Plus Therapeutics Inc (PSTV) 2022 Q4 法說會逐字稿

Good afternoon, ladies and gentlemen. Welcome to the Plus Therapeutics Fourth Quarter and Full Year 2022 Results Conference 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 in 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, Andrea. 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 fourth quarter financial results.

Joining me for the call today is Dr. Norman LaFrance, our Chief Medical Officer; and Mr. Andrew Sims, our Chief Financial Officer.

I'll begin the call by reviewing 2022 and then to Andrew to review our financials, and Dr. LaFrance will be joining us for Q&A.

At a high level, I was extremely pleased with our accomplishments in 2022. Going into the year, we set for ourselves some significant development goals, and we achieved or exceeded almost all of them. At the same time, we continued a very conservative approach to managing our balance sheet, ending the year with a similar cash level to the prior year, but we materially expanded our availability of cash, as Andrew will discuss.

Clearly begin by focusing on drug development, clinical, regulatory activities and related milestones. First, I ask that you wind the clock back over a year, and recall that we ended 2021 with a single drug, which was 186RNL, active in only a single Phase I clinical development program for recurrent glioblastoma, funded in large part by the NIH. That was, in essence, the whole of our active clinical development program at that time. It was a year ago.

Fast forward to the end of 2022, we ended the year with 2 investigational drug candidates, Rhenium-186 obisbemeda formerly called 186RNL and Rhenium 188 bioabsorbable alginate microspheres or 188RNL BAM as we call it.

Regarding our investigational drug, rhenium-186 obisbemeda - rhenium obisbemeda, we have 2 active clinical programs now ongoing, one for recurrent GBM and the other leptomeningeal cancer.

In terms of glioblastoma in 2022, we substantially expanded this program. Specifically, we advanced from Phase I to Phase II. We are continuing the dose escalation for larger tumors and higher dose volumes. We manufacture GMP drug allowing us to move into Phase II. We enrolled the first patient in the Phase II trial, and we negotiated with FDA to continue the Phase I dose expansion for larger tumors and now have an active retreatment protocol with FDA to explore retreating patients that happen to occur after a first treatment.

For leptomeningeal disease, we moved this program to essentially a co-lead program with GBM. And specifically, we advanced that program successfully from preclinical stage to an enrolling Phase I, and we obtained $17.6 million in funding for this program that in combination with Plus' 1/3 match as required by CPRIT the grant [award] that should be sufficient to fund this program through Phase II and the enrollment of approximately 150 patients.

For pediatric brain cancer, while we did not initiate this trial in the calendar year because of the discussions with the FDA that were acquired for this first and pediatric patient radiopharmaceutical trial, we did make significant progress, specifically after 3 rounds of FDA interactions on the nature of the IND for pediatric brain cancers, FDA reviewers have accepted our clinical protocol design, but still require and request some additional adult data, which we plan to submit relatively soon.

Our second drug, 188RNL-BAM was in-licensed in early 2022 from [academia]. And during 2022, we successfully transferred that technology to Plus, then successfully manufactured that drug internally last year. We then use that drug to successfully in a human organ ex vivo perfusion model, confirming the preclinical feasibility and the manufacturing of that drug and then we submitted a pre-IND information package to the FDA. So big picture in terms of milestones achieved, 2022 was a transformative year in the company's development.

Additionally, in 2022, we presented important data readouts in our 2 lead clinical programs, GBM and leptomeningeal cancer. First, in November 2022, results from the company's Phase I respect to GBM trial for recurrent glioblastoma was presented at SNO, the Society for Neuro-Oncology Meeting in Florida by the trial PI.

In the Phase I dose escalation trial, at that time, 24 patients with recurrent GBM across 7 cohorts received a single dose of rhenium obisbemeda, administered in the dose escalation phase, achieving up to 740 [inaudible] to the tumor. That's compared on average to about 35 gray total absorb radiation dose delivered to tumors using external beam radiation.

The data in our trial showed that rhenium obisbemeda can be safely administered and there is a statistically significant correlation between overall survival and both absorbed radiation dose to the tumor and present tumor volume in the treated volume.

The strength of this signal is unusually positive for a Phase I trial. And we found that specifically for every 100 gray increase in the absorbed dose correlated -- every increase in the absorbed dose that correlated with about a 36% decrease in the risk of death, the more radiation to the tumor, the lower the risk of death.

And also, in every 1% increase in the tumor volume treated up to a max of 100%, obviously, that is associated with the 4.5% decrease in the risk of death, and that was highly statistically significant. There were no dose-limiting toxicities reported, and the overall safety profile was very favorable.

The study concluded that a single administration of rhenium obisbemeda by convection-enhanced delivery in recurrent glioma patients with poor prognosis is feasible, safe and potentially effective in increasing overall survival when a therapeutic dose of radiation is delivered to the tumor. And in the latter cohorts, we were delivering a therapeutic dose in over 80% of the patients treated.

Based on the data from the Phase I trial, in Q4 2022, we initiated a Phase II dose expansion trial evaluating rhenium obisbemeda for the treatment of patients with recurrent GBM using our Cohort 6 dose, which is 22.3 millicuries and 8.8 milliliters of injectate for small and medium-sized tumors, and that's essentially tumors that are about 20 ccs or less.

This Phase II will enroll up to an additional 31 patients with small to medium-sized tumors in [approx] and we intend to roll that trial in approximately 24 months or less. That trial continues to be supported by an award from the National Cancer Institute.

While we have 5 sites authorized under the NIH with the PI and the NIH, we plan to expand the number of trial sites beyond the authorized 5 to facilitate faster enrollment.

The primary endpoint, as a reminder, is overall survival following single administration, which is an endpoint we agreed to with the FDA and secondary endpoints will assess the safety, tolerability, objective response rate, partial response, SAEs, event-free survival and progression-free survival at 6 months.

Also as mentioned above, key focus areas of ongoing clinical investigation and the GBM development program will be further dose exploration by increasing the dose and also increasing the number of doses to patients who happen to recur after a single administration and also to inform the design of future registrational trial.

As discussed previously, the company and FDA agreed to hold future meetings as facilitated by orphan and fast track designations on the registrational trial design, including the use of external data to augment the control arm and speed enrollment in a potential pivotal.

Now let me move on to our leptomeningeal metastases or LM development program. The LM trial is a multicenter Phase I/II dose escalation study -- rated dose safety and efficacy of rhenium obisbemeda. LM, as you may know, application associated with advanced cancers that infiltrate the fluid line structures of the central nervous system also called leptomeninges.

It so happens that the incidence of LD is growing with local and improved cancer care, and there are no approved FDA therapies. And there are about 120,000 patients per year that are affected with LM and is substantially under diagnosed.

Standard treatment includes external beam radiation therapy to the affected sites, potentially with chemotherapy given either orally, intravenously or often administered twice a week directly into the CSF space. Systemically administered therapies almost never work because of the blood-brain barrier preventing access to the leptomeninges.

So going back again to the SNO meeting back in November, we also presented the early Phase I data from the ReSPECT-LM trial at that meeting that demonstrated that a single administration of rhenium obisbemeda was feasible, safe and well tolerated across the 2 dosages just studied at that time in Cohort 1 and 2 with patients in that trial after treatment showing a decreased CSF tumor cell count by 48 hours following treatment that was between 46% to 90% in terms of reduction of the tumor cell count that was measured in the CSF.

The $17.6 million product development research funding award we received from the Cancer Prevention and Research Institute of Texas or CPRIT, began funding in the fourth quarter of 2022. As mentioned, this award will cover the majority of the development costs, including funding for up to 150 enrolled patients for the LM program over 3 years. And that's an important source of non-dilutive funding that materially strengthens the company's balance sheet.

In early 2023, we completed enrollment in Cohort 2 of the LM trial, and now 6 patients have been treated. Regarding next steps with that trial following the DSMB, the Data Safety Monitoring Board review, which is anticipated to be in March, we anticipate that we'll complete enrollment in Part A of the Phase I portion soon, perhaps in the next quarter, that will be 9 patients total. Thereafter, we plan a meeting with the FDA to determine the exact dose expansion plans for the Phase I Part B trial and then we expect to initiate that Part B trial in the second half of 2023. We also expect initial data from the Phase I Part A to be presented also in the second half of 2023.

As I mentioned on our third quarter '22 call in November, we have made and are making significant progress in building a more resilient and robust cGMP supply chain through our strategic partnerships that enable the development manufacturer and even future potential commercialization of our products.

Our current supply chain and key partners are positioned to supply cGMP rhenium obisbemeda for any ongoing and planned Phase II/III clinical trials in patients with GBM, LM or pediatric brain cancer, and that's now fully in place as of the end of last year.

In pediatric brain cancer. Based on extensive inaudible 27:52 we expect to submit an updated investigational new drug application for what will be called the respect PBC Phase I safety dose finding and efficacy study of rhenium obisbemeda for pediatric brain tumors. It will be submitted in conjunction with our lead academic institution, Lurie children's hospital at Northwestern University in Chicago.

Finally, regarding our novel recently in-licensed radio embolic microparticle technology 188 188RNL-BAM,, inaudible 2 objectives. Furthermore, based on the FDA feedback regarding the most appropriate regulatory designation for the investigation of products specifically, whether it should be a drug or device in terms of its regulatory path.

We are pursuing the request for designation process to define this in parallel to performing required developmental activities regardless of whatever the ultimate regulatory designation ultimately is.

It's our view that despite the fact that the competing legacy products that are on the market, which are permanently indwelling radio embolic products that have been in the market for, in some cases, over 2 decades, the bioresorbable nature of our RNL-BAM supports its ultimate designation as a drug. Nonetheless, we'll collaborate with the FDA to seek their ultimate guidance on this determination and proceed in parallel with those development activities that we can reasonably do irrespective of the ultimate regulatory determination.

The company plans, as mentioned previously on other calls to initially focus on developing the BAM technology as a next-generation bioresorbable radio embolic therapy for a first liver cancer.

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, Marc. Good afternoon, everyone. Please refer to our press release issued earlier today for a summary of our financial results for the 2022 fourth quarter and full year ended December 31, 2022.

As of December 31, 2022, cash and cash equivalents were $18.1 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 full year 2022 was $13 million compared to $10.3 million for full year 2021. During the fourth quarter of 2022, the company received its first CPRIT grant funds of approximately $1.9 million as planned.

The main year-over-year changes between full year '22 and full year '21 are as follows, grant revenue of $224,000 was reported related entirely to CPRIT. Total operating expenses for full year 2022 were $19.9 million compared to $12.5 million for the prior year.

The 2022 total included 2 main areas of spend that were one-off in nature. The first area of increase was CMC spend related to the development of GMP quality drug and key regulatory consulting activities necessary to advance the Phase II GBM clinical trial. These expenses were over $4 million in 2022. 2023 spend related to these activities is forecast to be less than $500,000.

In addition, and to a lesser extent, the company had a forecasted increase in litigation and legal spend related to a legal settlement disclosed in Form 10-K. The net result is that we expect an overall decrease in total burn in 2023 based on our currently disclosed milestones.

Interest expense decreased from $932,000 for full year 2021 to $711,000 for full year 2022. This decrease reflects the continued principal paydown that commenced in November '21 on the company's Oxford debt.

Net loss for full year 2022 was $20.3 million or $0.77 per share compared to a net loss of $13.4 million or $1.11 per share for full year 2021.

Now I'll turn it back to Marc.

Thank you, Andrew. Before we move on to Q&A, allow me to provide a very detailed guidance on anticipated milestones for 2023.

First of all, we intend to expand the glioblastoma clinical trial sites and make meaningful enrollment progress with ReSPECT GBM Phase II trial to support a target completion of enrollment date by the end of the year 2024.

We also plan to publish the ReSPECT Phase I GBM data in a high-impact factor peer-reviewed journal. We also plan to present clinical, safety and efficacy data of the Phase I and Phase II ReSPECT GBM trials in the second half of 2023.

In terms of LM leptomeningeal metastases, our plan is to complete enrollment in the Phase I Part A of the ReSPECT LM trial and begin enrollment in the Phase I Part B. We also intend in the ReSPECT LM trial to expand the number of clinical trial sites to support that expansion into Part B of that Phase I.

Also in the second half of 2023, we'll present clinical safety and efficacy data based on the Phase I Part A of the ReSPECT LM trial.

As per the CPRIT grants, we will explore potentially synergistic drug combination studies of locally delivered rhenium obisbemeda, coupled with promising systemic therapies in relevant preclinical models of leptomeningeal disease.

We also will initiate the IND to treat pediatric patients with a ependymoma in high-grade glioma and begin enrollment. The first clinical trial site should be Northwestern in the Lurie children's hospital.

In conjunction with the FDA, we intend to finalize the regulatory designation for the 188RNL-BAM technology and complete key developmental activities this year.

Furthermore, we think in 2023, there are opportunities to execute corporate partnerships to expand the business opportunities for Plus' unique CNS oncology platform. And then finally, building our success with CPRIT, we intend to submit multiple grants to raise non-dilutive capital to support expansion of the company's drug development pipeline.

So with that behind us, let me turn this back over to Andrea for the Q&A session. Andrea?

(Operator Instructions) Our first question comes from Justin Walsh with Jones Trading.

Hi. Congrats on the progress. To start, I was wondering if you could maybe provide some more color on what we can expect in the upcoming data readouts you just mentioned. So for ReSPECT GBM, I'm curious about any patient data. We haven't seen from the Phase I/IIa portion as well as what we might see from the Phase IIb portion and likewise for ReSPECT LM?

Justin, it's Marc. Obviously, we'll present what data we can to you. But -- and I'll let Norman take that question because he's up to his shoulders in evaluating that data. Norman?

Great question, Justin. And as you've seen over the past, say, years, we've developed progressive statistical valuation model, starting with the [KEM] in less than 100 gray, which was based on the preclinical, I'll call it a point where there's clear efficacy from that absorbed dose, and we know that radiation works and more radiation is better [inaudible] in those 2 cohorts.

And by comparison, it was roughly a [€2 OS] versus a 5-month OS for our specific data. We added to those evaluations, and these were presented at medical meetings and peer accepted presentations, one on the Cox proportional hazard ratio model, which is a -- it's a survival model in the statistics, that uses all the data and instead of the cutoff of 100 gray, which, as I said, was supported both by what is known with radiation absorbed dose in general and was supported by our specific preclinical data. Instead, we presented the totality of our data with that Cox model and showed -- which we reported in several meetings of an improved survival percentage, we used the increment of 100 gray and Marc mentioned that with a greater than 40%, closer to 45% improvement in survival for each additional 100 gray and absorbed dose. And the comparable survival that was 3% or 4% for each 1% and covered tumor treatment.

We expanded that model because of the -- it doesn't correct for all the co-variant per metric types of bias you might get with what is called the accelerated failure time model that showed consistent and actually better statistically significant. The Cox model was 0.003 values for both, whereas the AFT model showed a 0.00 -- so these -- and these were all on our data without -- in its totality without any differentiation of cutoff as we did with the initial leptomeningeal -- excuse me, Kaplan-Meier 100 gray cutoff.

So we'll continue to analyze these -- the Phase II trial that we started will build on these data. We have analyses that we'll present probably in our publication that is in draft now for a major publication on Phase 1 on what this means on the predictability of Phase II. We'll probably present that also at a future ASCO or snow ASCO meeting in the summer and certainly for the SNO meeting in fourth quarter.

So I'm very happy in a separate call we can't get into the statistics in great detail. But if there's any interest in really digging into that, just let us know and I'll be happy to spend some time with you.

Got it. Maybe one, you mentioned the - all the presentations you guys have been going to those different scientific meetings. I'm curious what some of the reception to be that the data is that you've presented so far. Obviously, the PI is quite enthusiastic about this. But how is the community received?

Yes, I'm glad you asked that because for me to bring it up, maybe is not as humble as we should be. And not to be a wise guy, I think you should ask some of the KOLs out there when they think what they tell us unprompted, is that this is surprising data for such an early program, and they've not seen it in typical therapeutic programs.

Now part of my answer to them and some of them know me is this is a radiopharmaceutical and it's not uncommon early in a program to get a very good sense on how it's going to work because the mechanism of action, first of all, is well known. It's well accepted energy transfer to the tumor is efficacious and more is better.

We have the delivery problem solved for both the GBM and LM. So that's very effective, as has been presented and as you're well aware. And we've shown that the increasing doses where we've done during the dose escalation, remain very well tolerated and quite in a sense, predictable because we're not using exhaustive doses or extremely high doses. They've all been well tolerated without any observed DLTs or limiting doses or maximum tolerated doses observed or identified.

So we're on very solid ground for a very good therapeutic index. The safety margin is very comforting and robust, and people have recognized this. And in fact, many times, we'll get unsolicited requests for interest in our programs because they've [seen our] presentations at one of the several meetings we participated in.

And last but not least is what we all know for both LM and GBM, but particularly LM, there's nothing out there for these folks. There's no therapies, nothing works. There's not really very many investigative programs. So LM is really a waste line of options for patients, unfortunately, and people are recognizing that this is something there. And then GBM, the data speaks for itself, and you really can't -- you can't ignore that preliminary signal at all.

And I think when we can report hopefully an acceptance in a major impact journal that Marc mentioned, there will be further recognition on this preliminary data. So thanks for that question.

Got it. Maybe the next one for Mark and kind of builds on what you were saying about some of the interest you guys have been getting. I'm sure you can't speak to specific potential partners, but I'm wondering if you can shed any light on the types of conversations you're having or would like to be having or are they primarily related to potential combination therapies or other types of opportunities?

Justin, I would like to -- we've done 3 transactions over the last – like one transaction a year as we've worked to expand the pipeline and build it out. And so they're kind of across the board, quite honestly. We're very promiscuous in terms of discussing and evaluating ways we can build value for shareholders, whether that's out-licensing or in-licensing.

So we just continue to expand those discussions. And as the data gets out there, the things that Norman presented, those get more and more notoriety. It increases the number of discussions. So it's going to be really hard to say much about that at this point. Although they accept that the conversations are increasing, not decreasing.

Got it. And one more for me. Just sort of speaking to the, I guess, some of the general tones here. It seems to me like we're at another inflection point in the radio therapeutic field with the significant increase in the use of targeted radiopharmaceuticals and prostate cancer.

So I'm wondering if you guys have seen any change in the tone or content of discussion you've been having as the commercial potential of some of these radio therapeutics has come even more into focus?

Yes. I may let the doctor comment scientifically. He is been doing this for a year or 2 and knows a lot about the space and has seen it evolve, probably has more drugs approved under his -- under his watch than anybody in the country in terms of radio therapeutic space.

But so starting maybe early 2021, and Justin, you know this because you know the space well. We're seeing banks increasingly add analysts that are dedicated to radio therapeutics. So that's I think an important milestone.

There's bank coverage, there's analyst coverage. There are capital flows into the space. There are - there's manufacturing infrastructure that's being funded and built out in anticipation of the market coming. So -- and then you see major players doing deals in the space.

So we see a lot of really promising movements in the capital markets that are pointing to years ahead of us of growing value in this space. So we cannot be more excited to be here at the ground floor.

And one thing that's different about us, I think you know, Justin, is we have real data. We have a lot of companies that have our building infrastructure, but we're building a data profile that I think is very exciting in a group of diseases that have don't have good options. So yes, we're very optimistic and bullish. Doc, do you want to elaborate...

I think what you're asking, you're mentioning the PSMA space, which is very crowded. It's been successful the recent approval. There are several out there. And as you well know, before that was the serotonin receptor, the dotatate approval, which has been successful. And quite frankly, in the literature and the meetings, that's what's been talked about understandably, and they've earned that with some good data and some good results.

And although [humility], I'd like to add that when we presented the European Association of Nuclear Medicine, you may know this that they have a highlights presentation at the beginning of the meeting to present what they -- the reviewers and the leadership of that society feel are the up and comers or the new data, things that pay attention to. And our GBM data presentation there, which I did was chosen for the highlights lecture as the first presentation.

Now admittedly, there was a PSMA paper and a dotatate paper and so forth, consistent with what they've been doing over the last years and those products are getting the attention they should get. But it was very, I think, rewarding and very appreciated by us. And in fact, the folks came up to me afterwards and got a picture for prosperity in the sense of noting that this was -- this is quite an advance that they recognized a definite radio pharmaceutical that rather than the classic systemically administered using some elegant biochemistry or targeting mechanism, which is elegant on something that's very straightforward and had some very incredible data that they pointed to very carefully.

So we've made the highlight lectures and I think this is recognition by the field that there are other candidates out there that are going to make a difference.

Well, I look forward to seeing the continued building of this data set.

Our next question comes from Ed Woo with Ascendiant Capital.

Congratulations on the progress in 2022. And definitely, congratulations on the CPRIT grant. Is there any possibility or visibility that you'll be able to apply for the grants for any other indication?

I think you mean the LM CPRIT grant, are we going to be able to apply that to other indications?

No. I mean in terms of getting grants for other indications, completely new grants?

Got it. Yes. No, thanks. I appreciate the question. So we've been successful, knock on wood in getting third-party grant support in terms of the NCI grant the CPRIT grant. One of the reasons we moved to Texas. Easy to say now that we have a grant under our sleeve, but was -- that we thought that $6 billion of capital for cancer funding, we might be able to get some of that to fund our programs and the whole that we were fortunate to be able to do that.

We know companies that have up to 3 CPRIT grants. So we do, in fact, think that some of our programs that aren't funded or aspirational programs that we like to bring on board, but because of our kind of internal frugality about capital deployment. In other words, we don't want to spend it until we raise it, that there might be some opportunities there.

So our plan, and that was a milestone in this year is we're going to submit more than 1 grants, including the CPRIT, but also potentially other grants -- some of the opportunities that we have available to us to fund additional programs to build out the pipeline.

So that's a goal. Those can be hard to get, but we're going to submit them, and we think we sort of cracked the code to a degree on SPRIT. And we think there might be some greater opportunities ahead of us there.

What was the timing in terms of when you submitted your application to when you got -- awarded the grant?

For CPRIT, the LM grant?

Yes.

Yes, actually, it was, I think, about 18 months. So we submitted a couple of iterations. We got close a couple of times. And like with the NI -- feedback, how you can improve the grant. We worked in the background to continue to advance the program, while we were continuing those dialogues.

So I think that treating a patient in LM really helped convince them and the data really help convince them that this is something that's worth funding. So yes, it's like all grants. It's typically sort of iterative. Key is being persistent.

And having data.

Yes, data helps.

That's right. Definitely, congratulations and definitely looking forward to more good news from you guys this year. Thank you.

Thank you. One moment for our next question. Our next question comes from Sean Lee with H.C. Wainwright.

My first question is on the Phase II GBM study. Can we expect the data readouts from that prior to full patient enrollment expected by the end of 2014?

It's an open-label non-blinded study. So the short answer would be, yes, to give you more details. It will be -- as I -- I think I was answering Justin's questions on the types of statistical analysis, I would expect us to have some reviews of the different types of analyses just because there's lots of ways to utilize those to form the design of a registrational trial.

So I'd like to give you more detail, but the short answer is yes, and it will depend on how the data develops. And if we can certainly accelerate the accruals even faster, we'll be in a position to move on that more quickly. And part of that will be in our preparation to go to FDA. So we'll - we plan to share that. I can't give you exact timing, however.

My second question is on the upcoming pediatric study. What are some of the key learnings and takeaways from the GBM trial that you feel could help you apply to the pediatric study and make it more successful?

Yes. Great question, very applicable, and we actually leveraged the pediatric questions and presentations to the FDA. We leveraged our adult data significantly That, in fact, result in the FDA asking -- not asking questions, but more clarifications on that data, which is a good thing because it gets them more involved in that data.

The first interactions with FDA was to kind of include all comers in pediatric brain tumors, which is a broad spectrum. And the -- and first, in pediatric patients for any drug, particularly radiopharmaceutical, FDA is careful and conservative.

We got that feedback. For example, we're limiting the tumors to super tentorial and the ones with high unmet medical need with terrible prognosis, ependymoma and high-grade glioma.. We've had most recently with the FDA agreement by the reviewers for the pediatric protocol and just sold them some last clarifications they have on some of the adult data, which is straightforward we have, and it's just a reanalysis and shows their interest in the adult data, which we'll be able to leverage for future adult considerations. And so Marc, do you have anything else to add on this?

Well, just the one thing I would add to that, Sean, is -- and we mentioned this before in the adult trial. Delivery is the key. If we can cover the tumor with enough radiation, we're going to kill the tumor period sort of in the discussion.

We translated that data directly into the pediatric population. And so I think that really gives us confidence in that trial that we can deliver the drug.

The other thing is it's very common to put electrodes into the brain in these [kids]. So we have a high degree of confidence that the convection delivery process will be well tolerated. So we're really able to leverage both that epilepsy treatment data, as well as our adult delivery data to feel confident going into this trial. We're able to convey that successfully, I think, to the FDA, given the fact that the clinical protocol.

That was very helpful. My last question is on the BAM product. I know it might be a little early, but are there specific indications where you feel the product will be particularly well suited for?

Yes. Our initial target is going to be for hepatoma. There are 2 drugs on the market that are kind of long in the tooth. They're non bioresorbable. They are used to treat [Epitome] I think it's about a $1.2 billion opportunity. But those are permanent. And we're providing a drug that has different radio therapeutic, different characteristics that are related to the rhenium that make it more attractive. So it's resorbable.

So the idea is that you kind of tune the bioresorption timing so that by the time the radiation is fully decayed or near fully decade. The embolic has been [bioresorbed] vascular patencys’ resumed. And you can go back in and retreat the patient multiple times. That's the idea.

So this would be a very differentiated, unique, novel product. And so livers first, but potentially we could go any tumor that you can target by radio embolization or angiographic catheters potentially tolerate even things like potentially pancreatic cancer and other things, sarcomas that are difficult to treat or get to potentially would lend themselves to therapy. But livers the, I think our initial target is there is an existing market

(Operator Instructions) Are there any written question today.

Andrea, we have written question. The other - the 3 other written questions that have been largely answered. This question revolves around our LM trial and the use of novel cell testing approach to determine biologic response. What's -- how is that important to your trial going forward in your development plans?

So yes, you're talking about - we used an interesting test called CNS side. It's manufactured by a California company. Thus far, we're -- I would say we're incredibly pleased with that test. I think it fills a critical gap in the diagnostic and therapeutic approach to these patients.

The current existing way that LM is diagnosed is by a mix of imaging and imaging is not great. Clinical findings, which are often very vague and non-specific. And then the CSF lumbar puncture results, which look at glucose, protein and cell count, which is the same thing that Norman and I use when we are in medical school a year or 2 ago that is very non-specific and very non-sensitive for that.

So I think as I mentioned, in the first 4 patients where we have data on, we have significant reduction in tumor cell counts as measured by that assay. So we're very pleased with what we've seen thus far, but it's very early.

Another relevant piece of information is LM is significantly under diagnosed. So only about 25% of patients with LM were diagnosed. We know that based on autopsy data. So there's an opportunity to increase the total addressable market of LM for our therapeutic by up to 4x. That's - that opens up a pretty significant increased application for the test.

And the other interesting thing is beyond just quantification of tumor cells, you can actually use that test potentially to tailor therapy. Although we don't use it for our trial, you can actually put in groups of antibodies and look at specific epitope expression, fluorescence situ hybridization and genomic analysis as part of that test to tailor therapy in terms of using systemics0and immunotherapy and so forth, which we're beginning to explore in our super grant.

So that's a good question. And we think it's going to be very important long term to pair the therapeutic with a diagnostic like this, an innovative - I kind of think about it almost like a companion diagnostic. And that's the only question that's unanswered. So Andrea, anything else?

I'm not showing any further questions right now. Marc, if you'd like to close it out.

Yes. So thanks, everyone, for participating on the call today. Appreciate your interest in the company. Once again, thanks to our employees and collaborating physicians and scientists that we work with on a daily basis, and we're very appreciative also for the patients who are on this trial that need this help and trust us to deliver for them and their family. So we're very appreciative to them. So we look forward to continuing the updating process as we move forward and thanks also to our stockholders for their continued support and confidence. Thank you.

Thank you for your participation in today's conference. This concludes the program. You may now disconnect.