Imunon Inc (IMNN) 2014 Q2 法說會逐字稿

Good morning, my name is Tony and I will be your conference operator today. At this time I would like to welcome everyone to the Celsion's second-quarter 2014 financial results conference call.

(Operator Instructions).

I would now like to turn the call over to Jeffrey Church, Senior Vice President and Chief Financial Officer of Celsion. Please proceed.

Thank you. Good morning, everyone, and thank you for joining us today to discuss our second-quarter 2014 financial results which we announced this morning.

Today's call will be archived. The replay will be available beginning today at 2 PM Eastern and will remain available by phone until Thursday, August 21, 2014, and will also be on Celsion'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 cost of our research and development activities, possible acquisition of other technology assets or businesses and possible adverse action by customers, suppliers, competitors, regulatory authorities and other risks detailed from time to time in the Company's periodic reports filed with the Securities and Exchange Commission. Following our formal remarks today we will open the call for questions.

I would like to turn the call over now to Michael Tardugno, President and CEO of Celsion. Mike?

Thank you, Jeff. Good morning, everyone. We have a lot to discuss today so I will get right to it.

Before doing so I want to remind you I am joined today by Jeff Church from whom you just heard, our CFO and Senior Vice President; doctors Borys and Anwer who normally would be with us for this call are not today, they are attending other business. But they will be on future calls, I can promise you that.

So welcome once again to our quarterly earnings call into the new Celsion, a company that all at once with the acquisition of EGEN, this marvelous science-based company in Huntsville, Alabama, all at once is a fully integrated development company with R&D capability from feasibility through MDA. With platform technologies in chemotherapy, immunotherapy and RNA therapy and clinical trials in Phase III, Phase II and Phase I and some of cancers globally most important forms, we are extraordinary will positions. Celsion now has multiple opportunities to create value for our shareholders and represents a development company, I'm sure that you will agree, of unique proportion.

On the development front as our recent news flow points out, we are having an extremely productive year thus far, one that I suspect will continue to demonstrate significant progress not only with ThermoDox for primary liver and recurrent chest wall breast cancers, but also with our equally important immunotherapy and RNA platforms. If I can take the liberty now to quote one of our great presidents, to those whom much is given, much is expected, to that I would add particularly this morning, with our EGEN acquisition you should expect much from Celsion.

So here is a short list. And I want to remind you it is a short list of what we will be reporting over the next 12 months.

From our first immunotherapy candidate EGEN-001, which I am going to refer to as GEN-1, by the end of the year we will be reporting translational data from our Phase Ib study of platinum-resistant ovarian cancer patients demonstrating the expression of IL-12 and the activation of an associated potent multi-mechanistic anticancer immune response. OS from the same study will be available early next year.

We also fully expect to report regulatory support from our planned Phase II study in first-line ovarian patients in the first quarter of next year. And a second indication for EGEN-001, one that could very well become a priority for the Company. We will be reporting substantial preclinical data in support of our planned IND submission for the GBM glioblastoma ovarian cancer indication.

Again we fully expect that the data will be followed by FDA agreement for a Phase I study in post-resection GBM patients. For this we are targeting the second quarter of 2015.

From our second product candidate, a PPC, that's a polyethylenimine nanoparticle that has the unique capability for delivering messenger RNA as well as other long and double chain nucleotide sequences. From the second product candidate we plan to report data from a non-human primate study.

The study is designed to corroborate in the second species data which reliably demonstrates highly prized and clinically very relevant messenger RNA lung expression. Lung expression of RNA is a characteristic uniquely associated with our proprietary PPC delivery technology making it a very attractive delivery platform.

And from our ThermoDox studies, you should expect ongoing data from the DIGNITY study, which if it continues to show overwhelmingly positive tumor response results we will approach FDA to discuss next steps. And if you recall from prior written agreements we know that FDA will accept local tumor control as a registrational endpoint in this unfortunate, highly refractory end stage population. And of course we will provide regular DMC updates from our Phase III OPTIMA study in primary liver cancer, a study that is currently recruiting patients.

For those of you who are new to our Company, I would like to spend a few minutes on our strategic asset acquisition purchase, a deal which by anyone's definition is incredibly investor friendly. I have asked Jeff to discuss the deal terms in a little bit more detail when he covers the financials.

In June we announced and completed our acquisition of EGEN, a privately held company whose primary focus is the development of nucleic acid-based therapeutics for the treatment of cancer among other therapeutic areas. This transformational event establishes Celsion, as I have said, as a fully integrated oncology company that provides us with programs on the leading edge of cancer research and with R&D talent and competencies end-to-end from drug discovery through to commercialization. With this deal we have improved the depth of our technology and research base and have created a new trajectory for Celsion in three distinct ways.

First, we now have multiple technology platforms -- three to be exact -- from which to generate future growth. They include of course our proprietary heat sensitive liposomal platform. We have an exclusive licensee from Duke University, the LTSL platform is the technology underpinning our ThermoDox product.

TheraPlas is the second platform. TheraPlas Is a synthetic nonviral nanoparticles for the delivery of double-strand DNA for oncologic immunotherapy products and for single- or double-strand therapeutic RNA. And third, TheraSilence, a liposomal nanoparticle for the delivery of siRNA should and miRNA, or microRNA.

Secondly, we now boast a pipeline that includes a robust preclinical development program and earlier stage research that represent potential leading edge technology to treat difficult disease targets. And third, we have multiple product candidates at the clinical level which I will now review.

Let's start with ThermoDox. Our Phase III OPTIMA study is designed to evaluate ThermoDox in combination with standardized radiofrequency ablation, or sRFA, hepatocellular carcinoma, or HCC, sRFA for HCC.

The study will enroll approximately 550 patients globally at up to 100 sites in North America, Europe, China and Asia Pacific. It is a two arm, double-blinded randomized study comparing ThermoDox in combination with standardized RFA, or sRFA, which will be standardized across a minimum of 45 minutes -- or will be standardized to a minimum of 45 minutes across all investigators in the study versus standardized RFA alone.

The primary endpoint is overall survival. The study is powered to show a 33% improvement in OS.

I want you to keep 33% in mind. We are going to refer back to that in a minute.

The statistical plan calls for two interim efficacy analyses by an independent data monitoring committee. The office spend is de minimis for these two looks.

The support for OPTIMA is significant and comes from one, an exhaustive retrospective analysis of the previous Phase III HEAT study; two, is based on convincing post hoc OS data; and three, is further reinforced with prospective confirmatory preclinical data and computational models. Post hoc findings and hypotheses supporting OPTIMA do not represent our view alone. The data were shared, along with our RFA learnings in particular, with HCC research community during major international medical conferences.

In the final analyses we have received full support and I would say share a great deal of optimism for the OPTIMA study with virtually all of the most important names in HCC research worldwide. I think with some modesty I would like to say that we now know more about the use of RFA to treat intermediate stage lesions in HCC than just about any company on the planet.

What we learned from the study is this. For tumors greater than 3 centimeters RFA device limitations have to be considered to be effective. That is to fully destroy the tumor, and create a clean margin multiple overlapping oblations creating longer dwell times are required.

Longer RFA dwell time, that is the treatment time greater than 45 minutes. Also improves the heat gradient to a larger volume and allows for increased local ThermoDox perfusion and ultimately a high tissue concentration of doxorubicin.

Longer times plus increased dox ensure a better outcome. The findings are convincing. The most recent clinical evidence supports this thesis and comes from our June 30 quarterly overall survival sweep of the HEAT study patients.

In this subgroup of 285 patients who received standardized RFA treatment, 285 represents 41% of the total study, we noted a 57% improvement in OS in the ThermoDox plus sRFA arm versus standardized RFA alone. 57% improvement.

Now I want you to reflect back on my earlier comment regarding the primary endpoint overall survival that we are planning for the OPTIMA study. In that case we were looking for 33% improvement.

So the evidence in our post hoc analysis suggests that we should be able to meet that target quite easily. Quite handily.

So 57% improvement versus sRFA alone. That is over two year's improvement in survival. That is pretty astounding.

Two years. A birth, a wedding, a graduation. If you will recall Nexavar or sorafenib was approved on just 11 weeks OS benefit.

And while there should be some caution since this is a retrospective analysis, these findings are nonetheless striking in that they have one, remained constant over each of the six quarterly data sweeps, they demonstrate impressive confidence with a P-value of 0.037, the magnitude of effect is unequivocal.

This is not a borderline improvement where a wobble in the data could have an impact. These data are further supported by a multivariate Cox Regression Analysis which do not discount in any way sRFA post-ThermoDox as the leading factor for the OS benefit.

The goal of OPTIMA is to support registration in key liver markets worldwide. To that end we are working with multiple agencies, multiple regulatory agencies, to advance our global registration strategy.

In addition to the US FDA clearance that we received in the first quarter this year we have received approval to commence the study in sights in Taiwan, Hong Kong, South Korea, Malaysia and Canada. We have also submitted an application for accelerated approval to the China FDA, Food and Drug Administration. The CFDA has reviewed the HEAT study data with Dr. Borys and myself including the subgroup of patients treated in China, and is committed to working with us to initiate the OPTIMA study in China as quickly as possible.

In Europe we are taking advantage of the harmonization process which allows for a central and parallel approval of the key countries including Germany, France, Italy and Spain. In addition, we plan to meet with the EMA later this year to discuss our ThermoDox MAA, or marketing approval filing strategy.

Beyond HCC we are evaluating ThermoDox in the Phase II DIGNITY study of ThermoDox plus hypothermia and recurrent chest wall breast cancer. As you know, we continue to report very impressive results in this difficult-to-treat refractory population. So patients post-mastectomy with failed at least two lines of chemotherapy and have failed radiation before enrolling in our trial.

In July we reported updated interim findings demonstrating that a local response rate of greater than 50% has been observed in the first 10 available patients with refractory disease notably with three complete responses. I would also point out that these findings are consistent and have been consistent with the objective responses that we have seen in two previous Phase I studies accounting for some 27 patients.

Additionally, we are supporting a broad range of study using HIFU to provide ThermoDox activation in multiple indications. The most advanced program is now recruiting patients in a Phase II liver met study in Britain followed closely by a breast cancer study, which we hope to initiate in the Netherlands. Both of these programs are co-founded -- are co-funded -- in Europe by government grants, one grant of which is up to $10 million.

Now I would like to turn our attention to EGEN-001. EGEN-001 is our Phase II radioimmunotherapy candidate for the treatment of ovarian and brain cancer. It is an IL-12 DNA plasmid encased in a PPC nanoparticle delivery system.

The system promotes transvection of the plasma into cells, which then use the cellular mechanism to enable persistent and durable local secretion of the IL-12 protein, the interleukin 12 protein, which lasts for several days or weeks depending upon the target. As many of you know, IL-12 is one of the most active cytokines for the induction of a potent anticancer immunity response.

It acts through the induction of T-lymphocyte and natural killer cell proliferation and has also shown an anti-angiogenic effect and has demonstrated the potential in a variety of cancers. As a recombinant protein, that is as a protein that is manufactured ex vivo in fermentation vats, this ex vivo, this outside of the body produced IL-12, when used either locally or systemically to treat cancers, has poor pharmacokinetics and is associated with serious toxicities.

Scientific evidence collected to date has shown that EGEN-001's potential to overcome these limitations. By controlling the expression of IL-12 in vivo we see very encouraging safety profile and similarly encouraging indications of efficacy.

Phase I clinical studies have established a safe therapeutic dose and have demonstrated strong disease control rates in a tough-to-treat platinum-resistant ovarian cancer population. 001 has been safely combined with first-line chemotherapies, carboplatin and docetaxel in platinum-sensitive ovarian cancer patients. While the end was small we noted impressive disease control in OS rates in this population.

We are currently completing a Phase Ib trial in platinum-resistant ovarian cancer patients under the direction of the GOG, that is the Gynecologic Oncology Group. By yearend we will be reporting translational data demonstrating the expression of IL-12 and the activation of the associated potent multi-mechanistic anticancer immune response. And early next year we should be able to assess an OS signal.

The data to date strongly support a rationale for advancing EGEN-001 into a Phase II combination trial with the goal of targeting first-line plus the standard of care, where activation of immune response is frequently more effective for subjects whose immune system is healthier and less compromised by previous chemotherapy. We are on track to meet with the FDA regarding our Phase II plan.

Our hope is to do so by yearend. With FDA concurrence in the first quarter of next year we could be treating patients in the second quarter.

I would also point out that applications for EGEN-001 extend beyond ovarian cancer. In parallel with our ovarian program we are working on a second and perhaps the most exciting clinical research for the Company, and that is a development program in a glioblastoma multi-form, or GBM. As I have said, this could well become a priority for Celsion.

As you know, a small, well-designed study may provide for a registrational opportunity or approval. We will see.

While preclinical studies have demonstrated that administration of EGEN-001 in the brain can lead to an IL-12 expression that lasts for at least one month. So we are fast moving towards an IND in this indication supported by follow-on preclinical proof of concept, safety and biodistribution studies which are now in the late planning stages.

Our goal is to submit an IND briefing book and protocol by yearend and plan for a Phase I study in the first half of next year. The study design contemplates combining IL-12 immunoactivation with the standard-of-care chemotherapy in post-resection patients.

OS, of course, will be an ideal endpoint and particularly in this population. You may also know that the EGEN-001 is a nonviral approach which could accelerate, or should accelerate regulatory acceptance over other approaches under development.

Now I'd like to turn to EGEN-002, our RNA therapeutic based on our TheraSilence platform, which is at the concept stage. At this concept stage setting the basis for partnering or collaboration.

EGEN-002 is a combination of two unique molecular targets for cancer therapy and has the potential as a treatment candidate for lung cancer. The concept uses a two-pronged approach, a combination designed to inhibit tumor growth by anti-angiogenesis and promote direct killing of the tumor with microRNA. We have demonstrated evidence of siRNA delivery and gene silencing into the lung and with this approach and look forward to advancing preclinical development of this program.

Beyond our own clinical development efforts we are also seeking to leverage the TheraPlas and TheraSilence platforms externally. You should know that we have a current joint development program focused on lung application of messenger RNA, the next milestone of which is to corroborate the [urine] data in a non-human primate study. Some very exciting news could come from this project near term.

From our press releases you know that we recently launched a commercialization of our reagent products based on these two validated platforms, that is TheraSilence and TheraPlas, and believe we can generate modest revenues from this business to help support our maturing oncology pipeline. But more importantly, however, reagent sales to leading research and academic centers will serve to validate our proprietary nonviral vector delivery platform.

So as you can see we have a very active clinical development effort focused on three promising candidates at the leading edge of cancer research and we look forward to updating you on our progress. So now I will turn the call over to Jeff for a review of our financials. Jeff?

Thank you, Mike. Before I review the financial results for the second quarter I would like to discuss the economics around the EGEN acquisition. The acquisition broadens our technology platforms and product pipeline in two of the most exciting areas of drug development, immunotherapy and RNA therapy.

The acquisition will help mitigate the risk associated with the single product, single technology platform. The negotiated deal terms, as Mike stated, are user-friendly and represent a deal structure that is one of shared confidence and shared risk. The EGEN investors fully share development risk with us. The initial upfront payment consisting of $3 million in cash and $10.6 million in common stock represented 30% of the total consideration for the acquisition and put no pressure on our balance sheet.

We completed the transaction on June 20 and ended the second quarter with over $50 million in cash. Our venture debt lender, Hercules Technology Growth Capital, after completing their due diligence and reviewing the transaction, fully endorse the acquisition through a second $5 million draw off our existing loan facility. This cash infusion more than covered the upfront cash payment and our transaction-related expenses.

In addition to the upfront payment, a total of $30.4 million in well defined value creating development milestones will trigger success-based earnouts payable to EGEN shareholders based upon the completion of important clinical objectives in our ovarian and GBM studies for EGEN-001 and joint development and clinical progress for TheraSilence including partnering in outlicensing initiatives.

70% of the acquisition price is tied directly to contingent value creating milestones. If these milestones are achieved both Celsion and EGEN shareholders win. This transaction is user-friendly, win-win, risk mitigating and value creating.

I would now like to turn to the second-quarter financial results. Starting with cash, we reported total cash and investments at June 30, 2014, of $50.1 million as compared to $43.8 million at the end of 2013. Our cash position reflects the proceeds from a registered direct common stock offering in January 2014 along with a second draw in June of $5 million under our Hercules loan facility.

Our current cash balance put us in a strong financial position to advance the development of our expanded product pipeline. Our projected cash usage is estimated to reach $2 million per month with the full implementation of the OPTIMA study and the integration and clinical development of the newly acquired assets from EGEN.

Our current cash is projected to carry us into the second half of 2016 well past the announcement of many key development and partnering activities. Net cash used for operations was $9 million the first six months of 2014, or approximately $1.5 million per month.

This compares to $3.4 million for the same six-month period in 2013. This increase was driven by a $5 million nonrefundable cash payment, which we received from Hisun Pharmaceutical Company in the first quarter of last year, coupled with a $600,000 increase in operating expenditures in the current year, largely the result of start-up costs for our Phase III OPTIMA study, which included site initiation expenses and the manufacture of clinical drug supply.

Research and development costs were $6.1 million in the first six months of 2014. That is an increase of $833,000 compared to the prior year due again to the above-mentioned increase in costs associated with starting up the OPTIMA study.

Our G&A expenses were $4.7 million for the first half of 2014 versus $3.6 million for the same period in 2013, primarily as a result of higher insurance premiums and personnel costs including an increase of $900,000 in non-cash stock option expense. The second quarter of 2014 also included one-time cost of $1.1 million associated with the June acquisition of EGEN. And this related to legal and banking fees as well as due diligence expenses we incurred in getting the transaction completed.

For the first half of 2014 the Company reported a net loss of $12.1 million compared to a net loss of $230,000 in the first half of 2013. Let me just point out last year's net loss was positively impacted by two non-cash, nonoperating items which included a non-cash benefit of $8.7 million from the change in valuation of common stock warrant liability associated with equity financings in September 2009 and June 2013.

The net loss for 2013 also was impacted by a non-cash deemed dividend from the beneficial conversion feature of $4.6 million from the preferred stock equity financing announced in February 2013. If you look at comparable periods in 2014 and 2013 without these items, our operating loss for the second quarter of 2014 was $2.6 million higher than the comparable period last year and $3 million higher in the first six months of 2014 when compared to the first six months last year.

Both of these three- and six-month periods ended June 30, 2014, included the $1.1 million in transaction-related acquisition costs. Our corporate focus has always been and will continue to be aligned with advancing our product pipeline through value creating clinical trials and outside collaborations. I will now turn the call back to Mike.

Thank you, Jeff. As always you have the talent to bring these financials to life for us.

Thoroughly enjoy your report. Thank you so much, particularly your comments regarding the deal terms for the EGEN acquisition. I hope people on the other end of the line appreciate the value of this deal not only from a technology perspective but also the economics and the financials.

Well, I hope you will agree with us this is an exciting time for Celsion. With our newly expanded pipeline we have a defined strategy in oncology that is devoted to evaluating innovative therapies in first-line settings.

I can't say enough for that. Very important area of research in first line. It provides us with access to patients who otherwise would not be interested in joining trials.

With active development efforts in primary liver cancer, ovarian cancer, recurrent chest wall cancer and glioblastoma, we have a broad range of activity in some of the most important cancers in the world. We are advancing our Phase III OPTIMA trial for ThermoDox targeting registration in these significant markets around the world and we are moving with our plans for important clinical trials for EGEN-001 next year.

I will be providing data, as I pointed out, and information as I pointed out, earlier in my comments to support our clinical program for EGEN-001 over the course of the next few quarters. EGEN-001 next year, a Phase II in ovarian cancer, a Phase I in glioblastoma and we are establishing a footprint in the breakout RNAi, or siRNA space, through the EGEN-002 product and through our TheraSilence program.

So I will conclude our remarks -- my remarks -- by saying that we have a strong balance sheet with the funding to advance our key development efforts. We believe that we have the right mix of programs and technologies in our pipeline to create value for our shareholders and most importantly to make a significant difference in the lives of cancer patients and their families.

As always, we greatly appreciate your interest in the Company and we look forward to updating you on our progress as we continue to move forward with these very important clinical programs. Now we will go to questions, operator, so I'd like to ask the audience to limit them to more than two so that everyone can have an opportunity to get answers. So, operator, if you would open up the line, please.

Thank you. (Operator Instructions). Keith Markey, Griffin Securities.

Good morning. Congratulations on making an excellent acquisition and a good report on the R&D programs. Quick question, could you tell us what the status of patient enrollment is, or might be in those foreign countries and regions where you have gotten regulatory approval for the OPTIMA study?

Good question, Keith. So we do not have a patient yet in the trial. I'm expecting that we will be reporting a patient very soon.

We have multiple sites that are actively recruiting. There has really been no -- we are right on track with initiating sites in the countries where we have approval. And I am actually very very encouraged by that.

It appears to us that China will meet their -- we will meet our timelines in China for achieving a clinical trial agreement, or a CTA. Typically for most companies the time period from application to approval is about 12 months.

We are following very closely -- and by the way, the progress of any clinical trial application in China is a matter of public record. You can follow it yourself. Of course you would have to be able to read Chinese characters but you can follow it yourself.

We do follow it very carefully. So China has accounted for about 30% of our patients in the previous trial and we enroll very quickly. So bringing China on board efficiently is important.

I want to go a little bit beyond your question because I think the first patient in only begins the effort. We have met at a couple of medical conferences, and we will be meeting again at the upcoming ILCA Conference in Kyoto, a number of our investigators.

I would like to report to everybody on the phone, as I mentioned earlier the enthusiasm for this trial among our investigator group is remarkable. I think it has become very clear to the medical community and particularly to our investigators that appropriately using RFA within its design limitations -- I don't want to say it was inappropriately used during the conduct of the trial but we now know more about the use of RFA in larger tumors than any group of researchers and sponsors.

The application of this new knowledge and the well-controlled clinical study is exciting. And I think what we are going to find is that once the study sites are initiated that enrollment will progress very nicely.

But for the most part we are on track. As I said and I continue to talk to as I continue to talk to investors, we believe that from the time the first patient is enrolled to the time we complete 550 patients, the time period will be somewhere between 32 and 34 months. I think we have a good handle on that.

With any luck at all we should be reporting at the first interim analysis some efficacy results, if in fact the clinical benefit is a sufficient unblinded trial, we will be reporting the results. But we should be able to conduct the first interim analysis in about 36 months following the first enrolled patient. So I know I answered a lot more than a question that you asked but thanks for the opportunity to get on my soapbox.

Thank you. One question, I will throw it at Jeff, a financial. Could you give us a sense as to what you expect the burn rate might be in 2015?

Yes, we have done a very thorough analysis. Right now we are utilizing about $1.5 million per month.

We expect that to increase to approximately $2 million a month over the next 18 months. So through 2015 about $2 million a month. (multiple speakers)

Keith, I'm going to add to that, so that's kind of like a straight edge, like an average. You know that there are peaks and valleys in spending, particularly as it relates to making payments to large payments to CROs.

But Jeff's earlier comment, I think, is the important one. We do believe -- he is like Snidely Whiplash when it comes to controlling expenses in the Company.

But we've taken a very sharp pencil. And my sense here is that we can talk with confidence about a 24- to 27-month runway with the cash that we have, which in the meantime should allow us to put some very important points on the board.

Thank you very much.

(Operator Instructions). Reni Benjamin, HC Wainwright.

Good morning, guys. Thanks for taking the questions. I guess just a couple.

One, in regards to EGEN-001, can you give us a little bit more color as to what the translational data may be? Are we going to be looking at biomarkers, or what should we be looking for?

Biomarkers for the most part. Those surrogates that represent the expression of IL-12, the activation of the immune system and all the appropriate components of the immune system, Ren.

So yes, would be biomarkers for the most part. The study has been accumulating tissue samples as well as blood samples.

We think we have enough patients now to be able to submit the samples for analyses. And I am hopeful to present that data sooner rather than later given what we know so far in earlier studies that should suggest that the activation in the immune response in a very profound way, we will see.

And can you remind us how big is this study? How many patients have been enrolled and what is the target enrollment?

Yes, so this has been a dosing escalation study. It combines, again, it is platinum sensitive -- I'm sorry, it is platinum-resistant patients. It is in combination with Doxil, so it has been dosing escalation for both the chemotherapy as well as the EGEN-001.

We have been through three cohorts. So up to this point don't hold me to it but I am going to be very close, we either have 9 or 12 patients but we are looking for 3 more to round out the last cohorts.

So what we haven't talked about is our interest in since we have not seen any significant safety issues with the immunotherapy with the IL-12 plasmid, we have been discussing with investigators in the GOG trial, the strategy for an additional dose escalation, at least one additional dose escalation. So there is a chance here that we could be putting as many as 6 more patients on the study but that would not stop us from gathering data from the translational analysis that we are looking for. So about 15 patients on the study, Ren; could be as many as 21 if we get an agreement to dose escalate the IL-12 plasmid.

And this is the only study that is ongoing right now with 001, correct?

That's correct.

Okay. So my second question, can you talk a little bit -- it's just a two-part question -- one, how many more sweeps of the HEAT study do you think might occur going forward, or have we kind of looked at the final data? And can you give us, I guess, your thoughts as to why -- how we should be interpreting further data sweeps, if that is going to happen?

Yes, so for the overall study we have reached the median, for the subgroup we have not. We are very close. We are within a few patients.

You know the statisticians like to point to a stable data set once you have reached the median. You probably know more about that than I do.

So we are close enough, I think, technically to be able to call it quits and claim success. On the other hand, we have been debating the value of this data set in support of a registrational program. And it seems, in our most recent discussion, it seems to me one more data sweep will take us to the median for the subgroup that we're following, the patients treated with radiofrequency ablation greater than 45 minutes with single lesions, 41% of the study.

So we think that the supportive data could ameliorate any concerns, if there are any, I don't think there are, but it could ameliorate any concerns for FDA need for some confirmation of the OPTIMA study data. So I say it with a little bit of caution, my first reaction to is as close as we were to the median was to this is probably our final study.

On reflection, after talking with our experts and some of the statisticians who have been involved with these kinds of applications, we may choose to continue for one more data sweep in which case of course we will publish the results. The results have been, as I said, have been consistent and the magnitude of effect here has been so strong that -- I said it would take a major change, you can't even imagine, it would take some sort of a major change in order to give us anything that would confound what we have seen to date, Ren. So the strategy here if we continue and the likelihood is 99% yes, we continue with one more sweep it would be for regulatory purposes, it would be to support a 33% improvement target, 80% power, 33% improvement target, in the OPTIMA study.

Excellent. Have a couple more questions but I will jump back in the queue.

No, no, go ahead. You can take one more, if you would like.

Okay. That would be great. DIGNITY, can you talk a little bit about the durable response rate, about how many more patients do you think you need to be recruited to kind of make that go/no-go decision before you go to the FDA to talk about a path forward?

I'm going to be speculating with you a little bit. So for everybody on the line, so this is an ongoing dialogue within the Company.

So we have recruited 27 now, almost 40 patients among three studies. The protocol in each of the three studies is essentially the same.

We have a little bit more data that we are collecting in the Phase II study. Essentially you can consider it to be a sparse sampling including pharmacokinetics that FDA I believe is interested in to try to show some kind of a relationship between blood plasma concentration and response.

Although in our study I don't think they're going to find anything. Because just about every patient at every dose treated for an hour with a thermal dose for an hour, or around an hour, and a systemic dose of ThermoDox starting at 20, actually, 20 milligrams per meter squared, we are currently dosing the MTD in the study is 40 milligrams per meter squared.

Virtually every patient has shown an objective response whether stable disease and you know this disease progresses. It's failed and it's moving. It's an aggressive recurrence of cancer.

So stable disease is an important outcome. Every patient, 100% of the patients for the most part have shown -- I may take that back. Maybe one patient did not.

But let me just say about approximately 100% of patients have shown an objective response. Many patients showing a partial response, or a remission and I think now with five or six patients among these three studies showing a complete response.

Pretty remarkable. It's a gasp from some of our investigators.

We would like to complete the enrollment on the study. I think we have 13 kind of which are valuable for efficacy, 7 more to run up to 20.

If the data continues, or the results continue to show that this tumor response -- you asked the question of durability. Right now the median durability and with patients still on the study, so they haven't progressed yet, is about 88 days overall.

That's a question you asked me separately and it took me a little bit of time to calculate related, or make the calculation -- we had to go back in the patient records. So it's clear to us that this threshold for the definition of durability, 90 days, is typically accepted according to RECIST criteria. It is something that is eminently achievable if we haven't already achieved it.

So let's assume that we have this durable response, we've met this durable response definition, and we pick up seven more patients, maybe six of which are valuable showing a 55% or 60% objective response rate, we are going to go to the FDA with I think a question and maybe a proposal with regards to next step in the study. And I have said, and again thanks for the soapbox, I have said I think a company like ours has very few opportunities like this.

We are treating patients who have simply no other options. These are brave brave brave women. They are facing the end of life with a disease that is going to take the integument off their chest.

In many cases a very debilitating infection and painful source. If we can prevent that during the course of the rest of their lives, I think we have an end point -- the FDA has agreed with us -- that deserves registrational consideration.

Do we have enough of an end to talk about some kind of a conditional filing? Probably not.

Do we have enough of an end to consider with FDA and maybe some of our key investigators on alternative to a continued clinical trial with all the limitations associated, maybe moving into a more humanitarian use kind of a program? That may be the next logical step here.

We can't give up on these patients. We won't. As long as they are willing, we are willing.

So I know that was a long answer. I hope that covered your questions.

Yes it did. Thank you very much and good luck.

Bob Greene, Private Investor.

Good morning, I just wanted to confirm something I thought I heard you say. We haven't reached the median overall survival yet for the HEAT study?

So may clarify that. So for the overall study we have.

For the cohort that we are following to assess a survival benefit, that cohort has the minimum treatment time with radiofrequency ablation of 45 minutes. We are close, but we have not.

Okay, and talking to the same group, those numbers look so good. Has there been any thought at all of going to the FDA and asking if you can put in NDA for that group?

I am with you. I really am.

I think there is a certain discipline and a generally accepted understanding about retrospective studies. It's stood the test of time.

Retrospective analyses more often than not, and I don't want to discount our results in any way. More often than not it's just not reliable.

But what we have, Bob, is we have a magnitude of effect meaning the improvement is substantial. It hasn't wobbled. It is incontrovertible.

We have what amounts to a high level of confidence. It is difficult to call it statistical significance because it is not perspective.

But had it been perspective we wouldn't have a P-value that is statistically significant. But the P-value that we calculated for this group is highly confident. We are highly confident.

96.5% confidence that we are on the right track. I think there may come a time when the FDA will accept a meeting with us to discuss this data but it is going to probably have to be in context with the OPTIMA study. I don't believe -- I just don't believe -- it's probably not scientifically or clinically responsible for us to try to conceive of a circumstance where we are the exception to FDA's rule on considering these kinds of data sets.

Have you looked at applying for the breakthrough therapy designations?

I think that's a step that we will take particularly for the current chest wall breast cancer program. But at this point for the HCC study, the advantage at this point really is probably lost.

We are already in a Phase III study. If the data is as strong as we think it is we'll have -- and we do of course have the fast track understanding for ThermoDox in HCC. We also have an orphaned assignation all of which provides us with a significant benefit in dealing with the agency assuming we have a positive data set.

Okay, sir. You answered my questions. Thank you very much.

And thank you. At this time I will turn the call back over for closing comments or remarks.

Well, thank you all. I just want to repeat a couple of things that I said earlier in closing.

It is always a pleasure first to speak with you, particularly now. This is an exciting time at Celsion. I hope you agree.

With our newly expanded pipeline we have a defined strategy in oncology, are devoted to evaluating these innovative therapies in cancer some of -- cancer's globally most important forms. Primary liver cancer, ovarian cancer, recurrent chest wall breast cancer, glioblastoma, could be a priority of the Company. We'll see soon.

I'll conclude by saying that we have a strong balance sheet, as Jeff points out. We are very careful and very mindful of our expenditures.

With this balance sheet, we have the funding to advance our key development efforts, we believe we have the right mix of programs, and more importantly, we have the support of loyal shareholders like you. So it's our pleasure.

We greatly appreciate your interest in the Company. And we do look forward to updating you on our continued progress. Thank you very much and have a nice day.

Thank you. This does conclude today's conference.

You may disconnect at any time. And have a great day.