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Edited Transcript of INO earnings conference call or presentation 12-Mar-19 8:30pm GMT

Q4 2018 Inovio Pharmaceuticals Inc Earnings Call

BLUE BELL Mar 20, 2019 (Thomson StreetEvents) -- Edited Transcript of Inovio Pharmaceuticals Inc earnings conference call or presentation Tuesday, March 12, 2019 at 8:30:00pm GMT

TEXT version of Transcript

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Corporate Participants

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* Ben Matone

Inovio Pharmaceuticals, Inc. - Director of IR

* J. Joseph Kim

Inovio Pharmaceuticals, Inc. - CEO, President & Director

* Peter D. Kies

Inovio Pharmaceuticals, Inc. - CFO

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Conference Call Participants

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* Christopher Joseph Raymond

Piper Jaffray Companies, Research Division - MD & Senior Research Analyst

* Gregory James Renza

RBC Capital Markets, LLC, Research Division - Analyst

* Joel Lawrence Beatty

Citigroup Inc, Research Division - VP & Analyst

* Jonathan Matthew Aschoff

National Securities Corporation, Research Division - MD & Senior Biotechnology Analyst

* Naureen Quibria

* Stephen Douglas Willey

Stifel, Nicolaus & Company, Incorporated, Research Division - Director

* Yi Chen

H.C. Wainwright & Co, LLC, Research Division - MD of Equity Research & Senior Healthcare Analyst

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Presentation

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Operator [1]

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Good afternoon, everyone, and welcome to the Inovio Fourth Quarter 2018 Financial Results Conference Call. (Operator Instructions) Please also note, today's event is being recorded. At this time, I'd like to turn the conference call over to Mr. Ben Matone, Director of Investor Relations. Sir, please go ahead.

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Ben Matone, Inovio Pharmaceuticals, Inc. - Director of IR [2]

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Thank you, operator. Good afternoon, everyone, and thank you for joining the Inovio Pharmaceuticals Fourth Quarter and Full Year 2018 Corporate Earnings Conference Call. This call is being webcast live on our website, ir. Inovio.com and a replay will be available as indicated in our press release. During this call, we will conduct a question-and-answer segment, which will be reserved for equity research analysts.

Before we begin, I would like to remind everyone that on this call, we will make certain forward-looking statements that relate to our business, which include our plans to develop our DNA immunotherapy platform, in combination with our proprietary delivery devices, developments and timing on certain clinical data and readout as well as our capital resources, which include our cash burn guidance for 2019.

These statements involve certain assumptions, risks and uncertainties and could cause actual results to differ materially from these statements. All these statements are based on the beliefs and expectations of management as of today. We assume no obligation to revise or update forward-looking statement 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, which is posted on our website as well as the risk factors included in our filings with the SEC. Joining us from Inovio is Dr. J. Joseph Kim, President and CEO; and Peter Kies, Chief Financial Officer. Now I would like to turn the call over to Inovio's President and CEO, Dr. J. Joseph Kim.

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J. Joseph Kim, Inovio Pharmaceuticals, Inc. - CEO, President & Director [3]

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Thanks, Ben. Good afternoon, everyone. Thank you for joining us. Today, I'll reflect on our progress from the last quarter and the past year and tell you what we can -- what you can expect from Inovio in 2019 from our HPV program, from our cancer combination trials, from our global health vaccine portfolio. Finally, I'll close with a progress report on our new and exciting dMAb program. Later in the call, you will hear from our CFO, Peter Kies, with the financial update and more detail from our recent financing. A financing, by the way, that nearly doubled our year-end cash position of $81.5 million, and thus supports us in achieving results that will move our product over the goal line to commercialization. For me, the highlight of 2018 was when 4 head and neck cancer patients who initially were treated with MEDI0457 and subsequently received a checkpoint inhibitor when their cancers progressed. The result, 2 of the 4 patients achieved a sustained complete response or full cancer remission for over 2 years. This is every oncologist's dream, achieving a sustained complete response using an immunotherapy in their metastatic cancer patient. The fact that the treatment with our synthetic DNA vaccine followed with 2 different PD-1 inhibitors, that showed a complete response in 2 out of 4 progressors is very encouraging. I'll do the math for you. That 50% complete response rate using our combo strategy compared to 4% complete response rate by PD-1 inhibitors as monotherapies in metastatic head and neck cancer, that's 8 -- that's only 8 out of 192 patients for KEYTRUDA, and only 6 out of 240 patients for OPDIVO. In this context, our MEDI0457 data is even more impressive. And to expand on these developments, we reported that 20 out of the 22 patients showed elevated CD8+ T-cell response, T-cell activity that lasted at least several months after the final vaccine dose. This strongly suggests that the sustained CD8 T-cell responses from the dosing of MEDI0457 in these patients drove the complete responses in combination with PD-1 inhibitors. While additional data from the ongoing MEDI0457 Phase II clinical studies will provide more insights and statistical power to these current data. The 2 complete responses demonstrate the potential of our overall cancer combination strategy using our T-cell activating products, combined with various checkpoint inhibitors against an array of cancers. We expect continued updates and future publications from this program, which is now owned by AstraZeneca as we continue to monitor these 2 full remission patients as well as the other 18 nonprogressors from our Phase I study. Let me add more on our ongoing partnership with AstraZeneca.

This is what you can expect in the coming months. First, a Phase II study of MEDI0457 in combination with their checkpoint inhibitor durvalumab in metastatic recurrent head and neck cancer is going well. Last December, we announced that AZ started a second Phase II study in collaboration with MD Anderson, to evaluate MEDI0457 plus durva targeting broad array of HPV-related cancers. Important to Inovio was that the treatment of the first patient with cervical cancer resulted in a milestone payment from AZ to Inovio with cervical cancer as the second major cancer indication for this product.

Looking forward, we expect 1 additional Phase II milestone payments from AZ for a third major cancer indication when they dose a patient in another HPV-related cancer indication in the same study being conducted at MD Anderson in 2019. Moving now to our INO-5401 cancer combination trial. I'll begin with our collaboration with Regeneron Pharmaceuticals. In this Phase II trial, we are evaluating INO-5401 plus INO-9012 in combination with Regeneron's PD-1 inhibitor in patients with newly diagnosed glioblastoma. This trial currently has 20 sites opened within The United States. The study continues to recruit extremely well with a total enrollment of 52 patients almost completed. We anticipate interim efficacy data in the second half of this year that will show progression-free survival at 6 months, accompany with immune responses and safety data. Inovio's other Phase II study of INO-5401 plus INO-9012 in combination with Genentech's PD-L1 inhibitor is under evaluation for the treatment of advanced or metastatic bladder cancer. Here, we recently opened sites in Europe to further accelerate enrollment, along with 13 active sites in the U.S. Just like our GBM program, we anticipate interim efficacy results in the second half of this year.

To remind you, INO-5401 is composed of 3 of our most active SynCon cancer antigens combined into a single product. Our goal is to see if we can replicate the level of T-cell responses and anti-tumor responses we observe in our head and neck cancer study. Taking a look at our prostate cancer product, INO-5150. Late last year, we presented data from our Phase I/IIa study at ESMO. INO-5150 demonstrated a slowing of prostate-specific antigen doubling time in men with prostate cancer. Additionally, the data also revealed that 86% of the patients remained progression free at week 72 of the study, and it's really exciting to see almost 9 out of 10 patients showed no growth in their tumors a 1.5 year after treatment. We hope to advance INO-5150 into a novel checkpoint combination Phase II trial for prostate cancer with a partner. Shifting now to our lead product, VGX-3100, which continues to move forward in global Phase III trials. At the beginning of the month, we announced another company milestone with the start of the second and final portion of our Phase III trial, REVEAL 2, to begin recruiting patients. To be clear, with REVEAL 1 enrollment nearly completed, we will be utilizing European and other ex-U. S. sites, including new sites in Latin America to complete REVEAL 1 study. We are jumpstarting REVEAL 2 initially with only U.S. sites, both new sites as well as those which have been our top U.S. recruiters for REVEAL 1. Once REVEAL 1 is completely enrolled, we'll shift all of these sites to focus on REVEAL 2. The decision to open REVEAL 2 ahead of schedule and utilize our relationships with both U.S. and ex-U. S. sites does 2 things. First, it ensures we won't interfere with and overburden the sites on active recruitment. And second, as previously guided, it keeps the company on target to have a BLA submission for VGX-3100 in year 2021. Turning our attention now to development within our infectious disease portfolio. We reported that Inovio's vaccines for HIV, Zika, Ebola delivered intradermally or through the skin generated robust long-term antibody and T-cell immune responses, demonstrating nearly 100% vaccine response rate with very favorable safety profile. In this regard, we expect to see -- we expect to have clinical data from several Phase I vaccine programs published in the next few months, which include Ebola vaccine study, MERS U.S. vaccine trial, HIV vaccine study and the Puerto Rico Zika vaccine trial. So why is this important. This data is important because they are among the highest responses we've seen in any DNA vaccine, actually with any vaccine. These results are important because they will help us bring in more partnerships as well as funding from extensive sources like CEPI, DARPA, Gates and the NIH.

We plan to further develop transformative vaccine with future partnerships and funding. In 2019, Inovio and its partner GeneOne Life Science, with the full funding from the International Vaccine Institute, are conducting a Phase I/IIa MERS vaccine study in South Korea with data report expected this year. Inovio also plans to initiate a Phase II MERS vaccine field trial in the Middle East with full CEPI funding in the second half of 2019. Regarding our other infectious disease targets with full funding from CEPI, we will move our Lassa vaccine into the first human trial in the second quarter and a Phase II study is planned for year 2020 in Africa. These CEPI programs are important because our vaccines represent the first-in-class product and the successful completion of Phase II study could lead to a stockpile of these vaccines by CEPI in preparation for emergency use. Finally, I am really pleased to say that all patient sample have been collected for Inovio's Zika vaccine trial in Puerto Rico. Inovio's partner GeneOne is analyzing all samples blindly and we will report safety, immune responses and infection rate data from this study later this year. Before I turn over the call over to Peter, I'd like to touch on this morning's release, where we announced the appointment of Dr. Jacqueline Shea as Inovio's Chief Operating Officer. Dr. Shea is an experienced life sciences senior executive with an extensive track record of leadership. She has most recently served as CEO and COO of Aeras, the leading organization dedicated to developing new and more effective TB vaccines.

At Inovio, she will be responsible for Inovio's manufacturing, commercial, BD, and alliance management operations. Jacqui will join us as a key member of the executive team, along with our CFO and CSO in formulating and implementing overall corporate strategy. Under Dr. Shea's leadership, Aeras and its partner GSK recently reported groundbreaking primary efficacy data in the New England Journal of Medicine that GSK's M72 TB vaccine in a Phase IIb efficacy study significantly reduced the incidence of pulmonary tuberculosis disease in adults with latent TB, giving much needed hope for a new, more effective TB vaccine. M72 vaccine, tested successfully under Jacqui's leadership, is a potential game changer and represents one of the greatest advancements in TB vaccine in the last 50 years.

Across the board, Inovio has taken steps to streamline our management responsibilities to better align comprehensive development strategy from discovery to commercialization. To make this happen, we announced today that Inovio's global clinical, regulatory and R&D functions will report to Dr. Laurent Humeau, Inovio's Chief Scientific Officer. As a part of this realignment, Dr. Mark Bagarazzi, formerly our Chief Medical Officer, has left the company. I have known Mark for 25 years and wish him the best in his next endeavor. In place for the Chief Medical Officer position, Inovio's newly formed medical council will oversee all clinical studies and medical-related reporting and monitoring activity and report to Dr. Humeau. Inovio's medical council is comprised of 3 of Inovio's current Vice Presidents of Clinical Development MD. Our strategic reorganization will improve execution of current clinical programs and provide management alignment to seamlessly connect new product research to commercial product candidate. Jacqui, Laurent and the MDs who will serve on our medical council are all accomplished industry executives who have demonstrated their leadership qualities and deliver commercial results.

With that, I'll turn the call over to our CFO, Peter Kies, who'll discuss Inovio's fourth quarter and financial -- year-end financials. Peter?

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Peter D. Kies, Inovio Pharmaceuticals, Inc. - CFO [4]

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Thanks, Joseph. Inovio's total revenue for the fourth quarter and year ended 2018 was $2.5 million and $30.5 million, respectively. This compares to $8.8 million and $42.2 million for the same periods in 2017. Beginning on January 1, 2018, due to an accounting rule change, all contributions received from current grant agreements have been recorded as a contra research and development expense as opposed to revenue on the consolidated statement of operations. For the quarter and year ended December 31, 2018, $2.8 million and $9.5 million, respectively, was recorded as a contra research and development expense, which would have been classified as grant revenue in the prior year. Had this change in presentation not occurred, total revenue would have been $3.5 million and $40 million for the quarter and year ended December 31, 2018, respectively, compared to $8.8 million and $42.2 million for the same periods in 2017. Total operating expenses would have been $34.8 million and $134.1 million for the quarter and year ended December 31, 2018, respectively, compared to $31.7 million and $125.9 million for the same periods in 2017. Research and development expenses for the quarter and year ended December 31, 2018 were $26.4 million and $95.3 million, respectively, compared to $24.6 million and $98.6 million for the same periods in 2017. The year-over-year decrease in research and development expenses was primarily due to the $9.5 million contra research and development expense recorded from grant agreements as previously discussed. This was offset by an increase in clinical trial cost and partnering expenses. Inovio's net loss for the quarter and year ended December 31, 2018 was $33 million or $0.34 per share basic and dilutive and $97 million or $1.05 per share basic and dilutive, respectively, as compared to $21.5 million or $0.24 per share basic and dilutive, and $88.2 million or $1.08 per share basic and $1.09 per share dilutive for the same periods in 2017. Total cash and cash equivalents as of December 31 were $81.2 million compared to $85.5 million as of September 30, 2018. During the year-end December 31, the company sold approximately about 5.7 million shares of its common stock under a current and prior ATM sales agreement for an aggregate net proceeds of $29.2 million. As Joseph mentioned earlier, following our latest offering in the first quarter of 2019 that resulted in net proceeds of approximately $75.8 million raised through a convertible senior note offering, the company has nearly doubled its year-end cash balance. We expect the company's net burn to remain consistent with prior years where we anticipate the net burn to be approximately $70 million annually. As a reminder, our fourth quarter 2018 balance sheet and income and statement of operations can be found in today's press release or in the Form 10-K filed with the SEC as well as on our website under Investor and Financial Reports.

With that, I'll turn the call back over to Joseph. Thanks.

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J. Joseph Kim, Inovio Pharmaceuticals, Inc. - CEO, President & Director [5]

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Thanks, Peter. The last thing I want to draw your attention to today is actually a first, just a few weeks ago, Inovio announced that a subject was dosed as part of the first-ever human study of Inovio's DNA-encoded monoclonal antibody or dMAb technology, funded fully by the Gates Foundation. This trial's focus is on evaluating this dMAb's ability to prevent or treat Zika virus infection. However, results from this trial will also help to broadly advance Inovio's dMAb platform in infectious disease and cancer. Remember, the innovation tapped in our dMAb, when delivered directly into the body, the genetic codes provided by the synthetic nucleic instruct the body cells to become the factory, which manufactures the therapeutic antibody product, enabling a major leap forward in antibody technology. While Inovio prepares a disruptive alternative to traditional monoclonal antibodies, remember that they represent the largest segment of pharmaceutical markets today accounting for more than $100 billion in pharmaceutical sales each year with treatment spanning cancer, infectious diseases, inflammation and cardiovascular diseases.

With this synthetic design and inpatient production, dMAb products may represent a transformative entrant to this important class of pharmaceutical. We're in a great position to execute on our innovation and expansion into other areas that utilize our immunotherapy technology, the technology that has exhibited a very favorable safety profile and one that generated continuous funding and interest from groups like the Parker Institute, the Gates Foundation, DARPA and many others, along with major pharma and biotech companies like AstraZeneca, Roche, Genentech and Regeneron.

In closing, we listen to our investors. And we've taken strategic actions to ensure Inovio's continued advancement and to improve our ability to deliver results. Let's face it, we had a good 2018, but I know we can do better. I can confidently say that we are entering the rest of 2019 as a very well financed organization with the right resources and leaders in place to advance our later stage programs into commercialization.

Now I look forward to taking questions and adding additional color on our programs and developments with you. Operator, please open the line for the analysts.

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Questions and Answers

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Operator [1]

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(Operator Instructions) Our first question today comes from Gregory Renza from RBC Capital Markets.

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Gregory James Renza, RBC Capital Markets, LLC, Research Division - Analyst [2]

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My question is that I just wanted to drill down a little bit on the REVEAL trials and the respective time lines. Helpful to hear about the alignment of REVEAL 1 and 2 as far as REVEAL 2's initiation as well as your reiteration of the BLA filing around 2021. However, I just want to get a sense of what the implications are around seeing that data. I think previously you had spoken about a 2020 time line. I just wanted to see how that squares with the trial alignment and also, just some observations on ClinicalTrials.gov, which suggest that the other may have been extension of the completion date for the trial around the 2021, for both trials?

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J. Joseph Kim, Inovio Pharmaceuticals, Inc. - CEO, President & Director [3]

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Yes. Thanks, Greg. REVEAL 1 and REVEAL 2, as you know, are -- we are enrolling 198 patients in each of these primary and confirmatory Phase III studies. Under our current assessment, we feel that we should be able to achieve clinical efficacy and safety data by the second half of 2020. Obviously, these are predicated upon our execution and closeout of the enrollments for both studies and execution of these studies. In terms of the ClinicalTrials.gov, we're going to adjust those based on some regulatory requirements from the government and it's going to reflect on full impact and estimates from all of the moving parts of the trial. But we're very optimistic and confident that we should be able to see the efficacy and safety data from both studies towards the end of 2020 as we had estimated previously, and we're on target for BLA filing by -- during year 2021.

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Gregory James Renza, RBC Capital Markets, LLC, Research Division - Analyst [4]

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Great. And just a quick follow-up with respect to the addition of some Latin America sites, I'm just curious on your expectations for that, to what extent that would potentially accelerate or bolster the enrollment trajectory to date?

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J. Joseph Kim, Inovio Pharmaceuticals, Inc. - CEO, President & Director [5]

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Yes, we're very bullish on those new sites and new countries. Certainly, there's lot of -- there are a lot of women with the cervical precancer in those areas. And we are very optimistic that those new sites will bring additional acceleration for enrollment going forward for both REVEAL 1 and REVEAL 2.

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Operator [6]

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Our next question comes from Chris Raymond from Piper Jaffray.

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Christopher Joseph Raymond, Piper Jaffray Companies, Research Division - MD & Senior Research Analyst [7]

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And sorry, this might be a little repetitive, but I'm not sure I heard you answer in the first question, but another one on REVEAL. So can you just confirm, I thought initiation of REVEAL was gated by -- REVEAL 2, I'm sorry, is gated by the completion of REVEAL 1. So can you just confirm, are you -- you announced that you're initiating it, but is first patient in, still a ways off or when will that happen?

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J. Joseph Kim, Inovio Pharmaceuticals, Inc. - CEO, President & Director [8]

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Yes. So thank you, Chris. So we were very simplistic in our description of the switchover previously. Obviously, you don't -- it's not a spigot that you turn off right away and opening up a second trial. So there's going to be an overlap between REVEAL and REVEAL 2. So we launched REVEAL 2 a couple of weeks ago, and we expect the first dosing from REVEAL 2 to occur in April. And we're continually finishing up the REVEAL 1 enrollment. So there's going to be a little bit of overlap and that is like the 2 curves overlapping in the front and the back end. So we felt this would provide the best crossover and best positioning of both studies. Because finishing 1 study before the other really doesn't buy us the -- any time in our BLA submission. So as we have been executing our REVEAL studies for the last year or so, we felt that this is the best way to maximize overall the time line or shorten the time line to BLA filing the best.

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Christopher Joseph Raymond, Piper Jaffray Companies, Research Division - MD & Senior Research Analyst [9]

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Great. And then maybe just a follow-up on -- I think you mentioned your GBM combo trial for 5401 is almost done with enrollment. Can you -- I'm sorry, if you said this already. But can you maybe talk about when it will be completed, what's your sort of sequence for providing the data or what can we expect to hear on that trial, I guess, this year?

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J. Joseph Kim, Inovio Pharmaceuticals, Inc. - CEO, President & Director [10]

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Yes, we're so excited about finishing the enrollment for 5401 GBM study. As just to remind you, our primary efficacy endpoint is the improvement in overall survival at both 18 months and also at 12 months. At 18 months, OS18 being more definitive, but obviously that's going to take some time. So this year, we have been projecting the data for PFS or progression-free survival at 6 months into the study as a early indicator for how well these patients are doing. But I have full confidence that we'll do that with a total of 52 patients before the year-end. I have also strong confidence that we'll have PFS 12 or at 12 months for a vast majority of our patients before the year-end. So what do these results mean? Well, we can track the progression-free status of these patients leading into our overall endpoints probably early next year. Obviously, OS numbers are more definitive and it's tracking certainly to our primary endpoints. But, I think, PFS will give us a pretty early good readout how well these patients and how well our trials are executing. But, overall, I'm very happy. We're ahead of the schedule in terms of enrolling these GBM patients and then we're challenging ourselves to catch up or bring our bladder study to the similar rate that we're enjoying in GBM. This goes back to all of our Phase II and Phase III studies. We've been doing well up to now. We want to make sure we can do even better and that's part of our strategic reorg and our renewed focus in reenergizing our programs to make sure we have full alignment, full devotion of our resources and efficiency. And ultimately, patients are waiting and we want to make sure that we can get to our final data as rapidly as possible.

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Operator [11]

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Our next question comes from Joel Beatty from Citi.

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Joel Lawrence Beatty, Citigroup Inc, Research Division - VP & Analyst [12]

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Great. First one is on MEDI0457. Obviously, the early data has shown a strong response rate in small number of patients, much higher than what you see with monoclonal antibodies. Could you discuss what data could be coming next and what remains to be seen before advancing that program into a pivotal study?

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J. Joseph Kim, Inovio Pharmaceuticals, Inc. - CEO, President & Director [13]

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Yes. So, I mean, thanks, Joel. We're very, very excited about MEDI0457. It's second of our efficacy readouts, the first being 3100 that's showing. And we're beginning to have larger body of evidence during the clinical efficacy of our programs really impacting the disease and we're very excited about that. Now that being said, this product was licensed out to AstraZeneca in 2015. So they have a full say and full development rights and so on. Inovio is a passenger in their vehicle. Certainly, a very profitable in that as they advance those programs we'll be collecting our milestone, and ultimately the royalties and so on, which are very significant and -- but as we observe these data to come out, we expect MEDI's Phase II trial targeted with about 50 head and neck metastatic cancer patients in combination of 457 plus their durva PD-L1 inhibitor to be the next study report to come out. AZ has complete control over that study results, but I can tell you that they're probably very excited to report those data in the coming months and quarters. But they have the full say. Now they've expanded into other indication in the second study. So I touched on that in our prepared -- in my prepared remarks. So the MD Anderson study is a pan-HPV cancer study, MEDI0457 plus durva study. So dosing of the cervical cancer patients as part of that study trigger a second Phase II milestone payments from MEDI to us or AZ to us. We expect the third indication to be dosed -- patient to be dosed later this quarter potentially or the second quarter, and that will trigger a -- any day now a third Phase II milestone payment from them. So these trials are moving. Obviously, AZ has the full control and cadence of executing these trials. But the data that will come out, we feel will comprehensively support our thesis, which is taking Inovio's T-cell -- CD8 T-cell generating immunotherapy, combined with a checkpoint inhibitor will bring about higher clinical efficacy than just the monotherapy with a checkpoint inhibitor, and it should work against all of these different cancers caused by or associated with HPV with MedImmune product. We want to expand that with our own study in INO-5401 into GBM and bladder and other cancers that we can hit with INO-5401. If we can completely -- if we can expand what we saw in MEDI0457 to INO-5401, there's no ceiling for what Inovio's platform or immunotherapy platform will do in cancer and we're very excited about what's to come.

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Joel Lawrence Beatty, Citigroup Inc, Research Division - VP & Analyst [14]

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Great. And then another question on the dMAb program. Just a few weeks ago or so, it sounds like you dosed the first patient. Can you discuss the process of monitoring that patient and where that's at? And what the steps would be towards dosing additional patients with dMAb?

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J. Joseph Kim, Inovio Pharmaceuticals, Inc. - CEO, President & Director [15]

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Yes, thank you. These are dose escalation studies. So the first 3 is standard 3-plus-3 design. So first 3 patients have been dosed. There's been 0 safety concerns at the lowest dose, and then after 28 days we move on to the second dose and so on. And once all those escalations has been done, we can complete and backfill all 24 patients. So our bar for the first study, our objectives are pretty low. We want to see measurable expression of these dMAbs in the patient blood -- patient's blood. Once we can detect that, we can utilize our optimization algorithm to improve the overall expression. So while this is a Zika dMAb study, it also has huge value for our dMAb platform development at the same time. And I can add here, that being able to democratize the uses of powerful monoclonal antibody therapy for additional people around the world has been a dream of Bill Gates, and that's a dream that I share, and we may have the true technology to be -- to be able to do that. So that's why Gates Foundation is interested because you can apply the dMAbs in a much practical fashion. Inovio has additional motives. We think this is a better product. All of our products are kept in the long term at 2 to 8 refrigeration instead of being frozen. We can express better. We just had a new paper that compares our optimized design of KEYTRUDA to have 3 or 4 higher expression gene-for-gene with additional potential patents covering those sequences. So the potential of our dMAb products platform is immense and we're at the -- we went from concept -- conceptual wish to animal test with high levels of expression in matter of 2, 3 years. Now we have progressed this program into clinical evaluation. So I don't know where we're going to be. We're certainly going to advance the ball quite a bit in the next 12 months with additional trials starting. We expect additional corporate partnerships in this regard. Certainly, a lot more funding from Gates and other sources. So far, we received funding from DARPA and the NIH and Gates Foundation. We expect additional supportive funding from multiple organizations in addition to corporate partnerships that we would like to strike, and we have discussions ongoing at this point. So I think, the dMAbs are not fully baked into any of your models, all of the analysts on the call. So I think, this is where we can bring more value to our shareholders moving forward.

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Operator [16]

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Our next question comes from Stephen Willey from Stifel.

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Stephen Douglas Willey, Stifel, Nicolaus & Company, Incorporated, Research Division - Director [17]

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Just to follow up on REVEAL. Joseph, the guidance for a year-end '20 data dissemination, is that the 40-week read from both REVEAL 1 and REVEAL 2 or is that just the REVEAL 1?

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J. Joseph Kim, Inovio Pharmaceuticals, Inc. - CEO, President & Director [18]

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Now REVEAL 1 -- yes, REVEAL 1 is a 36 primary endpoint with additional 1-year safety period. So that is a 88-week -- full 88-week study. REVEAL 2, in contrast, has 1-month follow-up or 4 weeks follow up. So that's the 40-week study. So that's the only difference between REVEAL 1 and REVEAL 2.

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Stephen Douglas Willey, Stifel, Nicolaus & Company, Incorporated, Research Division - Director [19]

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So in terms of the guidance for having data from these trials in the second half of 2020. Is that going to be the 36- and 40-week data from both of these trials?

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J. Joseph Kim, Inovio Pharmaceuticals, Inc. - CEO, President & Director [20]

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No. That's -- we expect 88 and 40 weeks data from REVEAL 1 and REVEAL 2, respectively.

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Stephen Douglas Willey, Stifel, Nicolaus & Company, Incorporated, Research Division - Director [21]

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Got it. And then just with respect to enrollment into the bladder cancer trial, it sounds like it's maybe occurring a little bit slower than expected. What's the attribution there? Is that -- I know it's a pretty competitive development landscape right now. Is it just difficulty in finding patients? Is it just site logistics?

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J. Joseph Kim, Inovio Pharmaceuticals, Inc. - CEO, President & Director [22]

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Yes. Well, I think, compared to a sister study in GBM our bladder study is behind. But that speaks to the desperation and the demand that GBM patients and sites have for that disease. So I wouldn't characterize that we're behind, but I will say that bladder is lot more competitive. But I think, our U.S.-based -- 13 sites we have in the U.S. are competitively enrolling patients. We wanted to bring in more sites ex-U. S. to accelerate this trial because we're -- we designed the 5401 study to be a book end study to looking at the spectrum of immune responsiveness tumors, bladder being one and more immune responsive type of tumor versus GBM being the other. So we would like to execute on both studies when we started to be in the similar cadence and timing. Now we were just -- we blew -- we got overblown by the demand and the enrollment velocity that we had for our GBM study. So we just want to push, give a nudge to our bladder study as well. So we have a little bit of sibling rivalry within our programs. I think that's healthy. And we want to -- the resources that we're saving in GBM in terms of the accrual, we can push into our bladder. So that's why we're doing this.

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Stephen Douglas Willey, Stifel, Nicolaus & Company, Incorporated, Research Division - Director [23]

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Okay. And then just on the dMAb program, is that presumably targeting a viral protein that's part of the...

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J. Joseph Kim, Inovio Pharmaceuticals, Inc. - CEO, President & Director [24]

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No. Well, so...

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Stephen Douglas Willey, Stifel, Nicolaus & Company, Incorporated, Research Division - Director [25]

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Or is it targeting a host protein?

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J. Joseph Kim, Inovio Pharmaceuticals, Inc. - CEO, President & Director [26]

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So this is a full length sequence -- optimized sequence for that binds to a Zika GP protein. This particular dMAb product that's in Phase I study. But in theory and we have developed a couple of dozen different dMAbs targeting anywhere from PCSK9 all the way to our own version of KEYTRUDA and OPDIVO, all the way to Humira equivalents. Yes, it really -- I don't think really matters what we target. We combined and maintained functionality just by adjusting our DNA sequence. That's really the beauty of this platform is we can transcend some of the folding and stability issues of protein-based monoclonals during their construct and during their manufacturing and during their formulation and delivery. So our dMAb platform has significant advantages over conventional MAb technologies, so -- and our goal is to make sure that we have the proper delivery and know-how and algorithm to design and execute on these dMAbs, and we're learning really tremendous amounts every week and every month. So there will be even more exciting scientific advancements in the dMAbs in the coming weeks. And this clinical study that we initiated last month just really points to the advancement of this in human subjects, and so far so good.

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Stephen Douglas Willey, Stifel, Nicolaus & Company, Incorporated, Research Division - Director [27]

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Okay. So the program is specifically targeting then a viral protein, that doesn't have any host homology?

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J. Joseph Kim, Inovio Pharmaceuticals, Inc. - CEO, President & Director [28]

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Yes.

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Stephen Douglas Willey, Stifel, Nicolaus & Company, Incorporated, Research Division - Director [29]

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Okay. And is the threshold -- I know you talked about some of the other targets that you've developed preclinically or at the bench, but does -- is the threshold for moving into patients in targeting, obviously, a functional host protein. Does the safety threshold there become higher?

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J. Joseph Kim, Inovio Pharmaceuticals, Inc. - CEO, President & Director [30]

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Well, higher than a viral protein, but a lot of our targets have already been tried like the PD-1 target. We don't believe we will add anymore safety concerns than protein PD-1 inhibitor like pembro or nivo, for instance. But these are -- I mean, we're going to take necessary care and due diligence when we dose escalate each of these programs.

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Operator [31]

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Our next question comes from Jason McCarthy from Maxim Group.

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Naureen Quibria, [32]

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This is actually Naureen on for Jason. So I'd like just to drill down on the GBM study that you have with Regeneron's PD-1. If you're looking at checkpoints, they've been -- it's been challenging in GBM indication and a lot of others haven't found much success if you look at CheckMate 143 with OPDIVO, the rationale was that it didn't [exceed] because 40% of the patients were taking steroids to control brain swelling, but they clearly interfered with the immune response. Are you taking that into consideration with your combination as part of your trial or how do you address to circumvent this issue?

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J. Joseph Kim, Inovio Pharmaceuticals, Inc. - CEO, President & Director [33]

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Yes, those are all considerations. Obviously, the doctors have to treat the patients as any complications develop during their cancer. The difference, I think, between the study that you referred to versus this one is we have targeted the newly diagnosed patients. I agree with you, GBM has been a challenge for checkpoint monotherapy. Let's face it, Naureen, the GBM has been a challenge for all therapies. So that speaks to a lower bar or high bar ensuring efficacy, but low bar ensuring marginal improvements in efficacy. So I spoke earlier, while talking to Steve about the tumor responsiveness spectrum. We think that's one of the reasons why GBM has been so hard to treat, especially within immunotherapy. We think we can improve that by generating CD8 T cells against our 3 targets, WT1, PSMA and hTERT. And combining with Regeneron's PD-1 inhibitor that has been tested in GBM as a monotherapy. We think we can improve the overall impact of the immunotherapy. That's our goal. As I said, the bladder has a higher probability of success, but higher threshold or higher bar in ensuring the marginal improvement. GBM as a sister study has got a higher threshold of efficacy, but lower bar to show marginal improvements in efficacy. So that's why we are concurrently conducting these 2 studies. We also feel that our immunotherapies, 5401 or MEDI0457, they should all work with any checkpoint inhibitors. And that's the reason why we've chosen to use 2 different checkpoint inhibitor with Regeneron's PD-1 for GBM and Genentech's PD-L1 for bladder, and we look forward to seeing the data and reporting the data in the coming months.

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Naureen Quibria, [34]

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Sure. And in the same study, these are postsurgical patients, correct?

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J. Joseph Kim, Inovio Pharmaceuticals, Inc. - CEO, President & Director [35]

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Yes.

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Naureen Quibria, [36]

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So just as a follow-up. Recently at UCLA, there was a small study that showed that if you treat with checkpoints prior to surgery, it's more effective. So would you consider putting an arm combining INO-5401 plus Regeneron's PD-1 prior to surgery and radiation treatment?

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J. Joseph Kim, Inovio Pharmaceuticals, Inc. - CEO, President & Director [37]

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No, we haven't looked. Well, we haven't considered all of different possibilities and study designs. As we develop this program through the current trial, we are very -- Jeffrey Skolnik, who heads up our Oncology Clinical Development, and his team are extremely well in tune with other going ons and other advancements. So if it rises to our interest to actively test that hypothesis or whether passively see how those results are going to evolve. We can't -- I can't really comment on that in this call. But rest assured, we are looking at all of our competitive approaches and other data and GBM is challenging. And that's why we chose this as one of our targets. And I think it speaks to the desperation of this disease, and certainly the opportunity to bring better medical intervention, utilizing hopefully with INO-5401 and Regeneron's PD-1 inhibitor, cemiplimab. So we're very optimistic with this program.

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Operator [38]

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Our next question comes from Yi Chen from H.C. Wainwright.

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Yi Chen, H.C. Wainwright & Co, LLC, Research Division - MD of Equity Research & Senior Healthcare Analyst [39]

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Is there any update regarding GLS-5700 in Puerto Rico, and whether that trial is going to read out before the dMAb study? And if both trials have positive results, does one product takes priority -- the dMAb product takes priority over GLS-5700 and which of them has potentially the fastest regulatory pathway available to reach the market?

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J. Joseph Kim, Inovio Pharmaceuticals, Inc. - CEO, President & Director [40]

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Great question, Yi. Very tough. GLS-5700, our Zika vaccine in Puerto Rico. As I updated in the comments -- prepared comments, all of the visit samples have been collected. The data analysis assays are being done now. It was just to recollect ourselves, it's a double-blinded trial. 80 patients receiving our vaccine, 80 placebo. And we're opportunistically looking at infection rates of Zika. So it's a very ambitious and very exciting study. And we'll report this as soon as we have the full set of data. But we're very much looking forward to this. We will present this and publish in just the way we do with all of our programs. Now I wouldn't say our Zika dMAb plus or the Zika vaccine, they're not necessarily competing per se. In fact, our DARPA contract that we received first for Ebola and for other programs, actually the beauty of our technologies, you can co-dose. Both the dMAb for short term, immediate protection and for vaccine to provide a longer-term protection. And these were deemed to be very important for U.S. military as well as perhaps the travelers and other health care professionals and highly risk groups and folks who are more exposed endemically. So I think one does not preclude the other, but that will be a great problem for us to have. But independently, I expect to have data from both studies, providing great information. The development path for each of those really will depend on partners and funders and a real -- and clinical end for these vaccines and dMAbs. But they both have their own strength in what we're trying to get out from these clinical studies.

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Operator [41]

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Our next question comes from Jonathan Aschoff from National Securities.

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Jonathan Matthew Aschoff, National Securities Corporation, Research Division - MD & Senior Biotechnology Analyst [42]

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I was -- I'm kind of wondering regarding both of the head and neck cancer patients that responded to PD-1's after progressing on 457, is there really any evidence that 457 contributed to either of those complete responses, given that the patients progressed between vaccination and PD-1 therapy?

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J. Joseph Kim, Inovio Pharmaceuticals, Inc. - CEO, President & Director [43]

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Yes, great question. So we're able to tease out the antigen specific T-cell responses in these patients, and some of that was included in the clinical cancer research publications from last fall. Obviously, we're doing a lot more follow-ups from these patients as well as more patients eventually progress, we'll be able to track that. Perhaps the best answer would be MEDI's concurrent study that they're dosing, already metastasizing recurrent head and neck patients with both durva and MEDI0457 and testing the immune responses in these patients and looking at clinical response compared to the patient experience with durva alone, I think, that's a more direct comparison. So a lot more data should be forthcoming from all of these studies.

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Jonathan Matthew Aschoff, National Securities Corporation, Research Division - MD & Senior Biotechnology Analyst [44]

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Okay. Outside of any ATM use or warrant exercise or receipt of milestones, how long does your $157 million last, would that be about mid-2020?

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J. Joseph Kim, Inovio Pharmaceuticals, Inc. - CEO, President & Director [45]

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No, it's -- our guidance is about $70 million in net burn for '19 and '20 each. So we think we'll have more than 2 years of cash runway.

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Jonathan Matthew Aschoff, National Securities Corporation, Research Division - MD & Senior Biotechnology Analyst [46]

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But that burn includes things like ATM and warrant and milestones or it excludes them?

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Peter D. Kies, Inovio Pharmaceuticals, Inc. - CFO [47]

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It is -- Jon, this is Peter Kies. It excludes ATM activity, but milestone activity would be included in that.

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Jonathan Matthew Aschoff, National Securities Corporation, Research Division - MD & Senior Biotechnology Analyst [48]

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Okay. And lastly, may I ask why Mark left?

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J. Joseph Kim, Inovio Pharmaceuticals, Inc. - CEO, President & Director [49]

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Can you say that again?

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Jonathan Matthew Aschoff, National Securities Corporation, Research Division - MD & Senior Biotechnology Analyst [50]

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Why did Mark leave?

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J. Joseph Kim, Inovio Pharmaceuticals, Inc. - CEO, President & Director [51]

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It was part of the strategic reorg. I felt that combining and aligning, I asked him to leave. And aligning clinical, regulatory and R&D functions under same supervision would benefit from better alignment and better execution. So -- and we explained that in the prepared remarks. But, I think, we should be able to -- we've been doing this well. But I feel that we can do better. We got to move faster, we have to execute better. We owe it to our shareholders. We owe it to the patients that we're looking to help. And the strategic reorg, and really, frankly, all of our efforts are trying to enhance our capabilities and our execution capabilities to improve on our delivery.

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Operator [52]

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And ladies and gentlemen, at this time, I'm showing no additional questions. I'd like to turn the conference call back over to management for any closing remarks.

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J. Joseph Kim, Inovio Pharmaceuticals, Inc. - CEO, President & Director [53]

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Well, thank you, everyone, for your questions and joining us on the call today. We look forward to sharing more on our trials and program advancements on our next earnings call in May. Have a great evening. Thank you.

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Operator [54]

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Ladies and gentlemen, that does conclude today's conference. We do thank you for joining. You may now disconnect your lines.