PLUS THERAPEUTICS, Inc.

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 0. 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 factor section included in 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 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.

Great. Thank you very much, Kathryn. 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 2021 second 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. Last quarter, I provided a detailed overview of the company, and I'll refer you back to that description. But in summary, for those new to the company, Pus Therapeutics is a clinical-age pharmaceutical company developing innovative, targeted radiotherapeutics for rare and difficult-to-treat cancers. Our lead drug is RNL, or rhenium nanoliposomes. It is a proprietary liposomal encapsulated radionuclide that is delivered local regionally via targeted three-dimensional convection-enhanced delivery directly to the tumor. The active agent is uranium-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. Uranium is a unique isotope, in part because of its energy profile. Its beta energy has a short path length, which gives one precision, a low dose rate, which provides a margin of safety, and a high energy density, which is particularly toxic for highly mitotic cells, which can overwhelm the innate DNA repair mechanism that can also 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 12,000 to 13,000 patients annually in the U.S., 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 medical challenge. Published studies indicate that external beam radiation provides the best incremental improvement and survival of all therapies currently used for glioblastoma and it remains an essential component of multimodal therapy for both glioblastoma and in fact many other cancers. In theory, glioblastoma and frankly any tumor can be fundamentally controlled if a sufficient dose of radiation can be delivered to a particular tumor. RNL is currently under evaluation in the U.S. RESPECT GBM trial, which is a dual phase 1 and 2 multi-center sequential cohort open-label volume and dose escalation study on the safety, tolerability, and distribution of 186 RNL. The trial is currently funded to a significant degree by the U.S. National Cancer Institute. In short, the trial is progressing nicely, and we have now moved into an eighth dosing cohort. As a reminder, in November 2020, at the Society for Neuro-Oncology Annual Meeting, we provided an interim analysis of the first five dosing cohorts and 15 patients. And in March of 2021, in our BioEurope corporate presentation, we updated those interim results to include Cohort 6, and that data can be found on our website. Subsequently, following the successful completion of Cohort 6 and without any dose-limiting toxicities, the Data Safety and Monitoring Board recommended enrolling an additional cohort of three patients, or a cohort seven, at the same volume and radiation dose, but with a higher maximum convection flow rate, specifically at 20 microliters per minute. Then in June of this year, we announced that through cohort seven, no dose-limiting toxicities had been observed, And the DSMB recommended proceeding to the next dosing cohort, representing a 40% increase in both volume and radiation dose. So specifically where we are now at, we're introducing a volume of 12.3 milliliters, a radiation dose of 31.2 millicuries, and we're staying at the same maximum flow rate of 20 microliters per minute. As announced this AM, the first patient in the additional cohort has been successfully treated. And I think it might be helpful at this point in the product development cycle to provide a summary of what we have learned thus far in the RESPECT GBM trial and then consider next steps. So specifically, what we've learned is that hemispheric or one-sided Supratentorial, which is into the upper part of the brain, highly targeted and continuously infused or convected volumes of up to 12.3 milliliters and 31.2 millicuries of radiation have been well tolerated thus far. Up to four catheters can be successfully placed for delivery to best accommodate a variety of tumor sizes and geometries. Tumors up to approximately 25 CCs and with various morphologies can be treated. RNL seems thus far to be safe despite delivering up to 740 gray of absorbed radiation to the tumor, which by the way is 20 times the radiation typically delivered by external beam radiation therapy in the recurrent setting. Patients receiving prior bevucizumab did not convect as well as bev-naive patients, and in the past, we elected to focus the current trial only on bev-naive patients. Furthermore, because of the very substantial doses of radiation administered, when a tumor dies, we found that it induces local swelling or edema, which we can observe on MRI scans, which is so-called pseudoprogression. which is very obvious to see on imaging. So traditional imaging analyses looking at response criteria is suboptimal and of lesser value in this particular clinical situation. Although the Phase I is not designed or powered for efficacy, today 8 of 22 treated patients are still alive, which is obviously a good thing, But because many of those patients have been treated relatively recently and at the higher dosing cohorts and volume cohorts, it understandably makes efficacy determinations today a challenging enterprise. 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 seemed to correlate with better tumor coverage and higher tumor-absorbed doses. And this, in turn, seems to correlate with overall survival. As I mentioned, 8 of 22 patients remain alive, and 3 of 22 patients have survived to 30 months or more, where average survival for a current GBM with standard of care is only about 8 to 10 months. This present cohort should complete enrollment this year, and later this year, we intend to provide a comprehensive update with safety and efficacy data as of that time point, including our updated proposed next steps for the clinical investigation of R&L and recurrent GBM. As mentioned last quarter, the go-forward clinical development plan depends in part on the observed safety outcomes in the present dosing cohort and the involving efficacy data readout of the dataset as a whole. There is the potential to further dose escalate following the current dose cohort dosing cohort as a protocol provides for another 33% increase in volume and radiation dose following the current cohort eight. Besides dose escalation, or perhaps in conjunction with dose escalation, we could potentially implement further changes to delivery parameters as we have done previously. It's also possible that the company may deem the present dose and delivery parameters to be acceptable to move forward and we could expand the enrollment at this present dose to generate further efficacy data to better inform and power a follow-on Phase II registrational trial. As mentioned previously, CMC activities and the availability of cGMP investigational drug product is the primary hard-gating item for a Phase II registrational trial. Therefore, CMC activities are a top priority for us. Our team continues to make excellent progress towards submission and is simultaneously laying the groundwork for commercial readiness. The team has been focused on CGMP drug product development, test method validation, material characterization, and supply chain planning. To that end, we have formally engaged with key suppliers for both critical materials and contract development work. Longer term, manufacturing relationships will be key to commercial success, and our team continues to make nice progress in developing those strategic partnerships. For example, Pyramal and Vicro and Eurofins are, to just name a few, and others are forthcoming. So we remain on track, without delay, to have the key CMC activities completed by year-end and stability testing complete thereafter such that we should be ready with CGMP product by mid-2022. Switching gears a bit, last quarter we noted that two pre-IND meetings had been requested from the FDA to discuss expanding the clinical indications for R and L. Both are complete, and based on the positive FDA feedback, we intend to move forward in filing INDs for both indications. The first is leptomeningeal metastases, an increasingly common secondary cancer complication occurring as a result of increasing overall survival rates that we are seeing for a variety of primary solid and hematologic tumors. LM affects over about 100,000 patients per year in the US, and patients can present with a broad range of signs and symptoms due to simultaneous involvement of multiple areas of the craniospinal axis. Most common tumors giving rise to LM are breast cancer, lung cancer, melanoma, gastrointestinal malignancies, and in cancers of unknown primary. There are no great current treatment options available And the goals of treatment in patients have been limited primarily to stabilizing or improving neurologic function, palliating symptoms, and improving quality of life. Median survival in this patient population is approximately and generously about four to six months if treated. In the planned forthcoming trial, we intend to treat... With RNL, the indwelling subcutaneous reservoir, called an amai reservoir, that sits under the skin and communicates directly with the ventricle and the leptomeningeal or cerebral spinal fluid space. And this is commonly placed in these patients. And it makes delivery a much more straightforward issue than we have in our current GBM trial. The trial will be an open-label, multi-site dose escalation trial evaluating feasibility, safety, dose, and potential efficacy. We plan to submit the IND for RESPECT-LM trial by Q3, perhaps as late as Q4 2021, and commence enrollment as soon as possible thereafter. The principal investigator will be Dr. Andrew Brinner, who's a professor of research at the Division of Hematology and Medical Oncology and clinical investigator at the Institute for Drug Development at the Mays Cancer Center at University of Texas San Antonio and MD Cancer Center. He's also the co-leader of the Experimental and Developmental Therapeutics Program there. Additionally, we believe there's an opportunity to help patients with pediatric brain cancer with R and L, and based on our pre-IND meeting feedback, we intend to submit an IND later this year or in early 2022 to investigate the use of R and L on kids with brain cancer. The details of that trial will be finalized later in 2021. The PI for that trial will be Dr. Ashley Plant, the Kochar Research Scholar, an attending physician in neuro-oncology and assistant professor of pediatrics at the LEAD trial site, which is the Lurie Children's Hospital of Chicago at the Northwestern University School of Medicine. Finally, I'd like to point out that we have been working diligently for some months to take our corporate communications to a new level. That includes in all areas, including public relations, investor relations, and scientific and clinical communications. You'll see the fruits of that work over the remainder of the year, but today you can find the first part of that, which is our clinical trial microsite for the Respect Trials. That can be found at respecttrials.com. The front end is intended to educate and illuminate potential patients and family members with GBM. On the back end that you won't see is a sophisticated compliance patient referral network to help match our clinical trials with patients that may be good candidates and facilitate that process of connecting them with the clinical trial site. And much more is to come in that regard. So at this point, I'll stop and turn the call over to my colleague, Andrew, for a brief review of the first quarter financial results. Andrew?

Thank you, Mark, and good afternoon, everyone. Please refer to our press release issued earlier today for a summary of our financial results for the second quarter ended June 30, 2021. As of June 30, 2021, cash and cash equivalents were $17.2 million compared to $8.3 million as of December 31, 2020. Cash used in operations for the six months of 2021 was approximately $5.4 million compared to $2.9 million in 2020. This difference is mainly due to timing differences on when certain accounts payable and accrued expenses were paid in 2020, in particular relating to the legacy government contract, together with increased R&D spend. There were no revenues in the six months of 2021 as compared to approximately $303,000 in the same period last year. This decrease was due to the closeout of the legacy government contract as previously disclosed. Research and development expenses were 2.2 million for the first six months of 2021 as compared to 1.3 million for 2020. The increase was anticipated and reflects additional RNL CMC development costs to obtain cGMP drug product. G&A expense was 2.8 million for the first six months of 2021 as compared to 3 million for 2020. The decrease was primarily driven by reduction due to tight management of professional and other fees. Interest expense decreased for the six months of 2021 to approximately $476,000 and approximately $601,000 for the same period in 2020, reflecting the pay down of debt principal to $4.3 million in 2020. Net loss for the six months to June 2021 was $5.5 million as compared to a net loss of $2.9 million for the equivalent period in 2020. The net loss was consistent year on year when excluding the book gains on the warrants reported in the first quarter of 2020. As noted in our quarterly filing, this required book transaction was eliminated in the second quarter of 2020 when the Series E warrants were amended. And now I'll turn it back to you, Mark.