Inovio Pharmaceuticals, Inc. (INO) H.C. Wainwright 25th Annual Global Investment Conference (Transcript)

Inovio Pharmaceuticals, Inc. (NASDAQ:INO) H.C. Wainwright 25th Annual Global Investment Conference Call September 12, 2023 4:30 PM ET

Company Participants

Jacqueline Shea - President and Chief Executive Officer

Conference Call Participants

Li Chen - H.C. Wainwright

Li Chen

Good afternoon, everyone, and welcome to H.C. Wainwright 25th Annual Global Investment Conference. My name is Li Chen, and I'm H.C. Wainwright Equity Research Associate.

I'd like now to welcome our next speaker, Dr. Jacqueline Shea, President and CEO of Inovio Pharma, a biotech company focused on developing and commercializing DNA medicines. Please go ahead.

Jacqueline Shea

Thank you. It's a pleasure to talk with you this afternoon. I'm Jackie Shea. I'm the CEO of Inovio Pharmaceuticals.

Before I move into the presentation, I'd like to provide the standard disclaimer that I'll be making forward-looking statements during this presentation. And I'd like to refer to you to our file 10-K and most recent 10-Q filed on June 30th for further details.

So, to provide a quick overview of Inovio, we are a biotech company focused on developing and commercializing DNA medicines to help treat and protect people from HPV-related diseases, cancer and infectious diseases. Our platform aims to optimize the design and delivery of our DNA medicines with the aim of creating therapies and vaccines that teach the body to manufacture its own disease fighting tools.

We have approximately $194 million in cash at the end of the second quarter of this year, with an expected cash runway into the third quarter of 2025. We've been building a really strong team with experienced and expertise in bringing innovative new products to market to benefit patients. And over the past year, I've added new leaders across regulatory of medical, R&D, and a new Chief Medical Officer. We're headquartered just outside of Philadelphia and we have R&D facilities and manufacturing facilities in San Diego, California.

Since I became CEO last year, my top priorities have really been to prioritize our pipeline and right-size the organization to enable us to focus our efforts on those later-stage candidates with what we believe are the greatest clinical promise, achievable pathways to market, and a strong commercial potential.

I'm pleased to say over the past year, we've announced positive data for -- from clinical trials for INO-3107 and INO-4201.

This INO-3107 is our lead candidate, which we're developing as a potential treatment for recurrent respiratory papillomatosis, or RRP, which is an HPV-related disease. And last week, we announced that we'd received a breakthrough therapy designation from the FDA. We're targeting initiation of a pivotal trial for 3107 in the first quarter of next year.

INO-4201 is a candidate that we're developing as a booster for Ebola vaccines. And here, we announced data last year that showed that in 100% of participants in our Phase 1 trial, we were able to boost the Ebola-specific immune responses. We're currently in discussion with collaborators and with regulators on the next steps for this promising candidate.

And finally, we're looking to move forward two of our immuno-oncology programs into the next stage of clinical development. And these include INO-3112 for HPV-related head and neck cancer and INO-5401 for newly-diagnosed glioblastoma. And I'll talk a bit more about these candidates later on in the presentation.

So, we see -- as part of our corporate strategy, we really see three steps to unlock the potential of DNA medicines and create value for our stakeholders and shareholders. As I mentioned in the near term, our lead program is INO-3107. We received breakthrough therapy designation from the FDA, which we announced last week. And we're really going to be leveraging our extensive experience in HPV-related diseases to enable us to bring this candidate to market as efficiently as possible.

We also have a diversified clinical pipeline with eight additional clinical-stage candidates targeting areas of unmet needs across HPV-related diseases, oncology and infectious diseases. And these will really build value in the mid-term.

In the longer term, we have some important and interesting candidates we believe coming out from our pre-clinical research and moving into early clinical development. And these include our DNA-encoded monoclonal antibodies, targeting infectious diseases, and also our DNA-launched nanoparticles. These are our next-generation vaccine candidates targeting COVID-19 and other diseases, including HIV. And finally, we have some new approaches to cancer vaccines in late pre-clinical development.

So, for those of you who are not familiar with our platform -- our DNA medicines platform is composed of two components. First of all is our precisely designed plasmids, which we deliver to either skin or muscle cells using our proprietary delivery devices called CELLECTRA. And this -- what this technology does really is to enable the body to make its own DNA medicines. And, we do this, as I mentioned, with our CELLECTRA delivery device, which enables the plasmids to enter the cells and generate in vivo produced proteins. Now, these in vivo produced proteins can either generate a targeted immune response, so generating antigen-specific T cells and antibodies, or they can encode therapeutic proteins themselves, such as the monoclonal antibodies.

Key features of our DNA medicines platform. There are -- our DNA medicines platform has many advantages, but some key features I'd like to bring to your attention are this ability to really generate those antigen-specific immune responses. Also, the ability to generate targeted T cell responses across multiple indications. Our DNA medicines are also generally well tolerated, and we've shown in more than 15,000 administrations across 5,000 participants.

Also importantly, we don't see any anti-vector responses unlike for viral vectors. And this we believe gives us the ability to re-administer our DNA vaccines and boost immune responses without any anti-vector immune responses interfering with this.

DNA medicines are also generally thermostable. They don't require frozen storage or shipping -- frozen storage or required to be frozen during shipping. And also due to the nature of the technology, it allows us to design and construct plasmids relatively rapidly and manufacture them using a platform manufacturing process.

So, before I talk about INO-3107 in more detail, I'd like to provide an introduction to HPV. So, HPV is a group of viruses with approximately 200 subtypes, and nearly everyone in the world will become infected with some form of HPV during their lifetime. The good news is that for most of us, our immune systems were able to clear the virus, and it doesn't result in disease. But unfortunately, in some people, the virus isn't cleared. And in those cases, it can lead to cell changes, which could lead to cancer and other debilitating and life-threatening diseases, which impact quality of life.

HPV falls into two types generally. Low-risk HPV, such as HPV-6 and HPV-11, an infection with these HPV types can lead to benign cell growths, such as warts or papillomas and that can develop into conditions such as RRP. High-risk HPV types, such as HPV-16 and HPV-18, can lead to more severe changes and -- more severe cell changes and lesions, often termed precancerous dysplasia, that can become malignant and lead to cancer. And an example of this is cervical HSIL or cervical dysplasia, which can lead to cervical cancer.

Whilst we do have effective HPV vaccines, unfortunately, global uptake of these HPV vaccines has not been as good as you would have hoped. And that means that there are still high levels of HPV around globally. And HPV continues to be a problem for many people and will continue to be a problem for many decades to come.

Here, I'd like to share with you some of the common observations that we've seen from the HPV-related trials we've conducted to date. We've conducted HPV trials in HPV indications from Phase 1 to Phase 3, and they've involved patients with RRP and cervical, anal and vulvar dysplasia, or HSIL, as well as HPV-related head and neck cancer. And what we saw across all of those trials were antigen-specific T cell generation, and those T cell responses were persistent. We also saw viral clearance or clearance of the HPV virus, and lesion regression, so regression of the cell changes associated with HPV infection. And importantly, we didn't see any anti-vector immune responses.

So, this is an example of one of our DNA medicines in HPV-related diseases. And this is actually for our candidate 3112 and from our Phase 1/2a trial in HPV-positive head and neck cancer. And if you look at the panels on the left-hand side, this is in HPV-positive head and neck cancer. And what we -- if you look prior to -- if you look in the tumor tissue prior to dosing with 3112, you see very few CD8 cells. However, after dosing, on the right-hand [side] (ph) panel, you can see a large number of brown stains, which are the CD8 cells entering into the tissue. And in the periphery in the blood, we can also detect these robust T cell responses in the periphery in the blood.

So moving on to INO-3107, which is our lead candidate for RRP, I'd like to tell you a bit about RRP, and then talk about some of the data from our recent Phase 1/2 study. So, RRP is a rare disease. It's caused by HPV-6 and HPV-11, so low-risk HPV types, and it occurs in both children and adults. RRP infection and disease can be lifelong. And the symptoms that you see in RRP result from those benign tumors growing in the throat and on the voice box, and it can affect the ability to breathe as well as voice quality.

Surgery is the current standard of care. And some people with RRP require a couple of surgeries a year. Other people require many more. And some RRP patients have hundreds of surgeries over their lifetime. In severe RRP, the papillomas can also spread to the lungs. And in rare cases, they can also become cancerous.

The best estimates that we have are that there are about 14,000 active cases of RRP within the U.S., with new cases occurring every year. And as you can see that from this quote from Kim McClellan, the President of the RRP Foundation, even a reduction of one surgery would make a great difference to patients in terms of how they manage their disease and improve their quality of life.

So, as I mentioned, INO-3107 targets HPV-6 and HPV-11. It's composed of two plasmids; one of which encodes the E6 and E7 antigens, and another plasmid, which includes human interleukin-12, which serves as a genetic adjuvant. And what we've seen from studies with INO-3107 to date is a reduced number of surgical interventions. We have seen the generation of antigen-specific T cells, which can potentially lead to the clearance of the underlying HPV infection and potential regression of papillomas. And we believe based on what we've seen to date, with our DNA medicines that there's the ability for re-dosing or boosting the immune response.

We announced last week that we received breakthrough designation, and we also have orphan drug designation in both the U.S. and Europe. We're planning to start our pivotal trial in the first quarter next year, and we presented the data at the recent ABEA conference in May as well as publishing the initial data in The Laryngoscope journal in June this year.

And this is some of the data from this Phase 1/2 clinical study. On the left-hand side in blue, you can see the number of surgeries that patients required in the year prior to the start of the trial. And on the right-hand side in green, you can see the number of surgeries required in the year after the start of the trial. And I'm pleased to say that overall 26 patients or 81% of patients enrolled in the study had a decrease in surgical interventions over the course the study.

It's also very important to note that we counted all surgeries from day zero. So, these included surgeries even during the dosing cycle and before we'd reached peak immune responses. Importantly, nine patients required no surgical intervention during the study. And the median change in the number of surgeries was a reduction overall of three surgeries.

If you look on the left-hand side, you can see that we enroll patients who had surgeries in the year prior to the trial ranging between two surgeries a year to up to eight surgeries a year. And we saw patients across the spectrum, as you can see here, who required no surgery in the year following the trial.

This slide captures the immune responses that we saw -- that we observed during the trial. On the left-hand panel, you can see the CD4 immune responses. And then, on the right-hand side, you can see the CD8 T cell responses which we think may be involved in viral clearance, which can lead to tissue regression and prevention of RRP. Importantly, the T cell responses that we observed lasted out to week 52, which indicates that we have a persistent, cellular memory immune response. And we're currently performing additional analysis to correlate these immune responses with the clinical responses that we saw.

So, what does this mean for patients? So, on the left-hand side, you can see one of the participants in our trial, who required frequent surgeries. These are the vocal cords that you can see here. And you can see here that the tissue is pretty grey, and doesn't look healthy. And then, on the right hand side, you can see the vocal cords much more clearly and you can see the tissue looks much pinker and healthier. So, this can really have a meaningful impact for patients.

So, moving on to our pipeline. So, we have a number of candidates across our clinical pipeline. On the preclinical side, we have monoclonal -- DNA-encoded monoclonal antibodies and also our DNA-launched nanoparticle vaccines currently in development. We also have Phase 1 studies ongoing for a number of different candidates. In the blue, you could see our infectious disease candidates. Orange shows our immune-oncology candidates. And then, green shows our -- sorry, our HPV-related disease candidates. So, a range of clinical candidates here.

Moving on to our ongoing clinical studies. I talked about INO-3107 where we're looking to start our Phase 3 in the first quarter of next year. We also have an ongoing Phase 3 clinical trial in cervical dysplasia for VGX-31100, which is being conducted by our partner ApolloBio in China. Anal dysplasia, we have a Phase 2 study that's ongoing that's being conducted by the AIDS Malignancy Consortium. And I think I briefly mentioned our candidate INO-5401 for glioblastoma, where we're just wrapping up a Phase 2 study which is being conducted in partnership with Regeneron. We hope to announce the next steps for those -- for some of these candidates over the coming months. And you can see we also have some new studies starting up in HIV as well, again, based on our DNA-launched nanoparticle technology.

And I think what this slide really does is show the power of partnerships. Inovio has partnered with a wide range of organizations from pharma companies to world-leading academic centers to not-for-profits and to government agencies to really enable us to advance our pipeline and move it forward.

And so, in closing, I'd like to focus on some of the key drivers of success for Inovio. As I mentioned, we have a diversified pipeline. And we're really advancing those candidates that we believe have the greatest scientific and clinical promise, achievable pathways to market, and strong commercial potential.

Our DNA medicines technology, we believe, has several compelling advantages. We have a growing body of research and late-stage clinical data, particularly in the field of HPV-related diseases, where we've shown generation of T cells, clearance of virus and lesions, and the ability to repeat dose.

We have an experienced leadership team, with extensive experience of bringing innovative products to market to benefit patients. And this team is really focused on operational excellence and financial discipline.

And we have a number of very important collaborations and partnerships really helping us move this pipeline forward.

And all of this is underpinned by our cash position, with a cash runway projected into the third quarter of 2025.

We look forward to providing further updates on our pipeline over the coming months and quarters. And, with that, I'd like to say thank you very much for your attention.

Li Chen

Thank you, Dr. Shea for the great presentation, and thank you for joining the conference.

Jacqueline Shea

Thank you.

Question-and-Answer Session

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