Core Insights - Plus Therapeutics is focused on scaling up the commercialization of CNSide and preparing for pivotal trials of REYOBIQ in 2026 [2][6] Company Overview - Plus Therapeutics, Inc. is a clinical-stage pharmaceutical company based in Houston, Texas, developing targeted radiotherapeutics for challenging CNS cancers [10] - The company aims to enhance clinical outcomes through a combination of image-guided local beta radiation and targeted drug delivery [10] Clinical Programs - REYOBIQ (rhenium Re186 obisbemeda) is a novel injectable radiotherapy designed for CNS tumors, with potential advantages over existing therapies [6] - The REYOBIQ clinical program includes trials for recurrent glioblastoma, leptomeningeal metastases, and pediatric brain cancer [6][8] - The ReSPECT-LM trial is expected to report data in Q3 2026, while the ReSPECT-GBM trial aims to complete enrollment and align with the FDA on pivotal trial design by Q4 2026 [7] Financial Updates - The company recently completed a $15 million offering to support its core business areas and extend its cash runway through 2027 [2] - Plus Therapeutics aims to cover 150 million US lives under various commercial payor agreements and achieve over 1,250 tests per year in commercial orders [7] CNSide Diagnostics - CNSide Diagnostics, a subsidiary of Plus Therapeutics, develops proprietary tests to identify tumor cells in the CNS, improving management for patients with leptomeningeal metastases [9]

Table of Contents As filed with the Securities and Exchange Commission on January 9, 2026. Registration No. 333- UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 Form S-1 REGISTRATION STATEMENT Under The Securities Act of 1933 PLUS THERAPEUTICS, INC. (Exact name of Registrant as specified in its charter) (State or other jurisdiction of incorporation or organization) Delaware 2834 33-0827593 (Primary Standard Industrial Classification Code Number) (I.R.S. Employer Identification Number ...

Core Insights - CNSide Diagnostics has received lab licenses to provide its proprietary CNSide CSF Tumor Cell Enumeration test in 48 U.S. states, covering over 90% of the U.S. population [1][2] - The CNSide CSF Assay Platform has demonstrated superior clinical utility over standard care, supported by 9 peer-reviewed publications and the FORESEE clinical trial [2] - More than 11,000 CNSide tests have been performed at over 120 U.S. cancer institutions since 2020, achieving high sensitivity of 92% and specificity of 95%, influencing treatment decisions in 90% of cases [3] Company Overview - CNSide Diagnostics, LLC is a wholly-owned subsidiary of Plus Therapeutics, Inc., focused on developing and commercializing proprietary laboratory-developed tests for identifying tumor cells in patients with CNS cancers [4] - Plus Therapeutics, Inc. is a clinical-stage pharmaceutical company headquartered in Houston, Texas, developing targeted radiotherapeutics for challenging CNS cancers, with a pipeline that includes programs for leptomeningeal metastases and recurrent glioblastoma [5]

Core Insights - Molecular Partners AG has established a Scientific Advisory Board (SAB) for its radiopharmaceuticals, chaired by Prof. Ken Herrmann, a leading expert in nuclear medicine [1][4]. Group 1: Scientific Advisory Board Formation - The SAB will guide the development of Molecular Partners' Radio-DARPin platform, focusing on transitioning from early clinical validation to strategic clinical development [3][5]. - Prof. Ken Herrmann expressed enthusiasm for the potential of Radio-DARPins to deliver targeted radiopharmaceuticals effectively [2][8]. Group 2: Radio-DARPin Technology - Molecular Partners' Radio-DARPin candidates, including MP0712 and MP0726, are designed to target specific tumor markers, with MP0712 aimed at DLL3 for small cell lung cancer and MP0726 targeting mesothelin in various cancers [8]. - The technology aims to balance the delivery of potent radioactive payloads to tumors while minimizing damage to healthy tissues [8]. Group 3: Expertise of SAB Members - The SAB includes experts such as James Cook, Jason Lewis, and Michael Morris, who bring extensive clinical and industry experience to support the company's strategic development [5][6]. - Ken Herrmann's leadership is expected to be crucial in shaping the company's direction as it moves towards pivotal development decisions [5].

Core Insights - Plus Therapeutics, Inc. presented positive clinical data for REYOBIQ at the WFNOS/SNO Annual Meeting, indicating no dosage limiting toxicity in the ReSPECT-LM trial and promising safety and efficacy in the ReSPECT-GBM trial [1][2][12] - The company aims to improve survival rates for patients with central nervous system (CNS) cancers through its expanding clinical data set and the CNSide diagnostic portfolio [2][12] ReSPECT-LM Trial - The Phase 1 trial for Leptomeningeal Metastases (LM) showed that REYOBIQ was well-tolerated at a maximum dose of 66 mCi, with a recommended Phase 2 dose of 44.1 mCi [7] - Enrollment in Cohort 1 has begun, with three patients treated without dose limiting toxicity [7] ReSPECT-GBM Trial - The Phase 1/2 trial for recurrent Glioblastoma (GBM) has enrolled 24 out of a planned 34 patients, with a recommended Phase 2 dose of 22.3 mCi based on safety profiles [8] - Efficacy data indicated a median overall survival of 17 months for patients receiving ≥100 Gy, compared to 6 months for those receiving <100 Gy, surpassing historical outcomes for bevacizumab monotherapy [14] Safety Profile - Most treatment-related adverse events in both Phase 1 and 2 trials were Grade 1 or 2, with no treatment-related deaths reported [9] - Common adverse events included lymphopenia (7.9%), cognitive disorder (7.0%), and headache (7.0%) [9] Imaging and Efficacy - MRI combined with SPECT imaging biomarkers effectively evaluates overall survival response in recurrent GBM treatment, aiding in personalized patient planning [12][14] - REYOBIQ's efficacy is positively correlated with treatment coverage ratio and progression-free survival, while negatively correlated with tumor volume [14] About REYOBIQ - REYOBIQ (rhenium Re186 obisbemeda) is a novel injectable radiotherapy designed for targeted high-dose radiation in CNS tumors, with potential advantages over currently approved therapies [15] - The drug is being evaluated in multiple clinical trials, including ReSPECT-GBM, ReSPECT-LM, and ReSPECT-PBC, with funding support from various institutions [15]

Core Insights - Plus Therapeutics, Inc. has announced positive results from its RESPECT-LM Phase 1 clinical trial and has introduced the CNSide® CSF diagnostics platform with a national coverage agreement with UnitedHealthcare, covering over 51 million people in the U.S. [1][9] Corporate Overview - The company is focused on three main business verticals: diagnostics, therapeutics, and capital structure, with plans to expand its commercial team and footprint for CNSide [3] - Plus Therapeutics reported a cash and investments balance of $16.6 million as of September 30, 2025, a significant increase from $6.9 million on June 30, 2025, and $3.6 million on December 31, 2024 [7] - The company regained compliance with Nasdaq listing criteria, including market value and stockholder's equity thresholds [8] Clinical Trials and Product Development - Positive results from the ReSPECT-LM Phase 1 trial were presented, indicating that treatment of leptomeningeal metastases with REYOBIQ is feasible and shows promising efficacy [5] - The CNSide CSF assay platform demonstrated the ability to quantify leptomeningeal metastases over time and monitor changes in targetable mutations, potentially aiding in treatment initiation [9] Financial Performance - For Q3 2025, Plus Therapeutics reported a net loss of $4.4 million, or $0.04 per share, compared to a net loss of $2.9 million, or $0.37 per share, in Q3 2024 [15][21] - Total operating loss for Q3 2025 was $4.5 million, an increase from a loss of $3.8 million in the same quarter of 2024, primarily due to higher compensation and professional fees [15] Strategic Partnerships and Market Position - The company received an additional $1.9 million advance payment from the Cancer Prevention and Research Institute of Texas (CPRIT) as part of a previously awarded non-dilutive grant for cancer-targeted radiotherapeutics [8] - CNSide Diagnostics, a subsidiary of Plus Therapeutics, has made its CSF assay platform commercially available in Texas, focusing on National Cancer Institute Designated Cancer Centers [9][12]

Core Insights - Plus Therapeutics, Inc. is advancing its commercial readiness and diagnostic capabilities through the launch of its subsidiary, CNSide Diagnostic LLC, focusing on a laboratory-developed test for cerebrospinal fluid tumor cell enumeration [1][2][3] Commercial Developments - The company has expanded its manufacturing footprint and made significant progress in commercial readiness, including the appointment of key leadership roles to drive the CNSide diagnostic business [2][3] - CNSide has signed a national policy agreement with UnitedHealthcare, providing coverage for over 51 million people in the U.S., marking a significant step in expanding payor coverage [3][4] Leadership Appointments - Russ Havranek has been promoted to Executive Vice President, Commercial and Corporate Strategy, while Daniel Ortega has been appointed Vice President, Development and Technical Operations, both expected to play crucial roles in the company's growth [2][3][4] - Havranek brings over 28 years of experience in developing and commercializing diagnostic and therapeutic products, while Ortega has nearly 20 years of experience in the pharmaceutical industry [4][7] Manufacturing and Operations - CNSide has secured a new state-of-the-art laboratory in Houston, which will support current and future commercial production needs and enhance collaboration opportunities [6][7] - The new facility is strategically located within the Texas Medical Center, the largest medical center globally, which will facilitate scientific advancement and clinical development [7][11] Product and Service Focus - CNSide Diagnostics develops proprietary laboratory-developed tests aimed at identifying tumor cells that have metastasized to the central nervous system, particularly for patients with carcinomas and melanomas [8] - The CNSide CSF Assay Platform allows for quantitative analysis of cerebrospinal fluid, improving patient management for those with leptomeningeal metastases [8][9]

Core Insights - CNSide Diagnostics, LLC has signed a national agreement with UnitedHealthcare Insurance Company, covering over 51 million people in the U.S. for the CNSide Cerebrospinal Fluid Tumor Cell Enumeration laboratory developed test [1] Company Overview - CNSide Diagnostics, LLC is a subsidiary of Plus Therapeutics, Inc., focused on developing proprietary laboratory-developed tests to identify tumor cells in patients with carcinomas and melanomas [4] - Plus Therapeutics, Inc. is a clinical-stage pharmaceutical company based in Houston, Texas, developing targeted radiotherapeutics for challenging cancers of the central nervous system [5] Product Details - The CNSide CSF Assay Platform supports rapid diagnoses, treatment monitoring, and guidance for patients with leptomeningeal metastases, demonstrating superior clinical utility over standard care [2] - More than 11,000 CNSide tests have been performed at over 120 U.S. cancer institutions since 2020, achieving high sensitivity of 92% and specificity of 95%, influencing treatment decisions in 90% of cases [3] Market Impact - The agreement with UnitedHealthcare is expected to enhance the accessibility of the CNSide CSF Assay, potentially increasing its market penetration and utilization among healthcare professionals [1][2]

Core Insights - CNSide Diagnostics has received accreditation from CMS for its lab in Houston, Texas, meeting CLIA regulations, which is essential for testing human specimens [1][2] - This accreditation is a significant milestone in the company's strategy to expand access to the CNSide CSF assay platform for patients with CNS cancers [2] - The CNSide CSF Assay Platform is designed to identify tumor cells in cerebrospinal fluid, aiding in the management of patients with leptomeningeal metastases [3] Regulatory and Market Access - The certification ensures compliance with proficiency testing, personnel qualifications, and quality control, which are critical for market access [2][6] - Achieving this milestone is necessary for obtaining state licensure in 48 of 50 states and ensuring broad commercial insurance coverage [6] - Lab accreditation is mandatory for enrolling in Medicare and Medicaid programs, which is essential for receiving payments for testing services [6] Company Overview - CNSide Diagnostics is a subsidiary of Plus Therapeutics, focusing on developing proprietary tests for identifying tumor cells that have metastasized to the CNS [3] - Plus Therapeutics is a clinical-stage pharmaceutical company based in Houston, developing targeted radiotherapeutics for challenging CNS cancers [4] - The company is advancing a pipeline of product candidates, particularly in leptomeningeal metastases and recurrent glioblastoma [4]

Core Insights - Plus Therapeutics, Inc. announced positive data from the ReSPECT-LM Phase 1 trial, demonstrating a clinical benefit rate of over 75% in three relevant outcome measures for the treatment of leptomeningeal metastases with REYOBIQ [1][2] - The trial showed no dose-limiting toxicities and an overall favorable safety profile, indicating the treatment is feasible and effective [1][4] Study Details - The Phase 1 trial involved 29 subjects across six cohorts receiving varying doses of REYOBIQ, ranging from 6.6 mCi to 75 mCi [2] - Early cohorts exhibited excellent tolerance at higher doses, supporting a broad therapeutic range [4] Efficacy and Safety - The study reported a radiographic response rate of 76% and a clinical response rate of 87% through day 112 [6] - CSF tumor cell enumeration assays showed a maximum reduction of 100% at day 28, with a median overall survival of 9 months across the first four cohorts, which is significantly better than the typical 2-6 months reported in literature [6] Future Directions - The trial results provide a foundation for moving into ongoing dosing optimization and potential approval trials [4] - REYOBIQ is being evaluated for multiple CNS cancers, including recurrent glioblastoma and pediatric brain cancer, with significant funding support from the National Cancer Institute and the Cancer Prevention & Research Institute of Texas [5][7]