Russell Bradley Named President & General Manager of CNSide Dr. Marc Hedrick, Rick Hawkins, and Russell Bradley Join CNSide Board of Directors Dr. Jonathan Stein Appointed CNSide Medical Director AUSTIN, Texas, Feb. 24, 2025 (GLOBE NEWSWIRE) -- Plus Therapeutics, Inc. (NASDAQ:PSTV) (the "Company"), a clinical-stage pharmaceutical company developing targeted radiotherapeutics with advanced platform technologies for central nervous system (CNS) cancers, today announced that is has appointed Mr. Russell Bradl ...

Core Insights - Plus Therapeutics, Inc. has appointed Michael Rosol, Ph.D., as Chief Development Officer to lead clinical, pre-clinical, and biomarker development activities as the company transitions from mid-stage to pivotal trials in 2026 [1][2] - Dr. Rosol brings 25 years of experience in clinical trial design and operations, having previously served as Chief Medical Officer at Navidea Biopharmaceuticals and held key roles at Novartis Pharmaceuticals [2][3] - The company is focused on developing targeted radiotherapeutics for central nervous system cancers, specifically recurrent glioblastoma (GBM) and leptomeningeal metastases (LM), which currently lack FDA-approved therapies [5] Company Overview - Plus Therapeutics is a clinical-stage pharmaceutical company developing targeted radiotherapeutics aimed at enhancing clinical outcomes for patients with difficult-to-treat CNS cancers [5] - The company utilizes image-guided local beta radiation and targeted drug delivery approaches, with a pipeline that includes lead programs in recurrent GBM and LM [5] - Plus Therapeutics has established a supply chain through strategic partnerships to support the development, manufacturing, and potential commercialization of its products [5] Disease Context - Leptomeningeal metastases (LM) occur in approximately 5% of cancer patients and are often terminal, with a one-year survival rate of only 7% [3] - Glioblastoma (GBM) affects around 15,000 patients annually in the U.S., with an average life expectancy of less than 24 months and a one-year survival rate of 40% [4] - There are currently no FDA-approved treatments for recurrent GBM that significantly extend patient life, highlighting a critical need for effective therapies [4]

Core Points - Plus Therapeutics, Inc. has closed a private placement financing of approximately $3.7 million and received a $2.0 million advance from CPRIT to support clinical development of Rhenium (Re) Obisbemeda for leptomeningeal metastases and the CNSide LM diagnostic test [1][8][12] Private Placement Financing - The private placement involved the issuance of secured convertible promissory notes totaling $3,362,251 and common stock purchase warrants for up to 3,002,009 shares at an exercise price of $1.12 per share [3][4] - The notes have a one-year maturity and are convertible into common stock at the investors' discretion [3][4] - The gross proceeds from the private placement were approximately $3.7 million before deducting offering expenses [5] CPRIT Funding Advance - The $2.0 million advance from CPRIT is part of a larger $17.6 million grant award, with approximately $5.2 million remaining after this advance [8][9] - This funding will accelerate the clinical development of Rhenium (Re) Obisbemeda and the CNSide LM diagnostic test [8] Company Strategy and Future Plans - The capital raised is expected to fully support the completion of two planned LM trials, positioning the company for a pivotal trial in 2026 [2] - The CNSide diagnostic test is planned for commercialization in the U.S. in 2025 [16][17] About Rhenium (Re) Obisbemeda - Rhenium (Re) Obisbemeda is a novel injectable radiotherapy aimed at treating CNS tumors, specifically recurrent glioblastoma and leptomeningeal metastases [13][18] - The treatment utilizes Rhenium-186, which is suitable for CNS therapeutic applications due to its properties [13] About Leptomeningeal Metastases (LM) - LM is a rare but serious complication of cancer, occurring in approximately 5% of cancer patients, often leading to terminal outcomes [12] - There are currently no FDA-approved therapies specifically for LM patients, highlighting a significant unmet medical need [12]

Core Insights - Plus Therapeutics, Inc. presented promising data on Rhenium (186Re) Obisbemeda for treating leptomeningeal disease, particularly in breast cancer patients, at the 2024 San Antonio Breast Cancer Symposium [1][2] Group 1: Clinical Trial Results - In the ReSPECT-LM Phase 1 clinical trial, 9 out of 20 patients with leptomeningeal metastases (LM) from primary breast cancer were treated, with the maximum tolerated dose not yet reached [3] - The patients received a single intrathecal dose of Rhenium (186Re) Obisbemeda, ranging from 6.6 to 66.14 mCi of radiation, with only one dose-limiting toxicity (thrombocytopenia) reported [3] - Best response rates included circulating tumor cell (CTC) response at 88% (7/8), MRI imaging response at 25% (2/8), and clinical response at 29% (2/7) [3] - Clinical benefit rates showed CTC at 100% (8/8), MRI imaging at 75% (6/8), and clinical at 71% (5/7) [3] - The median overall survival for the 9 breast cancer patients was 9 months, with 2 patients surviving beyond 600 days post-treatment [3] Group 2: Future Plans - The company plans to initiate a ReSPECT-LM Phase 1b single-dose breast expansion cohort in Q1 2025 to further evaluate the safety and efficacy of Rhenium (186Re) Obisbemeda [4] - Plus Therapeutics aims to rapidly advance into a breast cancer-focused expansion cohort alongside planned multiple-dose expansion trials [4] Group 3: Background on Leptomeningeal Metastases - Leptomeningeal metastases (LM) is a rare but serious complication of cancer, with breast cancer being the most common primary cancer associated with LM, affecting 3-5% of breast cancer patients [5][6] - The incidence of LM is increasing, partly due to longer survival rates of cancer patients and the ineffectiveness of standard chemotherapies in reaching sufficient concentrations in the cerebrospinal fluid [6] Group 4: About Rhenium (186Re) Obisbemeda - Rhenium (186Re) Obisbemeda is a novel injectable radiotherapy designed for targeted high-dose radiation delivery in CNS tumors, optimizing patient outcomes [7] - The radioisotope Rhenium-186 is noted for its short half-life and effectiveness in destroying cancerous tissue while allowing for real-time imaging [7] - The drug is currently being evaluated in clinical trials for recurrent glioblastoma and leptomeningeal metastases, with funding support from the National Cancer Institute and the Cancer Prevention & Research Institute of Texas [7] Group 5: Company Overview - Plus Therapeutics, Inc. is focused on developing targeted radiotherapeutics for challenging CNS cancers, aiming to enhance clinical outcomes through innovative treatment approaches [8] - The company has established a supply chain through strategic partnerships to support the development and potential commercialization of its products [8]

Core Insights - Plus Therapeutics, Inc. has renewed its Master Services Agreement with Telix IsoTherapeutics Group, ensuring a reliable supply of cGMP Re-186, a key radioisotope for its lead candidate Rhenium (186Re) Obisbemeda [1][2] Group 1: Agreement Details - The renewed agreement enhances Plus Therapeutics' supply chain strategy by securing Re-186 through IsoTherapeutics and utilizing SpectronRx for final drug manufacturing, establishing a scalable supply chain for late-stage clinical trials and future commercial needs [2][7] - The focus of the agreement includes the production of aluminum perrhenate and the final processing of cGMP Re-186, enabling just-in-time manufacturing to support the overall supply chain [2][7] Group 2: Product Overview - Rhenium (186Re) Obisbemeda is an injectable radiotherapy designed for targeted high-dose radiation delivery in CNS tumors, aiming to optimize patient outcomes by reducing off-target risks compared to existing therapies [3] - The product is currently being evaluated in clinical trials for recurrent glioblastoma and leptomeningeal metastases, with support from the National Cancer Institute and a $17.6 million grant from the Cancer Prevention & Research Institute of Texas [3] Group 3: Company Background - Plus Therapeutics is a clinical-stage pharmaceutical company focused on developing targeted radiotherapeutics for challenging CNS cancers, with a pipeline that includes recurrent glioblastoma and leptomeningeal metastases [4] - The company has established a strategic supply chain through partnerships to facilitate the development, manufacturing, and potential commercialization of its products [4]

CNSide Cerebrospinal Fluid (CSF) Assay analyzed 258 CSF samples across 66 leptomeningeal metastases (LM) patients at five institutions CNSide identified extensive, actionable mutational changes, and clinically relevant longitudinal biomarkers AUSTIN, Texas, Nov. 21, 2024 (GLOBE NEWSWIRE) -- CNSide Diagnostics, LLC, a wholly owned subsidiary of Plus Therapeutics, Inc. (Nasdaq: PSTV) (“Plus” or the “Company”), will present data demonstrating the utility of the CNSide CSF Assay Platform in identifying mutatio ...

Financial Data and Key Metrics Changes - The cash and investments balance was $4.8 million at September 2024, down from $8.6 million at December 2023 [20] - Year-to-date operating loss for 2024 was $10.8 million compared to $9.5 million in the same period of 2023, primarily due to increased spending related to the ReSPECT-LM trial [21] - Net loss year-to-date 2024 was $9.1 million or $1.46 per share, compared to a net loss of $9.5 million or $3.54 per share for the same period in the prior year [21] Business Line Data and Key Metrics Changes - The ReSPECT-LM program is advancing with a Phase 1 single-administration trial showing favorable safety and efficacy results, with a median overall survival of 12 months compared to a historical average of four months [7][8] - The CNSide Cerebrospinal Fluid Assay platform is being recognized for its diagnostic value, with plans for a limited market release in January 2025 [12][14] Market Data and Key Metrics Changes - The company is expanding its market access activities for the CNSide platform, including obtaining necessary certifications and negotiating with commercial payers [13][14] - The ReSPECT-GBM trial continues to enroll patients, with 42 patients enrolled across three sites, and the average absorbed radiation dose to tumors in Phase 2 was 300 gray, correlating with increased overall survival [15][16] Company Strategy and Development Direction - The company is focused on advancing its clinical programs, including the ReSPECT-LM and ReSPECT-GBM trials, while also expanding its diagnostic capabilities with the CNSide platform [10][12] - A research collaboration with Brainlab aims to enhance treatment planning and drug delivery for brain cancer patients [17] Management's Comments on Operating Environment and Future Outlook - Management expressed optimism about grant funding opportunities, particularly from CPRIT, and indicated that the company is well-positioned for continued success in Texas despite potential federal changes [39][40] - The company anticipates significant milestones in 2024, including presentations at major conferences and the initiation of new clinical trials [25][30] Other Important Information - The company has received a $3 million grant from the US Department of Defense to support a Phase 1 trial for pediatric brain cancer [18] - A second GMP manufacturing partnership has been established to support future commercial demand projections for RNL [19] Q&A Session Summary Question: Opportunities for CNSide and RNL in LM - Management sees increasing synergies between CNSide and RNL, with potential to double or quadruple the addressable market for LM by improving diagnostic sensitivity [34] Question: Landscape for Grants - Management believes there are continued opportunities for grants, particularly from CPRIT, and expects to maintain a strong position in Texas [38][40] Question: LM Multi-Dose Study Dose Selection - The selected dose of 13.2 millicuries for the multi-dose study was based on safety and response data from previous cohorts, with a Bayesian approach to clinical development being utilized [44] Question: Timeline for CNSide Assay Compliance and Reimbursement - The company aims to commercialize the CNSide test in Q4 2024, with CLIA compliance and reimbursement negotiations ongoing [46]

Financial Performance - The company's cash and investments balance was $4.8 million at September 30, 2024, down from $8.6 million at December 31, 2023[5] - Total operating loss year to date through September 30, 2024, was $10.8 million, an increase from $9.5 million for the same period in 2023[5] - Net loss year to date through September 30, 2024, was $9.1 million, or $(1.46) per basic share, compared to a net loss of $9.5 million, or $(3.54) per basic share, for the same period the prior year[5] - Net loss for the three months ended September 30, 2024, was $2,874,000, compared to a net loss of $3,219,000 for the same period in 2023, showing an improvement of 10.7%[14] - The company reported a net cash used in operating activities of $9,343,000 for the nine months ended September 30, 2024, compared to $10,970,000 in 2023, indicating a reduction of 14.8%[15] - Cash and cash equivalents at the end of the period were $1,223,000, down from $11,006,000 at the end of September 2023[15] - Net cash provided by financing activities was $6,187,000 for the nine months ended September 30, 2024, compared to $3,974,000 in 2023, indicating an increase of 55.5%[15] Revenue and Grants - The company recognized $4.4 million in grant revenue year to date through September 30, 2024, compared to $3.6 million for the same period in 2023[5] - Grant revenue for the three months ended September 30, 2024, increased to $1,456,000 from $1,240,000 for the same period in 2023, representing a growth of 17.5%[14] - The company received a $0.9 million grant payment as part of a $3 million award from the Department of Defense to support clinical development for pediatric brain cancer[3] Operating Expenses - Total operating expenses for the nine months ended September 30, 2024, were $15,207,000, up from $13,063,000 in 2023, reflecting an increase of 16.4%[14] - Research and development expenses for the three months ended September 30, 2024, were $2,858,000, an increase from $2,493,000 in the same period of 2023, marking a rise of 14.6%[14] - General and administrative expenses for the nine months ended September 30, 2024, totaled $6,813,000, compared to $6,167,000 in 2023, reflecting an increase of 10.5%[14] Clinical Trials and Developments - The company completed enrollment in the Phase 1 ReSPECT-GBM trial and obtained FDA agreement to begin enrollment in the ReSPECT-LM trial expected to start in early 2025[3] - The ReSPECT-GBM Phase 1/2 trial showed promising feasibility, safety, response, and efficacy signals across 42 treated patients[3] - A GMP manufacturing partnership was established with SpectronRx to meet late-stage clinical and commercial forecasts for Rhenium (186Re) Obisbemeda[3] - The company plans to complete the ReSPECT-LM Phase 1 single dose trial and determine the maximum tolerated and recommended Phase 2 doses by year-end 2024[4] - The company anticipates launching the CNSide Cerebrospinal Fluid Tumor Cell Enumeration Assay Platform as a laboratory-developed test in 2025[4] Shareholder Information - The weighted average number of shares of common stock outstanding for basic calculations increased to 7,855,763 for the three months ended September 30, 2024, from 3,225,351 in the same period of 2023[14] - The company experienced a change in the fair value of warrants, resulting in an income of $960,000 for the three months ended September 30, 2024, compared to no income in the same period of 2023[14]

Product Development and Clinical Trials - Plus Therapeutics is developing targeted radiotherapeutics for CNS cancers, utilizing innovative drug formulations to enhance radiation delivery and minimize exposure to healthy tissues[74]. - The lead candidate, rhenium (186Re) obisbemeda, aims to treat recurrent glioblastoma, leptomeningeal metastases, and pediatric brain cancers through localized delivery methods[77]. - Interim results from the Phase 1/2a ReSPECT-GBM trial indicate that rhenium (186Re) obisbemeda can deliver up to 740 Gy of absorbed radiation to tumor tissue without significant toxicities, compared to the typical maximum of ~30-35 Gray with external beam radiation therapy[91]. - The ReSPECT-GBM trial is set to proceed to Phase 2, with a focus on further dose exploration and collecting additional safety and efficacy data[95]. - The ReSPECT-GBM Phase 2 trial has enrolled 42 patients, with a median overall survival (mOS) of 13 months, which is 63% better than the standard of care of 8 months[98]. - The median progression-free survival (mPFS) in the same trial is reported at 11 months, compared to 4 months for the standard of care[98]. - Rhenium (186Re) obisbemeda has shown a favorable safety profile, with most adverse events being mild (73.5%) or moderate (18.8%) and only 2 out of 9 severe adverse events related to the study drug[99]. - The average absorbed radiation dose to the tumor in the Phase 2 trial was 300 Gy, with 88.9% of patients meeting key drug delivery parameters correlating with overall survival[99]. - The ReSPECT-LM Phase 1 trial has treated 26 patients with no dose-limiting toxicities observed at radiation doses up to 66.14 millicuries[107]. - The company plans to submit a pediatric brain tumor IND for the ReSPECT-PBC clinical trial in the fourth quarter of 2024[115]. Regulatory and Designation Achievements - The FDA granted Orphan Drug and Fast Track designations to rhenium (186Re) obisbemeda for GBM treatment, supporting its clinical development[92]. - The FDA granted Orphan Drug designation to rhenium (186Re) obisbemeda for the treatment of patients with breast cancer with leptomeningeal metastases in November 2023[108]. Financial Performance and Funding - Grant revenue recognized was $1.5 million for the three months ended September 30, 2024, compared to $1.3 million for the same period in 2023, reflecting an increase of approximately 15.4%[127]. - Research and development expenses for the three months ended September 30, 2024, totaled $2.858 million, up from $2.493 million in the same period in 2023, an increase of approximately 14.6%[128]. - General and administrative expenses increased to $2.397 million for the three months ended September 30, 2024, from $1.998 million in the same period in 2023, representing an increase of approximately 20.0%[131]. - The company incurred net losses of $9.1 million for the nine months ended September 30, 2024, with an accumulated deficit of $489.6 million[139]. - Cash and cash equivalents decreased to $1.223 million as of September 30, 2024, down from $8.554 million as of December 31, 2023[139]. - Current liabilities increased to $12.112 million as of September 30, 2024, compared to $10.727 million as of December 31, 2023[139]. - The company expects aggregate research and development expenses to increase for the remainder of 2024 compared to the same period in 2023[130]. - The company recognized a net fair value gain on warrant liability of $1.0 million for the three months ended September 30, 2024, and $5.7 million for the nine months ended September 30, 2024[136]. - In May 2024, the company completed a private placement, issuing 3,591,532 shares and raising approximately $7.3 million in gross proceeds, with potential additional proceeds of $12.0 million if all warrants are exercised[140]. - The company received a CPRIT Grant of $17.6 million to fund two-thirds of the development costs for rhenium (186Re) obisbemeda, recognizing $4.4 million in grant revenue for the nine months ended September 30, 2024[141]. - A DoD Award was secured for $3.0 million to support the expansion of clinical trials for pediatric brain cancer, with the first payment of $0.9 million received on October 4, 2024[142]. - Under the 2022 Purchase Agreement with Lincoln Park, the company has the right to sell up to $50.0 million in shares, with 527,166 shares sold for net proceeds of approximately $3.2 million from August 2022 to December 2022[143][145]. - For the nine months ended September 30, 2024, net cash used in operating activities was $9.3 million, a decrease from $11.0 million in the same period of 2023, primarily due to increased reimbursement under the CPRIT grant[160]. - Net cash used in investing activities for the nine months ended September 30, 2024 included $0.5 million for Biocept assets and $7.1 million for short-term investments[161]. - Financing activities for the nine months ended September 30, 2024 provided net cash of $6.2 million, primarily from the May 2024 Private Placement and a $3.3 million drawdown from the Pershing Credit Facility[162]. - As of September 30, 2024, the company had $0.8 million of deferred revenue related to the CPRIT Grant[141]. Operational and Strategic Developments - Plus Therapeutics has expanded its manufacturing capabilities through a services agreement in Indiana, ensuring a robust supply chain for ongoing clinical trials[81]. - The company is focused on addressing significant unmet medical needs in treating rare and difficult-to-treat cancers, with a pipeline that includes potential applications for head and neck, ovarian, and breast cancers[80]. - The CNSide® diagnostic portfolio is being developed alongside rhenium (186Re) obisbemeda, with plans for strategic partnerships to enhance its market presence[78]. - The company is developing a novel radioembolization technology combining Rhenium NanoLiposome with Biodegradable Alginate Microsphere technology for targeted radiation delivery[119]. - The company entered into a manufacturing services agreement with SpectronRx for drug product development and manufacturing, effective January 2025[123]. - The Department of Defense has awarded $3.0 million for research and development to support the expansion of the pediatric brain cancer clinical trial[118]. - The company has ongoing cash requirements for clinical trials, regulatory approvals, and operational expansions, with no assurance of future capital raising success[152][153]. - The company reviews goodwill for impairment annually, with the test conducted in the fourth quarter[164]. - The company experienced significant volatility in its share price during the year[164]. - In May 2024, the company issued Series A and Series B Warrants, initially classified as liabilities due to their potential exercise into common stock or Pre-Funded Warrants[165]. - The balance of the warrant liability at the amendment date was $5.2 million, which was reclassified to equity following amendments made on August 9, 2024[165].

Partnership and Manufacturing Agreement - Plus Therapeutics and SpectronRx signed a Manufacturing Services Agreement (MSA) for the production of Rhenium (186Re) Obisbemeda, a targeted radiotherapy for CNS cancers [1] - The partnership aims to enhance supply chain redundancy and meet the demands of late-stage clinical trials and future commercial needs [3] - SpectronRx will utilize its state-of-the-art facilities, including over 170,000 sq ft of radiopharmaceutical contract development and manufacturing space, to produce Rhenium (186Re) Obisbemeda [2] Rhenium (186Re) Obisbemeda - Rhenium (186Re) Obisbemeda is a novel injectable radiotherapy designed to deliver targeted high-dose radiation to CNS tumors, potentially reducing off-target risks and improving patient outcomes [4] - The therapy is being evaluated in the ReSPECT-GBM and ReSPECT-LM clinical trials for recurrent glioblastoma and leptomeningeal metastases, supported by a $17.6M grant from CPRIT [4] - Rhenium-186 is an ideal radioisotope for CNS therapeutic applications due to its short half-life, beta energy for destroying cancerous tissue, and gamma energy for real-time imaging [4] Company Overviews - Plus Therapeutics is a clinical-stage pharmaceutical company focused on developing targeted radiotherapeutics for CNS cancers, with lead programs in recurrent glioblastoma and leptomeningeal metastases [5] - SpectronRx is a radiopharmaceutical developer and manufacturer with expertise in radiopharmaceutical contract development, manufacturing, and isotope production, supplying products to 29 countries [6][8] - SpectronRx has over 170,000 sq ft of production space, 150 employees, and facilities in Indiana, Connecticut, and Europe, enabling it to condense timelines for bringing new medicines to market [7][8]