Q3 2022 Plus Therapeutics Inc Earnings Call
[music].
Okay.
Yeah.
Good afternoon, ladies and gentlemen, welcome to the plus Therapeutics third quarter 2022 results call before we begin we want to advise you that over the course of the call and question and answer session forward looking statements will be made regarding events trends business prospects and financial performance, which may affect plus therapeutics.
Future operating results and financial position, all such statements are subject to risks and uncertainties, including the risks and uncertainties described under the risk factors section included in plus Therapeutics annual report on Form 10-K, and quarterly reports on Form 10-Q filed with the Securities and Exchange Commission from time to time.
Plus therapeutics advises you to review these risk factors.
Considering such statements plus therapeutics assumes no responsibility to update or revise any forward looking statements to reflect events trends or circumstances. After the date. They are made it is now my pleasure to turn the floor over to Dr. Marc Hedrick, plus therapeutics, President and Chief Executive Officer, Sir you may begin.
Thank you Josh good afternoon, everyone and thank you once again for taking the time to join US today as we provide an overview of recent business highlights and discuss our 2022 third quarter financial results joining.
Joining me for the call today is Dr. Norman the France, our Chief Medical Officer, and Andrew Sims, Our Chief Financial Officer I.
I'll begin the call by reviewing our recent corporate and clinical progress before turning the call over to Andrew to review.
View, our financials and Dr. A France will be joining us for Q&A.
The company made perhaps the most progress ever in a single quarter that I can remember.
First in September 2022 results from the company's phase one respect trial for recurrent GBM was presented at the European Society for medical oncology meeting in Paris by Dr. Andrew Brenner the trial pie.
In summary.
21 patients across six dosing cohorts received one to 22 <unk> of radiation and <unk> six to $8 eight milliliters of volume.
The mean tumors treated in those 21 patients was eight three milliliters in patients had a mean of $1 seven recurrences and very poor prognostic factors.
All of our current glioma patients had computerized treatment planning and up to four intracranial catheters placed in each patient.
Each patient received a single administration of 186, arnelle by convection enhanced delivery and whole body Planer Spect imaging on days 128, following treatment assess dosimetry and radiation distributions patients were followed for safety.
Radiation delivery and overall survival.
The mean absorb radiation dose to the tumor was 271 gray with negligible systemic exposure.
There were no dose limiting toxicities and the overall safety profile was favorable.
Patients were stratified by mean absorbed radiation dose to the tumor.
Those receiving greater than 100 <unk> mean.
So a therapeutic dose and equals 12 in that group had a median and mean overall survival of 129, 7% and $106 four weeks, respectively with four patients still alive in that group.
Patients receiving less than 100, Gray mean absorbed dose essentially a sub therapeutic dose.
And was equal to nine and that group had a median and mean overall survival of $22 three and $24 six weeks, respectively. None of those patients remain alive.
Kaplan Meier analysis of patients receiving mean absorbed dose greater than 100, gray or therapeutic dose versus those with less than 100 gray non therapeutic dose showed a statistically significant difference in overall survival saving favoring those that received a therapeutic dose. The study concluded that a single administration of <unk>.
<unk> hundred 86, arnelle by convection enhanced delivery and recurrent glioma patients with poor prognosis is feasible safe and potentially effective and increasing overall survival when a therapeutic dose of radiation is delivered to the tumor.
Our recommended phase II dose of $22, three militaries and $8 eight milliliters was selected for patients with tumors of up to 20, <unk> or 20, <unk> leaders and the phase II trial planned for later this year and ill discuss the phase III plan further in a moment.
Okay.
Also during Q3, we received guidance from two type C meetings with the FDA on the next steps in our program for the development of our lead investigational drug Rhenium 186 nano episode.
The first type C meeting focused on the Companys current good manufacturing practice or cgmp clinical and commercial manufacturing process for 186 are it out.
The FDA indicated agreement with our proposed application of cgmp guidance for radio Therapeutics small molecule drug products and life somewhat drug products for 186, Arnelle in support of our ongoing and future Glioblastoma clinical trials manufacturing scale up and commercialization we.
We expect that this FDA feedback we will apply to 186 are now used in other clinical development programs, including Leptomeningeal metastases and pediatric brain cancer.
I am happy to report that we have now completed all key manufacturing objectives for cgmp 186 are in our production to support ongoing and planned clinical trials and 2022 and beyond.
During a separate clinically focused type C meeting the FDA and plus agreed that the respect GBM clinical trials should proceed to the planned phase III.
The key focus areas of ongoing clinical investigation in the recurrent GBM development program will be.
Further dose escalate exploration, including both increased dosing ie advancing to cohort eight and study of multiple doses.
And also collecting additional safety and efficacy data to inform the design of the future Registrational trial.
In addition, during the meeting there was agreement that in a planned future Registrational trial overall survival should be used as a primary endpoint.
The company and the FDA also agreed to hold future meetings to consider the use of external data to augment the control arm and the Registrational trial facilitated by our orphan and fast track designations.
Earlier this month, an IND amendment was submitted regarding this plan and that sits with the FDA as of today.
The planned phase II trial design, we will incorporate the following features.
Cohort six dose will be use which is also the recommended phase two phase two dose from the from cohort six as mentioned, which will be $22, three <unk> and $8 eight milliliters of volume the.
The study will enroll up to an additional 31 patients at five planned sites, including the current three sites plus an additional two sites, which are currently in process of coming online.
Subjects will remain on study until disease progression by raynaud criteria.
Recognizing of course, the potential for pseudo progression that complicates the use of rain a criteria. We are working on the imaging analysis today to be able to resolve that.
That issue or potentially a pie decision that's in the best interest of the patient.
The primary endpoint as mentioned will be overall survival. Following single administration secondary endpoints will assess the safety Tolerability objective response rate partial response serious treatment emergent adverse events up to three.
And free survival and progression free survival at six months.
We will make known the final details pending further feedback from our IND Amendment, which is with FDA as mentioned.
I will now pivot to discuss our Leptomeningeal metastases program.
Our team was very honored to learn in the third quarter that we had been awarded a $17 6 million dollar product development Research funding award from the cancer Prevention and Research Institute of Texas also called Secret. This.
This award will cover the majority of the development cost, including funding for up to 150 enrolled patients for our Leptomeningeal metastases program over three years.
For those that you aren't familiar with secret secret is the second largest global public funder of cancer research in the world after the NIH with $6 billion allocated by the state and.
And also of note plus 17 6 million Grant award is the largest and the most recent secret review cycle and one of the top 10 largest all time awarded by secret.
History.
Besides the.
The asset the award as a material source of non dilutive funding that significantly strengthens the company's balance sheet and extends our expected cash runway Andrew.
Andrew will provide some greater perspective on that momentarily.
While this is all exciting news let.
Let me let me just.
Back up a bit and recap our current development plan, starting with our rhenium 186 analyte for some development.
As I mentioned the company recently completed key manufacturing objectives for cgmp 186, or <unk> to support ongoing and planned clinical trials in 2022 and beyond.
And Pete drug of sufficient quality and scale to enable the completion of all further clinical investigation, including for ongoing and planned phase II and phase III clinical trials.
In patients with Glioblastoma, Lep dimension metastases, pediatric brain cancer, and really any conceivable future disease targets.
Having access to cgmp drug is an important milestone as we prepare to transition from early to late stage clinical investigation in commercialization.
Relatedly I am pleased to announce that the World Health organization has approved <unk> 186 Obispo Meda is the generic name for 186 are enel.
As required this generic name will be used in all future IND.
And NDA submissions and brand name development and related go to market planning is currently in process.
So here to forward will we will we will now use the 186 iridium Obispo maiden name in lieu of the 186 are Enel research name.
Regarding the GBM program based on the positive safety profile and promising efficacy signals observed thus far and with clear feedback from the FDA.
Most importantly, we intend to move into phase II in the U S. By the end of 2022 and that effort will be funded by us to a significant degree as it has in the past by the U S NIH national cancer Institutes.
Second pursuant to FDA guidance, we intend to continue the dose escalation cohort eight and Thats, a $16 six milliliter volume and $41 five military infused dose that's an approximate 33% increase in both volume and fused in radiation dosage.
Notably, we recently received <unk> approval to advance to cohort eight from cohort seven.
He further escalations in volume or dosage will be based on observations from cohort eight.
But again the overarching goal here is to dose escalate until we reached dose limiting toxicity or the maximum practical dose.
The ongoing phase one is intended to explore further dose escalation on large tumors as we have yet to observe.
Dose limiting toxicities and we also continue to work to further optimize the delivery and dosing approach.
This week at the 30 <unk> annual Congress for the European Association of nuclear Medicine. The company presented data, which indicates that the direct administration of radium Obispo Meda is safe in patients with recurrent GBM with no dose limiting toxicities and 24 total patients.
That's the total patients treated thus far and I refer you to that press release for.
Further information.
So now onto our Leptomeningeal metastases or <unk> development program that trial is a multicenter phase <unk> dose escalation study to determine the maximum tolerated dose safety and efficacy.
Of 186, Peridium Obispo Meda.
<unk> is an end stage fatal complication associated with advanced cancers that infiltrate the fluid line structures of the central nervous system or left them in <unk>.
The incidence of <unk> is growing with better local cancer care and there are no FDA approved therapies.
Standard treatment includes external beam radiation therapy to the affected sites followed by chemotherapy given either orally intravenously are often administered twice weekly directly into the CSF space.
In the third quarter of 2022, the company initiated enrollment of cohort two that is a doubling of the dose over cohort one and the respect <unk> dose escalation trial, we anticipate completing enrollment of cohort two by the end of 2022.
And cohort three by the end of Q1 2023.
<unk> one.
186, or any of our estimated was successfully delivered without dose limiting toxicities and the independent.
Respect.
The SMB approved the plan to move forward with cohort two.
By the way also at the annual Congress of the European Association of nuclear Medicine. This week the company presented from the podium data demonstrating that <unk> hundred 86 rename of estimated.
Administered through an intraventricular catheter at $6 six millet curious in five <unk> achieved absorbed dosages.
Of one point excuse me 18, seven to 29 gray to the ventricles and cranial subarachnoid space, which was well tolerated with no treatment related adverse events greater than grade one.
Additionally, all three patients in the cohort were observed to have prompt and complete 186 <unk>. They made a distribution throughout the CSF.
That was durable pass one week and very well tolerated all patients showed a decrease in CSF cell count by Microfluidic Chamber assay after treatment ranging from a decrease to 45% up to 92% which was also durable.
Now regarding our development program in pediatric brain cancer. The company is on track to meet its objectives to submit an investigational new drug application in the fourth quarter of 2022 for.
What will be called the respect PBC phase one dose finding an efficacy study of 186 for indium Obispo meda for pediatric brain tumors and that will be submitted in conjunction with our lead academic institution.
Hospital of northwestern University in Chicago.
Finally regarding our novel in licensed radio Embolic micro particle technology called 188 are in L. Band, We have completed the technology transfer phase and key CMC feasibility studies and we are on track to submit a pre IND meeting and have that meeting by year end.
This reserve above biomaterial embolic technology, coupled with our highly potent radiotherapeutic in this case 188, iridium, we can target almost any solid organ tumor in the body using standard interventional radiological beans, and leverage the breadth of the human vascular system.
Selectively reach almost any tumor radium.
<unk> 188, nano Episome biodegradable alginate microspheres is a next generation fully resorbable technology that solves many of the existing problems with current radio embolic technology that had been in the market for many decades and represents an existing total addressable market of about $1 3 billion.
The company will initially focus on developing the band technology as the next generation radio embolic therapy for liver cancer.
Liver cancer is a rare disease with an increasing annual incidents globally and a five year overall survival rate of only about 20%.
So with that summary, I'll turn the floor over to our Chief Financial Officer, Andrew Sims, who will review the financials Andrew.
Thank you Mark good afternoon, everyone.
Please refer to our press release issued earlier today for a summary of our financial results for the 2022 third quarter ended September 32022.
As of September 32022, cash and cash equivalents were $20 3 million compared to $18 4 million as of December 31, 2021.
The company believes the combination of current cash.
Committed grant funding in conjunction with existing discretionary capital sources secures our cash runway through 2025.
Cash used in operations for the nine months ended September 32022 was $10 7 million compared to $7 7 million in the same period.
For the previous year.
The main year over year changes between the third quarters of 2022 and 2021 are as follows.
<unk> revenue of 73000 was reported related entirely to see print.
Total operating expenses for the third quarter of 2022 were $5 2 million compared to $3 5 million for the third quarter of 2021 the.
The increase is due primarily to the following.
CMC related activities to develop and produce cgmp quality drug material as well as expenses associated with the development of the synthetic control arm platform for future clinical trials.
These projects and related spend have now been substantially completed.
To a lesser extent, an increase in legal IP and other general corporate expenses.
Interest expense decreased from 232000 in the third quarter of 2021 to 173003rd quarter of 2022.
This decrease reflects the continued principal paydown the commenced in November 2021 on the company's Oxford debt.
Net loss for the third quarter of 2022 was $5 2 million or <unk> 19 per share compared to a net loss of $3 7 million or 28 cents per share for the third quarter of 2021.
I would also like to take this opportunity to provide an overview of the positive impact on cash in the financial statements of the $17 6 million <unk> grant to develop their respective <unk> indication.
As disclosed in the September 22nd 2022 press release. This growing covers the three year period, ending August 31 2025.
With the funding tracking the company proposed clinical development plan.
The total planned crunch for year, one is $3 7 million increasing to $6 7 million in year, two and $7 2 million in year three.
Let me walk you through the cash impacts of Ctrip and the process to access to $17 6 million.
Secret initially fund, 50% of the first year budget, which for pluses just under $1 9 million.
First for this $1 9 million has been submitted and we expect to receive this funding within the next one to two weeks.
One is greater than 90% of this initial $1 $9 million is utilized the next request will be submitted.
<unk> typically takes less than two weeks to advance to requested funds.
The design of the funding is to ensure the company is not out of pocket for crop related expenses, which will obviously be substantial.
Quarterly reports are submitted summarizing payments and development progress during the previous quarter and.
Secret has the right to conduct an annual audit of expenses.
These are typical requirements, especially for such substantial levels of funding.
As plus incurs costs the costs will be reported in our income statement under the research and development line item.
And the matching grant will be reported as revenue and the revenue line on the income statement.
Seven on page 11 of the Form 10-Q outlines the accounting and finance.
<unk> for the ground and associated project specific costs.
Now I'll turn it back to Mark.
Thanks, Andrew.
Before we move to Q&A, let me just summarize key milestones anticipated for the remainder of 2022.
We plan to.
This trial of one of the six William Obispo Meda.
For recurrent GBM as mentioned.
We plan to present updated data from the respect GBM trial, the <unk> trial and forthcoming pediatric brain cancer trials at the society for Neuro oncology annual meeting an education day.
That will be held in Tampa in November .
At presentations and one poster presentation there.
We'll complete cohort two of respect <unk> phase <unk> dose escalation trial in Q4.
We will submit an IND for this study 486 rhenium obispo made in patients with pediatric brain cancer has mentioned and we plan to complete key CMC in IND, enabling studies for the band program.
And complete our related pre IMD meeting as planned all on track at this point now let me turn it back to Josh for Q&A session, Josh let's.
Questions. If there are any.
Thank you as a reminder to ask a question you will need to press star one one on your telephone please standby, while we compile the Q&A roster.
Our first question comes from Justin Walsh with Jones trading you May proceed.
Hi, Thanks for taking the questions and congrats on all the progress.
First one it's great that we're seeing decreases in the CSF tumor cell count in the <unk> patients, but it looks like the cell counts have rebounded and at least some of these patients treated so far I know that we're in the early phases of dose escalation here and repeat dosing might be key but how do you think we should think about it.
Interpreting these readouts is there reason to expect some potential benefit from a temporary reduction in the CSF tumor cell count or do you think the major takeaway is that we're just potentially seeing some anti tumor effects and we need to wait a little longer for clinically meaningful readouts.
So I'm going to take.
Yes, I appreciate the question.
Divide that up I'm going to take a little bit I'm going to refer.
Dr <unk> of France to talk about our recent recent patient experience.
No.
First of all one of the one of the great aspects of the <unk> indication is the ability to check tumor.
Tumor markers the first of which is the the tumor cell count, which we do over time in all of these patients and it's it's heartening to see it even the lowest possible dose of what I would consider almost up.
Maybe just north of a homeopathic dose we're seeing decreases are pretty significant magnitude in all patients every patient had a reduction so that's important.
Number two is that there is a duration of that effect. So it looks like it's lasting for four a month.
We know from the dosimetry data that radiation is there for at least a week probably longer seems to mirror, what we've seen in GBM patients. So there's a duration of effect there is a meaningful effect even at a very low dose.
Now the question is.
Yeah.
Is that the right tumor market to look at.
And the answer is maybe.
But we are actually working with the principal investigator.
Grant's been filed to look at additional tumor markers and evidence of radiation damage and our plan is to look at that with or without the grant and Theres a lot of opportunity here to look at tumor markers.
And this and this clinical model and then finally I would just say.
We don't know at this point, what these tumor cell markers actually mean inductive of France.
I think mentioned.
In Barcelona as recent meeting one of the patients had a pretty significant improvement in clinical symptoms and that was the one that had the lowest.
Decrease in tumor cell, maybe you want to comment on that a normal well I'll start with that and thanks Mark.
And I think it's a great question by the way and I'll start with the last patient Mark just alluded to.
One caveat that Mark had mentioned this patient was heavily.
Feature fecal chemotherapy. So in fact his cell counts were much higher and our continued therapy and he didn't tolerate that chemotherapy came off of it.
But we maintained that that benefit but more importantly, this unfortunate patient wheelchair bound.
Quite had lots of pain other other lab neurological manifestations unfortunate manifest eight Madison manifestations and <unk>.
After the therapy within a few days his doctor who was the Pi at the particular site reported a patient was.
It was out of the wheelchair.
Walking, albeit with some assistance, but minimal assistance and as painless significantly decreased.
Okay Eric.
And your point about well the duration of the benefit I want to really emphasize Mark's point.
We're at the absolute lowest dose.
We will.
We will continue the other cohorts surety in cohort two and doubling it will double again in cohort three so it's really crucial to see these next cohorts and we will have a fourfold range of doses that will give us a pretty good idea the.
The ultimate Registrational trial, which we don't know how that will look we need obviously this dose escalation trial.
May be on overall survival there may be another surrogate endpoint depends on FDA discussions and you raised a point that we've already talked about internally the best way for this.
As you know is devastating complication and it may make more sense to have multiple doses to make it a controllable.
Devastating complication because these really impact.
These patients' quality of life they get this leptomeningeal complication.
And even though there is some chemotherapy that works.
They will discontinue it just because of the tolerability. So multiple doses makes sense and that will be one of our analysis.
Thank you got it thanks.
A couple more questions if that's all right.
Sticking on the trial design.
I believe that the respect <unk> trial is enrolling <unk> patients with any primary tumor type I am wondering if you think that it's possible that that 180 <unk> could receive a broad <unk> label upon potential approval or do you think primary tumor type will play an important role in maybe limit the bread.
For the label down the line.
Good question as you probably know FDA, almost always was that disease specific indication.
And currently we and by the way, although all solid tumors have the potential for leptomeningeal complications breast and lung by far are the most common etiologies based on that and what we know now we will certainly drive those which will represent probably the most significant.
Commercial application.
<unk>.
We will discuss with FDA, depending on the findings in these first patients will be all comers and we can show with other tumor types that there potentially is a benefit we'll have that conversation with FDA.
But it may make regulatory sense, maybe regulatory Italy required that we be disease specific and we have already selected those that are the highest incidents contributors.
But there are others.
Theres other grant capabilities, we have for further funding.
I like your idea of a broad indication, but we are the most highly regulated industry and the planet and FDA has their criteria to repeat myself, it's usually disease specific.
Got it thanks, and one more for me I am just wondering if you can provide any color on what we might expect to see at the <unk> Conference. Obviously, there isn't a lot of time between now and the EBITDA.
The conference. So I was just wondering if you do you think that maybe we'll see one or two more patients are just what we can kind of look forward to you there.
Yes.
I wouldn't expect.
Transformational news I think the goal here will be the.
Provide incremental.
Incremental news and I think the what.
So you can understand the rationale behind it is.
We're very much in the marketing phase we're going from a.
Asleep be academic study.
Two.
Try to going into phase two in GBM and trying to accelerate enrollment in <unk>. So part of what we're trying to do here is get the word out to the neuro oncology community.
We will have an investigator dinner will bring in new sites into these trials very soon both the GBM trial and the <unk> trial as well as the pediatric brain cancer trial will have an opportunity to talk with them 101, one on one and to go into detail on the data so that the.
There are multiple reasons to present at a meeting like this and I think this is less about.
Presenting significant changes in the data will be incremental data, but but to be able to really get the word out to the community.
And I think thus far the community has been very accepting but we've got to go through the work to get that news out and Dr. La France would you like to add anything.
You are right the tie between the meeting is close.
Of course, they would.
The likelihood of a few of our patients is there and we'll share that importantly data. We've had is remarkably consistent both in the GBM as we get to these higher.
Efficacious dose levels and what's remarkable for these earliest doses in.
Every patient has behaved the same way they've had decreases in CSF tumor.
Accounts.
And their distribution and the durability of distribution and their tolerability have all been right.
Right on target and in exactly the same.
So usually you see a little more variability, but one of the strengths of Radiopharmaceuticals. Once you have some of this proof.
And preliminary data.
And particularly the way, we're giving it we don't expect.
We expect more of the same of course, we've got to develop that data but.
A few more patients, but we already have a very good signal.
Got it looking forward to it regardless, thanks for taking all the questions.
Thanks, Jeff and thank you.
Thank you one moment for questions.
Our next question comes from Edward Woo with <unk> you May proceed.
Yes. Thank you for taking my question I just wanted to clarifying question you mentioned that with the grant can your current source of cash you have enough cash to last through 2025 does that include all three clinical trials costs.
Okay. Thanks.
Thanks, Ed I appreciate the question.
So.
The short answer is yes, yes it does.
I'm still.
Still pinching myself from the kind of recovering from the announcement of the <unk>, which is obviously kind of a.
<unk> for the company so we're in a position today, where.
The lead indication GBM.
By the NIH.
A second indication.
Sure.
Leptomeningeal metastases.
The phase II for up to 150.
Then the third indication pediatric brain cancer, we expect to fairly slow enrollment for that is typically.
Kind of.
Six to 10 patients per year at most and I think what I would add is.
On that.
We do not yet have funding or grant funding for that indication, but I think as mark and I have said.
Previous earnings calls.
The management team is focused on.
Looking for non dilutive funding sources.
And given given the success that we've had we will continue that approach and we take that very seriously.
Okay.
Great well definitely congratulations for all of the guys that graph is definitely a game changer.
Sure.
Prevent vessels from getting too excited or whatnot, but what are the opportunities and other grants that are out there are there other stuff or is this pretty much maintained that you guys were focused on are there other grant and opportunities for stuff like that.
Yes, there are Ed Park.
So kind of look at it.
And Kevin two axes, one axis is to work with our academic collaborators.
To develop grants to study.
Maybe not maybe not specifically to.
Fund clinical research, but also potentially to the.
To fund side projects and were working on one specifically as it relates to.
Looking at.
Novel Biomarkers in the LTM.
And the <unk> trial, so that would be kind of one area of pursuit another area.
Suit us.
Frankly.
One of the reasons, we decided to move the company, Texas, because we felt like there was a real opportunity there to leverage.
Awful lot of state support for cancer funding, Fortunately were able to land.
A nice amount of support early on we know of one company that has three separate grants.
So so.
Think we've cracked the code on that I think we have ability to go back and get more.
Furthermore, I think theres some opportunities corporately beyond secret in terms of NIH.
Department of energy. These are radiopharmaceuticals nuclear energy. So there's some opportunities there so that that comes an area of significant interest and we've actually just brought on a real superstar Dr. Melissa Moore.
Director of clinical operations, but she has a Phd from UCLA and molecular imaging and knows this space very well so that brings an added dimension to to the team.
Great well, congratulations and wish you guys. Good luck. Thank you.
Thanks, Ed.
One moment for questions.
Our next question comes from Sean Lee with HC Wainwright you May proceed.
Good afternoon, guys and congrats on all the progress.
My first question is on the repeat dosing.
It's something that you've been mentioning for the last couple of quarters. So I was wondering whether that's something that you look to try in the upcoming phase II study or is it going to be.
A separate cohort in the current phase one study or do you plan to another but a new study carefully.
We don't see.
Yes.
Hi, Sean Thanks, it'll be a separate study.
The.
The protocol has been approved by the FDA.
You can imagine for repeat dosing.
Based on recurrence and.
And so with her.
A relatively small number of patients that have that.
We received the treatment so far this being relatively recent development.
That will it will be sporadic but.
Part of the rationale here is to explore safety of multiple doses to get the FDA comfortable with that.
The.
The other way to the other way to look at that is.
Are there instances where.
Maybe there are some areas of the tumor that we don't cover for whatever reason.
For example.
If the tumor hasnt very unique or difficult morphology.
It may be difficult to address it with three or even forecast or as we get the bigger tumors.
The morphology.
And the size of the tumors, such driving delivery efficiency, so having a.
Having a protocol in place that allows us to potentially go back and treat a patient.
Our dosimetry evaluation post operatively clearly shows that there is a nice potential recurrence.
That we would want to treat that so I think I've mentioned in previous call. This idea of getting really long term survivors here as possible, but it's likely because of the pesky ness of eradication of all the malignant cells is so difficult that we might have to provide some sort of.
The treatment strategy, either two or three years later, when the well treated tumor actually recurs or maybe early in the postoperative phase after a single administration, where.
Maybe the tumor was so difficult we just couldnt cover the whole thing reliably so thats the approach, but that'll be separate.
Two the phase two the phase II data is strong enough to support.
Alright.
The moving that forward as a single administration.
Trial for small to medium sized tumors.
And can we think can succeed on its own as a single administration.
I see thanks for the clarification.
With regards to the LMS study.
Inflammation destiny is likely going to favor a more.
Im going to any specific indication is there any one that you are leaning towards at this point.
Just to be clear is that in the <unk> indication youre speaking about there'll be breast and lung.
Great question and yes.
And for <unk>, the most prominent demographic contributors are breast.
And loan.
Right behind them are Gi, some head and neck.
Another area that would be potentially of great interest.
Would be melanoma, and we all know those melanomas.
The old way.
But for focus and the way we have separate funding. So we already have funding in place for the two biggest contributors to it.
Two leptomeningeal metastases.
Maybe if I could just add.
Right.
The.
The way the current IND is as written and we plan to continue this.
Would be that we will have all comers in the first nine patients and then after nine patients will be restricting down to breast and lung correct.
Alright, Thats all I had thanks for answering my questions.
Thank you Sean.
Thank you and as a reminder to ask a question you will need to press star one on your telephone.
Our next question comes from Juan <unk> with B Riley you May proceed.
Hi, This is Brandon on for you on.
So you mentioned the Earth.
But the.
The GBM study.
With a large or complex morphology.
We were wondering what percentage of patients you see to have those like very large tumors or the morphology that might be too complex to address with a single dose.
Thanks for the question.
The our current phase II will proceed at the doses March Mark mentioned.
We are putting a conservative volume limit at 20 cubic centimeters.
You would probably get a little bit more tumor volume with that of our data is showing that about two thirds to three quarters of all the glioblastoma presentations and that's a conservative number. So I would I would break then breakdown the answer for complex morphology, you'd think Oh nice sphere of cold tumors holiday present in many of them.
Do or ellipsoid or whatever once in a while you get funnier shapes.
Those are the ones, that's a small percentage almost single digit percentages that look funky.
And different.
But even even the regular tumors might benefit from additional administrations and Mark went over the the basic example of two options. One is our re treatment on recurrence, which is already approved for those patients who might qualify and the second would be.
A more forward looking study, where we will have a multiple dose paradigm based on tumor coverage.
No.
We have most of the tumor is already covered.
And that's why we're continuing dose escalation to get those last 25% to 30%.
Thanks Thats helpful.
And then regarding the <unk> study.
I think you mentioned the potential for repeat dosing in that earlier.
<unk>.
I was just wondering if you would continue the single dose escalation beyond the cohort three before attempting multi dosing.
Or if you would be able to do those.
Simultaneously.
Hey, Brandon good question.
The agreement with the FDA was that we would do nine patients with dose escalate.
Twice through three cohorts doubling each time single administration as you mentioned and then go back to the agency. So the plan is to do that once that cohort three is completed.
My view and Thats subject to.
Agency approval would be that we would continue.
Single dose escalation.
Till we get the dose limiting toxicity I think theres a good chance, we're going to see something similar to what we're seeing in GBM, we can get to.
Super Super normal dosages without significant toxicity, so thats based on.
The nature of the Iranian how it works.
It's it's.
Dose rate and dose density.
And the anatomy of the CSF space. So that you don't have.
The dose length of radium suddenly about two millimeters. So your penetration is going to be pretty small. So you are really going to youre going to coat, the CSF space and minimize damage to the white matter.
So I think the plan would be to continue to dose escalate the <unk> and then and then add a.
The multiple dose treatment as you may know some products that are an investigation that that are sort of a similar nature include multi dosing paradigms up to four doses and those patients one can envision perhaps may be titrated dosing two cell counts.
That's one of the benefits of having biomarkers that we hopefully will show that there is something that we could use to titrate dosing, that's kind of how I am looking at it but that will be subject to the data and feedback from the FDA.
Thanks Thats helpful.
The cell counting that you just mentioned does that mean.
Think that it's possible that.
The cadence of the multiple dosing would be on a per patient basis rather.
Then as set cadence for all patients.
Yes, I think so.
Norman mentioned that patient prior to a pretty significant symptomatic improvement and not much of a cell count but.
<unk> had a much higher cell count I think prior to that.
And have received some other therapy, but didn't tolerate it so.
I think ultimately as a doctor.
Peaking as a doctor Youre ultimately going to go on clinical.
On clinical symptomatology, but if you've got a patient that is.
Symptomatic and has zero cell count of zero.
Maybe from a previous treatment or two I think you'd be load the retreat them, but if you are a patient with.
With symptoms of worse than their cell counts going up that might be a trigger to retreat them. So.
I don't think it'll be a simplistic.
Our.
Model, just using cell count alone it will take clinical factors.
But.
Hey, it's great to have more data right now imaging is a poor measure of extent of disease.
These patients have debilitating neurologic symptoms.
There is survived four to six weeks and treat it so I think we'll use adding additional diagnostic tool.
Determined dosing cadence is going to be important going forward and making a big impact in these patients.
Okay, well, thanks for taking my questions and congratulations on your <unk>.
Projected quarter.
Thanks, Thanks, a lot Brandon I.
Appreciate it.
Thank you and I'm not showing any further questions. At this time I would now like to turn the call back over to Marc Hedrick for any further remarks.
Thank you Josh just to close I want to as usual thank everybody that joined us on the call today. We appreciate your interest in the company and what we're doing.
I also want to make sure to remember our employees the physicians and scientists we work with on a daily basis and of course, the patients who enter into these trials and trust us to deliver so we look forward to updating everyone. As we move forward and thank all of our stockholders also for their continued support and confidence back to you Josh.
Thank you. This does conclude today's conference call. Please disconnect. Your line at this time and have a wonderful day.
[music].
[music].
[music].