Core Insights - Plus Therapeutics, Inc. is advancing its ReSPECT-LM dose optimization trial for REYOBIQ, targeting leptomeningeal metastases (LM) with initial patient treatments underway [1][2] - The trial aims to identify optimal dosing regimens to maximize efficacy and safety, building on positive results from a previous Phase 1 study [3][4] - The company anticipates rapid enrollment due to the lack of FDA-approved therapies for LM and expects to complete Cohort 1 by the end of the year [2][4] Company Overview - Plus Therapeutics is a clinical-stage pharmaceutical company focused on developing targeted radiotherapeutics for central nervous system cancers [11] - The company’s lead product, REYOBIQ, is designed to deliver high-dose radiation directly to CNS tumors, potentially improving patient outcomes compared to existing therapies [8][11] - The ReSPECT-LM trial is supported by a $17.6 million grant from the Cancer Prevention & Research Institute of Texas (CPRIT), a significant funding source for cancer research [6][9] Clinical Trial Details - The ReSPECT-LM trial's primary objectives include determining the safety and tolerability of multiple REYOBIQ doses and identifying the maximum tolerated dose and minimum effective dose [3] - The previous Phase 1 trial demonstrated that a single dose of REYOBIQ could deliver an average absorbed dose of over 250 Gy, with significant tumor reduction observed in patients [4] - Data from the completed Phase 1 study will be presented at the upcoming SNO/ASCO CNS Metastases Conference in August 2025 [5] Industry Context - Leptomeningeal metastases occur in approximately 5% of patients with metastatic cancer, with limited treatment options available, highlighting the need for innovative therapies [7] - REYOBIQ is being evaluated for multiple indications, including recurrent glioblastoma and pediatric brain cancer, indicating a broad potential application in CNS oncology [8][9]

Core Viewpoint - Plus Therapeutics has initiated the ReSPECT-LM dose optimization trial for REYOBIQ™ to determine the optimal dosing schedule for treating leptomeningeal metastases, building on previous trial results and supported by a $17.6 million grant from CPRIT [1][7]. Trial Design and Objectives - The trial aims to optimize treatment dosing for maximum efficacy and safety, focusing on the safety and tolerability of multiple REYOBIQ doses administered via intraventricular catheter [2]. - Primary objectives include identifying the maximum tolerated dose and minimum effective dose for patients with LM from any primary solid tumor cancer [2]. Enrollment and Study Details - The trial will enroll up to 24 patients, evaluating REYOBIQ at a recommended Phase 2 dose of 44.1 mCi across three dosing intervals [4]. - Key cohorts include dosing intervals of 56 days, 28 days, and 14 days, with up to six patients per cohort [4]. Efficacy and Safety Data - Previous trials showed a clinical benefit rate of 76%, with 29% of patients achieving partial responses and 47% maintaining stable disease [5]. - No dose-limiting toxicities were observed in the first four cohorts, although one Grade 4 DLT occurred in each of Cohorts 5 and 6 [5]. Future Plans - The company plans to present data from the completed single-dose escalation trial at the SNO/ASCO CNS Metastases Conference in August 2025 and will request an End of Phase 1 Type B meeting with the FDA [6]. About Leptomeningeal Metastases - Leptomeningeal metastases occur in approximately 5% of patients with metastatic cancer, with median survival typically ranging from 2 to 6 months, highlighting the urgent need for effective treatment options [8]. About REYOBIQ™ - REYOBIQ™ is a novel injectable radiotherapy designed for targeted high-dose radiation in CNS tumors, with potential advantages over currently approved therapies [9]. Company Overview - Plus Therapeutics is a clinical-stage pharmaceutical company focused on developing targeted radiotherapeutics for challenging CNS cancers, with a pipeline that includes treatments for leptomeningeal metastases, recurrent glioblastoma, and pediatric brain cancer [10].

Summary of Plus Therapeutics (PSTV) Update - June 26, 2025 Company Overview - **Company**: Plus Therapeutics (PSTV) - **Focus**: CNS cancer diagnostics through the C Inside Diagnostics platform Key Industry Insights - **CNS Metastases**: Affects approximately 30% of all cancer patients, translating to over 1 million individuals in the US alone [6][14] - **Current Diagnostic Methods**: Outdated, with cytology dating back to 1904 and MRI from the 1970s, leading to inadequate diagnosis and treatment options [7] - **Market Opportunity**: Estimated total addressable market for CNS metastases diagnostics is approximately $6 billion in the US [14][35] Core Product Insights - **C Inside Diagnostics**: A comprehensive testing platform for CNS and CSF cancers, offering four tests from a single CSF sample with clinical specificity of 95% and sensitivity of 92% [8][11] - **Technological Advancements**: Capable of detecting tumor cells at a concentration of one cell per 5 ml of CSF, representing a significant improvement over existing methods [8] - **Regulatory Environment**: Operates under CMS regulations, exempt from FDA premarket review, facilitating a more predictable regulatory pathway [12][15] Acquisition and Business Strategy - **Acquisition Context**: C Inside was acquired in early 2024 as part of a distressed sale, with over $300 million previously invested in its development [5][11] - **Commercialization Plan**: Initial launch in Texas anticipated in Q3 2025, with plans for national expansion through 2027 [20][16] - **Testing Infrastructure**: Centralized lab in Houston, Texas, with plans for CMS accreditation expected in Q3 2025 [15][16] Financial and Market Projections - **Initial Market Traction**: Over 11,000 tests ordered by more than 200 physicians across 120 institutions since the initial launch in 2020 [11] - **Revenue Expectations**: Conservative forecasts for 2025 due to ongoing negotiations with payers and the need to re-establish agreements [18][21] - **Long-term Growth**: Anticipated meaningful revenue contributions from 2026 onwards as testing volumes increase [18] Reimbursement Strategy - **Value-Based Pricing**: Developing a pricing strategy based on clinical validation and market comparisons, aiming for favorable reimbursement decisions [26][27] - **Negotiation Status**: Engaged with previous payers and exploring new agreements, with a focus on establishing specific reimbursement codes [49][50] Future Expansion Plans - **International Opportunities**: While currently focused on the US market, there are considerations for international expansion in the future [57] Conclusion - **Market Need**: Addressing a significant unmet clinical need in CNS cancer diagnostics, with potential to improve patient outcomes and quality of life [19][35] - **Next Steps**: Continued communication with stakeholders as developments occur, with a focus on reintroducing C Inside to the market [60]

Core Insights - Plus Therapeutics is set to launch its CNSide CSF Assay Platform in the U.S. market in the second half of 2025, targeting a significant unmet need in CNS cancer diagnostics with a market opportunity exceeding $6 billion [1][2][4] Company Overview - Plus Therapeutics, Inc. is a clinical-stage pharmaceutical company focused on developing targeted radiotherapeutics for central nervous system (CNS) cancers [14] - The company has invested over $300 million in the CNSide technology, which aims to address the clinical need for better diagnostic tools in CNS cancer [3] Product Details - The CNSide CSF Assay Platform is designed for patients suspected of having CNS cancer metastases, with the first test, CNSide CSF Tumor Cell Enumeration (TCE), expected to be commercialized soon [2][4] - The platform has demonstrated high sensitivity (92%) and specificity (95%) in diagnosing CNS metastases, influencing treatment decisions in 90% of cases [5] Market Opportunity - CNS metastases affect approximately 30% of adult cancer patients, and the current standard of care for diagnosis is outdated, leading to missed or delayed diagnoses [4] - The CNSide platform is positioned to provide superior clinical utility compared to the current standard of care, which has been validated through real-world use and peer-reviewed publications [5] Commercial Strategy - Plus Therapeutics has established a scalable testing laboratory in Houston, TX, and is executing a commercial market access strategy that includes state licensure and reimbursement codes [6][7] - The company anticipates launching the CNSide platform in Texas first, followed by expansion into additional states [6] Financial Outlook - The revenue contributions from the CNSide subsidiary are expected to become meaningful to Plus Therapeutics' operations in fiscal year 2026 [9]

Core Insights - Plus Therapeutics, Inc. is set to provide a business update on June 26, 2025, before the market opens, followed by a conference call and webcast at 9:00 a.m. ET [1] Company Overview - Plus Therapeutics is a clinical-stage pharmaceutical company based in Houston, Texas, focused on developing targeted radiotherapeutics for challenging central nervous system cancers [4] - The company aims to enhance clinical outcomes through a combination of image-guided local beta radiation and targeted drug delivery approaches [4] - Plus Therapeutics has a pipeline of product candidates, with lead programs targeting leptomeningeal metastases and recurrent glioblastoma [4] - The company has established a supply chain through strategic partnerships to support the development, manufacturing, and potential commercialization of its products [4]

Core Insights - Plus Therapeutics has received FDA clearance for its Investigational New Drug application for REYOBIQ, aimed at treating pediatric patients with high-grade glioma and ependymoma [2][5] - The Phase 1/2a trial, named ReSPECT-PBC, is supported by a $3 million grant from the U.S. Department of Defense and will focus on determining the maximum tolerated dose and safety of REYOBIQ in children aged 6 to 21 [1][4][7] Company Overview - Plus Therapeutics is a clinical-stage pharmaceutical company based in Houston, Texas, specializing in targeted radiotherapeutics for central nervous system cancers [9] - The company is advancing a pipeline that includes treatments for recurrent glioblastoma, leptomeningeal metastases, and pediatric brain cancer [9] Trial Design and Objectives - The ReSPECT-PBC trial is a two-part, single-arm study designed to assess the safety and tolerability of REYOBIQ, with a focus on pediatric patients with rare and aggressive brain tumors [4][7] - The trial will enroll approximately 56 patients, with 24 in Phase 1a for dose escalation and 32 in Phase 2a to assess efficacy [7] Treatment Potential - REYOBIQ is designed to deliver high doses of beta radiation directly to brain tumors while minimizing damage to surrounding healthy tissue, potentially improving outcomes for patients with limited treatment options [5][8] - The targeted delivery method via convection enhanced delivery (CED) aims to bypass the blood-brain barrier, which is a significant challenge in treating CNS tumors [4][5]

Core Insights - Plus Therapeutics has announced a comprehensive restructuring of its previous $15 million equity financing, which eliminates the potential issuance of up to 1.5 billion shares of common stock, aiming to enhance shareholder value and simplify its equity capital structure [1][6]. Company Overview - Plus Therapeutics, Inc. is a clinical-stage pharmaceutical company based in Houston, Texas, focused on developing targeted radiotherapeutics for challenging central nervous system cancers, with a pipeline that includes programs for leptomeningeal metastases and recurrent glioblastoma [4]. Restructuring Details - The restructuring involves the cancellation of approximately 25 million shares of common stock or pre-funded warrants, which will further reduce stockholder dilution [6]. - The company has filed a request with the SEC to withdraw the resale registration statement related to the March 2025 equity financing [3]. - Future financing provisions state that 90% of proceeds from any capital raised after July 1, 2025, will be used to repay holders of 22,727,270 shares of common stock at 115% of the original price paid, based on an effective initial price of $0.66 per share [6].

Core Viewpoint - Plus Therapeutics (PSTV) has received an upgrade to a Zacks Rank 2 (Buy), indicating a positive trend in earnings estimates which is a significant factor influencing stock prices [1][2]. Earnings Estimates and Stock Price Movement - The Zacks rating system is based on the correlation between changes in earnings estimates and stock price movements, making it a valuable tool for investors [2][3]. - Institutional investors utilize earnings estimates to determine the fair value of stocks, leading to price movements based on their buying or selling activities [3]. Company Performance Indicators - The upgrade for Plus reflects an improvement in the company's underlying business, which is expected to positively influence its stock price [4]. - Over the past three months, the Zacks Consensus Estimate for Plus has increased by 78.7%, indicating a significant upward revision in earnings expectations [7]. Zacks Rank System - The Zacks Rank system categorizes stocks into five groups based on earnings estimates, with a strong historical performance, particularly for Zacks Rank 1 stocks which have averaged a +25% annual return since 1988 [6]. - Plus's upgrade to Zacks Rank 2 places it in the top 20% of Zacks-covered stocks, suggesting a strong potential for market-beating returns in the near term [9].

Core Viewpoint - Plus Therapeutics reported a quarterly loss of $0.56 per share, significantly worse than the Zacks Consensus Estimate of a loss of $0.17, marking an earnings surprise of -229.41% [1] - The company has consistently missed consensus EPS estimates over the last four quarters and reported revenues of $1.06 million, missing the estimate by 42.76% [2] Financial Performance - The loss per share of $0.56 is an improvement from a loss of $0.75 per share a year ago [1] - Revenues decreased from $1.68 million in the same quarter last year to $1.06 million [2] - Plus shares have declined approximately 75.1% year-to-date, contrasting with the S&P 500's gain of 0.5% [3] Future Outlook - The company's earnings outlook is crucial for investors, with current consensus EPS estimates at -$0.17 for the next quarter and -$0.67 for the current fiscal year [7] - The estimate revisions trend for Plus is currently favorable, resulting in a Zacks Rank 2 (Buy), indicating expected outperformance in the near future [6] - The Medical - Drugs industry, to which Plus belongs, is ranked in the top 28% of Zacks industries, suggesting a positive industry outlook [8]

Financial Performance - The net loss for Q1 2025 was $17.4 million, or $(1.19) per share, compared to a net loss of $3.3 million, or $(0.75) per share, for the same period in the prior year[10]. - Total operating loss for Q1 2025 was $3.5 million, slightly higher than the $3.3 million loss in the same period of 2024[10]. - Net loss for Q1 2025 was $17,401,000, compared to a net loss of $3,261,000 in Q1 2024, representing a significant increase in losses[20]. - Net cash used in operating activities for Q1 2025 was $6,172,000, up from $4,513,000 in Q1 2024[20]. - Cash paid for interest during Q1 2025 was $539,000, a significant increase from $23,000 in Q1 2024[20]. Cash Position - The cash balance increased to $9.9 million at March 31, 2025, compared to $0.1 million at December 31, 2024[10]. - Cash and cash equivalents at the end of Q1 2025 were $9,867,000, compared to $2,901,000 at the end of Q1 2024, indicating a substantial increase[20]. - The company experienced a net increase in cash and cash equivalents of $9,791,000 in Q1 2025, compared to a decrease of $5,653,000 in Q1 2024[20]. - Net cash provided by financing activities in Q1 2025 was $12,405,000, compared to a net cash used of $776,000 in Q1 2024[20]. - The company recorded a change in fair value of derivative instruments amounting to $9,143,000 in Q1 2025, with no comparable figure in Q1 2024[20]. Grants and Financing - The company raised gross proceeds of $15 million in a private placement financing and received a $2 million grant award advance from CPRIT to accelerate the development of REYOBIQ for the leptomeningeal metastases program[5]. - The company recognized $1.1 million in grant revenue in Q1 2025, a decrease from $1.7 million in Q1 2024[10]. Clinical Development - The company presented updated interim data on REYOBIQ at a conference, highlighting safety and clinical benefits in patients with leptomeningeal metastases[5]. - REYOBIQ has shown a median overall survival of 17 months for patients receiving a radiation dose greater than 100 Gy, more than double the standard of care for recurrent glioblastoma[5]. - The company completed the ReSPECT-LM Phase 1 trial and determined the maximum tolerated and recommended Phase 2 dose[5]. Management and Team - The company strengthened its management team with key appointments, including Dr. Michael Rosol as Chief Development Officer and Russell Bradley as President of CNSide Diagnostics[10]. - The company plans to commercialize the CNSide™ CSF assay platform in the U.S. in 2025[11]. Other Financial Activities - The company issued notes payable and warrants totaling $3,738,000 in Q1 2025, with no issuance reported in Q1 2024[20]. - The company reported a redemption of short-term investments amounting to $3,531,000 in Q1 2025, compared to a redemption of $324,000 in Q1 2024[20]. - The company had a supplemental disclosure of non-cash investing and financing activities, including an exchange of warrants for notes payable valued at $3,694,000 in Q1 2025[20].