Edited transcript of the conference call or presentation on the INO result from November 12 to 7:30 p.m. (GMT)

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BLUE BELL January 3, 2020 (Thomson StreetEvents) – Minutes of the conference call or presentation of Inovio Pharmaceuticals Inc results released Tuesday, November 12, 2019, 9:30 p.m. (GMT)

Inovio Pharmaceuticals, Inc. – Director of IR

* J. Joseph Kim

Inovio Pharmaceuticals, Inc. – CEO, President and Director

Inovio Pharmaceuticals, Inc. – Vice President of Clinical Development – Oncology

* Peter D. Kies

Inovio Pharmaceuticals, Inc. – CFO

Hello everyone, and welcome to the Inovio third quarter 2019 financial results conference call. (Operating instructions) Please note that today's event is also recorded.

At this point, I would like to hand over the conference call to Mr. Ben Matone, Senior Director Investor Relations. Sir, please keep going.

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

Thank you, operator. Hello and thank you for participating in the Inovio Pharmaceuticals earnings conference call for the third quarter of 2019. Today Inovios are President and CEO, Dr. J. Joseph Kim, in conversation. our CFO Peter Kies; and Dr. Jeffrey Skolnik, vice president of clinical oncology development.

Today's call will be broadcast live on our website ir.inovio.com, and a repeat of today's call will be provided shortly after the call is completed. After a general business update, we will conduct a question and answer segment reserved for stock analysts.

When prompted, we make forward-looking statements about our business, including our plans to develop Inovio's integrated platform for synthetic DNA immunotherapy in combination with our proprietary delivery devices, clinical and regulatory developments, and timing of clinical data readouts along with our capital resources , All of these statements are based on management's beliefs and expectations today. These statements involve certain assumptions, risks and uncertainties and may cause actual results to differ materially. We assume no obligation to revise or update forward-looking statements based on new information, future events or for any other reason. Investors should carefully read the risks and uncertainties described in today's press release and the risk factors contained in today's 10Q filing with the SEC.

I would now like to call Inovio's President and CEO, Dr. J. Joseph Kim, forward.

J. Joseph Kim, Inovio Pharmaceuticals, Inc. – CEO, President and Director [3]

Thank you very much, Ben, and thank you to everyone who attended the call and webcast. Towards the end of the year, I would like to spend some time thinking about our successes in 2019, but also focus more on 2020 as a transformation phase for Inovio.

Let me drive a time machine until November 2020. By that time next year, we will all show you the GBM overall survival data for INO-5401 after 12 and 18 months. REVEAL 1 data on the effectiveness of our phase III cervical dysplasia, VGX-3100; VGX-3100 Phase II results for vulvar and anal dysplasia; Our Lassa vaccine, an orphan-labeled UVP study, is being tested in Africa in a Phase Ib study and our MERS vaccine in the Phase II study in the Middle East with full funding from CEPI. Our China partner ApolloBio will be in Phase III in China with the VGX-3100. We expect AstraZeneca to report the results of the Phase II head and neck cancer efficacy study using MEDI0457 in combination with its checkpoint inhibitor.

Phew, what an incredible set of value drivers in a year, but let me turn off my time machine and focus on the present. Last week we reported positive interim results from our ongoing Phase II trial with our newly diagnosed glioblastoma multiforme or GBM that combines Inovios INO-5401, a T cell activating immunotherapy that works for 3 tumor-specific antigens, hTERT, WT1 and PSMA , encoded. and INO-9012, an immune activator encoding interleukin-12, in combination with Libtayo, Regeneron's PD-1 inhibitor.

In summary, the most important preliminary data from the clinical study with 52 patients showed that 80% of the patients methylated with MGMT gene promoter and 75% of the non-methylated patients after 6 months, measured from the time of their first dose, were free from disease courses. These results significantly exceed the historical standard of care data. These data were presented at the annual meeting of the Society for Cancer Immunotherapy last week. Inovio will release overall survival data for 12 and 18 months next year.

Before we look at the other updates to the cancer combination program, Dr. Jeffrey Skolnik, who leads the development of Inovio's immuno-oncology, presented this data at SITC last week to enable a more detailed analysis of this data and its comparability to historic nursing standards. Jeffrey?

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Jeffrey Skolnik, Inovio Pharmaceuticals, Inc. – Vice President of Clinical Development – Oncology [4]

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Thank you very much, Joseph. As Joseph mentioned in his opening speech, the past week has been very positive for our GBM program and we are very excited to provide this new clinical data to both the clinical and investment community. The excitement about this data was obvious to me as our groundbreaking SITC poster presentation attracted a lot of attention from the participants in the meeting.

We would like to underline that glioblastoma is a very difficult disease to treat, with most patients dying from their brain tumor within 1 to 2 years after diagnosis. In our most recent preliminary data, we showed that 75% of our unmethylated MGMT promoter patients and 80% of our methylated MGMT promoter patients were progression free after 6 months.

This is very cheap if we compare it with historical controls. We expect that only about 40% of unmethylated patients and about 60% of methylated patients will be without progression after 6 months. We were also very excited that almost all of the patients tested so far generated antigen-specific T cells against the tumor associated antigens generated by our therapy, and we look forward to our data next year, as you indicated, Joseph, to possibly do so confirm an overall survival benefit.

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J. Joseph Kim, Inovio Pharmaceuticals, Inc. – CEO, President and Director [5]

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Thank you very much, Jeffrey. While we certainly appreciate that this is a very difficult cancer to treat, we should all feel encouraged by this new data and know what it will do for the future of Inovio's immuno-oncology skills and for those with GBM who have none , really means witnessing new effective treatments for years.

I would also like to emphasize here that GBM data has two other far-reaching effects. First, because the tumor-associated antigens comprising INO-5401, namely hTERT, WT1 and PSMA, are also over-expressed in dozens of other cancers, we may be able to use them to treat many of these cancers. These are pancreas, kidney, HCC, lung, stomach and other cancers. We plan to potentially and methodically address these opportunities with a global partner.

Second, our GBM data also validate our entire SynCon platform for the use of other important tumor-associated antigens that we developed as additional cancer products. While our INO-5401 GBM program for patients with GBM is certainly very important and represents a great economic opportunity for Inovio, we are just watching the top of this summit with an even greater mountain of possibilities below.

I started our call today to call 2020 a year of transformation for Inovio, and we've been working on it for a while. We prepared it with strategic portfolio management, staff adjustments and funding support. When we look at where Inovio is today, I see a stronger determination than 2 years ago. Our main focus remains on the further development of our versatile HPV treatment options, which target HPV-related diseases that lack therapeutic alternatives to surgery. In addition, we are pursuing the strategy of quickly developing products such as RRP and GBM that come onto the market.

Let me start with our most advanced product, VGX-3100, starting with our Phase III treatment for women with high-grade cervical dysplasia. We completed the registration of 198 patients for REVEAL 1 in the second quarter and continue to strive to provide the most important efficacy data from the REVEAL 1 study by the fourth quarter of 2020. We are excited to see if we can achieve efficacy and safety data in REVEAL 1 that we had previously shown in a 167-patient Phase IIb study.

Keep in mind that cervical cancer is still one of the leading causes of death in women worldwide, and that HPV-16 and HPV-18 subtypes that can be treated with VGX-3100 are still responsible for approximately 70% of cervical cancer. All the more reason why we believe that our pre-cancer immunotherapy is an effective and proactive alternative to surgery is well received by the patient community.

At the same time, we continue to be vigilant, conscientious, and cost-effective in opening clinical locations for REVEAL 2 in the United States and worldwide. At the end of October we had 31 locations where patients were recruited and enrolled worldwide. We recently opened new locations in Argentina, Lithuania and Spain. Overall, the enrollment for REVEAL 2 remains on course.

Reminder: While both REVEAL studies are required to submit a BLA, you should keep in mind that these two studies are identical, with one exception regarding the safety surveillance schedule: REVEAL 1 is an 88-week study that includes a 1 -year safety follow-up versus a 40-week REVEAL 2 study that included a 1-month safety follow-up.

In conjunction with our upcoming clinical data and the improvement of the commercial profile for VGX-3100, we will develop the pre-treatment biomarker and the diagnostic kit, which we are developing together with our employee QIAGEN. Again, the purpose of this kit is to identify patients who are most likely to respond to VGX-3100. While the most important update for VGX-3100 will take place in the course of the next year, namely the phase III data from REVEAL 1, we expect data readings from our current phase II VIN and AIN programs in the coming months.

After completing the registration of 33 patients in our Phase II study with VGX-3100 for HPV-related high-grade vulvadysplasia and after completing the registration in our 24-patient Phase II study for patients with HPV-related high-grade anal disease, plan dysplasia we will publish preliminary data from both the VIN and AIN studies at a medical conference in the first quarter of next year. We are currently unable to provide precise information on the conference. However, we believe that this is the most appropriate place to exchange data on the tentative effectiveness and safety of VIN and AIN and to gain the greatest attention and appreciation for these disease goals.

As these are new significant HPV targeting opportunities, we continue to talk to the FDA and are confident that we will be able to initiate a crucial INO-3107 clinical trial for HPV-related RRP that we expect in the first Halfway through 2020 as a rare orphan product.

RRP, or recurrent respiratory papillomatosis, is a disease in which patients literally have to plan their lives after planning, performing, and recovering from surgery, sometimes having surgery three to ten times a year, and up to $ 500,000 annually, as many of them have multiple nights in the hospital and need multiple medications after surgery.

I know that you all share our willingness to launch the study and our enthusiasm for the enormous market opportunities of this program and, above all, for the clinical benefits it offers to patients who are constantly reminded of this terrible disease.

I should also mention that INO-5151, in addition to INO-5401, which was featured as a late burglary poster at SITC, was also featured in an ongoing test poster at the same conference. INO-5151, a combined formulation of INO-5150 and INO-9012, is included in one arm of this exploratory cohort platform study. The 3-cohort platform study is being conducted by the Parker Cancer Immunotherapy Institute and the Cancer Research Institute as part of the company's previously established clinical collaboration agreement. In this particular cohort, INO-5151 is combined with the Bristol-Myers PD-1 inhibitor, nivolumab, and the FLT3 ligand CDX-301 from Celldex Therapeutics.

Let me emphasize again that in our cancer combination portfolio, you can expect overall survival data from our INO-5401 cancer combination study with Regeneron for GBM, based on the promising PFS6 data that was recently presented. In addition, the fully enrolled Phase II trial of head and neck cancer sponsored by our partner AstraZeneca, combining MEDI0457 with AZ's checkpoint inhibitor, will be completed in the third quarter of next year. Taken together, these expected efficacy data in 2020 are promising for Inovio's product pipeline and solidify Inovio as the leader in synthetic DNA immunotherapy.

Before I hand it over to Peter for a financial update, although we're definitely looking forward to further developments in cancer and HPV, I don't want to mention the latest advances in our infectious disease business. An area that I believe is often used by investors is underestimated.

As we noted back in July, our previously established global partnerships were not affected by this realignment, even though we limited our resources and focused on infectious diseases. We continue to leverage and welcome our ongoing partnerships to develop vaccines, dMAbs and delivery devices that support the development and investigation of multiple targets for pandemics and infectious diseases. In fact, I have an update for you from our Lassa and MERS vaccines funded by our infectious disease partner, CEPI, or the Coalition for Epidemic Preparedness Innovations.

For Lassa, we have completed the enrollment for the first human vaccine study, which we started enrolling in May this year. Based on the implementation of the phase I study with INO-4500, our partner CEPI will continue to fund the next phase Ib study for Lassa in West Africa, in which a Lassa infection is endemic. This study is expected to start early next year.

In addition, Inovio, who is transitioning to our MERS vaccine, will again lead all other organizations and begin the first Phase II study in the Middle East and Africa that has seen outbreaks. We are also waiting for our partners to complete the analyzes for our Zika vaccine in Puerto Rico and our HIV vaccine studies.

We are also continuing to develop our dMAb and dBiTE technologies, and you will surely learn more about them in the future. Using direct local delivery into the body through the CELLECTRA platform, the synthetic genetic codes provided by the dMAbs instruct the body's cells to become a customized, patient-specific factory that manufactures their own therapeutic monoclonal antibody products a major step in antibody technology.

Traditional monoclonal antibodies represent the largest segment of the pharmaceutical market today and generated sales of more than $ 100 billion last year. The therapies extend to cancer, infections, inflammation and cardiovascular diseases. With a synthetic design and stationary production, dMAb products represent a disruptive and innovative entry into this important class of pharmaceuticals. Together, dMAb and dBiTE offer the possibility of providing superior and inexpensive therapy options for cancer and infectious diseases.

Inovio has already received over $ 60 million in third-party funding to support the advancement of this technology. Most recently, Inovio and his colleague The Wistar Institute received a $ 4.6 million grant from the National Institutes of Health to support the advancement of Inovio's dMAbs and their innovative use in developing antimicrobial resistance products.

Inovio's overall goal is to develop a paradigm shift approach to monoclonal antibody technology that leads to a pipeline of highly effective dMAb products for cancer infection that can be developed through business partnerships, external funding and collaboration. For example, Inovio earlier this year enrolled its first dMAb candidate, INO-A002, in the phase I dose escalation study to ensure the safety and tolerability and expression of dMAb-produced antibodies with full funding from the Bill & Melinda Gates Foundation to rate . Look forward to the data to be reported in 2020.

I would like to ask our CFO Peter Kies for a financial update. Peter?

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Peter D. Kies, CFO of Inovio Pharmaceuticals, Inc. [6]

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Thank you, Joseph, and good afternoon everyone. I will start with a general overview of the third quarter financial results and then I will go over the recent realignment that we announced in July.

Total revenue in the third quarter was $ 867,000 compared to $ 2 million in the same period in 2018. Total cost of ownership was $ 24.8 million in the three months ended September 30, 2019, compared to $ 28.6 million in same period last year. The year-on-year decline in research and development collaborations was primarily due to a decrease in reimbursed drug manufacturing activities related to our partnership with AstraZeneca.

Inovio's net loss for the quarter was $ 23.1 million or $ 0.23 per share (basic) and $ 0.25 per share (fully diluted) compared to $ 25 million or $ 0.27 per share ( basic and dilutive) for the same period last year. As of September 30, 2019, cash and short-term investments were $ 93.8 million compared to $ 81.2 million as of December 31, 2018.

In August, Inovio closed a private placement of 1% 2024 Maturity Notes with a total face value of KRW 18 billion or approximately $ 15 million, which was issued to a group of institutional investors led by Korea Investment Partners. These bonds can be converted into Korean depository receipts or KDRs, provided that Inovio has listed its security on the KOSDAQ market of the Korean Stock Market Exchange in the form of KDRs or other common stock, provided KDRs are available at the time of the conversion not listed. Net proceeds from the offer, after deducting the offer expenses to be paid by Inovio, were approximately $ 14.5 million.

In July, the company introduced a strategic cost reduction plan that included a 28 percent reduction in personnel and the discontinuation of several research and development programs and clinical programs, resulting in an approximately 25 percent reduction in annual burn risk. The reallocation of resources focuses the company's commercialization efforts for the major product 3100 and the development of high-quality, rapidly marketable HPV product candidates such as INO-3107 for the treatment of RRP and INO-5401 for the treatment of GBM.

As a reminder, you can read the details of our 10-Q at EDGAR on the SEC website. You can also find our third quarter 2019 financial statements in today's press release and in our Form 10-Q filed with the SEC. You can also find these on our website under Investor Relations, Financial Reports.

With that I turn back to you, Joseph.

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J. Joseph Kim, Inovio Pharmaceuticals, Inc. – CEO, President and Director [7]

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Thank you, Peter. Before we answer your questions, I think it is really important to repeat that the next year is a transformation phase for Inovio. At this time next year, we could reach several milestones in clinical and business development in many therapeutic areas. Within the next 12 months, we will release significant, breakthrough data on VGX-3100, INO-5401 and MEDI0457, while working hard to see if INO-3107 can bring them all to the market. We have worked very hard to achieve this moment.

My special thanks go to our committed employees and our long-standing shareholders for their trust and conviction.

Now I'm looking forward to your questions. Operator, please open the line for analysts.

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questions and answers

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operator [1]

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(Instruction manual) Our first question comes from Charles Duncan of Cantor Fitzgerald.

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Pete George Stavropoulos, Cantor Fitzgerald & Co., Research Department – Associate Analyst [2]

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This is Pete Stavropoulos for Charles. Congratulations on the quarter and congratulations on the GBM data you submitted last week. I know you mentioned ApolloBio in your prepared remarks, but I'm not sure I missed anything. So you mentioned in the last quarter that you submitted an IND to the Chinese FDA. Has the Chinese FDA responded to this? And have you started to open clinical locations in China and with other groups in REVEAL 2?

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J. Joseph Kim, Inovio Pharmaceuticals, Inc. – CEO, President and Director [3]

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Yes. So China FDA or [NPMA]has accepted the IND from ApolloBio. We are taking many steps with ApolloBio to open the trial version for VGX-3100 in China. We can't really discuss the details at the moment, but you can rest assured that ApolloBio's 2020 China plan for VGX-3100 will be fully implemented.

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Pete George Stavropoulos, Cantor Fitzgerald & Co., Research Department – Associate Analyst [4]

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Good. And a question about the biopsy-based companion diagnosis for VGX-3100, so that I somehow understand it better, is entirely in the hands of QIAGEN, except that you provide REVEAL samples? And will Inovio or QIAGEN have patent rights? And will it be part of the revenue?

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J. Joseph Kim, Inovio Pharmaceuticals, Inc. – CEO, President and Director [5]

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Yes. So it is still a common development cooperation. Much of the early development work has already been done, and then QIAGEN brings in its excellent commercialization and execution. You – that's what you do. They develop and sell diagnostic kits. Our goal, therefore, is to have this complementary kit available as a biomarker-based pretreatment kit that will help guide the use of VGX-3100, with patients who benefit the most using VGX-3100.

And that has an enormous impact on us. We can calculate more. We can make patients have a better overall effectiveness. So it has several positive effects. Overall, this would also improve health care spending as we can have this targeted use of 3,100 in patients who are most important. So I think the key is to really use Inovio's expertise and QIAGEN's expertise and really make this combination possible. We will provide more information as we continue to do so in 2020 and we are making great strides at the moment.

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operator [6]

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Our next question comes from Joel Beatty from Citi.

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Shawn Michael Egan, Citigroup Inc, Research Department – Senior Associate [7]

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This is Shawn Egan for Joel. A couple for me today. The first on 5401, your glioblastoma program, maybe if you could only speak at a high level, what are the next steps? Wait until the complete last data is ripe before making any further decisions. Or maybe some high-level thoughts about what a central line could look like. And then I also have a follow-up.

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J. Joseph Kim, Inovio Pharmaceuticals, Inc. – CEO, President and Director [8]

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Yes. I hand it over to Jeffrey for a detailed answer. But for us the big picture is that we are very excited about the early dates, and we begin to imagine and figure out what a crucial attempt could be. If we see the later survival data, we would of course be even more excited.

So I'm going to leave it to Jeffrey for more insight.

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Jeffrey Skolnik, Inovio Pharmaceuticals, Inc. – Vice President of Clinical Development – Oncology [9]

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Thank you, Joseph. And thank you, Shawn, for the question. I agree. So, as Joseph said, we'll only be looking for our overall survival data in the middle of next year and then in the third and fourth quarters of next year. Together with what we continue to learn from the current study, we can determine the design of our next study. But of course, as you can imagine, we have already invested a lot of time and effort to consider where we would like to take this opportunity and what this design might look like. So we're looking forward to the overall survival data for next year, which we're really looking forward to.

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Shawn Michael Egan, Citigroup Inc, Research Department – Senior Associate [10]

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And then I will continue to follow up on the diagnosis of QIAGEN. Are there any insights you can use to apply them across your platform? Or are they really tailored to the VGX-3100?

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J. Joseph Kim, Inovio Pharmaceuticals, Inc. – CEO, President and Director [11]

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Yes. Also – aber die Details müssen weiter untersucht werden, aber wir glauben, es gibt Erkenntnisse. Das könnte sich auf jeden Fall auf den gesamten HPV-Bereich auswirken und sich auch auf unsere E / A-Programme auswirken. Die Biomarker und gezielten Therapien für I-O sind also die Verbesserungen der nächsten Generation auf diesem Gebiet. Wir werden also alles, was wir aus allen Aspekten lernen, anwenden, insbesondere in der Biomarker-Arbeit, um unsere Programme zu verbessern.

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Shawn Michael Egan, Citigroup Inc, Forschungsabteilung – Senior Associate [12]

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Und ich habe nur eine letzte Frage. Ich habe auf ClinicalTrials.gov festgestellt, dass ihre Durvalumab MEDI0457-Studie die Einschreibung von 50 auf 35 gesenkt hat. Können Sie Gründe dafür anführen? Oder liegt das in Astras Händen?

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J. Joseph Kim, Inovio Pharmaceuticals, Inc. – CEO, Präsident und Direktor [13]

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Yes. Nun, es liegt wirklich in AstraZenecas Händen, aber wir sehen das als positiv an, dass sie genug Patienten haben, um sich anzusehen, was sie wollen. Und basierend auf den Angaben in ClinicalTrials.gov wollen sie die Studie bis zum dritten Quartal nächsten Jahres vollständig abschließen. Und wir erwarten – wir schätzen, weil sie das Sagen haben und wann und wo sie die Daten zu Kopf- und Halskrebs präsentieren. Aber wir denken irgendwann Mitte nächsten Jahres, geben oder nehmen Sie ein paar Monate, wo sie wahrscheinlich präsentieren würden. Ich denke also, dass dies das zusätzliche Arsenal unserer Erwartungen für 2020 in Bezug auf aussagekräftige Phase II- und Phase III-Daten für 2020 darstellt.

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Operator [14]

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Unsere nächste Frage kommt von Stephen Willey aus Stifel.

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Ellen Sands, Stifel, Nicolaus & Company, Incorporated, Forschungsabteilung – Research Analyst [15]

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Dies ist eigentlich Ellen für Steve. Also ich denke, zuerst nur über VGX-3100. Ich glaube, die Prognose hat sich seit Jahresende 19, erstes Quartal 20 möglicherweise geändert, und korrigiere mich, wenn ich mich dort irre. Ich habe mich also nur gefragt, ob dies darauf zurückzuführen ist, dass ich nur auf einer bestimmten medizinischen Konferenz im ersten Quartal 20 präsent sein wollte oder ob es überhaupt mit der Einschreibungsdynamik zu tun hatte. Und dann ging es auch darum, nur zu fragen, welche Datenpunkte wir von dieser Zwischenaktualisierung im ersten Quartal 20 erwarten können.

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J. Joseph Kim, Inovio Pharmaceuticals, Inc. – CEO, Präsident und Direktor [16]

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Yes. Ich denke, Sie beziehen sich auf unsere Phase-II-VIN- und AIN-Studien für VGX-3100. Ja, die Einschreibungsdynamik war also auf dem richtigen Weg. Wir haben die 33 Patienten in der VIN-Studie und 24 Patienten in der AIN-Studie abgeschlossen. Wir fühlen, wie Sie sagten, einen sinnvollen Ort, um unsere Daten zu präsentieren. Daher gibt es im späten vierten Quartal kaum Möglichkeiten zur Datenpräsentation. Wir werden es also nächstes Jahr auf einer medizinischen Konferenz im ersten Quartal tun.

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Ellen Sands, Stifel, Nicolaus & Company, Incorporated, Forschungsabteilung – Research Analyst [17]

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Okay. Big. And then can you talk about any commercial plans or any specifics you have outside of the diagnostic tool for VGX-3100 for REVEAL 1 and 2 as that kind of gets closer reading out?

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

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Yes. I mean we're very excited about the REVEAL 1 data. And really, that's the next near-term data major milestone. We've all been waiting for this for the last couple of years. And then REVEAL 2 comes after that. And certainly, we have internal preparations for commercialization, launch readiness and so on. We're talking to multiple interested potential partners who may work with us. And all these things, we're looking into the future, but we're very excited about what VGX-3100 can do for patients who are suffering with cervical pre-cancer today, where currently only treatment option is lofting off the tops of full top layers of their cervix, negatively impacting their ability to have future babies.

So we can — we think we have an immunotherapy solution that can treat the disease, clear the cause of the disease in HPV 16 and 18 viruses, and spare the cervix from surgery. So we're quite excited, and we think the market will embrace VGX-3100 as an immunotherapy option for cervical dysplasia and certainly to other indications, vulvar and anal dysplasia as well.

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Ellen Sands, Stifel, Nicolaus & Company, Incorporated, Research Division – Research Analyst [19]

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Okay. Big. And then one last one from me, it's related to the GBM study. Can you just remind us what the bar will be OS-wise to move forward once we see those readouts? Then additionally, do you think we'll get additional patient baseline data along with those 12- and 18-months OS readouts next year?

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Peter D. Kies, Inovio Pharmaceuticals, Inc. – CFO [20]

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Jeffrey?

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Jeffrey Skolnik, Inovio Pharmaceuticals, Inc. – VP of Clinical Development – Oncology [21]

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Thanks for the question, Ellen. So yes, in general, we would expect to be using standard-of-care numbers obviously around OS12 on OS18 and similarly to use median overall survival data based upon the current standards of care. And there, again, are several published numbers. We would anticipate that about 60% or so — 50% to 60% of patients will be alive at 12 months with glioblastoma if you look at all comers, and then obviously fewer to be alive at 18 months. That could drop to about 40%, 50%. So we'll continue to follow our data through 12 and 18 months, taking a look at what the standards are.

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Ellen Sands, Stifel, Nicolaus & Company, Incorporated, Research Division – Research Analyst [22]

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Big. And then the patient baseline, do you think there'll be any more information on that? Or it will be limited to what we saw at SITC?

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Jeffrey Skolnik, Inovio Pharmaceuticals, Inc. – VP of Clinical Development – Oncology [23]

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So when you say patient baseline, tell me a little bit more about what you mean?

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Ellen Sands, Stifel, Nicolaus & Company, Incorporated, Research Division – Research Analyst [24]

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Yes. So just specifically, if patients had a full surgical resection or partial?

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Jeffrey Skolnik, Inovio Pharmaceuticals, Inc. – VP of Clinical Development – Oncology [25]

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For sure. So yes, we would anticipate that as we continue to publish our data and we have our full data set, you'll get even more information about the baseline for these patients. Again, as you know, all patients, obviously, in the study are newly diagnosed. And all of our data, very importantly, are being calculated from day 0, the first day of our therapeutic intervention.

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Operator [26]

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

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Gregory James Renza, RBC Capital Markets, Research Division – Analyst [27]

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Just to follow up on 5401 in the GBM study, Joseph, in your prepared remarks. And subsequently, you've mentioned just the concept of working with or finding a global partner given the expansion potential. Just wondering if you could perhaps just remind us of the agreement and the arrangement you've got with Regeneron on this, and any detail there about future engagements would be helpful. And then I think similarly, just maybe broadly as well, what you see as sort of the optimal point of engagement from a partner as this program matures and moves forward.

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

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Yes. Regeneron has been a great collaborator in this regard. I say collaborator because it's not a full-blown license partnership like the one relationship we have with AstraZeneca for MEDI0457. So INO-5401 has not been licensed to anyone.

Now Regeneron is providing their important PD-1 Libtayo — inhibitor, Libtayo, to the study. They also get the benefit of looking at the data perhaps before everyone else. For that advantage, I think they have some timing and knowledge and information advantage over other potential partners. So — but we have not spoken for INO-5401 to Regeneron for GBM or other fields. But obviously, a perfect partner would look a lot like Regeneron and perhaps other big pharmas with their own PD-1 or PD-L1 inhibitors, as we have shown that our immunotherapies are almost equally effective in combining with these PD-1 or PD-L1 inhibitors.

Just a reminder, we have PD-L1 inhibitor combination with AstraZeneca with their durvalumab for 457; PD-1 with Regeneron; and our prostate cancer, 5151, is just entering a combination study with nivolumab from Bristol-Myers. So I believe our therapies can be effective combined with any of these checkpoint molecules, inhibitor molecules. But someone like Regeneron with a global reach, the goal of applying 5401 to make the checkpoint inhibitors perform even better, compared to the competitors in their space without adding any additional toxicity, increasing efficacy is something that we think someone like Regeneron or other big pharmas in this competitive space will be very much interested in.

And just to take short moment further, I mean I stated at this prepared remarks part, but 5401 success in GBM has — is great for GBM and for the patients and for Inovio. And that's a great opportunity on its own, but the way we designed this product is a multi-cancer targeting product, much like the similarity to Nektar's program where they can combine and address multiple different cancers. We can do that, utilizing very prolific, tumor-specific antigens or associated antigens in WT1, hTERT and PSMA. And then we have dozens more of these novel antigens in our toolbox, which could be utilized to create even more potent cancer immunotherapies to combine with checkpoint inhibitors.

So I think we are very excited about the GBM trial on its own, but we have other broader plans. And because our resources are certainly limited as a small biotech, bringing in a global partner that can fully utilize this versatility and potential broad range of efficacy, we think is — will be a great partnering opportunities going forward.

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Gregory James Renza, RBC Capital Markets, Research Division – Analyst [29]

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Big. And just one more for me on 3100. And as far as the timing, and I appreciate you putting a finer point on what we potentially can expect next year, I'm just curious if you can comment a bit on some of the thinking about having the top line efficacy data. Certainly, you've spoken in the past about landing REVEAL 1 and 2 plans, if you will, around the same time, but just curious about that cadence by fourth quarter. Would we expect to see some kind of safety there as well? Or do we wait for the full — wait for that following the full 88-week for REVEAL 1 at a later point?

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

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Yes, Greg, thanks for that question. So the top line is focused on group-level efficacy results. Full safety will be after the full 88 weeks for REVEAL 1 and full 40 weeks for REVEAL 2. Now these are 198-patient study. We did already demonstrate strong safety at week 36 and week 88, using our 167-patient Phase IIb study, which really is pretty much identical to our REVEAL 1 and REVEAL 2 studies. So — and we haven't seen any signals of safety throughout any of our DSMB meetings. So we're quite confident, as we always are, with our platform programs across our pipeline. So safety is not a real concern — overly concern for us.

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Gregory James Renza, RBC Capital Markets, Research Division – Analyst [31]

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Big. And then could you just perhaps just comment on your level of confidence to adhere to your previously stated prospect of having a BLA filing for 2021?

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J. Joseph Kim, Inovio Pharmaceuticals, Inc. – CEO, President & Director [32]

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Well, it really depends on the execution of REVEAL 2 because REVEAL 1 timeline will support potentially 2021. So we should have more guidance in the future.

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Operator [33]

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Our next question comes from Chris Raymond from Piper Jaffray.

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Nicole Ashley Gabreski, Piper Jaffray Companies, Research Division – Research Analyst [34]

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This is Nicole Gabreski on for Chris. So just had a few questions. So the first was on the RRP program. So with initiation of a pivotal clinical trial for INO-3107 in first half of '20, so I guess it sounds like you guys have had discussions with the FDA. So just wondering what still needs to be worked out with regulators and if you have any color at this point on endpoints for the trial.

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

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So we're still discussing that. This — as an orphan indication, we want to be as aggressive in timing and sizing of the studies as well. So we're not yet ready to unveil the overall design and the endpoints yet. But our overall objective is to use similar to what we've shown in our pilot study in RRP. By the way, we expect to have the clinical publication in the next few months to come out of this RRP study.

But just using as an immunotherapy to avoid or delay surgery would be a — we think is a meaningful clinical endpoint. And while this discussion is still going on with the FDA, I don't want to overstep that. But our — I can confidently say that we will be starting our RRP trial in the first half of 2020. We've been working to manufacture the clinical product, getting all of our clinical potential PIs motivated and marshaled. And so everything is getting prepared behind the scene. We look forward to sharing more information, more detail in the future.

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Nicole Ashley Gabreski, Piper Jaffray Companies, Research Division – Research Analyst [36]

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That's helpful. And then maybe a second question. Just after the Phase II GBM update, we went back through the literature. I noticed that there just seems to be some debate around whether PFS6 and GBM translates to overall survival. So just kind of wanted to get your thoughts on this and just what your confidence level is moving forward to the first OS readout next year.

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

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Well, I can just say, the field is split on the predictability of PFS6 to future overall survival. But actually, that's not the point. I think the point is — and Jeffrey can add to this, but we're excited about the data we have at 6 months for progression-free survival. We're not projecting we're going to be successful in OS, but we are waiting with bated breath. In less than 6 months from now, we will have OS12. And less than a year from now, we will have OS18.

So while the previous studies were not able to correlate the success of PFS6 to OS12 and 18, that's not the question we're trying to address. We think we have an immune-activating approach that combines with checkpoint inhibitor, brings better level of efficacy. And if our hypothesis is right, and so far, the PFS6 is supporting that, we think we're very confident and highly optimistic for the OS numbers. But by no means are we saying we can correlate and predict success.

Jeffrey, would you add any more granularity to that? Or…

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Jeffrey Skolnik, Inovio Pharmaceuticals, Inc. – VP of Clinical Development – Oncology [38]

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Thanks, Nicole, for the question. Yes, I completely agree with you, Joseph. I think what we've demonstrated is that we have immune responses to our T cell-enabling therapy and that we have an efficacy signal. And those 2 things give us the confidence to move on to an overall survival endpoint. And exactly as you said, Joseph, I would not prognosticate, but we are very excited to see what our overall survival data look like.

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J. Joseph Kim, Inovio Pharmaceuticals, Inc. – CEO, President & Director [39]

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I would say I like our chances.

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Operator [40]

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And our final question today comes from Jason McCarthy from Maxim Group.

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Naureen Quibria, Maxim Group, LLC – Senior Equity Research Associate [41]

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This is actually Naureen on for Jason. So congrats on the GBM data. And actually, I would like to follow up on a number of those questions. I was just wondering, with regards to the trial design for the GBM study, if we could drill down a little bit there, in the ClinicalTrials.gov, it says some of the patients received TMZ and radiation if it was clinically indicated. But then when I look back at the poster at SITC, it suggests that the entire cohort — the methylated cohort may have received additional TMZ, up to 6 additional cycles. So I was wondering if you could provide a bit of clarity on this, if there was a subgroup within the cohort B that received additional chemo or if it was the entire cohort. And if it's not the entire cohort, will there be a breakdown on the data as well in the future?

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Jeffrey Skolnik, Inovio Pharmaceuticals, Inc. – VP of Clinical Development – Oncology [42]

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For sure. Thanks, Naureen, for the question. So exactly as you've indicated, all patients on the study, whether they were MGMT methylated or MGMT promoter unmethylated, received 3 weeks of radiation and 3 weeks of temozolomide concurrently. And then exactly as you suggested, all patients on cohort B, the methylated — MGMT promoter methylated patients went on to receive adjuvant temozolomide up to 6 cycles. So again, all patients received radiation and temozolomide for 3 weeks, and then those that were methylated received additional temozolomide up to 6 cycles.

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

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So this is a standard of care for these populations. So yes, we followed the directions from the FDA and our KOLs, who helped us design the trial and helped us to execute the conduct of the trial.

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Naureen Quibria, Maxim Group, LLC – Senior Equity Research Associate [44]

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Yes, that makes sense. And I was just wondering — I actually brought this up in the past. Normally, with checkpoints, or at least in the past, all of them have failed in the past. And people have said or suggested that it's because there's a need for steroids, and steroids actually decreased the efficacy of a checkpoint. But in your study, you have these compelling results. So I was wondering, were steroids actually used? And all the population — what percentage of the population, patient population? And what are your thoughts on that if Inovio's platform is actually able to counteract the inhibitory effects of steroid on a checkpoint to promote its activity? Yes, I was just wondering as to whether there was steroid use and if you have any thoughts on that?

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

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Great question. Jeffrey?

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Jeffrey Skolnik, Inovio Pharmaceuticals, Inc. – VP of Clinical Development – Oncology [46]

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Yes, Naureen, that's a great question. So as Joseph mentioned, when we designed the protocol, we worked very closely with our key opinion leaders in the field, many of whom were and are part of the single-agent checkpoint studies, as you've mentioned. And they themselves have been very disappointed at the data that have come from those single-agent checkpoint studies. We, of course, feel that combining with a T cell-enabling therapy like INO-5401 plus INO-9012, we really give, as Joseph has said before, a one-two punch to the tumor, increasing the opportunity for efficacy.

But to your point, steroids certainly can be suppressive in generating an immune response. And so we did pay attention to the amount of steroid that was used, and our study does control for and collect that information. And those data should be forthcoming in an upcoming scientific presentation when we bring all those data together.

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Naureen Quibria, Maxim Group, LLC – Senior Equity Research Associate [47]

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That's great to hear. And just one more follow-up. Again, on the GBM study, there's been some suggestion that checkpoints may actually work better in the neoadjuvant setting. So I know it's thinking far ahead, but have you also considered a potential similar study with INO-5401 in such a setting?

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Jeffrey Skolnik, Inovio Pharmaceuticals, Inc. – VP of Clinical Development – Oncology [48]

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Yes, that's an outstanding question. The short answer is, of course, we are paying attention very closely to the literature. And as you are aware, there have been recently several publications looking at neoadjuvant checkpoint in GBM. And thankfully, the authors of one or more of those papers are KOLs that we have the opportunity to interface with. So we're excited to see the data from this trial, and we keep all opportunities open based upon the emerging literature and the science.

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Operator [49]

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And ladies and gentlemen, with that, we'll conclude today's question-and-answer session. And at this time, I'd like to turn the conference call back over to Joseph Kim for any closing remarks.

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J. Joseph Kim, Inovio Pharmaceuticals, Inc. – CEO, President & Director [50]

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Thank you very much. 2020 is going to be awesome. Stay tuned. Thank you.

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Operator [51]

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Ladies and gentlemen, that will conclude today's conference call. We do thank you for attending today's presentation. You may now disconnect your lines.