Q2 2020 Celsion Corp Earnings Call
[music].
Please standby.
Good morning, My name is Kashi and I'll be your operator today.
At this time I would like to welcome you all to sell she owns 2022nd quarter financial results Conference call.
All lines have now been placed on mute to prevent any background noise. Following this speakers remarks, there will be a question and answer session at that time, you May Press star one on your phone to ask your question. Please keep in mind, if you're using a speaker phone you must release your mute function to allow the signal to reach our equipment.
Again that star one to ask a question during the Q and a recession at this time I would like to turn the call of rich to Kim Golodetz. Please go ahead.
Thank you and good morning, everyone. This is Kim Golodetz with L.A.J. welcome to sell see on Corporation's conference call to discuss it second quarter 2020 financial results as husband Cellphones practice and as noted by the operator prepared remarks will be followed by our question and answer period.
Today's conference call will be archived on the telephone replay will be available. Beginning later today through August 28, 2020, the webcast will be available for the next 90 days on cellphones website.
During this call management will be making forward looking statements regarding cellphones 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 Cove at 19 pandemic. This means results could change at any time and the contemplated impact of covert 19, Ansel sounds operation.
<unk> financial results and outlook is the best estimate based on the information for today's discussion.
I also caution that the content of this conference call is accurate only as of the date of the live broadcast August 14th 2020.
So see on 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 Mark Michael toward doing young so see I'm, the chairman CEO and President Michael.
Good morning, everyone.
So to speak with you, particularly now.
Today's Jeffrey Church, or executive Vice President and Chief Financial Officer.
Right.
Recent financial results in a few minutes.
Also on the call for the Q1 and Diane.
Dr. Nicholas Force.
Second to watch President and Chief Medical Officer.
We reported a great deal of news during the second quarter in recent weeks.
Programs.
With what you're focused on Thermodox phase III.
Okay.
For the treatment of newly diagnosed and solar carcinoma.
Well known as a primary liver cancer.
Because we recently held the conference call to address the unexpected results.
Adjusting futility.
From a damn sees second preplanned interim efficacy analysis.
I'll touch on where we are with the Optima study and our analysis in some brief comments later in this call.
But first I'd like to focus on the state of positive news that we've announced regarding the development of Gen. One our gene mediated immunotherapy.
Evaluated in the ovation to study.
Having successfully completed a phase one.
Ovation too 'cause entered phase two is now recruiting patients who the newly diagnosed with advanced ovarian cancer.
I'm pleased to report that we initiated the phase two portion of this trial in July.
Five months ahead of the schedule that we announced earlier this year.
Oh plans for ovation to include an aggressive recruitment program.
With 10 investigator sites currently active.
Definitely active and 10 more being activated over the next few months, we anticipate completing enrollment of approximately 105 patients over the next 12 months or so.
Additionally, we are strongly consider and replacing.
For set of the control arm, that's about 25 patients using it propensity match population of control patients from other randomized ovarian cancer studies. This novel synthetic control arm approach will reduce trial costs.
As well as the time to complete enrollment.
The value however, the synthetic control arm goes beyond cost in time as many of you know recruiting patients into a randomized study is concerning for patients for the most part.
Joining a trial in order to receive the investigational drugs.
So with only a 50 50 chance of this outcome the patients into control arm can be quite disappointed.
Well I'd like to review the trial ovation too.
Hi, This is particularly for those of you are new to cross sell Shadow vision to is it to our one to one randomized study.
80% powered to show up 33% improvement in progression free survival PFS is its primary endpoint.
As you know, it's being conducted as an open label study.
So we'll be able to provide clinical updates as they become available throughout the course of treatment.
These updates will include overall response rates according to resist.
And surgical resection scores.
Both her secondary endpoints in the study in both our prognostic for overall survival. So have a pretty good idea of gen ones treatment effect is the trial progresses.
The study design calls for Gen. One to begin buying with Neoadjuvant chemotherapy.
Neoadjuvant chemotherapy is the.
Standard for a standard of care for advanced disease, among patients, whose cancer burden is judged to great to be immediately surgically removed without related complications.
Treatment, our patients will be compared to a control arm of Neoadjuvant chemotherapy alone.
They were doing chemotherapy is designed to shrink tumors in dry them off. These are tumors that are coffee and with a a great deal of societies or are we like fluid.
The dry them up the goal is to improve the surgical outcome.
And the real goal here is for an hour zero resection.
That being a virtually complete removal of all disease.
With no disease from the surgical margins.
Following this debulking surgery to patient want to go through cycles of edge of it chemotherapy.
Get up to nine weekly cycles of genuine treatments. If the patient has been randomize to the treatment are.
Our goal with its overall Gen. One treatment regimen is to recruit a high level of immune system activity over a six month.
Period.
The result, being a delay in progression that's our expectation.
Because we know clearly that progression portends a poor prognosis.
Well again for those of you will maybe new I'd like to a review Gen one technology and mechanism.
Gen. One is engineered using our proprietary theraplas technology platform.
Theraplas is a non viral nano particle gene delivery system that provides a means to transfected cells with DNA plasmid quoted for proteins of therapeutic value.
Unlike viral vectors are traditionally used for delivering a DNA plasmid. So I'm like viral vectors think that can only be administered once.
Theraplas is not subject to the neutralizing activity of the patience immune system.
So the beauty of this technology is that it does not carry the risk of viral vectors and it can be administered over and over again, making ideal for tight treating cancer treatments and particularly immunotherapy.
The course of multiple treatments are typically required for effective results.
The first drug on this theraplas platform is gen. One.
Gen. One incorporates a DNA plasmid quoted for the pro inflammatory protein.
There are cytokine interleukin 12 or aisle 12.
John one is administered local regionally local regionally into a body cavity.
As a such as the at the abdomen for advanced ovarian cancer treatment.
It's can find local regional activity avoids the systemic toxicity associated with the use of recombinant IL 12.
Systemic toxicity is the reason why I IL 12 cannot be administered intravenously and is not in widespread use.
Our approach invented by our scientists in our research center in Huntsville, Alabama provides an elegant solution.
That significantly improved vial twelves activity at the started the tumor well mitigating any toxicities.
So following administration sell transfection has accomplished resulting in a safe persistent durable local affective secretion vial 12 for up to one week.
I'll just take one when it's all about a 12. It was first recognized in the 19 eighties at the end age laboratory of Dr. Stephen Rosenberg.
It was then recognized as a potent immune system modulator and by recruiting a robust immune response, it was well known for being effective means to fight malignancy.
John One is our amazing solution to the decades old safety problem.
It has the potential to provide a very powerful cancer therapeutic.
So what are we stand with program and why are we still encouraged to during the second quarter, we now to the de SMB and its final recommendation unanimously supported proceeding to phase two with a higher dose of 100 milligrams per meter square.
The SMB concluded that genuine safety profile is satisfactory and that patients can be treated with up to 17 weekly doses.
During the course of treatment of about six months.
And no dose limiting toxicities were detected during this period.
The results so far of and based on small numbers I'll admit but impressive nonetheless.
So let me give me an example of the 15 patients treated in phase one.
Nine were treated with John one at a dose 400 milligrams per site per meter squared plus the vitamin chemotherapy.
And six were treated with you neoadjuvant chemotherapy alone.
Meanwhile, all 15 itself successful resections or tumors seven out of nine patients are 70% of the Gen. One treatment arm AD and our zero resection.
Which indicates as I said earlier microscopically margin negative resection in which no gross or microscopic tumor remains in the surgical margins.
This compares favorably to the control arm or three of six patients for 50% hit in ours or restructuring.
And our earlier phase one ovation one study at a population of patients with the same inclusion criteria is the phase one portion of the ambition to study that I just spoke of.
When we pull results from these two studies.
The data suggests dose dependent efficacy when combining gen one with new edge when chemotherapy.
Statistically significant to the small numbers. These findings were reinforced with a significant improvement in progression free survival. When we compared study patients to a propensity score matched synthetic control arm of similar patients from prior studies.
We talked about the synthetic control arm approach.
In the comparison that it can provide during our quarterly call in may.
And we reported having done that a hazard ratio 0.53, or doubling of time progression small numbers again, but approaching statistical significance in particularly impressive.
When taking into account the supportive in previously pug published translational data so tissue samples taken from our prior phase one study clearly demonstrating a gen. One is profoundly active.
In clinical data from our other phase one experiences showing dose dependent tumor responses.
But he can see with me you conclude with me to synthetic controller in comparison is very promising.
In a compelling bases from which to launch our phase two trial.
[noise] I'd like to conclude on Gen. One by saying that we're building a foundation for what could be very important asset worldwide.
Sure John one continue to show efficacy that is being noted in early work.
Oh I will suggest though we have watch to look forward to finally I'll also note.
So we have received orphan drug designation from both the U.S. ft, and European Medicines agency, which of course enhances the value of Gen. One in particular.
Orphan designation received from the you earlier this year provides for tenures market exclusivity in the United States. Similarly, orphan drug designation provides seven years market exclusivity following an NDA approval.
So before we turn to Thermodox I, just want to reiterate what they said about our financials during our recent call and reassure you.
Yeah, we are taking appropriate steps to ensure that the company is well positioned regardless of the outcome of the Optima study.
As I said.
We are we have begun to eliminate all non essential thermodox expenses, including Unfortunately, some headcount reductions.
And expect to save some $8 million to $9 million over the next 18 months versus our budgets.
Our plans will ensure that we have capital sufficient to complete enrollment of the ovation study. We're looking forward to reporting periodically on this phase two study as it progresses.
Oh now I would like 13 turned that thermodox.
A lot of work is going on at the company and through our advisors.
Oh, we still do that have a complete picture, but we're working on it.
Remember that the Thermodox is our heat sensitive liposomal formulation of doxorubicin for the treatment of primary liver cancer in July we reported that the independent data monitoring committee for the Phase three Optima study recommended that the company should consider stopping the study, but they left the decision up to us.
This recommendation was made following the DMC second Preplanned interim safety and efficacy analyses the DMC as analyses found that the pre specified boundary for stopping the trial for futility.
And foundry is zero point.
900, that's a futility foundry was crossed with an actual value of 0.903.
However, the P value of 0.5 to four essentially a flip a coin.
Well. This analysis provides a high level of uncertainty as to the actual hazard ratio valuable therefore in an unusual and I I might say an unprecedented step.
The DMC left the final decision of weather stop the study up to the company.
As we've been reviewing the data I'd say in hindsight, there appears to be some wisdom to the DMC his recommendation, but you know that yet the jury's still out.
Our review of the Unblinded data is ongoing.
And we recently provided an update disclosing that we will continue to follow patients for overall survival, noting that the unexpected and marginally cross futility Bronder foundry suggested by the Kaplan Meier analysis may be associated with the data maturity issue.
Maybe associated with it stayed at maturity ish.
Well, we also noted a 26 consecutive patient deaths represented exclusively in the second analysis remember this was the second an interim analysis exclusively in the second interim analysis, we have 26 consecutive debts.
Behave far differently from the balance of the patients who died of that as of that date.
Let the number of treatment us compared in the treatment arm does compared to the control arm more than doubled.
Completely reversing the favorable trend in the treatment on seen before and after.
The cohort of 26 does.
Well, it's 26th consecutive desk occurred between September 2019 in March 2021, we remove them from the data for the interim analysis.
So the outcome suggests.
The optimal studies overall survival pattern is similar to this prospect of heat study subgroup upon which the Optima study is faced.
But the approximate comparable time point.
Moreover.
Following the second interim analysis, there were eight additional patient deaths reported in a three to one ratio control arm to treatment arm.
Patients.
Which further supports our concern for data maturity.
So at this point, we are now at 168 deaths that calculates to a hazard ratio of 0.875 [noise].
[noise] or you know when I look at it and the statisticians would probably given you know.
You know a little Luxfer on this.
A hazard ratio 0.875, given where we see the control arm.
This is an improvement of about eight months in time to death or where the controller.
I had an insignificant amount.
Well, we also note that Optima study sites in China, Vietnam, which were enrolled over 30% of the patients in the trial.
Joining this study approximately 12 and 18 months respectively. After the trial was initiated.
The Kaplan Meier curves for both geographies demonstrate a potential maturity issue when compared with the behavior of the heat study sub group and the other Optima study testing site regions.
The China sites in particular.
Sean negative Kaplan Meier curve yet.
56% improvement in the treatment arm over the control arm in the median time the debt.
We Vietnam sites, Similarly show a marginal Kaplan Meier benefit if at all.
You had a 45% improvement in the treatment arm and the median time to death.
[noise] now we believe our that this dichotomy must be reconciled.
Most probably with longer follow up.
What has to be done so before we can determine the studies direction.
Well, we are engaging experts and statistical analyses for clinical trials looking specifically for proportionality issues.
<unk> between the Optima and the heat study Kaplan Meier projections, and we're conducting sensitivity test that may provide insights related to the of the observations that I just mentioned.
They finally and very importantly, we have sent the clinical trial data all of it including CMC data to the National Institutes of health for their independent analyses.
Including all C.T. scans, they're being prepared it takes a little bit of time.
So that the NIH can independently evaluate progression free survival.
[noise] I caution you depending on the trends noted during the overall survival follow up period, we may choose to discontinue the study at any time.
At this point, however, I can tell you definitely.
I can't tell you definitely have sorry, I can't tell you definitely well we plan to do what I assure you that.
We will be transparent transparent about our plans.
As I said in our August 7th press release, the trial outcome as predicted by the second interim analysis may not change.
Fortunately, we may be faced with futility.
[laughter] and as I said is unlikely as it may be.
In the event that we sit substantially beneficial clinical results, while we continue to monitor patients.
We will carefully review our options with an FDA and of course, the other 13 regulatory agencies around the world.
And have allowed the optima study to be conducted the ongoing support from our research investigators and clinical advisors demand.
[noise] excuse me.
Just want to say before I turn this over to Jeff that.
It can be sure that Celsius fundamentals continue to be strong.
Probation two studies directed to a large patient population.
With unmet medical needs and poor prognosis.
Our manufacturing strategy is solid.
[laughter].
As being built with redundancy.
Continue to execute our development programs at the utmost care.
Our relationship with regulatory agencies, both in and outside the United States continue to be exemplary and encouraging.
We have cash sufficient.
With smart spending and cash management and expect to deliver on our promises, but those comments I'll turn it over to Jeff Jeff. Thank you Michael detailed themselves. The on second quarter 2020 financial results were included in the press release, we issued this morning, and then our form 10-Q, which we filed today before the market open.
As of June Thirtyth, 2020 sales against cash and short term investments were $25.5 million, which includes net cash proceeds of $1.8 million from the sale of or unused New Jersey, net operating losses or enter wells.
We fully anticipate that an additional $2 million, if I use New Jersey, Anna Wells will be sold in the second half of this year and this will further increase our cash reserves on a non dilutive basis bottom line. We believe we have sufficient capital resources to fund our operations into the fourth quarter 2021.
We're currently evaluating our venture debt facility with horizon, including retiring all or restructuring a portion of alone. This will not impact our projected cash operating outlook. During the second quarter 2020, net cash used for operating activities were $7.9 million.
This compares to 10.2 million in the comparable prior year period, a 22.5% decrease.
With respect to future funding flexibility, we have a $75 million shelf registration statement on file with the FCC with $45 million remaining we also have a traditional aftermarket facility with jonestrading that allows us to raise money opportunistically with no warrants and at a very low commission.
Turning now to our second quarter Pan out for the quarter ended June Thirtyth, twentytwenty, including noncash expenses.
Does he had reported a net loss of $5.3 million or 18 cents per share. This compares to a loss of 5.9 million or 29 cents.
Per share for the quarter ended June 32019, operating expenses were down 14% from stuff 5.7 million last year to 4.9 billion in the current quarter.
Research and development expenses were $3 million compared to $3.6 million year ago, our clinical development costs for the phase three optima study or $600000 in the second quarter. This year down from 1.2 million last year and that was due to the completion of the patient enrollment.
In August of 2018 cost associated with the ovation to study increased modestly to about $200000 into second quarter is compared to $100000 and the same period last year.
Other costs related to clinical supplies and regulatory support for both of our programs increased to $2.3 million into current quarter from $2.2 million a year ago and this was driven largely by planned manufacturing costs for the Gen. One clinical supplies needed for our phase two portion of the ovation to study.
General and administrative expenses were 1.9 million in the second quarter. This year that compared to 2.1 million for the same period. In 2019. This 11% decrease was primarily attributable to lower professional fees [noise].
Other expenses included a non cash charge of $300000 for the change in the valuation of the earn out milestone liability.
For the Gen. One ovarian product candidate the company incurred interest expense of $300000.
During the second quarter this year in connection with their venture debt facility with Horizon. This compares to $400000 in the comparable prior year period, we anticipate that our net cash uses for the third quarter of 2020 will be approximately three and a half million dollars and this is aligned with our revised spending plans.
Which call for keeping operating expenses in cash utilization at approximately $15 million for the full year 2020, the cost of continuing to follow patients in the Thermodox trial. The Optima study are minimal and are largely behind us in closing we believe that further progress with gen. One in late stage are very.
In cancer with David were to be reported periodically will provide additional opportunities for building shareholder value now like to turn the call back to Michael.
Well. Thank you Jeff is always a very good summary of our financials.
Well, we appreciate that so operator, we'd like to now open the call to questions. Thank you at this time, we will open the floor for questions if you'd like to ask your question. Please press star keep all the other one team that was star one you're using a speaker phone. Please make sure that they get the handset to allow your signal to reach our.
Let me again that was star line.
Our first question comes from Jason Kim of Oppenheimer and company.
Hi, good morning, Thanks for taking your question.
I'm sorry, just actually your question Hi, I just had a question on Jan one <unk> walk us through the improvements made the manufacturing process than any future Glenn the further refine the process.
Oh, that's good question Justin.
We know we art strategy, all along for all of our investigational products, including Gen. One.
All right include redundancy.
Particularly now since the many of these contract manufacturing organizations, particularly those that are in a quite sophisticated like the parental injectable drug manufacturing facilities are being acquired in consolidated.
By venture capitalists.
Creating somewhat of a oh look awfully.
And Oh of course in that environment, you always have to worry about supply and price.
So we've taken the initiative phone as we've talked about earlier.
To work aggressively both inside the announced in the United States and outside or with some.
Chinese based manufacturers.
To reduce the cost of our major components for Gen. One.
There are two or the Oh, the polymer that's used as transfection factor.
And the plasma.
And I can I can tell you with confidence the cost of our.
Plasmid <unk> has.
Then reduced by almost an order of magnitude.
As a result of the work that we're doing to develop our competitive.
Quality manufacturing system for the plasmid.
So we're seeing cost come down both with our current manufacturer European based and the as a result of this work that we're doing to finalize the process for plastic manufacturing.
Outside the United States in China.
Paul we've taken that the a step again and redundant approach.
To provide a two sources for the polymer again, one in China, one in the United States Interestingly enough competition works.
All the cost anymore and by the way we've been successful with the transfer to the Chinese or using that polymer and current manufacturing for investigational product.
For the phase two portion of this study.
But interestingly enough as I said the competition works it looks like the U.S. manufacturer.
Not only will reduce their costs, but they may be substantially lower than the yet Chinese based manufacturing and finally, the third component is finish finishing its phil.
And finish and Lyophilization.
Scana second manufacturer that has become our primary source of this product.
In it's China again, a high quality manufacturer that currently ships product to the United States for commercial sale.
Recently.
While expanding its facilities at some of the state of the art facilities recently evaluated by the FDA and other regulatory agents.
And in an island by the way off of the cost of China, not even near or close to any of this.
Oh covert virus pandemic.
That's a concentrated in China.
Their cost of manufacturing is [noise].
Okay, and almost an order of magnitude lower than the supplier that weve qualified in United States.
So our goal here is to have a redundant system and competitive manufacturing low cost because you know that our treatment paradigm for Gen. One requires a large volume of plasma.
I want patient will receive up to 500 vials worth of product.
Oh over the course of a six month period, so getting the cost down not only is important to.
The company's financials, but it's very very important to ensuring that we have a commercially successful product.
Okay, Great Great Hey, I guess on maybe just shifting gears could you talk a little bit about the optima continuation and sort of you know is there a threshold of observation that might be meaningful and you know what sort of timeframe might be a better appear you too.
So the potential for data maturity issue.
Yes, so we're looking at this on a number of fronts.
And I I hesitate to give you a date.
Indeed, the easiest the answer with the just to continue follow patients until we have a sufficient number.
That.
Makes it very very clear that is studies either going to result in a oh, a failed trial or there's a potential for a positive trial.
Oh, the death rate in the study is full will.
I'll be the determiner for that.
As it appears now we could have an answer sometime in the fourth quarter, if we only take that stuff.
Oh, yes, that's that we're taking are looking looking at some of that discount annuities are the I pointed out earlier.
Although it could just read immediately give us some hope that the this data maturity issue is very real and it's predictable a statistical basis.
Well if in that case, so if we concluded that the sensitivity analysis.
Has a identified the these discount annuities Oh, we may take the in the immediate steps to begin to meet with the.
<unk>.
Not to discuss the direction of the study.
And ER and then we'll of course will provide feedback to.
The investment community as soon as we know something from the agency.
That's pretty much or strategy.
Okay got it I mean, maybe just a final question before a husband BQ I'm not going with conversation with regulators have have you had any initial conversations regarding the study and you know just what the perception of the positive result might look like in light of the Unblinding of this study.
She Erie repeat the first part of that.
Oh, just initial feedback with regulators on on sort of optimizing the potential for upon the read out given the data has been unblinded.
Yes, and we have not had that conversation with the regulatory agencies are we'd like to know more we'd like to have a little bit better understanding of some of these wells I'm going to call. This continuity, so like others stand of a little bit more and have a better idea of the trajectory should the trajectory of the trial.
Before we meet with the ages.
Got it understood. Thanks, so much and I'll hop back into queue.
Thank you.
Our next question comes from Tomorrow, as both Lane capital markets.
Thank God running a.
Good morning, Thank for taking my question.
And.
With regard to the I'll try and the basin from China Flash we have.
<unk>, but frankly they don't.
These patients make up the whole try and [noise].
And the.
I didn't sound, so greenpeace exceeded the third on before and how does dot com bad with EUR eight basins. So late on how do you see there devolving.
Yes.
We can give you some out some good detail on both those questions 30, 37% of the patients enrolled in the study [noise].
Were enrolled by the Chinese and the Vietnamese investigators.
And about an equal amount a few more patients from China hammer in Vietnam and log.
And as I pointed out there seems to be a dichotomy here.
Between the median time that Uh huh.
Median time to death.
And one thing capitalmark firms are suggesting.
I mean that that.
He just to believe that the data is quite immature so.
Two two regions.
Oh with regards to 26 basis.
No we are at the study.
Had been tracking I think as we mentioned in earlier pet.
A press release on a positive vein the separation of the two arms appeared to mirror.
Well, what we had been seeing in the heat study subgroup that prospective subgroup of 285 patients.
In it the first interim analysis and we did you know we did as much as we could to compare the same time points.
[noise] first interim analysis, we're looking at a hazard ratio of <unk> 0.78.
Subsequently a you know so that was at a 128 to us.
The next look is a 160.
So there are wrong.
32 patients enrolled.
Additional patients enrolled.
Oh for the second interim analysis.
Those 32 26 consecutive patients showed a complete reversal.
Solve the.
Treatment arm versus the controller.
The vast majority I believe it was a 17 out of 27 patients for 26 patients.
Who had died had died in the treatment.
The complete reverse.
Oh edited and can find time period, and you look at the Kaplan Meier I mean, it's just very hard to understand <unk>.
Oh, how that could happen, it's a phenomena I mean, it may be maturity related.
Bob but we're also looking at other causative factors.
So when we take those 26 patients out of the analysis <unk>.
For the most part the Kaplan Meier curves are very much on track with what we would have expected.
When we compare to the heat study subgroup cap of workers.
[noise] 11 point I'll make then the.
Subsequently as I mentioned in my prepared remarks subsequent.
To the interim analysis, there have been eight more patient deaths reported.
Oh and they are those patients are in a ratio of for every one of the treatment arm debt. We have three controller, that's actually taking to the a hazard ratio from where we had said earlier 0.90320 point he said.
<unk> five.
[noise] slowing down so this eight basins, we ought be this blade does that do you have got off because that's down from China, how do we have and also in the future events.
He is the expectation you start you know where this basin thought from that's going to drive that I love the differences.
Yes, so you know it could be a regional issue I, maybe that's what you're getting too.
It also maybe a time dependent issue at this baby.
Phenomena that we're seeing is a function of a a period of time during much these patients for being treated or follow.
So maybe regional and maybe time independent we don't know that's some of the sensitivity work that we have to yet complete.
As far as where the eight patients come from I don't off the top of my head you have that they were primarily from the China and Southeast Asia.
Area.
Okay and in terms of Jan one.
Well I know a you know <unk> deviation is the expectation.
Due to the global 19.
And how do you guys aren't any.
Yes, so I believe Dr. Boris is on the phone and that we can now we've we've been very careful about this code that issue isn't that.
Nick you are are you in a position to be able to answer that question. Please.
Yeah. Thank you.
In terms of coated 19 act on the.
And the ovation to study a we've been discussing is quite extensively with all of our investigators and our lead investigators. They are you there aggressively seeing a lot of patients that meet our study our junior they're anxious to get into the study and the way.
We're designing for would coal but is that we're going to be following ASCO guidelines.
For treating patients during this cold period, [laughter] thing that for coal bed and taking cobot precautions throughout so I'm not see any major protocol deviations a there might be challenges to meet your occasional visits being missed but the impact on the endpoint.
I would expect to be minimal.
Okay, and Dom South that and many time Alice is the low low watermark kind of.
What is the expectation from this analysis by the an age.
Okay. So the NIH Kumar head they took a different look at the data.
And.
And was.
Published by the company you recall, our our I'll look at the subgroup.
Oh, it was confined to those patients who had more than 45 minutes of.
Ah heating time.
You know age conducted a side by side analysis looking at the entire and excuse me intend to treat population.
For patient single lesion patients those are the ones they couldn't measure the heating time with precision.
And they developed an algorithm that shows the relationship between longer heating time and survival.
So will we expect from the NIH since we do have this concern for data maturity.
Is to a plug this data into their model.
Oh into it and by the way they were I'm, sorry, I missed a very important point here or they were evaluating heating time as a function of tumor volume.
Oh, and so we want them to plug it into the model they may have to make some modifications.
But.
Our expectation is that this model will either confirmed for us.
That we should wait that there may be a data maturity issue.
Or could it could confirm.
That the futility analysis has a high potential of being correct.
But that's a that's really what we're expecting from the age. We also separately are looking for all the PFS.
We'd like to know in their model looking at PFS weather.
Or not the PFS that we ours.
Currently seeing from the investigator reported events.
So is accurate.
And I take that Nick again, I interest on the phone Oh. Please can you address the use of the radiology and evaluating a patients and the overall study by the NIH.
Yeah.
As Michael stated.
And our H is particular interest was to take the different you the data different studies, meaning they did a volume based analysis. So as Michael said first question is going to be is for them to reproduce the same analysis that they did in the heat study and apply it to the Optima study and and we'll see.
<unk> herbs or similar or different and that will help us determine whether there's any kind of anomalies to be seen there and then going from there you know that we'll look at investigator rated DFS verses Central lab rated defense that would be done Bobby by the NIH to see if there's any significant differences to.
Thing so the data will be a treasure trove of how to really take a look at the optima data and compared to what we learned in the heat study.
Thank you.
Our next question comes from <unk> private Investor.
Hi, good morning drilling.
Good morning, many warning morning that <unk>.
Okay. Thank you raised your call 'em Andre cancer patient advocate and cellphone investor I want to accrete agreed and commence efforts on the company who work with all the regulatory bodies. However, as possible to hopefully bring this drug market, we know where the fact that at the same. We also know with effect from me studying from patients and investigator anecdote.
That it works and I would hope that these various countries would want a drug like that a treatment novel treated like this available because they're constituencies.
My question, probably more for Dr. Borys senior anomalous.
Data from a 26 patients totally different than our entire experience with thermodox or do you.
No. This time period from December Tomorrow, and that it was in southeast Asia <unk>.
Well, obviously, we'd want to question, whether it's always nice had an effect and I was wondering if there's any thought other possible called Valerie.
No no hypothermia itself, the radio frequency ablation or the interaction of an anthracycline.
On the immune system.
Possibly is having some interplay in the treatment arm with cold.
And whether the company does no we're not whether any of those patients were positive or possibly Perry.
Because of all partially because of complications of Kogas nicely.
That's a great question I'll turn that over the Doctor Bourse thinking that Mitch.
Thank you for that question Yeah, Let me just basically say that you know all possibilities are being evaluated right now I'm certainly cope it was an important consideration during this study and as we were collecting data.
And we were always keeping a careful watch on that make sure there wasn't much of an intact and we are reviewing the causes of death for these patients that were interviewing the investigators to see it's a they give us more insight into that so your points are well taken and Oh, we have been considering.
All possibilities are you know with this data.
Thank you so much I wish you all well.
I think taken Mitch.
And as a reminder, if you'd like to ask your question. Please press star can't So that's a one key.
Our next question comes from Jets importing.
Shareholder.
Good morning, gentlemen, thank you for holding the call.
A couple of questions.
Firstly I asked you for a statistical protection.
Yes.
Balance of the Das catered to the end of the study to be treated one.
The reason that's half Dan.
What hazard ratio would that produce.
Yeah, I don't know that we can give you that number off the that exact number off the top warehouse, but if it continues at this rate I believe we would be looking at a successful trial judge.
Okay second when he was a question of clarification.
Yeah.
Yes, well language that points out the dichotomy between the Uh huh.
Second 26 grouping of Das and de experienced a percentage improvement in overall survival.
The overall survival numbers presented in the press release.
I'm off.
Some heat from both combined.
[laughter].
Yeah.
So [noise].
[laughter] like that.
Over 50% increase in overall survival in.
On your Vietnam in over 40% of any other.
Got it got to kinda kinda <unk>, so what you're referring to is this.
Oh parents dichotomy, when we talk about a 50% improvement it could actually it's a 56% improvement in the treatment are.
Compared to control over the median time to Doug Hi that comes from the Optima study those patients.
Ah that were treated in China.
So we take all of the Chinese patients.
We plot them on a Kaplan Meier curve it goes through that very complex algorithms.
So we see the.
Actually a negative result.
For the treatment arm crosses the control arm pretty early on.
In a small number of patients, but still concerning on the loss.
And then we'll but when we look at each of the patients median time to debt her time to debt and we take the median.
Oh, there's a contradiction for the median kind of debt improved by 56%.
In spite of this Kaplan Meier curve that shows a negative result.
[noise]. So those are specific to answer your question specifically those comparisons the cap a marker.
And the overall survival median are coming from the Optima study.
In those regions in Vietnam and in China.
Okay, that's very encouraging new here one more question.
I know this is speculative.
And you may have already entered at it.
Yes, I mean.
When the studies to complete you wound up with a hazard ratios.
78.7 need instead of <unk> 0.75, which is excess that's still a very astute states will improve survival and there's no other treatment.
Is it reasonable to assume.
Right.
Your discussions with the various approval arms would still consider that you'd be successful long enough to go to market.
[noise]. So there's a question that though we we've we kinda debate quite a bit so the.
So then the and is very.
Importantly here Johnson.
You can have a hazard ratio that looks very good but not statistically significant because you don't have enough number of patients to.
Uh huh.
Have a a confidence of up P. equaled <unk> 0.05.
So those are the two interplaying factors here, but to your point.
[noise], if we see a 0.78 or maybe even something closer to the 0.8.
I think a given what we've seen in the treatment arm coming into control arm.
Median time the debt so far as approaching 60 months.
And then we will all be demonstrating a very a substantial improvement in the median time to death with Thermodox.
And we believe that this deserves a discussion with the FDA.
In May we named May not be well received.
And we may have to have a discussion with the and with that hold at committee in that regard, but Oh, we do believe that the magnitude of effect, that's really what we're talking about.
That the magnitude effect is very very important in new York consideration of whether or not thermodox should be a commercial product, particularly given the product safety profile [noise].
We know that the Thermodox is going administered now to a little over 700 patients and the safety profile for this drug is quite manageable.
Quite manageable.
Thank you very much for your answers.
I have a great day.
Okay your interest [noise].
At this time, we have no further questions.
Did turn it back to today's presenters.
Thank you very much operator on the for all of the do it who are on the call. A we certainly appreciate your support you know attention and your interest in the company.
You can see we're going through some a challenging time.
However, I want to point out that the Gen. One.
As a great potential in ovarian cancer, please as you're thinking about the company's dose to dismiss that by any means.
And as we continue to evaluate.
The Optima data as I said earlier, we will be very transparent with our analysis and where we Oh, what we expect to do as a result of that analysis.
So.
We're continuing to be driven by our commitment to these therapeutics.
While we know that are these are great potential to make a difference.
Oh for patients and clinicians and their families of cancer patients.
We are committed to that Ah. Thank you very much for your time and we look forward to keeping you apprised of our.
Progress thank you.
Thank you ladies though.
Oh. Thank you. Thank you, ladies and gentlemen, [laughter] teleconference. You may now disconnect.
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