Imunon, Inc. (IMNN) Q2 2012 Earnings Report, Transcript and Summary

Good morning. My name is Nancy ,and I'll be your conference operator today. Today's conference is being recorded. At this time, I would like to welcome everyone to the Celsion Corporation Second Quarter 2012 Shareholder Conference Call. [Operator Instructions] I would now like to turn the call over to Mr. Jeffrey Church, Celsion's Senior Vice President. Please proceed.

Good morning, everyone, and thank you for joining us. Our second 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, August 28, 2012. The replay can be accessed at 1 (877) 870-5176 in North America or 1 (858) 384-5517 internationally, using conference ID 8709649. 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. We are joined today by Michael Tardugno, President and CEO at Celsion, Dr. Nick Borys, our Chief Medical Officer; and Greg Weaver, our Chief Financial Officer. On today's call, Mike will provide a corporate update, including an outline of the important milestones ahead in our Phase III HEAT Study for ThermoDox in primary liver cancer. Greg will discuss our second quarter 2012 financial results. Following that, Dr. Borys will discuss in further details our overall ThermoDox clinical development program. We will now open the call for your -- After then, we'll open the call for questions which we ask that you keep to no more than 2. With that, I'd like to turn the call over to Mike.

Thanks, Jeff. Good morning, and thank you for joining us. I know of no better way to open this call than with a comment that I made at the annual shareholder meeting this last June. And that is this, this is a great time for Celsion and I daresay to be a Celsion shareholder. I'm pleased to report that your company has never been so well positioned. For those on the call who are shareholders, I'd like to express our thanks for your support and continued confidence in your company's strategic clinical focus and innovative heat-sensitive liposome technology. The HEAT Study, our Phase III pivotal trial combining the first drug in our tumor-targeting platform, ThermoDox, with RFA to treat hepatocellular carcinoma or HCC is fully enrolled. We are now looking forward to data by our best estimate in the fourth quarter of this year from the largest pivotal trial ever conducted in the intermediate stage, the largest unmet need in oncology. And we have the financial resources sufficient to see us through data and well beyond, which means to be clear, we have no current plans for equity financing prior to data, and Greg will discuss this in more detail during his comments. And if we are right about the outcome of the HEAT Study, we have every reason to believe that we will -- believe we will be bringing to market one of the most important new drugs in a generation, that's ThermoDox. You don't have to take our word for it. Look at the support we've had from multiple regulatory agencies around the world and, in particular, from the FDA. We've negotiated an SPA. We have Fast Track. We have Orphan Designation. We have an agreement to file using a 505(b)(2) approach, and we are candidate for priority review as a function of the strength of our data. The reason for this, well, it's clear. HCC is an enormous unmet medical need. Let's go through the facts because I think you'll agree with me, they are sobering. ThermoDox's principle indication is HCC, the world's fifth largest cancer and a disease of significant concern within the global oncology community and public health agency. Incidents is approximately 28,000 in the United States. It's tripled in incidents over the 30 year period from 1977 to 2007. There are 40,000 incidents in Europe, and is growing rapidly at 5% worldwide from a base of 750,000 new cases annually. Over 50% of these new cases will be in China, emphasizing the importance of this market for us and a rationale for a high concentration of investigator sites in that country. The World Health Organization predicts that HCC will become the #1 cancer worldwide by 2020, surpassing lung cancer. For countries in the West and Japan, during the 10-year period ending 2019, incidents is expected to increase by 20% and prevalence by 47%. It's also clear that the evidence for a successful HEAT trial is on our side. We know doxorubicin, the anticancer agent in ThermoDox is active in liver cancer. Our drug system technology is designed to improve its efficacy in the presence of heat. We know that combining ThermoDox with RFA has shown remarkable potential in early phase studies to delay disease progression. We know that delayed progression or PFS, progression-free survival, is both sensitive and specific as a surrogate for overall survival. In our target population, median time to progression is 12 months with median time to death 30 months. Outcome statistics in this population have remained constant since we began our research into HCC over 6 years ago. There are few nonsurgical therapeutic treatment options available as radiation therapy and chemotherapy, including Nexavar, are largely palliative in the treatment of these patients. For those of you who are following HCC developments closely, you know that Nexavar and ThermoDox have both been cited by the NIH for priority trial status, with ThermoDox in the HEAT Study, being the only one evaluated as a first line therapy. What this means is clear. So let's assume positive outcomes for both drugs. ThermoDox plus high radiofrequency ablation will always proceed and be complementary to, not competitive with, Nexavar. So we're convinced, as are more importantly, the KOLs interviewed in our early-market research that with positive data, the HEAT Study will provide a basis for perhaps the most important new therapeutic introduction in oncology, in the largest unmet medical need in cancer today. So what represents positive data? Total 380 events of progression will fully power the study to show a 33% improvement in PFS. I wish we could be more precise with our projections, but we continue to project that these events will occur late in 2012, after which data will be reviewed by the study's independent Data Monitoring Committee, and results will then be made public. I'd like to make a few more comments about the HEAT Study. We continue to work diligently to assure no surprises with clinical data. Through our clinical quality dashboard, we track and evaluate timeliness, currentness, radiologic concordance and certain trends in the clinical data set, which routinely are scoured by our data management team. This information is reviewed and discussed at each and every DMC meeting. The most recent of these meetings, which took place at the beginning of the second quarter, included a review of data from 652 patients and concluded with a unanimous recommendation that the study continue according to protocol. The next DMC meeting, as we have indicated, is scheduled for mid-September whereby the committee will review all safety data from 701 patients enrolled in the HEAT Study and evaluate our clinical quality dashboard. In addition, we'll get an update from our Independent Radiology Review Committee, the IRRC, on the number of confirmed events, which will allow us to better plan for the database lock to evaluate the primary endpoint. If as a result, there's any material change to our timeline estimates for 380 PFS events, we will advise in a press release that follows the DMC recommendations. We have instituted a re-monitoring program. Quality, quality, quality, for a high number of high-volume sites, which addresses almost 80% of the patients enrolled in Asia-Pacific. The goal of which is to check and double check the data supporting proper study conduct. We have also implemented a comprehensive clinical quality audit program as a check on our CRO and their work products. The goal here is, as I said, no surprises. We continue to conduct early market research, market landscape analysis and price ranging studies. Our research is with physicians, key opinion leaders and payors. The goal is to better understand the patients' journey, ThermoDox's positioning and its value in the treatment of HCC. Definitive pricing and pharmacoeconomics in our research where needed will be conducted following the availability of data because, as you know, price and economics are greatly influenced by clinical benefits. Now that said, at this point, based on our early research, we are reasonably convinced that in the U.S., ThermoDox will be reimbursed as a pharmacy benefit, that's ASP plus 6%. And initially, priced reimbursed under a J code. On the manufacturing front, we are establishing multiple manufacturing partners in the U.S. This is an important requirement to ensure supply continuity and a requirement by most pharma companies interested in the commercial license. In China, to assure a reliable quality supply chain with a cost of goods that can support higher gross margins, we announced the commercial supply agreement with Hisun Pharmaceutical, a highly respected Chinese company for the production of ThermoDox for the domestic China market. And Jeff will have more to say about this in a minute. Consistent with our global regulatory strategy, the HEAT Study is designed to address as many markets as possible with a single study. We continue to work closely with regulators in multiple countries, including the U.S., Europe and countries in Asia-Pacific to ensure that the HEAT Study meets each region's standards for regulatory review and approval. And the last point here, we have started the NDA process with the selection of a CRO with FDA portal access, publishing expertise and using a common technical document approach as a basis for NDA filing and MAA filings. As we announced at the end of last year, we have EMA scientific advice confirming that the HEAT Study will provide data acceptable as a basis for submission of an MAA for centralized filing and full approval in Europe. As you noticed, the time the European approval provides the basis for international filings in countries where reference approval -- typically, that's a CPP, a certificate of pharmaceutical product, from a globally recognized regulatory agency, which with FDA approval provides us with more than one option for international filings. Using the CTD, we'd expect to file in the U.S. and in Europe on about the same timeline. And Nick will speak more of this, but I'd like to report progress on our program to evaluate ThermoDox in multiple indications. The ablate study, a randomized Phase II study of ThermoDox in combination with radiofrequency ablation for the treatment of colorectal mes to the liver is underway. The DIGNITY Study. A difficult trial to enroll, as you know, but one that we refuse to give up on. This is a very needy population and deserves our support. The Phase II portion of the DIGNITY Study will begin enrolling patients later this year. An abstract for the Phase I results has been accepted for presentation at the prestigious 2012 Congress of the European Society of Medical Oncology in Vienna this coming September. Professor Hope Rugo from the University of California San Francisco School of Medicine will present our results. I think, I'd say and I'm not overstating this, we are consumed with potential to build the next-generation approach to treating difficult solid tumors without the need for a scalpel. Combining ThermoDox with high intensity focused ultrasound changes that paradigm. Our initiatives and collaborations with some of the top institution in medicine include: Support for pre-clinical studies at the University of Washington School of Medicine, where we are exploring the use of ThermoDox in combination with MR-guided HIFU for the treatment of pancreatic cancer. We're collaborating with the University of Oxford in England to begin a clinical study of ThermoDox in combination with ultrasound-guided HIFU to treat metastatic liver cancer. We expect treatment of the first patient in this study in late 2012. And finally, as we announced last week, plans to launch a Phase II study supported by a joint development program between Celsion and our partner, Philips Electronics that combines ThermoDox with Sonalleve MRI-Guided HIFU technology for the palliation of painful bone metastases caused by lung, prostate or breast cancers is expected to begin enrolling patients in the relative near term. Supporting all of this is a strong financial position, which Greg will discuss in a minute, that includes a new and creative $10 million loan facility. But before I turn it over to Greg, I'd like to ask Jeff, who we've asked to evaluate the dynamics of the rapidly changing China market to comment on the importance of Hisun and the China market. Jeff?

Thank you, Mike. The commercial role of ThermoDox will, of course, require global manufacturing and distribution, capabilities we have began to provide for. As Mike mentioned earlier, we announced this past quarter a long-term commercial supply agreement with Hisun Pharmaceutical Company, one of the largest manufacturers and suppliers of chemotherapy agents globally. Hisun is a leading manufacturer for multinational pharmaceutical companies like Pfizer, with whom they signed a $300 million joint venture this year. China and the rest of the Asia-Pacific are key markets for ThermoDox, as they represent over 1/2 of the global incidence and prevalence for HCC. The Chinese market is unique in the world. We simply can't look at this emerging market through the same prism that one would evaluate other markets. We believe that a local partner such as Hisun is critical, not only for success on the manufacturing or regulatory front, but in realizing the commercial potential of ThermoDox in a rapidly evolving market like China. This is an aspect of ThermoDox's commercial development we are paying close attention to. As we come closer to concluding the HEAT Study, these considerations will move front and center. As a late-stage product candidate with global multi-indication potential, unencumbered worldwide right and a growing presence within the ecology committee, ThermoDox has and will continue to attract a great deal of partnership interest by maintaining a strong cash position through careful cash management and by advancing ThermoDox to this late stage without significantly diluting our right for the product. Celsion is in a position to create significant value from our lease program once data is available. And now, Greg will provide an overview of our second quarter financial results. Greg?

Thank you, Jeff. The company completed the second quarter with cash and investments totaling $24 million as compared to $24.6 million at the end of the first quarter. Our end of the Q2 cash reflects the addition of $4.9 million in proceeds from our new term loan executed in June. The important point here is that we have cash on hand to fund operations including scheduled interest and principal amortization into the fourth quarter of next year. That's $24 million to run our business for an excess of 5 quarters with operating expenses on a declining trend over that period. This management team continues to focus on cost controls and make our cash work as hard as possible and the virtually non-dilutive loan proceeds provided additional strength to the balance sheet as we approach year-end and the critically important milestone of unblinding the HCC trial. Total use of cash in Q2 was $5.45 million as compared to $5.95 million in Q1, a reduction of $0.5 million. The reduction in cash usage was driven by the HEAT trials CRO costs globally trending down as we completed enrollment and have moved into the next phase of the study approaching end of trial results, all consistent with guidance provided on our previous quarterly call. We reduced our second quarter loss from operations by $600,000 to $5.7 million as compared to $6.3 million in Q1, again, consistent with the prior guidance. R&D expense in Q2 was $4.1 million, reflect a decrease of $800,000 from the same 3 months last year and down $600,000 from Q1 of this year. Again, R&D costs trending down for clinical activities from the HEAT Study, which is partially offset by some increases in development of commercial manufacturing activities for ThermoDox. G&A expenses of $1.6 million in Q2 reflect an increase of $300,000 from the same quarter last year and were flat with Q1 of this year. The year-over-year comparative increase reflects spending to support pre-commercialization activities and other professional fees. The 10-Q filed this morning includes disclosure of our manufacturing agreement with our partner in China, Hisun Pharmaceuticals. Hisun is responsible for the initial costs associated with the transfer of the manufacturing technology for the sale of ThermoDox in China, and accepting both technical and approval risks. We will repay Hisun for these activities along with a fee on a cost-plus basis upon Hisun's successful completion of planned registration batches of ThermoDox. We're pleased with the financial terms of the agreement and beyond that, this deal is strategically important to provide international manufacturing capability from one of the best in the business, and Hisun needed to support commercial success in the largest markets in Asia and at a very attractive costs of goods sold. And lastly, regarding the registration statements we filed aftermarket yesterday, first, the S-3 shelf-registration statement, similar to the one we had in place in prior years. This one registered $75 million for future financings and should provide flexibility and lower the cost of capital for future financing transactions. It made sense to get this filed now and clear any potential SEC review prior to reaching the upcoming unblinding of the HEAT trial clinical data and be clear we have no plans for issuing new equity prior the data. And we also filed an S-3 registration statement to register the underlying shares for stock options that were previously approved by shareholders over the past 2 years, which are a part of our employee incentive plan. And that concludes my financial comments. Thanks for your attention. I'll turn the call to Nick.

Thank you, Greg. I'd like to start by providing an update on our continued progress with the HEAT Study. For primary liver cancer, there exists fully defined treatment options between early-stage disease eligible for surgical 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% in our patient population. Its efficacy, however, is limited by tumor size showing significantly less effect on tumors greater than 3 centimeters in size. By combining RFA with ThermoDox, the margin surrounding the tumors 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. The team here at Celsion is working diligently to prepare for regulatory submission. Supporting our regulatory goals are a number of key designations, including Special Protocol Assessment, a 505(b)(2) agreement with the FDA, as well as Fast Track and Orphan Drug status. After our NDA submission is accepted, we expect a priority review in line with FDA's current PDUFA performance goals. We have confirmation from the EMA that the HEAT Study provides the basis for a centralized European filing application MAA. We will be afforded many of the same priority review benefits to what EMA calls a full mixed review registration process. While primary liver cancer is a priority for Celsion, ThermoDox's unique properties supports its potential well beyond this indication. As Mike mentioned, we've announced several important new collaborations recently that underscore not just our belief in this potential, but support for it within academia and industry. First, we announced recently FDA clearance to advance a joint development program for ThermoDox combined with Royal Philips Electronics Sonalleve, MR HIFU technology and the palliation of painful metastases to the bone. We expect to initiate a Phase II study in this indication within the next 6 months. There are between 300,000 to 500,000 patients in the U.S. with bone metastases. Many of these patients experience excruciating and unrelenting pain and are often treated with powerful analgesics such as opiates, resulting in only modest benefits. External beam radiation therapy is effective in palliating painful bone metastases, but is limited by accumulating toxic effects to help the organs. Philip's Sonalleve MR HIFU system has a potential to precisely and non-invasively target lesions with acoustic energy, creating sufficient heat to activate ThermoDox and preferentially release high concentrations of doxorubicin in the targeted treatment area. This multi-modality approach may have the effect of creating a next generation noninvasive treatment for this condition. It may also have other treatment potential. We also announced our collaboration with the University of Oxford in the U.K. to begin a clinical study of ThermoDox with HIFU in the treatment of metastatic liver cancer. This trial which was supported by the National Institute for Health Research Oxford Biomedical Research Center will be carried out as a multidisciplinary collaboration between Celsion, the Oxford University Institute of Biomedical Engineering and the Oxford University Hospital NHS Trust. This early phase clinical study is being finalized and will require approval from the local ethics committee. Treatment of the first patient is targeted for late 2012. The details of the study will be made public following approvals from the University. Lastly, Celsion and a Focused Ultrasound Foundation announced their support for preclinical studies designed to explore the use of ThermoDox in combination with MR-guided HIFU for the treatment of pancreatic cancer. The studies are being conducted at the University of Washington, School of Medicine by Professor Joo Ha Hwang. The UW research is expected to include animal models to confirm the ability of HIFU to target high concentrations of doxorubicin and proprietary pancreatic cancer cell lines at an in vivo study to assess the response of these tumors treated using ThermoDox with and without hypo-induced hypothermia. We believe that these collaborations are just the beginning for combining important device technologies such as HIFU with important drug technology such as ThermoDox. I look forward to reporting on the progress of these collaborations in the months to come. We continue to expand a number of institutions for our ablate study, our multicenter randomized Phase II study that's 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 this study is local tumor control at 1 year following treatment. This study, as you know, is enrolling patients but at a deliberate slow pace. The rationale is that we will accelerate patient recruitment following positive data from the HEAT Study. The treatment of colorectal cancer remains an area of significant unmet medical need in the field of oncology. The American Cancer Society estimates more than 140,000 people will be diagnosed with colorectal cancer and more than 50,000 are expected to die of the disease in the U.S. alone. Up to 25% of patients with colorectal cancer present with liver metastases and another 50% develop liver metastases within 5 years. RFA is both efficacious and a 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 by combining it with ThermoDox. In recurring chest wall breast cancer, we continue to move forward with our Phase II study, the DIGNITY Study. The DIGNITY Study builds upon promising data from Phase I. The Phase II study has been limited to 40 patients with this form of breast cancer, and will enroll patients who have received but failed priority treatment. As you can see, the ThermoDox research programs is diverse, has depth and is international in scope. We've taken advantage of the latest in the medical thermal technology and expect to make it better towards a cure for cancer that is less invasive and more durable. We look forward to advancing our internal programs and our collaborations as ThermoDox reaches maturity in the HEAT Study. With that, I'll turn the call back over to Mike.

As always, Nick, great update. Thank you. Jeff and Greg, good reports. Also, I hope we made clear to you we are preparing for what would be the most -- and one of the most important, if not the most important event, basically, in our company's history and is the validation of our technology platform and our lead therapeutic, ThermoDox, with results from the single largest study ever conducted in intermediate HCC. 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 cancer treatment introduced to the global oncology market in a generation. It is indeed a breathtaking time for Celsion. We're proud to be a part of it, and were delighted that many of you are with us. As always, we greatly appreciate your interest in the company, and we look forward to updating you on our continued progress. Now, operator, we'll go to questions [Operator Instructions] So operator, please open the line for questions.

[Operator Instructions] We'll go first to Joe Pantginis with Roth Capital Partners.

A couple of quick questions, a little related. I guess first a question on HEAT and then a question on HIFU. First, I just wanted to see what are your plans right now with regard to data release. I know you talked about potential timing and the sort of lag between the timing of events at the IDMC review, but what are you planning to actually release when you say top line results?

Yes, so we're taking a little bit of time to think about the answer to that question, Joe. We know for sure we'll be releasing information relative to the primary endpoint of PFS. There may be an opportunity to discuss the trends in an overall survival benefit. So what we intend to do is to make it very clear to the investment community that the trial has been successful in achieving its efficacy endpoint. But beyond that, as you know, many important conferences and publications require that submissions include information that has not been disclosed publicly. So there will be a lot -- an enormous amount of information coming out of this trial, much of which will be reserved for presentation at major conferences or included a reserve for the publication of the final trial data, which we hope will be in a major medical journal.

Sure, and that's very fair. And then just quickly, I know -- I was just wondering if you could provide a little additional color on the -- just the overall rationale to go beyond RFA about combining ThermoDox with HIFU and any potential supporting data?

Yes. So, I'm going to start the conversation. And then, I'm going to ask Dr. Borys to jump in. We've always seen HIFU -- since I've joined the company, we've seen HIFU as an enabling technology or heating technology for the use of ThermoDox in areas of disease where there currently is no FDA approved device to heat, ablate or treat the lesion. So HIFU brings us a very unique technology to noninvasively using acoustic energy to heat a large mass of tissue, either to temperatures above ablation or to dial back or defocus or to heat the tissue mass in question to the temperature above the transition temperature of ThermoDox. Now for us, in thinking about the combination of our drug system technology with this noninvasive heating technology, the doors to changing the paradigm to cancer open wide, and we think that Dr. LaBounty in an interview that he gave to another analyst suggested that this is really -- if you look at Star Trek, this is a Star Trek approach to treating serious disease. Think about it this way. An MRI-guided HIFU device locating a solid tumor proceeded with a dose of ThermoDox. Noninvasively, warming the tissue where we're seeing a high concentration that therapeutically killed the tumor in a patient following treatment, gets up off of the gurney and walks to his car. That's really the -- that's the vision that we have for the application of these 2 technologies. It opens ThermoDox up to a broad range of solid tumor indications. So that's a vision I -- Nick, would you add anything to that?

No, Mike, I think you said it all, basically, in your statements. And again, the interest to us is that this is totally noninvasive HEAT therapy, and the great part about being at Celsion is that these great centers that are developing HIFU technology are coming to us looking for ways to improve on that technology, and we believe ThermoDox is that answer.

I will just add one more thing. We talked about 3 trials, 1 preclinical, 2 clinical trials, 2 which are sponsored in -- we're supporting in collaboration with others sponsors. One of which we have a partner and agreement with one of the largest names in medical devices, electronic medical devices, Philips. There will be more coming. There is more interest, and we're looking for the right applications. We want to dilute our efforts or our resources that we will be talking about more in some areas of cancer for which there are very few options. Joe, this is exciting. It's an extraordinary opportunity for our small company to make an enormous difference in how cancer patients are treated.

The next question comes from Mike King with Rodman & Renshaw.

I just wanted to ask 2 questions regarding -- the first is the September -- if the September interim look -- also include the utility look? And then I have a follow-up to that.

Nick, do you want to get that?

Yes. In terms of utility, the way I approach that question is if there are safety problems. And that would be the way that the DMC looks at this issue. And if there are significant ones, they'll bring that to our attention. And as we previously stated, we don't anticipate any problems. Thus far, the safety and the overall safety in the program has been as expected. So we don't expect any surprises there. But that's what it will be based around in terms of futility analysis.

Okay. And then, I wonder if you could also perhaps help us think about the -- at the time that you got a medium PFS, how mature will your OS survival data be? Do you have any way for us to understand that because I know that for full approval you'll have to hit that. You'll have to hit that secondary endpoint.

Yes, I think, I'm going to start to answer this question, again, Mike. OS is an important confirmational endpoint as you point out, OS is included as a secondary endpoint, it's part of the trial design. The trial is properly powered to show an overall survival benefit. We certainly have a visibility to the number of patients who have died in the trial. And it appears to us that the death rate is consistent with what I've talked about earlier, adjusted for what could be the -- our expectation for an improvement in the therapeutic arm, but it appears to be our assumptions for survival or survival benefit are reasonably consistent with the way the study was designed. Now, that said, we will know more with regards to how mature this OS data will be following our DMC meeting. We may or may not choose to answer your question, specifically, as a result of our conversation with the DMC at that time. I think that captures it, Nick?

Yes, I don't think I can add more to what Mike said. I think, we have to wait a little bit longer to make more specific comments on overall survival.

We'll move next to Keith Markey with Griffin Securities.

Couple of questions. One, I was wondering can you tell us where you expect to see the fastest acceptance of ThermoDox in the Asian market? Would it be Korea, Taiwan, Singapore or possibly China at the end of all of that or in a different order?

So I think what we have to rely on is enrollment rates, investigator enthusiasm and our understanding of the regulatory process. In our point of view on both Korea and Taiwan is that we believe that -- or we certainly have enrolled enough patients to support registration without the need for bridging studies. But we have some reason to believe that in Taiwan, the filing given that, the filing directly without need for CPP may be acceptable to the Taiwanese FDA. We haven't asked -- we haven't assured ourselves with confidence that the same opportunity exists in Korea. But if we could take the regulatory process out of it, what we've seen in both of those countries without question has been enormous enthusiasm for the trial. We have among our investigators, some of the most important names, if not in the world, certainly in those countries and we believe that their leadership, their interest, their leadership, their enthusiasm for the trial would be significant driver for adoption of ThermoDox in adjunct to radiofrequency ablation. Now in China, China is, I mean, just a very interesting market. The -- from a clinical trial point of view, we have 17 -- I believe 19 sites there now. Again, some of the most important names in liver cancer in the entire country. The person -- the physician who is our lead principal data investigator for the Chinese contingent has written the definitive academic tax[ph] radiofrequency ablation. She has told us multiple times is that she will be amending that academic work with the result of the ThermoDox trial as soon as the data is available. She is an enormous supporter. She provides education broadly in many conferences to the intervention of radiology and surgical community treating patients with this disease. That said, the challenge in China is always establishing pricing. Its pricing is established in multiple levels. We could go into that if you'd like separately. But assuming we get through the price -- the timing and the pricing hurdles in the approval process, which by our best estimates, certainly could be 12 months and maybe more. We would see the adoption of ThermoDox plus radiofrequency ablation, I think spearheaded for the most part by the influence of our, again, of our principal investigators.

Very good. And then, you kind of anticipated my next question which was about pricing. Can you give us a sense as to how even between different geographies you might think that pricing could be?

Yes, I mean that's an interesting question. So we certainly look at other branded products who are marketed in countries throughout the world, including Asia-Pacific, Europe and the U.S. It's interesting that when we look at the discount given to the U.S. government on its purchase of branded drugs for Medicare, the discounts are not significantly different than those in Europe, by the way. I think we could find chapter and verse where that's true. In the Asian community, the premium market, obviously, is Japan. The dynamic in Asia-Pacific is reference pricing. So we do have the -- I think a reasonably good feel for what the pricing in some cases, discounted. In some cases, not. I might look relative to U.S. pricing but the goal here, I think our goal here would be to establish a launch strategy that maximizes our pricing potential without being predatory. Maximizing our pricing potential in the region because there is a natural tendency as a function of government regulation for prices to decrease as a matter of law over time. But I think we can be more definitive with you with regards to pricing once we have some more quantitative data, and more, I'd say, direct conversation with pricing authorities in regions outside the U.S. and Europe.

And the next question comes from Mara Goldstein with Cantor Fitzgerald.

I have a question on the HEAT Study and just so that Greg doesn't feel neglected, I'd like to ask a question to him as well. And my question is on the HEAT Study. And can you remind me of the stratification of the trial? And then, how will progression be measured and adjudicated?

Okay. This is Nick Borys, I'll take your question. The stratification for the study is based on lesion sizes, first off, and so lesions between the size of 3 to 5 will be in 1 strata and then lesions greater than 5 to 7 will be in the second strata. The study will also be stratified by what type of device was used as an RFA device. And there are 3 FDA approved devices at the moment, and we will also be looking at those separate strata. Your second question was regarded to how PFS is being measured. We follow the standard design that was recommended by a paper that was published right around the time that we designed the study, which is a modified rhesus criteria where we used CT scan using a triphasic approach to measure and evaluate liver tumors within the liver and extra hepatic as well. We image the patient for the first year every 2 months. And after month 9, then we image the patients every 3 months for progression. And that's an independent core laboratory.

Okay. What happens if a patient progresses prior to a scheduled scan?

Then the progression is counted from the last date when the scan was clear.

Okay. And then the scans are -- how are they -- I mean, obviously the patient's physician is seeing the scan, and then if somebody else -- is there a blinded participant looking at that scanning and confirming that. So there is concordance? Or is it just, I guess, obvious enough that it doesn't need to be -- doesn't need to occur.

Well, the official arbiter of progression of the data is our independent core lab, and we look at the data from the independent core lab and work very closely with investigators in order to maintain a very high concordance rate.

Okay, great. And if I could just follow up with Greg on the Hisun agreement, I thought I heard you speak to reimbursement to Hisun for supply material. And I'm just wondering how that comes into the P&L?

Thanks, Mara. Yes, we footnoted some of the detail in the 10-Q that we filed. But the -- essentially, the cost of the tech transfer, the batches that are being processed by Hisun over the next year are being fully funded by Hisun. We'll book a -- you'll book on our books a payable to Hisun as those activities occur, but we won't be paying any cash to Hisun until a few years from now. We have the agreement that allows for a 4-year window so there's plenty of opportunity here for us to have Hisun take the lead on funding of these things. We will be booking on to the balance sheet to payable.

Okay. In the unlikely event that you don't achieve commercial date, are you then required to close out that payable? Or does it go away?

It's a good question. I think the payable was intended to be reimbursed. But the -- again, Hisun is taking the technical risk here, the inventory risk and funding these things up front, which is really financially a really good deal for Celsion, so we're pleased with that. I'm pleased to be working with Hisun. We've got a good rapport with them. We've got the ongoing meetings with them from the operational side under Dr. Bob Reed, things are going well and look forward to continuing our relationship.

The next question is a follow-up from Mike King.

I wanted just to ask you to perhaps expand on an answer to -- I think it was Joe Pantginis' question earlier about, I'm just curious, when you guys look at the market opportunity of ThermoDox, can you help us understand what the -- if we look at all the tumor types to which may be amenable and which some -- some adjunctive heating source of other ablative therapy used. How large of a market opportunity do you think that is?

Large in terms of number of patients, Mike?

Yes, I think that's a good place to start, or a number of procedures, if you want to view it that way.

Yes. So I think we have a very clear picture of the current standard of care for treating these patients. It's very clear. It's described in a number of compendia, the NCCN has a very good outline, very consistent with the AASLD criteria published in -- Barcelona criteria published by the AASLD. But the primary approach of treating these patients is a function of staging. Dr. Borys can talk about stages in a little bit more detail, but the current addressable population with radiofrequency ablation and these are patients who are neither resection candidates who are possibly not transplant candidates, although some patients are put in a transplant list as a function of radiofrequency ablation, and I think that's a little bit more complicated discussion. But for patients who are not resection candidates, and for patients who have not -- who are not presenting with such an advanced state of disease that RFA has not indicated either because you have to ablate too much tissue or it's progress outside the liver. Those patients, we call them intermediate-stage patients. They're currently treated with RFA. Of the total incidence, about 25% of patients presenting who fall into that category. So remember, total incidents here globally is about 750,000. About 25% of those patients in this staging paradigm would be -- are treated with radiofrequency ablation. Our view is that only some percentage of that 25% would be treated with radiofrequency ablation plus ThermoDox. There's another heating technology on the horizon called microwave ablation. I think we evaluated, we concluded that although it's not included in our study, but it's a small percentage of patients treated with ablation. They -- given, assuming they have the right lesion size and are not contraindicated, they may also be given adjunct of ThermoDox to the microwave ablation. But overall, going back to your original question, how many patients or how many treatments? It's complicated by prevalence, too, and then our model includes prevalence. But if we just talk about newly presenting patients, we're counting on about 10% to build our revenue models. 10% of the total number of patients who are initially diagnosed, and we're assuming that, that will ramp up to the 10% over a 5- to 7-year period. Does that answer your question?

It sure does.

And the next question will come from Mike Seebeck [ph] with LWM.

I'll try to be very quick here. And I'm going to get off track a little bit because the other questioners asked some great question. But in terms of the trial, the Phase I trials for the bone palliation, the bone cancer. If you could wave your magic wand and establish an MTD[ph] tomorrow and into Phase II, what are you going to try to structure the endpoint for on that trial?

Yes, Tim [ph], and that's a good question. I think maybe we need to help you understand that this clinical trial, it is a Phase II and Nick, can you kind of take it?

Yes. First of all, I just want to reiterate that with the agreement we reached with the FDA that this will be a Phase II trial. The dose for ThermoDox has been already established so we're going to continue with that. In terms of its primarily endpoints, we're going to be looking at analgesic endpoints which would be pain. So we're going to be using pain scores as part of that and quality-of-life scores as part of the endpoints.

Okay. And that's the type of thing -- the type of information that could be gathered and evaluated in a fairly short period of time, correct?

Yes. And we're doing nothing new. These are the standard approaches that other treatments that are available for these patients. So we'll be comparing ourselves against external beam, against opiates and their standard approach to how to measure responses in these types of patients.

Terrific. One last question. In terms of the HIFU potential and other heating potential and other active ingredients to be encapsulated, I'm seeing advertisements for HIFU for prostate cancer in places like Mexico and Canada and I know the HIFU community is looking to drive the acceptance of HIFU into the U.S. market and there's going to be a lot of opportunities, I think, with Celsion's range of products. Is there any developmental work being done, especially now that we have relationships with the HIFU manufacturers that could be sponsored and paid for by them in other, shall we say, agents like cisplatin and docetaxel. I believe the company has the potential to encapsulate and deliver via this method?

Let me try to answer that for you, Mike. I think first and foremost, we have demonstrated the platform capability of our LTSL technology. We reported successfully incorporating 2 platinum compounds, cisplatin and carboplatin and we've incorporated docetaxel. We've seen some very encouraging results in tumor inhibition studies for all the compounds. We decided that we'd devote our financial resources to our clinical programs. So following feasibility, we just -- we set those compounds aside. It was a deliberate decision on the part of your management team here. Our goal was -- and has always been to demonstrate the full potential of the heat-sensitive liposome technology and following a successful clinical program then to fully finance the development of one or more of those compounds as we begin to evaluate them in a variety of different human cancer cell lines, some compounds maybe more effective in certain cancers than others. That early work, that preclinical and feasibility work, I think, is very important prior to initiating any discussion about co-development with a device partner or another pharmaceutical or biotech partner. Typically, what is required before a discussion of partnerships is demonstration, a robust demonstration of feasibility, and we are prepared to do that, assuming, of course, positive data from the HEAT trial which we have no reason to believe won't be positive.

That will come from private investor, Anthony Olich [ph].

Mike, you mentioned that the DIGNITY Study is difficult to enroll. Our Star Trek story lends itself well to a non-clinician presentation. Is it out of the question to try and do an education piece for women on one of the leading talk shows, to talk about our exciting new therapy, again, with the caveat that it is in clinical trials, but that we have a delivery system that targets and looks very promising in terms of prospects to attack this devastating disease. I mean is that something totally out of the question?

No, not at all. Not at all, Tony. As a matter fact, in the heyday of enrolling our Phase I trial, we tried multiple approaches to -- multiple outreach approaches directly 2 patients that have made themselves available to clinical trials throughout Thomson Reuters searchable database and also directly to physicians who treat these patients so we spent a significant amount of money. We also -- I mean your point here that this is a great human interest story that could inspire individuals with late-stage cancer on the chest wall to enroll in our clinical trial, and that hasn't gotten by us. It could really for a human interest story or a scientific writer in a major media publication like The Times or The Journal or even one of the weekly magazines, the quid really is some data to support our thesis that we can make a difference in these patients. And that goes now to Dr. Rugo, Professor Rugo, who will be presenting data from the -- our Phase I trial, which I think could be some very impressive results. That presentation will be made, as we said earlier, at the European Medical Conference, a very prestigious conference. We will also -- we are also providing a research publication, which includes combined data from not only our Phase I trial, but also the work that was done by Kim Blackwell at Duke, which is equally impressive if not remarkable in some of the results seen in the 16 patients that were treated there. I know this has taken some time. We're as impatient as everybody else. But a publication in a major journal, presentation at a major conference with now 2 investigators who are willing to stand up and talk about the potential of this treatment may give us the ability to attract the mainstream media or the public writers to discuss our story. So we were hoping that -- a very next -- it might be a very nice next step. I think, more importantly, we're looking for physicians who treat these patients now with clinical data to refer their patients to our trial. And operator, I think we've come to the end of our call. Nick, do you want to say something? I'm sorry, let me...

Yes, I wanted to clarify a previous question that was asked about stratification and I misspoke. We are stratifying the lesion size. The other stratification is not by device type, but it's by the RFA technique type. So I apologize to the questioner. We're stratifying according to whether the procedure was done percutaneously, laparoscopically or surgically. So sorry about that. I just wanted to clarify before we ended this call. Thank you.

Thank you, Nick. Thank you very much. Okay. So we've come to the end of our second quarter conference call. We have always -- as always, we appreciate the opportunity to share with you our work and the results of our efforts in bringing ThermoDox through the rigors of this very difficult clinical program. We are coming close to the end here, folks. So we are excited as possibly can be. We're delighted to have you with us on this journey. We're looking forward to the conference call, and we'll certainly be making available any material progress that the company realizes between now and then. So again, thank you very much for your attention, and we look forward to speaking with you in the future.

That does conclude today's presentation. Thank you for your participation.