This conference call transcript was computer generated and almost certianly contains errors. This transcript is provided for information purposes only.EarningsCall, LLC makes no representation about the accuracy of the aforementioned transcript, and you are cautioned not to place undue reliance on the information provided by the transcript.
spk15: Welcome to the Inovia Third Quarter 2021 Financial Results Conference Call. All participants will be in listen-only mode. Should you need assistance, please signal a conference specialist by pressing the star key followed by a zero. After today's presentation, there will be an opportunity to ask questions. To ask a question, you may press star then one on your telephone keypad. To withdraw your question, please press star then two. Please note, this event is being recorded. I would now like to turn the conference over to Ben Matan Senior Director of Investor Relations. Please go ahead.
spk06: 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 Keyes, Chief Financial Officer, Dr. Jackie Shea, Chief Operating Officer, Dr. Laurent Humeau, Chief Scientific Officer, Dr. Jeffrey Skolnick, Senior Vice President of Clinical Development, Dr. Anza Mammon, 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 30th, 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's various therapeutic and vaccine programs across our DNA medicine 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, INO4800, with our partner vaccine, as well as our announcement this morning that the U.S. Food and Drug Administration has lifted the partial clinical hold of 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 Medicine, which include clinical and regulatory development 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 is concluded. Now, I'd like to turn the call over to Inovio's President and CEO, Dr. Joseph Kim.
spk12: Thank you, Ben, and good afternoon, everyone. I appreciate you taking time to join us this afternoon. Let me begin by stating how pleased I am with the progress that we've made over the last few months, and I'm grateful for the opportunity to share some additional context and discuss our efforts during this call. The global community continues to deal with the impact of the COVID-19 pandemic, and evolving variants of concern. Global vaccination rates are approximately 50%, but rates are still below 5% in certain areas of the world. Too many people are still without access of COVID-19 vaccines. Inovio recognizes the important role we can play in supporting the global response to this public health crisis and remain focused on the continued need for safe and effective vaccines for both as primary vaccination series and as a booster vaccination. We're excited that dosing for our innovate trial is underway and enrollment continues globally. To that point, and just to recap, we have received regulatory authorization to proceed in a total of seven countries to date, which includes 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 three 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 three 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, INO4800, 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 a 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 INO4800 is one of the two vaccine candidates to be initially included in the Solidarity Trial Vaccines, which is an international randomized controlled phase three efficacy trial sponsored, funded, and conducted by the WHO. Per the 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 community still requiring greater access to vaccines, we believe certain positive attributes of a DNA medicines platform like ours, and specifically INO4800, could aid public health measures against infectious diseases like COVID-19. INO4800 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 thermal stability profile to facilitate global distribution. Additionally, Inovio's partner, a vaccine, is sponsoring a booster study in China where INO4800 is given as a booster after primary vaccination with an inactivated COVID-19 vaccine. Collectively, these trials are a testament to the attributes of INO4800 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 shared a positive data on homologous boosting from our phase one clinical trial as a preprint in MedArchive. The paper, which Dr. Anza Mamun will describe in further detail later in the call, found that INO4800 produced broad-based immune responses and was well tolerated as both a two-dose series and as a homologous booster in adults of all ages. Separately from our COVID-19 program, Inovio recently completed enrollment in our Lassa fever vaccine trial, which is 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 Mammon, our SVP of Clinical Development for COVID-19 Vaccine Program. Anza?
spk04: Thank you, Joseph. As Joseph shared in his opening remarks, Inovio's COVID-19 vaccine candidate, INO4800, is one of two vaccines currently included in the solidarity trial vaccine, a phase three 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 III efficacy trial is being conducted separately from Innovio's Global Phase III efficacy segment of Innovate. As for Innovate Phase III, We have now received regulatory authorizations in a total of seven 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 vaccines. 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 INO4800 in a two-dose regimen using the two milligram dose administered one month apart in a two-to-one randomization ratio between INO4800 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 I clinical data on homologous boosting of INO4800 as a preprint in MedArchive. The paper titled SARS-CoV-2 DNA Vaccine INO4800 Induces Durable Immune Responses Capable of Being Boosted in a Phase I Open Label Trial found that among the full phase one cohort of 120 participants, 99 or 82.5% of participants opted to receive a booster or third dose of INR4800 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 two-dose series and as a homologous booster dose in adults of all ages. Notably, we observed a durable antibody response six months following the second dose and significantly increased antibody and T cell responses following a homologous booster dose administered six to ten and a half months following the second dose. INO4800 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.
spk12: Thank you, Anza. As I mentioned during my opening remarks, we continue to be focused on advancing INO4800 through our global Innovate Phase 2 trial with the goal to demonstrate INO4800's ability to prevent COVID-19 when given as a primary two-dose vaccination series. I'll now ask Inovio Senior Vice President of R&D, Dr. Kate Broderick, to speak about related efforts in our broader work in infectious diseases. Kate?
spk00: 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 INO4800, Inovio is also developing INO4802, which is our next generation pan-COVID vaccine candidate to combat current and future variants of concern and potentially also serve as a boost for individuals previously immunized with wild type match vaccines. We presented preclinical results on INO4800 and INO4802 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 cells, 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 Synthetic DNA Vaccine. Our COVID-19 program, encompassing both our late stage advancements with INO4800 and our preclinical work with INO4802, 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 INO4500, our DNA vaccine candidate for Lassa fever. Our randomized blinded placebo control dose ranging study which is being conducted at the Noguchi Memorial 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 viral illness is endemic. There is currently no approved vaccine for the viral illness, which impacts an estimated 300,000 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 a Lassa fever on the African continent over the course of eight months during a global pandemic and with all the related travel restrictions. The funding for this trial comes from CEPI, whose grant is supporting the development of INO4500 against Lassa fever, as well as INO4700, our DNA vaccine candidate for MERS. And now I'll turn the call back to you, Joseph. Thank you.
spk12: Thank you, Kate. And now Dr. Jeffrey Skolnick, our Senior Vice President of Clinical Development, will provide an update on our other important clinical programs. Jeffrey?
spk05: 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 two phase three pivotal studies evaluating VGX3100 for the treatment of cervical high-grade squamous intraepithelial lesions caused by HPV16 and or HPV18 for safety and durability of 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 clinical decision-making for the use of VGX3100 in cervical H-cell, and we look forward to sharing an update on our progress in the coming months. Our REVEAL-2 study is on track to complete enrollment of approximately 198 adult women with histologically confirmed cervical H-cell before the year end. Regarding our immuno-oncology efforts, Inovio and our partners continue to evaluate findings from our Phase I-II novel combination study of the DNA medicines INO5401 and INO9012 in combination with the PD-1 checkpoint inhibitor simiplimab, which is being jointly developed by Regeneron and Sanofi in treating newly diagnosed glioblastoma, or GBM. And we look forward to sharing two-year overall survival data including correlative immunology and tissue data at a pre-conference workshop of the Society for Immunotherapy of Cancer, or CITC, the 36th annual meeting and pre-conference programs later this week, where Dr. David Reardon will be presenting and discussing the study's 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.
spk12: Thank you, Jeffrey. As we continue to address difficult-to-treat cancers such as GBM, I want to reiterate 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 CITSE later this week. Next, I will turn the call over to Peter Keyes, our CFO, for our third quarter financial summary. Peter?
spk09: 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. Anovio'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 30, 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 Gene 1. 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 grant 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 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.
spk12: 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, nothing moves forward. I also want to recognize and express my appreciation to the entire Inovio team for their unwavering efforts. Our organization's success results 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 four distinct global phase three trials for INO4800, and VGX3100 respectively now underway, the 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?
spk15: At this time, we will begin the question and answer session. To ask a question, you may press star then 1 on your telephone keypad. If you are using a speakerphone, please take up your handset before pressing the keys. To withdraw your question, please press star then 2.
spk13: At this time, we will pause momentarily to assemble our officer. Our first question comes from Jeff Meacham, Bank of America.
spk15: Please go ahead.
spk10: Hi, thank you for taking our question. This is Alex on for Jeff. So firstly, maybe you could talk about how the lifting of the partial clinical hold for the Phase III study, how that plays into your Phase III 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.
spk12: Yeah, thank you, Alex. So we really are not changing our strategy that much. You know, 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 an actual phase three authorization to proceed from the FDA means is we can now add the US participants into this global trial. And we look forward to adding US participants based on feasibility and availability of those participants. Second part of your question, yes, we have provided all of the necessary clinical, preclinical, and device-related information that fully satisfied the FDA's reasons for the clinical hold. So we're very excited and pleased about that.
spk13: Great. Thank you so much. Thanks.
spk15: The next question comes from of Oppenheimer and Company. Please go ahead.
spk14: Great. Thank you. And thanks for, I got a couple of questions. One is just the data you presented with the patients and homologous boost data. You know, assuming you have a positive phase three and you go ahead with EUAs in various countries, Joseph, what will you need to file an additional EUA for a booster? strategy also, you know, after your phase three for the initial vaccinations. And then number two, you know, your agreement with Columbia, you know, for example, companies like Vertex have used certain agreements as a framework to make other agreements with other countries all over the world. You know, is that the strategy that you're adopting with Columbia as sort of being a test case and then, you know, broadening that strategy to other countries? Thanks for the question.
spk12: Yeah, thank you, Hartaj. I'm going to answer the second question first, and I will ask Dr. Anzalmaman to address the first question for us. But yeah, 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 100% on your sentiments. Anza, would you like to address the first part of Hartaj's question?
spk04: Sure, absolutely. Thank you for the question. So just to summarize, so in the phase one trial, we did evaluate a two-dose regimen of INO4800, followed by a homologous booster that was an optional booster, anywhere between six and 10 and a half 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 INO4800 in a two-dose regimen. So subjects will be receiving two doses of INO4800, each administered one month apart. And however, you know, 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 Advaxine, our partners in China, are concurrently evaluating INO4800 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 INO4800. So with these multiple clinical trials, we hope to further establish INO4800 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. Yeah. Thank you, Anzal. So hopefully that covers your question.
spk12: So if I can add a little bit, Arkash, to Anzal's really good answer. From a strategic point of view, we realize for a while now, the final 4800 could be a great vaccine with the safety and hope to demonstrate the efficacy and innovate phase three or solidarity phase three 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 realize the changing landscape of the need for vaccines for booster is increasing and maybe even be greater need, medical need and market need. So we are looking at heterologous boost as an expansion of the utility of INO4800 against this global pandemic, but also looking forward in an endemic stage, as I touched on in my prepared remarks. So we think there's a huge advantage for INO4800 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 INO4800. So please stay tuned for later.
spk14: Great. Thank you, Joseph. And Joseph, just, I'm sorry, one housekeeping matter. You know, the IP issue seems to be flaring up again with vaccine manufacturers in the U.S. government. There's an article today in the New York Times, I believe, regarding Moderna. Do you have any IP, you know, that overlaps with the U.S. government or any government entity? And again, thank you for all the questions.
spk12: Yeah. 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.
spk13: Great. Thank you. Next question comes from Gregory Renta of RBC Capital.
spk07: Please go ahead. Yes, good afternoon, Joseph and team. Congrats on the clinical lift in 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 targets across enrollment countries? Certainly something like the clinical holistic 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 talk about in need. Thank you very much.
spk12: Yeah, thanks, Craig. A lot of really good questions. So 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 US. So we really didn't have material impact in opening countries and sites outside the U.S., as we've shown six other country openings for a trial in the last several weeks. But really, the clinical hold lift and authorization for phase three 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 to say that the dosing for Innovate Phase 3 trial has already begun and is 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, you know, faster 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 rate. 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, you know, our team is working really hard to open these sites, get approvals in the countries, open sites, and enroll subjects. Separately, the Solidarity Trial is operating independently. And we're really grateful that the WHO has selected, or their independent panel has selected, IN04800 as one of two initial vaccines. And I think there's two 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 COVID-19 vaccines, and we have the opportunity to demonstrate our efficacy and safety. You know, 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 2 trial that we're conducting with our partner of vaccines. as well as WHO's solidarity trial. So we couldn't be any happier or excited in our opportunities here. And our team is working really hard to achieve that.
spk13: That's helpful, Joseph. Thank you again. Yep. Thank you, Greg. Our next question comes from Charles Duncan of Cantor Fitzgerald.
spk15: Excuse me, please go ahead.
spk11: Hi, Joseph. This is Pete for Charles. Hey, Pete. Congratulations on all the progress made this quarter. Thank you. One question is, you know, 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, you know, 4800 when compared to Zycov-D and what advantages could 4800 provide?
spk12: Yeah, you know, I think India being a pioneering regulatory agency, having the experience, having the know-how to measure and test and grant approval, emergency approval for the Zytis' DNA vaccine, I think is a tremendous advantage for us to have INO4800 innovate trial conducting in India. And as Anza mentioned, there are many other reasons, you know, they have a huge population with a need for additional safe and effective vaccine. The difference between Zytosys DNA and Inovios 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 INO4800 would give us a huge potential differentiating factor to Zytis's DNA. But it's also perhaps more advantageous to be the second in their regulatory process through India. So they have, you know, India sites have a familiarity of working with DNA vaccines, and I think there are other many advantages for India. So 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, US, as well as Brazil and other places. But I think India, the reason why we highlighted India is their experience with the previous DNA vaccine.
spk11: Thank you. Thank you. One more question. Can you provide an update on ENO3107 for RRP?
spk12: Yes. We have Jeffrey Skolnick here, but I'm going to give a broad sort of update Our RRP immunotherapy currently is undergoing phase 1 slash 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. Yep.
spk11: Thank you. Congratulations again.
spk13: Yeah.
spk15: Thank you, Pete. Our next question comes from Aiden Horsenault, Benchmark. Please go ahead.
spk02: Hi, Joseph and the team.
spk12: Hi.
spk02: Thank you for my questions. Hi, Joseph. And congratulations on the progress this quarter, especially the announcement this morning with the ADA 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'll see the results from Solidarity Trial? Will it be before Innovate readout or after the Innovate readout? 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 countries being enrolled in the trial.
spk12: 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 differences in the trial design. But the overlaps, there's two countries that overlaps that within the Innovate and Solidarity, and those are Colombia and Philippines, but the actual sites do not overlap. So, you know, 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?
spk04: Yes, sure, Joseph. Thank you. Thank you for the question. So all in all, I would say that the designs are very similar between these phase three trials. INO4800 will be administered in a two-dose regimen with a two milligram dose. And each dose will be administered one month apart. And the surveillance period will begin 14 days after the second dose. So 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. So 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 will be able to enroll efficiently. We have, I think, both selected countries wherein there remains an 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. So I think at this point, it's our projection 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 Trust. I'd rather defer that those questions be posed to WHO.
spk12: Thank you, Anza. And, you know, I would say that our team is focused on 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. So we look forward to having both sets of data, you know, as soon as they become available.
spk02: Okay, thank you. This is helpful. And another question I have is on duration of protection. So right now, with all the vaccines on the market, it seems that we need to have boosters every six to 12 months after the second dose. I think you mentioned the longer duration of protection for INR or for 800. 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.
spk12: Yeah, I'll take that. Yes, you know, the benefits of having T-cell responses along with the antibody responses with INO4800, we believe, should provide a longer potential protection. But of course, we have to demonstrate that in clinical trial settings. So we look forward to gathering those data in the phase three trials and of course from our preprint in MedArchive we have seen antibodies persist through the six months period and then were boostable with our homologous boost. So strictly speaking of the clinical data we think the We're very excited about the potential of boostability of INO4800, 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.
spk02: All right. Thank you. Very helpful, Joseph. Congratulations for the progress in this quarter.
spk15: Thank you. Next question comes from Yi Chen of H.C. Wainwright. Please go ahead.
spk03: Thank you for taking my questions. Hi, Joseph. Hi. Could you talk about your expectations for the 18-month data readout for the REVIEW-1 trial versus the data previously reported for 36 weeks?
spk12: Yeah. Well, I'd like to ask Dr. Jeffrey Skolnick to address that broadly of his question.
spk05: Sure. Thanks, Joseph, and thank you for the question. So, you know, as you know, we shared earlier this year that from our first of the phase three pivotal studies, the REVEAL-1 study, Dr. We were able to show a statistically significant difference between women with cervical age, so who had received the GX 3100. Dr. versus those who had received placebo with respect to both histological clearance and viral clearance as well at that week 36 time point and again, as you know. Dr. And that's the primary endpoint of the study. So we met that we also met many of the secondary objectives. Dr. And, you know, again, 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've 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-month durability in both the regression and clearance, and importantly, again, absence of virus in the cervix at that 88-week time point. So 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.
spk03: Got it. Thank you. And regarding the phase 1-2 trial of 5401 for newly diagnosed GDN, the 24-month data is coming out soon. So can you talk about what are the potential next steps after that?
spk05: Joseph, would you like me to? Yeah, happy to answer that. So, you know, we're very pleased, as you say, being able to present our data later this week at the pre-conference symposium at the CITSE 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've previously demonstrated median overall survival in our MGMT unmethylated population that's been higher than what we would have 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. And so 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 a next opportunity specifically for 5401 in the GBM space.
spk13: Thank you. Thank you.
spk15: Next question comes from . Jefferies, please go ahead.
spk08: 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 US now. I guess 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'll get to your interim analysis. But I guess that has to be balanced with the fact that some of these countries have variants that at least in some phase threes have shown reduced efficacy for the vaccine. Any color there would be really helpful.
spk12: Yep. Absolutely. You know, there are multiple variants around the world, but the most predominant one is the Delta. Of course, these things can change in another month or a few weeks, but And we have demonstrated in our own internal testing and we've published some of those in our preprint that INO4800 does generate immune both antibodies and T cells against the Delta variant. The other analysis that really helps us is the the Zytus DNA vaccine, you know, they were able to demonstrate efficacy with their three-dose DNA regimen, not using the same delivery system that Inovio is with Selectra. We think that's, and they were able to achieve their efficacy during the spike of the Delta variant in India. We're very optimistic that INO4800 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. So we have a very sophisticated information hub that allows us to make those decisions pretty much in real time. So we try to use a lot of intelligence behind our resource allocation to these various regions.
spk08: Got it. That's helpful. And I guess another question, I guess 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? So the vaccine as well as the device, I guess.
spk12: Yeah, 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 3PSP commercial device is getting prepped and ready to be scaled up. So these work are getting done in parallel. So 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 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 operating our phase three 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 BLA in the US and MAA through Europe. So we have a pretty ambitious global plan. We're looking emergency approvals first in 22 and then full licensures in 2023.
spk13: Okay, thank you. Yep, thanks.
spk15: This concludes our question and answer session at this time. I'll now turn it back to Mr. Joseph Kim for any closing remarks.
spk12: Thank you. Thank you. You know, thank you for listening and thank you for great questions from our top analysts. You know, 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 INO4800, 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 BGX 3100. We expect Reveal 2 to fully enroll before the year end, as it was mentioned by Jeffrey Skolnick. So these are very transformative and exciting time for Inovio. I feel like Inovio is at the cusp of transforming from a pre-commercial R&D based company to a commercial company in the next several quarters. So 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. So 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.
spk15: Thank you for attending today's presentation.
spk13: You may now disconnect.
Disclaimer