PLUS THERAPEUTICS, Inc.

Final remarks, so after Q&A, just turn it back to me for a few seconds, please.

Good afternoon, ladies and gentlemen. Welcome to PLUS Therapeutics' fourth quarter and full year 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 risk and uncertainties, including the risk 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, Sherry. Good afternoon, everyone. Thank you once again for taking the time to join us today as we provide an overview of recent business highlights and discuss our fourth quarter and full year 2024 financial results and go-forward guidance. Joining me for the call today is Mr. Andrew Sims, our Chief Financial Officer. I'll begin the call by providing more detail on four important recent corporate announcements. Then I'll discuss progress in our most advanced clinical programs, and then discuss progress and plans for C-INSIDE and its commercialization. After that, I'll turn the call over to Andrew to review our financials. So first of all, in early March, closed on an underwritten equity financing of $15 million in gross proceeds with new stockholders. This was preceded by a smaller financing from existing stockholders. We also received, about that time, $2 million in its accelerated grant proceeds from CPRI. This capital, in combination with further anticipated grant funds, strengthens our balance sheet and provides funding through key milestones into mid-2026. Additionally, the financings enabled PLUS to regain compliance with NASDAQ's minimum stockholders' equity listing requirements. Andrea will, in fact, provide additional details on the transactions, future grant availability, and cash runway. On a personal note, and on behalf of our board of directors and our dedicated management team, I would like to express our collective gratitude to our current and new stockholders for their support of and confidence in PLUS in our mission. We are also grateful to those organizations with which we have substantial financial and grant support. specifically the U.S. NIH, and that's the NCI, National Cancer Institute, the U.S. Department of Defense, and the state of Texas, specifically CFRIT. Also, moving on, we recently taken to strengthen our senior leadership team. Specifically for plus therapeutics, Dr. Mike Rosel joined us as chief development officer. responsible for leading our preclinical and clinical development activities, including clinical operations. Mike has extensive experience in oncology, radiotherapeutics, and biomarker development, all highly germane to PLUS's pipeline. Specifically for C-INSIDE Diagnostics, our wholly owned subsidiary, Mr. Russ Bradley joined us as president and general manager of C-INSIDE. Russ is a seasoned and successful operator. field, previously holding top management positions at both major and smaller diagnostic companies, as well as related board positions. Russ has a deep knowledge of diagnostic operations, fast-growing commercial diagnostics, market access activities, and business development. Additionally, I'm pleased to welcome Dr. Jonathan Stein to the team at C-INSIDE as its medical director. Jonathan has extensive experience in all aspects of diagnostic operations, compliance, and regulatory affairs. Now, I'm excited to introduce you to Rheobic. We now have an FDA-accepted proprietary name, which is Rheobic, and that goes alongside the USAN-adopted and INN-recommended non-proprietary name or generic name, Rhenium RE186 Obispumata, All of these are required for our future marketing application with the FDA. Working with the leader in pharmaceutical brand name creation development, we are striving to develop a powerful brand identity for Rayobic, and that all begins with its global name. In parallel, we will be rolling out comprehensive branding materials that will strengthen and shape the Rayobic brand identity, and going forward, we'll use Rayobic to refer to our lead drug now in mid-stage clinical trials for use in patients with glioblastoma, leptomeningeal cancer, and soon in children with pediatric brain cancer. Finally, we recently received approval by the US FDA on our application for orphan designation for the use of Ryobic in patients with LM due to lung cancer. This adds to our previously received orphan designation for LM due to breast cancer and our fast-track designation for Ryobic. This is reflective of our strategy to focus on the top two causes of LM, specifically breast and lung cancer, which represents two-thirds of the LM market. Now, I'd like to switch gears and focus on our leptomeningeal metastases clinical development program, in which we are investigating our lead radiotherapeutic, RYOBIC, and the respect LM trials, which are substantially funded by the state of Texas. We recently announced the completion of the RESPECT-LM phase one single administration dose escalation trial. In that trial, we have determined a recommended phase two dose of 44 millicuries, as well as the maximum feasible dose of 75 millicuries. Based on these determinations and promising clinical safety and efficacy data, which I'll highlight in a moment, we have expanded our integrated clinical development plan for Rayobic as follows. First, because a single dose of Rayobic at the recommended phase two dose was deemed safe, well-tolerated, and exhibited a promising efficacy signal in terms of clinical response and overall survival, we intend to move forward on a dose expansion trial at 44 millicuries to gather additional safety and efficacy data for Rayobic. In terms of next steps, Once the final clinical study report is complete, we plan to conduct an end-of-phase one meeting with the FDA to align on an optimal path to approval for aobic and tailor the next clinical development steps. As there are no approved drugs for LM and a substantial clinical need, we intend to leverage promising clinical data for aobic, our orphan drug designations as mentioned, fast track designation, to identify the most expedited path to market for patients that are in desperate need for options. We think given the promising phase one data, a single dose of 44 millicuries warrants further evaluation for FDA approval for LM related to breast cancer. In parallel, the RESPECT-LM multiple dose escalation trial of Ryobic will begin enrollment soon for the purpose of dose optimization. Key details for the trial are as follows. The single dose at the recommended phase two dose of 44 millicuries will be fractionated into three doses of approximately 13 millicuries. Based on the PK and PD data derived from the phase one single dose trial, three doses will be given at diminishing intervals, or first every two months, then every month, and then every 15 days. There are options to expand the size of the treatment cohorts and extend the number of treatments beyond three to six doses total. Besides the pharmacokinetic and pharmacodynamic data and dose optimization, the trial will assess safety and efficacy. The trial will be a basket trial initially and has been approved previously by the FDA and site startup is ongoing. The plan to pursue both single and multiple doses in an accelerated clinical development approach is based on the positive clinical data specifically presented at the end of last year at the Society for Neuro-Oncology Annual Meeting and the San Antonio Breast Cancer Symposium in December, as well as data that has been obtained subsequently. Those conference presentations include important new data on PKPD safety, clinical response, and survival. Key highlights of the conference presentations and some of the more recent data that we will present in detail at upcoming conferences include 29 patients with LM received a single intraventricular dose of Rayovac between 6.6 and 75 millicuries. In terms of safety data, there was one DLT, which is a grade four platelet count reduction that was observed at the cohort five dose of 66.14 millicuries. And two DLTs were observed in one patient in cohort six. That was a grade four platelet and neutrophil count reductions, indicating at least some bone marrow exposure consistent with the PK analysis data. Notably, there were no SAEs that occurred in cohort four patients at what has been termed to be the RP2D. PK and PD analysis showed target to off-target radiation-absorbed dose ratios of greater than 100 to 1. To put that in perspective, such ratios are impressive because they mean the dose is much more effectively delivered to the area of interest, the tumor in this case, than to the other areas of the body where one desires to keep the doses as low as possible. In other words, our drug design and formulation strategy works. Clinical response to a single dose of Rayobic was assessed through four months or 112 days post-treatment to deliberately exclude the effect on patients receiving under a compassionate use protocol who survived well beyond the published median overall survival. Specifically in these patients, we assessed change in CSF tumor cells via our CN-side tumor cell enumeration assay, which is the best measure of tumor cell bulk or prevalence. Also, we looked at radiographic response and survival benefit was also assessed. Through cohort five and at the time of data cutoff for the conference presentations, data was available for 16 patients. Five or 31% of those patients showed a radiographic response based on investigator assessment. We also used clinical benefit rate or CBR as an outcome measure in this very fragile patient population as it encompasses complete response, partial response, and stable disease outcomes. An additional seven of the 16 patients I just mentioned showed stable disease through four months for a radiographically determined clinical benefit rate when combining the five I just mentioned before of 75%. So, 75% CBR related to imaging analysis. Additionally, in terms of clinical responses, a decrease in disease symptoms was noticed in two of 14 evaluable patients, or 14%, with 10 showing stable symptoms through four months for a clinical benefit rate of 86%. Lastly, when looking at the cerebral spinal fluid or the CSF tumor cell enumeration assay, again, our see-inside assay, which is the most sensitive measure we have for assessing tumor volume, which has also been shown to correlate with survival, this decreased up to 100% by day 28 following Rayobig treatment, with four of the 15 evaluable patients showing a response translating to a clinical benefit rate of 93%. In terms of survival, median overall survival was nine months, which compares favorably to the historically reported consensus in the literature of about four months, supporting the potential efficacy of Ryobic for LM. The full presentations from SNOW and San Antonio Breast Cancer Meetings are available on our website for further review. In terms of guidance for our integrated development plan for LM, we anticipate an FDA meeting, likely a Type B into Phase I meeting, as soon as possible to align on the following. First, a path to a registrational trial for a single dose of Ryobic in patients with LM resulting from breast cancer primaries. That includes a single-dose expansion trial that would provide an expeditious path to registration. Key issues to resolve in this meeting, if possible, are things like endpoints, comparators, tumor subtypes that we'll study, and so forth. Second, we seek to align on the integration of a future multiple-dose strategy given the promising data we have seen with compassionate use treatment in the single-dose phase one and anticipated data expected later this year in the formal multiple dose escalation trial. In the second half of 2025, we anticipate completion of the first and longest duration of the multiple dose expansion cohorts. By then, we anticipate having FDA alignment, a definitive clinical plan for a single dose expansion trial, and site onboarding should be ongoing. Furthermore, On May 9th, 2025, PLUS will be presenting response data from the RESPECT single-dose LM trial, essentially the full phase one data set as it exists at that time, at the Nuclear Medicine and Neuro-Oncology Symposium in Vienna, Austria. Other data presentations are anticipated throughout the remainder of 2025, and we'll update on acceptance and agreement to participate. Now, switching gears a bit to glioblastoma. In terms of respect, GBM and those trials, the Phase 1 trial results were recently published in Nature Communications, a prestigious high-impact journal. We have made that publication open access and is now available on PLUS's website or directly through Nature. The results show a strong safety and efficacy signal that has been further confirmed through the first half of the Phase 2 trial as previously reported. For the program as a whole, a total of 52 patients have been enrolled through both phase one and two. And we anticipate phase two completion in 2025, and the RESPECT trial continues to benefit from a grant from the NCI. An offshoot of the adult glioblastoma trial is our pediatric brain cancer program. We previously announced that we have received a U.S. Department of Defense award of a $3 million grant to substantially support a Phase 1 trial for children with pediatric high-grade glioma and ependymoma. Approximately a $900,000 payment was received in September 2024 as part of this award, and we anticipate an additional $1.1 million payment in 2025. Interactions with the FDA are ongoing towards final IND approval. We anticipate obtaining that approval in 2025 with Lurie Children's Hospital associated with Northwestern in Chicago serving as the initial clinical trial site. Now, regarding radiotherapeutic drug production and supply chain management, this remains an important and active focus ongoing behind the scenes. Recently, we announced partnerships with SpectrinRx, Isotherapeutics, Radiomedics, and ABX, the details of which can be found in previous press releases and earnings calls. Furthermore, to ensure our ability to meet the demands of expedited or accelerated late-stage clinical trials, as I mentioned before, and future commercial production requirements for Rayobic, We continue to expand key partnerships in 2025, as we have in previous years, but now with a focus geared more towards supply chain redundancy and backup supply. Now, fundamentally switching gears, I'd like to update you on our C&Side business, but I think it's important to give a brief background on C&Side for those of you that may not be as familiar with it. And frankly, we haven't talked much about it over the last few C-INSIDE is a CNS cancer testing platform we have been utilizing in our RespectLM clinical development programs as a biomarker and exploratory endpoint since 2022. Since then, and over that time, extremely high conviction of the value of C-INSIDE for RYOBIC's future commercial success. And specifically, I mean increasing the total addressable market by two to four times for RYOBIC. The immense value also for hundreds of thousands of cancer patients at risk for LM but are in a diagnostic quandary. And then finally, the substantial value of C-INSIGHT as a commercial diagnostic platform in and of itself. Given this, we seized on the opportunity last year to acquire it outright. Since then, we have been investing thoughtfully in the people, the means, and the materials to bring C-INSIDE back to market in a manner that can unlock its full value for patients, providers, and stockholders. What is C-INSIDE? What does it do? C-INSIDE, you know, in a brief way, brief description, is it's a cerebrospinal fluid or CSF assay platform that accomplishes three core things. First, diagnosis. Specifically, it can confirm the or importantly, reject the clinical suspicion doctors may have that a patient with almost any type of solid tissue cancer may have LM. It does so at a much higher sensitivity, or said differently, a true positive or true negative rate that's much better that can be done with existing technology, which is essentially cytology. It also accomplishes treatment monitoring. In patients with LM, monitoring of CSF tumor cells has been shown to correlate with survival and is now recommended in the NCCN clinical guidelines, i.e., one can address whether a patient is responding to treatment, do they need a different therapy or therapeutic choice, or perhaps can therapy be paused potentially, perhaps they may have safety issues related to their current course of therapy. And then finally, as a treatment selection tool, LN cancers often exhibit a drift in biomolecular signal that may influence treatment approaches and drug selection decisions in the future once drugs are approved by the FDA. Clinical data has shown that C-INSIDE can be important in this clinical decision-making process. Users of C-INSIDE are neuro-oncologists, neuroimmunologists, and medical oncologists or other practitioners caring for patients with common cancers such as breast and lung cancers, as well as melanoma and others. It's not strictly limited to patients that have LLM or highly suspected of having LLM. Now, let me talk about the status of the business in brief. As mentioned, we have hired a seasoned core team to both launch and manage the business day to day, specifically Mr. Bradley and Dr. Stein, who I mentioned previously. but other key hires have been made and onboarded in the past 12 months. We have also established a clear registered centralized laboratory for test operations in Houston, Texas that is actively testing patient samples from our clinical trial and ongoing pre-commercial pilot testing. Key market access activities have been ongoing for nine months in the areas of medical affairs and reimbursement. This includes negotiations with commercial payers as well as seeking expanded coding approvals, and NCCN CNS cancer change requests for LM diagnosis. Furthermore, key marketing, corporate and product branding, and sales planning activities have been completed. In terms of guidance, first of all, the company will be exhibiting C-INSIDE at key medical conferences in 2025 and plan to submit abstracts and publications as we move forward this year. Commercially, the CNSide tumor cell enumeration test is on track to launch fully this year, beginning in a geographically limited manner, expanding over the course of the year as market access activities such as state licensures, key payer agreements, and medical system contracts are expanded. Specific financial guidance will be forthcoming later this year as visibility improves. And finally, CNSide product offerings will also evolve in 2025 and more on that over the next few quarters. And with that, I'll now turn the call over to our Chief Financial Officer, Andrew Sims. Andrew?