PLUS THERAPEUTICS, Inc.

Good afternoon, ladies and gentlemen, and welcome to the PLUS Therapeutics third quarter 2021 results call. At this time, all participants have been placed in a listen-only mode, and the floor will be open for your questions following the presentation. If you would like to ask a question at that time, please press star 1 on your telephone keypad. If at any point your question has been answered, you may remove yourself from the queue by pressing the pound key. We ask that you please pick up your handset to allow optimal sound quality If you should require operator assistance, please press star zero. 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 said statements are subject to risk and uncertainties, including the risk and uncertainties described under the risk factors section included in the PLUS Therapeutics annual reports 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 risks and 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 that 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 very much, Ashley. 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 2021 third quarter financial results. Joining me on the call today is Mr. Andrew Sims, our Chief Financial Officer. Before Andrew provides a summary of our financial performance, I would like to provide an update on the company's business activities since our last call. Big picture, in the third quarter, we made good incremental progress toward our mission to become a global leader in developing and delivering precision-targeted radiotherapeutics for cancer. Specifically, we received clearance from the FDA for investigational new drug application for the use of RNL-186 in patients with leptomeningeal metastases. We also entered into an agreement for the commercial production of our radiopharmaceutical, RNL-186, and we continue to strengthen our leadership team with the appointment of a highly experienced chief medical officer, Dr. Norman LaFrance. Finally, we presented data at the AANS meeting, as well as obtained acceptances to present data from the RESPECT-GBM trial at both ASTRO and SNOW. I'll cover these achievements in more detail in a moment, but let me first provide a summary of plus for those new to the company. Our lead investigational targeted radiotherapeutic is RNL, or rhenium nanoliposome. This is a proprietary liposomal encapsulated radionuclide that is delivered local regionally via targeted three-dimensional convection enhanced delivery. It is administered directly to the tumors. The active agent is rhenium-186 isotope, which is a dual energy emitter releasing both cancer-killing beta particles, which are high-energy electrons, and gamma particles, which are useful for imaging and dosimetry. Rhenium is a very unique isotope, in part because of its energy profile. Its beta energy has a short path link, which provides delivery precision, a low dose rate, which provides a margin of safety, and a high energy density, which is particularly toxic for highly mitotic cells like cancer, which can overwhelm the DNA repair mechanisms that could otherwise contribute to radio resistance. Thus far, we've shown that we can successfully deliver 20 times the radiation dose one can deliver with traditional external beam irradiation. Our initial indication for RNL is recurrent glioblastoma. which affects approximately 13,000 patients annually in the US, and about the same number of patients in the EU. It is the most common and lethal form of brain cancer, and the treatment of this devastating disease remains a significant unmet medical challenge. Published studies indicate that external beam radiation provides the best incremental improvement in survival of all therapies currently used for glioblastoma, which is about five months, and it remains an essential component of multimodal therapy for both glioblastoma and, in fact, many other cancers, but is limited by the complications from higher dosages. RNL is currently under evaluation in our U.S. RESPECT GBM trial, which is a dual phase one and phase two multicenter sequential cohort, open label, volume and dose escalation study of the safety, tolerability, and distribution of 186 RNL. The trial is currently funded to a significant degree by the U.S. National Cancer Institute. We are now into an eighth dosing cohort following the Data and Safety Monitoring Board recommendation to proceed to the next incremental cohort, and to date, we have treated 22 total patients. We provided interim results during the recent Canaccord, Genuity, and Wainwright investor meetings and that data can be found on our website. Notably, cohort eight represents a 40 percent increase in both dose and radiation compared to cohort seven. Thus far in the RESPECT trial, highly targeted and continuously infused or convected volumes of up to 12.3 milliliters containing 31.2 millicuries of radiation have been well tolerated. Up to four catheters can be successfully placed for delivery to best accommodate a variety of tumor sizes and geometries. RNL has been shown thus far to be safe and well-tolerated, despite delivering up to 740 gray of absorbed radiation to the tumor, which again by comparison is 20 times the radiation dose typically delivered by EBRT in the recurrent setting. Regarding safety, and this data as of August 1, 2021, there have been no adverse events or AEs with the outcome of death or discontinuations due to AEs. The majority of AEs reported were mild and moderate, that's grade one or two, in intensity, and non-serious. The adverse events or AEs with the highest incidence were fatigue, muscular weakness, and headache, and also gait disturbance. Most AEs were considered causally unrelated to R and L, except one case of scalp discomfort, which was considered related to the surgical procedure, and one case of cerebral edema. AEs with grade three or leukocytosis, hyperglycemia, muscular weakness, seizure, brain edema, worsening avascular necrosis of the shoulder, vasogenic cerebral edema, and pneumonia. All of these events were considered unrelated to RNL by the investigator, with the exception of brain edema for one subject, which was considered possibly related to RNL. Serious adverse events, or SAEs, were reported for two subjects in cohort two, namely seizure and vasogenic cerebral edema. One subject each in cohort four and five, both seizure, and two subjects in cohort six, pneumonia and worsening avascular shoulder necrosis and cerebral edema. All these events were considered unrelated to RNL by the investigator, with the exception of cerebral edema for one subject, which was considered possibly related to RNL, and or tapering of oral corticosteroids, and none led to study discontinuation. There were no meaningful differences or patterns in the incidence of related treatment emergent AEs reported across individual treatment groups or cohorts. Neither the incidence nor severity of AEs appear to increase with increasing doses of RNL. As to the important issue of drug delivery feasibility, there have been no delivery failures thus far. We can safely deliver up to an average absorbed dose of 740 gray of radiation to tumors. The mean absorbed radiation dose to the tumor is 392 gray. Up to four catheters can be used for delivery, and the mean percent tumor coverage with the radiation is 90%. Although the phase one trial is not designed nor powered for efficacy, we see promising signals of biological effect and potential efficacy. As mentioned previously, imaging-based measures of progression are challenging, as the substantial tissue effects of the treatment often show pseudo progression. While we analyze the imaging results in an ongoing manner, we look closely also at the gold standard endpoint, survival. Three of 22 patients have survived up to 30 months or more, where average survival for the current GBM with standard of care is only about eight to 10 months. Because many of those patients have been treated relatively recently and at the higher dosing and volume cohorts, it understandably makes definitive efficacy determinations on overall survival challenging. But as to the issue of overall survival, what I can say is that we have observed that increases in both convective volumes and radiation dosage seem to correlate with better tumor coverage and higher tumor-absorbed doses. And this, in turn, seems to correlate with overall survival. And this is what one would expect based on the biology of radiation therapy in these tumors. Again, as of August 1st, 2021, 8 of 22 patients remained alive. In the early cohort of 13 patients enrolled between 2015, when the trial started, prior to our involvement, to 2019, where we had the longest follow-up, only 5 of 13 had absorbed tumor radiation doses greater than 100 gray and tumor coverage percentage greater than 75%. which in our view are key biological thresholds. The average survival, overall survival in these five patients was 769 days or about 25 months. And two patients are still alive in this cohort. In the more recent cohort, really since we took over the trial, of those nine patients treated, enrolled since 2020, seven of nine had both absorbed tumor radiation doses greater than 100 gray and a tumor coverage percentage of greater than 75%, a much better delivery success percentage because, obviously, of the higher volumes and radiation doses we're administering in these higher dosing cohorts. The average overall survival in these seven patients is 173 days, but six of these patients are still alive. We will provide a full update at the November Society for Neuro-Oncology meeting in Boston later this year. Furthermore, our team continues to make excellent progress in our drug scale-up and manufacturing activities and is simultaneously putting in place the essentials for commercial readiness. Specifically during the third quarter of 2021, the company entered into an agreement with Radiomedics Incorporated for the commercial production and logistical support of the company's investigational radiopharmaceuticals. Thus far in 2021, the company has entered into five collaboration agreements to support its process development and analytical chemistry activities, as well as to strengthen its supply chain in compliance with good manufacturing practices for the manufacture of the 186 RNL investigational drug. The company remains on track to deliver GMP 186 RNL by mid-2022. Looking forward, The company will present interim data from its RespectGBM clinical trial at the 2021 ASTRO annual meeting scheduled for October 24 to 27 this year, and at the 2021 Society for Neuro-Oncology Annual Meeting and Education Day scheduled for November 18 to 21 also this year. In addition, at 4 p.m. Eastern Standard Time on November 18 this year at Snow in Boston, The company will sponsor an in-person and virtual scientific roundtable discussion and Q&A period with respect to trial principal investigators. At that time, we'll provide a substantial clinical update on the safety and potential efficacy data as of that time point, including a discussion of potential next steps. In parallel, we expect to continue to enroll patients in cohort eight this year, ideally completing this cohort in Q4 of this year. And based on that timeline, We intend to present the clinical data set to the FDA in the first half of next year and determine next steps. Regarding additional indications, RNL is also being developed for other diseases, including leptomeningeal metastases and pediatric brain cancer. Leptomeningeal metastases, or LM, is an increasingly common secondary cancer complicating from other cancers, and based on their increasing overall survival rates that we're seeing with better therapies for primary solid and hematologic tumors. LM affects over 100,000 patients per year in the U.S., and patients can present with a broad range of signs and symptoms due to simultaneous involvement in multiple areas of the craniospinal axis. Earlier this week, we announced clearance of our IND application from the FDA for 186-RNL for the treatment of LM. We expect to initiate patient accrual in a phase one dose escalation trial in the fourth quarter of 2021. The trial will be called RESPECT-LM. It'll be a multicenter, sequential cohort, open-label, single-dose dose escalation phase one study of the safety, tolerability, biodistribution, dosimetry, and anti-tumor activity of 186-RNL given interventricularly via the standard OMAIA reservoir to subjects over 18 years of age with LM. The primary endpoints of the study are the incidence and severity of adverse events and SAEs, and the incidence of dose-limiting toxicities. The secondary endpoints are the overall response rate, duration of response, progression-free survival, and overall survival. In the planned forthcoming trial, really just speaking as a practical matter to help you understand what we're doing. We intend to administer RNL via a common end-going catheter, as I mentioned, a reservoir called the Elmira Reservoir that sits under the skin on the head and communicates directly with the ventricle in the leptomeningeal or cerebrospinal fluid space. And as I mentioned, this is commonly placed in all of these patients with LM and really makes the delivery a very straightforward issue. Furthermore, the reservoir allows periodic CSF, or cerebrospinal fluid sampling, to occur and facilitates the use of tumor-related biomarkers to follow patient response and enables the potential use of related surrogate outcome measures. Additionally, we believe there's an opportunity to help patients with pediatric brain cancer using Ardell. Based on our pre-MD meeting feedback received earlier this year, We intend to submit an IND in early 2022 to investigate the use of R&L in kids with brain cancer. Finally, as mentioned in September, the Board and I are pleased to welcome Dr. Norman LaFrance aboard as the company's Chief Medical Officer. Dr. LaFrance will join Andrew and me on our forthcoming earnings calls. Dr. LaFrance brings several decades of unique and highly relevant clinical, regulatory, and commercial expertise to the PLUS Therapeutics management team. He's actually a nuclear engineer, a board-certified internist, and a nuclear medicine physician. He joined industry a while back after leaving his clinical practice at Johns Hopkins in Baltimore. He has a proven track record in radiotherapeutics and drug development, regulatory affairs, drug lifecycle management, and related commercial experience. He has brought numerous radiotherapeutics successfully to market, and his background will be important to our success as we expand our pipeline, move key programs to late stage clinical development, and position the company for long-term regulatory and commercial success. At this point, I'll stop and turn the call over to my colleague, Andrew, for a brief review of the third quarter financial results. Andrew?