This conference call transcript was computer generated and almost certianly contains errors. This transcript is provided for information purposes only.EarningsCall, LLC makes no representation about the accuracy of the aforementioned transcript, and you are cautioned not to place undue reliance on the information provided by the transcript.
spk01: 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. Mark Hedrick, PLUS Therapeutics President and Chief Executive Officer. Sir, you may begin.
spk04: 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 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. So let me 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 186-RNL, active in only a single phase one 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. That was a year ago. Fast forward to the end of 2022. We ended the year with two investigational drug candidates, rhenium-186-obispumate, formerly called 186-RNL, and rhenium-188-obispumate, bioabsorbable alginate microspheres, or 188-RNL-BAM, as we call it. Regarding our investigational drug, rhenium-186-obispumata, or rhenium-obispumata, we have two active clinical programs now ongoing, one for recurrent GBM and the other for leptomeningeal cancer. In terms of glioblastoma in 2022, we substantially expanded this program. Specifically, we advanced from phase one to phase two, We are continuing the dose escalation for larger tumors and higher dose volumes. We manufactured GMP drug, allowing us to move into phase two. We enrolled the first patient in the phase two trial. And we negotiated with FDA to continue the phase one 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 one. And we obtained $17.6 million in funding for this program that in combination with PLUS's one-third match as required by CEPRIT, the grant awarder, that should be sufficient to fund this program through phase two 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 required for this first and pediatric patient radiopharmaceutical trial, we did make significant progress. Specifically, after three 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, 188R and LBAM, was in licensed in early 2022 from academia. And during the, during 2022, we successfully transferred that technology to PLUS, then successfully manufactured that drug internally last year. We then used 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 two lead clinical programs, GBM, and leptomeningeal cancer. First, in November 2022, results from the company's Phase I Respect 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 seven cohorts received a single dose of rinium obispumata and administered in the dose escalation phase, achieving up to 740 gray to the tumor. That's compared on average to about 35 gray total absorbed radiation dose delivered to tumors using external beam radiation. The data in our trial showed that rhenium-obispo-meta can be safely administered, and there's a statistically significant correlation between overall survival and both absorbed radiation dose to the tumor and percent tumor volume in the treated volume. The strength of this signal is unusually positive for a phase one 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 a 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 rinium-obispo-meta by convection-enhanced delivery in recurrent glioma patients with poor prognosis It's 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 and Q4 2022, we initiated a Phase II dose expansion trial evaluating rhenium-obispo-meta for the treatment of patients with recurrent GBM using our cohort six dose, which is 22.3 millicuries in 8.8 milliliters of injectate for small and medium-sized tumors, and that's essentially tumors that are about 20 cc's or less. This phase two will enroll up to an additional 31 patients with small to medium-sized tumors, and we intend to enroll 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 five sites authorized under the NIH, with the PI and the NIH, we plan to expand the number of trial sites beyond the authorized five 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 six months. Also, as mentioned above, key focus areas of ongoing clinical investigation in 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 trials. 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 multi-center phase 1-2 dose escalation study rated dose safety and efficacy of rhenium obispumata. LM, as you may know, is a complication associated with advanced cancers that infiltrate the fluid line structures of the central nervous system, also called the leptomeninges. It so happens that the incidence of LM 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 it's substantially underdiagnosed. 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 one data from the RESPECT-LM trial at that meeting that demonstrated that a single administration of virinium abyspamate was feasible, safe, and well-tolerated across the two dosages studied at that time in cohorts one and two 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 Reciproc 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 three 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 two of the LM trial, and now six 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 1 portion soon, perhaps in the next quarter, and that will be nine patients total. Thereafter, we plan a meeting with the FDA to determine the exact dose expansion plans for the Phase 1 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 1 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 GMP supply chain through our strategic partnerships that enable the development, manufacture, and even future potential commercialization of our products. Our current supply chain and key partners are positioned to supply C-GMP rinium-obispo-meta for any ongoing and planned Phase II-III clinical trials in patients with GBM, LLM, or pediatric brain cancer. And that's now fully in place as of the end of last year. And pediatric brain cancer. Based on extensive evidence previously, we expect to submit an updated investigational new drug application for what will be called the RespectPBC Phase 1 Safety Dose Finding and Efficacy Study of Rhenium Obispumata 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, radioembolic microparticle technology, 188R and LBAM, we successfully completed 72 objectives. Furthermore, based on the FDA feedback regarding the most appropriate regulatory designation for the investigational product 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 radioembolic products that have been in the market for, in some cases, over two decades, the bioreservable 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 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 bioreservable radial embolic therapy for, at 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?
spk02: 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 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 separate 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 CPREC. Total operating expenses for full year 2022 were $19.9 million compared to $12.5 million for the prior year. The 2022 total included two 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 2 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 pay down that commenced in November 21 from the company's Oxford debt. Net loss of full year 2022 was $20.3 million, or 77 cents 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 Mark.
spk04: 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 of the Respect GBM Phase 2 trial to support a target completion of enrollment date by the end of the year 2024. We also plan to publish the Respect Phase 1 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, with the meningeal 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 1. Also, in the second half of 2023, we'll present clinical safety and efficacy data based on the Phase 1 Part A of the RESPECT-LM trial. As per the SEPRT grant, we will explore potentially synergistic drug combination studies of locally delivered rhenium-obispoamide coupled with promising systemic therapies in relevant preclinical models of leptomeningeal disease. We also will initiate the IND to treat pediatric patients with ependymoma and high-grade glioma and begin enrollment. The first clinical trial site should be Northwestern and the Lurie Children's Hospital. In conjunction with the FDA, We intend to finalize the regulatory designation for the 188 RNL 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's unique CNS oncology platform. And then finally, building on our success with CPRET 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?
spk01: Thank you. At this time, we will conduct the question and answer session. As a reminder, to ask a question, you will need to press star 1-1 on your telephone and wait for your name to be announced. To withdraw your question, press star 1-1 again. Please stand by while we compile the Q&A roster.
spk03: Our first question comes from Justin Walsh with Jones Trading.
spk01: Please go ahead.
spk08: Hi, congrats on the progress. Thanks for taking the questions. 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 RespectLM.
spk04: Hey, Justin. It's Mark. Obviously, we'll present what data we can to you, but I'll let Norman take that question because he's up to his shoulders in evaluating that data. Norman?
spk05: Yeah. Thanks, Mark. Great question, Justin. And as you've seen over the past, say, years, we've developed progressive statistical evaluation models starting with the KM gray and less than 100 gray, which was based on the preclinical, I'll call it, point where there's clear efficacy from that absorbed dose. And we know that radiation works and more radiation is better in those two cohorts. And by comparison, it was roughly a two-year OS versus a five-month OS for our specific data. We added to those evaluations, and these were presented, you know, at medical meetings and peer-accepted presentations. One on the Cox proportional hazard ratio model, which, you know, is a survival model in 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 an increment of 100 gray, and Mark mentioned that with a greater than 40%, closer to 45% improvement in survival for each additional 100 gray and absorbed dose, and a comparable survival that was, you know, 3% or 4% for each 1% in covered tumor treatment. We expanded that model because of the, it doesn't correct for all the covariant treatments, parametric 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 0.003. So these, and these were all on our data without, you know, 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 two 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 one. on what this means on the predictability of phase two. We'll probably present that also at a future ASCO or snow ASCO meeting in the summer and certainly for the snow 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.
spk08: Got it. Maybe one, you mentioned all the presentations you guys have been going to, different scientific meetings. I'm curious what some of the reception to the data is that you've presented so far. Obviously, the PI is quite enthusiastic about this, but how has the community received it?
spk05: Yeah, 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 what 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 we're you know, we've done during the dose escalation remain very well tolerated and quite, you know, 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, you know, 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 waistline 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 ignore that preliminary signal at all. And I think when we can report hopefully an acceptance in a major impact journal that Mark mentioned, you know, there'll be further recognition on this preliminary data. So thanks for that question.
spk08: 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?
spk04: Hey, Justin, I would like to. We've done three transactions over the last, like, one transaction a year. We've worked to expand the pipeline and build it out. And so, you know, 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, except that the the conversations are increasing, not decreasing.
spk08: 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 radiotherapeutic field with the significant increase in the use of targeted radiopharmaceuticals in 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 radiotherapeutics has come even more into focus?
spk04: Yeah, you know, I may let the doctor comment scientifically. He's been doing this for a year or two and knows a lot about the space and has seen it evolve. Probably has more drugs approved under his watch than anybody in the country in terms of radiotherapeutic space. But so, you know, we 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 radiotherapeutics. So that's an important, I think, an important milestone. There's bank coverage. There's analyst coverage. There are capital flows into the space. There's manufacturing infrastructure that's being funded and built out in anticipation of the market coming. 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 of the things that's different about us, I think you know, Justin, is we have real data. We have a lot of companies that, you know, are building infrastructure, but we're building a data profile that I think is very exciting in a group of diseases that don't have good options. So, yeah, we're very optimistic and bullish.
spk05: Doc, do you want to elaborate? Yeah. I think what you're asking, you're mentioning, you know, the PSMA space, which is very crowded. It's been successful, a recent approval. There's several out there. And as you well know, before that was the, you know, serotonin receptor, the dotatate approval, which has been successful. And quite frankly, in the literature and the meetings, that's, you know, that's what's been talked about, understandably. And they've earned that with some good data and some good results. And all due 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, you know, the reviewers and the leadership of that society feel are the up-and-comers or the new data, things to 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 getting, you know, 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 quite an advance that they recognized a definite radiopharmaceutical that rather than the classic systemically administered using some elegant biochemistry or targeting mechanism, which is, you know, 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.
spk08: Well, I look forward to seeing the continued building of this data set, and thanks for taking the questions.
spk03: Thank you, Justin. Thank you. One moment for our next question. Our next question comes from Ed Wu with Ascendian Capital.
spk01: Please go ahead.
spk06: Yeah, congratulations on the progress in 2022. And definitely congratulations on the CIPR grant. Is there any possibility or visibility that you'll be able to apply for the grants for any other indication?
spk04: Hey, Ed, thank you for the question. I think you mean the LM CEPRT grant, are we going to be able to apply that to other indications?
spk06: No, I mean in terms of getting grants for other indications, completely new grants.
spk04: Oh, got it. Got it. Yeah, no, thanks. Appreciate the question. So, you know, we've been successful, knock on wood, in getting third-party grant support in terms of the NCI grant, the CEPRT 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 lo and behold, we were fortunate to be able to do that. We know of companies that have up to three CPRIT grants. So we do, in fact, think that some of our programs that aren't funded uh, or aspirational programs that we'd like to bring on board, but because of our kind of internal frugality about capital deployment, in other words, we don't, we don't want to spend it until we raise it, that there might be some opportunities there. So, uh, our, our plan, and I, that was the milestone this year is we're going to submit more than one grant, uh, including the secret, but also potentially other grants that some of the opportunities that we have available to us to fund, uh, additional programs to build out the pipeline. So that's a goal. You know, 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 CPRED, and we think there might be some greater opportunities ahead of us there.
spk06: What was the timing in terms of when you submitted your application to when you got awarded the grant?
spk04: For CPRED, the LM grant?
spk06: Yes.
spk04: Yeah, actually, it was, I think, about 18 months. So we submitted a couple of iterations. We got close a couple of times, like with the NIH 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, you know, I think that treating a patient in LLM really – really helped convince them and the data really helped convince them that this is something that's worth funding. So, yeah, it's like all grants. It's typically sort of iterative. The key is being persistent.
spk05: And having data.
spk04: Yeah, data helps. That's right.
spk06: Definitely, congratulations and definitely looking forward to more good news from you guys this year. Thank you.
spk02: Thank you, Ed.
spk01: Thank you.
spk03: One moment for our next question. Our next question comes from Sean Lee with HG Wainwright.
spk01: Please go ahead.
spk07: Good afternoon, guys, and thanks for taking my questions. My first question is on the Phase 2 GBM study. Can we expect the data readouts from that prior to full patient enrollment expected by the end of 24th?
spk05: It's an open-label, non-blinded study, so the short answer would be yes. To give you more details, it'll be, you know, as I think I was answering Justin's questions on the types of statistical analyses, 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... I'd like to give you more detail, but the short answer is yes, and it'll depend on how the data develops. And if we can certainly accelerate the accrual 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 plan to share that. I can't give you exact timing, however.
spk07: No issues. Thanks for the additional color. 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?
spk05: Yeah, 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, resulted in the FDA asking, you know, 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 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 supertentorial and the ones with high unmet medical need with terrible prognosis, the ependymomas and the high-grade gliomas. We've had most recently the FDA agreement by the reviewers for the pediatric protocol and just owe 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, you know, Mark, do you have anything else to add on this?
spk04: Well, just 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 discussions. we translated that data directly into the pediatric population. And so I think that really gives us confidence going to that trial that we can deliver the drug. The other thing is, it's very common to put electrodes into the brain in these kits. 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 were able to convey that successfully, I think, to the FDA given the fact that clinical protocol.
spk07: Thank you for that. 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?
spk04: Yes. Our initial target is going to be for hepatoma. There are two drugs on the market that are kind of long in the tooth. They're non-bioresorbable. They're used to treat hepatoma. I think it's about a $1.2 billion opportunity. but those are permanent. And we're providing a drug that has different radiotherapeutic, 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 irradiation is fully decayed or near fully decayed, the embolic has been bioresorbed, vascular patencies 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 a radioembolization or angiographic catheters potentially tolerated, 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 liver is, I think, our initial target as there is an existing market.
spk07: Great. Thanks, Mark. And that's all the questions I have.
spk04: Thank you, Sean.
spk01: Thank you. As a reminder, to ask a question, please press star 1-1 on your telephone. Are there any written questions today?
spk04: Hey, Andrea, we have one written question. The three 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. How is that important to your trial going forward and your development plans? So, yeah, you're talking about, we use an interesting test called CNS-SIDE. It's manufactured by a California company. Thus far, 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 nonspecific, and then the CSF lumbar puncture results, which look at glucose, protein, and cell count, which is The same thing that Norman and I used when we were in medical school a year or two ago that is very nonspecific and very nonsensitive for that. I think as I mentioned, in the first four patients where we have data on, we have significant reduction tumor cell counts as measured by that assay. 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 underdiagnosed. 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 four times. 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 in situ hybridization, and genomic analysis as part of that test to tailor therapy in terms of using systemics and immunotherapy and so forth, which we're beginning to explore in our SEPA 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 diagnostic. I think about it almost like a companion diagnostic. And that's the only question that's unanswered. So, Andrea, anything else?
spk01: I'm not showing any further questions right now. Mark, if you'd like to close it out.
spk04: Yeah. So thanks, everyone, for participating on the call today. Appreciate your interest in the company. Once again, thanks to our employees and the collaborating physicians and scientists that we work with on a daily basis. And we're very appreciative also for the patients who enroll in this trial that need this help and and trust us to deliver for them and their families. 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 continuous support and confidence. Thank you.
spk01: Thank you for your participation in today's conference. This concludes the program. You may now disconnect.
Disclaimer