PLUS THERAPEUTICS, Inc.

Good afternoon, ladies and gentlemen. Welcome to PLUS Therapeutics' second 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 positions. 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, and good afternoon, everyone. Thank you once again for taking the time to join us today as we provide an overview of of recent business highlights and discuss our second quarter 2024 financial results. Joining me on 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 second quarter, then turn the call over to Andrew to review our financials, and then we'll both come back on for Q&A. So let me begin with updates from the 2024 Society for Neuro-Oncology and Combined American Society for Clinical Oncology CNS Metastases Conference, which met last week in Denver. At SNOW-ASCO, PLUS was quite busy. We had four presentations, sponsored a symposium on novel emerging diagnostics and therapeutics for leptomeningeal metastases, and participated in a panel discussion on the opportunity for emerging therapies for brain metastases alongside senior executives from Novartis and Pfizer. Two of our four presentations warrant highlighting on our call this afternoon, and the full data from those presentations and from the symposium will be available soon on our website. First of all, Dr. Andrew Brinner, the Respect LM Trial Principal principal investigator, presented an interim update on the trial through cohort four, and that's N equals 16 patients. This is the most significant update that we provided since the SNOW 2023 presentation. His presentation showed that through cohort four, which is an administered dose of 44 millicuries, rhenium obispumata was safe and well-tolerated with no dose-limiting toxicities and the maximum tolerated dose had not been reached. Furthermore, supporting the relative safety of the drug thus far, the PK data demonstrated a high therapeutic window. Specifically, the mean absorbed radiation dose to the ventricles and cranial subarachnoid space was approximately 160 gray compared to only about one gray to the spleen. a linear increase in absorbed dose to the regions of interest, specifically the craniosubarachnoid space and cerebrospinal fluid, was noted from cohort one to cohort four to increase, but there was no increase noted in the spleen, which was the critical organ. In terms of response data, circulating tumor cell data was not available through cohort temporarily available unavailable at that time, but it's now available, and we are back up and using the test currently in cohort five. But recall that we observed a mean 53% reduction in CTCs, circulating tumor cells, in the CSF for the first three treated cohorts. It was observed out to 28 days post-treatment, but the CTC number came back up by 56 days post-treatment. Additional and significant response data through cohort five is currently being reviewed and will be presented in detail at SNO in November, and I'll talk more about that in a moment. In terms of the median overall survival signal, again, with 16 evaluable patients through cohort four, median overall survival was 12 months, with half the cohorts, that's eight out of the 16 treated patients, remaining alive at the time of analysis. This is an increase from that that was reported after cohort three last November, which showed a median overall survival of 10 months. To put that data in perspective, LM is a devastating disease, I think, as most of you know, from both the morbidity and mortality perspective, with typical survival rates ranging from two to six months after diagnosis, depending on primary tumor type. So this emerging efficacy signal, though early, is very encouraging vis-a-vis the standard of care. There was also a second presentation at Snow ASCO. I'd like to thank Dr. Priya Kumtekar, who reported the top-line clinical results from our 4C trial. 4C evaluated the clinical utility of C-INSIDE, our newly acquired novel CNS diagnostics, on leptomeningeal metastases treatment decision-making by physicians in 40 patients. The trial used a well-described trial design that's used commonly in the diagnostic space. Specifically, she reported that 4C met its primary endpoint with C-inside influencing treatment decisions in over 90% of clinical decisions. That's 50 clinical decision points evaluated. And that substantially exceeded the 20% level, which was the target for the primary endpoint to show effectiveness. Moreover, the study also showed that C-INSIDE helped identify actionable mutations in the CSF, such as HER2 amplification, that influenced 24% of therapeutic selection decisions. That's 14 out of 55 clinical decision points evaluated. Importantly, and related to the current state-of-the-art diagnostically that's found in major hospitals around the country, C-INSIDE demonstrated more than twice the sensitivity in detecting tumor cells in the CSF compared to what is now the gold standard, which is cytology. Specifically, it showed a detection rate of tumor cells of 80% versus 29% for cytology. Also important, C-INSIDE demonstrated exhibited a very high specificity in that no tumor cells were detected in patients without leptomeningeal metastases. We were pleased to see this data and present it formally, and these four C results highlight and validate our previous high conviction that C-INSIDE as a diagnostic and therapeutic selection and diagnostic therapeutic monitoring tool fulfills a critical clinical need in brain metastases that now has been shown to improve patient management and we believe will lead to better patient outcomes in the near future. Finally, in addition to our presentations at SNO-ASCO, we also reported important data at the 2024 Society for Nuclear Medicine and Molecular Imaging, known as SNMI Annual Meeting in June 2024. The reported study used dosimetry data from the RespectLM clinical trial to evaluate the safety and potential for spinal cord toxicity of beta emitters or beta emission radioisotopes in the related physics and found that lower beta energy radionuclides, such as rhenium-186, largely spare the spinal cord versus other beta radionucleotides that we studied. These findings further support the thesis that rinium-186 is an ideal radionuclide for CNS cancers, hitting the therapeutic window, delivering high therapeutic doses to the region of interest while minimizing toxicity. Now, kind of moving on in terms of our leptomeningeal program, broadly speaking. First of all, therapeutically, the current phase one single administration respect LM dose escalation trial We'll continue dosing until the next DSMB meeting, and at that time, we will determine if progressing to cohort six is advisable. But thus far, as mentioned, a maximum tolerated dose has not been reached, despite delivering up to a maximum of 66 millicuries to the CSF. In terms of upcoming data releases, a definitive trial update is planned for Society for Neuro-Oncology 2024 that will be held in Houston this November. To date, we have dosed a total of 25 patients and also treated a subset of patients with multiple doses of rhenium-obispo-meta under compassionate use, and those patients have done really well. Also, the company has filed a new protocol under its open FDA IND to treat individual patients with a multiple dosing regime. This submission follows a positive FDA type C meeting in Q2. Once formally approved with final agreement with the FDA, the company will share the details of that trial protocol. That trial is anticipated to begin enrolling later in 2024 at the current seven trial sites with a number of new sites to be added in the interim. The LeptomNinja program continues to be significantly supported by an approximately $18 million product development award from CPREIT that covers approximately two-thirds of programmatic expenditures. Also, the company continues to be involved in active dialogue with CPREIT regarding program advancement and are actively seeking expanded ways to work with CPREIT that are mutually advantageous. In terms of our diagnostic LM program, we are in the process of expanding our C&Side diagnostic capabilities at our facility in Houston, Texas, in specific, targeted, but strategic ways. First of all, we hired Dr. Greg Fuller, former chief of neuropathology at MD Anderson Cancer Center in Houston, and an LM expert to be the full-time medical director of the C&Side lab and oversee lab operations and also help support our LM therapeutic objectives. We have also improved the lab quality assurance systems and our capabilities to steadily increase testing capabilities as anticipated for growing research use, both from PLUS's growing trial number in LM, but also other trials that have contacted us with similar interest. In addition, we have applied for CLIA certification for a see-inside as a laboratory-developed test, and approval under CLIA is anticipated later in 2024. We anticipate providing further business updates on the see-inside diagnostic program later this year as developments warrant. Now I'd like to shift gears to our RESPECT-CBM trial. As most of you know, this trial evaluates a single dose of rhenium obispumata in patients with recurrent glioblastoma and is funded mostly through the NIH. We continue to enroll both Phase II patients with recurrent GBM, and that's for tumors that are less than or equal to 20 cc's, and also enrolling patients in our Phase I, now at Cohort 8, for patients with larger tumors. We anticipate three new active GBM convection enhanced delivery sites will be enrolling soon, and these should be able to transition to pivotal trial sites when the time warrants. Those are Ohio State University, providing us a site in the upper Midwest, and North Shore Hospital, part of the Northwell Lenox Hill Network in the greater New York region. We are also evaluating other additional sites with the intention of adding at least one site in the greater Southern California region. These sites, specifically OSU and North Shore Hospital Lenox Hill, are on track to enroll patients in 2024. Additional sites beyond those mentioned are also being investigated for activation to support a potential pivotal trial. We are working to complete enrollment by the end of 2024, but more likely to wind up completing enrollment in the first half of 2025. A faster timeline will be influenced to a significant degree by participation of these new sites. Our plan is to provide a substantial update on the phase one and phase two data this fall at the CNS, or Congress for Neurologic Surgeons, annual meeting, which is in late September, early October in Houston, Texas. And this will be our first time to be on the podium presenting this data to the neurosurgical community. In addition, I'd like to briefly update you on our pediatric brain cancer program. We've previously announced that we received a U.S. Department of Defense award for $3 million to substantially support the phase one trial for children with pediatric brain cancer, specifically pediatric high-grade glioma and ependymoma. That award is in an administrative phase and is anticipated to begin funding this September 2024. We are also on track to obtain IND approval for this trial, and Lurie Children's Hospital will be the initial clinical trial site. Finally, we are making good progress behind the scenes on a number of important business items, specifically building in redundancy and commercial readiness in our supply chain and enhancing our drug delivery capabilities, and we plan to make material public updates on those in the near future. And with that, I'll now turn the call over to our Chief Financial Officer, Mr. Andrew Sims, who will review the financials. Andrew?

Thank you, Mark. Good afternoon, everyone. Please refer to our press release issued earlier today for a summary of our financial results for the second quarter ended June 30, 2024. The cash and investments balance was $8.4 million at June 30, 2024, compared to $8.6 million at December 31, 2023. The company recognized $2.9 million in grant revenue in the first half of 2024, compared to $2.3 million in the same period of 23. This represents a separate share of the cost incurred for our rhenium abysmometer development for the treatment of patients with LM. We expect 2024 grant revenue to be in the range of $6 to $7 million. Total operating loss for the first half of 2024 was $7 million, compared to $6.2 million in the same period of 2023. The increase is primarily due to increased spend related to the Respect LM trial. Net loss for the first half of 2024 was $6.2 million or $1.15 per share of $6.3 million or $2.06 per share for the same period the prior year. an update on our runaway in cash position and provide guidance on our grant funding for the remainder of 2024. There are two additional sources of cash to which PLUS has access beyond the balance disclosed in cash on hand and liquid investments on our Q2 2024 balance sheet. First, and 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 at closing. In addition, there are up to $12 million of cash on exercise of the one- and five-year warrants. As a side note, at June 30, 2024, the warrants issued as part of this private placement were recorded as a liability on the balance sheet, and as outlined in the subsequent events footnote 14, The warrant form was amended, eliminating the liability, and henceforth, these warrants will be accounted for under the equity accounting method. The second source of cash remains our anticipated ongoing funding through now three awarded grants. First, the CPRIG grant to support the Respect LM trial. As reported, we received the first of two expected amounts from CPRIG in 2024, the first in Q2 of $3.3 million. We remain on track to receive the next advance from CPRIID of 3.7 million in mid to late Q4 2024. An additional 3.7 million is expected from CPRIID in 2025. Second, as reported on April 22nd, PLUS has received an award recommendation from the United States Department of Defense for 3 million to support the upcoming RESPECT pediatric brain cancer trial. This funding is expected to commence in September 2024 and materially cover the cost of the planned Phase 1 trial. Funding is received annually in advance and covers a three-year period, i.e. approximately $1 million will be received under this grant in 2024. Third, PLUS also continues to benefit from the NIH grant to support the RESPECT-GBM Phase 1-2 trial. Although expected to be complete in 2024, It currently covers approximately 90% of the overall trial costs. We also continue to source other non-dilutive sources of grant capital and have applied for approximately $13 million in additional grant funding year to date. We will continue to only report on individual grants when they are awarded. In summary, this provides incremental access to cash of $22 million. $10 million from CPRIID and DOD, and $12 million from the exercise of A&B warrants from the May private placement. And now I'll turn it back to you, Mark.