PLUS THERAPEUTICS, Inc.

Good afternoon, ladies and gentlemen. Welcome to the PLUS Therapeutics fourth quarter and full year 2022 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.

Thank you, Andrea. 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 2022 fourth quarter financial results. Joining me for the call today is Dr. Norman LaFrance, our Chief Medical Officer, and Mr. Andrew Sims, our Chief Financial Officer. I'll begin the call by reviewing 2022 and then Andrew to review our financials, and Dr. LaFrance will be joining us for Q&A. At a high level, I was extremely pleased with our accomplishments in 2022. Going into the year, we set for ourselves some significant development goals, and we achieved or exceeded almost all of them. At the same time, we continued a very conservative approach to managing our balance sheet, ending the year with a similar cash level to the prior year. But we materially expanded our availability of cash, as Andrew will discuss. So let me begin by focusing on drug development, clinical regulatory activities, and related milestones. First, I ask that you wind the clock back over a year and recall that we ended 2021 with a single drug, which was 186-RNL, active in only a single phase one clinical development program for recurrent glioblastoma. funded in large part by the NIH. That was, in essence, the whole of our active clinical development program at that time. That was a year ago. Fast forward to the end of 2022. We ended the year with two investigational drug candidates, rhenium-186-obispumate, formerly called 186-RNL, and rhenium-188-obispumate, bioabsorbable alginate microspheres, or 188-RNL-BAM, as we call it. Regarding our investigational drug, rhenium-186-obispumata, or rhenium-obispumata, we have two active clinical programs now ongoing, one for recurrent GBM and the other for leptomeningeal cancer. In terms of glioblastoma in 2022, we substantially expanded this program. Specifically, we advanced from phase one to phase two, We are continuing the dose escalation for larger tumors and higher dose volumes. We manufactured GMP drug, allowing us to move into phase two. We enrolled the first patient in the phase two trial. And we negotiated with FDA to continue the phase one dose expansion for larger tumors and now have an active retreatment protocol with FDA to explore retreating patients that happen to occur after a first treatment. For leptomeningeal disease, we moved this program to essentially a co-lead program with GBM. And specifically, we advanced that program successfully from preclinical stage to an enrolling phase one. And we obtained $17.6 million in funding for this program that in combination with PLUS's one-third match as required by CEPRIT, the grant awarder, that should be sufficient to fund this program through phase two and the enrollment of approximately 150 patients. For pediatric brain cancer, while we did not initiate this trial in the calendar year, because of the discussions with the FDA that were required for this first and pediatric patient radiopharmaceutical trial, we did make significant progress. Specifically, after three rounds of FDA interactions on the nature of the IND for pediatric brain cancers, FDA reviewers have accepted our clinical protocol design but still require and request some additional adult data, which we plan to submit relatively soon. Our second drug, 188R and LBAM, was in licensed in early 2022 from academia. And during the, during 2022, we successfully transferred that technology to PLUS, then successfully manufactured that drug internally last year. We then used that drug to successfully, in a human organ ex vivo perfusion model, confirming the preclinical feasibility and the manufacturing of that drug. And then we submitted a pre-IND information package to the FDA. So big picture, in terms of milestones achieved, 2022 was a transformative year in the company's development. Additionally, in 2022, we presented important data readouts in our two lead clinical programs, GBM, and leptomeningeal cancer. First, in November 2022, results from the company's Phase I Respect GBM trial for recurrent glioblastoma was presented at SNO, the Society for Neuro-Oncology meeting in Florida by the trial PI. In the Phase I dose escalation trial, at that time, 24 patients with recurrent GBM across seven cohorts received a single dose of rinium obispumata and administered in the dose escalation phase, achieving up to 740 gray to the tumor. That's compared on average to about 35 gray total absorbed radiation dose delivered to tumors using external beam radiation. The data in our trial showed that rhenium-obispo-meta can be safely administered, and there's a statistically significant correlation between overall survival and both absorbed radiation dose to the tumor and percent tumor volume in the treated volume. The strength of this signal is unusually positive for a phase one trial. And we found that specifically for every 100 gray increase in the absorbed dose correlated, every increase in the absorbed dose, that correlated with about a 36% decrease in the risk of death. The more radiation to the tumor, the lower the risk of death. And also, in every 1% increase in the tumor volume treated, up to a max of 100%, obviously, that is associated with a 4.5% decrease in the risk of death, and that was highly statistically significant. There were no dose-limiting toxicities reported, and the overall safety profile was very favorable. The study concluded that a single administration of rinium-obispo-meta by convection-enhanced delivery in recurrent glioma patients with poor prognosis It's feasible, safe, and potentially effective in increasing overall survival when a therapeutic dose of radiation is delivered to the tumor. And in the latter cohorts, we were delivering a therapeutic dose in over 80% of the patients treated. Based on the data from the Phase I trial and Q4 2022, we initiated a Phase II dose expansion trial evaluating rhenium-obispo-meta for the treatment of patients with recurrent GBM using our cohort six dose, which is 22.3 millicuries in 8.8 milliliters of injectate for small and medium-sized tumors, and that's essentially tumors that are about 20 cc's or less. This phase two will enroll up to an additional 31 patients with small to medium-sized tumors, and we intend to enroll that trial in approximately 24 months or less. That trial continues to be supported by an award from the National Cancer Institute. While we have five sites authorized under the NIH, with the PI and the NIH, we plan to expand the number of trial sites beyond the authorized five to facilitate faster enrollment. The primary endpoint, as a reminder, is overall survival following single administration, which is an endpoint we agreed to with the FDA. And secondary endpoints will assess the safety, tolerability, objective response rate, partial response, SAEs event-free survival and progression-free survival at six months. Also, as mentioned above, key focus areas of ongoing clinical investigation in the GBM development program will be further dose exploration by increasing the dose and also increasing the number of doses to patients who happen to recur after a single administration, and also to inform the design of future registrational trials. As discussed previously, the company and FDA agreed to hold future meetings as facilitated by ORPHAN and FAST-TRACK designations on the registrational trial design, including the use of external data to augment the control arm and speed enrollment in a potential pivotal. Now, let me move on to our Leptomeningeal Metastases, or LM, development program. The LM trial is a multi-center phase 1-2 dose escalation study rated dose safety and efficacy of rhenium obispumata. LM, as you may know, is a complication associated with advanced cancers that infiltrate the fluid line structures of the central nervous system, also called the leptomeninges. It so happens that the incidence of LM is growing with local and improved cancer care And there are no approved FDA therapies. And there are about 120,000 patients per year that are affected with LM, and it's substantially underdiagnosed. Standard treatment includes external beam radiation therapy to the affected sites, potentially with chemotherapy given either orally, intravenously, or often administered twice a week directly into the CSF space. Systemically administered therapies almost never work because of the blood-brain barrier. preventing access to the leptomeninges. So going back again to the SNO meeting back in November, we also presented the early phase one data from the RESPECT-LM trial at that meeting that demonstrated that a single administration of virinium abyspamate was feasible, safe, and well-tolerated across the two dosages studied at that time in cohorts one and two with patients in that trial after treatment showing a decreased CSF tumor cell count by 48 hours following treatment that was between 46 to 90% in terms of reduction of the tumor cell count that was measured in the CSF. The 17.6 million product development research funding award we received from the Cancer Prevention and Research Institute of Texas Reciproc began funding in the fourth quarter of 2022. As mentioned, this award will cover the majority of the development costs, including funding for up to 150 enrolled patients for the LM program over three years. And that's an important source of non-dilutive funding that materially strengthens the company's balance sheet. In early 2023, we completed enrollment in cohort two of the LM trial, and now six patients have been treated. Regarding next steps with that trial, following the DSMB, the Data Safety Monitoring Board Review, which is anticipated to be in March. We anticipate that we'll complete enrollment in Part A of the Phase 1 portion soon, perhaps in the next quarter, and that will be nine patients total. Thereafter, we plan a meeting with the FDA to determine the exact dose expansion plans for the Phase 1 Part B trial, and then we expect to initiate that Part B trial in the second half of 2023. We also expect initial data from the Phase 1 Part A to be presented also in the second half of 2023. As I mentioned, on our third quarter 22 call in November, we have made and are making significant progress in building a more resilient and robust GMP supply chain through our strategic partnerships that enable the development, manufacture, and even future potential commercialization of our products. Our current supply chain and key partners are positioned to supply C-GMP rinium-obispo-meta for any ongoing and planned Phase II-III clinical trials in patients with GBM, LLM, or pediatric brain cancer. And that's now fully in place as of the end of last year. And pediatric brain cancer. Based on extensive evidence previously, we expect to submit an updated investigational new drug application for what will be called the RespectPBC Phase 1 Safety Dose Finding and Efficacy Study of Rhenium Obispumata for Pediatric Brain Tumors. It will be submitted in conjunction with our lead academic institution, Lurie Children's Hospital at Northwestern University in Chicago. Finally, regarding our novel, recently in-licensed, radioembolic microparticle technology, 188R and LBAM, we successfully completed 72 objectives. Furthermore, based on the FDA feedback regarding the most appropriate regulatory designation for the investigational product specifically, whether it should be a drug or device in terms of its regulatory path, we are pursuing the request for designation process to define this in parallel to performing required developmental activities, regardless of whatever the ultimate regulatory designation ultimately is. It's our view that Despite the fact that the competing legacy products that are on the market, which are permanently indwelling radioembolic products that have been in the market for, in some cases, over two decades, the bioreservable nature of our RNL-BAM supports its ultimate designation as a drug. Nonetheless, we'll collaborate with the FDA to seek their ultimate guidance on this determination and proceed in parallel with with those development activities that we can reasonably do, irrespective of the ultimate regulatory determination. The company plans, as mentioned previously on other calls, to initially focus on developing the BAM technology as a next-generation bioreservable radial embolic therapy for, at first, liver cancer. So with that summary, I'll turn the floor over to our Chief Financial Officer, 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 2022 fourth quarter and full year ended December 31, 2022. As of December 31, 2022, cash and cash equivalents were $18.1 million compared to $18.4 million as of December 31, 2021. The company believes the combination of current cash Committed grant funding in conjunction with existing discretionary capital sources secures our cash runway through 2025. Cash used in operations for full year 2022 was $13 million compared to $10.3 million for full year 2021. During the fourth quarter of 2022, the company received its first separate grant funds of approximately $1.9 million as planned. The main year-over-year changes between full year 22 and full year 21 are as follows. Grant revenue of $224,000 was reported related entirely to CPREC. Total operating expenses for full year 2022 were $19.9 million compared to $12.5 million for the prior year. The 2022 total included two main areas of spend that were one-off in nature. The first area of increase was CMC spend related to the development of GMP quality drug and key regulatory consulting activities necessary to advance the Phase 2 GBM clinical trial. These expenses were over $4 million in 2022. 2023 spend related to these activities is forecast to be less than $500,000. In addition, and to a lesser extent, the company had a forecasted increase in litigation and legal spend related to a legal settlement disclosed in Form 10-K. The net result is that we expect an overall decrease in total burn in 2023 based on our currently disclosed milestones. Interest expense decreased from $932,000 for full year 2021 to $711,000 for full year 2022. This decrease reflects the continued principal pay down that commenced in November 21 from the company's Oxford debt. Net loss of full year 2022 was $20.3 million, or 77 cents per share, compared to a net loss of $13.4 million, or $1.11 per share, for full year 2021. Now I'll turn it back to Mark.