Good day, and welcome to the Inovio Third Quarter 2021 Financial Results Conference Call. All participants are in listen-only mode. [ Operator Instructions] After today's presentation, there will be an opportunity to ask questions. [ 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 third quarter 2021 earnings conference call. Joining me on today's call are Dr. Joseph Kim, President and CEO; Mr. Peter Kies, Chief Financial Officer; Dr. Jackie Shea, Chief Operating Officer; Dr. Laurent Humeau, Chief Scientific Officer; Dr.

Jeffrey Skolnik, Senior Vice President of Clinical Development; Dr. Anza Mammen, Senior Vice President of Clinical Development; and Dr. Kate Broderick, Senior Vice President of Research and Development. For today's call, we will review our corporate and financial information for the third quarter ending September 30, 2021.

We will also discuss our COVID-19 vaccine development efforts that address both current and future variants of concern, as well as our efforts around both homologous and heterologous boosting. Additionally, we will review other recent developments associated with Inovio various therapeutic and vaccine programs across our DNA medicines platform.

Among our recent updates, we'll address the progress from our Company's global Phase 3 INNOVATE trial, which involves our COVID -19 DNA vaccine candidate, INO-4800, with our partner, Advaccine, as well as our announcement this morning that the U.S.

Food and Drug Administration has lifted the partial clinical hold on the Phase 3 segment of INNOVATE in the U.S. Following prepared remarks, we will be conducting a question-and-answer segment reserved for equity research analysts.

During the call, we will be making forward-looking statements regarding future events and the future performance of the Company.

These events relate to our business plans to develop Inovio's integrated platform DNA medicines, which include clinical and regulatory developments and timing of clinical data readouts, along with capital resources and strategic matters. All of these statements are based on the beliefs and expectations of management as of today.

Actual events or results could differ materially. We refer you to the documents we file from time to time with the SEC, which under the heading, Risk Factors, identify important factors that could cause actual results to differ materially from those expressed by the Company verbally, as well as statements made within this afternoon's press release.

This call is being webcast live on our website, ir.inovio.com, and a replay will be made available shortly after this call has concluded. Now, I would like to turn the call over to Inovio's President and CEO, Dr. Joseph Kim..

Mexico, Brazil, the Philippines, Colombia, India, the United States, and Thailand, with additional countries projected to follow. Together, we're aiming to have the interim Phase 3 efficacy data from this trial in the first half of 2022. Pending clinical efficacy data, the Company plans to apply for emergency use authorization in respective countries.

Very quickly and just to further expand on Colombia, in addition to receiving regulatory authorization to conduct our Phase 3 trial, Inovio also signed a non-binding memorandum of understanding with Colombia's Ministry of Health and Social Protection, reflecting our mutual intent to advance efforts to combat the continued threat posed by COVID-19, as well as to better prepare for future public health emergencies in Colombia.

The agreement creates a framework for collaboration under which Inovio and Colombia's government can explore knowledge sharing, technology licensing, and capacity-building towards developing and producing vaccines, along with other biopharmaceuticals in Colombia. This morning, as you probably have read, Inovio announced that the U.S.

FDA provided authorization to proceed for our INNOVATE Phase 3 segment of our COVID-19 vaccine candidate, INO-4800, in the U.S. Inovio now has the opportunity for the U.S. participants to potentially contribute to enrollment in our INNOVATE Phase 3 segment.

The FDA has lifted the partial clinical hold following its review of additional non-clinical, clinical, and device information provided by Inovio. As I stated in this morning's release, I would like to recognize and express my appreciation to all of my Inovio colleagues for their hard work throughout this process.

Separate from our INNOVATE Phase 3 trial, the World Health Organization shared on October 26 that INO-4800 is one of the two vaccines -- two vaccine candidates to be initially included in the Solidarity Trial Vaccines, which is an international, randomized, controlled Phase 3 efficacy trial sponsored, funded, and conducted by the WHO.

Further, WHO Solidarity Trial Vaccines is designed to rapidly evaluate the efficacy and safety of promising new candidate vaccines selected by an independent Vaccine prioritization advisory group composed of leading scientists and experts.

They also shared that the trial has the additional potential to uncover second-generation vaccines with greater efficacy, conferring greater protection against variants of concern, offering longer duration of protection, and/or using needle-free routes of administration.

With uncertainty about future outbreaks and much of the global communities still requiring greater access to vaccines, we believe certain positive attributes of a DNA medicines platform like ours, and specifically INO-4800, put eight public health measures against infectious diseases like COVID-19.

INO-4800 is well-positioned to combat this global pandemic, having shown to be well-tolerated to generate a balanced immune response that includes both cellular and humoral immune responses and to offer a favorable thermostability profile to facilitate global distribution.

Additionally, Inovio's partner, Advaccine, is sponsoring a booster study in China, where INO-4800 is given as a booster after primary vaccination with an inactivated COVID-19 vaccine.

Collectively, these trials are a testament to the attributes of INO-4800 and its potential contribution globally as a primary vaccine series and as a booster, including for those who have received a primary series with other COVID-19 vaccines.

Given the impending endemic nature of the virus transmission, that underlies this global health crisis and the need for boosters to ensure sustained protection, DNA medicines may offer advantages compared to other approaches.

This quarter, Inovio's share at a positive data on homologous boosting from our Phase 1 clinical trial, as a pre-print in MedRxiv. The paper, which Dr.

Anza Mammen will describe in further detail later in the call, found that INO-4800 produced broad-based immune responses and was well tolerated as both a two-dose series and as a homologous booster in adults of all agents.

Separately, from our COVID-19 program, Inovio recently completed enrollment in our Lassa fever vaccine trial, which was funded by CEPI or the Coalition for Epidemic Preparedness Innovations. These milestones collectively demonstrate the significant progress that Inovio continues to make across our DNA medicines platform against infectious diseases.

With that, I'd like to turn the call now to Dr. Anza Mammen, our SVP of Clinical Development for COVID-19 vaccine program.

Anza?.

Thank you, Joseph. As Joseph have shared in his opening remarks, Inovio 's COVID-19 vaccine candidate INO-4800 is 1 of 2 vaccines currently included in the Solidarity Trial Vaccines, a Phase 3 trial sponsored and being conducted by the World Health Organization. Recruitment for the trial is already underway.

More than 40 clinical sites have been identified to implement the trial in Colombia, Mali, and the Philippines. WHO's Solidarity Phase 3 Efficacy trial is being conducted separately from Inovio's global Phase 3 efficacy segment of INNOVATE.

As for INNOVATE Phase 3, we have now received regulatory authorization in a total of 7 countries across the Americas and Asia Pacific. Most recently, the FDA has lifted the partial clinical hold on INNOVATE Phase 3. I'm especially pleased to report that we have recently received regulatory authorization to proceed in India.

This is a notable addition to the regulatory authorizations received from Brazil, Mexico, Colombia, the Philippines, and Thailand, given the impact of the pandemic on the Indian population and the persistent need for safe and effective vaccine.

We continue discussions with countries in Africa to provide us the greatest flexibility to enroll according to the ongoing medical need, the changing epidemiology of SARS-CoV-2, and the availability of vaccines in these countries.

As a reminder, INNOVATE Phase 3 is designed to evaluate the efficacy and safety of INO-4800 in a 2-dose regimen using the 2-milligram dose administered 1 month apart in a 2-to-1 randomization ratio between INO -4800 and placebo.

Healthy men and non-pregnant women, at least 18 years of age are being enrolled with the primary endpoint of virologically confirmed COVID-19. As Joseph noted earlier, Inovio recently shared Phase 1 clinical data on homologous boosting of INO-4800 as a preprint in med archive.

The paper title, "SARS COVID -2 DNA vaccine INO-4800 ", induces durable immune responses capable of being boosted in a Phase 1 open-label trial.

Found that among the full Phase 1 cohort of 120 participants, 99 or 82.5% of participants opted to receive a booster or a third dose of INO-4800 in the setting of available vaccines under Emergency Use Authorization, reflecting the tolerability of the vaccine.

The booster dose produced broad-based immune responses and was well tolerated as both a 2-dose series and as a homologous booster dose in adults of all ages.

Notably, we observed a durable antibody response 6 months following the second dose and significantly increased antibody and T cell responses following a homologous booster dose administered 6 to 10.5 months following the second dose. INO-4800 was well tolerated with no treatment-related serious adverse events reported.

Most adverse events were local reactions that were mild in severity and did not increase in frequency with age and subsequent dosing. With that, I will turn it back over to you Joseph. Thank you, Anza.

As I mentioned during my opening remarks, we continue to be focused on advancing INO-4800 through our global INNOVATE Phase 3 trial with the goal to demonstrate INO-4800 's ability to prevent COVID-19 when given as a primary 2-dose vaccination series. I'll now ask Inovio 's Senior Vice President of R&D, Dr.

Kate Broderick, to speak about related efforts in our broader work in infectious diseases.

Kate?.

Thank you so much Joseph, and hello to everyone who's joined us on the call today. It's a real pleasure to be here.

In parallel to our efforts advancing INO-4800, Inovio is also developing INO-4802, which is our next-generation pan - COVID vaccine candidate to combat current and future variance of concern, and potentially also serve as a boost for individuals previously immunized with wild-type [Indiscernible] vaccines.

We presented pre -clinical results on INO-4800 and INO-4802 during this year's ID Week 2021 Conference. Early results demonstrated consistency with Inovio's platform wide safety and tolerability profile, in addition to the ability to generate CD8 and CD4 T cell, as well as binding and neutralizing antibodies against SARS-CoV-2 and the VOCs.

This data is available in pre -print on BioRx under the title, "Design and immunogenicity of a Pan-SARS-CoV-2 synthetic DNA vaccine.

" Our COVID-19 program, encompassing both, our late-stage advancements with INO-4800 and our pre -clinical work with INO-42, builds on our deep experience and expertise in combating infectious diseases and our dedication to supporting global public health.

In another update, since the end of the third quarter, we announced full enrollment of our Phase 1B clinical trial for INO -4500. Our DNA vaccine candidate for Lassa fever.

Our randomized blinded placebo-controlled, dose-ranging study, which is being conducted at the Noguchi Institute for Medical Research in Accra Ghana is the first vaccine clinical trial for Lassa fever ever to be conducted on the African continent where the vital illnesses is endemic.

That is currently no approved vaccine for the vital illness which impact s an estimated 300 thousand people in the region annually and is responsible for 10 % to 16% of hospital admissions in some parts of Liberia and Sierra Leone.

The WHO classifies Lassa fever as one of the pathogens with epidemic potential to be urgently addressed, thereby making the development of a safe and effective vaccine a global health priority.

We are extremely proud to reach this important milestone with many thanks to our partners for completing enrollment in this first ever clinical trial for the Lassa fever on the African continent over the course of 8 months during a global pandemic, and with all the released travel restrictions.

The funding for this trial comes from CEPI, who's grant is supporting the development of INO -4500 against Lassa Fever, as well as INO -4700, our DNA vaccine candidate from [Indiscernible]. And now I will turn the call back to you Joseph. Thank you..

Thank you, Kate. And now Dr. Jeffrey Skolnik, our Senior Vice President of Clinical Development, will provide an update on our other important clinical programs.

Jeffrey?.

Thank you very much, Joseph.

As it relates to our HPV -associated disease programs, we've completed follow-up of our subjects in our REVEAL 1, the first of 2 Phase 3 pivotal studies evaluating VGX-3100 for the treatment of cervical high-grade squamous intra ephitelial lesions caused by HPV -16 and/or HPV -18, for safety and durability, a virological clearance for 18 months following the last administration.

We expect to report our findings from REVEAL 1 later this year. In addition, we're continuing our partnership with Qiagen to co-develop a diagnostic tool to guide the clinical decision-making for the use of VGX-3100 in cervical HSIL. And we look forward to sharing an update on our progress in the coming months.

I'll reveal 2 studies is on track to complete enrollment of approximately 198 adult women with histologically confirmed cervical HCL before the year-end.

Regarding our immuno -oncology efforts, Inovio and our partners continue to evaluate findings from our Phase 1-2 novel combination study of the DNA medicines INO -5401 and INO -9012, in combination with the PD-1 checkpoint inhibitor cemiplimab, which is being jointly developed by Regeneron and Sanofi in treating newly diagnosed glioblastoma or GBM.

And we look forward to sharing 2-year overall survival data, including correlative immunology and tissue data at a pre -conference workshop of the Society for Immunotherapy of Cancer, or SITC, the 36th Annual Meeting and pre -conference programs later this week, where Dr. David Reardon will be presenting and discussing the studies' latest findings.

These will include overall survival at 24 months in both our MGMT promoter methylated and unmethylated subject cohorts, as well as correlative immunology and tissue data. And with that, I'll turn the call back over to Joseph. Thank you very much..

Thank you Jeffrey. As we continue to address difficult-to-treat cancer such as GBM, I want to reiterate our -- my appreciation to our team focused on immuno-oncology and extend our thanks to Regeneron for their continued collaboration. We look forward to sharing further information at SITC later this week.

Next, I will turn the call over to Peter Kies, our CFO, for our third quarter financial summary.

Peter?.

Thanks Joseph. And good afternoon everyone. We ended the third quarter with $394.9 million in cash, cash equivalents, and short-term investments. Our revenue for the third quarter of 2021 was $292,000, which compares to $236,000 for the same period in 2020.

Our total operating expenses were $60.2 million compared to $36.6 million for the same period in 2020. Inovio's net loss for the third quarter of 2021 was $60.2 million or $0.29 per share basic and dilutive, which compares to a net income of 19.2 million or $0.12 per share basic and $0.11 per share dilutive for the quarter ended September 30th, 2020.

Just as a reminder, net income for 2020 -- for the 2020 quarter was primarily due to a 35.3 million change in fair value of the derivative liability related to the embedded conversion feature in our August 2019 convertible bonds. The Company also recorded a gain on investment in affiliate entities of 27 million.

This was primarily related to the sale of its equity investment in GeneOne. Our R&D expenses were $47.1 million for the third quarter of 2021, which compares to $26.5 million for the same period in 2020.

The increase in R&D expenses was primarily related to higher drug manufacturing, outside services, and clinical study expenses related to INO-4800 and INO-4802, and also higher employee and contractor compensation.

This increase was also due to a decrease in the contra revenue and development expenses recorded from grand agreements of $2.4 million, among other variances. Lastly, G&A expenses were $13.2 million for the third quarter of 2021 versus $10.1 million for the same period in 2020.

The increase in G&A expenses was primarily related to an increase in employee compensation, which included non-cash stock-based compensation. This partial -- this was partially offset by lower expenses from work performed related to corporate marketing and communications, among other variances. And with that, I'll turn it back over to you, Joseph..

Thank you Peter. Before we take analyst questions, I want to take a moment to thank and recognize our trial participants, collaborators, and partners across our clinical programs. Without their commitment moving, nothing moves forward. I also want to recognize and express my appreciation to the entire Inovio team for their unwavering efforts.

Our organization's steadfast resolve supporting the global response to COVID-19, as well as critical public health measures worldwide reflects the continued urgency of this pandemic, as well as the potential of Inovio 's DNA medicines platform in combating other infectious diseases, cancers, and HPV -associated diseases.

While we have achieved progress, we understand and accept that there is still much work to do. We remain focused, committed, and vigilant in our efforts. In closing, we are focused on delivering on the benefits of our DNA medicines platform, with 4 distinct global Phase 3 trials for INO-4800 and VGX-3100, respectively, now underway.

So Inovio team is committed and working tirelessly to fulfill the promise of DNA medicines. Our portfolio, as well as our efforts to expand the portfolio of available COVID-19 vaccines, and become the part of global solution against COVID-19 underscores this commitment. With that, let's open the call for questions.

Operator?.

At this time, we will begin the question-and-answer session. [Operator Instructions] At this time, we will pause momentarily to assemble our roster. Our first question comes from Geoff Meacham with Bank of America. Please go ahead..

Hi. Thank you for taking our question. This is Alex on for Geoff.

So firstly, maybe you could talk about how the lifting of the partial clinical holds for the Phase 3 study, how that plays into your Phase 3 development plans, given that you were previously running that study primarily outside the United States? And then secondly, what additional data do you provide to the FDA to review, you mentioned non-clinical, clinical, and device information? Thank you very much..

Yes. Thank you, Alex. We really are not changing our strategy that much. We have focused on global strategy to go take our INNOVATE Phase 3 trial where there is a huge unmet need -- the need for safe and effective vaccines in those countries and the number of cases that exist in these countries.

So that's why we're so excited to have received authorizations in countries like India, Thailand, Brazil, Colombia, Mexico, and the Philippines, as well as the U.S. What the clinical hold lift and actual Phase 3 authorization to proceed from the FDA means is we can now add the U.S. participants into this global trial. And we look forward to adding U.S.

participants based on feasibility and availability of those participants. Second part of your question. Yes, we have provided all of the necessary clinical, pre -clinical, and device-related information that fully satisfy the FDA's reasons for the clinical hold, so we're very excited and pleased about that..

All right. Thank you so much..

Thanks..

Our next question comes from Hartaj Singh of Oppenheimer & Company. Please go ahead..

Great. Thank you, and thanks for -- I got a couple of questions. One is just the data you presented with the patients in homologous boost data.

Assuming you have a positive Phase 3 and go ahead with EUAs in various countries, Joseph, what would you need to file an additional EUA for a booster strategy also, off your Phase 3 for the initial vaccinations? And then number two, your agreements -- your agreement with Colombia -- for example, companies like Vertex have used certain agreements as a framework to have -- make other agreements with other countries all over the world.

Is that the strategy that you are adopting with Colombia, sort of being a test case and then broadening that strategy to other countries? Thanks for the questions..

Yes. Thank you, Hartaj. I'm going to answer the second question first, and I will ask Dr. Anza Mammen to address the first question for us.

But yes, Colombia is the first of, I believe, many countries that Inovio looks forward to doing either advanced market commitment contracts or other collaborative arrangements where we can share our technology or manufacturing capabilities and capacity.

So we really felt that Colombia's government had a positive and constructive outreach to us and we reciprocated properly. So I do think our relationship with Colombia can be an example to other countries. So I do agree a 100% on your sentiments.

Anza, would you like to address the first part of Hartaj's question?.

Sure. Absolutely. Thank you for the question. So just to summarize - so in the Phase 1 trial, we did evaluate a two-dose regimen of INO-4800, followed by a homologous booster, that was an optional booster anywhere between 6 and 10.5 months after the second dose.

And as I mentioned earlier, the safety and tolerability profile was quite favorable and we were able to induce a broad-based immune response with the booster dose. Now, with INNOVATE Phase 3, that will be evaluating INO-4800 in a two-dose regimen, so subjects will be receiving two doses of INO-4800, each administered one month apart.

And -- however, once we are able to establish efficacy in that trial, then we may follow the subjects for a longer period of time following their immune responses over time to further understand what the optimal timing for a booster might be. So that would be a homologous booster setting.

Now, I should mention that Advaccine, our partners in China, are concurrently evaluating INO-4800 as a potential heterologous boost. And so they are initiating a trial in the coming weeks that will evaluate subjects who have received two doses of an inactivated vaccine and followed by a boost with INO-4800.

So with these multiple clinical trials, we hope to further establish INO-4800 as a viable booster, not only in a homologous setting, but also as a heterologous setting, following the primary vaccination series with other COVID-19 vaccines..

Yes. Thank you, Anza..

I hope that covers your question..

So if I can add a little bit, Hartaj, to Anza's really good answer, from a strategic point of view, we realize for a while now, INO-4800 could be a great vaccine for -- as a -- with the safety and hope to demonstrate the efficacy in INNOVATE Phase 3, or Solidarity Phase 3, or both.

It's a great vaccine as a DNA vaccine and will provide attributes that are different than other approved vaccines there -- as a primary series, but we also realized the changing landscape of the need for vaccines, for booster is increasing and maybe even the greater need -- medical need and market need.

So we are looking at the heterologous boost as an expansion of the utility of INO-4800 against this global pandemic, but also looking forward in an endemic stage and as I touched on in my prepared remarks.

So, we think there's a huge advantage for INO-4800 due to its safety and tolerability, and hopefully, we can demonstrate that in a heterologous boost setting, not just from the vaccine -- inactivated vaccine boosting setting, but for other future studies where we can demonstrate the boostability of INO-4800. So please stay tuned for later..

Great. Thank you Joseph. And Joseph just -- I'm sorry, one housekeeping matter. The IP issue seems to be flaring up again with vaccine manufacturers in the U.S. government. There's an article too in the New York Times, I believe, regarding Moderna. Do you have any IP that overlaps with the U.S.

government or any government entity? And again, thank you for all the questions..

Yes. Thank you. We have received DOD funding on some of our device, 3PSP development, but IP belongs to Inovio, so we don't believe there is any overlap, but that's the thing that we -- as we work with various governments, including the U.S. government, we want to be very careful with..

Great. Thank you..

Our next question comes from Gregory Renza of RBC Capital. Please go ahead..

Yes. Good afternoon Joseph and team. Congrats on the clinical lift and progress and thanks for taking my questions..

Thank you..

Joseph, as you've guided towards potential interim efficacy data in the first half of 2022 for INNOVATE, I just wanted to ask you if you could provide some color on what the parameters would be there as far as biologically confirmed cases, the enrollment pace, or at least remind us of some of that as we think about when that could occur.

And related to that, what needs to break right just within the environment for you to reach your target across enrollment countries? It certainly sounded like the clinical lift has been helpful. And then just a second, perhaps related question.

With the clinical hold lift, I'm just curious if you could comment on how you think about the device needing to evolve in order to meet the evolving needs of the international market opportunity for you to deliver doses and 4800, alongside the device to those patients that you talked about in need. Thank you very much..

Yes. Thanks Greg. You had a really good question. I'll try addressing it and if you need deeper answers, I have folks Anza and Jackie and others that can help me out. I would just say the devices are really important and obviously the partial hold was just in the U.S.

so we really didn't have a material impact in opening countries and sites outside the U.S. As we've shown, 6 other country openings for our trial in last several weeks. But it really -- the clinical hold lift and authorization for Phase 3 in the U.S., it provides us additional validation, and it shows that we have met all of the concerns of the U.S.

FDA satisfactorily. That being said, we're really pleased that -- to say that the dosing for INNOVATE Phase 3 trial has already begun and it's underway. And interim efficacy -- it's a case-driven study so magic number is around 150 lab-confirmed cases and of course, interim will be at the 50% of those cases.

So faster re-enroll and the percent of attack rate in those countries or those regions will really impact when exactly where we will meet that 50% efficacy -- these are all blinded until we hit about 75 cases. So that's why we left that as a broadly first half 2022. So that's what we're looking for.

And it's always been the same design from when we started the INNOVATE Phase 3 trial. So our team is working really hard to open these sites, get approvals in the country's open sites, and in all subjects.

Separately, the Solidarity trial is operating independently, and we're really grateful that the WHO has selected, or their independent panel has selected INO-4800 as one of 2 initial vaccines.

And I think there's 2 more being added in the future, but out of 20 or so candidates of second wave COVID-19 vaccines out there, so we're highly grateful for that selection. Obviously, we think we are the leader of the second wave of COVID-19 vaccines, and we have the opportunity to demonstrate our efficacy and safety.

I have no qualms about our safety, but we still have to get to that efficacy data. And we have two shots on the goal with our INNOVATE Phase 3 trial that we're conducting with our partner vaccine, as well as WHO's Solidarity trials. We couldn't be any happier. We're excited in our opportunities here and our team is working really hard to achieve that..

That's helpful Joseph. Thank you again..

Yes. Thank you Greg..

Our next question comes from Charles Duncan of Cantor Fitzgerald. Excuse me. Please go ahead..

Hi Joseph, this is Pete Stavropoulos on for Charles..

Hey Pete..

Congratulations on all the progress made this quarter..

Thank you..

My one question is -- several months ago, India granted an Emergency Use Authorization for a DNA -based COVID-19 vaccine. Can you tell us what you believe are differentiating factors for INO-4800 when compared to ZyCoV-D.

And what advantages could 4800 provide?.

Yes. I think India being a pioneering regulatory -- its regulatory agency having the experience, having the know-how to measure, and test, and grant approval, emergency approval for the Zydus's DNA vaccine. I think it's a tremendous advantage for us to have INO-4800 INNOVATE trial conducting in India.

And as Anza mentioned, there are many other reasons. They have a huge population with a need for additional safe and effective vaccine. The difference between Zydus's DNA and Inovio 's is delivery. We use in vivo electroporation Selectra system that we feel has been demonstrated to optimize the delivery of DNA plasmids.

We've tested this in tens of thousands of administrations. We've done a lot of clinical and preclinical studies around that. So we think our intradermal delivery of INO-4800 would give us a huge potential differentiating factor to Zydus 's DNA. But it's also perhaps more advantageous to be the second in their regulatory process through India.

They have -- India sites have a familiarity of working with DNA vaccines and I think there are other many advantages for India.

So we -- we're very, very fortunate to have authorization in India, and we look forward to really having participants and data come out of India, as well as other parts of the world, in Mexico, Colombia, U.S., as well as Brazil, and other places.

But I think India -- the reason why we highlighted India by Anza is their experience with the previous DNA vaccine..

Thank you. One more question.

Can you provide an update on INO -3107 for RRP?.

Yes. We have Jeffrey Skolnik here. I'm going to give a broad update. Our RRP immunotherapy currently is undergoing Phase 1/2 trial. Enrollment is continuing and we hope to have both immune responses and early clinical benefit data, potentially in the first half of 2022..

Thank you..

Yes..

Congratulations again..

Yes. Thank you Pete..

And our next question comes from Aydin Huseynov of Benchmark. Please go ahead..

Hi, Joseph and the team..

Hi Aydin..

Thank you for taking my questions. Hi Joseph, and congratulations on the progress this quarter, especially the announcement this morning with the clearance. I have a couple of questions. First, I want to ask you about the WHO Solidarity trial.

If you could share with us the estimates of when do you think we will see the results from Solidarity trial? Will it be before INO - A3 is out or after INO - A3 is out? And also, if you could give us some ideas about how the design of the trial is different from INNOVATE and how much of the overlap is in terms of the contracts being enrolled in the trial..

Yeah. In terms of speaking around the WHO trial, we have to defer to their communications. But what I can tell you -- and I'll again turn to Anza. But the difference is in the trial design. But the overlaps, there is two countries that overlaps that within the INNOVATE and Solidarity, and those are Colombia and Philippines.

But the actual sites do not overlap. I think there's some synergies in that but we don't expect there to be any conflict.

Anza, would you like to touch on the differences in overall design of the trial?.

Yes. Sure, Joseph. Thank you. Thank you for the question. All-in-all, I would say that the designs are very similar between these Phase 3 Trials. INO-4800 will be administered in a 2-dose regimen with 2 milligram dose, and each dose will be administered 1 month apart, and the surveillance period will begin 14 days after the second dose.

In a very similar way, both trials will be collecting cases that are virologically confirmed. And I think in terms of the timing of getting the interim results, that's largely going to be dictated by the force of infection, as well as the rate in which each of these trials will enroll. It's really -- I think probably not.

I don't think we can really project at this point, which trial will provide the interim efficacy data first, but we're really hoping that both of these trials would be able to enroll efficiently.

We have, I think both selected countries, we're in their remains and unmet medical need, that the vaccination rates are still relatively low, and the force of infection remains quite impressive. And so I think both trials are well-positioned to accrue the cases.

But again, the rate with which we are able to accrue the cases, I think remains to be seen. I think at this point, it's our projection that -- or our target that we'll be able to do our interim analysis within the first half of next year. I'm not really able to comment on the timing with regards to the WHO Solidarity trial.

I'd rather defer that you -- that those questions be post to WHO..

Yeah. Thank you, Anza..

Okay..

And I would say that it's -- our team is focused on enrolling INNOVATE as rapidly as possible and also providing the support to WHO for their Solidarity but they're driving that trial and I'm sure the efficiency and productivity is very good with the WHO. We look forward to having both sets of data as soon as they become available..

Okay. Thank you. This is helpful. Another question I have is on duration of protection. Right now, with all the vaccines on the market, it seems that we need to have boosters every 6 to 12 months after the second dose.

I think you mentioned the longer duration of protection for INO-4800 so I wanted to ask how much longer do you think this protection is expected to be and whether this is based on presumed cellular immunity enrollment. Thank you..

I'll pick that. Yes, the benefits of having T cell responses along with the antibody responses with INO-4800, we believe should provide a longer potential protection. But of course, we have to demonstrate that in clinical trial setting.

So we look forward to gathering those data in the Phase 3 trials, and of course, from our pre -print in Med Archive, we have seen antibodies persist through the 6 months period, and then were boostable with our homologous [Indiscernible].

Strictly speaking of the clinical data, we think -- we're very excited about the potential of boostability of INO-4800 but we'll follow the immune responses to determine the durability of the immune response and also gather the data for durability of protection in the future readouts..

All right, thank you. Very helpful, Joseph. Congratulations for the progress in this quarter..

Thank you..

Next question comes from Yi Chen with H.C. Wainwright. Please go ahead..

Thank you for taking my questions. Hi, Joseph..

Hi..

Could you talk about your expectations for the 18-months data readout for the REVEAL 1 trial versus the data previously reported for 36th week?.

Yes. Well, I like to ask Dr. Jeffrey Skolnik to address that broad question..

Sure. Thanks Joseph. And thank you for the question. As you know, we shared earlier this year that from our first of the Phase 3 pivotal studies, we reveal 1 study.

We were able to show a statistically significant difference between women with cervical HSIL who had received VGX-3100 versus those who had received placebo with respect to both histological clearance and viral clearance as well. At that week, 36 time points. And again, as you know, that's the primary endpoint of the study. We met that.

We also met many of the secondary objectives. and again, I had previously shared this. Really, the week 88 data was meant to give us confidence around the durability of the immune response and potentially to demonstrate whether or not there's still virus. I will note that we previously demonstrated that we have shown durability in our Phase 2b study.

So you may be aware that we previously published on those data demonstrating up to 18 months durability in both the regression and clearance. And importantly, again, an absence of virus in the cervix at that 88 time point. We don't anticipate essentially any surprises. We really expect to see what we have already shown in a randomized study.

And again, that would be related to the durability of response, and also immunogenicity..

Got it. Thank you. And regarding the phase 1, 2 trial of 5401 for newly diagnosed GBM, the 24 months data is coming out soon.

So can you talk about what are the potential next steps after that?.

Joseph, would you like me to?.

Yeah..

Happy to answer that. We're very pleased, as you say it, being able to present our data later this week at the pre -conference symposium at the SITC meeting, where Dave Reardon will be presenting the OS24 data, again, with some updated immunology and some tissue-based data which we're particularly excited.

I think utilizing those data, along with what we've known before -- again, we previously demonstrated median overall survival in our MGMT-unmethylated population that's been higher than what we would've expected with respect to historical controls, and we still have yet to have reached median overall survival in our MGMT - methylated patients.

That's a good thing that we haven't met that median yet. Pending those data, we'll really make decisions as to where we can bring this opportunity forward but in general, we're very encouraged by what certainly the key opinion leaders and the scientists and clinicians are telling us in this space.

We're very encouraged by the fact that again, we have the opportunity to present at a peer-reviewed scientific meeting. And so I look forward to next opportunities specifically for 5401 in the GBM space..

Thank you.

Thank you..

Next question comes from Kelechi Chikere from Jefferies. Please go ahead..

Yes. Thank you for fitting me in. Congratulations on the removal of the partial clinical hold this morning, as well as the ability to enroll patients in the U.S. now. Related to that, could you provide any additional color on your strategy around enrollment in the various countries? Obviously, you want cases, that's how you get to your interim analysis.

But that -- but that has to be balanced with the fact that some of these countries have variants that at least in some Phase 3s have shown reduced efficacy for the vaccine. Any color there would be really helpful..

Yep. Hi, Kelechi. Absolutely. There are multiple variants around the world, but the most predominant one is the Delta.

Of course, these things can change and in another month or few weeks, but -- and we have demonstrated in our own internal testing, and we published some of those in our pre -print that INO-4800 does generate immune -- both antibodies and T cell s against the Delta variant. The other analysis that really helps us is the Zydus 's DNA vaccine.

They were able to demonstrate efficacy with their three-dose DNA regimen, not using the same delivery system that Inovio is. With Selecta, we think that's -- and they were able to achieve their efficacy during the spike of the Delta variant in India.

So we're very optimistic that INO-4800 would fare well around the globe, especially in the countries that we have selected. In terms of where, we have selected these countries and we're recruiting these sites within those countries to maximize our likelihood of increasing the probability of getting to our endpoint as soon as possible.

We have a very sophisticated information hub. It allows us to make those decisions pretty much in real time. We try to use a lot of intelligence behind our resource allocation to these various regions..

Got it. That's helpful. And another question, assuming success with the INNOVATE trial or even the Solidarity trial in 2022, how much vaccine do you anticipate being able to launch with? And how much vaccine do you anticipate producing in 2022 as well? The vaccine as well as the device..

Yes. We have been working to scale up our plasmid -manufacturing capacities, working with various global collaborators like Thermo Fisher and others that we have in our consortium. And of course in the device side, our 3 PSP commercial device is getting prepped and ready to be scaled up. These work are getting done in parallel.

These are intensive efforts to do that. Our current plan is to -- assuming we have the interim efficacy in the first half of '22, we plan to utilize that data along with the safety -- to safety data to that point to pursue emergency-use approvals in various countries where the mechanisms are available.

And of course, we would probably look to the countries that we're upgrading our Phase 3 trials in first. We also plan to pursue the emergency-use license through the WHO.

And with the full efficacy data, as well as the full safety follow-up data, we plan to utilize the data in 2023, potentially for full licensures in these countries, as well as potentially PLA in the U.S. and EMEA through Europe. We have a pretty ambitious global plan. We're looking emergency approvals first in '22 and then full licensures in 2023..

Okay. Thank you..

Yes. Thanks..

This concludes our question-and-answer session. At this time, I will now turn it back to Mr. Joseph Kim for any closing remarks..

Thank you. Thank you for listening and thank you for great questions from our top analysts. Last several -- last couple of months, our team and our collaborators have made tremendous progress. And as I mentioned before, we still have a lot to do.

We have both INNOVATE and Solidarity trials for INO-4800 and potentially the interim efficacy data in the first half, which isn't that far off, which is very exciting. We have our REVEAL 2 and REVEAL 1 trials completing for VGX-3100. We expect REVEAL 2 to fully enroll before the year-end, as it was mentioned by Jeffrey Skolnik.

These are very transformative and exciting times for Inovio. I feel like Inovio is at the cusp of transforming to -- from a pre -commercial R&D-based Company to a commercial Company in the next several quarters. This is very exciting and tremendous time for us and I want to thank you all for sharing in these details and sharing in our excitement.

Thank you very much. And I look forward to the next call in a few months, where I hope we're much further along in many of these aspects. Thank you very much..

The conference is now concluded. Thank you for joining today's presentation. You may now disconnect..