Imunon, Inc. (IMNN) Q1 2015 Earnings Report, Transcript and Summary

Good morning. My name is Laurie, and I will be your conference operator today. At this time, I’d like to welcome everyone to Celsion’s First Quarter 2015 Financial Results Conference Call. Today's conference is being recorded. All lines have been placed on mute to prevent any background noise. After the speakers’ remarks, there will be a question-and-answer session [Operator instructions]. I would now like to turn the call over to Mr. Jeffrey Church, Senior Vice President and Chief Financial Officer of Celsion. Please proceed sir.

Thank you. Good morning, everyone, and thank you for joining us today to discuss our first quarter 2015 financial results, which were announced yesterday after the market closed. Today’s call will be archived. The replay will be available beginning tomorrow and will remain available by phone until May 26, 2015, it will also be on our website for 30 days. Before we begin the call, we wish to inform participants that forward-looking statements are made pursuant to the Safe Harbor Provision of the Private Securities Litigation Reform Act of 1995. You are cautioned that such forward-looking statements involve risk and uncertainties including, without limitation, the risk of clinical failures, delays or increased costs, unforeseen changes in the cost for our research and development activities; possible acquisition of other technologies, assets or businesses; and possible adverse action by customers, suppliers, competitors, regulatory authorities and other risks detailed from time-to-time in the Company’s periodic reports filed with the Securities and Exchange Commission. Following our formal remarks today, we will open the call for questions. I’d like to turn the call over to Mr. Michael Tardugno, Chairman, President and CEO of Celsion. Mike?

Thank you, Jeff. Good morning. I want to start by thanking all of you for taking the time to join us for today's call. I am here with Dr. Nick Borys, Celsion's Chief Medical Officer and Jeff Church from whom you’ve just heard, our Chief Financial Officer. As always we are delighted to have this opportunity to update you on our progress. 2015 has gotten off to a great start setting the stage for what we believe will be a very productive and very successful year for our company and for our shareholders. Celsion's announced acquisition on EGEN this marvelous biology based early stage Development Company in Huntsville, Alabama. With that announcement our company entered 2015 all at once as a fully integrated development stage company with proven, effective capabilities and experience from product concept to NDA,from the bench to the market and everything in between. The combined assets of our new company are highly complementary, oncology focusedand based on nano-particle technology and all by the way with first line therapy potential in combination with the standard of care. Our press releases over the last quarter have chronicled continued progress with our now three platform technologies in chemotherapy, DNA therapy and RNA therapy, with programs in virtually every stage of development Phases III, II and I, targeting some of the most globally important cancers of our lifetime. We are well positioned with multiple opportunities to create value for our shareholders and new medicines for the medical community. And this year only through April so far, I'd like to summarize what we have announced and remind you that this is just in the last three months. First is great momentum in our breast cancer research program, with interim data showing continued remarkable results and refractory recurrent chest wall patients over two-thirds of which are showing clinically meaningful durable tumor responses, results so impressive at the request of some of the most well-known European KOLs, we announced plans to launch a parallel European study, a 100 patient trial that depending on the data could in my view very well be registrational. Results so meaningful to this population, that we have initiated an Early Access Program in our partnership with myTomorrows, A Dutch Company that makes a business bringing promising investigational therapies to patients who've exhausted their options. The Early Access Program is exclusive to the European Union, it's not compassionate use, it's not a named patient IMD and among other things allows Celsion to charge commercial rates for ThermoDox to imbursement authorities and while it won’t be a huge revenue generator, more importantly our interest in bringing ThermoDox a drug that we know safely works in this population to the medical community will be rewarded, so Europe is now on our radar, great momentum with RCW and I'd like to talk about HCC, the primary liver cancer. As we continue to follow an extraordinary subgroup from the HEAT study, this quarter we announced results from the 285 HCC patients primarily liver cancer patients, who received an optimized RFA treatment plus ThermoDox in this well founded, well defined subgroup overall survival quarter-after-quarter now for two years just continues to get better and better. The most recent sweep shows a 59% improvement, that’s over 2 year improvements in time of death with statistical significance p-value 0.02, when compared patients who received ThermoDox plus optimized RFA versus optimized RFA alone. The data is striking especially to those who have dedicated their careers to HCC research, in my recall that this subgroup was identified following our review of the data from our Phase III HEAT trial that did not meet its primary endpoint DFS. Optimized RFA now forms a basis for our Phase III OPTIMA study. The [enlightened] OPTIMA study is now enrolling patients at over 40 sites in 12 of 13 targeted countries and with the support of regulatory and the medical community, the OPTIMA study is now nearly 10% enrolled. I am going to talk a little bit about the technology that we acquired from -- with EGEN. The pipeline we acquired has brought us a promising lead candidate using our DNA delivery platform and immunotherapy and is now supported with a comprehensive clinical development strategy. This past quarter we announced impressive preliminary data from our GOG managed Phase 1b study in ovarian cancer. This data will be presented at ASCO and ongoing will be supplemented with translational research findings as they become available over the coming weeks. We also announced that FDA provided clearance for follow-on study to the Phase 1b and first-line ovarian patients. The goal of which is to continue dose escalation and to develop our understanding of the potential for a population that maybe best responders to our immunotherapy. This study is designed to bridge us to a pivotal program starting in Phase I that combines immunotherapy not only with Doxil but now also with Avastin. This ubiquitous drug recently approved for platinum-resistant patients with ovarian cancer. Now we're excited about this so I refer you to our corporate presentation on our Web site pages 24 and 25. Preclinical data presented is incontrovertible. When we add immunotherapy to Avastin in the murine model and implanted with disseminated sculptor ovarian cells the tumor burden simply goes away. Plus the immunotherapy candidate I’m referring to is none other than our GEN-1, our IL-12 DNA plasmid incorporate into our proprietary non-viral factor, synthetic polymer, nano-particles delivery system, this system which we call TheraPlas is definitively demonstrated its capability to transfer of its plasmid payload into human cells. The cellular machinery then is co-opted to produced and enable persistent durable local secretion of the [indiscernible] IL-12 the interleukin 12 protein which last for several day a week depending upon the target. The good news, IL-12 is a well-known, well-characterized anti-cancer agent which accrues multi mechanisms of the human cellular immune system to attack a broad range of cancers. Unlike the toxicities, poor tolerability and poor pharmacokinetics are systemically administrated recombinant IL-12, this IL-12 that’s made in a factory. We have even better news, it is that GEN-1 enables production and secretion of highly-tolerable endogenous IL-12. This IL-12 is produced by the cellular factories that I just refer to. The value of this approach -- endogenous production of IL-12, the value of this approach is the subject of research in two indications ovarian cancer, glioblastomamultiforme or brain cancer. I’d like to cover a little bit more detail although it may be somewhat redundant with my comments on ovarian cancer. Recently we announced the two pronged development approach for ovarian cancer based on three elements. The results from our recent Phase 1b study that I just spoke of, the extraordinary pre-clinical results that we’ve see when combining GEN-1 with Avastin posted on our website and our understanding of the mechanism of both. In February we reported preliminary filings from the 16 platinum-resistant patient Phase 1b study. In this study we evaluated safety, tolerability and efficacy of GEN-1 in combination with Doxil. Study ended per protocol, before an [MTD] for GEN-1 was found. Nonetheless the filings demonstrated that there were overlapping toxicity, between the two therapeutics. Data demonstrating clinical efficacy including disease control and survival rate that I mentioned earlier will be presented in a post of presentation at the upcoming ASCO Conference in June. This data well position GEN-1 for a trial in the neo-adjuvant study. Next step neo-adjuvant study, where patients typically have no prior treatment with immunosuppressive drugs. The Phase 1 trial of this design was recently agreed to with FDA. The primary goal of which is dose findings start where the Phase 1b study ended. The previous study ended at 36 milligram per meter square of GEN-1. We will start this neo-adjuvant trial Phase 1 at 36 milligrams per meter square. The study will enroll up to 12 patients, 9 to 12 patients in up to five centers in the U.S. In addition with GEN-1 patient even the study we’ll be treated with the combination of [indiscernible] platinum therapy followed by surgery. Tissue samples will be taken at base line from these patients and then again following surgery to establish the relationship between higher doses of GEN-1 and it’s a fact on the immune system. Starting initiation is clearly underway, our plan to complete the study over the next 9 to 12 months. Data from this study, the neo-adjuvant study will be just to inform a dose escalating trial evaluating GEN-1 in combination with the vast and plus Doxil and platinum resistant ovarian cancer patients. Supporting the strategies I pointed to earlier are multiple pre-clinical studies combining GEN-1 and Avastin. These studies have shown unmistakable synergy even at varying dose levels of Avastin, observable reduction in tumor burden and diseases progression is statistically significant. These studies repeatedly show no obvious toxicities were associated with combined treatments and importantly the pre-clinical observations are consistent with the mechanism of action for GEN-1 which exhibit similar to Avastin anti-angiogenic properties by suppressing [indiscernible]. Our clinical strategy ovarian cancer not only reflects the growing use with Avastin in combination with therapies for wide range of cancers. It also serves as a first step in evaluating Avastin plus GEN-1 and combination for GBM or brain cancer. Again, our pre-clinical studies forming the basis in this case our pre-clinical studies that demonstrates that the administration of GEN-1 in the brain can lead the therapeutic expression of IL-12 with immune system activation that can last for up to a month. And now we know if Avastin is going to prove second line GBM so we’ve initiated a pre-clincial program to evaluate the potential of GEN-1 plus Avastin this combination in glioblastomamultiforme. We have multiple pre-clinical experiments underway assuming of favorable results. These studies will be used to support an IND filing later this year. So let me provide a more detailed update and I’ll move on to ThermoDox with more detail update ThermoDox, our proprietary heat-activated liposomal encapsulation of doxorubicin. ThermoDox has demonstrated the ability to enable high concentration of doxorubicin to deposited and targeted manner into tissue and surrounding -- into tumor masses and tissue surrounded tumor masses, when heated just above body temperature. ThermoDox is being evaluated in two clinical programs, our global Phase III clinical trial in primary liver cancer, the OPTIMO study and the Phase II clinical study of recurrent chest wall breast cancer, our U.S. DIGNITY trial. In March we reported positive interim data from the open-label DIGNITY trial, in combination, ThermoDox in combination with hyperthermia and this is for RCW. The interim data in repeat show that two-thirds of evaluable patients expansion the clinical benefit of highway refractory disease with a local complete response and partial response rate of 58% when combined. We observe this in 12 evaluable patients and it included five complete responses, again a refractory population and two partial responses. These data are consistent with our prior peer reviewed published Phase I results and are striking given the expected trajectory of the chest wall lesions at the stage. We expect to wrap up enrollment of the U.S. DIGNITY study in the third quarter with potential reporting final clinical results at the San Antonio Breast Cancer Conference later this year. The published data from this program referred to earlier has caught the attention of a number of European investigators, we used hypothermia and radiation to treat this aggressive cancer. This intention offered us an opportunity to accelerate the development of ThermoDox in the syndication in Europe. We are now in the process of initiating Euro-DIGNITY. A study that will be conducted in five countries with the support of these key European investigators and with funding assistance from a European based hypothermia company in Metalogix. Building our new centers in Europe in January we entered into an agreement with myTomorrows, as I mentioned earlier to implement an early access program for ThermoDox in all countries of the European Union plus Switzerland for the treatment of patients with RCW breast cancer. The program allows Celsion to provide eligible patients with access to ThermoDox. Access is provided in response to physician requests in a fully compliant manner, [indiscernible] no alternative treatment options available. Through our partner myTomorrows, we have launched the Early Access Program. Everything is in place to roll out country-to-country now and we expect to treat our first patient very soon. Together the Euro-DIGNITY study plus the Early Access Program offers us the opportunity to accelerate development and eventual commercialization of ThermoDox for the syndication in Europe and more importantly get ThermoDox into the hands of doctors and patients, who desperately need new and more effective treatment options. Now turning to our OPTIMA study and ThermoDox in primary lever cancer. We continue to advance our Phase III studying, as more data emerges from our earlier HEAT study retrospective analysis become more, we become more and more confident in the trial protocol design and a significant potential of ThermoDox in the syndication. As we discussed in our previous call, just a month or so ago, the latest OS data sweep from the HEAT study again reconfirmed our hypothesis that ThermoDox plus optimized Radio Frequency Ablation or optimized FRA has significant potential in treatment of primary lever cancer [both] along with its key clinical investigators and medical advisors had used the data from the HEAT study to help standardized a broader use of RFA in treating non restructure able intermediate stage, primary liver cancer lesions. The use of multiple overlapping ablations to treat three to seven centimeter tumors, translates into a longer heating duration which allows for a higher concentration of doxorubicin to be released at the site of the lesions. As of February 23rd, we noted the statistically significant 59% improvement in the OS, in the ThermoDox plus standardized RFA arm, part of a standardized RFA alone. The Hazard Ratio at this analysis was 0.628 for statisticians with a p-value of 0.02 and meaningful outcome, permitting survival outside of the HEAT study is relatively short 30 months. This data represents the seventh consecutive data set collected over two years, each of which demonstrating impressive OS benefit, each with an improving p-value. These consistent, continually strengthening data reinforce our confidence in the ongoing pivotal Phase III OPTIMA Study, our global double blinded randomized study comparing ThermoDox in combination with optimized RFA, which will be standardized for minimal 45 minutes across all investigators in the study versus standardized RFA alone. The study will include sites from numerous key markets with up to 72 sites in North America, China and Asia Pacific. At present we're allowing patients to some 40 sites, including sites in the U.S., Asia Pacific as well as Spain, Italy and Germany. Now with that update, I will turn it over to Jeff, who will review our financials, Jeff?

Thank you, Mike. Starting with the cash, we reported total cash and investments at March 31, 2015 of $30.1 million, this compares to $37.1 million at the end of 2014. Cash used for operations in the first quarter of 2015 was $5.9 million compared to $4.8 million in the same period of 2014. We estimate our average cash use to be approximately $1.5 million per month over the next three years, with the full implementation of the OPTIMA study and the integration and clinical development of our newly acquired assets from EGEN. We continue to monitor our cash expenditures to ensure the most efficient use of cash to generate shareholder value. Our first quarter cash usage was higher than our projected run rate, due in large part to one time manufacturing costs for clinical supply needed for both the ThermoDox and GEN-1 development program. We now have sufficient inventories of clinical supplies for our global Phase III OPTIMA Study, as well as the numerous Phase I and Phase II studies, we have planned for the GEN-1 immunotherapy program in 2015 and 2016. We do not expect to repeat this level of cash usage in the coming quarters due to the one time nature of these manufacturing costs for clinical materials. We continue to maintain a strong cash position and we remain in a strong financial position to ensure the development of our pipeline including the expansion of GEN-1, a very exciting development for our company. Our current cash is projected to support operating activities will past the announcement of many of the key development milestones Mike discussed earlier. R&D costs were $4.5 million in the first quarter of 2015 compared to $2.9 million a year ago. The increase mares the higher cost associated with our expanded pipeline, following our EGEN acquisition, including our GEN-1 TheraSilence program as well as the ramp-up of the OPTIMA study and the cost associated with the manufacturing of clinical supply needed for these development programs over the next two year, which I discussed earlier. G&A expenses were $2 million in the first quarter of 2015. This was down 400,000 or about 17% from a year ago. This was due primarily to lower insurance premiums. I will now turn the call back to Mike.

Thank you, Jeff. As Jeff mentioned, we ended the quarter in a strong financial position, and believe we have sufficient funds to take us through many of the exciting upcoming milestones I discussed on today’s call. With our strong balance sheet and proven development capabilities, we remain committed to our efforts of bringing forward a portfolio of therapies to address some of the most underserved cancer indications worldwide, in liver cancer, RCW breast cancer, ovarian cancer and GBM brain cancer, which I’ve said in the past coming upon the outcome of these pre-clinical studies could become the focus of the Company in the relative near-term. We’re moving quickly and thoughtfully as we advance GEN-1 and we look forward to exploring its potential in both frontline ovarian cancer, as well as, and importantly, with combination with Avastin. As I mentioned earlier, if the synergies we have seen with Avastin in pre-clinical studies have gone out in the clinic, we will have a tremendous opportunity with GEN-1 to combine with one of the most widely used cancer treatments and hopefully in multiple indications. In the near-term, though we’re focused on expanding the GBM and we are on track with an IND filing in that indication for later this year. For ThermoDox, we are successfully executing our OPTIMA trial very much on target. And at the same time we are leveraging the positive data in the RCW breast cancer study to accelerate the development of ThermoDox in this indication in Europe. The third-party support from investigators from our European partners underscores the significant, near opportunity for ThermoDox in this indication. So, I hope, I’ve given you a good snapshot of what we’ve been doing over the past few months, and the opportunities that our work in ThermoDox and with GEN-1 and with other opportunities, platform opportunities, that provided us with the consolidation with the merger with EGEN. They’ll be a good opportunity -- good overview of what the company plans for and the opportunities that exists for you, our shareholders, as well as the medical and the patients that we serve. As always, we greatly appreciate your interest in the Company. And we look-forward to updating you on our progress as we continue to move forward with these very important clinical programs. With that, we are happy now to take your questions. So please keep them to two to give everybody a chance to speak. Operator, if you would please open the lines.

[Operator Instructions] We’ll go first to Daniel Brims with Cantor.

Can you give us some idea of what the, I guess, scientific underpinning is for synergy that you might see with Avastin in those ovarian cancer studies?

Nick, do you want to take this?

Sure. As you know, Avastin is an axon VEGF in order to start the cancers of their blood supply. And with the GEN-1 product, it also when you release IL-12 it also is a VEGF inhibitor. So, we prove that concept, as Mike mentioned before, in our animal studies and we aim to show that as well in HEMO study. So, I think the science there as a very powerful VEGF inhibitor in the ovarian cancer and other models as well is there. So pretty excited about getting that started.

And I guess the immunosuppressive effects of Doxil, you are not too worried about in those studies?

Yes, that’s a very good question. We know that from this mechanism of action, there will be -- there isn’t much an inhibitory effect on the VEGF activities on the side of that. But whether we’ll have any affects from Doxil is doubtful from our animal studies and also when you look at previous IL-12 study, you don’t see it that much. I mean something we keep an eye on and I think it’s a very good question.

Our next question is from Keith Markey with Griffin Securities.

I was wondering in your conference -- in your earnings release, you talk about a strategic options being pursued for ThermoDox in China. And I was wondering if you could elaborate on that.

We can’t give you much more information than we have included in our press release Keith we see the opportunity for ThermoDox in China to be enormous. Frankly, you know that primary liver cancer is, I mean, over-used term, but ubiquitous. So I mean there's over 400,000 new cases diagnosed every year in China. I think we see a great deal of support, Dr. Borys and I had met numerous times with the CFDA with the CDE section signed for drug evaluation section of the CFDA. They’ve encouraged us in a number of ways to consider the Chinese population, in addition to our work in the OPTIMA Study. We are considering those options and we are considering them in -- I'm going to be careful with this, but considering them in conjunction with our work with HISUN. Beyond that I can't say too much more. But it's obvious to us that China remains a very strategic opportunity, not only for the Company, our Company, but for the universe of multinational pharmaceutical companies. We’ll see ThermoDox not only as an entry into the, a branded product entrée into the largest future pharmaceutical market on the planet, but also the largest syndication, in oncology indication, in the largest pharmaceutical market on the planet. So, exploring all of those options, I am, and I don't want to get ahead of myself or over my skis, on this one. But we think the work that we're doing is very much appreciated by the regulatory community as well as our partner and importantly with the medical advisors and investigators who have been working with us diligently on this development program.

But the Chinese regulatory agency hasn't allowed you to start the OPTIMA study locally yet, have they?

No, I think there's -- and we're little disappointed with the timing. But I can give you some background on that too. We saw recent publication. Of course we follow or clinical -- it's all online. It's very transparent and absolutely transparent where the status of the review of our clinical trial application is. We started out with a filing at the same time, I think 18,000 other filings were made -- potentially the backlog -- maybe I'm saying that incorrectly. The backlog at CFDA I understand to be 18,000 filings for clinical trial agreements and similar kinds of requests. So, they took a great deal of time to get to a point where they had reviewed our application. We have recently gotten two or three, what I consider to be more informational side questions, regarding CMC which is interesting, mostly on methods. How do you do this? How do you do that? Nothing that goes to the heart of -- no nothing, no serious questions that go to the heart of the protocol. We've submitted our responses to -- we're in the processes related to our prior responses to those questions. And I would expect the CFDA to act pretty quickly on now with the responses in hand. That's the best I can give you. I don’t think there's any difference. And we may be even getting a little bit of benefit, I don't know, I don't think there's any difference in the time it's taken, CFDA, to review our application than it has for the 18,000 other applications they've seen over the last year.

Okay thanks, if I could ask one more….

It's really just in 18,000….

That is size of the market, so it’s pretty amazing.

And an enormous number, if I could just ask you one other thing. I was just wondering if you could tell us a little bit about your pricing strategy in the Early Access program, and what the starting price is, or would be for the average patients in that program?

That's going to vary little bit from country-to-country. And I'm somewhat reluctant to give you the exact numbers. But I can share with you this is -- but what we’ve decided to do, we think so there is already this price intension between what we see is this enormous clinical benefit in the HCC development program, if we’re right, if we were right. And we see two or three years improvement, and no less, when you add ThermoDox to standardized RFA, if we’re right. The value of this treatment is just spectacular. I can’t even put, at this point, I wouldn't put a number on it. We know that Sorafenib, for example, for 12-week survival benefit, cost the patient, or cost the healthcare system somewhere between $60,000 and $70,000 for 11-weeks. So, we want to be very conscious to the value of ThermoDox, single-treatment of ThermoDox, single treat to treat HCC, on the one hand. On the other hand, we have an non-approved medical product that it will be prescribed, is in the process of being prescribed, to treat patients who have serious lesions on the chest-wall who will be treated multiple times, maybe as many as six or up to the lifetime maximum exposure to anthocyanins. So six cycles, and these things come in vials, so it's about 18 vials to treat a patient with RCW versus three to four vials to treat a patient with HCC. So, we got a little bit of price intension here. So, what we've decided for the Early Access program is not to price on a per vial basis, at this point in time. I mean we’ll eventually get there, but we're not ready to do that, so we decided to price on a per patient basis, not on a per vial basis. So, if a patient has six-cycles, five-cycles and four-cycles of ThermoDox, they're probably going to pay the same amount of money for this treatment regimen. Now we may negotiate that a little bit. Depending upon the market and the reimbursement conditions for -- depending on the country and the reimbursement conditions for the particular hospital or physician, it varies a little bit by hospital, actually some of the countries in Europe. So, I tried to give you a sense and the value of our drug is comparison to an approved drug. And what we're trying to deal is this tension of non-approved medical product being used to treat patients pretty much on a fairly sub-setting versus the real value of ThermoDox and providing an overall survival benefit to primary liver cancer patients. It didn't answer your question. But I hope I gave you the outline of what we're dealing with.

[Operator Instructions] We’ll go next Ren Benjamin with H.C. Wainwright.

I guess, just a couple of quick ones. The first, Mike, can you tell us exactly what studies are ongoing right now? And by the end of the year, I know we'll have the GDM study ongoing, and the Avastin, and Doxil. Can you just tell us when those studies -- you anticipate those studies beginning? And I know OPTIMA, is going on now. I get that. But, for example DIGNITY, are we still following patients, do we still expect to see updates or is everything being shifted to Euro-DIGNITY, just a sense of that would be great?

Yes, so as long as we take more time, of course you’ve got OPTIMA, we’re enrolling patients that's kind of the all-in that’s the best case of 3.5 year study. RCW in the U.S., the U.S. Dignity study, now is -- we didn't talk about this on the call but we petition, we asked the FDA, they agreed with us that we have met our primary endpoints in this study with above 50% of the patients that expected to enroll. The data is so convincing. The bio-comparability data, and efficacy data, the safety data, is so convincing, FDA has agreed with us that we can reduce the population. But I think it was written and projected to be 40-patients, and we're going to complete enrollment in this study. I think we have one more patient -- well we've actually hit the target, but we're going to enroll one more patient and certainly on a compassionate-of-used basis kind of compassionate-of-use. And so that will be 17 patients which is at the fraction of our original target to give some sense of that confidence we have in the data and the FDA has agreed with us. Of course, it's a matter of reviews. They haven't reviewed it completely. So, that study, if we enroll our last final patient in the next month with five-cycles 21-days in each cycle, study would be completed before the end of the year. That's why we're reasonably confident that the data can be presentable, presented at the San Antonio Breast Cancer Conference in December. The Euro-DIGNITY study, the protocol has been Nick and Professor Grabelli in-turn have finalized the protocol absolutely finalized, and we have all the investigator sites, six investigator sites lined-up clinical trial agreements are signed and ready to go. The last step, we're hoping to enroll a patient, the first patient in June before the ESHO conference in Zurich, European Society for Hyperthermic Oncology. So that the last step in the process to get that study up and running is the Ethics Committee review in Italy, everything else has been done. The products made that's ready to go. We went down the GOG study, completed enrollment in December, the Phase 1b study, data now is going to be presented. I think all of the follow-up, I believe all the follow-up with every patient that has been treated, has been completed. I don't believe we're following these patients to a survival benefit formally but that's, I think that's probably something that we will ask the investigators to do outside of the protocol. So, when I mentioned two more studies now coming in the ovarian cancer space, we have identified, and this protocol has been accepted. It was submitted before the end of the year for the chemo adjuvant study run, or we’ll be enrolling patients first-line looking for the -- I want to call them best respond, a single for best responders, I don't know if we can do that in the small end, but we'll be looking for best responders by taking tissue samples, also dose escalating. The goal is to complete this study in about nine-months to inform the pivotal program when we combined with that, so that trial has been approved by the agency, all of the infrastructure has been built. The CRO contracts and our monitoring schedules and data management contracts are behind us. We expect to enroll, begin enrolling patients in July that’s where that study is. On the Avastin study now with some -- we're making some pretty major assumptions with the data that's coming from this new adjuvant program. Our protocol has been -- is in draft form and it’s being circulated among the KOLs, who have been providing us advisors, scientific advisory group. And I expect that protocol to be finalized in the next few months, R&D amendment midsummer. And hopefully once we have an agreement with the agency, we can begin early next year initiating the trial. And the glioblastoma program, so we've been -- I think we’re now on our 24th cohort, preclinical cohort one more step here we want to evaluate, so evaluated Avastin with GEN-1 and this year end model because we want to add GEN-1 to the current standard for platinum failures and that standard is Avastin plus Doxil. We have one more safety target turnover. And that preclinical study, it’s just ready to go now where we will add GEN-1 to track -- I mean to Avatin plus Doxil, on checklist boxes before we submit the protocol amendment to the agency, which could happen as early as third quarter this year.

So, I just wanted to confirm the neo-adjuvant study will likely start enrolling in July, the combination study with Avastin in ovarian cancer could begin by early next year, did I hear that right?

That is exactly right.

And then the glioblastoma study, the preclinical studies are likely getting finished. But by the third quarter of this year, you could have filed an IND?

Yes, that's our objective. The kind of -- we originally had planned this GBM program to combine GEN-1 with temodar, temozolomide. And then the synergies with Avastin have just been comparable, I mean that's just the -- so we're very excited about that and what we don't want to do is initiate a trial with temodar only to find out later on that we should have crossed the few Ts and few Is an evaluated GEN-1 in combination with Avastin in that setting. So, we’re little bit behind. We originally maybe drift almost behind where we originally projected, and it’s only because of this evolving standard of care in GBM.

And just one final question regarding the OPTIMA enrollment rate, how is everything going, how many sites are on-board and how many are left to be activated?

So, we have 40 sites on-board, 45 hopefully within by the end of the month. I think that's our latest projection. We’re going to get to 72 that we’ve done it. We originally, if you recall, we originally targeted to have 100, but after reviewing points of feasibility and meeting with a number of investigators and sites, we've concluded that 72 sites have the capability and quality, and standardization of the use of RFA consistent with our objectives in the clinical protocol. So, we’ve identified all those sites. Where we are little bit, I mean where we’re behind is in the approval from China. We talked about that a little bit earlier. So the balance of those sites after this 45, probably 47 outside of China, the balance have been identified in as Chinese sites. They will come on over the balance of the year. And as far as enrollment goes, as I said in my comments, we’re approaching about 10% of the study. That's not too far off from where our projections were, even without China.

That will conclude the question-and-answer session. I'd like to turn the conference back over to Mr. Tardugno, for any additional or closing remarks.

Well, again, I want to thank everyone for joining us on the conference call. I hope you can see that not only are we committed to the work that we’re doing and the opportunity that these multiple platforms provide us, we’re also making great progress across the board. So, we’re delighted to talk to you about it. And as always, we appreciate your interest. And we will make sure that as developments work, press releases come out, so you are aware what's going on in the company. And we look forward to again to your participation in our future conference calls. Thank you very much for your time. And have a great week.

That does conclude today’s conference. Thank you all for your participation.