Good afternoon, ladies and gentlemen. Welcome to Plus Therapeutics Third Quarter 2024 Results Conference Call. Before we begin, we want to advise you that over the course of the call, including any 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. and uncertainties, including the risks and uncertainties described under the Risk Factors section included in Plus Therapeutics' Annual Report on Form 10-K and Quarterly Reports on Form 10-Q filed with the Securities and Exchange Commission from time to time. Plus Therapeutics advises you to review these risk factors in considering such statements. Plus Therapeutics assumes no responsibility to update or revise any forward-looking statements to reflect events, trends or circumstances after the date they are made. It is now my pleasure to turn the floor over to Dr. Marc Hedrick, Plus Therapeutics' President and Chief Executive Officer. Sir, you may begin.

Thank you, Sheri. Good afternoon, everybody, 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 third quarter 2024 financial results. Joining me for the call today is Mr. Andrew Sims, our Chief Financial Officer. I'll begin the call by reviewing our recent clinical and corporate progress in the third quarter and then turn the call over to Andrew for review of our financials, and then we'll both come back for Q&A. I'll begin this afternoon with an overview of our leptomeningeal metastases program in which we are investigating our lead radiotherapeutic Rhenium (186Re) Obisbemeda in ReSPECT-LM trial. As a note, going forward for this call, I'll refer to Rhenium (186Re) Obisbemeda as RNL, which is its research name for the sake of brevity. Part one of our development program, our ongoing ReSPECT-LM Phase 1 single-administration, dose-escalation trial, is perhaps closing in on a maximal [Technical Difficulty] 5 in which we administer a very substantial dose of RNL approximately 66 millicuries. Data Safety and Monitoring Board, the Board recommended proceeding to a modified lesser cohort 6 dose of 75 millicuries, and the first patient has been treated. To date, 21 [Technical Difficulty] including a subset of three patients who responded well to the initial dose and have received multiple doses under compassionate use. Part two of our integrated development plan is to expand the Phase 1 ReSPECT-LM trial to a multiple dose administration trial. Relatedly, in Q3, we reached agreement with the FDA to proceed under a multiple dose escalation protocol, and we are currently in site start-up phase for that trial. I'll review that trial design more fully in a moment. In terms of clinical data from the ReSPECT-LM single administration trial, we presented…

Thank you, Marc. Good afternoon, everyone. Please refer to our press release issued earlier today for a summary of our financial results for the third quarter ended September 2024. The cash and investments balance was $4.8 million at September '24 compared to $8.6 million at December '23. In addition, we received the first advance from the DoD grant in October '24 of $0.9 million and are on track to receive the next CPRIT advance of $3.9 million within 90 days of today. The company recognized $4.4 million in grant revenue year-to-date '24 compared to $3.6 million in the same period of '23. This represents CPRIT share of the cost incurred for our RNL development for the treatment of patients with LM. We expect 2024 grant revenue to be in the range of $6 million to $7 million. The total operating loss year-to-date 2024, was $10.8 million compared to $9.5 million in the same period of 2023. The increase is primarily due to increased spend related to the ReSPECT-LM trial. Net loss year-to-date 2024 was $9.1 million or $1.46 per share compared to a net loss of $9.5 million or $3.54 per share for the same period in the prior year. I'd also like to provide an update on our runway and cash position based on the previously announced private placement and provide guidance on our grant funding for the remainder of 2024 and into 2025. There are three additional sources of cash that Plus has access to beyond the balance disclosed in cash on hand and liquid investments on our Q3 2024 balance sheet. First, as a reminder, we announced in May that we closed a private placement financing of up to $19.25 million from new healthcare focused institutional investors and company insiders with a total of $7.25 million received…

Great. Thank you, Andrew. Appreciate it. Before we move on to Q&A, I'll take a moment to provide a specific summary of guidance for anticipated key events and milestones taking us through the remainder of 2024. First in terms of conferences, we'll have a substantial presence at the SNO, its Society for Neuro-Oncology Annual Meeting from November 21 to November 24 this year. There, we will present three abstracts, host an educational symposium on LM and GM, conduct our annual investigator meeting and showcase our CNSide Cerebrospinal Fluid Assay Platform in our booth as we will showcase our investigational drug, RNL for LM, GBM and pediatric brain cancer. More specifically, in terms of the three abstracts. As mentioned for our LM therapeutic program, we will present data on the safety and feasibility of ReSPECT-LM Phase 1 single administration dose escalation trial through cohort 5, including important PK/PD response and survival data. We'll also provide an update on our integrated development plan for both single dose and multiple dose ReSPECT-LM programs and linking them to an FDA approval plan and time line. For our CNSide Assay Platform, we will present data on first, the 4C clinical trial data on CSF tumor cell detection, including its clinical utility and accurately diagnosing LM patients with high sensitivity and specificity compared to the gold standard cytology, and also its clinical utility in enhancing clinical management of patients with LM. Second, we will show the results of a retrospective analysis of CNSide's real-world ability to detect a variety of gene mutations in CSF tumor cells, offering insights in the potential treatment strategies and also ways LM patients may benefit from complementary regional therapies such as RNL and other treatments. As mentioned, the company will host an educational symposium featuring 3 subject matter experts, Dr. Kumthekar,…

[Operator Instructions] And our first question will come from the line of Justin Walsh with Jones Trading. Your line is open.

Hi, thanks for taking the question. Congrats on all the progress. I'm wondering how you view the opportunities for CNSide and RNL in LM as complementary products versus on their own?

Hi, Justin, great question. You know what, we continue to see more and more synergies. And you may recall when we first considered this acquisition, it made sense solely on one factor and that is it could potentially increase the total addressable market for LM by 2 times to 4 times just by improving diagnostic sensitivity. But since then, there's more and more data that shows that using circulating tumor cells can be a proxy for survival and for disease monitoring. And there's -- we see more and more papers coming out related to that. And then we're now increasingly relying on it as an exploratory endpoint in the Phase 1. And we're going to be providing more insight into that data next week. I think it's highly relevant supporting the other signals we've seen in terms of response and efficacy. And I think there's a recent publication by actually one of the key opinion-leading doctors in our symposium, Dr. Yang who treated patients with targeted radiation, in that case from proton beam craniospinal irradiation, which showed in that trial targeted radiation therapy. It correlated very highly. The CNSide assay, actually our assay correlated very highly with survival and progression. So I think over time, we'll see more and more reliance on that. Is it ready to be used as a primary endpoint in a pivotal trial? I don't think so. But I think as a secondary endpoint, it provides substantial collaborative data to other progression data and survival.

Great. Thank you for taking the question. Looking forward to the presentation.

Thanks, Justin.

Thank you. One moment for our next question. And that will come from the line of Edward Woo with Ascendiant Capital. Your line is open.

Congratulations on the progress. I was just wondering what does the landscape look for grants? Has this changed in terms of the opportunities that are available? And do you anticipate any change with, I guess, the change in the incoming government? Thank you.

Ed, to answer your latter question, I don't know. It's hard to tell. I think we're in a good -- pretty good spot through the next year as it relates to grants. We think there -- being in Texas insulates us a bit from what's going on at the Federal level. We've been very successful in -- at CPRIT. As I think we have almost $18 million active grant from them in an aggregate $25 million total in active grants. What we're hearing, no guarantees, but what we're hearing from CPRIT is that there -- from time to time, there's additional capital that they can deploy and they're -- they tend to reach out to companies who are executing and we're executing precisely to our proposed and planned time line. So we're kind of hoping there might be some opportunities there. But also we'll continue, as Andrew said, to talk about grants as they come in, but we think there's continued opportunity in Texas if things change at the federal level.

Great. Well, thanks for answering my questions, and I wish you guys good luck. Thank you.

Thank you.

Thank you. One moment for our next question, and that will come from the line of Sean Lee with H.C. Wainwright. Your line is open.

Hey, good afternoon guys and thanks for taking my questions. I just have two quick ones. One is -- first is on the LM multi-dose study. So how do you guys come up with the 13 millicuries dose to be used in that study? And how does that compare to what patients have received so far through the compassionate use program?

Hey, Sean, thanks for the question. It's a good one. So as we were -- we're increasingly taking a Bayesian approach to clinical development. We'll talk more about that in our integrated development plan both next week in an ongoing manner. But we found, as we were getting into cohort 4, which is approximately 44 millicuries, that we were seeing excellent safety and also strong response cohort. And so we -- as we began our negotiations with FDA on a multiple dose approach, we felt like we could support taking that cohort 4 dose and then fractionating it. And that follows approaches that FDA is very comfortable with. So we're able to get them to go along with that. And so I think that because of -- based on what we're seeing clinically, that earlier compression of doses will be very important and getting that long tail survival that I mentioned. In terms of the compassionate use, we've had, I think two patients that have received three aggregate doses. We're actually giving them the -- whatever dose is currently enrolling. So they're getting actually in the neighborhood of 40 or more higher dose, but their dose frequency is much longer. They're being treated when they come back with symptoms. In other words, patients seem to -- are responding to the initial dose, and then they're doing well for an extended period of time, maybe up to a year or so. They're coming back with symptoms or progression and asking to be retreated. So we treat them with that dose that's available. So back to my original point, I think increasingly, we recognize the Bayesian design is appropriate. We're modeling that right now. That's integrated into the multiple dose trial. And then as we'll talk about over time, how we -- how do we leverage that and get to approval.

My second question is on the CNSide assay. So in the prepared remarks, you mentioned that you needed to get the CLIA compliance followed by a CMS inspection, as well as getting the Z-Code and PLA-Code. So do you have a rough guideline for the approximate time line for these process?

I'm sorry, Sean, just to clarify, what's the time line for getting additional reimbursement?

Yeah, for getting the inspection done as well as having -- getting the reimbursements online. So like when can we expect CNSide to start selling commercially and getting reimbursed?

Yes. So I think we're on track to being able to commercialize the test in Q4 of this year. I think the issue is going to be that we need to -- we're more likely to get imbursed if we have a CNSide CLIA compliance and that inspection is -- it's not been scheduled, but it's going to be Q1 and we're pushing to make that as early in Q1 as possible because we want to try to accelerate that time line. And then number two, I think some of these -- some of the laboratory services agreements, which were -- I think they were approximately 10. Is that right, Andrew? 10 in place with Biocept. We've hired market access team that is actively negotiating with those 10 institutions on a regionally focused basis based on my comments, where are the patients and where the highest level of reimbursements? So we're prioritizing those areas just sort of being practical, obviously. I think we're going to have some more things to talk about in Q1 as it relates to reimbursement. And I think once those reimbursement dominoes fall, then I think we'll feel more comfortable talking about pricing ramp, margins and so forth. And I think right now, it's just a bit premature until we get those things in place. We want to be really cautious in terms of guiding in the early phases until we get comfortable that we can stand behind that guidance. I can tell you that with the time that Biocept quit offering the test, they had 200 unique customers. They were growing at about 30% per year CAGR. And that was with no data, no NCCN guidelines, no specific reimbursement, no foresee clinical trial data. So we have all those elements behind us at this point today, and that's only going to grow. There are only more papers coming out and so forth. So I think the environment continues to look really positive for that as a standalone product.

Got it. Thank you for that. That makes it a lot more clear. That's all the questions I have.

Thanks a lot, Sean. Appreciate it.

Thank you. I'm showing no further questions in the queue at this time. I would now like to turn the call over to Mr. Andrew Sims.

Thanks, Sheri. We have two written questions. So the first is, can you elaborate on the therapeutic ratio you are seeing in your trials and safety data profile?

Yes. So that's a good question. We'll talk probably more in detail. We will talk more in detail about that at next week at SNO. But I think it's a key point that the therapeutic ratio that we're seeing going out to cohort 4 is very high. In particular, for LM, we're seeing about -- a ratio of about 50-plus in cohort 4 in terms of therapeutic to target versus off target. I can give you a preview of cohort 5. I think we're seeing that as greater than 100:1 ratio. So we're continuing to see a linear dose -- as we dose escalate a higher and higher absorbed dose in the spinal subarachnoid space and really relatively flat absorption in the key critical organs. Bone marrow is starting to tick up a bit in cohort 5, and we'll talk about that, and that was part of the rationale for the DSMB to cut back the cohort 6 dose. And I think we're increasingly becoming more comfortable that the cohort 4 dose will be the recommended Phase 2 dose, and the maximum tolerated dose will be cohort 5. But the FDA has been very consistent about us continuing to dose escalate to failure, hence, the cohort 6 dose. In terms of GBM, I think the therapeutic ratio is really hard to calculate because we're seeing essentially very minimal systemic absorption and very high delivery of radiation to the region of interest, tumor in the infiltrated margin. So yeah, I think we're seeing -- what we're seeing is very favorable, much higher than other companies are reporting with their systemically delivered technology. So I think that's really strong part of the technology.

And the second question is, can you provide details on your integrated development plan for LM?

Yeah, I think I've mentioned some of the details, and I think we'll present more at SNO and roll that out over the first part of 2025. I think -- right now, I think there is -- based on the data we're seeing in single dose, there is clearly activity and there's a strong potential for advancing to single dose in an expansion cohort for -- specifically on breast and lung cancer, non-small cell lung cancer, that data continues to look strong. We can use that data to help derisk a pivotal Phase 2/3 trial thereafter. And I anticipate getting that into the clinic pretty soon next year, but we'll talk more about that. In terms of multiple dose, I think we could follow a similar pattern where we pick as we complete each cohort, a promising dose, cohort expand it, confirm that there's an efficacy signal there as well as safety signal and then move that forward. And I could potentially see taking 2 different doses to market, a high single dose and a lesser multiple dose regime. And then -- so more on that next week and then first half of next year. Are there any other questions? That's okay. Thank you, Andrew.

Well, just to conclude, thank you, Sheri, and thank you, everyone. I appreciate you being on the call. On behalf of the Board, I'd just like to thank our employees and team members and the physicians we work with and very much thank you to the patients who continually trust us to enter into these trials. Thank you for your participation. Have a good evening.

This concludes today's program. Thank you all for participating. You may now disconnect.