Earnings Call Transcript - IMNN Q1 2020

Operator, Operator

Good morning. My name is Cathy and I will be your operator today. At this time, I would like to welcome you all to Celsion’s 2020 First Quarter Financial Results Conference Call. All lines have now been placed on mute to prevent any background noise. Following the speakers' remarks, there will be a question-and-answer session. I would like to turn the call over to Kim Golodetz. Please go ahead, ma'am.

Kim Golodetz, VP of Corporate Communications

Thank you and good morning everyone. Welcome to Celsion Corporation’s conference call to discuss its first quarter 2020 financial results. As has been Celsion’s practice and as noted by the operator, prepared remarks will be followed by a question-and-answer period. Today’s conference call will be archived and the replay will be available beginning later today through May 29, 2020 and the webcast will be available for the next 90 days on Celsion’s website. During this call, management will be making forward-looking statements regarding Celsion’s expectations and projections about future events. Generally, forward-looking statements can be identified by terminologies such as expects, anticipates, believes or other similar expressions. These statements are based on current expectations and are subject to a number of risks and uncertainties, including those set forth in the Company’s periodic filings with the Securities and Exchange Commission. No forward-looking statements can be guaranteed and actual results may differ materially from such statements. In particular, there are significant uncertainty about the duration and contemplated impact of the COVID-19 pandemic. This means results could change at any time and the contemplated impact of COVID-19 on Celsion’s operations, financial results and outlook is the best estimate based on the information for today’s discussions. I also caution that the content of this conference call is accurate only as of the date of the live broadcast, May 15, 2020. Celsion undertakes no obligation to revise or update comments made during this call, except as required by law. With that said, I’d like to turn the call over to Michael Tardugno, Celsion’s Chairman, CEO and President. Michael?

Michael Tardugno, Chairman, CEO and President

Thank you, Kim, and good morning everyone. Joining me today is Jeffrey Church, our Executive Vice President and Chief Financial Officer, who will provide a review of Celsion’s recent financial results in a few minutes. Also on the call for the question-and-answer portion is Dr. Nicholas Borys, our Chief Medical Officer. As always, it's a pleasure to speak with you. But it's hard to believe once again, I'm speaking with many of you who are confined to home as this COVID epidemic continues to impact our daily lives. I hope that all of you have remained safe and healthy and will continue to do so. We've had a great deal of exciting news during the first quarter in recent weeks from both of our lead programs. First and critically important, our ThermoDox Phase III OPTIMA Study for the treatment of newly diagnosed hepatocellular carcinoma or primary liver cancer reached the prescribed number of events in April for our second pre-planned interim efficacy analysis and I will discuss this more in a minute. Equally important, however, is the wave of ongoing positive news that we reported regarding the development of GEN-1, our immunotherapeutic currently being evaluated in the OVATION 2 study, a Phase I/II trial in newly diagnosed advanced ovarian cancer patients. In addition to our steady drumbeat of positive clinical research, as I've outlined in my letter to shareholders last month, after seeing the extraordinary volatility and signals of economic retrenchment, we have smartly taken steps in the most shareholder-friendly ways to strengthen our financial position. Jeff will talk about this more, but our goal as you know is to further assure that our cash runway extends into the second quarter of 2021, during which we expect to report several key milestone events. I'd also like to report, as I have in the past and said many times Celsion's fundamentals continue to be strong. Our advanced clinical programs are directed to large patient populations with unmet medical needs, with poor prognosis. We have sufficient cash to see the Company through several important value-creating milestones, and execution of our clinical development programs, as I said before, have been with the utmost care and with a strategic focus, all supported with extraordinarily talented and loyal staff. So, it's appropriate then to recognize our employees and include our partners, the research physicians and their staffs and our consultants and professional members of the CROs who are engaged in our studies and other development projects. We recognize them for their grace under pressure during the current pandemic and to let them know that their dedication is very much appreciated, not only by this management team, but by the medical community and the patients, who ultimately will benefit from our research programs. I'd like to start by discussing our Phase III OPTIMA Study of ThermoDox or HEAT sensitive liposomal formulation of doxorubicin for the treatment of primary liver cancer. We recently announced the study reached 158 events or deaths triggering our second preplanned interim efficacy analysis by the study's independent Data Monitoring Committee or DMC. At the time of cutoff date, we actually had 160 deaths that will be reviewed by the DMC. The meeting of the committee members has been scheduled. Data lock has been implemented. Data quality control is being conducted and reports are being prepared. We expect to report the interim results following the DMC meeting early in July. Now, as I said before, we believe that there's a very good potential for success at this analysis, but of course, it's not short, the Company remains blinded. I'd like to give you some insight into the support for our belief that the study is on track for success. Supporting our belief is our comparison of the threshold for success to the data from that the OPTIMA Study was based on. The P-value and the hazard ratio for OPTIMA success and 158 events are 0.022 and 0.7 respectively. P-value for success is 0.022. The hazard ratio for success is 0.70 respectively. This compares favorably to the P-value and hazard ratio observed for the 285 patients in the prospective subgroup from our earlier Phase 3 HEAT Study, upon which the OPTIMA Study protocol was based. This prospective subgroup from the HEAT Study demonstrated a two year overall survival advantage for patients treated with a single dose of ThermoDox, when compared to the study's control and a remarkable median time to death of more than seven and a half years. Why do I say remarkable? At the time the HEAT Study was conducted, median time to death was expected to be only 36 months. The subgroup hypothesis and trial design were confirmed by the National Institutes of Health. At the institute's request, not ours, they asked us for the data to review independently, in their independent review of the HEAT studies, 432 patients with single lesions that's over 60% of the study population. They concluded that a thesis supporting the OPTIMA trial is valid. Taking all of this into account throughout, I can summarize by saying the bar for success at this second analysis is lower than what we’ve seen in the prospective HEAT studies subgroup, a subgroup again, that was validated by the NIH using a different slice of the data. So, we look forward to receiving the DMC's recommendation on the potential for a positive outcome regardless, however, I believe the OPTIMA Study is ultimately well positioned for success, if a third and final analysis is necessary it will be based on 197 patient deaths. At that point, the bar for success will be even lower. The P-value and the hazard ratio required at the final analysis, if it's necessary, are 0.043 and 0.75, respectively, which is far lower than the values observed in the prospective HEAT Study subgroup. If it's necessary, we anticipate this final analysis will occur in the first quarter of 2021. I will again remind you also that our confidence of any underlying hypothesis supporting the OPTIMA Study is not ours long. Thought leaders from the medical community and distinguished scientists have weighed in. Conclusions from peer-reviewed manuscripts including published preclinical data supporting the OPTIMA Study, the public HEAT Study manuscript validating the subgroup results, and again, the NIH's published analysis in support of the HEAT studies hypothesis all point in the same direction. And we're further encouraged we look at the trends comparing the studies current combined timeline for disease progression and patient death rates, both of which are tracking in line almost perfectly with the prospective HEAT Study subgroup. I’ve been asked, has the COVID virus pandemic affected our OPTIMA Study? I'll point out that our plans for the DMC meeting in July include the impact of COVID-19 which accounted for a few extra weeks to ensure that all of the data input is clean and current before presenting to DMC. We discussed this during the last conference call. We took a few extra weeks just to make sure that all the monitoring, the appropriate monitoring was complete largely due to the restrictions for our monitors being able to visit the hospitals in some of the areas of the world where the restrictions were in place. Otherwise, other than this very short delay for the DMC meeting, the coronavirus has virtually had no impact on the conduct of the study or patient follow-up despite many of the clinical trial sites being in China and other countries where the virus has had an impact. I want to discuss GEN-1. As we prepare for the TMC review, we are making progress in developing our immunotherapy candidate GEN-1, which is currently being assessed in the OVATION 2 Study, a randomized Phase I/II trial for patients with newly diagnosed advanced stage ovarian cancer. In this trial, GEN-1 is combined with standard neoadjuvant chemotherapy, compared to a control group receiving chemotherapy alone. The Phase I portion involves a dosage of 100 milligrams per meter squared, which is 30% higher than the dose used in the initial Phase I study of GEN-1. This previous study included 12 patients, evenly split between the treatment and control groups, all of whom have been treated, enrolled, and evaluated. We are now preparing to move into Phase II, which will bring in up to 118 additional patients for a total of 130 participants in this trial. For those unfamiliar with Celsion, GEN-1 is developed using our proprietary TheraPlas platform technology. TheraPlas is a non-viral nanoparticle system designed for gene delivery, allowing cells to be transfected with plasmids that encode therapeutic proteins. GEN-1 includes the gene sequence for interleukin 12 (IL-12) and is administered locally to treat ovarian cancer. After administration, IL-12 results in a lasting local secretion lasting up to a week, effectively activating the immune system to combat cancer cells. The functionality of this technology, specifically the durability of the immune response for a week, enhances the repeat administration of GEN-1 in our Phase II study, where it will be given over 17 weekly cycles. This approach aims to keep the immune system active enough to target any cancer cells that may remain after surgery or chemotherapy. Initial results indicate that this mechanism is working, and I will provide more details on that later. Throughout the quarter, we have received encouraging updates about GEN-1. In February, the DSMB confirmed the safety of the 100 milligram per meter dose and recommended continued oversight to verify the safety of the maximum 17 doses, especially after interval debulking surgery as outlined in the treatment protocol for these patients. We anticipate a follow-up evaluation of the 100 milligram per meter dose in about two weeks and expect that the DSMB will recommend continuing Phase II at this dosage based on the positive safety profile of GEN-1. In March, we received news that GEN-1 was awarded Orphan Drug status by the European Medicines Agency, which is a significant achievement. This designation is not easily granted and requires evidence of both incidence data and some early-phase efficacy demonstration. The benefits of this status include 10 years of market exclusivity after approval, EMA’s protocol assistance, access to a centralized procedure for quick marketing authorization in EU member states, and potential reductions in regulatory and marketing fees. GEN-1 also received orphan designation from the FDA, which grants 7 years of regulatory exclusivity post-approval, both of which are favorable for GEN-1. Mid-March brought additional positive news from our OVATION-1 study, highlighting encouraging dose-dependent tumor response and surgical scores, which predict overall survival improvements. In late March, we reported notable progression-free survival findings comparing patients from OVATION-1 to a statistically validated synthetic control arm provided by Medidata, a leader in clinical data management. This innovative method aims to replace some or all of the control group in trials. Our comparison in the Phase I study involving 15 patients demonstrated a hazard ratio of 0.53, indicating a significant increase in median time to progression for those treated with GEN-1 compared to the synthetic control. These results are remarkable and are further supported by strong translational and clinical data from previous studies. We were not surprised by the improvement in progression-free survival, which aligns with the mechanism of action demonstrated in our prior research. We are excited about these findings and believe they provide a strong case for the FDA to expedite the clinical development of GEN-1 for patients with newly diagnosed advanced ovarian cancer, and we are currently in discussions with them. We have submitted a request to the FDA outlining our results and perspectives, and I look forward to updating you on their response in the next 30 to 60 days. Overall, we are establishing a strong foundation for what we believe could become a valuable global asset if GEN-1's development continues to show positive outcomes. However, it's important to mention that there is a modest delay anticipated for the Phase II study. During our year-end call in March, I indicated that we did not foresee significant impacts on our GEN-1 program due to COVID-19, and any delays would likely be minimal. However, after reevaluating the situation in recent weeks, we've opted to postpone the Phase II portion of the OVATION 2 Study by about 3 to 5 months. This decision was made out of caution to ensure that our investigational product meets our quality standards. We've always required our formulation scientists to be present during manufacturing runs, but due to COVID-19 travel restrictions, we couldn't have them onsite. Consequently, we decided to delay manufacturing until we can ensure that these critical resources are available; this could push back our timeline to September. It's crucial for us to have a sufficient supply of investigational product for treating patients. Therefore, we have chosen not to initiate Phase II until production can safely resume. While this is a precautionary measure and generally a good practice, this slight delay does not seem material to our overall program success, whereas having GEN-1 produced is vital. We are also seeking methods to speed up patient enrollment, so we expect that this few-month delay will have a limited impact on the study's completion timeline. Specifically, we now expect to begin the Phase II portion of OVATION 2 in early to mid-fourth quarter, rather than the second half of 2020 as previously indicated. I want to discuss our recent press release regarding the return of the $630,000 SBA loan we received through the payroll protection program of the CARES Act. We believed our loan application was aligned with the intentions of Congress and the administration. However, after some reflection and legal consultation, I realized that the guidance for loan eligibility is still changing. We've received recent clarifications from both the SBA and the SEC. To avoid uncertainty for the Company, we chose to return the funds by the deadline set by the U.S. Treasury Department. To compensate for this small financial impact, we've made some payroll adjustments and temporary reductions, and we're implementing additional measures to enhance cash flow. For instance, Mr. Church has renegotiated a deferral of a principal payment on our Horizon Venture Loan, which may more than cover the $630,000 returned to the government. Our aim, as I’ve mentioned repeatedly, is to ensure we have sufficient cash runway to reach several key milestones before the end of the second quarter of 2021, and I assure you that we will do everything possible to achieve this. I want to emphasize that the fundamentals of the company are strong. As time goes by, we are becoming stronger. Our ongoing discussions with various regulatory agencies, which have been regular, have not revealed any significant issues and have, in fact, been quite encouraging, as evidenced by our recent orphan drug designation for GEN-1 from the EMA. Our manufacturing strategy is robust, and our emphasis on redundancy during this pandemic has proven beneficial. Our product costs are competitive, and we anticipate high gross margins regardless of the market or region. For example, ThermoDox targets HCC, which is prevalent in China and Southeast Asia, areas where low production costs will enable us to maintain good margins and provide this potentially life-saving drug to HCC patients globally. As Jeff will emphasize, we have been diligent in managing our spending and cash flow for both of our investigational products. To conclude, I want to reiterate that each of our two investigational products has major market potential. The OPTIMA Study is close to yielding significant and possibly transformative results. We have complete confidence in our trials, our investigators, our collaborators, our product technologies, and, most importantly, our employees. Despite the challenges posed by COVID-19, Celsion is looking ahead with a strong focus for the remainder of 2020, a year we believe will be transformative for patients, the medical community, and our investors. I'd now like to hand the call over to Jeff. Jeff?

Jeffrey Church, CFO

Thank you, Mark. Details of Celsion's first quarter 2020 financial results were included in the press release we issued this morning and in our Form 10-Q, which we filed today before the market open. As Mark stated, in recent weeks as clinical progress has accelerated as we near the important milestone for the second preplanned interim data review, which is expected to occur in less than two months. In the meantime, we've been smart about raising capital and keeping tight control on all of our corporate expenses. We've also kept a careful eye on cost of goods while making sure we're able to tap into adequate supplies of our lead compound both in the U.S. and abroad. As of March 31, 2020, Celsion's cash, short-term investments, and interest receivable were $15.7 million. In addition, we had a receivable of $1.8 million from the sale of our New Jersey State net operating losses, which we were able to monetize in April, bringing our cash balances to $17.5 million. Our quarter-end cash position includes $6 million in net proceeds from the sale of equities during the first quarter, which includes $4.3 million from the registered direct offering of stock and warrants priced at the end of February. We have opportunistically strengthened our balance sheet to buffer against the potential for continued erosion of our share price in the face of current public market uncertainty while we complete the OPTIMA Study. Our current cash plus future planned sales of our New Jersey State NOLs will extend our operating runway through the second quarter of 2021. Importantly, this is well beyond the final data readout of the OPTIMA Study, which if needed, would occur during the first quarter of 2021. Our cap table includes approximately 29.3 million common shares outstanding and approximately 3.6 million warrants, of which 3 million of these warrants are exercisable at $1.24 a share beginning in early September 2020. These are the warrants associated with the February equity raise. Note that the share price now is above the exercise price of these warrants which may provide additional capital in the coming quarters to further extend our cash runway. With respect to future funding flexibility, we have a $75 million shelf registration on file with the SEC. We have $60 million left on that shelf. We also have a traditional at-the-market facility with JonesTrading that allows us to raise money opportunistically with no warrants and a very low commission. The use of the ATM facility is entirely under our control. Turning now to first quarter financial results, operating expenses were $4.9 million in the current quarter, which represented a 2% decrease from the $5 million in the first quarter of 2019. During the current quarter, we incurred $0.5 million in non-cash stock option expense compared to $700,000 in the prior year. Research and Development expenses were $3.1 million compared to $2.8 million in the first quarter of 2019, up its clinical development expenses for the OPTIMA Study were $700,000 in the first quarter of this year, compared to $900,000 last year. These costs have decreased as expected, as the trial has moved into the follow-up phase after full patient enrollment was announced in August 2018. Expenses associated with the OPTIMA 2 Study increased to $300,000 in the first quarter of 2020, compared to $100,000 in the same period last year. The Company announced initiation of the follow-on phase one to OVATION 2 study in September 2018 with full enrollment of the phase one portion of this trial completed during the first half of 2020. Expenses associated with research and development activities for GEN-1 and TheraPlas increased to $900,000 in the first quarter of this year compared to $600,000 last year, as the Company continued to expand its manufacturing capability and implement programs to reduce manufacturing costs for GEN-1. General and Administrative expenses were $1.8 million in the first quarter of 2020, compared to $2.2 million for the first quarter of 2019. This 17% decrease was primarily attributable to lower personnel costs and other expenses related to non-cash stock compensation, which was partially offset by increases in premiums on our D&O insurance in 2020. Other expenses included a non-cash charge of $41,000 for the change in valuation at the earn-out milestone liability for the GEN-1 ovarian cancer candidate. This compares to a net cash gain of $2.7 million net of a charge of $400,000 per warrants issued related to an amendment for the earn-out milestone payments for GEN-1 during the first quarter of last year. The Company realized $100,000 in interest income from a short-term investment in both first quarters of 2020 and 2019 and in connection with our venture debt facility with Horizon, we incurred interest expenses of $300,000 during both first quarters in 2020 and 2019. In summary, Celsion is in excellent financial shape with sufficient capital to fund operations through the second quarter of 2021. We anticipate that our net cash usage for the second quarter of 2020 will be approximately $4.3 million, which is in line with their full year budget which calls for keeping operating expenses and cash utilization at approximately $4 million per quarter. We anticipate that our net cash usage during the second half of 2020 will be approximately $7 million or $3.5 million per quarter. In closing, we believe that a successful clinical outcome for ThermoDox opens up a billion-dollar market opportunity and will result in significant value inflection points for the Company as well as our shareholders.

Michael Tardugno, Chairman, CEO and President

Thanks Jeff. Well done. Before we open the call to questions, I want to remind you all of the memorandum of understanding that we signed last year with officials from the Hangzhou Yuhang Economic Development area to establish a subsidiary in the Yuhang District of Hangzhou. The MoU, I'll remind you, provide the Company with significant financial incentives. The area for the subsidiary is located in one of China's biotech hubs, where the Chinese government has made development of advanced medical technologies that address unmet patient needs a high priority. The primary purpose of this subsidiary is to commercialize innovative cancer therapy starting with ThermoDox. In addition, China, the subsidiary will focus on all nearby developing markets including the Philippines, Malaysia, Thailand, and Vietnam. Hisun, our local manufacturing partner for ThermoDox is expected to provide an economically viable cost structure by establishing a low cost and has established a low cost of production for these geographies. Registration of the subsidiary has been completed. This subsidiary's name in English, if you see it, is Celsion Hangzhou Pharmaceutical Limited. Best point, we've begun drafting, as I said, the NDA and MAA for Europe for ThermoDox and HCC. Our goal is to have both sufficiently prepared to complete a filing within six months for the unbinding of the OPTIMA Study. For example, if we announced positive data from the second interim analysis in July, we would hope to have a filing made around the beginning of 2021. We remain active with investors, albeit by telephone during this time. We will continue to remain so as we have so many exciting milestones ahead of us this year. And with that, we'll open the call to your questions.

Operator, Operator

Thank you. At this time, we will open the floor for questions. First questioner, your line is live.

Hartaj Singh, Analyst

It's Hartaj Singh from Oppenheimer. I apologize. I did not know what that was supposed to be me. Thanks Mike. Thanks Jeff. Just a quick question. A couple of questions on ThermoDox and then on GEN-1, and by the way, congratulations for all the good work that you're doing, following through on all of the expectations that you had set and we do understand the delay COVID-19 I think that's almost every company that we know is having some kind of impact. So, on ThermoDox can you talk a little bit, you've been updating investors with the OPTIMA blinded PFS, over the last couple of years. Can you talk a little bit about how that has changed since the last interim, when you did the first interim, the blinded PFS that you've been monitoring for the OPTIMA Study? And then also could you specifically talk about while you be working, dropping the NDA and the MAA, MAA assuming OPTIMA successful. What are the specific rate limiting steps? What are the things that take those six months to get you to that early 2021 filing, assuming this interim is successful? And I just got a couple of quick follow-up on GEN-1. Thank you.

Michael Tardugno, Chairman, CEO and President

Yes, sure. Great question. Thank you very much. So, with regards to the blinded PFS data, the most recent information comes from the first interim analysis. So, we don't do the comparison except, otherwise it may not be accurate, except for presentation to the DMC. In that analysis, we saw that, when we pulled the two arms from the HEAT Study subgroup, that 285 patient prospective subgroup, median time to progression for the two arms together is 16.8 months. When we pull the 2 arms of the 556 patients, in the current OPTIMA Study, median time to progression is 17.2 months. So, they're virtually on top of each other. So, the basis for the study was the Kaplan-Meier that we generated from these 285 patients showing a two-year improvement in overall survival. We as a marker now are following PFS from that group, as compared to the OPTIMA Study, and we see that they're falling almost exactly. We recall that the threshold for success for the OPTIMA Study is lower than the hazard ratio and it has a higher P-value but a lower threshold, than what we saw in HEAT Study subgroup. So we're encouraged, we're really encouraged by that. The second and I think, I believe it was one of the rate limiting steps for filing the NDA. So, much of the rate limiting activity has to do with engaging with the FDA, Hartaj. So tomorrow we were to have a positive result from the DMC, we would immediately place a call to the FDA. We would let the FDA know that, we have a positive outcome and would like to have a pre-NDA meeting with them.

Hartaj Singh, Analyst

Great, Mike. And then just on that, specifically in terms of just the I know, an NDA or an MMA would have three sections, right, the preclinical CMC and clinical. So, I assume your preclinical and CMC section should be good to go, I mean, the OPTIMA trials are going for a while. It's really the clinical section and the results from the OPTIMA second interim that you'll need to discuss with the regulators, correct?

Michael Tardugno, Chairman, CEO and President

Correct. Yes, I should have mentioned that. So for the most part, the preclinical and CMC sections are complete. So, in the narrative for the critical section, we haven't drafted. It's just a matter of populating it.

Hartaj Singh, Analyst

Okay. And then on GEN-1, I was noticing that you have those good hazard ratios against the synthetic control study, which is really interesting. I think the future of clinical trials will see more of those. But one question I had was, why did you see such a big dispersion? When you look at the hazard ratios and it's reflected in the P-values being 0.1 and above 0.1. The hazard ratios were dispersed from like a little as 0.15 or 0.16, all the way up to 1.7. Why was that happening? Is it just small numbers or what was the reason for that?

Michael Tardugno, Chairman, CEO and President

Yes, so I'm not sure I understand the question completely. The hazard ratio that we just discussed was 0.53, 0.53. The P-value is…

Hartaj Singh, Analyst

The confidence intervals around that are pretty wide, right. So, that's how I'm asking, where's that coming from?

Michael Tardugno, Chairman, CEO and President

I think it's largely due to small numbers. I'm Dr. Borys Nick, do you have any insight?

Dr. Nicholas Borys, Chief Medical Officer

Yes, that's right, Mike. When I talked about this with the statisticians from the Aspen group, they mentioned that the P-value shouldn't be the main focus in this type of analysis, but rather the hazard ratio.

Hartaj Singh, Analyst

Great. For future reference, since I know the relation to is designed with a hazard ratio of 0.75, can you explain, based on this synthetic control arm study, why some patients showed a poor hazard ratio? I'm concerned because while your overall hazard ratio is strong, if there's significant variance, it would be interesting to understand why those patients with suboptimal hazard ratios performed that way, if that information is available.

Michael Tardugno, Chairman, CEO and President

Yes, Nick, do you want to fill that?

Dr. Nicholas Borys, Chief Medical Officer

Yes, I think that's why it's important to work closely with the FDA. And currently, our next phase study is a 130 patients study which will address, all the variability that we see in a biological system, such as a cancer. And that's where I think you'll start seeing tighter P-values at a stronger HR.

Hartaj Singh, Analyst

Great, all right. Thank you. And I understand that. My last question is. I appreciate all the questions. It's just the delay, which is completely understandable. Michael, we've seen it with a lot of other companies, in fact, most of our companies. But one question I want to have is your manufacturing lots. Can you just talk about how many lots you need for the Phase II? Where are you with that manufacturing campaign? And then why specifically do you want to have the formulation scientists on site? I mean, will this be an ongoing issue, meaning, if OVATION 2 successful, maybe you get quick therapy. I mean, will you always need to have formation scientists at the manufacturing site in order to be able to produce these lots? And thank you.

Michael Tardugno, Chairman, CEO and President

Yes, we produced the clinical supplies in smaller batches to ensure we can scale within FDA limits. We can increase the clinical batch size tenfold, provided that the batch is well-engineered, validated, and its quality is established through registration studies. The challenge lies in the infrequent production of clinical supplies. If we operated like a regularly produced product, I wouldn't hesitate to produce commercial products without oversight. However, clinical supplies are made less frequently, and there are often minor adjustments to the batch records during manufacturing, especially in Phase I and Phase II. While not all companies prioritize this, I believe it's essential to have someone onsite during the production of infrequently manufactured products. Manufacturing staff are exposed to various processes, and over time, they can lose some of their knowledge—whether it’s after six, nine, or twelve months. Having our experts present helps ensure we don’t lose product integrity due to this infrequent manufacturing, especially for GEN-1, which is particularly crucial. It usually takes about a year to schedule a batch for any manufacturer or sponsor using a plasmid or gene therapy. If we were to use plasmid in the finished product that didn’t meet our standards, we’d have to waste it, causing significant delays and costs for the next batch needed for the clinical trial. We see this as a risk, and even if it’s a small one, it’s a risk we prefer to avoid.

Hartaj Singh, Analyst

Yes, no, Mike, that makes a lot of sense. And I actually lodged you for it. I think that's a very smart on your part. I'm very prudent. I'm agreeing. Thanks for all the questions we're looking forward to July. Take care.

Michael Tardugno, Chairman, CEO and President

Thank you so much, Hartaj.

Matthew Cross, Analyst

First off, I guess, I'll start with OPTIMA given that it sounds like the next time we may be talking about this program that you may have a positive result here hopefully. And so just wanted to get kind of a reiteration of your plans regarding commercialization, I know you've previously spoken to wanting to handle things in the U.S., internally, and partner out in places like Europe and China. Just wanted to get kind of the latest on that positioning given, taking into account COVID and this kind of ever changing landscape? And then second was one GEN-1. Was hoping you could kind of remind us of any plans that you might have to look at longer term follow-up from the phase one portion of OVATION 2, maybe to confirm some of the benefits of maintenance dosing and potential read through to the phase two portion, I guess, particularly because maintenance dosing is the more novel exploratory parts to speak OVATION 2 to relative to OVATION-1?

Michael Tardugno, Chairman, CEO and President

Thank you for your questions. I’d like to begin by discussing the commercialization of ThermoDox. I do not foresee the COVID situation impacting our commercial plans. After a positive study outcome, we anticipate that it could take 12 to 14 months to launch a product, even for large companies, assuming that we receive a fast track priority review from the FDA or other regulatory bodies. I hope that the medical community better understands and manages the COVID situation moving forward. While we face challenges, ThermoDox addresses a significant unmet medical need in oncology. By the time this drug is approved, there will be nearly a million cases globally, particularly concentrated in China, which represents a key market for pharmaceutical companies. China has about 50% of the global cases of this major unmet medical need, with inadequate therapeutic options for newly diagnosed patients. This creates considerable interest in our drug for a specific population. Our business models are conservative, and as Jeff mentioned, we are looking at a blockbuster market exceeding a billion dollars. Therefore, I believe we will have no trouble finding suitable partners. We expect to have options with partners who possess strong capabilities to launch this product at competitive prices while ensuring quick market penetration and robust sales and marketing efforts. Nevertheless, we are also preparing to market ThermoDox ourselves in the United States, as we believe we can effectively manage it there. It’s important to note, however, that we will prioritize what is best for our shareholders. If a licensing opportunity arises that reduces financial risk and enhances market penetration, while also benefiting our investors, we will take that into serious consideration. At this stage, our expenditures have been limited to some market and pricing research, as we are being cautious with our cash. With a positive outcome on our plans, we intend to be more aggressive in developing our marketing strategies for the U.S. market. However, we may end up discovering an unexpected but effective strategy for launching ThermoDox in the U.S. Well with regards to your question on GEN-1, we have talked about maintenance therapies in which I assume what you're talking about is, continuing to treat patients, following the full cycle of treatments in the current protocol and some schedule, some frequency to continue to recruit the immune system over a longer period of time. I think that's a very interesting strategy. But we haven't explored it with any sufficient consideration at this point to present anything. I mean, Nick, you're on the line. Do you have any thoughts on how a maintenance program beyond the 17 doses might look like for patients in our study?

Dr. Nicholas Borys, Chief Medical Officer

Yes, I agree. It's a very interesting opportunity for GEN-1. We're already proving that the drug has a very nice safety profile, both in patients that have bulky disease pre-surgery, and now we're proving post-surgery that the drug has a nice safety profile. So, it is very well-positioned for looking at as a maintenance therapy. So, if the data that we're establishing through seeing our synthetic control the data from the first phase one, if all that keeps on lining up the way we're seeing it right now, there are further opportunities, as you suggest.

Michael Tardugno, Chairman, CEO and President

And I'd just add to Nick's point. Nick has been instrumental in developing a kind of a home health care approach. We've been working with a third party who pre-prepares ID type demonstrations for home administration. So, just thinking about it more broadly, that this strategy really fits nicely into a commercial potential where patients would be required to administer this GEN-1 add up, some frequency throughout the course of the rest of their lives perhaps.

Raj Kumar, Analyst

Hi, thanks for taking my questions. So first, regarding the following the 158 patient tests, what are you seeing in terms of further follow-up? Are you seeing events as expected? And if you need to stop the trial for efficacy, how long will this patient continue to be followed up and are there any changes expected because of the COVID-19 situation?

Michael Tardugno, Chairman, CEO and President

Yes, I think you're asking if the trial is successful. Will we stop the study and stop following patients? Is that the question?

Raj Kumar, Analyst

Yes, kind of sense of whether you stop following the patient or if you follow how long you will be following? And whether there will be any changes because of this COVID-19 situation.

Michael Tardugno, Chairman, CEO and President

Yes, I don't see COVID impacting this or our OVATION studies at all, frankly. But that's a question that we'll ask the FDA, I think our point of view is that we will continue to follow patients for survival, and I think that only strengthens our hand. But Nick, do you want to weigh in on that?

Dr. Nicholas Borys, Chief Medical Officer

Yes, this is Nick Boris. And I agree that we're going to take the counsel from FDA. And also remember, as Mike mentioned earlier in the presentation, we are also looking to submit in China and Europe. And the Chinese authorities may want to see continuation of some of their patients or other regions as well. So, we're going to leave that option open to whatever the best sciences and whatever the regulatory authorities are indicating to us.

Raj Kumar, Analyst

And with regard to GEN-1, once you start manufacturing, at what time point do you think we'll be comfortable to reinitiate the Phase II?

Michael Tardugno, Chairman, CEO and President

Well, as soon as we start manufacturing, I don't see any real potential of manufacturing failure. It's just a matter of having a person in the facility to provide the guidance, the institutional knowledge, to assure that the setup is correct at the times. There's some time dependencies and temperature dependencies that we don't want to be overlooked. So as soon as we are ready to manufacture. So we can put a person in a facility, it could be as early as September. We will initiate the Phase II program.

Raj Kumar, Analyst

And you also talked about continuing the screening of the patient. And so what do you expect in terms of bolus of patients at that time point once you think of resuming the Phase II?

Michael Tardugno, Chairman, CEO and President

We have developed a model for recruiting patients and have gained some experience in this area. The model indicates that we can anticipate recruiting about one patient per month for each site. Currently, we have around 19 active sites, and we aim to enroll up to 25 sites in the U.S. and an additional two in Canada. Due to the ongoing COVID situation, we are proceeding cautiously with the initiation of the remaining sites. However, once we restart Phase II, we expect all activated study sites to begin patient recruitment right away. Our model suggests we will average one patient per month at each site. In the meantime, we want to maintain momentum and engagement with our investigators, as losing their enthusiasm could pose a significant challenge. Therefore, Nick and his clinical operations team are organizing an investigator meeting just before launching Phase II to reiterate the requirements and review the protocol, ensuring that none of the critical information is forgotten. This is crucial, especially since our patients typically have a limited life expectancy, often less than three years post-diagnosis. The meetings we hold have shown that the enthusiasm generated among investigators for our product is remarkable. Our goal is to keep our investigators motivated, and we have a solid number of sites prepared to proceed. We will add more sites as soon as manufacturing starts. There is an aspect we need to address regarding our discussions with the FDA: we hope to replace some organically recruited control arm patients with synthetic control arm patients. Specifically, if we could substitute 25% of the control arm with the synthetic group, it would significantly lessen the number of patients we need to recruit, speeding up the trial's completion. This is a key focus for us.

Mitch Landgraf, Private Investor

Thanks for taking calls from individual investors. I'll try to be brief. One question, Mike, in regard to the few extra weeks that were wisely taken when you're getting making sure that all the information was correct for the submission for the OPTIMA trial. Just curious, was data already locked? Or is there a chance that those few extra weeks actually provided a little bit more time of separation of the two arms which I think would be good in our case?

Michael Tardugno, Chairman, CEO and President

Yes, the answer is yes. A few extra weeks allows for more maturity and additional patients to be included in the evaluation. Unfortunately, a few more patients have passed away. Therefore, the number that the DMC will be reviewing, as I mentioned in my prepared remarks, is 160 patients.

Mitch Landgraf, Private Investor

Yes, that's actually bodes well for even slightly increased likelihood of success at this interim, coming interim which would be awesome. Finally, not a complaint, just some feedback, I'm not sure if there's a technical issue on the website. I can just share from my own direct experience and also that of other individual private retail investors. There seems to be a difficulty with getting any kind of response to non-material just every day, individual investor, retail investor questions that are being submitted through the web portal or phone calls to Mr. Church. And again, that's not meant to be a personal or anything that it's feedbacks that company that somehow that communication channel isn't working. I do appreciate that you take individual investor questions on these calls. In the past investor-friendly thing you used to do is to limit questions even from financial advisors than that to two to afford the opportunity for everyone to get in. That also would be appreciated. So didn’t know if you want to address that or just as a quick feedback to the Company, that's something and somewhere in that communication change, there's the breakdown.

Michael Tardugno, Chairman, CEO and President

Well, I was not aware of any particular problem. We'll look into it, Mitch. Thanks for pointing it out.

Mitch Landgraf, Private Investor

Thank you as well, best to all.

Operator, Operator

Thank you. Ladies and gentlemen, this concludes today's teleconference. You may now disconnect.