Inovio Pharmaceuticals, Inc. (INO) Q1 2019 Earnings Report, Transcript and Summary

Good day and welcome to the Inovio Pharmaceuticals First Quarter 2019 Financial Results Conference Call. All participants will be in a listen-only mode. [Operator Instructions] Please note this event is being recorded. I'd now like to turn the conference over to Ben Matone, Director of Investor Relations. Please go ahead, sir.

Thank you, operator. Good afternoon everyone and welcome to the Inovio Pharmaceuticals first quarter 2019 investor conference call. With me today are, Inovio's President and CEO, Dr. J. Joseph Kim, our CFO, Peter Kies and our Chief Scientific Officer, Dr. Laurent Humeau. Today's call is also being webcast live on our website ir.inovio.com and a replay of today's call will be made available. Following a general business update, we will conduct a question and answer segment which will be reserved for equity research analysts, as a reminder we will be making certain forward looking statements that relate to our business which include our plans to develop our immunotherapy platform in combination with our proprietary delivery devices as well as developments and timing of certain clinical data readouts and our capital resources. These statements involve certain assumptions risks and uncertainties and could cause actual results to differ materially from these statements. All of these statements are based on the beliefs and expectations of management, as of today. We assume no obligation to revise or update for looking statements whether as a result of new information future events or otherwise. Investors should read carefully the risks and uncertainty 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. With that I would like to turn the call over to our CEO, Dr. J. Joseph Kim

Thanks, Ben. And good afternoon everyone. I will first provide you today with my statistical review and then our CFO, Peter Kies will detail our financials. Our Chief Scientific Officer Dr. Laurent Humeau, also joins our call today. Dr. Humeau will update you on our exciting R&D efforts with focus on our dMAb and dBiTE programs. Our new area were extremely excited about given the potential these technologies have for both patients and our shareholders. I would like to start off by saying that Inovio remains on track on meeting our clinical development timelines along with our business development and commercial plans. You've heard me say many times before Inovio aims to be the go to player for treating all HPV related diseases from pre cancers to cancer. We're an aggressive management team that isn't just waiting for Phase 3 VGX-3100 data to come in. To that end, we have applied for an were granted an advance therapy medicinal product certificate by the European Medicines Agency. Second we continue to make a significant advancement in our efforts to develop a pre treatment biomarker kit they could target patients most likely to respond positively to treatment with VGX-3100 which in turn can potentially enhance absolute efficacy of the product. I'll tell you what each of these strategic activities mean for the product and our company. First the EMA certificate was awarded following an extensive evaluation of our CMC quality and non-clinical data by the EMA's committee for advanced therapies. This is a big deal, it's a huge accomplishment for us, because since the inception of the program in 2009, only 11 ATMP certifications have been awarded by the EMA. The certificate represents an important developmental milestone for VGX-3100 as it will facilitate a next flight to expedite the preparation, filing and review of a future European market authorization application for VGX-3100. A similar caliber review will also be conducted during the BLA approval process with the FDA for VGX-3100. Thus this latest recognition we believe also provides a foundation for the FDA when they review our data and manufacturing capabilities and helps to deal with the regulatory submission. Additionally, this latest recognition is a testament to Inovio's technical excellence, cross-functional development expertise and high quality standards beyond VGX-3100 and towards Inovio's overall technology which in turn helps bolster our ongoing partnership discussions on other programs. As it pertains to the EMA and what it means for VGX-3100 commercial potential, we estimate that in Europe alone there are roughly to 250,000 new cases annually of cervical precancer deaths caused by HPV 16 and 18. For which the current standard of care just like it is in the US is surgery. The proportion of cervical high grade precancers caused by HPV 16 and 18 is about 55% and it's estimated that about 325 million women at aged 15 years or older are at risk of developing cervical cancer where 26,000 women will die from this cancer in Europe each year. In addition, there are almost 40,000 annual cases in the rare diseases caused by HPV 16 and 18 such as vulvar and anal dysplasia. Remember that our CELLECTRA-5PSP device is already CE Mark and already approved in Europe. So while we continue to execute our ongoing Phase 3 and Phase 2 clinical trials that target HPV related diseases with VGX-3100. These latest milestones bring us closer to commercialization. Moreover, we see a real to treat patients in Europe and the latest certificate from the EMA offers an important step towards approval for VGX-3100 and helps form the valuation potential for this therapy globally. Same on HPV therapies, at last month AACR annual conference, Inovio made scientists and investors take notice. We presented data for the first time on our novel HPV therapy, INO-3106 against HPV type 6 which demonstrated clinical efficacy in a study of two patients with recurrent respiratory papillomatosis or RRP. RRP is an HPV associated rare disease that can cause non-cancerous tumor growths leading to life threatening airway obstructions and occasionally progressing to cancer. Currently the disease is incurable and can only be treated by surgery to remove the tumors which only temporarily restores the airway. The tumor always recurs and the surgery must repeated usually multiple times a year. In this pilot clinical study, we enrolled two adult patients with RRP who tested positive for HPV 6. Their condition had required surgery approximately every six months to clear their tumor growth from their throats. Since their last dose of HPV -- Inovio's HPV therapy, both patients have been surgery free due to lack of tumor recurrence. One patient has not needed surgery for over two years, the other for over one year. You will certainly see a more complete report now being prepared for a medical publication. Based on these early breakthrough results, we plan to develop further develop INO-3106 as a novel non-invasive immunotherapy for the treatment of RRP, a rare orphan disease for both adult and pediatric populations. Please note the same HPV strains that cause RRP also predominantly cause genital warts another of these diseases. What we see here is more support, more giant steps towards our goal of being recognized as the built to immunotherapy provider to effectively treat all major HPV related precancers and cancers. Let me summarize and let five achievements towards that goal. First, we demonstrated already strong efficacy in our phase to be study with VGX-3100 for treating cervical dysplasia and for eliminating the root cause HPV virus. Second we add two patients who achieved a complete response or four cancer remission and they had a neck cancer study of the patients treated with MEDI0457 [ph] followed by a checkpoint inhibitor. Third, we just reported a recent clinical efficacy in patients with RRP through treatment with INO-3106. Fourth, as mentioned above we were granted in the EMA certificate validating two or three sections of our future European and potential FDA application for non-clinical and manufacturing processes. And fifth we're accelerating our quest for commercializing a VGX-3100 pre treatment biomarker diagnostic tests potentially with a partner. These advancements taken together, add up to Inovio having the potential for a robust and much needed therapeutic products for treating HPV associated diseases. Therapies that most importantly provide a non-invasive option for patients suffering with diseases caused by HPV. And for women with cervical dysplasia, a therapy that provides an alternative to surgery an option that doesn't complicate women's reproductive health a mission that we add Inovio take great pride in preserving. Before I pivot to our oncology combination study, I want to provide a brief update regarding our pivotal Phase 3 programs and the two trials REVEAL 1 and REVEAL 2. Last month we announced the initiation and opening of sites to enroll REVEAL 2 the confirmatory portion of our Phase 3 program. The early initiation of REVEAL 2 marks another milestone for our lead product VGX-3100. In addition we are still exploring with our China partner Apollo Bio to have sites within China potentially contribute to their recruiting efforts for REVEAL 2. I am confident in our team's experience and expertise, the events REVEAL program towards four [ph] deliver on our goal to file a BLA application for VGX-3100 and 2021. And most importantly remember that patients are waiting and our efforts are bringing an innovative impactful therapy to people where surgery is their only option. You can certainly expect to hear more about our Phase 3 progress on our next earnings call in August. Shifting to our oncology combination programs. I will begin with MEDI0457 in our ongoing global partnership with AstraZeneca. We announced in early April, a third milestone payments from AZ triggered by the dosing of a patient in a Phase 2 trial evaluating MEDI0457 in combination with their PD-1 checkpoint inhibitor targeting cervical, anal, penile and vulvar cancers associated with HPV. This third Phase 2 milestone stresses the potential breadth of MEDI0457 including multiple HPV associated cancers and it also complements our overall goal that I stated earlier on leading the HPV treatment market. We remain appreciative and delighted to see -- expand the use of MEDI0457 and continues an evaluation of the combination of immunotherapy with their checkpoint inhibitor and multiple cancer types that are caused by HPV. Turning to our own INO-5401 which continues to be evaluated in two combination studies for bladder cancer and glioblastoma or GBM. I will begin with GBM study. Moving forward in a combination with Regeneron's PD-1 checkpoint inhibitor Libtayo, in this GBM trial, our goal is to increase the overall survival of patients facing a disease where neither the standard of care, our clinical outcomes have really changed clinically significant way in more than a decade. We started the month of April with an exciting milestone that was the completed enrollment of 52 patients, three months ahead of schedule. We expect to report interim results from our GBM study before the end of this year, by then, we'll have PFS 6 or progression free survival at six months, data from 100% of the patients. We will also have progression free 12 month survival data from roughly 50% of the patients at that time. We're also targeting the unmet need in metastatic bladder cancer. Here we are utilizing INO-5401 in combination with Genentech, TB-01 checkpoint inhibitor concentric. This Phase 2 trial continues to enroll and we remain proactive on opening up additional sites across the US and Europe, the events recruitment process. We remain on track to have interim data for this study announced before year end. We believe this study along with GBM will help bolster our objective to demonstrate the synergistic and type tumor effects with our immunotherapy combined with a checkpoint inhibitor. Before I turn the call over to our CSO, I want to provide a brief update on a couple of key developments within our infectious disease portfolio. The March edition of the peer-reviewed journal of Infectious Diseases highlighted very positive data from Inovio Ebola vaccine INO-4201. But journal article detailed that the vaccine was safe, tolerable and generated strong T cell and antibody responses. Significantly that data -- the study demonstrated that intradermal or skin administration of Inova's CELLECTRA delivery device resulted in 100% vaccinated subjects generating antigen specific antibody responses that persisted more than one year in most subjects and generate a robust T cell responses. INO-4201 has already demonstrated protection 100% percent of non-human primates following a lethal challenge of Ebola virus. With strong preclinical and human data Inova is executing on our overall development strategy in advancing INO-4201 as a viable stockpile of vaccine. Most importantly because Inovio's Ebola vaccine can be boosted multiple times without any anti-vector response. It could be employed to boost viral vector vaccines that cannot be effectively re administered. We now look to secure partner funding to further advance our Ebola vaccine as a stand alone or as a boost for those previously immunized with viral vector vaccine. In our upcoming August Investor Call, also expect to update you more on the initiation of our first in man vaccine trial against Lassa fever. You'll recall that this is part of our partnership with CEPI the Coalition for epidemic preparedness innovations a $56 million grant to support Inovio's clinical development through phase 2 field trials of INO-4500 or Lassa fever vaccine and INO-4700 or merged vaccine the shared goal of Inovio and CEPI is for our Lassa and MERS vaccines to be successfully tested and to be available as a stockpile as soon as possible for emergency use. Overall Inovio's class leading synthetic nucleic vaccines deliver intradermally with our CELLECTRA efficacy enhancing systems are well suited to rapidly produce countermeasures against emerging viral threats potentially protecting large populations from pandemic. Inovio has rapidly advanced several global health vaccines including vaccines against HIV, Ebola, MERS and Zika and has reported near 100% immune response rates from multiple clinical studies. In this regard, I would like to share that Inovio had started the development of commercial scale intradermal device, which we call CELLECTRA 3PSP. You will hear more about this in the coming weeks. With that I would like to turn the call over to our CSO, Dr. Laurent Humeau, who will discuss some of our exciting R&D advancements. Laurent?

Well, thank you, Joseph and good afternoon to our investor. And my goal today is to paint a picture of what's on Inovio product, our new horizon and how quickly this new developments may appear in the foreground. I am talking about Inovio's d-maps and ph d-BiTEs. That is Inovio DNA encoded monoclonal antibodies [indiscernible] (inaudible) technology and our DNA encoded by [indiscernible] First, dMAb, earlier this year, we initiated the first human studio of our dMAb technology to prevent Zika virus infection, which is first clinical study dMAb are poised to be a disruptive entrant to the larger segment of pharmaceutical markets today accounting for more than $100 billion pharmaceuticals sell it's share. With treatment spanning cancer, infectious diseases, inflammation and cardiovascular diseases. With its sensitive design and efficient production. dMAb present a disruptive enthroned to this important class of pharmaceuticals. Inovio and his collaborators have already received over $60 million in non-dilutive ground funding to add them to ph DMA platform in the last few years. Please remember what its initial trial targeted Zika virus infection, we will again import on product expression data from his study towards development of a broad range of dMAb programs targeting infectious disease, cancer immunotherapy, inflammation and as well therapy for cardiovascular disease. dMAb are really amazing science. Considering that when deliver directly into the body, the genetic instructions provided by the design synthetic dMAbs and struck the body's set to become the factory which manufacture the therapeutic antibody products, enabling a major leap in antibody technology. At this year AACR meeting you could feel the buzz when we announced our first for batch result. As a global conference we told the world how our Bi-specific T Cell Engagers generated product [indiscernible] activities in clear established tumors in preclinical studies. For this published study, Inovio developed a novel dBTE targeting the HER2 molecule which was testing a therapeutic model for the treatment, sorry of ovarian and breast cancer. Importantly just a single dose of Inovio HER2 dBTE resulted in high levels of corresponding BiTE in mice for upto four months.exceeding what is typically displayed with our currently approved BiTE's short half-life of only a few hours. The HER2 dBTE treatment effectively killed HER2-expressing tumor cells resulting in a near-complete tumor clearance. Also presented was Inovio's CD19 dBTE which can kill B cell cancers by targeting B cell specific marker CD19. Data [ph] is promising preclinical results, we plan to rapidly advance our dBTE candidate into clinical testing, as well as develop a more tumor targeting dBTE for potential partnership. Let me give you some background on dBTE in the advantages they offer over gene therapy. First, bites on a class of artificial by BiTE specific monoclonal antibodies that has the potential to transform the immunotherapy landscape for cancer. The direct at whole immune system and more specifically the T cells statistical activity against cancer cells. In Lehman’s term bites are like a double side effect that binds to a tumor and through a cancer killing cell T cell. One demand on the BiTe down to the target a tumor like HER2 or CD19 is suppressing cells while the other engages the immune system by banding directly to CD molecule on T cells. This double binding activity derived T cell activation directly other tumor resulting in the killing function and tumor destruction. Now you might be confused our dMAb and Dbte. In fact in dBTE will present new transformative application of Inovio dMAb platform. The dBiTE's share many advantages of Inovio dMAb as they both are composed of engineer sequences which include antibody fragments. When administered by Inovio's CELLECTRA device -- delivery device, the patient on cell become the factory to manufacture functional bites -- by the deliver of dBiTE sequences. Inovio dBiTE are developed with Inovio strategic nuclear design using plasmid vectors and unique formulations allowing for RPDG of development, known -- product stability refrigeration is a validated both manufacturing and deploy ability. I look forward to updating you on the progress of these two programs with mass potential. I will now turn the call back over to Joseph.

Thank you, Laurent. I speak for everyone here at Inovio when I express how excited we are about the future of these Inovio technologies hold and the value potential they can offer for both therapeutic field and for our patients. I would now ask our CFO, Peter Kies to provide a financial update. Peter?

Thank you, Joseph. I'll first begin with our cash position as of the end of March and then I'll wrap up with our total revenue for the quarter and the quarter end financials. As of March 31, 2019 cash, cash equivalents and short term investments were $128 million which compares to $81.2 million for the previous quarter. During the first quarter, Inovio completed a private placement of $78.5 million aggregate amount of 6.5% convertible senior notes due 2024 resulting in net proceeds of approximately $75.7 million. Turning now to revenue for the quarter. Total revenue was $2.8 million for the three months ended March 31, 2019 which compared to $1.5 million for the same period in 2018. Total operating expenses were $31.4 million which compares to $34.3 million for the same period in 2018. Year-over-year increase in revenue under collaborative research and development arrangements was primarily due to the milestone payment recognized in the first quarter of 2019 from AstraZeneca Net loss for the quarter ended March 31, 2019 was $29.2 million or $0.30 per share basic and dilutive. This compares to $32.4 million or $0.36 per share basic dilutive for the quarter ended March 31, 2018. As a reminder, our financial statements for the first quarter of 2019, the balance sheet, income statement of operations can be found in today's press release or in the Form 10-Q filed with the SEC. This can also be accessed on our website under Investor Relations financial reports. With that, I'll turn it back to Joseph.

Thank you, Peter. Before we open the line for questions let me just say that the last several months have been extremely productive for Inovio by validating the Company's versatile technology platform. We ended the first quarter by featuring positive data from our Phase I Ebola vaccine study in a prestigious publication and starting our second phase retrial of VGX 3100 ahead of schedule. Inovio further highlighted its capabilities in treating HPV associated disease, after representing positive data from patients diagnosed with RRP where we demonstrated a clinical benefit for these patients. Don't forget about our completion of Phase II GBM study enrollment ahead of the schedule too. Additionally, we initiated the first ever clinical study for our dmAP platform. During the first quarter, an unveil an exciting new component within our platform involving our dBiTE technology, which we're working rapidly to prevent the first product into clinical testing. Lastly, we're entering the second quarter well financed following February Grace, which places us in a prime position to continue to deliver on our game changing clinical programs. In closing, Inovio remains on track on meeting our clinical development timeline along with our business development and commercial plans. With that I'll look forward to taking your questions. Operator, please open that line for the analysts.

Thank you. We will now begin the question-and-answer session. [Operator Instructions] And our first question today comes from Charles Duncan with Cantor Fitzgerald. Please go ahead.

Hi guys. This is Pisaf Rubbles on for Charles. Thanks for taking my questions and congratulations on all the progress on multiple fronts.

Thanks.

So a question about a REVEAL 1 and the data. So how management [ph] of the primary end point is at 36 weeks. We'll be releasing the efficacy data when it's an end or we wait to complete the follow up through week 88?

At week 88, as we discussed previously.

Okay. And now for the RRP study, have you met with the FDA to discuss the path forward? And since it's a rare disease do you believe there's a possibility of going straight into a pivotal study?

We plan to meet with the FDA later this year and we are certainly very excited about the data and I feel that - we feel that we would have an accelerated trial design and potentially going into pivotal. But of course, we have to meet with the FDA to confirm that.

Okay. Thank you for taking my questions.

Thank you, Pete.

And our next question comes from Gregory Renza with RBC Capital. Please go ahead.

Hey guys, thanks for taking my question.

Hi, Greg.

How are you? Joseph, I just wanted to start with respect to your mention of having a potential update in August on the REVEAL trial, just stay tuned for that, could just elaborate on a little further what we can look for as far as that update?

Well, we expect to complete the enrollment of VO 1 [ph] shortly and certainly by way before August fall and we'll be able to give you some trajectory on how well we're doing initially and REVEAL 2. We have lots of other commercialization and other plans including our biomarker work that we look forward to sharing in some detail in our next call.

Got it. Thank you. And then just with respect to the back half of the year, certainly a lot going on now not just REVEAL and now RRP, meeting with the FDA but also of course with 5401. So how could you help investors just put that all into context as far as how you are prioritizing and what you are looking for as far as those key value driving potential events for Inovio? Thanks.

Yeah, thank you, Greg. Well I know 5401 the first with the GBM study, we completed enrollment of 52 patients in a very rapid fashion. It is a very difficult disease to treat but we think combining our T cells generating 541 with Regeneron lip tail PD1 inhibitor provides us with perhaps the best shot at this very difficult disease. So before the year and we expect to have PFS6 in 100% of the patients in about half the patients it's the progression free survival at month 12. We will continue to be able to generate overall survival data leading into 2020 and beyond. But as I said by year-end PFS6 100%, PFS12 in about half the patient population. Latter, we're looking forward to generating overall response rate. Also this is a very high bar as the cohort - our larger cohort we're targeting previous checkpoint refractory population, so patients who have already failed either PD-1 or PDL-1 inhibitors. So these are very sick patients as well. And we're hopeful to have a significant percentage of the first populations and in terms of the overall response rates before the year end. As for VGX-3100 obviously we are putting a lot of humans effort in executing REVEAL 1 and completing it, as well as really getting REVEAL 2 launch and globally and in about 20 countries to execute the REVEAL 2 equipment process. I talked about the China potential we haven't baked in the china. That's just an upside for us. So we continue our efforts with a follow by in that regard. And in terms of our infectious disease we expect to see a lot more publications validating, clinical publications from our Phase 1 MERS vaccine study, from our HIV vaccine study with HVTN also we will be starting a new Lasa [ph] vaccine study in the US funded by CEPI and we look forward to updating on those efforts in the next call as well, dBTE along with RRP these are very high potential targets for their own rights. As Laurent explains, we can - we feel that our dBiTE technology is a dramatic transformative improvement over the conventional BiTE efforts where we think we can finally fulfill the promises of a bispecific T-cell engager programs using our synthetic DNA efforts. So we are in the process of sound selecting our top candidates to bring it into the clinical evaluation as rapidly as possible and the other would just then be available for partnerships, because we think each of these dBiTe candidates are of high value. RRP already stated before, its orphan disease, it's a very tough disease for the patients to deal with having to schedule their lives around the surgeries that for - to remove the tumor that recurs all the time. We're very excited about a small sample size but dramatic impact on these patients and we look forward to bringing that to the next trial. Hopefully, a pivotal trial as rapidly as possible after meeting with the FDA. So we're very excited about all of these programs.

Great. Thank you, Joseph and congratulations again on the progress.

Thank you.

And our next question comes from Chris Raymond with Piper Jaffray. Please go ahead.

Thanks, guys. Joseph, I don't want to split here on timing but I think and REVEAL 1 last quarter I think you guys talked about enrollment being sort of nearly done. I know this might be a move question, but you're stating that it's almost done now. Or I guess mid-year. Was there something that sort of happened in the last three months that I guess when we heard last quarter it was nearly done we anticipated it might have already been enrolled. Was there some slowdown in enrollment that happened or is there something that took place the last three months? Thanks.

Thanks, Chris. No, I think we are in the efforts of juggling, wrapping up a REVEAL 1, as well as launching. So we feel too. So these are - these things happen in large trials and perhaps you know we want to make sure that we're projecting our projections - we will certainly done by mid-year and full enrolment of REVEAL 1 and we're very bullish on how we're progressing in enrollment in REVEAL 2. So I don't think there's - I can tell you there's not been a slowdown, but perhaps giving a more detailed projection, we're closer to the detailed projection now. So we're very happy to do that and in by mid-year. And of course the most important thing is getting to our data, and filing BLA in 2021 and remain on track on that and certainly we're doing everything we can to execute that big picture. And I don't want to - I just want to touch on the ATMP Certification again. It is a big deal. It is a huge accomplishment because as you know there are three sections in MAA or BLA both for Europe and the FDA. And ATMP just validates that the two out of three sections. Obviously we don't have clinical data and efficacy data from Phase 3 yet but all but that is certifying that our CMC section and our non-clinical sections are our approvalable based on the high level of quality that we perform. So we think this is a huge accomplishment for our team but also the risks for our shareholders in that - there are countless small to mid-sized companies who are delayed and getting their products approved because of either CMC shortcoming or the non-clinical section. So we still have one big section to complete and that's where we're devoted – we’re devoting our efforts in executing both REVEAL 1 and REVEAL 2 and I have full confidence in our team to accomplish those efforts.

Great. Thanks very much.

Thanks, Chris.

And our next question comes from Joel Beatty with Citi. Please go ahead.

Hi, guys. This is John Hagen on for Joel. Thank you for taking my question. The first can you talk about the dMAb platfor, maybe kind of - can you frame one of the most important things you hope to kind of learn or show in the initial study and also give us a sense of based on your preclinical work what type of serum levels and concentrations of antibody we could expect and speed to onset like how quickly after administration are we going to get antibody in the blood?

Okay. Well, thank you. So our first dMAb trial targets Zika as Laurent explained, obviously we want to check for the expression of those mabs circulating in the patients activity of the binding to Zika proteins. But for the platform perspective, we are escalating the dose to make sure what kind of expression levels we're getting with our first trial. So we will be able to report on those. In non-human primates, we have been able to scale up from several hundred nanograms per ML to several micrograms per ML in our development process. So this is just the first human study and what we learn in terms of the blood level expression of these monoclonal antibodies, as well as the pharmacokinetics of that the half life the C Max and so on is going to give us a great information for the whole platform. Now let me just add here even though it wasn't specifically asked, I think, it would be hegemony [ph] to touch on this. Is that dBiTEs one of the reasons why we're so excited about dBiTEs, as well as our dMAb, but dBiTEs even so is - and I didn't mention that and prepare or Laurent had mentioned that earlier is that the BiTEs are effective in human serum in patients at 100 Picogram levels. So those are - in just in layman's terms the bites are effective in its functionality and type of tumor effects in the blood at 2000 to 10,000 fold less in concentration. So as we continue to optimize the expression of dMAbs, in our clinical studies we think we can achieve the dBiTE expression run rate now with the first trial for dBiTE. So that really pushes a urgency to target dBiTE as one of our next major thrust into to our oncology program.

Great, thank you. And then a follow-up on the HPV 6 program, INO-3106, congratulations on the data and based on your initial work. Could you kind of frame how big the RRP population is and now you've mentioned works as well, but are there any other HP 6 positive indications with an unmet need that you could [indiscernible] therapy?

Yes. Thank you. Yes, so there's about 20,000 RRP patients in this country. There are about 2000 new cases every year, throughout the world, you can multiply that by several four. So this is a rare indication, you may even say ultra rare indication. What we're so excited about is this is a third clinical efficacy example of our products targeted to HPV caused diseases that we have seen very dramatic efficacy levels sort of clinical benefits. So with the dysplasia in 167 patient double-blind study some early completed responses and head and neck cancer with MEDI0457 and now with INO 3106. Now HPV 6 and HPV 11 are the major causes of RRP and our pilot study we just tested HPV 6 effects, we are planning to expand to include HPV type 11 which will comprehensively cover RRP indications prior to going into the next study hopefully thorough. In terms of other indications we cannot address, general awards are really the big thing for should be 6 and 11. There are about half a million new cases in the US. So these are much bigger targets, obviously different clinical manifestation compared to a life-threatening RRP. But nevertheless, we think we have a potential to develop this orphan and rare targeted disease program which over time could have the potential to treat other indications like general awards and we are extremely excited about potential of our program against these diseases.

That's very helpful. Thank you. And then just a really quick final question, could you provide any update and kind of the blinded sensory radar discontinuation rates from the oncology checkpoint kind of things going on?

We don't have that and - you mean the 541 study?

Yes.

Yeah, we don't see dramatic discontinuation or any rates like that compared to our other studies that we've done in our platform. So there is nothing in either other 541 study about the discontinuation or drop out compared to all of our other vaccine or immunotherapy studies.

Great, thank you so much for answering my question Joseph.

Great. Thanks, John.

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

Yes, good afternoon, thanks for taking the questions. Just maybe wondering if you had any commentary around the principle disclosure today with respect to the 498 study not meeting OS and in GBM. And I guess if you view that outcome as supportive of the fact that you need some kind of additional immuno stimulant onboard to generate n immune response in this disease?

Your question answer - your question or your statement actually, I concur with what you just said. It's not surprising that checkpoint 498 fail. In fact, it's not just [indiscernible] issue. None of the other PD1 or PDL1 inhibitors on their own have shown significant clinical benefit either anti-tumor responses or more importantly on survival benefit on their own. That's the reason why we've targeted GBM with our T-cell generating INO541 in combination with a checkpoint inhibitor in this case with Regeneron's PD1 inhibitor. So yeah, I think your analysis I concur is PD1 alone without the presence of antigen or tumor specific T cells around is not going to be successful. So what does that mean for our 541 GBM study, we're certainly optimistic that and hopeful to see overall survival benefits compared to these checkpoint therapy alone or even just standard of care. So we are very cautiously but very optimistic that our data will pan out in the next few quarters. But before the year-end, we will be able to progressively show our PFS6, PFS12, OS12, OS18, the first two - before the year-end and then OS information in early 2020.

Okay, that's helpful. And with respect to 3106 is that something that you look -- you intend to look at with respect to intradermal delivery and just given, I guess some of the immunological data that you had shown I think it was the Zika vaccine showing kind of improved T cell responses with intradermal versus intramuscular, how should we think about you're leveraging that data to maybe pursue intradermal as kind of like the go forward administration method of choice.

As Steve I love your enthusiasm for intradermal CELLECTRA Delivery and I share that, but if I had a NRP here is the situation or entry we are facing literally today is these 2 patients have had clinical benefit received 4 doses with our intramuscular delivery, we are - and as we discussed at our last call and so on, we have just factor of 10 more data on 5P or intramuscular delivery of our therapy is generating very high levels, and specifically activated CD8 T-cell. That's not to say that we are not working to bring in intradermal delivery into all of these potential targets, including first of all vaccines and then into our oncology or other immunotherapy programs. In fact, I might have glass over very quickly, but we've initiated our commercial development or met design of CELLECTRA 3PSP very analogous to our 5 PSP commercial level Intradermal delivery system and you'll hear a lot more about these efforts in the coming weeks. But we are accelerating our efforts to bring about a commercial delivery system that targets intradermal and I share your enthusiasm that more tolerable, better potentially immunological compartments through the skin gives us a lot of versatility and target ability improvements for all of our vaccines and therapy. So we are moving ahead. Every quarter, you're going to see differences and additional data set, that not only validates our intramuscular delivery but also add additional validation of our intradermal delivery of our therapy.

All right. And then just one last one for me. So with respect to the dBiTE program. And I guess it kind of sounds like this is something that we could possibly see in the clinic at some point. How do you envision getting around the FDA NABL requirements for T-cell redirecting therapies, specifically, just given that you have such a prolonged onset of effect and it's going to take a while to clear each individual dose? How do you envision dose escalation playing out in the clinic with dBiTE?

Again that is great question. We plan to work very closely with the FDA. As you know, the FDA is extremely interested and overall bispecific antibody programs in particular the BiTE. And how do we go about that with the new trials and new efforts? We do it just like we did with our Zola dMAb. You start at very low doses, you test expression, you move up escalate to the next dose and so on. We think the vantages -- potential vantages of our ph de-BiTE technology is so overwhelming compared to the potential risk, we and perhaps future partners will certainly be in a position to advance this as rapidly and safely as possible. So this is not anything we haven't done before either with our immunotherapy, our vaccines, now with dMAbs and then within the next couple of few quarters, as you said and as I said, we'd love to bring our first candidate to the clinical evaluation. I can give you a hand as either going to be HER 2 targeted dBiTE or the CD19 targeted dBiTE, two of which we have presented at AACR and you will certainly hear a lot more about our plans in the future.

All right. Thanks for taking my questions.

And the next question comes from Jason McCarthy with Maxim Group. Please go ahead.

Hi, this is actually Norine for Jason this afternoon. Congrats on the progress. So I've a question with regards to your dBiTE program. You had amazing great data preclinical data with HER-2-directed agent preclinically and more recently, you probably saw AstraZeneca and again ICHI [ph] they reported fantastic data with their antibody-drug conjugate with HER 2 directed towards metastatic breast cancer patients. So I was just wondering to help us understand conceptually how you would see a dBiTE program in -- with the advantages of that overseeing ADC?

Norine and I think that's a great question. So I think the HER-2 targeted ADC is a great program. I guess our partner AZ talk to us as well. I think they invested $5.5 billion in this. So certainly - it really strikes to the value of these anticancer products when you're successful these are highly valuable. There are different mechanisms that come into play, drug conjugated, antibody-drug conjugates certainly have their role. We also think tapping into the bodies are or the immune system zone killer T-cells to target thus cancers using the dBiTE program will also be very important development. So without having the same level of data its hard to cross compare certainly if we can achieve the similar level or even more successful clinical levels compared to that HER 2 ADC, we and our shareholders will certainly be very pleased. The potential also of our dBiTE is, we've just shown that two of our first candidates and certainly we have the focus of developing our first one and then we are at the same time, Laurent and his team in R&D are pumping out several additional candidates. I mean, we are only limited by resources of partners to help us execute in the clinic but our T dBiTE technology now is well-validated in science and we look forward to bringing multiple candidates. The first one by ourselves, but multiple others with partners in the future.

Great, that's really helpful and continuing along the same lines with the dBiTE program. Sometimes with bispecific you do see generation of product time syndrome and your dBiTE, it appears that can elicit potent effects. So how would you – [indiscernible] something of concern with yours as well.

Yeah, I mean, certainly the class when ever you're only potently engaging T-cell, especially the killer T-cells, that's again in the gang where T-cells, we want to be able to harness it but also be able to manage it. So as I answered Steve Willey's question, we're going to be very careful and methodical in our dosing escalation in our first trial, Number 1. Number 2, looking at the pharmacokinetic of dBiTE expression compared to the bolus injections of traditional BiTEs where you see the Cmax right and they dissipate and matter of ours. And as you know, lot of the cytokine storm and other toxic effects occurred during the early peaking of the concentrated antibodies. So, of course, I'm just waving my hands here because I only have pre-clinical data, but we think the photo expression profile of dBiTEs can be potentially beneficial in limiting the potential cytokine storm. But obviously we going to go in with our eyes wide open. So our clinicians, our clinical team, RPI's, our sites for all, be ready to manage any side effects and so on. Now what I can't point to is how do we manage cytokine storm and CAR-T patients. As you know every CAR-T patients convey some level of cytokine storm or side effects with this type of toxicity and they manage it in the clinic. So the clinical benefit certainly overwhelmingly outweigh, the clinical management of side effects that they're able to utilize CAR-Ts. We are going to look at this approach this in a similar fashion, that may be the worst-case scenario, but we will see, I think as I said earlier, the expression profile of dBiTE maybe beneficial in this regard as well.

Great and just one last question, you mentioned biomarker diagnostics for VGX 3100 program. Have you actually had any discussions with potential partners on that front?

Yes.

Okay, thank you.

So what we have done is discovered and our honing the biomarkers that we have discover, certainly developing commercial kits are not in our wheelhouse, currently, so we'll make a lot of sense for us to bring in additional innovative leaders in that field to partner with us and again you'll hear more about that in the coming weeks.

Great, thank you for taking my questions.

Thank you.

[Operator Instructions] And our next question comes from Yi Chen with H.C. Wainwright. Please go ahead. Yi Chen, your line is open. Mr. Chen, your line may be muted. This will conclude the question-and-answer session. I would like to turn the conference back over to Joseph Kim for any closing remarks.

Yeah, thank you for staying with us. As you can tell from our voices, we're extremely excited about our later stage clinical executions of VGX 3100, as well as our execution of our immuno-oncology programs. At the same time, we're making great progress of our vaccine our CELLECTRA 3 PSP initiation is a very, very important and highly valuable. We think in our technology as well as you can tell from the analyst questions, I think half the questions revolve around RFP and our exciting dBiTE programs. We're very excited about those as well. And look forward to bringing more information in the next few weeks and months to come. So thank you very much for your time.

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