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.
spk00: Good afternoon, ladies and gentlemen. Welcome to the Plus Therapeutics first quarter 2023 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.
spk06: Thank you, Jonathan. 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 2023 first quarter financial results. Joining me for the call today is Dr. Norman LaFrance, our Chief Medical Officer, and Andrew Sims, our Chief Financial Officer. I'll begin the call by reviewing our recent clinical and regulatory progress with a focus on the first quarter, and then turn the call over to Andrew to review our financials. Dr. LaFrance then will be joining us for Q&A. I can say we had a very productive start to 2023, highlighted by the increased enrollment momentum of our two lead programs in glioblastoma, or GBM, and leptomeningeal metastases, or LM. Starting with our GBM program and the Phase IIb trial, we are actively enrolling the Phase IIb clinical trial of rhenium obispumata in patients with small to medium-sized GBM tumors with a 20-centimeter, a 20cc, or a 20-milliliter cutoff. The single administered dose is 22.3 millicuries and 8.8 mLs, and the primary endpoint is overall survival, and there are a number of typical secondary endpoints, such as safety, objective response rate, partial response, and PFS at six months. Our goal is to complete Phase 2b enrollment of 31 patients by the end of 2024, and we are on schedule to do that. The trial is substantially funded by the National Cancer Institute at present for up to 55 patients at five sites. We are in the process of negotiating with the NIH to expand the trial sites to a number sufficient such that we can rapidly complete the Phase 2b and a presumed Phase III pivotal trial thereafter. In parallel to our discussions with the NIH, we are actively engaged with over 17 sites in the U.S. and Europe as possible new trial sites, and we're pleased with the interest we see in that trial. Now, regarding the ongoing Phase I GBM dose escalation trial for larger and more complex tumors over 20 cc. As announced, we have now enrolled the three required dose escalation patients in cohort 8 and administered a dose of 41.5 millicuries and 16.3 milliliters. That dose and volume are approximately double the dose and volume used in the current phase 2b. In total, since trial initiation, 27 patients have been enrolled in just the phase one dose escalation portion of the trial. Since we have yet to reach a phase one trial stopping point based on reaching a maximum tolerated dose, we have several options in terms of how we may proceed. We are in the process of analyzing the data from cohort seven and eight from the phase one and intend to provide guidance on next steps once the data is analyzed and a plan is formulated. Now, a bit of a side note or perspective on this phase one dose escalation portion of the trial. Irrespective of whatever we do in terms of next steps, I want to highlight the fact that we are breaking new ground in medicine here with this trial. Specifically, if you look in terms of the amount of radiation and volume that we are now safely delivering to a single cerebral hemisphere in a patient that may have a tumor of 30 cc's or more. It's truly remarkable that we've been able to do that safely, including administering up to 740 gray in a single administration administered dose to the tumor. Don't want that to be lost here. And we haven't reached a maximum tolerated dose. So moving on to the LM development program. As announced, we completed part A of the phase one respect LM trial. In total thus far, have been treated across three dosing cohorts. And in fact, one patient was retreated under compassionate use protocol. The maximum administered dose thus far, and that was administered in cohort three, is 26.4 millicuries up from 6.6 millicuries that were delivered in the three patients in cohort one. At the cohort three dose, the computed maximum absorbed dose to the CSF is approximately 200 gray of radiation. Thus far, no dose-limiting toxicities have been observed, and the safety profile, as is in our GBM trial, appears to be favorable, and nine of the 10 LM patients treated thus far remain alive. The go-forward plan is to conduct a cohort three DSMB meeting followed by an FDA type C meeting to finalize the dosing regime for part B of the phase one as requested by the FDA during our original negotiations for the trial. Presumably, we will continue to dose escalate through a single administration until a maximum tolerated dose is reached and then incorporate multiple doses over time thereafter. it's helpful to us to be able to have already treated one patient under compassionate use with two separate treatments. Separately, we're working on a single institution leptomeningeal metastases trial specifically for melanoma primaries and more about that as that develops. In addition, we plan to treat patients at the cohort three dose to gain additional safety and efficacy data until cohort four is approved And we will consider, as I mentioned, selectively retreating patients after the stipulated trial follow-up period of 90 days if patient and their physician feel it would be . As with the GBM trials, we are focused heavily in 2023 on onboarding new LM trial sites for the Phase I Part B, and 20 sites are currently under evaluation. Finally, PLUS continues to receive support for the program through our $17.6 million SEPRINT grant awarded last year. Now, regarding our development program for pediatric brain cancer, based on the back-and-forth communication we've had thus far with the FDA, which goes back almost a year, we expect to submit an updated investigational new drug application soon for what will be called the RESPECT, PBC Phase 1 Safety Dose Finding and Efficacy Study of Rhenium Obispumata for Two Pediatric Brain Tumors, specifically ependymoma and high-grade glioma. The FDA has essentially signed off on the clinical trial plan, but they've asked for additional safety data from the human trial, which we've put together and will be refiling as part of that IAD update. That will be submitted in conjunction with the lead academic institution that we've been working with along the way on this trial, and that's Lurie Children's Hospital of Northwestern University in Chicago. Now, a bit about supply chain. It's very important that we have drug available for any patient we treat and that we're at a stage appropriate to where we are in the development clinically as it relates to our supply chain. So, maintaining a robust and redundant supply chain for rhenium-obistumate supply is critical. In previous quarters, we have added key suppliers and consummated important CMO relationships as we have developed GMP drug for our trials. We anticipate continuing in 2023 to expand those relationships and, in fact, add new relationships such that we are ready for a potential phase three trial or alternatively an accelerated approval tract if that presents itself. Now a bit about commercial planning. Commercial go-to-market planning, including relevant medical economic research, billing and coding considerations, and ultimately drug pricing and commercial launch planning decisions, are proceeding in the background consistent with our stage of development. Now, regarding our novel in-license radioembolic microparticle technology, RNL-BAM. Recall that in 2022, we closed the license for RNL-BAM, transferred the technology, successfully manufactured the product, and completed product feasibility work in a human ex vivo kidney perfusion model. We also sought the FDA's opinion on regulatory designation at the end of 2022. Currently, we have an active dialogue ongoing with the FDA, including a previously submitted preliminary request for designation. The outcome of that determination will dictate many of the next steps in preclinical development program and the timeline to the clinic, specifically whether that ultimate designation is a device, drug, or combination product. Notably, the legacy products that have been out for 20 plus years our devices, we think likely this should be regulated as a drug, but we await the outcome of that back and forth. So with that summary on our clinical development programs, I'll turn the floor over to our Chief Financial Officer, Andrew Sims, who will review the financials. Andrew?
spk01: Thank you, Mark. Good afternoon, everyone. Please refer to our press release issued earlier today for a summary of our financial results for the 2023 first quarter ended March 31, 2023. As of March 31, 2023, cash and cash equivalents were $12.7 million compared to $18.1 million as of December 31, 2022. In addition to current cash on hand, the company benefits from grant awards of $3 million from the NIH and $17.6 million from CPREC. The company also has discretionary or stockholder-approved access to capital from its ATM and equity line of credit of at least $49 million. In aggregate, these capital sources could provide sufficient capital to fund currently planned and anticipated activities through 2025, if fully utilized. The company recognized $506,000 of grant revenue in the first quarter of 2023, which represents a separate share of costs incurred to fund a portion of our LM clinical program. Total operating expenses for the first quarter of 2023 were 5.2 million compared to total operating expenses of 3.9 million for the same period the prior year. The increase is due primarily to a 750,000 license payment to Nano TX Corp for successfully meeting a key clinical milestone and related clinical expenses due to increased enrollment in the company's lead development programs. Interest expense decreased from $198,000 for the first quarter of 2022 to $134,000 for the first quarter of 2023. This decrease reflects the continued principal pay down that commenced in November 2021 on the company's Oxford debt. Net loss for the quarter for the first quarter of 2023 was 4.8 million, or 14 cents per share, compared to a net loss of 4.1 million, or 19 cents per share, for the same period the prior year. Now I'll turn it back to Mark.
spk06: Thank you, Andrew. Before we move on to Q&A, allow me to provide guidance on anticipated milestones for the remainder of 2023. Importantly, we intend to publish the RESPECT-GBM Phase 1 data in a peer-reviewed journal. Second, we intend to present safety and efficacy data from the RESPECT-GBM trials in the second half of 2023, as well as present safety and efficacy data of the Phase 1 Part A of the RESPECT leptomeningeal metastases trial in the second half of 2023 as well. We also intend to initiate phase one part B of the RESPECT-LM trial in the second half of 2023 following an anticipated FDA type C meeting mid-year. We intend to complete key enrollment and site expansion activities as mentioned in the RESPECT-GBM phase two B trial such that we can meet full trial enrollment by year end 2024. We plan to initiate the Phase I RESPECT pediatric brain cancer trial, or PBC trial, for pediatric patients with ependymoma and high-grade glioma. We intend to determine the appropriate FDA regulatory designation for RNL-BAM technology and complete the key development activities as mentioned. We also intend to complete preclinical synergistic drug combination studies of rhenium-obispumate along with systemic therapies for GBM and LM, and we intend to submit multiple grant applications in order to try to secure additional non-dilutive capital to support expansion of the company's drug development pipeline. So at this point now, let me turn it back over to you, Jonathan, and we'll go through our Q&A session.
spk00: Certainly. Ladies and gentlemen, if you'd like to ask a live audio question at this time, please press star 11 on your telephone. If your question has been answered and you'd like to remove yourself from the queue, simply press star 11 again. And I understand that we also have some questions that were pre-submitted from Justin Walsh from Jones Training, and we'll take those questions first.
spk01: Thanks, Jonathan. Justin, thank you for emailing the questions in. The first question is, radiopharmaceuticals seem to be in the spotlight with notable commercial success in imaging and therapy in prostate cancer. Any comments on the evolving development landscape for radiopharmaceuticals in brain cancer? And as a follow-up to that, can you remind us of the potential benefits of your approach versus molecularly targeted and or systemic approaches in the context of brain cancer? Norman, do you want to?
spk12: Yeah, thank you. Thanks for that question, Justin. I think it it gets to the core of what's, um, you know, what we're doing that's very typical of, uh, radiopharmaceuticals, but what distinguishes us and de-risks our efforts based on, uh, particularly our, um, our delivery platform. Um, your first question was kind of the radio, you know, having commercial success. So the PSMA and the serotonin products, lutetian products were well aware of and, and, um, you know, they're welcome and fill an important medical need. But I think they're very good representatives of what's required in the classic targeted systemically administered radiopharmaceuticals where you have the extra requirement of preclinical and clinical trials to both confirm and optimize that targeting technology. the time and risk to accomplish that, the money, and then the package insert language that goes along with that. Again, both of these are fine products, but I'll use the serotonin product for the neuroendocrine tumors as those were developed starting in the mid-2000s. There was both a DOTATATE and DOTATOC product. The Lutera is the lutetium product, the Ytrium-90. both had similar efficacious doses, both had a common safety profile, and it was recognized during the excellent clinical trials and development for these that there was some renal toxicity. So the community had to spend time dealing with that, and they did that successfully with, I think folks know, the amino acid cocktail that goes in at the time of administration to enhance and accelerate the renal excretion of the product so you decrease the unnecessary absorbed dose to the kidneys and be able to get best benefit to the targeted therapy. So that gets me to what we're doing. So the common approach is we all know radiation works very well in cancer. That's non-controversial. It's been well accepted for decades. What we're leveraging is the well-established, and I'll use GBM first, the well-established access to a lesion in the central nervous system by convection-enhanced delivery catheters, the CED catheters, an elegant discovery by NIH in the late 90s, early 2000s, that have been used extensively in administrations, and with the hope to avoid the blood-brain barrier challenges, and so forth and get the appropriate chemotherapy right where it's needed, when it's needed. Well, these molecules typically did get there very effectively with that excellent delivery technology, but quickly also diffused away and unfortunately didn't result in any significant improvement in how these patients were doing despite the initial promise in some early promising phase one preliminary studies. But at the end of the day, People have recognized that that holy grail for delivering chemotherapy because of the way those molecules behave locally sadly was not realized. Because of that delivery, however, because of our formulation with a bifunctionally chelated rhenium isotope, which is the rhenium-186, and I won't go into details now of why that is nearly an optimal choice for a radiation therapy isotope, bifunctionally chelated and encapsulated in nanoliposome for durable localization after direct local regional delivery to the tumor. And I think folks have seen our presentations. They've been peer-reviewed and accepted at meetings. And as Mark mentioned, we're going to be publishing the Phase I data in the coming weeks or submitting it for publication. So the differentiation is we're able to successfully get the isotope, which is, you know, what is providing efficacy to where it needs to go. And our formulation allows it to stay there through the decay cycles, you know, the physical half-lives that are there. So it works out very well. And your question touched on, you know, maybe other radiopharmaceutical systemic therapies. They suffer some of the same challenges that the systemic chemotherapies establish, the blood-brain barrier challenges and so forth. So the direct delivery, and we're told by both the neurosurgeons and the neuro-oncologists that that's the way to go. And in a comparable way, our direct delivery via an intraventricular catheter or myoresebor to the subarachnoid space and leptomeningeal metastases accomplishes the same local delivery that the GBM paradigm and administration paradigm accomplishes. Hopefully that satisfies your question, Justin. Thanks.
spk01: Second question. It's great to see the addition of Northwestern Memorial Hospital as a trial site. Can you provide any color on how easy or challenging it is to onboard new sites? And then do you have a sense of how that could translate to potential commercial success down the line And what type of sites do you imagine these assets could be administered at, e.g., only top centers versus any hospital with a working radiopharmacy? Norman?
spk12: Yeah, I'll take that, too. Some very good points on this that I'd like to touch. You know, I smile at your easy or challenging for sites. I'd rather use the word, you know, getting a site on board is very straightforward. You know, we have three major, you know, collaborators that have to mesh nicely with and the protocol and the various documents we have, the scope events and things like that, coordinate how the neuro-oncology, neurosurgery, and nuclear medicine have to collaborate, cooperate in a well-defined manner and a well-defined sequence of events to get patients treated. So all that's well-defined in our protocols and in our processes to involve a site. We're very proud that Northwestern's involved. We have a number of others in the pipeline that are there. And, you know, the processes are well established to get them on board. And the contractual process is such that we have plenty of time to do that in a very effective, thorough manner. I do have to say that the sites, all the sites are evolving and coming out of, I call it the COVID era. era of staffing issues and virtual at-home work and things like this. But we have found our processes and how we get folks involved and the fact that each of the three major areas that I mentioned, neurosurgery, neuro-oncology, nuclear medicine, all are doing activities they typically do. We just give them a process that they're collaborating with that for a particular patient at particular well-defined points in time. In terms of elite sites, these are the sites that you would expect. We're very pleased that we're actually getting inquiries from a lot of sites because we've been presenting at meetings. They hear the data. They see the data. They talk to each other. They see the tolerability and the safety of what's going on. So we have let the data speak for itself. They're coming along. And, of course, they'll be the core of any future commercial success platform. But as time goes on and as we present more data, we're getting inquiries and interest from even, I don't want to call them non-elite sites, but the large commercial hospitals. And you mentioned the radiopharmacy. The product is shipped to the site ready to use and administer. Most sites do not have an active radiopharmacy that they used to have In prior decades, you have local large pharmacies that deliver patient-ready doses for both imaging and therapy. So that will not be an issue whatsoever. And we find that the sites we're using will be the platform for commercial launch. And by then, we expect to have 20 to 40 sites in a pivotal trial or more. Hopefully, I think that covers all that you asked in this last question. Thanks.
spk01: Question three. Can you provide any additional color on what we should expect from the data readouts in the second half of 2023, for example, estimates on patient numbers, et cetera?
spk06: I'll take that. That's okay. So, yeah, kind of reiterating, Justin, what I mentioned earlier. The plan for GBM is, A, to get the phase one That's cohorts one through six. That will be a comprehensive publication with full statistical evaluation of the data, and we've been invited by a top-tier peer-reviewed journal, High Impact Factor, to submit. So that's largely done. So hopefully that will go well, and that will be helpful also, as Norman said, to get new sites on board, because that's peer-reviewed data that we could use in discussions with sites. In terms of ongoing data in the Phase I, II, GBM, as well as the LM trial, the plan would be to present second half of the year, coinciding most likely with the Society for Neuro-Oncology meetings. We had a podium presentation there last November. And the plan would be to present there as well, update both Phase I, Phase II for GBM, as well as present the Phase I, Part A trial from LM. And I think the second part of the question was estimate enrollment. So our plan, I mean, this is not a 5,000 patient, any hypertensive trial. Our plan here is to, we've got a timeline in place to get to phase two, for example, enrolled by the end of 2024, perhaps a bit ahead of schedule. We'll provide guidance on quarterly calls as to whether we're on schedule or not. If something materially happens that's better or worse, we'll mention that. However, my preference is not to present specific patient numbers in the absence of the data itself. And so, for example, at Snow, we'll update in terms of trial numbers, or when we hit a major milestone in terms of enrollment, we'll announce that or discuss that, but not on our earnings call to present individual numbers. patient numbers. As it relates to the LM trial, we'll continue our current practice, which is to present when we hit major regulatory milestones or cohort enrollment milestones. We'll announce those, but that will be more frequent likely as we hit each milestone. So that's the plan, and we'll update folks accordingly.
spk01: Last question from Justin. Based on your updates, you're obviously keeping pace with enrollment. Can you comment on investigator and patient enthusiasm that you've encountered?
spk05: Norman? Yeah.
spk12: Justin, as Mark mentioned, enrollment is going well, and that's always nice to see. But I think as everyone on the call might appreciate, you know, it's all about getting sites and making sure we expand those sites. And Mark has also mentioned our plans to do that, and it's on track. depending on what we hear from FDA and the rapidity of the Phase II enrollment, the number of sites we add will be within the scope of what we have to perform for the agency feedback. And I like the way you asked this. You asked about both investigator and patient enthusiasm, and we're getting both. And I think it's really important to emphasize that, and I'll give you maybe a couple of quick examples. what we consistently get from the investigators and I'll get, you know, I think folks know I have a Hopkins heritage and I know a lot of folks there. And at the recent snow meeting, skip Grossman got the, um, or oncologist, you know, uh, had their, uh, past colleague of mine and got the lifetime achievement award. And he saw our presentation on LM and, you know, we know each other and we got to speaking and his comment paraphrase is These LM patients really have nothing and we're very motivated to get involved in this trial. And for example, that's one of the sites and something that one of the person I respect and I think is well known in the field and respected by others have recognized. And and we've gotten this in many different ways. I can give you other institutions and names that have, you know, have presented a similar plea and and. and observation of the peer-reviewed data we have presented. Equally important are the patients we've done. And I sometimes go to sites, particularly when the site asks for my involvement for just a second set of eyes and ears if they're a newer site or maybe a difficult patient to be just an observer. But to put it in some perspective, More than once, the patients have said, you know, I'm grateful for this opportunity and this option. I have no other options. And when they've gone through it and we've heard some follow-up, it's, you know, I didn't realize that it was this easy. And what they've asked both Mark and I is, is there a way that I can participate in communicating to other patients what you know what i've experienced and how i feel about it in some way that's acceptable and i'll i think i'm going to embarrass mark now and give you a specific example from the site on a patient uh an rgbm patient who you know had your typical gbm complications he had difficulty walking and you know and other things i won't go into that detail um and uh and lamented and about having to drop out of his senior softball league and so forth. To make a long story short, within about two to three weeks after his treatment, he was back to playing softball. He asked me to send him pictures of his treatment because as everyone knows, we have real-time evaluation because of the simultaneous gamma decay. So we're able to very accurately validate where the treatment goes. So in this patient's case, he wanted to be able to have that. He has his own website and things, and he was kind of commenting to folks who know his challenge of the success he has. And to make a long story short, he again raised the question about, is there a way that I can share my story? And we're in the process of doing that. And part of sharing that story is 5K, this gentleman, will be running next month. And I think our esteemed chief executive officer will be running the 5K with him. So, Mark, I'm sorry to embarrass you, but I figured this is a prime example of how not only the investigators but the patient enthusiasm for this product has really been very gratifying for me both personally and professionally. So thank you, Justin, for that answer.
spk06: Okay, Jonathan, I think Dustin got his money's worth on those questions, so who do we have next?
spk00: Certainly. Then our first question from the phone line comes from the line of Sean Lee from HC Wainwright. Your question, please.
spk09: Hey, Sean. Good afternoon, guys, and thanks for taking my questions. My first question is on the GBM side. Now, you mentioned that the study for treating larger tumors has been going well, and you've been able to test the higher doses of RM. I was wondering whether that's something that you consider roll into a potential future phase three in GBM, or would you keep the two separate, like the regular dose and the higher dose?
spk06: It depends on the data. You know, I think, as I mentioned, we're in the process of analyzing cohort seven and eight. Important part of that is looking at the distribution and the effect of increasing volume and radiation. And I think as you probably, I'm sure you do know, Sean, back in cohort six, we actually increased the flow rate from the first three patients to the second three patients in cohort six. So there are a lot of levers we can pull. I wouldn't rule anything out at this point. But I would just say, to kind of finish, we're going where no man's gone before in terms of the volume we're putting in the brain, the amount of radiation. There's real value in continuing to do patients and tweaking the delivery parameters, and our plan is to continue to do that. And that's what FDA wants, and I think that's what the NCI wants. I see.
spk08: Thanks for your thoughts on that.
spk09: My second question is on the LM study. You mentioned that you were testing it in particular with melanoma patients. I was wondering why melanoma? And is there something you see or you think in that case that makes it particularly well suited for RMG?
spk12: Go ahead, Nora. Let me take that one. And I appreciate that question because it brings up another aspect of LM, which we, I think folks on the phone know, can be caused from any solid tumor, any, you know, many of the liquid tumors and even the primary brain tumors. Of course, the most prevalent, you know, breast, lung, GI, head and neck and melanoma are most frequent. Regulatory requirements by FDA typically require And they've said this much will be what I call a disease-specific indication. So going forward, given the most likely etiologies for LM are lung and breast, I would see us, and our current protocol is written with that focus, although on our initial dose escalation, we do have it with all comers. but regulatorily we will have to focus it in a disease-specific way and pick the ones that would target the most people that we can help. Melanoma is an example of another disease indication, but the reason we're splitting that out is because it's a more difficult complication, and melanoma has shown some systemic therapeutic effects, particularly with the immunotherapy in general and checkpoint inhibitors in particular. And I won't go into the systemic therapies now, but there's a real opportunity for a combination approach for leptomeningeal treatment with our product and a combination approach with whether checkpoints or other immunotherapy in a way that we're determining now with some select slides.
spk09: Thank you. That was very helpful. My final question is on the upcoming pediatric study. I was wondering whether you had to make specific adjustments to your delivery method because I know it uses the convection catheters. Is there going to be any difference than what you've done so far for the adults?
spk12: Yeah, great question, and the short answer is no, but let me give a little bit more color. I'm not known for my one-word answers, so sorry about that. It'll be the same approach, and what is interesting is the pediatric neurologists are used to for epileptic and evaluations. You know, you would think, oh, my goodness, putting a catheter in a child's brain is going to be tough. Well, they're used to doing this not only with two or three or four catheters as we're doing with adults, but, you know, six, eight, ten or more catheters. So the catheter and CED approach is something they're very comfortable with. They do all the time with, you know, epilepsy, left probe, targeting and tracing, for example. And the only thing I would anticipate that might be different is, particularly for ependymomas, some of these can be quite large volumes. And that will be something as we get into later dose escalations for those larger volumes that we'll have to evaluate may be different. Mark already mentioned in the adult cohort eight, we're going to be increasing the volumes. So I would anticipate that in adult administrations, although we have very tolerable infusion times, of course, depending on which dose we're using and the volume of infusate that I see reducing that by 50%. And I think the same possibilities for reduction and even greater reduction occurs in kids. And I already mentioned the fact that in the larger tumors, more catheters will be likely, and the more catheters mean the larger volume can be given over a fixed unit of time. Does that answer your question, Sean?
spk09: Yes, it does. Thank you again for picking up my questions. That's all I have.
spk00: Thank you, Sean. Thank you. One moment for our next question. And our next question comes from the line of Edward Wu from Ascendant Capital. Your question, please.
spk11: Yeah, congratulations on all the progress. My question is on the CPIRC grants. Are there any restrictions to where you can locate your sites or any other requirements that you guys have when you guys run these clinical trials?
spk06: Hey, Ed, no, there's no restrictions on where those clinical sites can be. There's some restrictions around having sites in Texas and so forth and having employees and office space and so forth in Texas, but not in terms of sites.
spk10: Great. Well, that's all the questions I have. Thank you.
spk00: Okay.
spk10: Thanks.
spk00: Thank you. Once again, if you have a question at this time, please press star 1-1. And this does conclude the question and answer session of today's program. I'd like to hand the program back to Dr. Mark Hedrick for any further remarks.
spk06: Thank you, Jonathan. Appreciate the questions today and appreciate your attention. And we want to finish up by thanking our employees and patients and physicians and collaborators we work with and our stockholders for their continued support. Thank you for the questions today, and we wish you a nice evening. Thank you.
spk00: Thank you, ladies and gentlemen, for your participation at today's conference. This does conclude the program. You may now disconnect. Good day. Thank you. Thank you. Thank you. Thank you. Thank you. Good afternoon, ladies and gentlemen. Welcome to the Plus Therapeutics first quarter 2023 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.
spk06: Thank you, Jonathan. 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 2023 first quarter financial results. Joining me for the call today is Dr. Norman LaFrance, our Chief Medical Officer, and Andrew Sims, our Chief Financial Officer. I'll begin the call by reviewing our recent clinical and regulatory progress with a focus on the first quarter, and then turn the call over to Andrew to review our financials. Dr. LaFrance then will be joining us for Q&A. I can say we had a very productive start to 2023, highlighted by the increased enrollment momentum of our two lead programs in glioblastoma, or GBM, and leptomeningeal metastases, or LM. Starting with our GBM program and the Phase IIb trial, we are actively enrolling the Phase IIb clinical trial of rhenium obispumata in patients with small to medium-sized GBM tumors with a 20-centimeter, a 20cc, or a 20-milliliter cutoff. The single administered dose is 22.3 millicuries and 8.8 mLs, and the primary endpoint is overall survival, and there are a number of typical secondary endpoints, such as safety, objective response rate, partial response, and PFS at six months. Our goal is to complete Phase 2b enrollment of 31 patients by the end of 2024, and we are on schedule to do that. The trial is substantially funded by the National Cancer Institute at present for up to 55 patients at five sites. We are in the process of negotiating with the NIH to expand the trial sites to a number sufficient such that we can rapidly complete the Phase 2b and a presumed Phase III pivotal trial thereafter. In parallel to our discussions with the NIH, we are actively engaged with over 17 sites in the U.S. and Europe as possible new trial sites, and we're pleased with the interest we see in that trial. Now, regarding the ongoing Phase I GBM dose escalation trial for larger and more complex tumors over 20 cc. As announced, we have now enrolled the three required dose escalation patients in cohort 8 and administered a dose of 41.5 millicuries and 16.3 milliliters. That dose and volume are approximately double the dose and volume used in the current phase 2b. In total, since trial initiation, 27 patients have been enrolled in just the phase one dose escalation portion of the trial. Since we have yet to reach a phase one trial stopping point based on reaching a maximum tolerated dose, we have several options in terms of how we may proceed. We are in the process of analyzing the data from cohort seven and eight from the phase one and intend to provide guidance on next steps once the data is analyzed and a plan is formulated. Now, a bit of a side note or perspective on this phase one dose escalation portion of the trial. Irrespective of whatever we do in terms of next steps, I want to highlight the fact that we are breaking new ground in medicine here with this trial. Specifically, if you look in terms of the amount of radiation and volume that we are now safely delivering to a single cerebral hemisphere in a patient that may have a tumor of 30 cc's or more. It's truly remarkable that we've been able to do that safely, including administering up to 740 gray in a single administration administered dose to the tumor. Don't want that to be lost here. And we haven't reached a maximum tolerated dose. So moving on to the LM development program. As announced, we completed part A of the phase one respect LM trial. In total thus far, have been treated across three dosing cohorts. And in fact, one patient was retreated under compassionate use protocol. The maximum administered dose thus far, and that was administered in cohort three, is 26.4 millicuries up from 6.6 millicuries that were delivered in the three patients in cohort one. At the cohort three dose, the computed maximum absorbed dose to the CSF is approximately 200 gray of radiation. Thus far, no dose-limiting toxicities have been observed, and the safety profile, as is in our GBM trial, appears to be favorable, and nine of the 10 LM patients treated thus far remain alive. The go-forward plan is to conduct a cohort three DSMB meeting followed by an FDA type C meeting to finalize the dosing regime for part B of the phase one as requested by the FDA during our original negotiations for the trial. Presumably, we will continue to dose escalate through a single administration until a maximum tolerated dose is reached and then incorporate multiple doses over time thereafter. it's helpful to us to be able to have already treated one patient under compassionate use with two separate treatments. Separately, we're working on a single institution leptomeningeal metastases trial specifically for melanoma primaries and more about that as that develops. In addition, we plan to treat patients at the cohort three dose to gain additional safety and efficacy data until cohort four is approved And we will consider, as I mentioned, selectively retreating patients after the stipulated trial follow-up period of 90 days if patient and their physician feel it would be . As with the GBM trials, we are focused heavily in 2023 on onboarding new LM trial sites for the phase one part B, and 20 sites are currently under evaluation. Finally, PLUS continues to receive support for the program through our $17.6 million CPRIT grant awarded last year. Now, regarding our development program for pediatric brain cancer, based on the back-and-forth communication we've had thus far with the FDA, which goes back almost a year, we expect to submit an updated investigational new drug application soon for what will be called the RESPECT, PBC Phase 1 Safety Dose Finding and Efficacy Study of Rhenium Obispumata for Two Pediatric Brain Tumors, specifically ependymoma and high-grade glioma. The FDA has essentially signed off on the clinical trial plan, but they've asked for additional safety data from the human trial, which we've put together and will be refiling as part of that IAD update. That will be submitted in conjunction with the lead academic institution that we've been working with along the way on this trial, and that's Lurie Children's Hospital of Northwestern University in Chicago. Now, a bit about supply chain. It's very important that we have drug available for any patient we treat and that we're at a stage appropriate to where we are in the development clinically as it relates to our supply chain. So maintaining a robust and redundant supply chain for rhenium-obispoamate supply is critical. In previous quarters, we have added key suppliers and consummated important CMO relationships as we have developed GMP drug for our trials. We anticipate continuing in 2023 to expand those relationships and, in fact, add new relationships such that we are ready for a potential phase three trial or alternatively an accelerated approval tract if that presents itself. Now a bit about commercial planning. Commercial go-to-market planning including relevant medical economic research, billing and coding considerations, and ultimately drug pricing and commercial launch planning decisions are proceeding in the background consistent with our stage of development. Now, regarding our novel in-license radioembolic microparticle technology, RNL-BAM. Recall that in 2022, we closed the license for RNL-BAM, transferred the technology, successfully manufactured the product, and completed product feasibility work in a human ex vivo kidney perfusion model. We also sought the FDA's opinion on regulatory designation at the end of 2022. Currently, we have an active dialogue ongoing with the FDA, including a previously submitted preliminary request for designation. The outcome of that determination will dictate many of the next steps in preclinical development program and the timeline to the clinic, specifically whether that ultimate designation is a device, drug, or combination product. Notably, the legacy products that have been out for 20 plus years our devices, we think likely this should be regulated as a drug, but we await the outcome of that back and forth. So with that summary on our clinical development programs, I'll turn the floor over to our Chief Financial Officer, Andrew Sims, who will review the financials. Andrew?
spk01: Thank you, Mark. Good afternoon, everyone. Please refer to our press release issued earlier today for a summary of our financial results for the 2023 first quarter ended March 31, 2023. As of March 31, 2023, cash and cash equivalents were $12.7 million compared to $18.1 million as of December 31, 2022. In addition to current cash on hand, the company benefits from grant awards of $3 million from the NIH and $17.6 million from CPREC. The company also has discretionary or stockholder-approved access to capital from its ATM and equity line of credit of at least $49 million. In aggregate, these capital sources could provide sufficient capital to fund currently planned and anticipated activities through 2025 if fully utilized. The company recognized $506,000 of grant revenue in the first quarter of 2023, which represents a separate share of costs incurred to fund a portion of our LM clinical program. Total operating expenses for the first quarter of 2023 were $5.2 million compared to total operating expenses of $3.9 million for the same period the prior year. The increase is due primarily to a $750,000 license payment to Nano TX Corp for successfully meeting a key clinical milestone and related clinical expenses due to increased enrollment in the company's lead development programs. Interest expense decreased from $198,000 for the first quarter of 2022 to $134,000 for the first quarter of 2023. This decrease reflects the continued principal pay down that commenced in November 2021 on the company's Oxford debt. Net loss for the quarter for the first quarter of 2023 was 4.8 million or 14 cents per share compared to a net loss of 4.1 million or 19 cents per share for the same period the prior year. Now I'll turn it back to Mark.
spk06: Thank you, Andrew. Before we move on to Q&A, allow me to provide guidance on anticipated milestones for the remainder of 2023. Importantly, we intend to publish the RESPECT-GBM Phase 1 data in a peer-reviewed journal. Second, we intend to present safety and efficacy data from the RESPECT-GBM trials in the second half of 2023, as well as present safety and efficacy data of the Phase 1 Part A of the RESPECT leptomeningeal metastases trial in the second half of 2023 as well. We also intend to initiate phase one part B of the RESPECT-LM trial in the second half of 2023 following an anticipated FDA type C meeting mid-year. We intend to complete key enrollment and site expansion activities as mentioned in the RESPECT-GBM phase two B trial such that we can meet full trial enrollment by year end 2024. We plan to initiate the Phase I RESPECT pediatric brain cancer trial, or PBC trial, for pediatric patients with ependymoma and high-grade glioma. We intend to determine the appropriate FDA regulatory designation for RNL-BAM technology and complete the key development activities as mentioned. We also intend to complete preclinical synergistic drug combination studies of rhenium-obispumate along with systemic therapies for GBM and LM, and we intend to submit multiple grant applications in order to try to secure additional non-dilutive capital to support expansion of the company's drug development pipeline. So, at this point now, let me turn it back over to you, Jonathan, and we'll go through our Q&A session.
spk00: Certainly. Ladies and gentlemen, if you'd like to ask a live audio question at this time, please press star one one on your telephone. If your question has been answered and you'd like to remove yourself from the queue, simply press star one one again. And I understand that we also have some questions that were pre-submitted from Justin Walsh from Jones Training. We'll take those questions first.
spk01: Thanks, Jonathan. Justin, thank you for emailing the questions in. The first question is, radiopharmaceuticals seem to be in the spotlight with notable commercial success in imaging and therapy in prostate cancer. Any comments on the evolving development landscape for radiopharmaceuticals in brain cancer? And as a follow-up to that, can you remind us of the potential benefits of your approach versus molecularly targeted and or systemic approaches in the context of brain cancer? Norman, do you want to?
spk12: Yeah, thank you. Thanks for that question, Justin. I think it it gets to the core of what's, um, you know, what we're doing that's very typical of, uh, radiopharmaceuticals, but what distinguishes us and de-risks our efforts based on, uh, particularly our, um, our delivery platform. Um, your first question was kind of the radio, you know, having commercial success. So the PSMA and the serotonin products, lutetium products were well aware of and, and, um, you know, they're welcome and fill an important medical need. But I think they're very good representatives of what's required in the classic targeted systemically administered radiopharmaceuticals where you have the extra requirement of preclinical and clinical trials to both confirm and optimize that targeting technology. the time and risk to accomplish that, the money, and then the package insert language that goes along with that. Again, both of these are fine products, but I'll use the serotonin product for the neuroendocrine tumors as those were developed starting in the mid-2000s. There was both the DOTATATE and DOTATOC product. The Lutera is the lutetium product, the Ytrium-90. both had similar efficacious doses, both had a common safety profile, and it was recognized during the excellent clinical trials and development for these that there was some renal toxicity. So the community had to spend time dealing with that, and they did that successfully with, I think folks know, the amino acid cocktail that goes in at the time of administration to enhance and accelerate the renal excretion of the product So you decrease the unnecessary absorbed dose to the kidneys and be able to get best benefit to the targeted therapy. So that gets me to what we're doing. So the common approach is we all know radiation works very well in cancer. That's non-controversial. It's been well accepted for decades. What we're leveraging is the well-established, and I'll use GBM first, the well-established access to a lesion in the central nervous system by convection-enhanced delivery catheters, the CED catheters, an elegant discovery by NIH in the late 90s, early 2000s, that have been used extensively in administrations, and with the hope to avoid the blood-brain barrier challenges. and so forth and get the appropriate chemotherapy right where it's needed, when it's needed. Well, these molecules typically did get there very effectively with that excellent delivery technology, but quickly also diffused away and unfortunately didn't result in any significant improvement in how these patients were doing despite the initial promise in some early promising phase one preliminary studies. But at the end of the day, People have recognized that that holy grail for delivering chemotherapy because of the way those molecules behave locally sadly was not realized. Because of that delivery, however, because of our formulation with a bifunctionally chelated rhenium isotope, which is the rhenium-186, and I won't go into details now of why that is nearly an optimal choice for a radiation therapy isotope, bifunctionally chelated and encapsulated in a nanoliposome for durable localization after direct local regional delivery to the tumor. And I think folks have seen our presentations. They've been peer reviewed and accepted at meetings. And as Mark mentioned, we're going to be publishing the phase one data in the coming weeks or submitting it for publication. So the differentiation is we're able to successfully get the isotope, which is, you know, what is providing efficacy to where it needs to go. And our formulation allows it to stay there through the decay cycles, you know, the physical half-lives that are there. So it works out very well. And your question touched on, you know, maybe other radiopharmaceutical systemic therapies. They suffer some of the same challenges that the systemic chemotherapies establish, the blood-brain barrier challenges and so forth. So the direct delivery, and we're told by both the neurosurgeons and the neuro-oncologists that that's the way to go. And in a comparable way, our direct delivery via an intraventricular catheter or myoresebor to the subarachnoid space and leptomeningeal metastases accomplishes the same local delivery that the GBM paradigm and administration paradigm accomplishes. Hopefully that satisfies your question, Justin. Thanks.
spk01: Second question. It's great to see the addition of Northwestern Memorial Hospital as a trial site. Can you provide any color on how easy or challenging it is to onboard new sites? And then do you have a sense of how that could translate to potential commercial success down the line And what type of sites do you imagine these assets could be administered at, e.g., only top centers versus any hospital with a working radiopharmacy? Norman?
spk12: I'll take that, too. Some very good points on this that I'd like to touch. You know, I smile that you're easy or challenging for sites. I'd rather use the word, you know, getting a site on board is very straightforward. You know, we have three major, you know, collaborators that have to mesh nicely. and the protocol and the various documents we have, the scope events and things like that, coordinate how the neuro-oncology, neurosurgery, and nuclear medicine have to collaborate, cooperate in a well-defined manner and a well-defined sequence of events to get patients treated. So all that's well-defined in our protocols and in our processes to involve a site. We're very proud that Northwestern's involved. We have a number of others in the pipeline that are there. And, you know, the processes are well established to get them on board. And the contractual process is such that we have plenty of time to do that in a very effective, thorough manner. I do have to say that the sites, all the sites are evolving and coming out of, I call it the COVID era. era of staffing issues and virtual at-home work and things like this. But we have found our processes and how we get folks involved and the fact that each of the three major areas that I mentioned, neurosurgery, neuro-oncology, and nuclear medicine, all are doing activities they typically do. We just give them a process that they're collaborating with that for a particular patient at particular well-defined points in time. In terms of elite sites, these are the sites that you would expect. We're very pleased that we're actually getting inquiries from a lot of sites because we've been presenting at meetings. They hear the data. They see the data. They talk to each other. They see the tolerability and the safety of what's going on. So we have let the data speak for itself. They're coming along. And, of course, they'll be the core of any future commercial success platform. But as time goes on and as we present more data, we're getting inquiries and interest from even, I don't want to call them non-elite sites, but the large commercial hospitals. And you mentioned the radiopharmacy. The product is shipped to the site ready to use and administer. Most sites do not have an active radiopharmacy that they used to have In prior decades, you have local large pharmacies that deliver patient-ready doses for both imaging and therapy. So that will not be an issue whatsoever. And we find that the sites we're using will be the platform for commercial launch. And by then, we expect to have 20 to 40 sites in a pivotal trial or more. Hopefully, I think that covers all that you asked in this last question. Thanks.
spk01: Question three. Can you provide any additional color on what we should expect from the data readouts in the second half of 2023, for example, estimates on patient numbers, et cetera?
spk06: I'll take that. That's okay. So, yeah, kind of reiterating, Justin, what I mentioned earlier. The plan for GBM is, A, to get the phase one That's cohorts one through six. That will be a comprehensive publication with full statistical evaluation of the data, and we've been invited by a top-tier peer-reviewed journal, High Impact Factor, to submit. So that's largely done. So hopefully that will go well, and that will be helpful also, as Norman said, to get new sites on board, because that's peer-reviewed data that we could use in discussions with sites. In terms of ongoing data in the Phase I, II, GBM, as well as the LM trial, the plan would be to present second half of the year, coinciding most likely with the Society for Neuro-Oncology meetings. We had a podium presentation there last November, and the plan would be to present there as well, update both Phase I, Phase II for GBM, as well as present the Phase I Part A trial from LM. And I think the second part of the question was estimate enrollment. So our plan, I mean, this is not a 5,000 patient, any hypertensive trial. Our plan here is to, we've got a timeline in place to get to phase two, for example, enrolled by the end of 2024, perhaps a bit ahead of schedule. We'll provide guidance on quarterly calls as to whether we're on schedule or not. If something materially happens that's better or worse, we'll mention that. However, my preference is not to present specific patient numbers in the absence of the data itself. And so, for example, at Snow, we'll update in terms of trial numbers, or when we hit a major milestone in terms of enrollment, we'll announce that or discuss that, but not on our earnings call to present individual data. patient numbers. As it relates to the LM trial, we'll continue our current practice, which is to present when we hit major regulatory milestones or cohort enrollment milestones. We'll announce those, but that will be more frequent likely as we hit each milestone. So that's the plan, and we'll update folks accordingly.
spk01: Last question from Justin. Based on your updates, you're obviously keeping pace with enrollment. Can you comment on investigator and patient enthusiasm that you've encountered?
spk05: Norman? Yeah.
spk12: Justin, as Mark mentioned, enrollment is going well, and that's always nice to see. But I think as everyone on the call might appreciate, you know, it's all about getting sites and making sure we expand those sites. And Mark has also mentioned our plans to do that, and it's on track. depending on what we hear from FDA and the rapidity of the Phase II enrollment, the number of sites we add will be within scope of what we have to perform for the agency feedback. And I like the way you asked this. You asked about both investigator and patient enthusiasm, and we're getting both. And I think it's really important to emphasize that, and I'll give you maybe a couple of quick examples. what we consistently get from the investigators and I'll get, you know, I think folks know I have a Hopkins heritage and I know a lot of folks there. And at the recent snow meeting, Skip Grossman got the, um, neuro-oncologist, you know, uh, head there, uh, past colleague of mine and got the lifetime achievement award. And he saw our presentation on LLM and, you know, we know each other and we got to speaking and his comment paraphrased is These LM patients really have nothing and we're very motivated to get involved in this trial. And for example, that's one of the sites and something that one of the person I respect and I think is well known in the field and respected by others have recognized. And we've gotten this in many different ways. I can give you other institutions and names that have, you know, have presented a similar plea and and. and observation of the peer-reviewed data we have presented. Equally important are the patients we've done. And I sometimes go to sites, particularly when the site asks for my involvement for just a second set of eyes and ears if they're a newer site or maybe a difficult patient to be just an observer. But to put it in some perspective, More than once, the patients have said, you know, I'm grateful for this opportunity and this option. I have no other options. And when they've gone through it and we've heard some follow-up, it's, you know, I didn't realize that it was this easy. And what they've asked both Mark and I is, is there a way that I can participate in communicating to other patients what I've experienced and how I feel about it in some way that's acceptable. I think I'm going to embarrass Mark now and give you a specific example from a site on a patient, an RGBM patient, who had your typical GBM complications. He had difficulty walking and other things. I won't go into that detail. And lamented about having to drop out of his senior softball league and so forth. To make a long story short, within about two to three weeks after his treatment, he was back to playing softball. He asked me to send him pictures of his treatment because as everyone knows, we have real-time evaluation because of the simultaneous gamma decay. So we're able to very accurately validate where the treatment goes. So in this patient's case, he wanted to be able to have that. He has his own website and things, and he was kind of commenting to folks who know his challenge of the success he has. And to make a long story short, he again raised the question about, is there a way that I can share my story? And we're in the process of doing that. And part of sharing that story is 5K, this gentleman, will be running next month. And I think our esteemed chief executive officer will be running the 5K with him. So, Mark, I'm sorry to embarrass you, but I figured this is a prime example of how not only the investigators but the patient enthusiasm for this product has really been very gratifying for me both personally and professionally. So thank you, Justin, for that answer.
spk06: Okay, Jonathan, I think Dustin got his money's worth on those questions. So who do we have next?
spk00: Certainly. Then our first question from the phone line comes from the line of Sean Lee from HC Wainwright. Your question, please.
spk09: Hey, Sean. Good afternoon, guys, and thanks for taking my questions. My first question is on the GBM side. Now, you mentioned that the study for treating larger tumors has been going well, and you've been able to test the higher doses of RM. I was wondering whether that's something that you consider roll into a potential future phase three in GBM, or would you keep the two separate, like the regular dose and the higher dose?
spk06: It depends on the data. You know, I think, as I mentioned, we're in the process of analyzing cohort seven and eight. Important part of that is looking at the distribution and the effect of increasing volume and radiation. And I think as you probably, I'm sure you do know, Sean, back in cohort six, we actually increased the flow rate from the first three patients to the second three patients in cohort six. So there are a lot of levers we can pull. I wouldn't rule anything out at this point. But I would just say to kind of finish, we're going where no man's gone before in terms of the volume we're putting in the brain, the amount of radiation. There's real value in continuing to do patients and tweaking the delivery parameters, and our plan is to continue to do that. And that's what FDA wants, and I think that's what the NCI wants.
spk08: I see. Thanks for your thoughts on that.
spk09: My second question is on the LM study. You mentioned that you were testing, in particular, with melanoma patients. I was wondering why melanoma, and is there something you see or you think that makes it particularly well-suited for IMG?
spk12: Go ahead, Nora. Let me take that one. And I appreciate that question because it brings up another aspect of LM, which we, I think folks on the phone know, can be caused from any solid tumor, any, you know, many of the liquid tumors and even the primary brain tumors. Of course, the most prevalent, you know, breast, lung, GI, head and neck and melanoma are most frequent. Regulatory requirements by FDA typically require And they've said this much will be what I call a disease-specific indication. So going forward, given the most likely etiologies for LM are lung and breast, I would see us, and our current protocol is written with that focus, although on our initial dose escalation, we do have it with all comers. But, regulatorily, we will have to focus it in a disease-specific way and pick the ones that would target the most people that we can help. Melanoma is an example of another disease indication, but the reason we're splitting that out is because it's a more difficult complication, and melanoma has shown some systemic therapeutic effects, particularly with the immunotherapy in general and checkpoint inhibitors in particular. And I won't go into the systemic therapies now, but there's a real opportunity for a combination approach for leptomeningeal treatment with our product and a combination approach with whether checkpoints or other immunotherapy in a way that we're determining now with some select slides.
spk09: Thank you. That was very helpful. My final question is on the upcoming pediatric study. I was wondering whether you had to make specific adjustments to your delivery method, because I know it uses the convection catheters. Is there going to be any difference than what you've done so far for the adults?
spk12: Yeah, great question, and the short answer is no, but let me give a little bit more color. I'm not known for my one-word answers, so sorry about that. It'll be the same approach. And what is interesting is the pediatric neurologists are used to for epileptic and evaluations, you know, you would think, oh, my goodness, putting a catheter in a child's brain is going to be tough. Well, they're used to doing this not only with two or three or four catheters as we're doing with adults, but, you know, 6, 8, 10 or more catheters. So the catheter and CED approach is something they're very comfortable with. They do all the time with, you know, epilepsy, left probe, targeting and tracing, for example. And the only thing I would anticipate that might be different is particularly for ependymomas, some of these can be quite large volumes. And that will be something as we get into later dose escalations for those larger volumes that we'll have to evaluate may be different. Mark already mentioned in the adult cohort eight, we're going to be increasing the volumes. So I would anticipate that in adult administrations, although we have very tolerable infusion times, of course, depending on which dose we're using and the volume of infusate, that I see reducing that by 50%. And I think the same possibilities for reduction and even greater reduction occurs in kids. And I already mentioned the fact that in the larger tumors, more catheters will be likely, and the more catheters mean the larger volume can be given over a fixed unit of time. So does that answer your question, Sean?
spk09: Yes, it does. Thank you again for taking my questions. That's all I have.
spk00: Thank you, Sean. Thank you. One moment for our next question. And our next question comes from the line of Edward Wu from Ascendant Capital. Your question, please.
spk11: Yeah, congratulations on all the progress. My question is on the CPRIG grant. Are there any restrictions to where you can locate your sites or any other requirements that you guys have when you guys run these clinical trials?
spk06: Hey, Ed, no, there's no restrictions on where those clinical sites can be. There's some restrictions around having sites in Texas and so forth, and having employees and office space and so forth in Texas, but not in terms of sites.
spk10: Great. Well, that's all the questions I have. Thank you.
spk00: Okay.
spk10: Thanks.
spk00: Thank you. Once again, if you have a question at this time, please press star 1-1. And this does conclude the question and answer session of today's program. I'd like to hand the program back to Dr. Mark Hedrick for any further remarks.
spk06: Thank you, Jonathan. Appreciate the questions today and appreciate your attention. And we want to finish up by thanking our employees and patients and physicians and collaborators we work with and our stockholders for their continued support. Thank you for the questions today, and we wish you a nice evening. Thank you.
spk00: Thank you, ladies and gentlemen, for your participation at today's conference. This does conclude the program. You may now disconnect. Good day.
Disclaimer