Q4 2020 Inovio Pharmaceuticals Inc Earnings Call

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Operator: Good day, and welcome to the Inovio 4th quarter 2020 financial results conference call. All participants will be in a listen-only mode.

Good day and welcome to the and all of your fourth quarter, 'twenty and 'twenty financial results Conference call. All participants will be in a listen only mode should you need assistance. Please signal a conference specialist by pressing Star then zero. After today's presentation there'll be an opportunity to ask questions to ask a quick.

Operator: Should you need assistance, please signal a conference specialist by pressing star, then zero. After today's presentation, there will be an opportunity to ask questions. To ask a question, you may press star, then 1 on a touchtone phone.

And you May Press Star, then one on and I touched on phone.

Operator: To withdraw your question, please press the star, then please note this event is being recorded. I would now like to turn the conference over to Ben Matone. Please go ahead. Thank you, operator. Good afternoon, and thank you for joining the Inovio fourth quarter and year-end 2020 earnings conference call. The callers from the company are Dr. Joseph Kim, President and CEO, Mr. Peter Kies, Chief Financial Officer, Dr. Jackie Tse, Chief Operating Officer, Dr. Lermont Emo, Chief Scientific Officer, Dr. Kate Broderick, Senior Vice President of Research and Development, and Dr. Prakash Bhuyan, Senior Vice President of Clinical Development and Medical Lead for RevealOne, the company's Phase III clinical trial for cervical

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 Bend My tone. Please go ahead.

Thank you operator, good afternoon, and thank you for joining the <unk> fourth quarter and year end 2020 earnings conference call.

The call from the company.

And on the call from the company are Dr. J, Joseph Kim President and CEO, Mr. Peter Keyes, Chief Financial Officer Dr.

Dr. Jackie say, Chief operating officer, Dr. Larry Martin M O Chief Scientific Officer, Dr. Kate Brodrick, Senior Vice President of research and development and Dr. Prakash Gui Arndt Senior Vice President of clinical development and medical leave for reveal one and the company's phase III clinical trial for cervical dysplasia.

Operator: On today's call, we will review our corporate and financial information for the fourth quarter and full year ended December 31st, 2020, as well as provide an update on our clinical program's progress, which includes our COVID-19 vaccine program and today's release regarding our phase three clinical study for cervical dysplasia known as Reveal 1. This call is being webcast live on our website, ir.inovio.com, and a replay will be made available.

For today's call, we will review, our corporate and financial information for the fourth quarter and full year ended December 31, 2020, as well as provide and update on our clinical programs progress, which includes our COVID-19 vaccine program and today's release regarding our phase III clinical study for cervical dysplasia and as reveal one.

This call is being webcast live on our website IR dot and Novo dot com and a replay a replay will be made available.

Ben Matone: Following prepared remarks, we will be conducting a question and answer segment reserved for the Equity Research Channel. During the course of this 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 of DNA medicine, which include clinical and regulatory developments and timing of clinical data readouts, along with capital resources and strategic matters, as well as the impact of the COVID-19 pandemic on Inovio's business operations. All of these statements are based on the beliefs and expectations of management as of today. These statements involve certain assumptions, risks, and uncertainties that could cause actual results to differ materially.

Following prepared remarks, we will be conducting a question and answer segment reserved for equity research analysts during.

During the course of this 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 and develop and nobody was integrated platform of DNA medicines, which include clinical and regulatory developments and timing of clinical data readouts, along with capital resources and strategic matters as well as the impact of the COVID-19 pandemic and I know he was business operations.

All of these statements are based on the beliefs and expectations of management as of today. These statements involve certain assumptions risks and uncertainties that could cause actual results to differ materially.

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'd now like to turn the call over to and nobody was president and CEO Dr. Joseph Kim.

Thank you Ben and good afternoon, everyone.

We have a lot to discuss following this afternoon space 331, and their announcements and I wanted to ensure we cover our other key programs and allow time for analyst questions.

Ben Matone: 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 10k filing with the SEC. I would now like to turn the call over to Inovio's President and CEO, Dr. Joseph Kipp. Thank you, Ben. And good afternoon, everyone

Well, we know that you are all eager to get updates about our COVID-19 vaccine program I want US first spend some time on our latest announcements for reveal one trial and what this means for both H b therapeutic landscape.

And there's no real platform validation later in the call Doctor for cash Boolean and Doctor and Kate Brodrick, well discuss the latest developments and our HPV and COVID-19 vaccine programs and also our CFO, Peter keys, well outlined and <unk> strong financial position.

Dr. Joseph Kim: We have a lot to discuss following this afternoon's Phase 3 BGX 3100 announcement, and I want to ensure we cover our other key programs and allow time for endless questions. While we know that you are all eager to get updates about our COVID-19 vaccine program, I want to first spend some time on our latest announcement about the Revio 1 trial and what this means for both the HP therapeutic landscape and Inovio platform validation.

<unk> to support our deep pipeline clinical development and anticipated commercialization of multiple products over the next several years.

What does today's news reveal one top line data means for the patients for <unk>.

Today's date of announcement represents a potential big step forward towards a therapeutic option for women, who currently suffer from high grade cervical dysplasia, and who would like to avoid surgery, which is the current standard of care.

Dr. Joseph Kim: Later in the call, Dr. Prakash Buyan and Dr. Kate Broderick will discuss the latest developments in our HPV and COVID-19 vaccine programs. Additionally, our CFO, Peter Kies, will outline Inovio's strong financial position to support our deep pipeline, clinical development, and anticipated commercialization of multiple products over the next several years.

The data demonstrated that and responders three doses of V. J F 3100 resulted and regression of high grade dysplasia and clearance of underlying HPV 16, and <unk> 18, and virus, which causes the disease and the first place.

Today also represents a giant milestone for the company.

Dr. Joseph Kim: What does today's news of reveal one top line data mean for the patients for Inovio? Today's data announcement represents a potential big step forward towards a therapeutic option for women who currently suffer from high-grade cervical dysplasia and who would like to avoid surgery, which is the current standard of care. The data demonstrated that in responders, three doses of VGX-3100 resulted in regression of high-grade dysplasia and clearance of the underlying HPV-16 and or 18 virus, which caused the disease in the first place. Today also represents a giant milestone for the company.

This afternoon's release and positive reveal one efficacy data is the first phase III data reported by our company for you and nobody else DNA Medicine technology.

Further validating the company's platform technology that supports all of our therapeutic areas of focus.

We are proud to advance the development of P. J F 3100 and.

The first DNA medicine to achieve efficacy endpoints and a phase III clinical trial.

And I'm, so thankful for all trial volunteers study staff and partners as well as and the team who are dedicated to bringing D. G X 3100 and.

A much needed non surgical therapeutic option, another step closer to commercialization and especially in the face of a global pandemic.

Dr. Joseph Kim: This afternoon's release of positive Revio 1 efficacy data is the first phase 3 data reported by our company for Inovio's DNA medicine technology, further validating the company's platform technology that supports all of our therapeutic areas of focus. We are proud to advance the development of BGX3100 as the first DNA medicine to achieve efficacy endpoints in a Phase III clinical trial. I am so thankful for all trial volunteers, study staff, and partners as well as the Inovio team who are dedicated to bringing VGX 3100 as a much needed non-surgical therapeutic option, another step closer to commercialization, especially in the face of a global pandemic.

Before I turn it over to Dr. <unk>, who will discuss reveal one data and greater depth and doing that remind everyone that reveal and is the first of two phase III trials with Fuji ex 3100 for the treatment of cervical H. So.

And these trials are still ongoing.

Reveal and subjects will continue to be followed for safety and durability of responses for 18 months. Following the last administration of <unk>.

For the V P. J F 3100 for placebo with the trial competing later this year.

Reveal two continues to enroll across eight countries, including the us.

Both trials are designed to assess and confirm the safety Tolerability and efficacy of video ex 3100, and women 18 years of age or older.

Dr. Joseph Kim: Before I turn it over to Dr. Booyan, who will discuss REVEAL-1 data in greater depth, I do want to remind everyone that REVEAL-1 is the first of two Phase III trials with VGX3100 for the treatment of cervical H cells, and these trials are still ongoing. The V01 subjects will continue to be followed for safety and durability of responses for 18 months following the last administration of either VGX3100 or placebo, with the trial completing later this year. Revio, too, continues to enroll patients across eight countries, including the U.S.

Histologically confirmed cervical dysplasia or <unk>.

With an eye towards optimizing the commercial attractiveness of Egypt 3100, just last week <unk> expanded its master collaboration agreement with Qiagen to co develop a companion diagnostic based on RNA sequencing technology to <unk>.

And I couldn't recall decision, making for the use of <unk> 3100.

The goal of this project is to develop a pretreatment RNA based blood tests for perspective did you ex 3100 patients to better identify the patients who would most likely to respond to VEGF City 100.

Dr. Joseph Kim: Both trials are designed to assess and confirm the safety, colorability, and efficacy of VGX3100 in women 18 years of age or older who have histologically confirmed cervical dysplasia or so. With an eye towards optimizing the commercial attractiveness of VGX 3100, just last week, Inovio expanded its Master Collaboration Agreement with QIAGEN and co-developed a companion diagnostic based on RNA sequencing technology to help guide clinical decision making for the use of EGX 3100.

Which complements and raises the eventual commercial profile for VEGF 3100.

This biomarker technology had previous to be and employed and a post tax assessment.

V. Jack 3100 phase two b data by Novo, where it correctly predicted efficacy and 85% of.

Vijay ex 30 130 subjects.

And we plan to have the companion diagnostic available prior to the licensure of <unk> 3100.

Dr. Joseph Kim: The goal of this project is to develop a pre-treatment RNA-based blood test for prospective DGX-3100 patients that better identifies the patients who are most likely to respond to VGX3100, which complements and raises the eventual commercial profile for VGX 3100. This biomarker technology has previously been employed in a post-hoc assessment of VGX3100 phase IIb data by Inovio, where it correctly predicted eff We plan to have the companion diagnostic available prior to the licensure of VGX 31. With that, I would like now to turn the call over to Dr. Booyan, who will discuss today's release of Reveal 1 data. Prakash?

With that I would like now to turn the call over to Dr. Brian who will discuss today's release of reveal one data for cash.

Thank you Joseph and good afternoon to everyone joining us on the call us.

As Josef mentioned in his opening remarks. This afternoon, we announced positive results from reveal one which is our phase III pivotal trial evaluating Vg ex 3100 <unk>.

And immunotherapy for the treatment of high grade pre cancerous cervical <unk> caused by HPV 16, <unk> HPV 18.

Importantly, the company achieved the primary and secondary efficacy objectives amongst all the valuable subjects M. I T T modified intention to treat population, which we reported this morning.

Results.

Our significant step forward for women's health.

Potentially giving women a choice to treat cervical pre cancer without surgery, which can have known negative impacts upon reproductive health.

The reveal one trial included women 18 years of age or older with <unk>.

<unk> HPV 16.

And or HPV 18, driven cervical age so.

But who are otherwise healthy participants received either V G ex nerdy 100 or placebo.

Dipesh A. Patel: Thank you, Joseph, and good afternoon to everyone joining us on the call. As Joseph mentioned in his opening remarks, this afternoon we announced positive results from Reveal 1, which is our Phase 3 pivotal trial evaluating VGX3100 as an immunotherapy for the treatment of high-grade precancerous cervical H cells caused by HPV16 and or HPV18. Importantly, the company achieved the primary and secondary efficacy objectives amongst all the valuable subjects. MITT, the Modified Intention to Treat Population, which we reported this morning, is a significant step forward for women's health by potentially giving women a choice to treat cervical precancer without surgery, which can have known negative impacts on reproductive health.

Zero for and 12 weeks randomized two to one and powered at 90% for the evaluation of the primary endpoint.

The M I T T analysis and its prespecified in the trial protocol includes all subjects, who received at least one dose and had endpoint data.

The primary endpoint of his to pathologic regression of <unk> combined with virological clearance of HPV 16, and or HPV 18 at week 36 was met.

<unk> the percentage of responders as 23, 7% 31 out of $1 31, and the treatment group.

11, 3% seven out of 62, and the placebo group respectively.

Resulting in a P value of 0.0 to two with a difference and percentage regression of 12, 4% and and 95% confidence interval of zero point for and $22 five which was statistically significant.

All secondary objectives were achieved.

Dipesh A. Patel: The REVEAL-1 trial included women 18 years of age or older with HPV-16 and or HPV 18-driven cervical H cells but who are otherwise healthy; participants received either VGX3100 or placebo at 0, 4, and 12 weeks, randomized at 2 to 1, and powered at 90% for the evaluation of the primary endpoint. The MITT analysis, as pre-specified in the trial protocol, includes all subjects who received at least one dose and had endpoint data

These were regression of cervical H soul to normal tissue combined with HPV 16, HPV 18 viral clearance.

Regression of cervical eight so alone.

Regression of cervical eight still to normal tissue.

And HPV 16, HPV 18 viral clearance alone.

We also reported the intention to treat or ITT analysis, which includes all trial participants irrespective of being dosed or having data automatically considering those without and valuable data to be non responders.

The ITT analysis did not meet significance for the primary objective and one secondary objective on account of a disproportionate number of subjects with missing data and the V. G X 3100 group, which had seven compared to one and the placebo group.

Dipesh A. Patel: The primary endpoint of histopathologic regression of HCL combined with virologic clearance of HPV16 and or HPV18 at week 36 was met, showing the percentage of responders as 23.7%, 31 out of 131 in the treatment group versus 11.3%, 7 out of 62 in the placebo group, respectively, resulting in a p-value of 0.022, with a difference in percentage regression of 12.4%, and a 9 All secondary objectives were achieved.

Based on blinded aggregate data and the overall safety findings are consistent with previously reported trials and considered generally safe and well tolerated having undergone reviews by our external data safety monitoring board.

Lastly.

I want to remind everyone that in addition to the continued progress towards treating cervical dysplasia. We are also exploring the capabilities of <unk> 3100 towards treating vulvar and anal high grade dysplasia.

We plan to seek regulatory guidance on the pathway to develop EEG ex 3100 to treat HPV, driven vulvar and anal age though.

We're also seeking orphan designations for these indications.

Before I turn the call back over to Joseph I, just want to thank our investigators study participants site personnel and all involved in making this critical research possible.

Dipesh A. Patel: These were regression of cervical H cell to normal tissue combined with HPV16, HPV18 viral clearance, regression of cervical H cell alone, regression of cervical H cell to normal tissue, and HPV16, HPV18 viral clearance alone. We also reported the Intention-to-Treat, or ITT, analysis, which includes all trial participants, irrespective of being dosed or having data, automatically considering those without valuable data to be non-responders. The ITT analysis did not meet significance for the primary objective and one secondary objective on account of a disproportionate number of subjects with missing data in the VGX 3100 group, which had seven compared to one in the placebo group.

Thank you.

Back to you Joseph.

Thank you for cash and to your team for amazing work on providing patients with an alternative therapeutic option to surgery will.

We look forward to the team's continued effort to bring beech ex 30, 102 patients dealing with cervical pre cancer.

Moving now to INR 54, one and J P M and theirs.

And if you had a productive fourth quarter across all of our DNA medicines platform.

And in addition to the continued developments and events and that's occurring within our HPV and COVID-19 programs, we presented encouraging results and the landmark combination trials for GBM at the snow 'twenty and 'twenty annual meeting last November.

Along with our partner Regeneron, we are continuing to review I don't know 54, one in combination with submit for Mad branded Essilor Teo, which is co developed by Regeneron and Sanofi with an emphasis on identifying patients who are most likely to benefit from this innovative combination.

Dipesh A. Patel: Based on blinded aggregate data, the overall safety findings are consistent with previously reported trials and considered generally safe and well-tolerated, having undergone reviews by our external data safety monitoring board. Lastly, I want to remind everyone that in addition to the continued progress towards treating cervical dysplasia, we are also exploring the capabilities of VGX3100 towards treating vulvar and anal high-grade dysplasias. We plan to seek regulatory guidance on the pathway to develop VGX3100 to treat HPV-driven vulvar and anal H cells.

Our immunotherapy approach.

In particular, we will evaluate overall survival at 24 months, along with immunology work focus on three specific antigens that make up I don't know 54 O. One.

We also will update the median overall survival for methylated patients S. This still has not been met.

Additional work and analysis remain in close collaboration with our partner Regeneron and we plan to share additional data this year.

Now turning art and turning to our COVID-19 vaccine program.

And I'm extremely proud of the dedication and efforts of our team and contributing to the global efforts to combat COVID-19.

Dipesh A. Patel: We are also seeking orphan designations for these indications. Before I turn the call back over to Joseph, I just want to thank our investigators, study participants, site personnel, and all involved in making this critical research possible. Thank you.

And we are thankful for all the phase one and two trial participants.

And grateful for the continued support of our partners for all of our innovative clinical trial and for their help and and the ongoing fight against the pandemic.

Dr. Joseph Kim: Thank you, Prakash, and to your team for amazing work on providing patients with an alternative therapeutic option to surgery. We look forward to the team's continued effort to bring BGX 3100 to patients dealing with cervical pre-cancer.

And no 40, and 48 hundreds key differentiators for the safety and Tolerability data as well as us excellent thermal stability profile.

Making it possible to manufacture at scale and transport without frozen cold chain and requirements.

Dr. Joseph Kim: Moving now to INO5401 NGVM. Inovio had a productive fourth quarter across all of our DNA medicines platforms. In addition to the continued developments and advancements occurring within our HPV and COVID-19 programs, we presented encouraging results in a landmark combination trial for GBM at the Snow 2020 Annual Meeting last November. Along with our partner Regeneron, we are continuing to review INO5401 in combination with Semiplimab branded as Lucteo, which is co-developed by Regeneron and Sanofi, with an emphasis on identifying patients who are most likely to benefit from this innovative combination. Immunotherapy Approach

And a 4800 also maintains the ability to be safely re administer.

And is further differentiated by its ability to stimulate both city for and CDA positive T cell responses, along with generating antibody responses as published in clinical medicine, a peer reviewed open access journal published by the Atlanta.

In parallel to our extensive ongoing I N O 4800. The work we are co developing a next generation Pan Covid vaccine candidate.

Which is designed to provide protection against both known and unknown Sars Covid two variants.

Next Dr. Kate Brodrick, who will provide some important updates about I don't know 4800 and.

It's worth us to speak to the measures and work being done to address the new COVID-19 variance that have become topical and the news Kate.

Dr. Joseph Kim: In particular, we will evaluate overall survival at 24 months, along with immunology work focused on the three specific energies that make up INO5401. We also will update the median overall survival for methylated patients as this still has not been met. Additional work and analysis remain in close collaboration with our partner Regeneron, and we plan to share additional data this year. Now, turning to our COVID-19 vaccine program. I am extremely proud of the dedication and efforts of our Inovio team in contributing to this global effort.

Thank you Joseph for.

Firstly I'd like to see how grateful we are to have the continued support from the department of defense for both directly funding the company's phase II, III and IV clinical trial as well as the Dod's funding of the large scale manufacture of our proprietary.

Select truck and EPS P smart device production of doses and the procurement of select for 2000 devices.

As we stated in this afternoons earnings press release, we continue to be focused on and we will complete the phase two segment of our phase two three and if the trial I know for 200 early second quarter.

As a reminder, there is a dose finalization component selection of the doses based on weak sex Immunogenicity and week eight safety.

Dr. Joseph Kim: Combat COVID-19. And we are thankful for all the Phase 1 and 2 trial participants and grateful for the continued support of our partners for all of our innovative clinical trials and for their help in the ongoing fight against the pandemic. INO4800's key differentiators are its safety and colorability data, as well as its excellent thermostability profile, making it possible to manufacture at scale and transport without frozen cold chain requirements. INO4800 also maintains the ability to be safely re-administered and is further differentiated by its ability to stimulate both CD4 and CD8 positive T cell responses along with generating antibody responses. As published in eClinical Medicine, a peer-reviewed, open-access journal published by the Lancet, in parallel to our extensive ongoing INO4800 work.

Safety data.

Our phase two study is designed to evaluate safety tolerability and immunogenicity or buy a new <unk> hundred and a two dose regime, either one or two milligrams and.

And 321 randomization to receive either <unk> hundred or placebo.

And to confirm the most appropriate tools couldn't.

Each of three age groups with high risk of infection.

That's 18 to 50 year old 51 to 64 year olds, and 65 and older for.

For the subsequent phase III efficacy evaluation.

Additionally, we are also complete and with you over the Internet and expanded phase one safety.

<unk> data and 120 subjects and that included those older subjects, 51% and 64 years of age and elderly subjects 65 and older.

We are also actively preparing for the start of the phase three portion of and clinical trial, which remains a partial clinical hold at this time due to the Fda's remaining question for Lisa to this electric two types and device that will be used to deliver INR 4800.

Dr. Joseph Kim: We are co-developing a next-generation pan-COVID vaccine candidate, which is designed to provide protection against both known and unknown SARS-CoV-2 variants. Next, Dr. Kate Broderick will provide some important updates about INO4800, as well as speak to the measures and work being done to address the new COVID variants that have become topical in the news.

We are continuing to work closely with the ft contracts, all remaining device questions and plan to resolve them concurrently by the time, we obtained the phase II results from the second quarter and prior to the start of the phase III segment of the trial.

Moving to and to move us ex U S activities and <unk> collaborators advancing the clinical testing of <unk> hundred and a phase two setting.

Dr. Kate Broderick: Thank you, Joseph. First, I'd like to say how grateful we are to have the continued support from the Department of Defense for both directly funding the company's Phase 2-3 Innovate clinical trial, as well as the DoD's funding of the large-scale manufacture of our proprietary Selectra 3PSP smart device, production of doses, and the procurement of Selectra 2000 devices. As we stated in this afternoon's earnings press release, we continue to be focused on and will complete the Phase 2 segment of our Phase 2-3 Innovate trial of INO4800 early in the second quarter. As a reminder, there is a dose finalization component. Selection of the dose is based on week 6 immunogenicity and week 8 safety data.

Vaccine with whom maneuver you entered into and exclusive collaboration and license agreement for <unk> 100, and greater China is conducting a 640 subject phase II clinical trial and final four to 800.

And the International Vaccine Institute and South Korea is also and a phase Iia segment of it things one slashed to a trial of <unk> hundred.

We expect the data from these two trials will be available later this year.

And complement to our iron ore 4100, and clinical trial efforts and moving it was also advancing work to assess the potential usage of our candidate and the seasonal booster and.

Why is this important well the W. Two recently stated that COVID-19 could likely become and endemic disease.

Dr. Kate Broderick: Our Phase 2 segment is designed to evaluate safety, tolerability, and immunogenicity of INO4800 in a two-dose regime, either one or two milligrams, in a three-to-one randomization to receive either INO4800 or placebo for each dose to confirm the most appropriate dose for each of three age groups with high risk of infection, that is, 18 to 50-year-olds, 51 to 64-year-olds Additionally, we are also completing a review of the interim expanded phase one safety and immunogenicity data in 120 subjects, which included those older subjects 51 to 64 years of age and elderly subjects 65 and older.

It is therefore and important to consider the potential use of iron ore <unk> hundred for seasonal boosting for those who have already received doses of <unk> hundred.

If successful this could extend projections protections against the COVID-19 fight I suppose it becomes endemic.

We believe the booster and the offer the ability to stimulate both CB for the T.

T cell responses, along with augmenting the antibody responses, which we have already demonstrated in our phase one trial and our non human Primate studies.

Given our overall safety profile and nobody was DNA vaccines may have the potential to serve us a safe and effective booster.

We also plan to further evaluate and the capabilities and the potential to boost other vaccine using an old deals COVID-19 DNA vaccine.

We believe this ability to repeatedly boost at a very significant long term differentiator for our DNA platform.

Dr. Kate Broderick: We are also actively preparing for the start of the Phase 3 portion of an EVATE clinical trial, which remains on partial clinical hold at this time due to the FDA's remaining questions related to the Selectra 2000 device that will be used to deliver INO4800. We are continuing to work closely with the FDA to address all remaining device questions and plan to resolve them concurrently by the time we obtain the Phase 2 results in the second quarter and prior to the start of the Phase 3 segment of the trial.

In this regard and it will be or have you been able to provide a third booster with INR 40, 893 out of 120 subjects from our phase one clinical study.

The subjects received a booster doses six to 10 months post the second vaccination.

To date and safety and Tolerability data has been consistent with what we observed from our platform data and from our phase one trial of <unk> hundred.

Dr. Kate Broderick: Moving to Inovio's Ex-U.S. activities, Inovio's collaborators are advancing the clinical testing of INO4800 in a Phase II setting. A vaccine with which Inovio entered into an exclusive collaboration and license agreement for INO4800 in Greater China is conducting a 640-subject phase 2 clinical trial of INO4800, and the International Vaccine Institute in South Korea is also in a Phase 2a We expect that data from these two trials will be available later this year. In complement to our INO 4800 clinical trial efforts, Inovio is also advancing work to assess the potential usage of our candidate as a seasonal booster. And why is this important?

We look forward to sharing the immune response data with you and the second quarter.

And nobody was also being diligent and the manufacturers' cited by and a 4100 development. We continue to build our global manufacturing consortium, which includes thermo Fisher scientific registered hailed biologic and <unk> biosciences to ensure the ability to meet global demand.

And the fourth quarter, we added Konica and Euro Gen Tech to the consortium.

And moving it was also in active discussions with additional manufacturers to join the consortium.

We have also brought on several contract manufacturers to produce global supply of single use agree which would be used both by the select for 2000 and us electricity SP devices.

Next on the top of mind for many at the moment I'll speak to the potential advantages for our DNA based vaccine technology may provide and addressing today of current and future variant strains of Sars Covid two.

Dr. Kate Broderick: The WHO recently stated that COVID-19 could likely become an endemic disease. It is therefore important to consider the potential use of INO4800 for seasonal boosting for those who have already received doses of INO4800. If successful, this could extend protections against the COVID-19 virus as it becomes endemic. We believe the booster may offer the ability to stimulate both CD4 and CD8 T-cell responses, along with augmenting antibody responses, which we have already demonstrated in our Phase 1 trial and our non-human primate studies. Given our overall safety profile, Inovio's DNA vaccines may have the potential to serve as a safe and effective booster.

One of the hallmarks of a new abuse DNA vaccine technology is the ability to respond to emerging infectious diseases through rapid vaccine construct design and manufacture.

And as an example, I know for 100 was rapidly design and following the Ctrip the Wuhan Sars Covid two vital sequence from China and.

In addition, the optimization process for the <unk> DNA medicines confirms the ability to potentially deliver cross screen presentation and.

<unk> radiant coverage mitigating the risk of the currently circulating strain variant as well as potentially the new recent strains that could appear.

We have previously demonstrated the functional capability of this technology.

And we'll sit and Colin and vaccine design approach uses the company's proprietary algorithm to combine multiple existing strain sequences together to generate a synthetic design.

Dr. Kate Broderick: We also plan to further evaluate the capabilities and the potential to boost other vaccines using Inovio's COVID-19 DNA vaccine. We believe this ability to repeatedly boost is a very significant long-term differentiator for our DNA platform. In this regard, Inovio was able to provide a third booster dose of INO4800 in 93 out of 120 subjects from our Phase 1 clinical study. The subjects received their booster doses six to ten months post the second vaccination.

We use this approach and applied it to influenza and multiple preclinical studies and generated broadly protective antibody responses against the most deadly strains of the H, one and one and H and two influenza viruses since 1918th.

Demonstrating complete protection against petrol against lethal challenge it.

And it'll be a was also been closely monitoring the development and evolution of COVID-19 mutations with a particular focus on the U K, South African and Brazilian variant.

And with incidences of variance from the rise globally and with the U K variant and expect it to be the dominant screen and the United States. This month. This has been and area of high priority for our COVID-19 vaccine.

Dr. Kate Broderick: To date, the safety and tolerability data have been consistent with what we observed from our platform data and from our Phase 1 trial of INO4800. We look forward to sharing the immune response data with you in the second quarter. Inovio has also been diligent in the manufacturing side of INO4800 development. We continue to build our global manufacturing consortium, which includes Thermo Fisher Scientific, Rifter Helm Biologic, and Ology Biosciences, to ensure the ability to meet global demands. In the fourth quarter, we added Kanika EurogenTech to the consortium.

And there'll be able us taking a two pronged approach to the emerging crisis caused by the new variants.

With INO 400, we are currently testing the impact for these new streams, how about the immunogenicity profile of the vaccine to do an assessment of neutralizing antibodies and both light and sudo bite us oxy as well as assessing the impact of the January to T cell responses on these variants.

In addition to the ongoing iron ore <unk> hundred work. We are also developing a next generation per.

Covid vaccine candidate.

Using our proprietary AI drip and Suncor and gene sequence I'll get us to create synthetic Sars COVID-19 two genetic design.

Dr. Kate Broderick: Inovio is also in active discussions with additional manufacturers to join the consortium. We have also brought on several contract manufacturers to produce a global supply of single-use arrays which would be used both by the Selectra 2000 and the Selectra 3P SP devices. Next, and at the top of mind for many at the moment, I'll speak to the potential advances that our DNA-based vaccine technology may provide in addressing the threat of current and future variant strains of SARS-CoV-2.

PON Covid candidate is designed to provide protection against the U K, South African and Brazilian strength as well as potentially the covenant currently unknown Sars Covid two variant.

I should also note that the PON Covid vaccine candidate is expected to share a similar safety and thermal stability profile to I know for 800.

And with that I'll hand back to Joseph.

Thank you Kate.

I wanted to summarize the capabilities of and nobody else platform.

As it relates to the emerging very and crisis that Keith touched on.

Our DNA vaccine and stuff for them has the potential to mitigate the risks of the new viral variance for the three main mechanisms one.

Dr. Kate Broderick: One of the hallmarks of Inovio's DNA vaccine technology is the ability to respond to emerging infectious diseases through rapid vaccine construct, design, and manufacturing. As an example, INO4800 was rapidly designed following the receipt of the Wuhan SARS-CoV-2 viral sequence in China. In addition, the optimization process of Inovio's DNA medicines confers the ability to potentially deliver cross-strain presentation and pan-variant coverage, mitigating the risk of the currently circulating strain variant, as well as potentially new mutant strains that could appear.

Rapid design and testing of new DNA based vaccine candidates based on newly emerging sequencing data.

<unk> ability to generate broad immune response profile, which are less susceptible to viral strains shifts three ability to repeatedly booths with no anti vector immunity or reactor generosity issues on an annual or semi annual basis to provide participants.

Persistent and tailor protection.

And additional two key characteristics for the platform are also important thermal stability of profile thermal stability profile.

Vaccine does not need to be frozen drink transport or storage a critical element when considering the feasibility of global distribution and.

Dr. Kate Broderick: We have previously demonstrated the functional capability of this technology. Inovio's Syncon vaccine design approach uses the company's proprietary algorithm to combine multiple existing strain sequences together to generate a synthetic mosaic design. We used this approach and applied it to influenza in multiple preclinical studies and generated broadly protective antibody responses against the most deadly strains of the H1N1 and H3N2 influenza viruses since 1918, demonstrating complete protection against heterologous lethal challenges.

And characterize the ball and scalable highly characterized simple nature of the vaccine enables timely scaling of manufacturing and with multiple manufacturing facilities able to be utilized.

With that I will turn now the call over to our CFO Peter Keys for a brief financial update Peter.

Thank you Joseph.

Good afternoon, everyone as Joseph mentioned, and OBO enters 2021, and well positioned financially with total cash cash equivalents and short term investments of 411 6 million as of December 31, and 2020.

Additionally in January 2021, the company closed an underwritten public offering of the company's common stock, resulting in net proceeds of 162.1 million.

Dr. Kate Broderick: Inovio has also been closely monitoring the development and evolution of COVID-19 mutations, with a particular focus on the UK, South African, and Brazilian variants. With incidences of these variants on the rise globally and with the UK variant expected to be the dominant strain in the United States this month, this has been an area of high priority for our COVID-19 vaccine team. Inovio is taking a two-pronged approach to the emerging crisis caused by the new variant.

Our current cash position provides us with multiple years of cash runway.

We have all we also have continued financial support from the D. O D for a pivotal phase two and three trials for <unk> 4800 per.

Turning now to our quarterly financial results.

Total revenue for the three months ended December 31, 2020 was $5 6 million compared to 279000 and for the same period and 2019.

Dr. Kate Broderick: With INO4800, we are currently testing the impact that these new strains have on the immunogenicity profile of the vaccine through an assessment of neutralizing antibodies in both live and pseudovirus assays, as well as assessing the impact of the generated T cell responses on these variants.

The increase and revenue is primarily compiled.

Comprised of upfront and milestone payments of $5 million related to our license agreement with that vaccine.

Our net loss for the quarter.

And at December 31, 'twenty, and 'twenty was $24 3 million.

Dr. Kate Broderick: In addition to the ongoing INO4800 work, we are also developing a next-generation pan-COVID vaccine candidate, using our proprietary AI-driven Synchron Gene Sequence algorithm to create a synthetic SARS-CoV-2 genetic design. The pan-Covid candidate is designed to provide protection against the UK, South African, and Brazilian strains, as well as potentially the currently unknown SARS-CoV-2 variant. I should also note that the pan-Covid vaccine candidate is expected to share a similar safety and thermostability profile to INO4800. And with that, I'll hand it back to Joseph.

Our 14 cents per share basic and dilutive.

Compared to a net loss of $37 7 million or <unk> 38 per share basic and dilutive for the quarter ended December 31 2019.

Research and development expenses for the three months ended December 31, 2020 were $26 3 million compared to 22 million for the same period and 2019.

The increase in R&D expenses was primarily related to an increase and drug manufacturing and outside services related to I know for 800, and and an increase and engineering services related to our select Euro three P. S. P device. These increases were offset by an increase.

And our Contra research and development expense.

Recorded from grant agreement among other variances.

Dr. Joseph Kim: Thank you, Kay. I want to summarize the capabilities of Inovio's platform. It's related to the emergent variant crisis that Kate touched on. Our DNA Vaccines Plus platform has the potential to mitigate the risk of new viral variants through three main, 1, Rapid Design and Testing of New DNA-Based Vaccine Candidates Based on Newly Emerging Sequencing Data. 2. Ability to generate broad immune response profiles, which are less susceptible to viral strain

Lastly, general and administrative expenses were $8 6 million for the three months ended December 31, and 2020 versus eight seven for the same period and 2019.

As a reminder, you can find our full financial statements and this afternoon's press release, as well and as well.

And the company's form 10-K filed with the SEC.

Back to you Joseph.

Thanks, Peter and.

Clothing.

I want to thank day Navios team for their tireless effort to support pandemic response and across our for DNA medicines platform.

Dr. Joseph Kim: 3. Ability to repeatedly boost with no anti-vector immunity or reactogenicity issues on an annual or semi-annual basis to provide participants with persistent and tailored protection. Additionally, two key characteristics of the platform are also important. The thermal stability profile.

I recognize the heightened interest and concerns about the variant strains and their implications.

I am pleased with the significant progress we continue to make on INR 4800, as well as our ability to concurrently support exploration of a pan Covid Darien vaccine candidate designed to protect against existing there and strains as well as dose yet.

Dr. Joseph Kim: Our vaccine does not need to be frozen during transport or storage, a critical element when considering the feasibility of global distribution. And it is characterisable and scalable. The highly characterisable nature of the vaccine enables timely scaling of manufacturing with multiple manufacturing facilities able to be utilized. With that, I will now turn the call over to our CFO, Peter Kies, for a brief financial update.

Come <unk>.

Equally our ability to potentially serve as a safe and effective season, a booster for those who have received INR 4800.

As well as those who have received other vaccines, but potentially offer extended protection and that's the virus evolves and becomes endemic.

Look to sharing additional details about these concurrent efforts in the months ahead with that operator, please open the lines for questions.

Peter D. Kies: Thank you, Joseph. Good afternoon, everyone. As Joseph mentioned, Inovio enters 2021 well-positioned financially, with total cash, cash equivalents, and short-term investments of $411.6 million as of December 31, 2020.

We will now begin the question and answer session to ask a question you May Press Star then one on your Touchtone phone, if you're using a speakerphone. Please pick up your handset before pressing the keys is that day.

Any time your question has been addressed and you would like to withdraw your question. Please press Star then two at this time, we will pause momentarily to assemble our roster.

The first question comes from Heartburn, Zhang with Oppenheimer. Please go ahead.

Great. Thank you just a couple of quick questions.

And.

And good work and all of them and all the progress, especially the trial today.

Peter D. Kies: Additionally, in January 2021, the company closed an underwritten public offering of the company's common stock, resulting in net proceeds of $162.1 million. Our current cash position provides us with multiple years of cash runway. We also have continued financial support from the DoD for our pivotal Phase 2 and 3 trials of Inovio 4800. Now, to our quarterly financial results. Total revenue for the three months ended December 31, 2020, was $5.6 million compared to $279,000 for the same period in 2019.

Focusing on the on your.

On INR 4800, and Covid vaccine.

And if you can detail a little bit <unk> been working on the boosters.

Ah patient population and gathering that data and you're also working on the mutations assuming you start your phase three and the second quarter of this year, how could the clinical path forward look for.

Additional getting boosters approved or the various vaccines approved.

And then secondly.

The department of Defense funding for innovation in the press release, you indicated you'll be getting funding from the department would that also entail a certain amount of vaccine doses that the U S government expects to get for anymore and <unk>.

And at a certain cost for example, like other companies have done.

Thank you for the questions.

Yes, thanks for to US first question first.

We're currently working through INR 4800 development and our AR.

Peter D. Kies: The increase in revenue is primarily comprised of upfront and milestone payments of $5 million related to our license agreement with Advaxine. Our net loss for the quarter ended December 31, 2020 will be $24.3 million, or $0.14 per share, basic and dilutive, compared to a net loss of $37.7 million, or $0.38 per share, basic and dilutive, for the quarter ended December 31, 2019.

Fluoridation of and Covid.

<unk> vaccine candidate in parallel so we're marching along and executing our plans for phase II and phase III part of the innovate trial, which is funded through the Dod funding as mentioned.

In terms of the <unk> COVID-19 vaccine candidate and we're looking to move that along as rapidly as possible and leveraging our technology platform.

Peter D. Kies: Research and development expenses for the three months ended December 31, 2020, were $26.3 million compared to $22 million for the same period in 2019. The increase in R&D expenses was primarily related to an increase in drug manufacturing and outside services related to INO 4800 and an increase in engineering services related to our Selectra 3PSP device. These increases were offset by an increase in our contra research and development expense recorded from grant agreements, among other variants. Lastly, general and administrative expenses were $8.6 million for the three months ended December 31, 2020, versus $8.7 million for the same period in 2019.

The second part of your question Us.

The funding from the <unk> ex.

We've been receiving multiple.

I've also funding.

As it was covered and the prepared remarks, the first direct funding of our phase II and phase III innovate trial. So that's directly funded through our a CRO partner.

And from coming from the Vod and then there's a second level of funding that we have announced.

In June of last year.

And it involves the <unk>.

Funding and.

Completion of the PSP device.

Well as some limited number of doses for the D O D. A few hundred thousand doses.

And we.

We could.

Could project that as we advance our program those numbers can be increased.

Peter D. Kies: As a reminder, you can find our full financial statements in this afternoon's press release, as well as in the company's Form 10-K filed with the SEC. Back to you, Joseph. Thanks, Peter. In closing...

Potentially so.

And I hope.

These answers.

Our satisfactory too.

Yes, no. Thank you Joe just a quick follow up so you know the FDA has released some initial guidelines and correlates of protection to help us.

Dr. Joseph Kim: I want to thank the Inovio team for their tireless efforts to support pandemic response and across our full DNA medicines platform. I recognize the heightened interest and concerns about the variant strain and its implications. I am pleased with the significant progress we continue to make on INO4800, as well as our ability to concurrently support exploration of a pan-COVID variant vaccine candidate designed to protect against existing variant strains, as well as those yet to come.

Companies that have vaccines against Abboud here for example, a booster shot trauma against variance.

And as the FDA broadened both Geiger and guidelines out do you foresee that helping you for it.

Example, with 4800 gets approved.

And then you have follow up vaccine falling quickly afterwards, using that correlates and protection guidance that seems to be kind of arriving and thank you for all the questions.

Absolutely I think that.

A positive development for <unk>.

Provided by the FDA and respect piece of guidance as to evolve as the landscape evolves.

The concerns of the variance so we expect to leverage all of these are helpful guidance is as we develop both INR 4800, and as well as our Pan Covid vaccine and the future.

Dr. Joseph Kim: Equally, our ability to potentially serve as a safe and effective seasonal booster for those who have received INO4800, as well as those who have received other vaccines, would potentially offer extended protection as the virus evolves and becomes endemic. We look forward to sharing additional details about these concurrent efforts in the months ahead. With that, Operator, please open the lines for questions. We will now begin the question and answer session. If asked a question, you may press a star, then one.

Great. Thank you Kim.

Great.

The next question comes from Gregory and so with RBC capital markets. Please go ahead.

Hey, Joseph and team. Thank you for taking my question today.

Just on us.

Just on 4800, just wanted to get a better sense perhaps.

The timelines and perhaps to your best estimation, how they potentially lineup just for the phase two would that day to be coming second quarter.

And as we think about the fee.

Operator: After using the speakerphone, please pick up your handphone. If at any time your question has been addressed and you would like to withdraw your... Please press star. At this time, we will pause momentarily to assemble our... The first question comes from Hartaj Singh with Oppenheimer, please go ahead.

<unk> III up and running I'm, just curious the timeline on the.

FDA.

Apply just had a sense that it may have been in March but maybe on recent disclosures that might be looking more like a bad debt for any clarity on how we should think about things lining up there would be great. Thank you very much.

Thanks, Greg and where we're going to have a very busy.

Busy second quarter.

As I think we have alluded to.

We expect the phase III top line data to be available and the early part of the second quarter.

Hartaj Singh: Great. Thank you. Just a couple of quick questions, and good work on all the progress, especially the trial today. Focusing on your INO4800, the COVID vaccine, Joe, if you can detail a little bit, you've been working on the boosters, you know, patient population, GABA, and VAT data. You're also working on the mutations.

As for all of US a completion of all of the device related submission to be available by that time. So all of these submissions will be filed with the F. D. A.

At the same time and once everything is a file they have up to 30 days to concur with our plan or not.

Dr. Joseph Kim: Assuming you start phase three in the second quarter of this year, how could the clinical path forward look for, you know, additional getting boosters approved or the variant vaccines approved? And then secondly, you know, Department of Defense funding for INOV8. In the press release, you indicated you'll be getting funding from the Department of Defense. Will that also entail a certain amount of vaccine doses that, you know, the U.S. government expects to get from Inovio at a certain cost, for example, like other companies that have those agreements?

And we are very hopeful that we can do that this time.

Help us, allowing us to move forward with the phase III portion and the later part of the second quarter of this year.

Okay got it and then just turning to <unk> 3100, and just curious if you could provide some context on and your thoughts on that significance of the 12, 4% difference there. How you think about these results comparing to the previous studies and the phase two and.

I'm just thinking more broadly about the differences between the modified intent to treat vs. The intent to treat and non those.

The subjects, who either discount or lost to follow up thank you again.

That's great.

Address the first part.

Initially and then I'll ask Dr Bryan to comment.

Yes, I think the data is very significant for us.

Dr. Joseph Kim: Thank you for the question. The first question is, we're currently working through INO4800 development and our exploration of a pan-COVID vaccine candidate in parallel. So we're marching along and executing our plans for the Phase 2 and Phase 3 parts of the INNOV8 trial, which is funded through the DoD funding, as mentioned. In terms of the pan-COVID-19 vaccine candidate, we're looking to move that along as rapidly as possible, leveraging our technology platform. The second part of your question was about funding from the DoD.

So first a successfully met phase III trial data.

And in terms of our.

Meeting all our primary and secondary endpoints with regards to the HPV.

Treatment.

We're very excited about that and looking for to executing and the reveal two trial.

With the confirmatory data for for this important product.

We're really looking for to bringing this product out.

S. A first non surgical treatment for these women who are suffering from HPV caused high grade cervical dysplasia right and now the one true treatment option is surgery.

Dr. Joseph Kim: Actually, we've been receiving multiple levels of funding, as it was covered in the prepared remarks. The first is direct funding for our Phase 2 and Phase 3 Innovate trials. So that's directly funded through our CRO partner and coming from the DoD.

With potential to damage their cervical integrity and impact for reproductive health. So I think this is a very important product for for us.

Dr. Joseph Kim: And then there's a second level of funding that we announced in June of last year that involves the funding and completion of the 3PSP device, as well as some limited number of doses for the DoD, a few hundred thousand doses. [inaudible] So I hope that these answers are satisfactory to you. Yeah, no, no, thank you, Joe.

For women's health and all of these patients who are seeking for a non surgical option.

Not only to treat the disease, but also eradicate the virus that caused the disease from the cervix so for.

We couldn't be any more excited about the data for cash would you like to add anything else regarding greg's question.

Sure. So I'll just add that a good efficacy outcome is really the achievement of the primary endpoint and so really we're excited.

Dr. Joseph Kim: Just a quick follow-up. The FDA has released some initial guidelines and correlates of protection to help, you know, companies that have vaccines against, you know, for example, a booster shot or a shot against variants. As the FDA broadens those guidelines out, do you foresee that helping you? You know, for example, if 4800 gets approved, then you have follow-up vaccines falling quickly afterwards, you know, using that correlates of protection guidance that FDA seems to be kind of arriving at. Yes, absolutely. I think that's a positive development provided by the FDA. And we expect these guidances to evolve as the landscape evolves with the concerns of the variants.

To have achieved that and our.

And all the valuable subjects for the reveal one trial.

And.

Looking back at Phase two we also achieved the primary and secondary efficacy objectives and that trial. So having now met that and both that trial and well know a pivotal phase III trial.

And it gives us really a great step forward and Ah.

And we went into and the prepared remarks, some of the descriptions of the M. I T T. All evaluable subjects analysis, and the ITT analysis and.

And.

And so we you know the reasons really for the differences were where the.

And point data that.

We're missing and included as subjects, who were considered non responders and the ITT analysis and.

Dr. Joseph Kim: So we expect to leverage all of these helpful guidance as we develop both the INO4800 as well as our pan-Covid vaccine. Great. Thank you, Jim.

So we provided both really for completeness and but.

But we're really excited in terms of what we've seen now not just for phase III, but also for phase III.

Gregory Rinza: The next question... and Gregory Rinza with RBC Capital. Hey, Joseph and team, thank you for taking my question today. Absolutely. Joseph, just on, hey, just on 4800, just wanted to get a better sense, perhaps of the timelines and, perhaps, to your best estimation, how they potentially line up. Just with phase two, would that data be coming in second quarter? And as we think about phase three up and running, I'm just curious about the timeline on the FDA reply. I had a sense that it may have been in March, but maybe on recent disclosures it might be looking more like a May event. So any clarity on how we should think about things lining up there would be great. Thank you very much. Yeah, thanks, Greg. We're going to have a very busy second quarter.

That's great. Thanks for price Thanks Joseph.

Thank you.

The next question comes from Stephen Willey with Stifel. Please go ahead.

Yeah, good afternoon, and thanks for taking the question.

Joseph.

So maybe just to clarify than us.

And I just want to make sure that the modified intent to treat was the prespecified primary endpoint of reveal one and is also reveal two.

Yeah, both for MA.

To fight and intent to treat took us one should take that.

And so both both the modified intention to treat and the ITT or analyses that are pre specified.

We're also going to be doing a per protocol analysis. Once we have complete data for those all three of those analyses are pre specified and the trial protocol.

Are they cope.

Co primaries or are they is there some kind of hierarchy involved.

And in terms of how they're statistically.

Yes.

Well, they're assessed in total so they they actually stand.

They they stand together and so the evaluation is really done with all of the analyses once one has complete data.

So it isn't.

It isn't really.

The primary us based.

Dr. Joseph Kim: As I think we have alluded to, we expect Phase 2 top-line data to be available in the early part of the second quarter, as well as the completion of all of the device-related submissions to be available by that time. So all of these submissions will be filed with the FDA at the same time. And once everything is filed, they have up to 30 days to concur with our plan or not.

And in any one of them. The primary is evaluated under all three analysis condition.

Okay.

M I T T. The ex specifically the M. I T T evaluates under having subjects who had data.

Okay.

And I know that the patients are being followed to demonstrate durability of response and I guess.

And do we know from the phase two data and what the durability of response and looked like 18 months following last administration and.

Has there been any kind of regulatory dialogue around what that durability needs to look like.

Dr. Joseph Kim: And we are very hopeful that we can do that this time, allowing us to move forward with the Phase III portion in the latter part of the second quarter. Okay. And then just turning to VGX 3100, just curious if you could provide some context and your thoughts on the significance of the 12.4% difference there, how you think about these results compared to the previous studies in phase two, and perhaps just thinking more broadly about the differences between the modified and tentatory versus.

So we did actually publish a manuscript last year on the durability data from the phase II cohort and.

And that did follow subjects 18 months after their last administration and what it showed was that for the women who.

Who responded to the G X 3100 that there were no.

Breakthroughs in terms of.

Recurrence and viral infection and that their Pap smears remained.

Remained improved and so there were no sort of regression from that and that was very encouraging looking out 18 months.

And as far as the second part of your question.

Dr. Joseph Kim: Thomas Hong, Anish Nikhanj, Hartaj Singh, Yi Chen, Michael Sumner, Roger Song, Mark Twyman, Yes, I think the data is very significant for us. It's our first successfully met Phase 3 trial data, and in terms of our meeting all the primary and secondary endpoints with regard to the HPV treatment. We're very excited about that and looking forward to executing the REVEAL-2 trial with the confirmatory data for this important product. We're really looking forward to bringing this product out as a first non-surgical treatment for these women who are suffering from HPV-caused high-grade cervical dysplasia. Right now, the one true treatment option is surgery with the potential to damage their cervical integrity and impact their reproductive health.

Actually the reason why this trial goes out to week 88 is actually to provide that that durability information and we'll be continuing the trial.

Out to week 88 to get that information.

Okay, that's very helpful and.

I guess, maybe just last thing and 3100 and I think.

Have you talked about what proportion of the treatment eligible patient population would be.

And would be eligible I guess under this.

Under this plan and biomarker utilization.

So we did put that in and <unk>.

Joseph touched on it and the and the.

And our prepared remarks and.

And we put some of that information also and our and our press release today.

But we are.

Really aiming for a biomarker that would have a very high level of predictability.

In terms of of identifying women, who are likely to respond and Vg ex 3100.

And in phase two we actually observed 85 per cent.

And we're working with as Josef mentioned earlier, our close partnership with Qiagen to develop them.

Okay.

And it's affected and predicting.

Bonds and 85% of patients and.

It could be used and all all treatment eligible patients I guess I'm just trying to figure out that and you were to apply what the biomarker is telling you about response to the.

Dr. Joseph Kim: So I think this is a very important product for us, for women's health, and all these patients who are seeking non-surgical options. [inaudible] Sure. So I'll just add that a good efficacy outcome is really the achievement of the primary endpoint. And so we're really excited to have achieved that in all the valuable subjects for the REVEAL-1 trial. And, you know, looking back at phase two, we also achieved the primary and secondary efficacy objectives in that trial.

To the 3100 eligible patient population.

What would that haircut and look like in terms of and in terms of treatment eligible patients.

He's gone biomarker criteria.

Okay.

I think as we continue to develop the biomarker with Qiagen will have more information on the specific characteristics and performance of the biomarker. So I think.

It's something.

That I would say you should look forward to us we as we go through the rest of the year.

Joseph is there anything you would add to that.

Yeah, No I think you were pretty comprehensive we look forward to.

Confirming and lot of that information and bring bring those out.

Dr. Joseph Kim: So having now met that in both that trial as well as now a pivotal phase three trial gives us really a great step forward. And, you know, we went into, in the prepared remarks, some of the descriptions of the MITT, all the valuable subjects analysis, and the ITT analysis. And so the reasons, really, for the differences were the endpoint data that were missing or included as subjects who were considered non-responders in the ITT analysis.

And the in the coming year.

Okay, and I guess, just lastly, sorry wood with the biomarker and also be used for the anal and vulgar trials as well.

So we haven't made that determination, yet, but I think our first step is really to look.

With Qiagen at our lead indication, which is the cervical dysplasia indication, but but you know you're touching on an important question and I think as we as we continue to develop the biomarker and we hope to give.

More of that information as we go along.

Great. Thanks for taking my questions.

Great. Thank you Steve.

Dipesh A. Patel: And so we provided both, really, for completeness. But we're really excited in terms of what we've seen now, not just for phase two but also for phase three. That's great. Thanks Prakash. Thanks Joseph. Thank you. The next question... and Willie with Stiefel.

The next question comes from eight and accusing of with benchmark. Please go ahead.

Yeah.

Hi, good afternoon and alright.

Alright, and congratulations with the odds of a core with Clearbridge ex sort of 100 and.

Thanks for taking the questions. So the first one and I'll have above all and.

For 800.

You mentioned about Covid vaccine candidates.

And and potential unknown also scope to variance.

<unk>.

Would you need another phase one trial for these potential vaccine candidate and how difficult for other companies would be to create uncle with candidates and how differentiated is this for all of them.

Yeah, very briefly Oh, yeah, we think so but based on some of the earlier guidance is from the FDA.

Willie: Please go ahead. Yeah, good afternoon. Thanks for taking the question. So maybe just to clarify, then, is that the modified intent to treat is the pre-specified primary endpoint of Reveal1 and is also of Reveal2. Yeah, both modified intent to treat. Procraz, why don't you take that?

Regarding the the variance for the vaccine developers and also based on our overall safety profile.

Of our platform and our Covid and.

And the 4800, thus far we think we can.

Moving quite rapidly and the development of that program.

Dipesh A. Patel: Yeah, so both the modified intention to treat and the ITT are analyses that are pre-specified. We're also going to be doing a protocol analysis once we have complete data. So all three of those analyses are pre-specified in the trial protocol. Are they co-primaries or are they, Is there some kind of hierarchy involved? in terms of how they're statistically treated.

But more more information will be given you know we just started that.

Process, So we will share with the street.

As we make our progress.

Okay.

And for the third booster I think and you mentioned 93 patients.

And.

And the phase two trial and.

Could you specify what was the time lag after the second dose and when do you expect.

<unk> and efficacy and.

Dipesh A. Patel: Well, they're assessed in total, so they actually stand together, and so the evaluation is really done with all of the analyses once one has complete data. So it isn't really... that the primary is based on uh... you know, in any one of them the primary is evaluated under all three analysis conditions. Okay.

And that specific sub population.

Yeah, so for.

First of all this this was a phase one subjects, where we had a total of 100 and 'twenty total pool of maximum under and plenty of people.

From phase one.

And amazingly and 93.

120 signed up to be boosted with 4800, and the fact that I think is quite interesting itself.

Dipesh A. Patel: But the MITT, specifically the MITT evaluates under having subjects who have data. And I know that the patients are being followed to demonstrate their ability to respond. And I guess, Do we know from the phase two data what that durability of response looked like 18 months following the last administration? And I guess, Has there been any kind of regulatory dialogue about what that durability needs to look like?

<unk> was so showed us duration from the last vaccination for six months the longest was around 10 months.

So I think we can see.

First of all I'm really.

Good information about the safety and.

And tolerability of our boosting our number one.

Dipesh A. Patel: So we did actually publish a manuscript last year on the durability data from the Phase II cohort. And that followed subjects 18 months after their last administration, and what it showed was that for the women who responded to VGX 3100, there were no breakthroughs in terms of recurrence of viral infection and that their pap smears remained improved. And so there was no sort of regression from that.

And so far is consistent to our first two doses.

And that we had seen and phase one and then we're hopeful that we can show the expansion of antibody responses.

US CD for and CDA T cell responses.

Those data are getting process as for samples come in.

From the booster, Saudi and we should have that available and.

Dipesh A. Patel: And that was very encouraging looking out 18 months. As far as the second part of your question, actually, the reason why this trial goes out to week 88 is actually to provide that durability information, and we'll be continuing the trial out to week 88 to get that information. Okay, that's very helpful.

And there are very.

Productive second quarter of this year so.

And what we're excited about is confirming the safety of our boosting.

Our vinyl and 4800 and the potential.

And two.

To expand and and augment the immune responses.

Two I don't know 4800.

Alright, I appreciate that thanks, a lot and.

Willie: And, I guess maybe just lastly, on 3100, I think you have talked about what proportion of the treatment eligible patient population would be eligible under this, under this planned biomarker utilization? So we did put that, you know, and Joseph touched on it in our prepared remarks, and we put some of that information also in our press release today, really aiming for a biomarker that would have a very high level of predictability in terms of identifying women who are likely to respond to VGX 3100. And in phase two, we actually observed 85%. And we're working in, as Joseph mentioned earlier, a close partnership with QIAGEN to develop that. So it's effective in predicting.

And another one I have on major excluded 100.

Just wanted to confirm the timing of the expected results will reveal too because it seems like it's being run in parallel and.

Also for a companion diagnostic would you think that.

And given England and without companion diagnostic that would have been approved by the FDA. If you had similar results moving to and companion diagnostic is more for adoption purposes.

One second.

Second question first.

We we've been working with Qiagen and internally to develop a biomarker for P. J F 3100 for last several years since the phase two results and.

And.

We think that's a significant step towards.

Really raising the commercial attractiveness of <unk> 3100 during launch and post launch.

Being able to target the patients who would most benefit from our immunotherapy I think it provides additional boost pardon my time and to the.

Dipesh A. Patel: It could be used in all treatment-eligible patients, I guess. I'm just trying to figure out that if you were to apply what the biomarker is telling, about RESPOND, to the 3100 eligible patient population, what would that haircut look like?

And the commercial attractiveness.

This immunotherapy.

The first part of the question you know reveal two enrollment was hampered.

And throughout last year.

And and and and we're still trying to recover from that from the global Covid pandemic just like many of the other companies are large trials.

Dipesh A. Patel: in terms of treatment-eligible patients based on biomarker criteria. I think as we continue to develop the biomarker with QIAGEN, we'll have more information on the specific characteristics and performance of the biomarker. So I think, you know, it's something that I would say you should look forward to as we go through the rest of the year. Joseph, is there anything you would add to that?

So we haven't provided the guidance on when we will finish but once we have a more solid visibility are we where we will share.

With the street.

What I can tell you is due to the incredible hard work by our team.

And we're pretty much back to the pre pandemic levels of early last year in terms of the recruitment. So I think were beginning of the strong track back.

Dr. Joseph Kim: Yeah, no, I think you were pretty comprehensive. We look forward to... Confirming a lot of that information and bringing those out in the coming weeks. Okay, and I guess just lastly, sorry. Would the biomarker also be used for the anal and vulvar trials as well? So we haven't made that determination yet, but I think our first step is really to look, you know, with QIAGEN at our lead indication, which is the cervical dysplasia indication.

For reveal two enrollment during a global Covid pandemic.

Okay. Thank you very much congrats again with the quarter.

Thank you Ed.

Just a quick reminder to limit yourself to one question and one follow up the.

The next question comes from Charles Duncan with Cantor Fitzgerald. Please go ahead.

Hi, Hi, Joe Thanks for taking my questions and.

Congratulations on the progress.

Particularly the.

Release of the 3100 reveal.

Dr. Joseph Kim: But, you know, you're touching on an important question, and I think as we continue to develop the biomarker, we hope to give more of that information as we go along. Thanks for taking the call. Thank you, Steve. The next question comes from Aidan Huzinov with Benchmark. Please go ahead. Hi, good afternoon.

<unk> one reveal one results today that was nice surprise I guess I'm wondering when you when you consider reveal one and and the enrollment of patients in that trial versus say the phase two.

And experience how would you compare and contrast, those two clinical trial samples.

Aidan Huzinov: Hi. Congratulations on... All right, for GraviGx 3100, and thanks for taking the questions. So the first one I have is about INO4800.

Okay. Thank you I'll briefly address and then I'll ask Dr.

Dr Brian to comment as well so.

You know, it's important and thanks for for Reentering that Charles Us.

Dr. Joseph Kim: So you mentioned pan-COVID vaccine candidates, you know, for known and potential unknown SARS-CoV-2 variants. Would you need another phase one trial for this potential vaccine candidate? And how difficult would it be for other companies would be to create pan-COVID candidates? And how differentiated is this for Inovio?

Both in our phase III reveal one and our phase two b trial.

They were both large.

167, and phase two and two and a little over 200 and phase III trials and.

And both trials, we met all of the primary and secondary endpoints.

Based on the modified intention to treat.

Aidan Huzinov: Yeah, very briefly, yeah, we think so, but based on some of the earlier guidance from the FDA. So, we'll share with the street as we make progress. And for the third booster, I think you mentioned 93 patients got the third booster in the phase 2 trial. And could you specify what the time lag was after the second dose?

And statistical analysis.

Now these two trials for ore.

Not designed to be cross compared.

But I'm going to ask.

Statistically there there were not design phase III, there wasn't that design to be compare to to be but I will ask for cash to come in on.

Dr. Joseph Kim: And would you expect an increase in efficacy in that specific subpopulation? Yeah, so first of all, this was a phase one subject. We had a total of 120 total pool of maximum 120 people from phase one. And amazingly, 93 out of 120 signed up to be boosted with 4800. The fact, I think is quite interesting, itself. The shortest duration from the last vaccination was six months. The longest was around 10 months.

This little further Prakash.

Sure.

So your question is really about the enrollment in phase two and then what we observed and the enrollment in phase III and and and what we you know what we did and phase three was we expanded our geography.

Considerably, we actually were enrolling and five continents.

And we actually pre pandemic, we're on track to that.

To actually beat the enrollment rate and that we had observed in phase two and.

Dr. Joseph Kim: So I think we can see, first of all, really good information about the safety and tolerability of our boosting doses number one. And so far, it's consistent with our first two doses that we saw in phase one. And then we're hopeful that we can show the expansion of antibody responses, as well as CD4 and CD8 T cell responses. Those data are getting processed as the samples come in from the booster study, and we should have that available in our very productive second quarter of this year.

And and we were really really I think and.

And a different world at that point, and then of course with the pandemic.

Really we had to pivot and and and tried to work with our trial sites are as best as we could to address their local challenges and their patient level challenges and.

And you know we were still I think and the middle of that struggle, but so it's really in that sense and in order to compare the enrollment and characteristics of the two trials I would say.

Dr. Joseph Kim: So what we're excited about is confirming the safety of our boosting of INO4800 and the potential to expand and augment immune responses to INO4800. All right, I appreciate that. So, and another one I have on VGX 3100, just want to confirm the timing of the expected results for Rebuild 2, because it seems like it is being run in parallel. And also for companion diagnostic, would you think that... given, even without? [inaudible] Second question first, Aidan.

They were similar if not actually better enrollment that we were starting to observe which was really encouraging.

And in terms of a global and much more extensive global footprint. So but you know now we're dealing of course with a different a different situation, which is to make sure that our trial staff and their patients are all safe in terms of how they participate and art.

Trials, so, but you know I'm I'm encouraged by.

And what we've seen we've not.

Lost sight of what we need to do and really.

I think more and more trial sites have have really been.

Dr. Joseph Kim: We've been working with QIAGEN internally to develop a biomarker for VGX3100 for the last several years since the Phase 2 results. We think that it's a significant step towards really raising the commercial attractiveness of VGX3100 during launch and post-launch. Being able to target the patients with the most benefit from our immunotherapy, I think it provides an additional boost, pardon my pun, to the commercial attractiveness of this vaccine. [inaudible] The first part of the question, you know, enrollment was hampered throughout last year, and we're still trying to recover from that, from the global COVID pandemic, just like many of the other companies' large trials. So we haven't provided guidance on when we will finish.

Caged they've never lost their engagement and the fact is that that this disease. It simply does not go away it hasn't gone away and so we're simply not going to stop trying and and I'm hopeful that as the pandemic improves we'll actually be able to get back to that that rate.

Yeah.

Okay.

Yes inherent and my question I know that it's tough to compare us.

Cross trials, but inherent my question is when you consider the results of the phase two b versus the reveal one result, which was I was happy to see this statistical significance. It just seems like the effect size, where a little bit more.

More modest than in phase two b and that's not uncommon, but I'm wondering if there are particular compounding variables that youre looking at to help explain the differences or do you think that really one sample doesn't necessarily reflect the broader population.

Dr. Joseph Kim: But once we have more solid visibility, we will share it with the street. Now, what I can tell you is, due to the incredible hard work by our team, we're pretty much back to the pre-pandemic levels of early last year in terms of recruitment. So I think we're beginning a strong track back for reveal to enrollment during a global COVID pandemic. Okay, thank you very much. Congratulations again on the quarter.

Well the two samples really do stand independently and the key result is really the ability to meet the primary endpoint which were met.

And as we go through the trial once we have.

Completed reveal one and fully unblinded the trial will be looking at the complete dataset.

Aidan Huzinov: Thank you. Just a quick reminder to limit yourself to one question and one follower. The next question comes from Charles Duncan with Cantor Fitzgerald. Please go ahead. Hi. Hi, Joe.

And to be able to understand the population characteristics better.

Okay. That's fair and then if I can hop over to 4800 in terms of next steps and sorry, if I missed.

Charles Duncan: Thanks for taking my questions and congratulations on the progress, particularly the release of the 3100 Reveal 1 results today. That was a nice surprise.

Yes, it was presented before us but.

In terms of this year being able to complete phase two b and then phase three how do you feel about the current.

You know I guess infection rates, and and then case rates being able to provide even phase III data yet yet in 'twenty one.

Charles Duncan: I guess I'm wondering, when you consider Reveal 1 and the enrollment of patients in that trial versus, say, the Phase 2 experience, how would you compare and contrast those two clinical trial samples? Yeah, thank you. I'll briefly address these questions and then ask Dr. Buyan to comment as well.

Yeah. Thanks Jess.

And as I said, we expect to have the completed data from phase two studies and the early part of second quarter.

And well submit to the FDA to start the phase III. So our goal is to start the phase III trials and the latter part of the second quarter of this year.

Dr. Joseph Kim: You know, it's important, and thanks for reiterating that, Charles, is both in our Phase 3 Reveal 1 and our Phase 2 Dequile. There were both large 167 in phase two and a little over 200 in phase three trials. In both trials, we met all of the primary and the secondary endpoints based on the modified intention-to-treat statistical analysis. Therefore, these two trials were not designed to be cross-compared. But I'm going to ask you, statistically, they were not designed. Phase 3 was not designed to be compared to 2B. But I will ask Prakash to comment on this a little further. Prakash?

Now and all.

UA vaccines are getting rolled out.

And and there is couple of landscape changes, that's one and then and then of the new variants.

And really dominating for instance, the U K very and should be the dominant and varian and the U S. By later this month so.

And the landscape changes.

One thing we're doing us it was alluded to during the prepared remarks is we're looking to look both in the U S and ex U S.

To execute our phase III trial so.

And we're looking to accelerate all of these are first to make sure.

Dipesh A. Patel: Sure. So yeah, your question is really about the enrollment of phase two and then what we observed in the enrollment of phase three. And what we did in phase three was we expanded our geography considerably. We were enrolling in five continents.

That we can get to our efficacy data of INR 4800.

And as soon as possible.

And then in parallel.

And we are also working.

To test, what's the variance impact on 4800 Immunogenicity.

S well us to a low.

Average our silicon technology.

Dipesh A. Patel: We actually, pre-pandemic, were on track to actually beat the enrollment rate that we had observed in Phase 2, and we were really, really, I think, you know, in a different world at that point. And then, of course, with the pandemic, we really had to pivot and try to work with our trial sites as best as we could to address their local challenges and their patient-level challenges. And, you know, we're still, I think, in the middle of that struggle.

Two two.

To come up with our next generation Pan Covid vaccine.

Could address their U K, and South Africa, and Brazil, and variance directly but also have the broad protection and ability.

To protect against us secure variance because otherwise you're just playing catch up.

And.

We have utilized.

Utilized us and hone this technology against influenza and HIV and other rapidly changing viruses.

And we're very confident that we have a strong technology.

Dipesh A. Patel: But so, in that sense, you know, in order to compare the enrollment characteristics of the two trials, I would say they were similar, if not actually better enrollment, which we were starting to observe, which was really encouraging, you know, in terms of a global, a much more expansive global footprint. So, but, you know, now we're dealing, of course, with a different situation than we've seen. We've not lost sight of what we need to do, and really, I think more and more trial sites have really been engaged. They've never lost their engagement.

<unk> technology to go after these ever changing variance with the new program and we plan to develop both concurrently.

And we're very excited about the just the fact that our technology would allow us to do that.

Last question, Joe and this may be a total flavor and I apologize if it seems like it but.

And it's not meant to be my my question is what do you think about using your technology platform and.

As a follow up or booster to other vaccines and I guess any in particular, you think that that may be effective or additive in terms of efficacy without.

Dipesh A. Patel: And you know, the fact is that this disease simply does not go away. It hasn't gone away. And so we're simply not going to stop trying, and I'm hopeful that as the pandemic improves, we'll actually be able to get back to that rate. Okay. I guess inherent in my question, I know that it's tough to compare across trials, but inherent in my question is when you consider the results of the Phase IIb versus the Reveal I results, which I was happy to see the statistical significance of, it just seems like the effects guys were a little bit more modest than in Phase IIb. And that's not uncommon, but I'm wondering if there are particular compounding variables that you're looking at to help explain the differences, or do you think that really one sample doesn't necessarily reflect the broader population?

Increasing tolerability issues is is it possible that your platform could serve well as a plant and it's a booster.

Yeah, absolutely and and recover some of those potential and the prepared remarks and in fact, one of the reasons why we're doing a booster study and.

And between six to 10 months of the last vaccination and our phase one cohorts.

To demonstrate the safety and tolerability of that and the ability to boost immune response as a booster now of course, we've published a lot of papers around DNA vaccines for me and I'll view sister vessel booster to other vaccines and select a viral vectors and.

And maybe even messenger RNA.

Dipesh A. Patel: Well, the two samples really stand independently, and the key result is really the ability to meet the primary endpoint, which was met. And as we go through the trial, once we have completed Reveal 1 and fully unblinded the trial, we'll be looking at the complete data set to be able to understand the population characteristics better. Okay, that's fair. And then if I can hop over to 4800 in terms of next steps, I'm sorry if I missed it.

Yes.

Quick quickly and we know we can tolerability and deliver.

Such us and our GBM study.

Our patients receive half a dozen to a dozen.

Bruce across the timeframe of about two years.

And the clinical trials without any anti vector response or any stunting of the immune response.

And from INR 54, O one and we've seen similar impacts from other vaccines and that we've been testing and Ebola and HIV and others. So we're very confident that this may be a very strong and and and potential long term.

Dr. Joseph Kim: This was presented before, but in terms of this year, being able to complete Phase 2B and then Phase 3, how do you feel about the current, you know, I guess, infection rates and then case rates being able to provide even Phase 3 data yet in 2021? Yeah, thanks, Chas. As I said, we expect to... have the completed data from phase two studies in the early part of the second quarter. [inaudible] The UK variant should be the dominant variant in the U.S. by later this month.

Upsides for for AWS vaccine program.

Thank you for taking my questions Joe Great. Thank you for us.

The next question comes from E channel with H C. Wainwright. Please go ahead.

Alright. Thank you for taking my question first question just to follow up on the variability.

Between the.

Number of responders for the primary endpoint between reveal one study and the phase III study. So should we expect similar variability and the review to readout and how this kind of variability.

Dr. Joseph Kim: So within these landscape changes, one thing we're doing, as it was alluded to during the prepared remarks, is looking to recruit patients both in the U.S. and outside the U.S. to execute our phase 3 trial. And we're looking to accelerate all of these efforts to make sure that we can get to our efficacy data for INO4800 as soon as possible. And then, in parallel, you know, we are also working to test what the variant's impact on 4800 immunogenicity is, as well as to leverage our Syncon technology to come up with a next-generation pan-COVID vaccine that could address the UK and South African and Brazilian variants directly but also have the broad protection ability to protect against future variants. Because otherwise, you're just playing catch-up.

How should we expect that variability.

For it to translate to commercial prospects for per truck.

Yeah.

Yeah, Let me just quickly address that our and.

Number one and that's why.

So call it variability, but we call this oh right design.

That's why we have a placebo controlled and randomized double blinded and designed to make sure that we can account for us.

For any variability within the trial and.

And we think the the reveal one works as redesign.

As the phase <unk> study and were very optimistic that same thing will continue and reveal to us.

And in terms of the commercial attractiveness.

No. That's that's why we're also adding the biomarker portion.

Dr. Joseph Kim: And you know, as we have utilized this and honed this technology against influenza and HIV and other rapidly changing viruses, we're very confident that we have a strong technology to go after these ever-changing variants with the new program. And we plan to develop both concurrently. And we're very excited about just the fact that our technology would allow us to do so.

To increase the overall efficacy.

Absolute efficacy of VEGF, 3100 by focusing and helping the clinicians and and and.

And all of US focus on the right patient population, who have the best chance of being helped.

And by P. J F 3100 treatment so.

And where we're under right track and we're certainly excited.

Charles Duncan: Last question, Joe, and this may be a total flyer, and I apologize if it seems like it, but it's not meant to be. My question is, what do you think about using your technology platform as a follow-up or booster to other vaccines? And I guess any in particular you think that may be effective or additive in terms of efficacy without increasing tolerability issues. Is it possible that your platform could serve well as a booster?

And with our reveal one data and the progress, we're making with reveal to us.

Not to mention the progress, we're making and the biomarker.

And development with our partner Qiagen, So a lot more data to come and the and then.

Coming here.

Got it.

Second question, so considering the Johnson <unk> Johnson's covenant too bad things about you and to the market.

Dr. Joseph Kim: [inaudible] Quickly, we know we can tolerably deliver. We're very confident that this may be a very strong and potential long-term upside for Inovio's vaccine program. Thank you for taking my question. Great, thank you. The next question comes from Yi Chen with HC Raindroid. Please go ahead. Hi.

Do you think a large portion of the population would prefer a one dose regimen and to you.

And using your next generation and COVID-19 Best Inc.

A one dose regiment and set up too.

But you know I think.

Certainly one dose regimen and has a lot of attractiveness.

But as I mentioned before I think the one dose regimen and there's a full school and that you would likely almost every K O. L is predicting that as we deal with this COVID-19 Sars Covid two virus.

Yi Chen: Thank you for taking my question. First question, just to follow up on the variability between the number of responders for the primary endpoint between the Review 1 study and the Phase 2 study. So, should we expect similar variability in the Review 2 readout? And how does that variability, I mean, how should we expect that variability to translate to commercial prospects of the drug?

And that makes stage and as we look at the net term and the long term of this virus, we're not going to eradicate the virus from from from the Earth.

It's going to be with us for many years, so likely there will be additional boost so really what the initial administration to us.

Dr. Joseph Kim: Let me just quickly address that. Number one, you know, that's why we call it variability, but we call this, you know, the right design. That's why we have a placebo-controlled and randomized double-blinded design to make sure that we can account for any variability within the trial. And we think REVEAL-1 worked as we designed, as did the Phase 2B study, and we're very optimistic that the same thing will continue

I think it's less of an importance than what you do and the long term now that being said of course, one could be better than two.

But I think it's really the the overall efficacy and safety.

And then you know one thing to be concerned about is the potential tolerability of each booths.

Some platforms are not set up to be used us a booster.

Dr. Joseph Kim: And in terms of commercial attractiveness, you know, that's why we're also adding the biomarker portion to increase the overall efficacy and absolute efficacy of VGF3100 by helping the clinicians and all of us focus on the right patient population who have the best chance of being helped by VGF3100 treatment. So we're on the right track, and we're certainly excited about our REVEAL-1 data and the progress we're making with REVEAL-2, not to mention the progress we're making in biomarker development with our partner, QIAGEN.

Like the viral vector platforms.

And they're not really amenable because of the anti vector response.

There may be concerns about.

Formulations and messenger RNA delivery that may increase the severity and frequency.

Adverse events for each dosing.

But.

We'll need to track more data from the field in that regard one thing I can tell you is what we have seen with <unk> vaccines.

And as we can boost almost forever as I mentioned and our cancer vaccine trials patients to receive up to half a dozen to a dozen.

Dr. Joseph Kim: So a lot more data to come in the coming year. Got it. Second question: considering that Johnson & Johnson's COVID-19 vaccine is about, do you think a large portion of the population would prefer a one-dose regimen, and do you think that your next generation co-inhibitors would prefer a one-dose regimen? But, you know, I think. Certainly, a one-dose regimen has a lot of attractiveness

Doses of our vaccine same DNA with a different answer.

And without any tolerability or safety issues.

And we have we look forward for demonstrating that with our booster study from INR 4800, but we've seen and and have published around Ebola and HIV vaccine clinical studies and the past so.

Yi Chen: And then, you know, one thing to be concerned about is the potential tolerability of each boost. Some platforms are not set up to be used as boosters, like the viral vector platform.

We have a strong.

Confidence that INR 4800, and.

And our overall COVID-19 vaccines based on our platform could.

Dr. Joseph Kim: [inaudible] on our platform could be used as a booster, both for our vaccine, certainly, and then potentially for other vaccines. Got it. Thank you. The next question comes from Chris Raymond with Piper Sandler. Please go ahead. Hey, thanks for squeezing me in at the end. Two questions. So first, on VGX 3100, I know others have asked about Reveal 1 in the readout, but I don't think I really understand... which population is used for the primary endpoint?

Could be used us a a booster both for for vaccine certainly and then potentially for for other vaccines as well.

Got it thank you.

The next question comes from Chris Raymond with Piper Sandler. Please go ahead.

Oh, Hey, thanks, Thanks for squeezing me in here at the and.

Two questions. So it firsthand and P. J D 100, I know others have asked around reveal one and read out, but I don't think I really understand.

Which population is used for the primary endpoint.

Chris Raymond: And I apologize, I'm getting this question from a few investors. So I know all three, you know, ITT, modified ITT, and per protocol were pre-specified, but can you just say with clarity, Joseph, did the FDA agree that it's just the modified ITT that can serve as the primary endpoint, and that ITT is not part of the analysis? Or is there some sort of statistical hierarchy?

And I apologize if I'm getting this question from a few investors. So I know all three ITT modified ITT and per protocol were pre specified but can you just say with clarity Joseph J D.

The FDA agree that it's just the modified ITT to conserve as the primary endpoint.

And then I T. T is not part of the analysis or is there some sort of statistical hierarchy.

Chris Raymond: Well, no; we plan to present all three, MITT, ITT, and PERP protocols as well. And those were all specified. So you can think of that as three different methods.

Well no.

We plan to present, all three M I T T ITT and and per protocol as well.

And those were all specified so you can think of that.

As S. A a three different methods.

Dipesh A. Patel: But Prakash, would you like to comment on that question? Yeah, I'll just add that, you know, our expectation is that the FDA will review everything, of course, and so they will review, as Joseph said, all three analyses that were pre-specified in the trial protocol, and they'll also be reviewing the data from our Reveal-2 trial. And so it really is, you know, a comprehensive review of everything. The reason we put in the MITT and ITT results was really just to be complete and show you all of the data in terms of what was analyzed.

Cash would you like to comment on that question.

Yeah, I'll just add that.

So the.

Our expectation is that the FDA will review everything of course, and so they will review it.

Joseph said, all all three analyses that were pre specified and the trial protocol and there'll also be reviewing the data from our reveal two trial and so it really is a comprehensive review.

Of of everything.

<unk>.

The reason, we put the M I T T and ITT results and it was really just to be complete and and show you all of the data.

In terms of what was analyzed.

Dipesh A. Patel: So just to quickly add, Chris, to what Prakash said, the only difference between MITT and ITT was eight subjects whose endpoint data was not available at week 36. And they were confounding the breakdown of seven of those missing endpoints in the TRIA group versus the one in the placebo group, as it... You know, that was very skewed and unbalanced.

So okay just to quickly add Chris to pick US said, the only difference between that and it might T T and ITT is a eight subjects who was.

And point they are what's not available at week 36.

And there were a confounding.

And break you know.

The break breakdown of seven of those are missing and points.

And the treated group versus the one and the placebo group.

Yes.

You know that.

It was very skewed and unbalanced.

Chris Raymond: [inaudible] Right, okay. Thank you. And then maybe just a follow-up on, I know, 4800.

So that occurring and reveal too and I think is highly unlikely as the trial is two to one randomized so.

Chris Raymond: So just on the response time to the FDA, I was just looking back at your January prospectus, and that was, I think, about five weeks ago. You guys were still guiding the march as the goal to respond to the FDA, and I know on this call now you're saying it's May, or at least in your regulatory filings you said it was May. So can you maybe provide any specifics as to what's causing that pushback? This just kind of seems like it just really happened very recently.

If you look at the stats are only difference and that's only the only way only reason you're we're talking about this is because of those unbalance missing data points.

Right Okay.

Thank you and then maybe just a follow up and I don't know 4800, and so just on the response time to the FDA.

I was just looking back and at your January prospectus and that was I think about five weeks ago. You guys were still getting the March is the goal to respond to the FDA and I know on this call and now you're saying it's may.

Or at least and your and your and your regulatory filings you said for me. So can you maybe provides.

Any specifics as to what's causing that pushback.

And just kind of have it seems like it's just really happened very recently.

Dr. Joseph Kim: Well, we've been guiding by the end of March or early second quarter. I believe... beginning of this year as well. It's just compiling all of the data, and even from the data from our booster studies, which would provide a comprehensive package for the FDA, including all of the device-related and other responses. We are on track to do that in the early part of the second quarter now.

Well, it's and now we've been guiding them by.

By the end of March or early second quarter.

I believe are beginning of this share as well.

And it's just.

Compiling all of the data.

And even from the.

And the data from our booster studies.

And which would provide a comprehensive package for for the FDA.

Including all of the device related and that their responses. So.

We.

We we are on track to do that and early part of second quarter.

Dr. Joseph Kim: Okay. All right. Thanks very much. Yeah, thank you. This concludes our question and answer session. I would like to turn the conference back over to Joseph Kim for any closing remarks. Yeah, thank you very much, everyone. Have a great evening. The conference is now concluded. Thank you for attending today's presentation. You may now disconnect. BF-WATCH TV 2021

And now.

Okay, alright, thanks, very much guidance.

Yep. Thank you.

This concludes our question and answer session I would like to turn the conference back over to Joseph Kim for any closing remarks.

Yes, thank you very much.

Everyone have a great evening.

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

Yeah.

[music].