Executive Summary / Key Takeaways

• Plus Therapeutics (PSTV) is a clinical-stage pharmaceutical company focused on addressing significant unmet needs in Central Nervous System (CNS) cancers through its targeted radiotherapeutic candidate, REYOBIQ, and its newly acquired CNSide diagnostic platform.
• REYOBIQ, a rhenium-186 nanoliposome, offers a differentiated approach to delivering high, localized radiation doses to CNS tumors, potentially providing superior efficacy and reduced off-target toxicity compared to conventional external beam radiation therapy.
• The CNSide diagnostic platform, a wholly-owned subsidiary, is poised for commercial re-launch in 2025, offering significantly higher sensitivity in detecting leptomeningeal metastases (LM) tumor cells than traditional cytology, and has secured a national coverage agreement with UnitedHealthcare .
• While the company faces ongoing liquidity challenges and Nasdaq compliance requirements, strategic non-dilutive grant funding (from NIH, DoD, CPRIT) and recent equity financings are intended to provide runway through key clinical and commercial milestones into mid-2026.
• The core investment thesis hinges on the successful advancement of REYOBIQ through pivotal trials for LM and glioblastoma (GBM), coupled with the commercial ramp-up and market penetration of the CNSide diagnostic, which management believes can substantially expand the addressable market for REYOBIQ.

A Focused Approach to Challenging CNS Cancers

Plus Therapeutics, Inc. (PSTV) is carving out a specialized niche in the biotechnology sector, concentrating on the formidable challenge of Central Nervous System (CNS) cancers. The company's core strategy revolves around developing and commercializing innovative targeted radiotherapeutics and advanced diagnostic tools for these difficult-to-treat diseases. This focused approach is a direct evolution from its origins as Cytori Therapeutics, Inc., with a pivotal rebranding in 2019 that signaled a dedicated shift towards oncology. Key acquisitions, such as the REYOBIQ technology from NanoTx, Corp. in 2020 and the CNSide Platform from Biocept, Inc. in 2024, have been instrumental in shaping its current pipeline and strategic direction.

The company's overarching strategy is to leverage non-dilutive capital, primarily through substantial grants from institutions like the NIH, U.S. Department of Defense, and the Cancer Prevention and Research Institute of Texas (CPRIT). This funding mechanism is designed to support preclinical and clinical development while minimizing shareholder dilution. This strategic financial scaffolding is crucial as PSTV advances its lead therapeutic candidate, REYOBIQ, and prepares for the commercial launch of its CNSide diagnostic platform. The company aims to address significant unmet medical needs in conditions like recurrent glioblastoma (GBM) and leptomeningeal metastases (LM), where current treatment options are often limited and outcomes are poor.

Technological Edge: Precision Radiotherapy and Advanced Diagnostics

At the heart of Plus Therapeutics' investment thesis lies its differentiated technology. REYOBIQ (rhenium 186 Re obisbemeda) is a novel injectable radiotherapy designed to deliver targeted, high-dose radiation directly into CNS tumors. This is achieved through innovative formulations, such as encapsulating rhenium isotopes with nanoliposomes, and precise delivery methods like convection-enhanced delivery (CED) and intraventricular brain Ommaya reservoir catheters. This approach allows for radiation doses up to 20 times greater than conventional external beam radiation therapy (EBRT), while significantly sparing healthy tissue and the brain from radiation exposure. Unlike EBRT, which passes through normal tissue, REYOBIQ is infused directly, bypassing the blood-brain barrier and reducing systemic toxicity. The ability to visualize REYOBIQ in real-time during administration also offers clinicians enhanced control over dosing, distribution, and retention, potentially leading to more effective treatment of both bulk tumors and microscopic disease.

The company's R&D initiatives are focused on optimizing these benefits. For instance, the ReSPECT-LM clinical trial has shown a high therapeutic index, with target-to-off-target radiation absorbed dose ratios exceeding 100:1 in later cohorts, indicating effective delivery to the tumor while minimizing exposure to critical organs like the spleen. This technological advantage is expected to translate into improved patient outcomes, including extended survival, and forms a strong competitive moat against less targeted therapies. The company is also developing Rhenium-188 NanoLiposome Biodegradable Alginate Microsphere (188 RNL-BAM) for solid organ cancers, which the FDA regulates as a medical device, further expanding its targeted delivery capabilities.

Complementing its therapeutic pipeline is the CNSide Cerebrospinal Fluid (CSF) Assay Platform, a proprietary laboratory-developed test (LDT) designed to identify and characterize tumor cells that have metastasized to the CNS. CNSide offers significantly higher sensitivity in detecting tumor cells in the CSF (80%) compared to the current gold standard, cytology (29%). This enhanced diagnostic capability is critical for early and accurate diagnosis of LM, a condition where diagnosis is often challenging and delayed. The FORESEE clinical trial demonstrated CNSide's clinical utility, influencing over 90% of treatment decisions and identifying actionable mutations in 24% of therapeutic selection decisions. For investors, CNSide represents a dual opportunity: it is an invaluable tool for optimizing REYOBIQ's clinical trials and expanding its addressable market by 2 to 4 times, and it also stands as a substantial revenue-generating commercial diagnostic platform in its own right.

Competitive Landscape and Strategic Positioning

Plus Therapeutics operates within a highly competitive oncology market, where it faces both large, diversified pharmaceutical companies and smaller, specialized biotechs. Key direct competitors include established players like Novartis (NVS), Merck (MRK), Bristol-Myers Squibb (BMY) (BMS), and AstraZeneca (AZN), all with significant oncology portfolios. These larger entities benefit from extensive R&D budgets, broad global distribution networks, and established regulatory expertise. For instance, Novartis and Merck demonstrate consistent revenue growth and strong profitability from their diversified oncology segments, while BMS and AstraZeneca also show robust pipelines and market presence.

PSTV's strategic positioning is to differentiate through its highly targeted radiotherapeutic approach and its advanced CNS diagnostic. While it cannot compete on the sheer scale or breadth of product offerings of a Novartis or Merck, REYOBIQ's ability to deliver substantially higher, localized radiation doses with reduced systemic toxicity provides a distinct advantage in specific CNS cancer indications. This technological specificity allows PSTV to potentially achieve superior efficacy in niche markets like recurrent GBM and LM, where traditional treatments often fall short. The median overall survival of 12 months observed in early ReSPECT-LM cohorts, compared to a historical consensus of four months, qualitatively highlights this potential differentiation.

The CNSide platform further strengthens PSTV's competitive stance. By offering a diagnostic tool that is more than twice as sensitive as cytology, PSTV addresses a critical diagnostic gap that its larger competitors may not directly fill. This not only enhances patient management but also creates a synergistic relationship with REYOBIQ, potentially increasing its market adoption. While larger companies might have faster innovation cycles due to greater resources, PSTV's focused R&D and strategic partnerships, such as with SpectronRx for manufacturing redundancy, aim to accelerate its specialized development. The company's reliance on non-dilutive grant funding also helps mitigate some of the financial pressures faced by smaller biotechs, allowing it to compete for talent and resources in a capital-intensive industry.

Financial Performance and Liquidity: A Growth Trajectory Amidst Challenges

Plus Therapeutics' financial performance reflects its stage as a clinical-stage company with significant R&D investments. For the nine months ended September 30, 2025, the company reported a net loss of $16.70 million, contributing to an accumulated deficit of $510.20 million. Net cash used in operating activities for the same period was $14.50 million. These figures underscore the substantial capital requirements inherent in drug development and raise substantial doubt about the company's ability to continue as a going concern without further financing.

However, the company has actively pursued various funding avenues. Grant revenue, primarily from CPRIT for REYOBIQ's LM development, was $3.846 million for the nine months ended September 30, 2025, and $5.8 million for the full year 2024. Management projects 2025 grant revenue to be between $6 million and $8 million. Recent financing activities include a private placement in March 2025, which generated approximately $15 million in gross proceeds, and a purchase agreement with Lincoln Park Capital Fund, LLC in June 2025, allowing for the sale of up to $50 million in common stock. As of September 30, 2025, $19.60 million had been raised under this agreement, with an additional $1.90 million through October 29, 2025. These efforts, combined with anticipated grant funds, are expected to provide funding through key milestones into mid-2026.

Operating expenses have seen some shifts. Research and development expenses decreased by approximately $3 million for the nine months ended September 30, 2025, compared to the same period in 2024, primarily due to reductions in clinical and compensation expenses, partially offset by increased licensing and diagnostics costs. Conversely, general and administrative expenses increased by $1.2 million over the same period, driven by higher compensation and professional fees, reflecting preparations for the CNSide commercial launch.

The company has also addressed Nasdaq listing compliance issues, regaining compliance with equity standards by August 2025, though it continues to work towards meeting the minimum bid price requirement by November 12, 2025.

Outlook and Strategic Roadmap

Plus Therapeutics' outlook is characterized by a clear strategic roadmap focused on advancing its lead programs and establishing a commercial foothold with CNSide. For REYOBIQ, the company anticipates meeting with the FDA in 2025 to align on a clinical development path for LM, aiming for a Phase 2/3 registrational trial for a single dose in breast cancer-related LM, with site startup in the second half of 2025. The ReSPECT-LM multiple dose escalation trial has initiated enrollment, with the first cohort expected to complete in 2025, providing crucial data for dose optimization. Management believes that while a single dose may offer an expedited path to market, multiple doses will be optimal for long-term disease suppression or cure.

In glioblastoma, the company aims to complete enrollment for the ReSPECT-GBM Phase 2 trial by the end of 2025, leveraging new clinical sites like Ohio State University and North Shore Hospital. IND approval for the ReSPECT-PBC Phase 1 trial for pediatric brain cancer is also expected in 2025, with enrollment targeted to begin at Lurie Children's Hospital. These clinical advancements are supported by a robust supply chain strategy, including a second GMP manufacturing partnership with SpectronRx, capable of producing approximately 15,000 doses per year, and plans to secure a third partner for redundancy and commercial readiness through 2028.

The CNSide diagnostic platform is a significant near-term commercial driver. Following CLIA accreditation in September 2025 and a national coverage agreement with UnitedHealthcare (UNH), CNSide is on track for a full U.S. launch in 2025, beginning with a geographically limited introduction in Texas in August 2025 and expanding into other states in 2026. Management estimates the total addressable market for CNSide at over 0.5 million tests annually. The company plans to provide specific financial guidance for diagnostic growth later in 2025 as market visibility improves, with product offerings evolving to include cellular biomarker and molecular assays. This commercialization effort is expected to increase general and administrative expenses due to the need for increased administrative and sales headcount.

Conclusion

Plus Therapeutics stands at a pivotal juncture, poised to transform the treatment and diagnosis of challenging CNS cancers. Its core investment thesis is built upon the differentiated, targeted radiotherapeutic REYOBIQ and the highly sensitive CNSide diagnostic platform. The company's strategic use of non-dilutive grant funding and recent equity raises provides a critical financial foundation to advance its clinical programs and commercialize CNSide. While the path forward involves inherent risks associated with clinical development, regulatory approvals, and ongoing capital requirements, the promising early clinical data for REYOBIQ in LM and GBM, coupled with CNSide's superior diagnostic capabilities and commercial traction, present a compelling narrative for long-term growth. The successful execution of its clinical and commercialization strategies, particularly in securing FDA alignment for pivotal trials and expanding CNSide's market penetration, will be key determinants of its future success and its ability to deliver on its mission to address critical unmet needs in oncology.