PLUS THERAPEUTICS, Inc.

Good afternoon, ladies and gentlemen. Welcome to the 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. 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.

Thank you, Cherie. 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-186-obispo-meta, in the RESPECT-LM trial. As a note, going forward for this call, I'll refer to rinium-186-obispo-meta as RNL, which is its research name for the sake of brevity. Part one of our development program, our ongoing RESPECT-LN phase one single administration dose escalation trial, is perhaps closing in on a maximal tolerance in which we administer a very substantial dose of RNL for approximately 66 millicuries. Data Safety and Monitoring Board, the board recommended proceeding to a modified lesser cohort six dose of 75 millicuries, and the first patient has been treated. To date, 21 of those, 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 one 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 startup 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 an interim update at the SNO-ASCO conference in August through cohorts one through four. Here are the key highlights from that presentation. Doses of RNL up to 44 millicuries were found to be safe and well-tolerated with no dose-limiting toxicities. Pharmacokinetic data demonstrated a very high therapeutic index specifically about a 50 to 100 target to off-target ratio. Through cohorts one through three, mean circulating tumor cells were reduced on average 53% at day 28 post-treatment, and median overall survival for cohorts one through four was 12 months, which is quite favorable compared to the historically reported consensus of approximately four months with treatment in breast and non-small cell lung cancer. The full presentation from that meeting is available on our website. Later this month at the SNO, Society for Neuro-Oncology annual meeting, which is going to be November 21st to the 24th in Houston, we will provide a comprehensive update on the phase one single administration dose escalation trial through cohort five with important new data including PK, PD response and survival data. We will also host a luncheon symposium to discuss the data in greater detail with leading subject matter experts, Dr. Priya Kumtekar, Dr. Jonathan Yang, and Dr. Andrew Brenner. As I mentioned before, we have reached agreement with the FDA to initiate enrollment in a phase one trial of multiple dose administrations of RNL for treating patients with LM. Favorable outcomes observed in compassionate use patients receiving multiple doses of RNL from our single-administration dose escalation trial reinforced the safety and potential value of multiple-dose administration regime to obtain long-tail survival in patients with LM. More specifically, the Phase I RespectLM multiple-dose administration trial is an open-label, two-part study aimed at evaluating the safety, dosing intervals, and efficacy of administering multiple doses of RNL to patients with LM. Primary objectives are to assess safety and tolerability and to identify both the maximum tolerated and the maximum feasible doses at various dosing intervals and frequencies. The secondary objectives include evaluating response and survival. The first part of the study will treat up to 24 patients administering at minimum three doses of RNL at 13.2 millicuries at progressively shorter intervals, starting at 56 days and then every 28 days and finally every 14 days, and then potentially up to six doses in a subsequent cohort. The trial is expected to begin enrollment in Q1 2025 with the aim to utilize current seven active U.S. trial sites being enrolling patients in our RESPECT-LN phase one single administration dose escalation trial. We plan to provide further details on the integrated development plan and path to approval for leptomeningeal cancer at the 2024 Snow Annual Conference in Houston. Now, for discussion around our diagnostic. Increasingly, we are recognizing the importance of our CNSIDE cerebral spinal fluid assay platform in both the investigation of RNL for LM and the assay's commercial value as a standalone diagnostic product in the broader group of patients at risk for LM or other CNS malignancies. The CNSIDE cerebral spinal fluid assay platform consists of four lab-developed tests, or LDTs, and may be used by neuro-oncologists, neuroimmunologists, medical oncologists, or other practitioners for the diagnosis treatment selection, and monitoring of patients with or at risk for LM, as well as other CNS malignancies. In terms of market access activities related to the planned CNSide launch in January, as you may recall, step one was tech transfer and initiating lab testing, which was completed earlier this year. Step two, at our wholly owned sub based in Houston, Texas, we obtained a CLIA certificate of registration in Q3, and we intend to obtain a CLIA certificate of compliance in Q1 2025, following inspection by CMS. This quarter, we will apply for expanded reimbursement with a Z code to the Diagnostics Exchange, which helps ensure that both healthcare providers and payers understand which test is being and it also allows payers to automate the preauthorization or adjudication of claims. Specifically, the Z code is required by well-known payers such as Medicare, UnitedHealthcare, Humana, Blue Cross Blue Shield, and so forth. Next quarter, following receipt of the CLIA certificate of compliance, we intend to apply for a CPT proprietary laboratory analysis code or PLA code with the American Medical Associations. This code is required by Medicare and certifies labs for complex testing, ensuring they meet federal standards for quality, accuracy, and safety. And the PLA code further specifically identifies the test. In parallel to these activities mentioned above, we are negotiating with a number of commercial payers which previously had agreements in place for the C&Side assay. Specifically, we're informing them that we acquired the assets of C&Side from the previous owner and plan to make the test platform commercially available again, and new agreements will be put in place. Also, we are focused on pairs that cover regions containing the highest number of LM patients. Currently, the see-inside tumor cell enumeration, LDT, continues to be used in the RESPECT-LM clinical trial. We are on track to commercially reintroduce the test as part of a limited market release in the U.S. in January of 2025. At the same time, we are expanding the CNSI test menu on a rolling basis to include specific cellular biomarker assays and molecular assays, and we'll talk more about that in 2025. Aggregate 2024 investment in the test will remain limited as test costs are offset in a meaningful way by our current CPIRT grant. In 2025, post-expanded market access, We will guide more specifically toward forecasted diagnostic growth ramp and related economics. Now shifting gears to our Respect GBM trial, which evaluates a single dose of RNL in patients with recurrent glioblastoma. Enrollment in the Phase I portion for patients with recurrent glioblastoma tumors greater than 20 mLs has been completed successfully. and we will be evaluating that data into 2025 and completing the final Phase 1 clinical study report. Enrollment continues for the RESPECT-GBM Phase 2 trial, limited to patients with tumors less than or equal to 20 mLs. The last RESPECT-GBM trial update was at the Congress for Neurological Surgeons annual meeting in October of this year. As a reminder, key highlights include a total of 42 patients had been enrolled across three sites at that time. In phase two, most adverse events were mild or moderate with over half deemed unrelated to the study drug. Only two of the nine severe adverse events were related to the study drug, and systemic radiation exposure remains low. Moreover, the average absorbed radiation dose to tumors in phase two was 300 gray, well above the 100-grade threshold observed preclinically and in phase one that is highly correlative with increased overall survival. Furthermore, approximately 90% of patients achieve critical drug delivery parameters also correlating with improved survival. Finally, objective tumor response analysis using both cerebral bud volume and volumetric analyses showed a statistically significant relationship between tumor control and absorbed dose. Specifically, patients receiving doses above 100 gray showed effective tumor control within the treated areas. The RESPECT-GBM trial continues to benefit from substantial NIH support, and we are pleased to announce we have added two new large-volume clinical trial sites to support Phase II enrollment and potentially a pivotal trial. We've added Ohio State University, which provides us coverage in the upper Midwest, and North Shore Hospital, part of the Northwell and Lenox Hill Network in the greater New York metropolitan area. With these two new additional sites activated and screening patients for enrollment, we expect phase two completion with 34 total patients by mid-year 2025 in a data readout in the second half of 2025. Additionally, we would like to announce that we recently entered into a research and collaboration agreement with BrainLab, a software-driven medical technology company, to develop and implement optimized case planning software for convection-enhanced delivery of R&L for brain cancers. BrainLab's software, married to their CED device ecosystem, will enhance treatment planning, procedure execution, and more precise drug delivery for GBM patients anticipated to further improve patient outcomes. Now, just a bit about our pediatric brain cancer program. Recall we previously announced that we have received a U.S. Department of Defense award of a $3 million grant to substantially support a Phase I trial for children with pediatric high-grade glioma and ependymoma. Approximately 900,000 payment was received in September of 2024 as part of this award. We anticipate obtaining IND approval in the first half of 2025 at Lurie Children's Hospital in Chicago, serving as the initial clinical trial site.

And moving on to drug production and manufacturing.