Imunon, Inc. (IMNN) Q1 2012 Earnings Report, Transcript and Summary

Good morning. My name is Roxanne, and I will be your conference operator today. At this time, I would like to welcome everyone to the Celsion Corporation First Quarter 2012 Shareholder Conference Call. [Operator Instructions] I would now like to turn the call over to Jeff Church. Please proceed.

Thank you. Good morning, everyone, and thank you for joining us. Our first quarter 2012 financial results were released this morning before the market opened and are available on the SEC's EDGAR system and on the company's website at www.celsion.com. Today's call will be archived, the replay beginning today at 2 p.m. Eastern, and will remain available until Tuesday, May 22, 2012. The replay can be accessed at 1 (877) 870-5176 in North America or 1 (858) 384-5517 internationally, using conference ID 3066549. An audio replay of the call will also be available on the company's 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 risks and uncertainties including, without limitation, the risk of clinical failures; delays or increased costs; unforeseen changes in the costs of our research and development activities and clinical trials by others; possible acquisition of other technologies, assets or businesses; and possible adverse actions 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. With that, I'd like to turn the call over to Michael Tardugno, President and CEO of Celsion Corp.

Thanks, Jeff. Good morning, and thank you for joining us and for your interest in Celsion, a company I'm sure you'll find to be one of the more interesting in biotech, with arguably one of the most important clinical trials in oncology today. The message today is momentum. With positive data, we will be bringing to market a first-line treatment for the intermediate stage of a very difficult cancer and the largest unmet medical need in oncology, that's hepatocellular carcinoma or HCC, sometimes commonly referred to as primary liver cancer. We're joined today by Dr. Nick Borys, our Chief Medical Officer; Greg Weaver, our Chief Financial Officer; and Jeff Church, our Senior Vice President in Investor Relations. On today's call, Greg will review our first quarter 2012 financial results, including balance sheet and P&L highlights. Following that, Dr. Borys will discuss progress and future milestones for our global Phase III HEAT Study in primary liver cancer, as well as an update on the expansion of the ThermoDox platform. I will then provide an overview of other key corporate goals as we work towards data readout, regulatory approval and the subsequent commercialization of ThermoDox. After that, we will open the call to your questions. As always, I'd like to make a few comments first. Our Phase III HEAT Study in primary liver cancer has technically reached all of its enrollment goals. With our primary endpoint data projected by year end, Celsion is in acceleration mode as we prepare for global commercialization of ThermoDox, which I'd like to cover for you briefly. On the regulatory front, we are taking advantage of the extraordinary positioning of the HEAT Study. The HEAT Study is a Special Protocol Assessment, as you know, and has Fast Track Designations in the U.S., both of which promise timely action on the trial after submission. The EMA has indicated its support for centralized filing of a marketing application authorization. With the consequence of global enrollment, we are engaging regulatory agencies in all major markets to discuss our registrational application, and local requirements for submission. To support rapid launch, we've enrolled patient cohorts in key markets, countries where HCC is a particular problem, sufficient to support filing on it without the need for bridging studies. We're hopeful to file directly, particularly in the PRC, People's Republic of China and Taiwan, without the need for approval for a reference country. Then we enjoy Orphan Drug Designation in the U.S. and Europe, providing, among other things, regulatory exclusivity of 7 and 10 years, respectively, and in the U.S., substantial pricing power. On the clinical front, we're working diligently to assure no surprises with trial data with this 3-step program. First, we've established a clinical quality dashboard where we track and evaluate timeliness, currentness, trends and anomalies in the clinical data set. This information is reviewed and critiqued at each and every DMC meeting, which you know have been regular and frequent. Number two, we have instituted a remonitoring program for a number of high-volume sites, the goal of which is to check and double check data entry from source documents. And number three, we've implemented a comprehensive clinical quality audit program as a check on our CRO and their work product. We're also moving forward with branding, market research and pricing analysis. We are conducting preliminary research with physicians, KOLs and payers to better understand the patient journey, ThermoDox's positioning and its value in the treatment of HCC. We have registered our trademark ThermoDox in virtually every country where it will be sold. We have also been given approval for ThermoDox as a brand name in all countries where we've applied, except one, and that's Mexico. And the reason there is that ThermoDox can be confused with another drug marketed for veterinary use. On the manufacturing front, what we're doing here is nothing short of remarkable. We are working to establish multiple manufacturing partners in the U.S., as well as in China, to assure reliable, quality supply chain with a cost of goods that can support substantial margins on a global basis. As for the NDA submission process, we have engaged our principal investigators and KOLs for discussions around the treatment landscape and standard of care as we consider label negotiations with FDA, SFDA, EMA and other regulators. And we are moving forward with the selection of a CRO with FDA portal access and using a common technical document approach as a basis for our NDA and EMA filings. What this means for us as a company is that preparation for commercialization and launch of ThermoDox is now fully underway. And we're not just considering the U.S., we are also addressing the broader global opportunity efficiently and effectively with a single global trial in a manner I suspect is incredibly unique for a nonrevenue-generating company. In important recent events along this path is the commercial supply agreement we recently signed with Hisun Pharmaceuticals, a world leader in the manufacture of chemotherapies and now a key partner of ours in China, which we will speak of more during the call. Now a little more background on the promise of our technology platform and ThermoDox, in particular. Some of you who have followed oncology know that a considerable number of thought leaders today, including many, if not all, of the more than 200 principal investigators and some investigators in our trial will tell you that a multi-modality approach is the future of care in a list of difficult cancers. One modality leading this charge is heat-based therapy. Hyperthermia, which has seen a significant technological advancements in recent years, is being used or developed in an increasing number of indications from liver cancer to breast, colorectal, bone, pancreatic and many others. Recognizing this potential, Celsion embarked on the development of a heat-activated liposome technology invented at Duke University. But unlike any other, it has the potential to greatly extend the curative or palliative benefits of hyperthermic treatment. Our heat-activated liposomal encapsulation technology can incorporate many approved chemotherapies, delivering their well-characterized activity in a highly concentrated manner. This targeted delivery takes place thanks to both the natural delivery of liposomes to the organs such as the liver and through the leaky blood vessels of many tumors. Most importantly, only when triggered by the presence of applied heat is the drug released. This activation approach is critical, patented characteristic of our technology. It concentrates the therapeutic benefit only to the targeted area as compared to the same dose of a similar chemotherapy. It is a uniquely simple and an elegant solution. ThermoDox, as the name implies, incorporates doxorubicin, a therapy known to be active in liver cancers. ThermoDox is an adjunct to our Phase III [ph] subject to HEAT Study, which I will remind you, is the largest trial ever conducted in the intermediate hepatocellular carcinoma. The goal is to improve the outcome in patients with intermediate stage HCC. And Dr. Borys will cover this in more details during his remarks. While liver cancer provides a significant market opportunity, it is just a first step. ThermoDox is a drop-in treatment for procedures like RFA. It has the potential to substantially improve outcomes, and in doing so, to change the standard of care for many cancers. We believe, in fact, that it could become one of the most important new drugs in oncology in recent memory. Now I'd like to focus on our immediate issue, and that's liver cancer. Ladies and gentlemen, the statistics here are sobering. The incidence of primary liver cancer today is approximately 26,000 to 28,000 in the United States, approximately 40,000 cases per year in Europe, and is rapidly growing at 5% annually on a base of 750,000 incidents globally. This increase is due, in a large measure, to the prevalence of hepatitis B and C in developing countries. For countries in the West and in Japan, during the 10-year period ending 2019, incidence is projected to increase by 20%, prevalence by 47%. Over half of new cases will be in China. The World Health Organization estimates that primary liver cancer may become the #1 cancer worldwide, surpassing lung cancer by 2020. Without new and effective therapies, the threat to public health presented by this disease is considerable. One of the -- of the 27 emerging therapies in development, only 6 are in Phase III, only one is for first line, and that's ThermoDox. More importantly, as a recent research publication spectrum points out, and I quote, "Any company that can develop a targeted agent to treat HCC has tremendous potential for success commercially. Particularly, those in the intermediate stage who are currently treated mainly with TACE or chemoembolization." So now, reflecting on Celsion. The last 6 months or so have been marked by significant progress in a number of important accomplishments with and in addition to the HEAT Study. Among our recent developments are the following: Yesterday, we announced a joint resubmission with Philips Healthcare under our combined IND/IDE, a protocol with the FDA for a Phase II clinical study of ThermoDox, combined with MR-guided high intensity focused ultrasound, known as HIFU, for the treatment of prostate cancer mets to the bone. The resubmission was made with extensive supporting data from Philips Phase I HIFU trials, and this submission was made in response to earlier questions required or asked by the agency of both Celsion and Philips in the original submission of our Phase II protocol. We expect to initiate the clinical study in the second half of 2012 assuming, of course, we have agreement with the agency to move forward. Earlier this month, we were very pleased to announce our collaboration with Focused Ultrasound Foundation to support preclinical studies exploring the use of ThermoDox in high-fluid pancreatic cancer. This phase will be funded by the FUF and carried out under the guidance of Joo Ha Hwang at the University of Washington School of Medicine. Celsion will provide ThermoDox for these studies, among other research support. Pancreatic cancer is the fourth leading cause of cancer-related death in the United States, and with an exceptionally high mortality rate. Any advancement in therapy would be an important step forward for treatment. Dr. Hwang is particularly excited about the prospect of combining these 2 modalities as a potential avenue for achieving this objective. This is the first of what we hope will be other cooperative programs with FUF and its affiliated researchers. In April, we announced the successful completion of a planned safety review by the HEAT Study's independent Data Monitoring Committee. The DMC reviewed comprehensive data from 652 patients, and unanimously recommended that the study continue according to protocol. The DMC reviews comprehensive -- study data at regular intervals, with the primary responsibility of ensuring the safety of all patients enrolled in the study, the quality of data collected and the continued scientific validity of the study design. To date, the study has undergone 7 unblinded reviews and one preplanned interim efficiency, efficacy and futility analysis by the DMC, all with positive recommendations to continue the HEAT Study as planned. The HEAT Study remains on track with its over-enrollment objective to treat a total of 700 patients by the end of this quarter. This is an event-driven trial, with PFS as its primary endpoint as progression-free survival. The study's powered at 80%, to show a 33% improvement in PFS. 380 events are required to reach the planned final analysis of the study. These events are projected to occur in late 2012, and as we have said, with top line results announced following the DMC's review. As I mentioned, we have reached our technical enrollment targets in all key markets for ThermoDox, most recently in China. China requires a minimum of 200 patients for registrational filing, an enrollment figure we reached in April. We are -- we continue to enroll additional patients in China to ensure robust data set, and of course, no surprises. While the HEAT Study has reached its key execution goals, we are looking to the various components of the regulatory and commercialization process. On the manufacturing front, as I mentioned earlier, we recently signed a very important long-term commercial supply agreement with the Zhejiang Hisun Pharmaceutical for the production of ThermoDox in China. Hisun is a leading manufacturer for a number of multinational pharmaceutical companies and the largest marketer of finished oncology drugs in China. They have recently entered a $300 million JV with Pfizer, with the goal to expand their commercial footprint in China. The value of a Chinese partner goes well beyond the supply agreement, however. Our relationship with Hisun is an important component of our regulatory strategy in that country, and it affords us access to an accelerated SFDA review and a potential for regulatory exclusivity for the approved indication. I cannot express Hisun's optimism any better than their Chairman, Mr. Bai, has, which certainly is reinforced with their willingness to finance the project. It should not go unnoticed that after some diligence, and I would suggest validation, Hisun accepts both the technical and financial risks associated with the project. Hisun will provide us with nondilutive financing and the investment necessary to complete the technology transfer of our proprietary manufacturing process and the production of registration batches to support our registrational filing. Out-of-pocket cost for the program will be in the range of about $2 million and will be repaid to Hisun only after technical success, as the completion of 3 successful registration batches and after data from the HEAT Study is unblinded. Our supply agreement is initially limited to China, which I had mentioned, is the single largest global market for primary liver cancer. Hisun has been granted, however, an option for global supply after local regulatory approvals have been secured in countries other than China. The manufactured price for ThermoDox under this agreement supports a generous gross margin across all global territories. Through our other markets, the HEAT Study remains well positioned. In addition to a Special Protocol Assessment in the U.S., we have agreement with the EMA that the HEAT Study is acceptable, as is, for the basis of a submission for centralized filing for marketing authorization and potential full approval. This adds to other designations that provide for a rapid review of ThermoDox, once our global applications are submitted. And for those of you who may have questions regarding Japan and Yakult's continuing interest, I'm pleased to convey from our recent conversations with Yakult, Yakult's recent and continuing sentiment that they remain enthusiastic and that we should expect initiation of their clinical bridging study, among other development objectives, with positive data from the HEAT Study. With data in sight for primary liver cancer, we continue to strategically expand our clinical programs for ThermoDox, something Nick will talk about in a minute, but first, I'd like to turn this over to Greg, to cover our first quarter financial results. Greg?

Thank you, Mike. The company ended the first quarter with cash and investments of $24.6 million. This provides us with sufficient cash to fund operations into the third quarter of 2013, which is beyond top line data in our ThermoDox pivotal trial in primary liver cancer and through the period of evaluating our strategic and financial options for bringing ThermoDox to market. Our first quarter use of cash is not indicative of our forecast run rate going forward. The run rate forecast reflects a gradual decrease in our quarter-to-quarter use of cash as the HEAT trial clinical costs and the initial cost of manufacturing registration batch development, which trended higher as expected over the past 6 months, are expected to lighten up later this year. We reported a net loss of $6.2 million in the first quarter of 2012 or $0.19 a share, compared to a net loss of $3.8 million, $0.28 a share for the same period of 2011. At Q1 2011, income statement included $2 million in revenue from licensing fees received from Yakult. Net cash used in operations for the first quarter was $5.7 million in total operating expenses in Q1, $6.3 million as compared with $5.6 million in Q1 of last year. Research and development costs increased by approximately $350,000 to $4.7 million in the first quarter of 2012 compared to the same period of 2011. The increased R&D costs are related to our 3 ongoing clinical studies and to the development of commercial manufacturing capabilities for ThermoDox. G&A expenses for the quarter increased approximately $350,000 to $1.6 million as compared to Q1 of 2011, and the increase is the result of professional fees and personnel costs to support the company's growth. We filed an 8-K last week, describing a new relationship with our partner in China, Hisun. I'd like to briefly review the financial terms of this long-term commercial supply agreement. Hisun will provide technical and regulatory support services to complete the tech transfer of our manufacturing process and the production of registration batches for ThermoDox. Hisun will be paying for the cost of this work and Celsion will then repay Hisun for the aggregate amount of these development costs and certain fees calculated on a cost-plus basis, upon the successful completion of the 3 registration batches of the product, which will be repaid within 4 years of signing the agreement. We expect the registration batches will be completed next year and we initially estimate the total cost of the manufacturing technology transfer will be approximately in the range of $2 million. I expect we'll capture these costs as a payable to Hisun in our future company financial statements and we'll be repaying this cost investment by Hisun after we see the unblinding of the pivotal trial data and after Hisun delivers the successful registration batches. So we're very pleased with the financial terms of this manufacturing supply agreement and the fact that following their diligence process, Hisun agreed to take on the technical and inventory risk in advance of seeing data from the HEAT Study. And beyond the financial terms, this deal is strategically important to provide ThermoDox the international manufacturing capability needed to drive commercial success into the largest markets in Asia, again, funded with a nondilutive cost structure and at very attractive future cost of goods sold. Thank you for your attention. I'll now turn the call over to our Chief Medical Officer, Dr. Dick Borys.

Thank you, Greg. I'd like to start by addressing our pivotal HEAT Study program. The HEAT Study is a multinational double-blind, placebo-controlled, pivotal Phase III clinical trial evaluating ThermoDox in combination with RFA in patients with non-resectable primary liver cancer. For primary liver cancer, there exists poorly defined treatment options for intermediate disease, which is between the early stage of disease, which is eligible for curative resection; and later stage disease, subject only to palliative treatment. RFA, a treatment with curative intent, is the predominant choice for non-resectable liver cancers, with average local recurrence rate of around 50%. Its efficacy, however, is limited by tumor size, showing significantly less effect in tumors greater than 3 centimeters in size. By combining RFA with ThermoDox, the margin surrounding the tumor is heavily treated with doxorubicin, an effect which our data strongly indicate may extend the cure rate of RFA to larger more locally advanced tumors. Having a direct understanding of ThermoDox's effect in larger tumors is, therefore, a critical component of the ThermoDox clinical value proposition. We are working to ensure that the HEAT Study is supportive of international filings, particularly in the Asia-Pacific region, where over 70% of the 750,000 worldwide annual incidence of liver cancer occur. The HEAT Study recently surpassed sufficient enrollment to support our registrational filing in China, which adds to study population sufficient for registration in South Korea and Taiwan, 2 other large and important Asian markets for ThermoDox. A team here at Celsion is working diligently to prepare for commercialization. Supporting our regulatory goals are a number of key designations, including Special Protocol Assessment and 505(b)(2) agreements with the FDA, as well as Fast Track, and upon submission, priority review status. We are planning for a rolling NDA submission and a 6-month regulatory review in a simplified review process. We also have confirmation from the EMA that the HEAT Study, if successful, could form the basis for our European filing application as well as a second avenue for global registration. We may be afforded many review benefits to what the EMA calls a full mixed review registration process. While primary liver cancer is a priority for Celsion, ThermoDox's unique properties support its potential well beyond this indication. We are currently exploring ThermoDox's use in 4 other prominent oncology indications and are taken care to ensure that each of these programs, assuming positive outcome, can form a basis of support for the use of ThermoDox in additional indications. In January, we enrolled our first patient in the ablate study, a multicenter Phase II study that is expected to enroll up to 88 patients with colorectal cancer metastasized to the liver. Patients will be randomized to receive either RFA plus ThermoDox or RFA alone for the treatment of their liver tumors. The primary endpoint of the study is local tumor control at 1 year. With secondary endpoints of time to local progression and overall survival and, of course, safety. There are an estimated 140,000 new cases of colorectal cancer and about 50,000 colorectal cancer deaths each year in the United States alone. Up to 25% of patients with colorectal cancer present with liver metastases and another 50% develop liver metastases within 5 years. Unresectable liver metastases frequently represent a poor prognosis. RFA is both efficacious and widely-accepted local treatment modality for this disease, however, it, too, has limitations. As in our work with HCC, we believe we can improve RFA's efficacy in colorectal liver metastases with an adjuvant such as ThermoDox. In recurrent chest wall breast cancer, as many of you know, data from an early Duke University Phase I study in very advanced recurrent disease were exciting. We are currently moving forward with a Phase II study in this indication, the DIGNITY Study. This Phase II study has been limited to 40 patients with this form of breast cancer, and will enroll patients who have received but failed prior treatment. As many of you know, Celsion is also working with Philips Healthcare, a division of Royal Phillips Electronics, to develop treatments for painful bone metastases using ThermoDox and HIFU. This, I believe, will just be a beginning for combining important device technology, such as HIFU, with important drug technology, such as ThermoDox. I am personally very enthusiastic about the potential of ThermoDox enabling technologies such as HIFU in making tumor removal become less invasive, while more effective. With that, I'll turn the call back over to Mike.

Thank you, Nick. And I hope we've made clear to you, Celsion is steadily focused as we are preparing for what will be the most important event in this company's history, the validation of our technology platform in our lead therapeutic, ThermoDox, through results from the single largest study ever conducted into intermediate primary liver cancer. The outcome of the HEAT Study will set into motion a transformative process at Celsion, one that will take us from a development stage organization to an integrated commercial biopharmaceutical company with, perhaps, the single most important new therapeutic introduction to the global oncology market in years. Data, expected within months, is now clear in sight. And at the year end, projected events, target approaches, we expect to announce several milestones, including enrollment completion of the HEAT Study, which should occur this quarter and various milestones related to our NDA application with the FDA. We also look forward to advancing our non-pivotal study, our preclinical work in colorectal cancer metastases, recurrent chest wall breast cancer, colon cancer and pancreatic cancer. This work will give the oncology community a snapshot of the broad potential of ThermoDox around the time where its approval is being considered by several regulatory agencies around the world. As always, we greatly appreciate your interest in the company and we look forward to updating you on our continued progress. Now we will go to questions. [Operator Instructions]. So operator, if you will, please, open the line for questions.

[Operator Instructions] We'll go first to Keith Markey with Griffin Securities.

Congratulations on the deal that you signed with Hisun. It sounds like a very interesting one. I was wondering if you might expand upon the reasonw for choosing them, for instance, will they have any marketing -- do they have marketing capability? And would they be supplying areas outside of Asia, for instance?

Yes, Keith, I'll answer that for you. The agreement that we have with Hisun exclusively focuses on manufacturing of ThermoDox. At the moment, the supply will be limited to the territories represented by the People's Republic of China, which includes Mainland China, Macau and Hong Kong. Hisun will have an option to expand distribution into territories outside of the PRC, following approval of their manufacturing process by other regulatory agencies like the FDA. And of course, with the consent of any licensed partner that may have responsibility for commercializing ThermoDox in their respective territory. Now with regards to Hisun's aspirations for a commercial relationship with Celsion, I really can't comment on that, Keith. At the moment, our relationship with Hisun is exclusively related to a supply agreement.

Very good. And if I could ask, did I understand that Yakult plans to resume their trial once they see the HEAT data?

Yes. So just to restate, we've had a number of conversations ongoing and recently, with Yakult. As I shared in my prepared remarks, Yakult remains very enthusiastic not only with regards to the potential for ThermoDox to treat Japanese patients, but also with the outcome of the trial. While that said, the pathway for filing a drug derived outside of Japan follows a typical pattern. And that pattern is approval outside of Japan first, followed by typically our bridging or safety studies followed by a submission to the PNDA for local approval. That's a pathway that was always contemplated in our original agreement with Yakult. And not to get into -- to confuse the question, but we try to accelerate that, as many of you know, by including a cohort of patients from Japan in our Phase III trial. Be that as it may, the pathway we're following currently is the traditional pathway. And so Yakult, under our agreement, has been conducting some preclinical research that's required specifically for filing in Japan. I believe that's all completed. And, will, once the data from the Phase III trial is available -- and of course, we expect it to be positive -- they will commence their bridging studies to support registration in Japan as had been originally contemplated.

Great. If I could just expand upon that. How long do you think their bridging study will take then?

I'm not sure I'm in a position to comment on that. But I will just say this is -- it's typically a smaller study, Keith. I don't know the exact number of patients that will be included in this study, but typically, they're smaller studies, largely focused on kinetics and safety.

We'll go next to Edward Nash with Cohen and Company.

I wanted to find out just on -- with regard to Hisun, do they actually have the capacity right now to be able to supply for worldwide material -- do they have that ability right now? Or would you have to have a backup supplier?

Yes. So let me try to answer that in a couple of different ways for you, Edward. Number one is, it's our objective to have multiple manufacturers for reasons of supply continuity. We want to make sure that there is no interruption of supply of ThermoDox to any market, number one. So -- and so we won't be capacity-constrained by a single manufacturing entity. Number two is -- and it goes to your -- the first part of your question, is Hisun has just completed what appears to me to be an almost -- well, I'm not sure I should quote a number, but hundreds of millions of dollars have been invested in capacity expansion in their manufacturing sites in China. They are some of the most modern manufacturing facilities that I've seen. They rival European and U.S. manufacturing sites with regards to the quality of their facilities and certainly, the modern equipment that they're importing from the U.S. and the European manufacturers of pharmaceutical equipment. So I suspect that they will have more than sufficient capacity not only to supply China, but if they were to gain approval, if we were to authorize them to manufacture for us -- territories outside of China, they would have sufficient capacity to support that.

Okay, that's helpful. And then my last question is, just with regard to the indications that you're going after beyond primary liver cancer. So you've got recurrent chest wall and then you're -- in the pipeline you're looking at the colorectal liver mets and then prostate mets to the bone. What's kind of the rhyme or reason here for the indications? Are you doing some type of assay or testing to show that you're having greater applicability with the technology with these particular types of cancers? Or is it -- are you particularly looking at historically what we're able to see Doxil be effective in and going after maybe cancers where you're seeing less effect and maybe higher incidence? What's kind of the thought process there?

You want to take that, Nick?

Yes, I'll jump into that question, Mike. I think the basic thread that's holding this approach moving forward is, number one, looking at cancers that are sensitive to anthracyclines. And as you know, breast cancers are treated with anthracyclines. And early data from Duke University in patients that have previously been heavily pretreated also may have received radiation treatment, shows very interesting response rates when given ThermoDox and superficial mild hyperthermia. So we're just continuing with those Phase I programs into a Phase II program. And then our early Phase I studies, we had a little bit of a mixed population where much of our population were primary liver cancer patients and also almost half of those patients were metastatic liver cancer patients, and both of them showed, again, very interesting results in our Phase I studies. Our first goal is to get the HCC indication, and that's through our HEAT study. And then now, we've embarked on going on the ablate study to look at the metastatic liver cancer population. Then following that, now with the HIFU technology, one area that is a big unmet need is metastatic pain -- metastatic bone pain cancer. And this again is an area where HIFU, by itself, is showing some activity. But I think adding high concentrations of anthracyclines such as ThermoDox follows along where we could improve upon that technology there. So that's a bit of an opportunistic area, particularly with this new technology to try to piggyback one upon the other. So I hope that answers your question and I hope you understand the strategy moving forward.

Thank you, Mike, for your question. I just want to add a little bit more to what Dr. Boyrs said, and it relates to the HIFU. Our underlying technology is effective with heating devices which are somewhat limited, hyperthermia and radio frequency ablation, microwave ablation, are all in use in one manner or another on treating oncology of patients. So HIFU brings -- opens a wide -- a very wide door for us. HIFU, of course, is a noninvasive means to use acoustic energy focused on large tissue masses and elevating the temperatures. And in some cases, it elevates the temperature above the temperature of necrosis or causes ablation. When we look at the opportunity to combine ThermoDox with HIFU, we really appreciated the breadth and the depth and the application of our HEAT-sensitive liposome technology to a broad range of cancers. So as Dr. Borys is pointing out, we are focused on a number of indications, some which expand the use in areas -- where -- for ThermoDox, in areas where we have seen some clinical benefit in HIFU, where we have been working with Philips to show the potential of this multimodality approach. But the potential that ThermoDox in combination with HIFU bring to a broader range of cancers, I think, is -- we're just opening the door. So thank you for that question. We look forward to your continued interest.

We'll go next to Ren Benjamin with Rodman.

Just a couple of questions. Mike, I'm curious as to how many more DSMB meetings are scheduled. And I guess even more importantly to that, I'd like to get a sense as to how the events -- the event rate might be occurring if -- since we haven't delayed when the results will be announced, I expect they're occurring according to plans, but at what point or at what meeting might that update change?

Yes, Ren, so the -- not to confuse the other people on this call, the DSMB, or the DMC, as we've been referring to it, I guess, has been meeting about every 100 patients or about every 3 or 4 months during the course of the trial. That meeting schedule will continue. So if you project off of the last April meeting, the next meeting should be August, September timeframe. I believe it has been scheduled, right? Correct me -- so it has been scheduled. So you can expect a meeting about mid-September. The event rate is currently proceeding as we would expect it to. We really haven't given guidance on the number of events or the event rate other than to announce a number of PFS and breadths of the interim analysis. We thought it was appropriate to do it them. But one of the big responsibilities we have here as a accompany is to protect the integrity of the trial and the integrity of the data. And so that's an important focus for us. It's not a question that's inappropriate, but we have been guarded with information like that not only to protect the integrity of the trial and the data, but also at the request of the DMC. So I can only tell you this, with regards to progressions and event rates, we believe they're substantially following what we would consider to be consistent with a successful trial. So that's my view on it.

Fair enough. And then just one question regarding the DIGNITY trial and when that will officially start and conclude, as well as how is the recruitment for the ablate trial goes on?

So I'm just going to comment on the ABLATE trial and maybe a couple of comments and then ask Dr. Borys to comment. So the ABLATE trial really leverages our experience in 2 Phase I studies. It was -- all-comers study, as Nick pointed out earlier, where we demonstrated local control of patients with metastatic disease. So that's on one hand. On the other hand, you know the primary focus of the company is to complete the HEAT study with sufficient resources to be able to begin the commercialization process. So we have been very interested in moving forward with colorectal liver met study for 2 reasons. One is we've demonstrated a clinical activity, which could support an improvement in the outcomes of patients treated with radio frequency ablation. And number two, and this is very important, both in Europe and in the United States, the incidence of colorectal mets to the liver exceed that of primary liver cancer by a factor of 5 or 6. So it's truly a needy market and it's a large one. So our goal here with the ABLATE study has been to organize the infrastructure, and that's number one is to get agreement with the FDA that the protocol is sound and they can proceed as designed in the Phase II study. Number two, is to design a Phase II study in a, I would say, a very well-disciplined, controlled, double-blinded, randomized trial such that the data coming from the trial would be beyond question. That if the data were to be positive, that it would be sufficiently positive that it would be reviewed and accepted by any peer review journal. So it's a double-blinded randomized trial. We're using, in fact, a core lab to adjudicate the results for progression. So all that said, long-winded answer, our goal here is to complete the 88-patient trial in a timeframe that matches up with our expectation for -- of the approval of ThermoDox for primary liver cancer, which could be as early as around the end of 2013. Okay? With regards to the DIGNITY trial, the goal here is to -- well, first was to get acceptance that the trial was sound both medically and scientifically-valid. We've gotten that agreement with the FDA when we submitted the protocol. I believe that was at the end of last year. It was accepted without comment by the agency after its 30- or 45-day review period. In the meantime, we've been recruiting investigator sites where I'll have a little bit more to say about that, most likely in a -- when we enroll the first patient in the trial. But it's safe to say that a number of the investigator sites who were involved with our Phase I trial are keenly interested to continue the study. But I think as everybody knows who has followed the company, recruiting patients into a trial like this has not been an easy task. So one of the things we're looking forward to is the publication of data from our Phase I trial in order to be able to encourage physicians who treat these patients to consider this trial as an option for their patients.

Yes, I could only underline Mike's remarks right now that when it comes to the ABLATE trial, our efforts right now are in working with the sites, optimizing our recruitment efforts and adjusting the number of sites as needed in order to complete the enrollment as planned. And the same thing with the DIGNITY study, again, I wanted to emphasize that the key sites that were involved in the Phase I enrollment have resigned up for the Phase II, and we're in the process with working with them as well, and all I could say at this point is we look forward to reporting on the news as we start that trial in the near future.

And just regarding presentations, guys, we have ASCO coming up. Do we have anything in way of update from Celsion?

We have no presentations planned in ASCO.

[Operator Instructions] We'll take our next question from Tron Hildo [ph] with Hearthstone Capital Management.

I do have 2 questions for you. The first one is regarding timing of various countries' approvals. I'm pretty comfortable with the timing in the U.S. with priority review. Can you comment on the timing it would take in Europe and in China in particular please?

So what we have -- good questions, Tron. And we have a broad sense. I think historically, our review in Europe is no less than 9 months, more likely 12 months, following submission of an MAA. In China, it really depends on the classification of the therapeutic and the indication for which it's being treated. Now we believe we fall into a category of a novel compound that has been evaluated in a cancer with serious significance and high mortality. Well, that puts us essentially in a category similar to FastTrack in the United States. The benefit of that is the typical turnaround, if we -- and it's one of the reasons why we're working so closely with Hisun. Frankly, they have -- as a local manufacturer, they give us quite a bit of access to the SFDA. But typically, turnaround for an application, an NDA-type application in China can take anywhere from 12 to 15 to 18 months. Our understanding is that with the appropriate designation, applied for the appropriate indication, let's say, again, a novel compound treating a significant disease, the review and approval time could be cut by as much as half.

Okay, appreciate that. As a follow-up to the timing then, did you specifically say that the final or the 380th event would occur in quarter 1 or that we will also know the results in the quarter -- I'm sorry, by quarter 4 or will we also know the results by quarter 4?

Well, it depends on when the 300 -- and I'm not trying to be cute here. But it's a very good question. So we're dealing with biological systems, Tron, and progression happens as it happens. So we have used the regression analysis to estimate and have had some validation from -- in prior reviews from our statistician that we can expect the 380th event by the end of the year. Whether it happens a little bit sooner or a little bit later, I -- it's just hard for me to comment. But everything that we see suggests that before the end of the year. For the -- [Audio Gap] got that, then I think anyone in the company and is in fact, we'll put him on the spot here a little bit, has put a program in place to -- as they occur, to just absolutely ensure that the company is aware of each of them as it occurs. But once we end the 380th event, we have to lock the database. So we will anticipate the 380th event with the database -- a planned database lock. We'll have to gather the data from the investigator sites as we typically do. So it -- that takes a little bit of time and turnaround. The studied data -- it's comprehensive data, it's not just a number of events, I want to be clear about that. The studied data is tabularized in a format that's -- reviewable by the DMC. And once we have a DMC concurrence, that the 380 events represent a positive outcome or God forbid, the other way -- otherwise, we'll make that information available.

Perfect, appreciate that. All right, the second question then is about the HIFU trial with Philips. Can you go into a little bit of detail about the number of patients you expect to enroll, and what the endpoints will be on that?

Sure. But that's just -- I'm going to be a little countable here, that's your third question, Tron. But I'm going to ask Dr. Borys to comment on that.

Well, the protocol is the way it's written at the moment. I believe that our target number of patients is in the 20s. And our primary endpoint is for the control of painful bone metastases. And that would be the primary endpoint, and that will be looking at painful bone metastases over time, and of course, secondary endpoints of safety.

We'll go next to Mara Goldstein with Cantor Fitzgerald.

I actually have a, I guess, a forward-looking type of question. And I'm curious to know once the Phase III HEAT trial is completed, and let us just assume for a minute a successful outcome in that trial, how does that inform, I guess, the other additional Phase III studies in different settings from the perspective of FDA and what would be known versus what's unknown at this point in time?

Okay, I want to make sure we have the question right, Mara. And by the way, thank you for joining in the call. So if I understand it correctly, what you're asking is once we have data, and the data has been reviewed with the FDA in a pre-NDA meeting. Are you asking if that data is somehow used to inform other sponsors of Phase III trials?

You design other trials in terms of when you meet with FDA for your end of Phase II meetings and to the extent that there are unknown questions, and this is essentially working in a relatively new area combining some of that with RFU. So I'm just curious as to how that might change possibly timelines or considerations in the trial, number of patients, those types of things.

For other sponsored trials?

Yes.

Okay. So let me just give you - I don't know the answer to that question, maybe Nick does, but [indiscernible]. I can give you a little bit of experience that we had in our discussions, during our SPA discussions with the FDA, that supply completed the -- both Bayer and Onyx had completed their Phase III trial in primary liver cancer with sorafenib and Nexavar. So the agency was in possession of that information. They never disclosed what the results of the trial was to us. But it seems to me, it certainly helped to guide FDA's view -- you know you negotiate an SPA. But it seemed to help guide -- the FDA's view of the construct of our statistical plan in the powering of our study. It just seemed to me. I have -- I can't say for sure. But we were told by a member of the panel at FDA that another therapy had completed, but they didn't tell us much more than that about the study. And, Nick, the FDA...

Maybe as a another -- I'm not sure if I fully understand your question, but what I think I'm hearing is -- well, what I'd like to emphasize is what Mike's recent comment on the fact that we have a Special Political Assessment with the FDA. So when we go to the FDA at our pre-NDA meetings -- this is about the end of Phase II, as you just mentioned. So it's going to be a pre-NDA meeting. We're going to be going with the merits of our data. At this point, the FDA is in no position to challenge the size of our trial, the design of our trial, the impact of our trial. They have to judge our data on its own merits in terms of safety and efficacy. And then they make a -- and then based on that, if we met our predetermined targets, then they have to make a decision based on all that. So what impact current clinical care might have had over the last few years will have minimal impact on their decision process because they have to judge it based on the merits. Also, I think it's very important for everyone that follows Celsion to know that our target is intermediate HCC, and this is an area that has very, very little good data. Our study is the largest study ever conducted in intermediate HCC. So our data will be very powerful and be able to elbow our way into that area because we're going to have powerful safety data and powerful efficacy data. So with that, I think we're going to have a lot of confidence going into our NDA meetings.

We'll take our next question from CS Yasi [ph], private investor.

A couple of quick questions, and I'll try to make them fast. And I'm not sure if this has been asked before, has the company reported on the average lesion size from the HEAT Study, and can we even make that public? I'm just curious where patients fall in that 3 to 5 versus 5 to 7 range.

We have not discussed that publicly. And really, until all the data is in, we're not -- I'm not sure we're in a position to be able to discuss that.

That's understandable. I actually expected that answer. It's no problem. The next question -- there was a question earlier about ASCO, arguably, The World Conference on Interventional Oncology is probably a more direct audience. I'm curious if you guys will be presenting there and have some kind of impact there?

At the WCIO?

Yes.

We're not presenting at WCIO. I believe the first conference we will be presenting at this year where we'll be in -- will be data from our breast cancer trial.

It's being submitted.

So we don't know that we have been accepted yet, so it's premature to announce that.

We'll go next to Mitch Landrieu [ph] with Odat Enterprises [ph].

I can only echo, I think, what Ms. Goldstein was saying in that -- from a layman's point of view is the idea with doxorubicin. We know the nature of the drug with our delivery model. By the time we're doing later NDAs, we're going to be well aware of the delivery mechanism and RFA, microwave and at least in other parts of the world HIFU is well known. It's kind of a common man's -- common person's expectation that we would hold those types of things, could lead to much more rapid trial processes for later indications with all of the knowns coming into that. I think that's kind of what she was trying to get at, and I share that point of view. My question is about Philips. I don't expect you to answer for another company. I'm just concerned about what -- if we really look back, what is going with HIFU-mediated drug delivery and how the FUS Foundation is taking a leadership with it. This is a historical breakthrough. This study would be the first with HIFU-mediated drug delivery for cancer treatment. It's huge news. And the PR was great. My concern is, if you look at the news PRs for Philips on their website, there are things like they've put a new system of electronic medical records. That's great. But there's absolutely nothing about this historical groundbreaking news about HIFU and drug-mediated delivery and no quotes from anybody from Philips and the PR about the trial. I just -- I don't expect you to answer for them. I guess, from a company's point of asset, do we approach Philips to see if they want to be a part of our PRs in regard to this collaboration. I just don't see the presence of Celsion on their website or in their news, and yet, we are years and years ahead breaking ground as a company of our size, with Philips, and you just don't see it. Can you comment at all about Philips' collaboration with us with the PR and things like that?

Well, sure. It's not an unreasonable conclusion to make, Mitch. We are -- obviously, we're not as visible as we'd like to be with the Philips' IR and PR. And that said, HIFU is still an investigational device in many countries, particularly in the United States -- Philips' HIFU, it's still an investigational device. So I think you're seeing a little bit of cautiousness on the part of not only the research arm of Philips, but also their general management. It might be a little bit different story. I can't speak for them. But it might be a little bit of a different story with what we have, with the device core and commercial sales at the moment. So it still is an investigational device. With regards to their interest and their support, the conclusion you're drawing from their lack of visibility is not correct. In fact, we announced, I think it was just about a year ago, that the FDA had provided us with some questions with regards to our Phase II approach to treating painful bony mets. And the majority of the difficult questions surrounded the use of HIFU to treat these patients, and they asked -- you can respond anecdotally or with information from preclinical trials. But I can tell you this, Philips went right to work and they're conducting 2 Phase I studies in bone cancer patients, the data from which is used to support our resubmission of the Phase II protocol. So their commitment to this multi-modality approach or I like it better the way you say this, HIFU-mediated drug delivery using ThermoDox is -- it's enormous. They're completely committed to it. Whether or not the company culture is one that requires this kind -- the kind of investor enthusiasm that's noted in a non-revenue generated biotech company or non-entity, is I guess for you to conclude. Obviously, Philips is big. It's multibillion dollars in sales, multibillion dollar market cap, it's investing strategically in what they think are promising new technologies, their research. And now their general management believe that HIFU has some potential. I don't know if they can say great potential, I don't want to speak on their behalf, but has some real potential to treat oncology patients when combined with our HEAT-sensitive liposome ThermoDox. And I if -- I think our actions speak louder than words in many cases. And they're funding it. So they're putting their money where their mouth is. Well with regards to, do they get involved with our press release? Well, we have a very professional and courteous relationship with Philips. Our press release was reviewed since we used their name. And actually, was even agreed to by the Philips organization before we announced it. I mean their lack of a quote, I don't think should be misinterpreted here. All right? It's a company that's -- got tens of millions -- got hundreds of millions of dollars invested in a very promising state-of-the-art, probably best-in-class HIFU technology, who's extended their research to include financing some very important preclinical work. And now, will hopefully will be clinical work to support the expansion of ThermoDox into the other indications for which we would not have access. Now all that said, let me just take it a little bit further with you. [indiscernible] out of the West coast, and he's doing some groundbreaking stuff. And I think we're about as excited as he is, but he may be more so with regards to the pancreatic cancer indication. We also have developing relationships in the areas of clinical research and preclinical research, so what are we talking about? Well, It's too soon other than to just give you an allusion that we're not sitting on our -- I guess what may be perceived as a mountain that moves slowly, to get our drug to market. We think we have other avenues to get our drug to market using HIFU. We think we have other avenues from very interesting clinical and preclinical approaches. Does that answer your question?

It does, very well. I know it's a sensitive issue so I appreciate the thorough response. And I am not alone, especially among people much more qualified than I am, believing that Celsion and HIPU-mediated drug delivery is literally going to revolutionize the oncology world, period. So I'm very grateful for the answer. I have another question, but I'm going to retroactively grant it to my friend, Tron, who took 3 questions.

Okay. And so -- yes, we have to -- we'd like a business card, please, so we'll take calls from Odat Enterprises.

At this time, I'll turn the conference back to Mike Tardugno for any closing or additional remarks.

I want to thank everybody for joining us today and for your interest in Celsion. The comment I made when we opened the conference call was the watch word here is momentum. We are moving aggressively to evaluate the regulatory and commercial pathways for ThermoDox, now looking forward to data from one of the most important, if not the most important, clinical trials being conducted in oncology today, and that's in primary liver cancer. We believe the HEAT Study can provide a basis for -- the basis for the commitment -- a return on the commitment, that's what I'm trying to say. A return on the commitment and the patience that we've seen from our investors. And we look forward to presenting you with that data, hopefully, at or about the end of this year. Thank you.

Thank you for your participation. That concludes today's conference.