PLUS THERAPEUTICS, Inc.

Good afternoon, ladies and gentlemen. Welcome to the Plus Therapeutics fourth quarter and full year 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 the star and 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 for optimal sound quality. If you should require operator assistance, please press star and zero. Before we begin, we want to advise you that over the course of the call and the 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 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 which they are made. It is now my pleasure to turn the floor over to Dr. Mark Hendrick, Plus Therapeutics President and Chief Executive Officer. Sir, you may begin.

Thank you very much, David. 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 fourth quarter and full year financial results. Joining me on the call today is Andrew Sims, our Chief Financial Officer. In addition, joining Andrew and I on the call today for the first time is Dr. Norman LaFrance, our new Chief Medical Officer who joined PLUS at the end of 2021. We are very excited to have Dr. LaFrance on board. as he brings many years of highly relevant clinical, regulatory, and commercial expertise in radiotherapeutics and oncology to the PLUS Therapeutics Management Team. Welcome aboard, Norman. I'll begin the call by reviewing our recent corporate and clinical progress before turning the call to Norman, who will provide commentary on our clinical expectations for the remainder of 2022. Following Norman, Andrew will review our financials. 2021 and early 2022 has been marked by significant progress as we work toward our mission to become a global leader in developing precision targeted radiotherapeutics for cancer. In 2021, we continue to advance our lead investigational targeted radiotherapeutic drug, rinium nanoliposome, or RNL, in our U.S. respect GBM trial. As a reminder, the trial is a dual phase 1-2 multicenter sequential cohort open label volume and dose escalation study. The trial is currently funded to a significant degree by the US NCI or National Cancer Institute. 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 Europe. It's the most common and lethal form of brain cancer and the treatment of this devastating disease remains a significant unmet challenge. Recall also that RNL is proprietary liposomal encapsulated radionuclide that is delivered local regionally via targeted three-dimensional convection enhanced delivery. It is administered directly to the tumor bypassing the blood-brain barrier. The active agent is the rhenium-186 isotope, which is a dual-energy emitter releasing both cancer-killing beta particles, which are high-energy electrons, as well as gamma particles, which are useful for imaging, localization, and dosimetry. We provided positive interim data from the Phase I to respect GBM trial in patients with recurrent GBM at the Society for Neuro-Oncology Annual Meeting and Education Day last November 2021, and then we updated the data set at the BioCEO Conference in New York this month. Both of those presentations can be found now on our website. According to the most recently presented interim clinical data set, 186-RNL delivered via convection-enhanced delivery is feasible up to at least 31.2 milliliters of radiation and 12.3 milliliters of volume. No delivery failures were observed. An average absorbed dose of 276 gray of radiation was delivered to the tumors over the course of the trial thus far. Average absorbed radiation to the tumor increased and correlated with dose escalation. In fact, we've shown that we can successfully deliver up to 740 gray or 20 times the amount of radiation dose one can deliver with traditional external beam radiation in the recurrent setting. As an aside about radiation therapy, published studies indicate that EBRT external beam radiation provides the best incremental improvement in survival of all therapies currently available for glioblastoma, which is about five months in improved survival. And it remains, to this day, an essential component of multimodal therapy for GBM and many other cancers. So there's no question radiation works in GBM. Furthermore, in their SPECT trial, key drug delivery parameters, such as flow rate, catheter number, et cetera, were increased during the course of the trial. And that increase correlated with better drug delivery outcomes and improved overall survival. 186 RNL is also thus far well tolerated without those limiting toxicities. It has an acceptable safety profile. There were no adverse events thus far in the trial with the outcome of death or discontinuations due to adverse events. And placement of up to four catheters in a patient has thus far been safe. As to efficacy, And it's interestingly similar, the efficacy results thus far, to our preclinical results. An absorbed radiation dose of greater than 100 gray in patients correlates with increased overall survival. Although the phase one trial has neither design nor power for efficacy, we are observing promising signals of both biological effect and increased overall survival. In the latter cohorts of the trial, specifically cohorts 5 through 8, receiving greater drug volumes and radiation doses and, frankly, more optimized delivery parameters, 9 of the 12 patients, or 82% of those patients in cohorts 5 through 8, received a therapeutic dose of 100 gray or better. And we believe it's entirely possible to achieve a 90% or greater coverage of 100 gray or better going forward. Thus far, in 23 total subjects treated in respect with recurrent GBM, the median, excuse me, the mean and median overall survival for the entire group is currently at 38 weeks and 50 weeks, respectively, with seven patients remaining alive. It's interesting to note that in this current trial, which was initiated by the academic physicians back in 2015, it's very unusual to have such long-term overall survival data, which we do in this trial. Therefore, when we take the logical step and take advantage of what's been done by the academics that started the trial and assess a subset of patients who received At least a minimum therapeutic dose of radiation, and as I mentioned, that's greater than 100 gray of radiation. They were treated in the initial five cohorts, which ranged from a start date of March 2015 through to July 2020, which is the longest survival data we have in the trial thus far. Immediate and mean overall survival stands at 82 and 88 weeks, respectively, with two patients still alive. That compares very favorably with the 32 weeks overall survival published in a recent meta-analysis covering nearly 700 patients with recurrent GBM treated with Bevucizumab monotherapy in the recurrent setting. And that reference can be found on our website in our corporate presentations. Furthermore, our team continues to make excellent progress in our drug scale-up and manufacturing activities. Specifically, during 2021 and thus far in 2022, the company entered into multiple collaboration agreements to support its process development in analytical chemistry activities, as well as to strengthen our supply chain in compliance with GMP practices for planned late-stage clinical trials. The company remains on track to deliver GMP-186-RNL by mid-2022. Before I turn the call over to Norman, and he will update you on the path forward for 186-RNL, I'd like to highlight the agreement that we announced right at the beginning of January and consummated at the end of December that substantially expands our oncology portfolio. As we stated before, We fundamentally believe in the future of cancer therapy is going to be in the precise targeting of tumors with the most potent cancer killing agents while minimizing damage to normal tissues. To that end, we entered into an agreement with the University of Texas for a worldwide exclusive license to develop and commercialize novel interventional therapeutics for cancer. The licensed patents include composition and matter patents for biodegradable alginate microspheres, which we call BAM, containing nanoliposomes loaded with imaging and or therapeutic payloads. Therapeutic payloads may include radiotherapeutics, chemotherapeutics, or thermotherapeutics. The BAM technology is delivered into the vascular system via standard interventional vascular technology that are placed precisely in the vessels feeding blood to the tumors. Once injected, BAM both blocks all blood flow to the tumors and simultaneously delivers very high doses of cytotoxic compounds for an extended period of time. Many days later, following full radiation decay, BAM resorbs, are physiologically metabolized and then excreted from the body. With this technology, we can target almost any solid organ tumor in the body using standard interventional radiologic methods to leverage the breadth of the human vascular system and deliver a resorbable biomaterial embolic technology coupled with a highly potent radioisotope. The company will initially focus on developing 188 RNL-BAM as a next-generation radial embolization therapy for liver cancer, in which BAM blocks the hepatic artery segments that supply blood to the malignant tumor, while also providing 188-RNL radiotherapy and directly irradiating the tumor. Next steps in this program are technology transfer from academia and completing key IAD-enabling CMC and preclinical work. And with that, I'll turn the call over to Norman.

Thank you, Mark. I'm delighted to have joined PLUS Therapeutics and to be joining you here today for this call. PLUS Therapeutics' focus on radiotherapeutics positions is firmly for long-term growth. I'm excited to lead the development expansion of its promising pipeline. Following on Mark's comments on the RESPECT GBM trial in patients with recurrent pleoblastoma, In 2022, we expect to materially advance the investigational drug, 186-RNL, recurring GBM, and other indications. First, we plan to meet with FDA mid-year to propose taking our 8.8 milliliter and 22.3 milliliter as our recommended Phase II dose. We believe this dose is appropriate for 50 to 75% of patients with recurrent glioblastoma based on tumor size and morphology. As publicly announced earlier this week, we are currently exploring potential Phase II pivotal trial designs that may incorporate the use of real-world data, also known as synthetic control arm, to improve trial costs and facilitate enrollment. In addition, as we have yet to reach dose-limiting toxicity in the respect GBM trial, and we anticipate to be able to treat larger tumors with 186-RNL, our goal is to keep the phase one dose escalation trial open and report data both on the previously treated patients and on future potential cohorts. We may also consider exploring improved drug dosing parameters. Recently, we have filed a new clinical protocol with the FDA to allow us to treat patients with recurrent glioblastoma previously treated once with RNL that may benefit from an additional RNL dose. GBM is notoriously difficult to eradicate from the brain, and we believe a subset of patients may benefit in terms of greater safety and efficacy following two or more administrations of 186-RNL. Furthermore, in 2022, the company will review other GBM disease subtypes to potentially expand the use of 186-RNL. Regarding additional indications, 186-RNL is also being developed for leptomeningeal metastases and pediatric brain cancer. Leptomeningeal metastases is an increasingly common secondary cancer affecting 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. The RESPECT-LM trial is a multi-center, sequential cohort, open label, single dose, dose escalation phase one study. It will evaluate the maximum tolerated dose, maximum feasible dose, safety, and efficacy of a single administration of 186-RNL via intraventricular catheter for the leptomeningeal metastases treatment following standard surgical radiation or chemotherapy treatment in these patients. The primary endpoint of the study is the incidence and severity of adverse events and serious adverse events and dose-limiting toxicities, if any. Secondary endpoints include overall response rate, duration of response, progression-free survival, and overall survival. In addition, we have received FDA Fast-Track designation for 186-RNL for the treatment of leptomeningeal metastases. Following IND clearance from the FDA last year, in fourth quarter of last year, the company began screening and consenting patients in respect on phase one trial and patients with leptomeningeal metastases. Regarding pediatric brain cancer, based on our pre-IND meeting feedback received in 2021, the company expects to submit an IND for Phase 1 trial with 186 R&L this year for the treatment of pediatric brain cancer and to investigate the use of R&L on kids with brain cancer. At this point, I'll stop and turn the call over to Andrew for a brief review of the full-year financial results.