Inovio Pharmaceuticals Inc (INO) 2019 Q4 法說會逐字稿

Good day and welcome to the INOVIO Fourth Quarter 2019 Financial Results Conference Call. (Operator Instructions) Please note, this event is being recorded. I would now like to turn the conference over to Ben Matone, Senior Director of Investor Relations. Please go ahead.

Thank you, operator. Good afternoon and thank you for joining the INOVIO Pharmaceuticals' Fourth Quarter and Year-end 2019 Investor Conference Call. With me today are INOVIO's President and CEO, Dr. J. Joseph Kim; our Chief Financial Officer, Mr. Peter Kies; and Senior VP of Research and Development, Dr. Kate Broderick, who will provide an overview on INOVIO's continued efforts regarding the company's DNA vaccine, which is targeting the current COVID-19 outbreak.

Today's call is being webcast live on our website, ir.inovio.com, and a replay of today's call will be made available. Following a general business update, we will conduct a question-and-answer segment, which will be reserved for equity research analysts.

During this call, we will be making forward-looking statements that relate to our business, which include our plans to develop INOVIO's integrated platform of DNA medicines as well as clinical and regulatory developments and timing of clinical data readouts, along with our capital resources. All of these statements are based on the beliefs and expectations of management as of today.

These statements involve certain assumptions, risks and uncertainties and could cause actual results to differ materially. We assume no obligation to revise or update forward-looking statements, whether as a result of new information, future events or otherwise. Investors should read carefully the risks and uncertainties described in today's press release as well as the risk factors included in today's 10-K filing with the SEC.

I would now like to turn the call over to INOVIO's President and CEO, Dr. J. Joseph Kim.

Thank you, Ben, and good afternoon, everyone. It seems much longer than 2 months ago when we provided our clinical program update announcement in January. We have accomplished much in the last 2 months, even in the midst of all that has emerged and continues to evolve with the coronavirus.

Back in January, we remarked that this year is setting up to be a transformational period for INOVIO. And while investor attention over the last couple of months has been on our COVID-19 vaccine development, this call is timely, as I think it allows us to reconnect investors to our core fundamentals and pipeline programs and exciting upcoming data catalysts.

But before the update on our core pipeline programs and our upcoming catalysts, I would like to address the emerging novel coronavirus pandemic. For an overview of our COVID-19 vaccine development, I'd like to introduce our Senior VP of R&D and our COVID-19 Team Lead, Dr. Kate Broderick. Kate?

Thank you, Joseph, and good afternoon, everybody. Yesterday, March 11, according to the WHO, approximately 118,000 cases of COVID-19 have been reported globally with more than 4,292 deaths. The CDC has reported a total of 938 cases in the U.S. with 29 total deaths. This alarming situation is rapidly evolving and requires a swift, collective response from biotech and pharma companies around the world.

During our time together today, I'd like to cover 3 main points: number one, why INOVIO may have one of the best platforms to respond to emerging infectious diseases; number two, INOVIO's progress to date developing INO-4800, our vaccine against COVID-19; and lastly, point number three, our next steps and anticipated milestones.

So first, why is INOVIO optimally suited to rapidly respond to emerging infectious diseases like COVID-19? Well, we have consistently demonstrated potent CD8 killer T cell and antibody responses from all of our previous immunotherapy and vaccine clinical trials. In fact, INOVIO has extensive experience working with coronaviruses, specifically with MERS, or Middle Eastern Respiratory Syndrome.

In fact, INOVIO is the only company with a vaccine candidate against MERS in a Phase IIa clinical trial. We are leveraging our experience with MERS coronavirus and applying it here to COVID-19 with support from the same organization, CEPI, who is funding our larger Phase II MERS trial in the Middle East.

In addition, INOVIO's DNA medicines are stable at room temperature for over a year and at 2 to 8 degrees for more than 3 years. When you contrast that to other vaccine approaches like recombinant proteins, viral vectors and the messenger RNA after the LNP formulation step, these must be kept at minus 80 degrees. Perhaps more importantly, our DNA medicines have demonstrated an acceptable safety profile in over 2,000 patients.

So let's move on to INOVIO's COVID-19 vaccine development progress to date. On December 31, 2019, INOVIO's scientists learned about a novel coronavirus named SARS-CoV-2, which caused an outbreak of respiratory disease in Wuhan, China. Shortly thereafter, on January 10, 2020, Chinese researchers shared the genetic sequence of the novel coronavirus. Using this information, we designed a DNA vaccine, INO-4800, in 3 hours.

So how were we able to do this so quickly? While DNA vaccines do not require the possession of the virus to make a vaccine, we just need the viral gene sequence and then we employ our proprietary algorithm to design a DNA vaccine. In addition, our deep understanding and expertise in coronavirus vaccine development from our previous and ongoing work with the related coronavirus that causes MERS allowed us to be able to move very quickly.

In the second half of January and into February, we began small-scale manufacturing of the vaccine and completed the first phase of preclinical testing. I'm pleased to say that we saw the expected type of immune responses in these studies. Robust preclinical data has been shared with our public and private partners and is currently in consideration for publication in a peer-reviewed scientific journal.

And I can assure you that our dedicated research team and our global collaborators are generating even more preclinical data as we speak. In addition, INO-4800 is the 16th product to enter the clinic using our DNA medicines platform. We are able to leverage this extensive clinical and regulatory experience and expertise to rapidly advance this vaccine into the clinic.

My third and final point is related to future steps and milestones. Our goal is to begin human clinical trials in the U.S. in April. We are also planning to begin human clinical trials soon thereafter with our clinical partner Advaccine in China and potentially in South Korea with additional collaborators and funders. Contingent upon positive data and public urgency and funding, we are capable of delivering 1 million doses of INO-4800 by year-end, based on our existing resources and capacity.

As Joseph mentioned, during his White House meeting with the U.S. Coronavirus Task Force, we will need additional resources to scale up and make enough doses to help protect the American public from COVID-19 as well as to contribute to the collective global efforts to curtail this virus. INOVIO is committed to leading the fight against this global pandemic, and we look forward to updating you on our progress in the near future.

Lastly, as you will have probably seen in our release this morning, we announced a new $5 million grant from the Bill & Melinda Gates Foundation to accelerate the testing and scale-up of the CELLECTRA 3PSP proprietary smart device for the intradermal delivery of INO-4800. Initial development of CELLECTRA 3PSP was started in 2019 with an $8.1 million funding support from the medical arm of the U.S. Defense Threat consortium.

Collectively, these grants will support continued development of our intradermal delivery smart devices, which are essential for our vaccine disease platform. This latest grant comes in addition to the funding that we received from CEPI earlier in the year of $9 million, which fully funds the development of INO-4800 through U.S. Phase I clinical testing.

Altogether, these grants convey the continued confidence and support in INOVIO's technology and platforms with the ability to address both urgent pandemics such as COVID-19 as well as potential future ones. We sincerely appreciate our partners' support on these endeavors, and we look forward to sharing more with you in the coming months. And with that, I'd like to turn it back to you, Joseph. Thank you.

Thank you, Kate. We really appreciate all the work that you and your team are doing. I can tell you from my recent interactions with President Trump and the Coronavirus Task Force, they are looking to INOVIO as one of the leaders to address this ongoing public health threat and cooperate with other companies and organizations on this important effort as a part of the COVID-19 vaccine community.

You and our INOVIO team continues to be a vital part of this development, working around the clock towards getting a vaccine into humans as quickly and safely as possible. We can't thank everyone enough at INOVIO. This has truly been a team effort.

With that, let's continue on our core pipeline program updates. First, our new product candidate, INO-3107. In February of this year, we received IND acceptance for a Phase I/II trial to evaluate INO-3107, our DNA immunotherapy for treating recurrent respiratory papillomatosis, or RRP. RRP is a rare disease caused by HPV Type 6 and 11 infections. This condition causes noncancerous tumor growth leading to life-threatening airway obstructions and occasionally can progress to cancer.

Currently, the disease is incurable and is mostly treated by invasive surgery, which temporarily restores the airway. However, the tumor almost always recurs, and the surgery must be repeated, often multiple times a year. You can imagine how RRP severely impacts the quality of life for those living with the disease.

INO-3107 is designed to destroy and clear tumors caused by HPV 6 and 11 infections. It has the potential to provide people living with RRP a long-term improvement in their disease, especially as an alternative to often frequent and debilitating surgeries that do not address the underlying disease-causing virus.

We first saw INO-3107's potential in results from a pilot study of 2 RRP patients with HPV 6 infection, which were published in the peer-reviewed scientific journal, Vaccine, recently. Four injections of immunotherapy allowed 2 RRP patients to delay the need for surgery to a robust degree. Both had previously required 2 surgeries per year to manage this disease. But after dosing with our immunotherapy, 1 patient was able to delay surgery for over 1.5 years, and the second has remained surgery-free for almost 3 years.

The multi-center Phase I/II trial will evaluate the efficacy, safety, tolerability and immunogenicity of INO-3107 in approximately 63 adult patients with HPV 6 and/or 11 associated RRP who have required at least 2 surgical interventions per year for the past 3 years.

The subjects will first undergo surgical removal of their papillomas and then receive 4 doses of INO-3107, 1 every 3 weeks. The primary efficacy end point will be a doubling or more in the time between surgical interventions following the first dose of INO-3107 relative to the frequency prior to study therapy.

In addition to initiating this efficacy trial, INOVIO also plans to apply for Orphan Disease designation with the FDA's Office of Orphan Products Development. This very exciting opportunity for INOVIO adds to the growing body of evidence that INOVIO's DNA medicines drive clinical efficacy in multiple HPV-related diseases.

We have already demonstrated clinical efficacy in 3 separate clinical indications: first, in cervical pre-cancers with VGX-3100; also in head and neck cancer with MEDI0457; and now in a challenging respiratory tumor with INO-3107. Our goal remains to be the go-to immunotherapy provider to effectively treat all major HPV-related pre-cancers and cancers, and I think we are on our way there.

Now to our Phase III program and lead asset, VGX-3100. Our Phase III REVEAL 2 trial for cervical HSIL continues to enroll patients and now has a total of 43 sites opened globally for recruitment, including new sites opened in Brazil and South Africa, along with 4 new U.S.-based sites. Also, top line efficacy data from REVEAL 1 Phase III trial is on track to be reported in the fourth quarter of 2020.

We're also evaluating VGX-3100 in 2 separate Phase II trials for the treatment of vulvar HSIL and anal HSIL. Preliminary efficacy and safety data are planned to be provided later this month at The American Society For Colposcopy and Cervical Pathology, or ASCCP, 2020 Scientific Meeting on Anogenital & HPV-Related Diseases.

Now turning to immuno-oncology and our exciting progress on INO-5401 for treating glioblastoma. In November of last year, INOVIO reported positive interim data on our Phase II trial evaluating INO-5401 for treating newly diagnosed GBM at the SITC 2019 Annual Meeting.

INO-5401 is T cell-activating DNA immunotherapy encoding for 3 tumor-specific antigens, hTERT, WT1 and PSMA, and combines INO-9012, our immune activator encoding interleukin-12. We're also evaluating these combinations with Libtayo, a PD-1 blocking antibody produced by Regeneron Pharmaceuticals in collaboration with Sanofi.

Key early interim data from the 52-patient trial show that 80% of MGMT gene promoter methylated patients and 75% of MGMT unmethylated patients were progression-free at 6 months measured from the time of their first dose. This substantially exceeded historical standard-of-care data of approximately 60% for MGMT promoter methylated patients and about 40% for unmethylated patients. Again, just to reiterate, that was 80% versus 60% control -- historical control for MGMT methylated patients and 75% versus 40% for MGMT unmethylated patients.

INOVIO's hoped that our data continues to be positive with respect to historical controls. The median overall survival for patients newly diagnosed with GBM is approximately 12 months for MGMT unmethylated patient population and slightly better in MGMT methylated population.

Just to give us a gauge, historically, about 60%, 6-0 percent, of all patients including both unmethylated and methylated patients are alive at 1 year. We expect to report 12-months overall survival from our trial in June of this year in 2020, followed by 18-months overall survival in the fourth quarter.

With that, I will now ask our CFO, Peter Kies, to provide a financial update. Peter?

Thanks, Joseph. INOVIO enters 2020 with a very strong balance sheet and cash position to continue funding research and development and the programs that Joseph just talked about.

As we reported in our 10-K filed today, cash, cash equivalents and short-term investments were $89.5 million as of December 31, 2019. This compares to $93.8 million on our last reported quarterly earnings.

In addition, in the first quarter of this year, from January 1 through March 11, 2020, the company brought in net proceeds of $208.2 million by selling common stock under its ATM agreement. Based on the programs in development, as of today, our year-end cash position, plus whatever we've raised since year-end, provides INOVIO with a strong multiyear cash runway.

For the quarter and year ended December 31, 2019, research and development expenses were $22 million and $88 million, respectively. This compares to $26.4 million and $95.3 million for the same periods in 2018. The year-over-year decrease in R&D expenses was primarily due to a decrease in employee compensation expense and drug manufacturing expenses related to our partnership with AstraZeneca, among other small variances.

This decrease -- these decreases were offset by an increase in expenses related to clinical trials and a onetime personnel-related restructuring charge incurred during the third quarter of 2019. Total operating expenses decreased by roughly 8% this year, where we reported $115.2 million for the full year in 2019, which compares to $124.6 million in 2018.

Lastly, revenues for the fourth quarter and year-end were $270,000 -- $279,000 and $4.1 million, respectively. This compares to $2.5 million and $30.5 million for the same periods in 2018. This year-over-year decrease in revenue under collaborative research and development arrangements was primarily due to the recognition of a onetime upfront payment of $23 million from ApolloBio during the second quarter of 2018.

As a reminder, you can find our complete financial statements for the fourth quarter of 2019 in today's press release and also in our 10-K filed with the SEC. Today's 10-K can also be accessed on our website under Investor Relations, Financial Reports. With that, I'll turn it back to you, Joseph.

Thanks, Peter. Before we begin the Q&A session, I want to recognize and thank all INOVIO employees for their countless hours of work that you have completed in response to the COVID-19 outbreak while still executing your work on our core pipeline programs.

INOVIO's DNA medicines platform is well suited to respond to disease outbreaks like this, and it is our responsibility to play our part in serving public health interests. INOVIO is dedicated, capable and flexible to rise up and provide a solution for COVID-19, and we look forward to sharing progress updates and results in the near future.

Please also stay tuned regarding our very important Phase II and Phase III data catalysts for VGX-3100 for HPV-related diseases and INO-5401 for GBM. 2020 will truly be a transformational year for INOVIO.

I look forward to taking your questions now. Operator, please open the line for the analysts.

(Operator Instructions) The first question comes from Charles Duncan from Cantor Fitzgerald.

Appreciate all the commentary on COVID-19 earlier in the call, and sure do live in interesting times. I had a question about that program and then a couple of your core pipeline programs.

My question on COVID-19, I'm just kind of wondering about the variability in the spike protein, if you could provide us some sense of that. Looking at COVID-19 versus other Coronaviridae, do you expect not only activity for COVID-19 but also cross-reactivity and potentially protection against other coronaviruses that could come out in the future?

Yes. Thank you, Chaz. So the coronaviruses as a family are not as variant as some of the other RNA or DNA viruses like HIV or flu or such. So we haven't really seen so much mutation to date, but we're still early. And there's been various reports of variance and diversity, but I think those are still being determined and still controversial.

What I can tell you is our overall DNA medicines platform, our approach with DNA vaccines using full-length antigenic proteins but also being able to generate both CD8 killer T cell responses as well as our antibody responses, we should be able to address any sort of minor drifts, much better than other vaccine modalities such as proteins or viral vector delivery programs.

So while we will be continually surveying the potential of the changes in the COVID-19 virus or SARS-CoV-2, we are quite confident in our approach using INO-4800.

Okay. That's very helpful, Joe. And moving on to the core pipeline programs, considering the cervical dysplasia or 3100 program. For REVEAL 1 and 2, I know REVEAL 1 is fully enrolled. But in terms of 2, do you see any timing impact on enrollment due to any of the quarantine effects that you saw in Asia or social distancing that you are seeing in the States or maybe we will see in the States going forward?

Yes. Fantastic question. And I think it's just not for our program, which we address in the risk -- additional risk factors in the 10-K. I believe this pandemic, coronavirus pandemic, has the potential to disrupt many of the clinical trials and drug development efforts, not just for INOVIO but across the whole sector and across the globe.

That being said, I don't expect major impact of this pandemic on our ongoing trials, not just for REVEAL 1 and 2 but also for our GBM and RRP. Now that's not to say that there won't be a future impact. But so far, there hasn't been any significant impact on our time lines and execution.

Okay. And then one last one for you and then one quick one for Peter. In terms of -- you're seeing clinical meetings being canceled. And I know you've got some results, some Phase II results coming up as well, eventually the Phase III results with REVEAL 1.

But at least for the Phase II results, if the clinical meetings are canceled or postponed that you're planning on presenting those results in, would you just press release the results? Or would you actually hold them and delay that for later on the year for a presentation in a peer-reviewed form?

Yes. Great question. This pandemic has been a unprecedented event for many ways. While I believe some of the banking conferences can be postponed, science moves. So I think having delayed conferences may not make a great sense for some of these scientific and medical conferences.

So we're going to be evaluating and reacting to some of these opportunities, where some of these conferences are going to be held in a -- virtually. Abstracts will be published, and maybe even posters and oral presentations can be made in a virtual fashion. That's not the most ideal situation. Obviously, we would like conferences like AACR or ASCO to be where you're unveiling important data.

But I think we have to react logically and wisely to this outbreak situation. So we're going to be evaluating this then very quickly because we have a conference coming up originally by end of this month for our VIN and AIN Phase II data. So most likely, we will publish a press release and also, when appropriate, be able to talk about the abstract and the poster presentation.

Okay. That sounds great. One quick one for Peter. Congrats on the use of the ATM bolstering the balance sheet. You've had a lot of trading volume, and that helps. But I'm wondering, is it -- I'm not all that enamored with ATMs just because it's not always clear where that demand is coming from. But do you sense that there is institutional investor demand that is part of that? I mean what has been the feedback in terms of clearing that?

Yes. Definitely. There is a sense that there is combination of retail and definitely institutional investors are mixed into that.

Yes. With that more -- I expect there will be updated filings at appropriate times. But yes, when you have 100 million-plus average in the last few days, per day shares, I expect -- we expect it's going to be a mix of both retail and institutions.

The next question comes from Chris Raymond from Piper Sandler.

This is Allison Bratzel on for Chris. So another on the coronavirus. Obviously, acknowledging that COVID-19 is a fluid situation. But I guess I'm hoping you can help us understand your expectations for the regulatory path forward for INO-4800.

I think maybe it would be helpful if you could discuss your takeaways from discussions with regulators. And maybe just talk about what you see as the most likely path forward from now to 1 million doses in hand by year-end to widespread use in 2021. And kind of talk about what kind of milestones we should be looking for in the coming months.

Yes. Thanks, Ally. Great question. I would preface this by saying, there are still a lot of uncertainties and things that are moving. I used this word before, unprecedented, NBA canceling and other major sports canceling their -- suspending their seasons and NCAA tournaments canceling, so -- and our kids' school district has suspended for 2 weeks. So I expect this type of interruptions and disruptions to occur in the homeland. And certainly, we saw this type of dire situations in China and Italy and South Korea and elsewhere.

That being said, what we know today is we have our laser focus. Our team's laser-focused on getting INO-4800 into a first-in-man Phase I clinical trial in the U.S. Everything is really executing well. Our ducks are lined up in order, and I believe our team is working very hard to live up to what our target was in starting our Phase I trial in the U.S. in April.

That being said, we're also looking forward to additional opportunities, not just looking at the Phase I objective of safety and immunogenicity and the dosing levels of INO-4800, we're looking at potential to seek early signals of efficacy. And we're looking at in 3 geographical areas.

The first is China. We have a partnership with Beijing Advaccine to enter that territory with INO-4800, again, with Phase I, and -- but we're looking to accelerate into an efficacy setting as soon as we are able to. Second, similar opportunistic trial, opening in South Korea.

And thirdly, as President Trump impressed upon to me during our conversation at the White House task force meeting, he said, "Why don't you go to Seattle?" So -- but unfortunately, these could be in Philadelphia, where we are, or San Diego or Los Angeles or New York City. So I believe we will be able to act nimbly and opportunistically after getting our early safety and immunogenicity of our vaccine.

Just putting on a crystal ball, as situations calls for it and as the -- from the outbreak, and as our funding partners and others support, we can provide up to 1 million doses of INO-4800 by the end of this year.

Now I just want to be clear. This could be used -- the 1 million doses could be used for further testing in Phase II or Phase III setting, number one. Number two, if the regulatory and government agencies need them, they could make arrangements to have them utilized in an emergency situation.

But again, our goal is to make 1 million doses, which is our current capacity using our existing and our network of contract manufacturers and our own manufacturing capacity to deliver about 1 million doses by the year-end. And we have our focus on delivering on that, assuming the continuous need from the outbreak and the support of our very strong team of funders that we expect from globally and from the United States.

And maybe as a follow up to that, on the device. So we saw -- you got some more funding to advance the CELLECTRA 3PSP device. Can you talk about additional testing work that needs to be done with the 3PSP and your overall just confidence level in the ability to scale up manufacturing capacity for that?

And just to clarify, I think VGX-3100 had a brief trial hold for an issue that was related to that delivery device, the 5PSP. So I just want to understand if that could be a gating factor.

All right, Ally. Let me just clarify very quickly, last things first. CELLECTRA 5PSP currently is being tested without any delay in REVEAL 1 and REVEAL 2 trials. And prior to starting those Phase III trials, the FDA asked for additional testing. So prior to the start, we had a slight delay of about 6 months.

That CELLECTRA 5PSP is currently operating extremely well in the field in the trials, which is a completely different device than our newly engineered and scaling commercial level vaccine delivery device. We call that CELLECTRA 3PSP.

And I'm sure everyone has seen the announcement this morning that the Bill & Melinda Gates Foundation has generally -- generously supported, and they have been a very strong supporter of INOVIO for many of our R&D programs in the past for accelerating the scaling up and finalizing the testing for CELLECTRA 3PSP. This funding is going to go a long way in making that happen.

We also had $8.1 million funding just for this device about a year ago, and that had us start that development. This additional funding is going to help us accelerate the completion of the testing as well as setting up the automated manufacturing lines in anticipation of delivering multimillion doses of VGX-40 -- INO-4800 in the coming year -- in the coming years.

1 million doses can be delivered utilizing our current pilot device. But if we're planning for 50 million doses or 500 million doses, as some of the public health experts are forecasting, that will require a massively manufacturable device, which CELLECTRA 3PSP represents and cost-effective arrays, the disposables that we have engineered in to CELLECTRA 3PSP.

So we're quite happy and grateful for the Gates Foundation funding. But also, we're happy to tackle this challenge of scaling up. And we -- I believe you should be hearing more about these type of efforts that we're putting in with a lot of directed external funding from various sources. We're very happy and grateful to CEPI and the Gates Foundation, but we expect this coalition of funders will continue to grow in the coming weeks and months.

The next question comes from Stephen Willey from Stifel.

A couple for me. I guess first, just regarding the 3100 update in the other anogenital HPV types. Can you just frame up, I guess, what we should be expecting in terms of just the magnitude of patient data that we'll be seeing from each subgroup? And maybe just give us a little bit of a framework for some of the historical outcomes data that you would expect to see in this setting.

Yes. So vulvar and anal HSIL are orphan disease, so the number of prevalence and incidence are not as high as a cervical pre-cancer that we're addressing with VGX-3100 in the Phase III REVEAL 1 and 2 testing.

As you know, we have -- we are conducting 2 small Phase II trials for each of the indications, anal and vulvar HSIL. While the indications have similar name, these 2 diseases are very distinct, and we have enrolled 24 anal HSIL patients in this very targeted trial as well as enrolling 33 vulvar HSIL patients in a separate trial.

At the conference end of this month, maybe in an electronic virtual form, we plan to present at least 50% of this population. What we're looking for are the regression of vulvar or anal HSIL down to low grade or full clearance as well as the impact on HPV-16 or 18 viral infection.

So in that regard, the settings are -- and the approach are similar to our cervical HSIL Phase II and Phase III studies. We're very hopeful to see the -- and present positive response in regressing HPV-16 or 18 specific HSIL in a vulvar and anal setting.

Okay. That's helpful. And then I guess, one on COVID. So I think the MERS vaccine that you guys have in Phase II is currently on a 3-dose schedule, which I think requires patient visits at -- I think it's 0, 4 and 12 weeks.

Just kind of curious if you know now, I guess, based on some of your preclinical data, whether or not you would expect a similar dosing schedule with COVID? And I guess maybe if you can just talk a little bit about how you envision kind of a protracted 3-dose regimen kind of playing out from a mass deployment type of perspective.

Yes. Steve, great question. And we've learned a lot. As we stated, Kate and I stated at the -- during our prepared remarks, we learned a lot from our MERS Phase IIa study as well as our earlier studies in Ebola, HIV and Zika and others. We know 100% that 3 doses -- 3 shots are better than 2, and 2 are better than 1. That's an absolute fact.

But we've also learned that 2 injections or administrations in many times are sufficient. And sometimes in the MERS vaccine's case, we were able to completely protect or have a very high protection in nonhuman primates with just a single dose.

So I can tell you -- well, I'd rather not say that's not public, but I'm pretty sure we're not going to be able to deploy a 3-dose regimen or 3 visits for dosing in a pandemic setting, maybe in Philadelphia or L.A. but not across the globe. So we're looking for what the WHO and others have looked at as a target product profile in a successful vaccine for COVID-19. That's the level that we will be testing.

So I'm trying to dance around without providing any nonpublic information. But guess what? You're going to be able to see that very quickly in another month. So I think you should stay tuned. But I can tell you, it's not -- pandemic response is not going to be optimally done with 3-dose regimen.

And is there a maximum amount of vaccine, I guess, from a milligram per dose perspective that can be administered via the 3PSP device?

Yes. It's about 100-microliter volume. So it's -- that's intradermal route. While you and I are both enamored with that delivery route for a vaccine, one limitation is the volume to deliver.

So we are able to -- in preclinical models and some of which we have submitted to Nature Communications, and it's available for anyone to look, we're able to generate robust immune responses in those animal models even with a single dose at the level that we're looking at for clinical studies.

So I don't believe our vaccine delivery is going to be volume-dependent so much. I believe we will be able to generate the relevant immune responses using our vaccine dose that we are aiming to test in the Phase I studies.

Okay. So maybe just asked another way, I guess the top dose that was explored in the MERS trial was 0.6 mg. Should we assume that that's the highest dose of vaccine that you can provide for COVID? Or is there more room in terms of being able to concentrate down?

No, no, not at all. Yes. Not at all. In our Ebola vaccine studies with a similar type of setting, our higher dose was at 2 milligrams. The MERS study was testing a different part of a hypothesis, where we were coming from a Phase I study in the U.S. for MERS up to 6-milligram dosage using an intramuscular delivery.

So we wanted to have a full spectrum of dosing capability, and we were able to learn a lot from that. So obviously, less you have to dose in the vaccine, whether milligrams or volume, more you can dose [spare] in the pandemic setting. So we will be looking at escalating doses in the levels in these early Phase I trials.

But we have a pretty good idea based on our long expertise and experience in these vaccine studies, including MERS and Ebola and HIV and others, where an appropriate dose of INO-4800 might be. But that's why we do clinical studies to optimize those conditions.

The next question comes from Gregory Renza from RBC Capital Markets.

Thank you for the update today. I just wanted to follow up on your commentary on the CELLECTRA device. I think as you are advancing with the COVID effort, increasing interest and demand on hearing you basically frame up the user experience with the device, the patient experience, given that there are scores of data sets available from your historical studies. And just remind us of what that is, the pros and the cons of the CELLECTRA administration experience?

Yes. Thanks, Greg. Our CELLECTRA 3P delivery intradermally, and we have published on this, the level of tolerability in vaccine studies has been very good. In a 0 to 10 VAS score, the patient-reported pain score is around 2, which is within the magnitude of what you may expect from conventional flu vaccines that one could expect from seasonal flu vaccination. So we're quite happy with the intradermal delivery using CELLECTRA 3P.

Obviously, from a user standpoint, the health care professional standpoint, 3PSP is a sleek -- slick and well-designed, easy-to-use and easy-to-manufacture device that's quite well suited for mass production, for pandemic-prepared efforts and preparing for large delivery of these vaccines.

So we're quite excited about the progress that we're looking to make in this arena. And accelerating the 3PSP device was a very important component of our overall COVID-19 vaccine scale-up strategy. And again, I can't be any more grateful, and we couldn't be any more grateful to the Bill & Melinda Gates Foundation for their continuing support.

Great. And then another follow-up, as you have guided to trials beginning for the COVID-19 asset in April. I just want to clarify the 30 healthy volunteers is what you have shared, are there efforts also with respect to positive cases? Just hearing your earlier commentary on Seattle and other regions, just trying to get a sense of the patient population that you're identifying for the next steps and what we can expect.

Yes, Greg, thanks. The Phase I study is going to target healthy volunteers. And we'll screen for patients or volunteers to make sure they're not already infected with coronavirus. Probably, it's low even today with about a little over 1,000 persons. It's a growing number. But with 300 million-plus people in the U.S., I think we can find 30 or 40 healthy volunteers.

But that's an opportunity post-Phase I, where there will be increasing potential volunteers that we can test the early signals of efficacy appropriately even in the U.S. So while it is a growing concern for those of us who live in the U.S., it's an opportunity to test our vaccine closer to home over time.

The next question comes from Jonathan Aschoff from Roth Capital Partners.

I was wondering, are you guys going to use a coronavirus degenerative sequence such that perhaps maybe the fourth time around, you have something already there to use for a broadly useful vaccine?

I'm sorry. Can you say that again, Jonathan?

Are you going to use a degenerative sequence to generate perhaps a coronavirus vaccine that could be useful against potentially all the coronaviruses that we might encounter such that there is one that you have in hand to tested already the next time there's one of these outbreaks?

Yes. That's a very, very good question. There's -- there are divergence in these different viruses in the coronavirus family. So quick answer is, we don't have that yet. Our focus is on dealing with this COVID-19 pandemic. But we have research programs where we have extensive work that was done in researching and developing in early stages of universal or very broadly protective flu vaccines, and we can certainly rely on some of those approaches. So quick answer is no.

There are -- in the early stages of the outbreak, there were a lot of questions, very valid questions, either could we use our MERS vaccine that's been produced and already been tested to be safe and immunogenic in people? Could we use that? The -- we found out later, most likely, it wouldn't have a positive outcome. Could you use SARS vaccine there? I think there are some researchers trying to address that.

From our understanding, in vaccinology and immunology, those are good trials and good questions. I think it's not going to end up in a very positive outcome. But you're thinking of creating preset vaccines for future outbreaks, it's almost similar to the -- what started CEPI, the global organization that's really at the forefront of combating these future and current epidemics. That's what their thesis was, that we should at least make vaccines against known, crazy pathogens, really scary pathogens. And that's how they were able to fund our MERS and Lassa fever vaccine development. And having them in 2020 outbreak with COVID-19, I believe, made a huge difference compared to when we didn't have CEPI just 3 years ago. So I believe organizations like CEPI and other rapidly responding, even companies like INOVIO and Moderna and Novavax and others, we are the frontline fighters against this true enemy in this battle, which is the SARS-CoV-2 or COVID-19-causing virus. So while we may have a friendly competition in creating the best vaccine, most safe and effective for COVID-19, we -- INOVIO, at least, we have our eyes focused on who our real targets are and who our true enemy is in this SARS-CoV-2 virus.

Joe, how long do you think someone has to wait after receiving the first dose to have a useful immunity?

Great question. We wouldn't really be able to answer that definitively in patients until we have opportunities to do an efficacy setting trial. In animal models, again, we have various challenge models that we're working with collaborators across the globe. Animal challenge studies will help us address that question more definitively. But in MERS and Zika or other pathogenic challenge models in nonhuman primates, sometimes as early as 2 weeks, 3 weeks after the vaccination, you have built sufficient level of immune responses. And more different arms of the immune responses that you can generate, I believe, could be additive. So one of the advantages I see that INOVIO's DNA medicines platform has is the hallmark of the immune responses for our vaccines or immunotherapies has been our ability to generate very strong antigen-specific CD8 killer T cell responses, along with antibody responses directed to the target antigen. So I think the higher the level, the better, and multiple arms that you can access through vaccination should be helpful.

Okay. And then lastly, when you said multiyear for a cash runway, it looks on my model to be about 3 years. Is that in the ballpark?

Yes. That's in the ballpark.

The next question comes from Ram Selvaraju from H.C. Wainwright.

So just a few that are non-COVID-19 and then a couple on COVID-19. Firstly, can you comment on when we might see the first clinical data from the 4700 program, please?

Our MERS vaccine in Phase I/IIa?

Yes.

I believe this year. Study is finishing up now, and we should be able to see -- we should -- I mean we have some of the data that's driving a lot of our planning of 4800, and we should be able to present and publish the study from Phase I/IIa study this year in 2020.

Okay. And then I know this question was asked pertaining to the REVEAL -- the second REVEAL study that has not yet reached full enrollment. But are you seeing any COVID-19-related potential perturbation of enrollment in any of the other ongoing non-coronavirus vaccine program studies?

No. Not yet. While it's always a possibility and has been a concern, it has not impacted any of our REVEAL or other clinical studies. It could, as the outbreak has just been declared pandemic. And as the virus spread even more widely, it could be more pervasive, and it could be a problem. But it's not just INOVIO-specific. I think it'll be a society or the whole sector-specific potential threats. But so far...

Yes. And then -- okay. So then specific to the COVID-19 program, just a couple of questions here. When do you project your partner, Beijing Advaccine, would be able to kick off the clinical testing in China?

Yes. We can't really provide an exact date at this time, our projected date. We know as soon as possible, and it's going to be after April.

Okay. Are there any plans to test 4800 in South Korea?

Yes. We're also planning for that with additional collaborators and funders.

Okay. And then just with respect to the CEPI grants, can you give us a sense of what specific activities relating to 4800 development that amount of grant funding would cover? And does that indeed cover all of the expenses associated with the Phase I study?

Yes. So they are -- and as I said, we've had a 2-year working relationship with CEPI on MERS and Lassa. This $9 million -- up to $9 million grant is supporting all of the preclinical efforts, including clinical product manufacturing and also the conduct of Phase I clinical studies in the U.S., so really what you would expect from the completion of Phase I studies in the U.S.

There are no more questions in the queue. This concludes our question-and-answer session. I would like to turn the conference back over to Joseph Kim for any closing remarks.

Thank you, everyone, for joining us today. We look forward to speaking with you again soon. Have a great evening.

The conference has now concluded. Thank you for attending today's presentation. You may now disconnect.