Michael Tardugno
Analyst · Maxim Group
Thank you, Jeff. Good morning. Thank all for taking the time to join us for today’s call. It’s a pleasure to be with you, particularly today as we are in Huntsville, Alabama proud to be meeting with the scientists and technicians who are responsible for the development of GEN-1, our immuno-oncology therapeutic now showing early, but nonetheless remarkable results in the Phase I trial of newly diagnosed stage 3 and 4 ovarian cancer patients. We call this study, the OVATION study. Today with me are Dr. Khursheed Anwer, Ph.D., Celsion’s Chief Science Officer, and Jeffrey Church, from whom you’ve just heard, our Chief Financial Officer, Dr. Borys - Dr. Nick Borys, just back from meeting with our OPTIMA Study TIs in South Korea, is on the line in Lawrenceville and will be available to take questions. I’d like to start by saying that we could not be more pleased with our product portfolio and progress we are making and investments that we have made in GEN-1, our gene-based therapeutic. For those of you who have been following Celsion, you know that we are an oncology-focused development stage company with two of our three technology platforms in the clinic, one in chemotherapy, and one in gene-mediated immunotherapy. For today’s call, we will focus on the two very important, and I’d say highly promising clinical trials for the product candidates that have been developed from these platforms. The first is our neoadjuvant study in first-line ovarian cancer that I just spoke of, the OVATION study combining GEN-1 with standard of care therapy followed by interval debulking surgery. The second is the primary liver cancer OPTIMA Study of first-line Phase III global study of ThermoDox in combination with radiofrequency ablation that has been standardized to a minimum of 45 minutes of time interval where we now know that this ablation technology is most effective in combination with ThermoDox. ThermoDox of course, as you know, is our elegant heat-sensitive liposomal dosage form of Doxorubicin. You should know that both GEN-1 and ThermoDox are unencumbered assets. Both are being evaluated at some of the most prestigious research hospitals in the world. Both are in studies that are being professionally and rigorously managed and both address potential billion dollar market opportunities. I’d also say, with both of these studies, there is virtually no trial execution CMC or regulatory risk. Both product candidates are in development at the sweet spot of Celsion’s competencies. Clinical stage development is what we do and do well. From a commercial standpoint, both trials address large unmet needs. If we are right, if either study demonstrates a meaningful clinical benefit, we would expect global regulatory approval, rapid adoption, and generous gross margins. Now I’d like to talk about the TheraPlas technology platform, specifically as it relates to GEN-1. TheraPlas is a synthetic non-viral nanoparticle engineered to transport DNA plasmas into living human cells. These infected or transfected cells are then turned into mini factories that produce and secrete sustained tolerable levels of the therapeutic protein for which the plasmid is coated. The beauty of this technology is that it can be administered repeatedly and as we have seen without concern for safety, or the inhibitor effects of neutralizing antibodies. So in the case of GEN-1 for example, our first therapeutic using this platform the immune system can be repeatedly put into overdrive to address and attack cancer cells in micro metastases that have suppressed body’s own natural defenses and have escaped the initial treatments. To only talk about GEN-1 specifically, this marvelous little nanoparticle that carries an IL-12 coated plasmid payload Interleukin-12, IL-12 is a well-known inflammatory protein and a well-characterized anti-cancer agent that up regulates the immune system, inhibits the production of tumor supporting blood vessels and suppresses the ability of the cancer to put the brakes on the immune system. Historically, the development of IL-12, particularly using factory-produced recombinant IL-12 proteins has been hindered due to its poor pharmacokinetics. Our thesis is that, GEN-1 overcomes this limitation by teaching the body’s own cells to locally secrete tolerable therapeutic levels of IL-12. The proof of our thesis is inarguable. In a study conducted by the GOG in second-line ovarian cancer patients, translational data from tissue biopsies demonstrate that locally administered GEN-1 does produce an immunologically distinct IL-12 protein that remains locally active in the tumor environment. IL-12 secretion continues then for approximately one week after treatment. That IL-12 can – the GEN-1 can be administered repeatedly and that GEN-1 shows a dose-dependant immunological activity. In the study we also observed very encouraging clinical findings. The one I just talked about are translational findings, but also clinically we found some very encouraging results, with partial response for stable disease observed in 100% of evaluable patients treated at the highest cohorts. That said, however, our most significant findings were announced recently. These data comes from the first cohort of three patients in the OVATION study, our Phase I, as I said, our Phase I dose escalation study in newly diagnosed stage 3 and 4 ovarian cancer patients, patients who present with high tumor burden in local or distant metastases. While it’s difficult to draw definitive conclusions from a small sample size, we are as our investigators, who have talk to me personally, we are excited nonetheless. The results are simply remarkable. Remember again, that these are advanced stage patients who after treatment all experience a dramatic drop of greater than 96% in their cancer antigen 125 protein levels, a 50% reduction in CA 125 is considered meaningful and it’s a comparison, 96% reduction versus what clinically is considered meaningful of 50% reduction. Surgical reports indicate that all patients had successful resections of their tumors with two patients reporting R0 resection. Our R0 indicates a microscopically margin negative resection in which no growth or microscopic disease remains in the tumor bed. We also report one very advanced patient with an optimal R1 resection. But perhaps the most compelling data comes from the first cohort of patients is the fact that one patient demonstrated a pathologic complete response. PCRs as they are known are seen in less than 7% of patients receiving neoadjuvant chemotherapy followed by surgical resections and they have been associated with a median overall survival of 72 months, that’s more than three years longer than those who do not experience a PCR. Interestingly enough, by the way, as Dr. Borys points out to me, this patient also skipped two doses of chemotherapy. The FDA has stated publicly that the agency would support the use of PCR as a surrogate endpoint for a registrational study in difficult to treat ovarian cancer. We are continuing to follow the data closely in the OVATION study and opened up discussions with the FDA if we see additional PCRs in the upcoming next dosage cohorts. These results, along with previously announced pre-clinical findings provide more than enough evidence to explore the potential application of this promising therapy, not only in first-line ovarian cancer patients, but in second-line as well in combination with Avastin and Doxil, which is the next step in our development strategy. From the literature, we know that Avastin combined with Doxil produces a modest response rate of 27%. We believe that, by adding GEN-1, we will see a substantial improvement in patient outcomes and plan to move forward with an IND submission for a Phase I 2 study clinical trial using this combination later this year. As I said, our interest in – our interest is supported by some remarkable pre-clinical data that I like to share with you. So we talked about the clinical data and I want to just drop back a little bit and give you an update on the pre-clinical data which was announced at the AACR this year in 2016, American Association of Cancer Research. We had the opportunity to present these findings demonstrating that GEN-1 when combined with Avastin and Doxil produced a greater than 98% reduction in tumor burden when compared to the unresected control group and a statistically significant 92% reduction when compared to the combination of Avastin and Doxil. Let me summarize GEN-1 for you briefly before we go on. Positive second-line clinical and translational findings in the studies performed by the GOG. Completely unexpected, extraordinary findings and the first cohort of a Phase I study of newly diagnosed late-stage ovarian cancer patients. Clinical and pre-clinical findings highly supportive of the synergy of Avastin and GEN-1 in a Phase I 2 trial to begin enrolling later this year. That’s the brief update on GEN-1, a product - an investigational product for which we could not be more excited. Now let me turn to ThermoDox, our most advanced product candidate, but before I get started, I want to refer you to an article that was written by our own Dr. Nicholas Borys in the online journal, Advanced Healthcare Network, the title of which is, Testing a Cure for Hepatocellular Carcinoma Analyzing the Use of Lyso-thermally Sensitive Liposomal Doxorubicin. A link to this article is posted on our website. In this publication, Dr. Borys clearly lays out the basis for our confidence, confidence in the OPTIMA study. I believe that you will appreciate his insights, particularly if you are on the fence with regard to this study. We are continuing to execute our Phase III OPTIMA study in primary liver cancer. I am pleased to report that the Independent Data Monitoring Committee, the IDMC, held its first data review and recommended continuation with no significant, no significant concerns. OPTIMA’s power and design to evaluate ThermoDox in combination with optimized RFA, which will be standardized – which is standardized to a minimum of 45 minutes across all investigators in clinical sites for treating lesions, three to seven centimeters versus standardized RFA alone, standardized for 45 minutes. We ensure this procedure is being conducted with a minimum of 45 minutes with online data management, online data capture and rigorous monitoring of the investigator sites. I say that to you because I get asked that question all the time. This study is expected to enroll up to 550 patients globally in up to 75 clinical trial sites in North America, Europe, Asia-Pacific and now in China. China of course, as you know, represents an extraordinary market opportunity with approximately 50% of the 850,000 new cases of primary liver cancer or HCC Hepatocellular Carcinoma diagnosed each year. We expect strong participation from all of our clinical sites in this country. It’s important to note that the OPTIMA study is informed by the consistently impressive and statistically significant sub-group of data from our HEAT study, a trial that while failing to meet its primary TFS endpoint, vastly improved our understanding of radiofrequency ablation in the intermediate stage, intermediate size, HCC or primary liver cancer. We now know more about RFA, I can say this with confidence. We now know more about RFA and intermediate stage HCC than just about any company on the planet. What we know is that, RFA, radiofrequency ablation, must be used within its engineered design limitations to be effective. For tumors greater than three centimeters, the treatment time becomes exceedingly important when we add ThermoDox to a procedure of 45 minutes or greater, the outcome is extraordinary. For the past three years, we’ve been following this well-balanced, well-bonded sub-group of 285 patients that represents over 42% of the 700 HEAT study subjects whose RFA treatment was greater than 45 minutes. 285 patients RFA, plus minus ThermoDox, greater than 45 minutes. With each quarterly overall survival data sweep, the clinical benefit observed in the ThermoDox arm improves, as does statistical significance. Tested at multiple international symposia and supported with prospective animal studies and computational models these data more than reinforce our confidence in the OPTIMA study. Our most recent data sweep conducted in July of last year, the median overall survival in the ThermoDox plus standardized RFA arm was approximately 80 months or 6.5 years following treatment, 6.5 years, which by any standard or measure would be considered curative treatment. In an indication for curative treatment in patients with intermediate size lesions are unprecedented. In contrast, our optimized RFA alone results in a median survival of only 54 months, which is slightly better than chemoembolizational alternative local therapy to be clear, ThermoDox plus standardized RFA that’s greater than 45 minutes shows a greater than two year improvement over all current interventional procedures. Two year overall survival improvement. One more point and this maybe that premature, but we are also looking forward to an independent confirmation of our hypothesis that longer heating time, when activating ThermoDox translates into a significant improvement in overall survival. Celsion, as you may know has accredited with the NAH under which the three terabytes of data, three terabytes of data representing the entire intensive treat population from the HEAT study with independently analyzed. And while there isn’t a lot more refinement yet to do before the findings are ready for publication, it’s clear that initial conclusions from this analysis support our thesis that standardizing RFA with an adequate amount of heating time, in particular for intermediate size tumors is a significantly positive effect in overall survival when combined with ThermoDox. As we continue to execute our global strategy for OPTIMA, we were extremely pleased to announce that the first patient in China has been enrolled. China represents as I said, one of the most important markets for ThermoDox with – more than half of all new diagnosed cases each year in China. So we are working hard to support registration in this region. We plan to enroll a minimum of 200 patients in the China territory. That’s the minimum required or CFDA, the China Food and Drug Administration to accept an NDA application. If we are successful, the OPTIMA strategic positioning, in OPTIMA we strategically position our investigator sites. To this end, we will support product approval filings in all major global markets, in addition to China, Southeast Asia, South Korea, the European Union and Canada and the United States. So we structured the study, say it little bit more clearly, we structured the study with investigator sites in all the major markets for which if we are successful, we can immediately file an NDA. In summary, primary liver cancer represents the largest unmet medical need remaining in oncology. We are committed to fully exploring the potential that ThermoDox has demonstrated so far. We are pleased with the progress we have seen in the OPTIMA trial and we remain on track to complete enrollment on or around, tough, now with China coming on, on or around the end of 2017. That would be followed by a preplanned interim efficacy analysis, the first of two which should read out in the first half of 2018. So it’s quick update on OPTIMA. I want to turn now in addition to the OPTIMA study, we are advancing our development program for ThermoDox in recurrent chest wall breast cancer, you know this indication. We’ve talked about it many times. These are patients who have had mastectomy that seen a recurrence on their chest wall, when it recurs it recurs and one of the most virulent ways. Data represented from our Phase I 2 HEAT study that our DIGNITY studies that were conducted in the United States were presented at the San Antonio Breast Cancer Symposium last December. These data demonstrated that a combined – demonstrated a combined local response of 62% among the evaluable patients treated with ThermoDox in mild hyperthermia. So this is a highly, highly, highly compelling result. These are patients, as I pointed out, are refractory. They failed at least two, maybe three lines of chemotherapy, they failed radiation. What we know is this, is local tumor control in this patient population provides a sufficient clinical benefit that it can be a registrational endpoint as if we have agreed to with the FDA. Building on this data coming from the US this astounding data coming from the US. Our European DIGNITY study will evaluate complete and partial responses after three cycles of ThermoDox plus hyperthermia and now we are adding radiation as well as local regional tumor breast – breast tumor control – breast tumor control in patients undergoing this tri-model therapy. It’s important follow-on study, hyperthermia as you may know is a standard of care for the addition of – it is a standard of care for many cancer indications. We expect to have an easier time enrolling patients with a group of very highly motivated investigators who approached us to conduct this trial. We expect to enroll 70 patients in this open-label study and expect the first site activation in mid-2016 with the first interim efficacy analysis expected in the first half of 2017. As a reminder, this trial is a great deal of interest. This trial is being funded in par with support in time from our partner MedLogix, the manufacturer of the heating technology and our investigational hospitals. As I mentioned earlier, we have a third very, very promising platform, it’s at pre-clinical stage and we spend a lot of time on it today. Promise you, we continue to see positive results, we’ll spend more time on in upcoming conference calls. But this is a lung-directed platform that provides a basis to take therapeutic RNA to treat lung disease. This promise is being evaluated under collaborative arrangements with companies that own and are developing therapeutic micro RNA technologies. We are currently focused on this regulatory construct of RNA, known as microRNA or miRAs or anti-miRAs. It’s safe to expect as I have been saying, if we do see an ongoing positive results in this very exciting next-generation of medicines, we will continue our research through joint development agreements. We are very excited about the potential of both GEN-1 and ThermoDox and we look forward to providing you with updates as we advance these programs. So let me now turn the call over to Jeff Church for a review of our financial results. Jeffrey?
