybe we start off a little bit high level and you could just talk about how Inovio is dealing with the pandemic these days. Any lingering impacts to your underlying business, thinking about regulatory interactions, clinical trial operations, anything along those lines?

Yes. Globally, the pandemic has slowed us down in terms of clinical recruitment. We have trials going in 5 different continents. So lockdowns are not helpful in that regard. But our team has been working diligently with our CRO partners to just gut through those challenges. And I think we're pretty much on track on all of our programs.

Okay. Great. Sounds good. All right. With that, maybe we can jump into the -- some of the meat here. So INO-4800, that's your COVID vaccine candidate. Maybe start off by just giving us a brief overview of the Phase II data you announced -- I think it was on Monday and maybe put that into context with respect to your expectations for the Phase III study?

Yes. Thank you. So we reported our Phase II data, which is a randomized placebo-controlled in high at-risk infection subjects in the U.S. So we enrolled over 400 people. It's 1-milligram dose or 2-milligram dose compared to the placebo. And we're very excited about the immune responses data we got, both antibody responses, neutralizing and binding as well as T cell responses. So we're looking to -- we knew our vaccine was in the day. We wanted to look at the best immune-response dose, which clearly is the 2-milligram dose. The primary objective of our Phase II trial was to help find the selected dose for Phase III. And I think we've achieved that successfully. In terms of safety, we maintain strong safety profile, a very favorable mostly grade 1s with some grade 2s. And we're very excited about the lack of antigenicity and those type of things that other vaccines have seen. So we think it's a full clear sail to Phase III in terms of the trial data. And we're preparing for a global multi-country Phase III trials to start later this summer.

So on the Phase II data, I think there may have been some confusion on the investment piece side about the convalescence and sera levels as they compare it to the antibody levels generated by the vaccine itself. So maybe you could help put us -- put that into context and help us understand what the difference there is and how that compares to maybe some of the other vaccine candidates in development?

Yes. We've gathered the convalescence and sera sample from a local metro center, and we use that transparently. We utilize all the samples, using the assays that we have been used to measure our subject samples as well. It's just there as a transparent comparator. We're very pleased with the immune responses that we've seen with INO-4800, especially with the 2-milligram level, both the neutralizing antibody titers and T cells. And as we published with respect to the variance of concern, we know our T cell responses maintained across all of the major variants. We published that a couple of weeks ago. So I think our vaccine-induced responses are very robust and strong. Even the neutralizing antibody titers, we're able to maintain against the U.K. variant as well as the Brazil variant with a small reduction against the South Africa variant. So that -- this data helps us to plan our Phase III where we want to concentrate our efficacy trial around the globe. And by the way, Aspen, we're almost getting complacent in the U.S. in terms of the vaccine availability. Now the teenagers can get it down to 12 years old, which is great for this country. But if you look at outside the U.S., only 5% of the world has been vaccinated. So there's a remaining great demand for additional vaccines, especially if you look at INO-4800's superior temperature stability as well as better safety and tolerability profile that we've been demonstrating, we think there's huge room for INO-4800 in the global fight against this pandemic.

Got it. That's very helpful. I appreciate that. And one more quickly on the convalescent serum and -- or not the convalescent serum necessarily, but the efficacy data from Phase II. I think last time we spoke, you mentioned there's not necessarily a one-to-one correlation in antibodies with vaccine efficacy. Maybe you can talk through how you're thinking about that? And what maybe is a better predictor in your study of the data you've shown of what will translate to vaccine in the Phase III study?

Yes. Many studies have shown that the antibodies are important, right? So neutralizing antibody, binding antibodies can be correlated to protection. What's less known, although most of the experts agree that T cells are very important in fight against these infections and clearing these infections, it's been harder to measure across the platforms. So what we've shown in preclinical models is even the absence of antibodies, we can protect animals just with the T cell responses alone against a SARS-CoV-2 infection. So I think we're -- INO-4800, where we're very excited about is we can see the generation of both antibodies and T cell responses. And in our planned Phase III efficacy trials, we're very hopeful that the dual punch, once you punch antibodies and T cells generated by INO-4800 will come through. So we're very optimistic on the -- our ability to generate the strong efficacy results from our planned Phase III global trial.

Great. And on that subject in Phase III. So the FDA still has that clinical hold on the Phase II portion of the study. Maybe talk about how critical that is to the global Phase III study. And how comfortable you feel about getting that study back up and running in the summer time frame?

Yes. The global big picture, the FDA partial clinical hold on Phase III is not as important. We plan to enroll more than 90% of our Phase III participants outside the U.S. So that's to put it into the proper context. Still, we've submitted all of our device-related responses. That was the part of the Phase III home to the FDA in May. We also plan to submit all of our Phase III submissions to the FDA for 2 reasons. One is the optics. The other is the credibility to and optionality as we plan to bring the total global package back to the U.S. for a regulatory application to get INO-4800 not just approved around the world, but also in the U.S. because it's not just for the primary vaccination that we're going after. We're also looking at the long-term annual boosting or seasonal boosting potential of INO-4800. And as you and I discussed previously, Aspen, that our boostability of our vaccine has been already demonstrated across our other vaccine, and our other vaccines in our pipeline. We also have a separate COVID vaccine booster study that we will be reporting later this summer from our Phase I participants. So we had 120 subjects. Out of 120 Phase I subjects, about 100 people signed up to get a third dose or the booster between 6 months and 10 months in their second dose of INO-4800. So we will be able to demonstrate the boostability of 4,800 in a publication later this summer.

Okay. Great.

And on that note as well, do you think INO-4800 or 4802 would be able to boost adenoviral vaccines or the other mRNA on the market currently?

Yes. We believe both of our vaccines, INO-4800 or even our second-generation pan-COVID vaccine, which we published a preprint today, can be a booster to other first-generation COVID vaccines. In the past, we've demonstrated our ability to boost adenovirus vaccines in a collaboration with Merck. Several years ago we did a prime boost study in monkeys with our HIV testing with that five vaccine from Merck as a prime and being a vaccine as a boost, then we're able to demonstrate strong boostability. And while it wasn't -- it was published a few years back, we also were able to demonstrate a continuous boosting with our DNA vaccines, so in a safe and efficient way. So we think this is a possibility for us. Our -- don't get me wrong. Our primary focus is getting INO-4800 through the Phase III efficacy trial to get this product approved, bring it to the market as a primary vaccine to the world. And then we will work on how to work through the regulatory pathway to be able to serve as a booster for other adenovirus vaccines or mRNA vaccines or even inactivated vaccines. In that regard, we're doing a lot of the preparatory work to make that achievable in the future.

Okay. On that note of 4802, maybe you can walk us through the data update today. And maybe how light some of the differences between 4802 and 4800 and how you're thinking about either of them or each of them in the context of the boosting strategy?

Yes. As we discussed, INO-4800 is a vaccine, a DNA vaccine that uses spike protein sequence from the original Wuhan strain. Similar to all of the first-generation vaccines, whether they're mRNA or adeno. So this is designed with a match to the original strain. Now what we've shown is that the INO-4800 can be cross-protected or cross-reactive against other major variants like the U.K. and Brazil. And we do sway to the South Africa. So we're -- our plan is to get INO-4800 through Phase III efficacy trials and to the market around the globe and in the U.S. as well. Now at the same time in parallel, we're taking the second part of this strategy of advancing a more pan-variant or pan-COVID vaccine that uses all of our gene engineering and gene optimization approaches that we've been honing against flu viruses and HIV viruses in the past. We call this a same kind approach. And we've designed INO-4802 with all of the different gene sequences from thousands of different variants, and we can use our artificial intelligence to predict and prepared a sequence that looks a lot like every other sequence, but it's not identical to one. So that's the conceptual design. And of course, we biased against the current variants of concern. But we also allowed for this diversity and our efficient intelligent design to allow for potentially able to be cross-reactive against the future unknown variants that we haven't even seen yet. So to test this, of course, you can't do the test against the future variant right now. In animal models we tested this vaccine against the South Africa variant, the Brazil variant and the U.K. variant and also the Wuhan original strain. And to our surprise and excitement, we were able to generate a strong neutralization against all of these variants and strong T cell responses as well as a control. We have also created a South Africa spike matched vaccine as well as the wild-type match vaccine. And this 4802 actually performed better against a South Africa variant in terms of the antibodies and T cells than the actual matched variance. So we're quite pleased with the data, and we think this is a vaccine that can serve as a next-generation vaccine that we're preparing for a clinical trial accelerated Phase I/II trial to be conducted in 2021.

Got it. Okay. I appreciate that. That was very helpful. Maybe we can move on to the commercial aspects of 4800 and for 4802 as well. I guess, first off, maybe talk about where you are in discussions with government bodies in terms of securing supply contracts and stuff of the like? What regions are you kind of focused on? Have you had any of those discussions yet? Yes, that would be helpful.