PLUS THERAPEUTICS, Inc.

Good afternoon, ladies and gentlemen, welcome to the Plus Therapeutics third quarter 2022 results 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 risk and uncertainties, including the risk and uncertainty 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, Josh. 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 third quarter financial results. Joining me for the call today is Dr. Norman LaFrance, our chief medical officer, and Andrew Sims, our chief financial officer. I'll begin the call by reviewing our recent corporate clinical progress before turning the call over to Andrew to review our financials. And Dr. LaFrance will be joining us for Q&A. The company made perhaps the most progress ever in a single quarter that I can remember. First, in September 2022, results from the company's phase one respect trial for recurrent GBM was presented at the European Society for Medical Oncology meeting in Paris by Dr. Andrew Brinner, the trial PI. In summary, 21 patients across six dosing cohorts received one to 22 millikuries of radiation and 0.6 to 8.8 milliliters of volume. The mean tumors treated in those 21 patients was 8.3 milliliters, and patients had a mean of 1.7 recurrences and very poor prognostic factors. All recurrent glioma patients had computerized treatment planning and up to four intracranial catheters placed in each patient. Each patient received a single administration of 186-RNL by convection enhanced delivery and whole-body planar SPECT CT imaging on days 1 through 8 following treatment assessed dosimetry and radiation distribution. Patients were followed for safe radiation delivery and overall survival. The mean absorbed radiation dose to the tumor was 271 gray with negligible systemic exposure. There were no dose-limiting toxicities, and the overall safety profile was favorable. Patients were stratified by mean absorbed radiation dose to the tumor. Those receiving greater than 100 gray mean therapeutic dose, N equals 12 in that group, had a median and mean overall survival of 129.7 and 106.4 weeks, respectively, with four patients still alive in that group. Patients receiving less than 100 gray mean absorbed dose, essentially a subtherapeutic dose, N was equal to 9 in that group, had a median and mean overall survival of 22.3 and 24.6 weeks, respectively. None of those patients remain alive. Kaplan-Meier analysis of patients receiving mean absorbed dose greater than 100 gray or therapeutic dose versus those with less than 100 gray, a non-therapeutic dose, showed a statistically significant difference in overall survival, favoring those that received a therapeutic dose. The study concluded that a single administration of 186-RNL by convection-enhanced delivery in recurrent glioma patients with poor prognosis is feasible, safe, and potentially effective in increasing overall survival when a therapeutic dose of radiation is delivered to the tumor. A recommended phase 2 dose of 22.3 millicuries and 8.8 milliliters was selected for patients with tumors of up to 20 cc's or 20 milliliters in the phase 2 trial planned for later this year. And I'll discuss the phase two plan further in a moment. Also during Q3, we received guidance from two type C meetings with the FDA on the next steps in our program for the development of our lead investigational drug, rinium-186 nanoliposome. The first type C meeting focused on the company's current good manufacturing practice, or CGMP, clinical and commercial manufacturing process for 186 R&L. The FDA indicated agreement with our proposed application of CGMP guidance for radiotherapeutics, small molecule drug products, and liposomal drug products for 186-RNL in support of our ongoing and future glioblastoma clinical trials, manufacturing scale-up, and commercialization. We expect that this FDA feedback will apply to 186-RNL used in other clinical development programs, including leptomeningeal metastases, and pediatric brain cancer. I'm happy to report that we have now completed all key manufacturing objectives for CGMP186 RNL production to support ongoing and planned clinical trials in 2022 and beyond. During a separate clinically focused type C meeting, the FDA and PLUS agreed that the respect GBM clinical trials should proceed to the planned phase two. The key focus areas of ongoing clinical investigation in the recurrent GBM development program will be further dose exploration, including both increased dosing, i.e., advancing to cohort eight and study of multiple doses, and also collecting additional safety and efficacy data to inform the design of the future registrational trial. In addition, during the meeting, there was agreement that in a planned future registrational trial, overall survival should be used as a primary endpoint. The company and the FDA also agreed to hold future meetings to consider the use of external data to augment the control arm in the registrational trial facilitated by our ORPHAN and FAST-TRACK designations. Earlier this month, an IND amendment was submitted regarding this plan, and that sits with the FDA as of today. The plan phase two trial design will incorporate the following features. The cohort six dose will be used, which is also the recommended phase two dose from cohort six, as mentioned, which will be 22.3 millicuries in 8.8 milliliters of volume. The study will enroll up to an additional 31 patients at five planned sites, including the current three sites plus an additional two sites, which are currently in process of coming online. Subjects will remain on study until disease progression by renal criteria. recognizing, of course, the potential for pseudoprogression that complicates the use of Raynaud criteria. And we're working on the imaging analysis today to be able to resolve that issue. Or potentially a PI decision that's in the best interest of the patient. The primary endpoint, as mentioned, will be overall survival following single administration. Secondary endpoints will assess the safety, tolerability, objective response rate, partial response, serious treatment, emergent adverse events, up to three years, and progression-free survival at six months. We'll make known the final details pending further feedback from our IND amendment, which is with FDA, as mentioned. I'll now pivot to discuss our leptomeningeal metastases program. Our team was very honored to learn in the third quarter that we had been awarded a $17.6 million grant product development research funding award from the Cancer Prevention and Research Institute of Texas, also called CPRET. This award will cover the majority of the development costs, including funding for up to 150 enrolled patients for our leptomeningeal metastases program over three years. For those that you aren't familiar with CPRET, CPRET is the second largest global public funder of cancer research in the world after the NIH with $6 billion allocated by the state. And also of note, PLUS's $17.6 million grant award is the largest in the most recent CPRIT review cycle and one of the top 10 largest all-time awarded by CPRIT in its history. Besides the of the asset, the award is a material source of non-diluted funding that significantly strengthens the company's balance sheet and extends our expected cash runway. Andrew will provide some greater perspective on that momentarily. While this is all exciting news, let me just back up a bit and recap our current development plan, starting with our rhenium-186 nanoliposome development. As I mentioned, the company recently completed key manufacturing objectives for CGMP-186-RNL to support ongoing and planned clinical trials in 2022 and beyond. NP drug of sufficient quality and scale to enable the completion of all further clinical investigation, including for ongoing and planned phase two and phase three clinical trials in patients with glioblastoma, leptomangia metastasis, pediatric brain cancer, and really any conceivable future disease targets. Having access to C-GMP drug is an important milestone as we prepare to transition from early to late stage clinical investigation and commercialization. Relatedly, I'm pleased to announce that the World Health Organization has approved rinium-186-obispo-meta as a generic name for 186-RNL. As required, this generic name will be used in all future IND and NDA submissions and brand name development in related go-to-market planning is currently in process. And so, here to forward, we will now use the 186 rhenium obispo-meta name in lieu of the 186 RNL research name. Regarding the GBM program, based on the positive safety profile and promising efficacy signals observed thus far, and with clear feedback from the FDA, Most importantly, we intend to move into phase two in the U.S. by the end of 2022, and that effort will be funded to a significant degree as it has in the past by the U.S. NIH National Cancer Institutes. Second, pursuant to FDA guidance, we intend to continue the dose escalation to cohort eight, and that's a 16.6 milliliter volume and 41.5 millicuri infused dose. That's an approximate 33% increase in both volume infused and radiation dosage. Notably, we recently received DSMB approval to advance to cohort 8 from cohort 7. Any further escalations in volume or dosage will be based on observations from cohort 8. But again, the overarching goal here is to dose escalate until we reach dose-limiting toxicity or the maximum practical dose. The ongoing phase 1 is intended to explore further dose escalation on large tumors as we have yet to observe any dose-limiting toxicities, and we also continue to work to further optimize the delivery and dosing approach. This week, at the 35th Annual Congress for the European Association of Nuclear Medicine, the company presented data which indicated that the direct administration of rhenium-obispo-meta is safe in patients with recurrent GBM with no dose-limiting toxicities in 24 total patients. That's the total patient set treated thus far. And I refer you to that press release for further information. So now on to our leptomeningeal metastases, or LM, development program. That trial is a multicenter phase 1, 2 dose escalation study to determine the maximum tolerated dose, safety, and efficacy of 186 rhenium of ispameda. LM is an end-stage fatal complication associated with advanced cancers that infiltrate the fluid line structures of the central nervous system or leptomeninges. The incidence of LM is growing with better local cancer care, and there are no FDA-approved therapies. Standard treatment includes external beam radiation therapy to the affected sites, followed by chemotherapy given either orally, intravenously, or often administered twice weekly directly into the CSF space. In the third quarter of 2022, the company initiated enrollment of Cohort 2. That's a doubling of the dose over Cohort 1 in the RESPECT-LM dose escalation trial. We anticipate completing enrollment of Cohort 2 by the end of 2022 and Cohort 3 by the end of Q1 2023. In Cohort 1, 186-renium-obispo-meta was successfully delivered without dose-limiting toxicities in the independent RESPECT LMDSMB approved the plan to move forward with cohort two. By the way, also at the annual Congress of the European Association of Nuclear Medicine this week, the company presented from the podium data demonstrating that 186 rhenium abysmated administered through an intraventricular catheter at 6.6 millicuries in 5 cc's achieved absorbed dosages of 18.7 to 29 gray to the ventricles and cranial subarachnoid space, which was well-tolerated with no treatment-related adverse events greater than grade 1. Additionally, all three patients in the cohort were observed to have prompt and complete 186 rhenium-obispobamide distribution throughout the CSF that was durable past one week and very well-tolerated. All patients showed a decrease and CSF cell count by microfluidic chamber assay after treatment, ranging from a decrease to 45% up to 92%, which was also durable. Now, regarding our development program in pediatric brain cancer, the company is on track to meet its objectives to submit an investigational new drug application in the fourth quarter of 2022 for what will be called the RESPECT PBC Phase I Dose Finding and Efficacy Study of 186 rhenium obispumata for pediatric brain tumors, and that will be submitted in conjunction with our lead academic institution hospital of Northwestern University in Chicago. Finally, regarding our novel in-licensed radioembolic microparticle technology called 188 RNL-BAN, we have completed the technology transfer phase and key CMC feasibility studies and we are on track to submit a pre-IND meeting and have that meeting by year-end. With this reservable biomaterial embolic technology, coupled with a highly potent radiotherapeutic, in this case, 188 rinium, we can target almost any solid organ tumor in the body using standard interventional radiologic means and leverage the breadth of the human vascular system to selectively reach almost any tumor. Rhenium-188 nanolepisome biodegradable alginate microspheres is a next-generation fully-resorbable technology that solves many of the existing problems with current radioembolic technology that have been in the market for many decades and represents an existing total addressable market of about $1.3 billion. The company will initially focus on developing the BAM technology as a next-generation radioembolic therapy for liver cancer. Liver cancer is a rare disease with an increasing annual incidence globally and a five-year overall survival rate of only about 20%. 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 third quarter ended September 30, 2022. As of September 30, 2022, cash and cash equivalents were $20.3 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 the nine months that ended September 30, 2022 was $10.7 million compared to $7.7 million in the same period for the previous year. The main year-over-year changes between the third quarters of 2022 and 2021 are as follows. Grant revenue of $73,000 was reported, related entirely to SIPRIT. Total operating expenses for the third quarter of 2022 were $5.2 million compared to $3.5 million for the third quarter of 2021. The increase is due primarily to the following. CMC-related activities to develop and produce CGMP-quality drug material, as well as expenses associated with the development of the synthetic control arm platform for future clinical trials. These projects and related spend have now been substantially completed. to a lesser extent an increase in legal, IP, and other general corporate expenses. Interest expense decreased from $232,000 in the third quarter of 2021 to $173,000 in the third quarter of 2022. This decrease reflects the continued principal pay down that commenced in November 2021 on the company's Oxford debt. Net loss for the third quarter of 2022 was $5.2 million, or 19 cents per share, compared to a net loss of 3.7 million or 28 cents per share for the third quarter of 2021. I'd also like to take this opportunity to provide an overview of the positive impact on cash and the financial statements of the 17.6 million CPREC grant to develop the Respect LM indication. As disclosed in the September 22nd, 2022 press release, This grant covers the three-year period ending August 31st, 2025, with the funding tracking the company proposed clinical development plan. The total planned grant for year one is $3.7 million, increasing to $6.7 million in year two and $7.2 million in year three. Let me walk you through the cash impact of CPRIP and the process to access the $17.6 million. CPRED initially funds 50% of the first year budget, which for PLUS is just under $1.9 million. A request for this $1.9 million has been submitted, and we expect to receive this funding within the next one to two weeks. Once greater than 90% of this initial $1.9 million is utilized, the next request will be submitted. CPRED typically takes less than two weeks to advance the requested funds. The design of the funding is to ensure the company is not out of pocket for grant-related expenses, which will obviously be substantial. Quarterly reports are submitted summarizing payments and development progress during the previous quarter, and CPRED has the right to conduct an annual audit of expenses. These are typical requirements, especially for such substantial levels of funding. As PLUS incurs costs, the costs will be reported in our income statement under the research and development line item, and the matching CPRIG grant will be reported as revenue in the grant revenue line on the income statement. Note 7 on page 11 of Form 10Q outlines the accounting and financial for the grant and associated project-specific costs. Now I'll turn it back to Mark.