Plus Therapeutics Inc (NASDAQ:PSTV) is a clinical-stage pharmaceutical company at the forefront of developing innovative targeted radiotherapeutics for the treatment of central nervous system (CNS) cancers. With a robust pipeline and a commitment to advancing its proprietary platform technologies, Plus Therapeutics is poised to make a significant impact in the fight against these devastating diseases.
Business Overview and History
Plus Therapeutics was founded in 1994 and has since established itself as a leader in the field of targeted radiotherapeutics. The company's origins trace back to its initial focus on the development of cancer drugs and drug delivery technologies. Over the years, Plus Therapeutics has evolved its strategic focus to concentrate on advanced platform technologies for the treatment of CNS cancers, including glioblastoma (GBM), leptomeningeal metastases (LM), and pediatric brain cancers.
In May 2020, Plus Therapeutics made a significant move by acquiring the licensed radiotherapeutic portfolio containing the Rhenium-186 (Re-186) Obisbemeda technology from NanoTx Corp. This acquisition has been pivotal in shaping the company's current focus on targeted radiotherapeutics for CNS cancers.
The company has also benefited from substantial grant funding to support its research and development efforts. In September 2022, Plus Therapeutics secured a $17.6 million grant contract with the Cancer Prevention and Research Institute of Texas (CPRIT) to fund the continued development of Rhenium-186 (Re-186) Obisbemeda for the treatment of patients with leptomeningeal metastases. As of September 2024, the company had received $10.4 million of the available CPRIT funding, providing crucial financial support for its ongoing clinical programs.
Plus Therapeutics has faced challenges throughout its history, including the need to maintain compliance with Nasdaq listing requirements. In 2024, the company received a notice from Nasdaq that it no longer complied with the minimum stockholders' equity requirement for continued listing, a situation that the company is actively working to address.
The company's most advanced investigational drug is Rhenium (186Re) Obisbemeda, a patented radiotherapy that has shown promising results in preclinical and clinical studies for several cancer targets, including GBM, LM, and pediatric brain cancers. In September 2020, the U.S. Food and Drug Administration (FDA) granted Orphan Drug designation and Fast Track designations to Rhenium (186Re) Obisbemeda for the treatment of GBM, underscoring the potential of this investigational therapy.
Plus Therapeutics has also expanded its portfolio through strategic acquisitions and licensing agreements. In April 2024, the company acquired the intellectual property and assets related to the CNSide Cerebrospinal Fluid (CSF) Assay Platform from Biocept, Inc. This diagnostic tool is designed to detect, quantify, and monitor tumor status in LM, further strengthening Plus Therapeutics' ability to address this challenging condition.
Financial Performance and Liquidity
As a clinical-stage company, Plus Therapeutics' financial performance is primarily focused on managing its research and development expenses and securing non-dilutive funding sources to support its ongoing operations. The company reported a net loss of $9.1 million, or $1.46 per share, for the nine months ended September 30, 2024, compared to a net loss of $9.5 million, or $3.54 per share, for the same period in the prior year.
The company's cash and investments balance as of September 30, 2024, was $4.8 million, down from $8.6 million as of December 31, 2023. This decrease in cash and investments was primarily due to the company's ongoing research and development activities, as well as the repayment of debt obligations.
To support its liquidity position, Plus Therapeutics has accessed various sources of funding, including a private placement financing completed in May 2024, which provided up to $19.25 million in gross proceeds, with $7.25 million received at closing and an additional $12 million remaining available. The company also continues to benefit from grant funding, including a $17.6 million grant from the Cancer Prevention and Research Institute of Texas (CPRIT) and a $3 million award from the U.S. Department of Defense, both of which are expected to provide significant non-dilutive support for the development of Rhenium (186Re) Obisbemeda.
For the fiscal year 2023, Plus Therapeutics reported a net loss of $13,316,000, with negative operating cash flow of $12,851,000 and negative free cash flow of $13,011,000. In the most recent quarter (Q3 2024), the company reported no revenue, a net loss of $2,874,000, negative operating cash flow of $3,680,000, and negative free cash flow of $3,694,000. These figures reflect the company's ongoing investment in research and development for its product candidates.
As of September 30, 2024, Plus Therapeutics had $1.22 million in cash and cash equivalents, $3.56 million in investments, and $12.11 million in current liabilities. The company's debt-to-equity ratio stood at -0.6494, with a current ratio and quick ratio both at 0.44. Plus Therapeutics also has access to a $3.29 million line of credit facility with Pershing LLC, an affiliate of The Bank of New York Mellon Corporation.
The company expects grant revenue for 2024 to be in the range of $6 million to $7 million. Additionally, Plus Therapeutics has approximately $27 million in total cash and committed grant funding available to support its ongoing operations and research initiatives.
Clinical Pipeline and Key Milestones
Plus Therapeutics' clinical pipeline is primarily focused on the development of Rhenium (186Re) Obisbemeda for the treatment of CNS cancers. The company's lead program, the ReSPECT-GBM trial, is evaluating the safety, tolerability, and efficacy of Rhenium (186Re) Obisbemeda in patients with recurrent glioblastoma (rGBM). In the ReSPECT-GBM Phase 2 trial, the company reported that the average absorbed radiation dose to the tumor was 300 Gray (Gy), well above the 100 Gy threshold that has been shown to be highly correlative with increased overall survival. Additionally, approximately 90% of patients achieved critical drug delivery parameters, which also correlated with improved survival outcomes.
In the company's leptomeningeal metastases (LM) program, the ReSPECT-LM Phase 1 single-administration, dose-escalation trial has progressed to Cohort 5, with doses of Rhenium (186Re) Obisbemeda up to 66 millicuries found to be safe and well-tolerated. Importantly, the trial has demonstrated a favorable pharmacokinetic profile, with a target-to-off-target ratio of approximately 50 to 100, indicating a high therapeutic index. Based on these positive results, Plus Therapeutics has received FDA agreement to initiate a Phase 1 multiple-dose administration trial of Rhenium (186Re) Obisbemeda for the treatment of LM, which is expected to begin enrollment in the first quarter of 2025.
In addition to the clinical trials for Rhenium (186Re) Obisbemeda, Plus Therapeutics is also advancing its CNSide Cerebrospinal Fluid (CSF) Assay Platform. The company recently presented data from the FORESEE trial, which demonstrated that the CNSide assay more than doubled the diagnostic sensitivity compared to the gold standard cytology and influenced clinical management decisions in over 90% of LM cases. The CNSide assay is expected to be commercially launched in a limited market release in the United States in early 2025.
Plus Therapeutics has outlined several upcoming milestones and guidance for its clinical programs. The company plans to present comprehensive data from the ReSPECT-LM Phase 1 single-administration trial through cohort 5 at the upcoming SNO conference in November 2024. Enrollment for the ReSPECT-GBM Phase 2 trial is expected to be completed by mid-2025, with data readout anticipated in the second half of 2025. Additionally, Plus Therapeutics anticipates obtaining IND approval for its pediatric brain cancer trial in the first half of 2025 and initiating enrollment at Lurie Children's Hospital in Chicago.
Product Portfolio and Technology Platforms
Plus Therapeutics' product portfolio includes several innovative technologies and investigational therapies:
1. Rhenium-186 Re obisbemeda: This is the company's lead radiotherapeutic candidate, designed specifically for CNS cancers including recurrent glioblastoma (GBM), leptomeningeal metastases (LM), and pediatric brain cancers (PBC). It is delivered directly into the tumor via precision brain mapping and convection-enhanced delivery (CED) catheters. Preclinical and clinical data have shown that rhenium-186 Re obisbemeda can deliver radiation doses up to 20 times greater than standard external beam radiotherapy while sparing healthy tissues.
2. Rhenium-188 NanoLiposome Biodegradable Alginate Microsphere (RNL-BAM): This preclinical investigational device combines Plus Therapeutics' rhenium nanoliposome technology with biodegradable alginate microspheres for the intra-arterial embolization and local delivery of high-dose targeted radiation for solid organ cancers such as hepatocellular cancer, hepatic metastases, and pancreatic cancer.
3. CNSide Diagnostic Portfolio: Acquired in April 2024, the CNSide diagnostic portfolio includes the CNSide Test, which is designed to detect, quantify, and monitor tumor status in LM. Plus Therapeutics is currently evaluating and developing its business plan for commercializing the CNSide diagnostic portfolio alongside the development of rhenium-186 Re obisbemeda.
Risks and Challenges
As a clinical-stage biopharmaceutical company, Plus Therapeutics faces several risks and challenges common to the industry, including:
1. Regulatory Uncertainty: The company's ability to obtain regulatory approvals for its investigational therapies, such as Rhenium (186Re) Obisbemeda and the CNSide assay, is critical to its success. Delays or setbacks in the regulatory process could significantly impact the company's timeline and development plans.
2. Competitive Landscape: The CNS cancer treatment market is highly competitive, with various emerging therapies and diagnostic tools vying for market share. Plus Therapeutics must continue to innovate and differentiate its products to maintain a competitive edge.
3. Funding and Liquidity: As a clinical-stage company, Plus Therapeutics is heavily dependent on external funding sources, such as grants and equity financing, to sustain its operations. Failure to secure adequate funding could hamper the company's ability to advance its pipeline and meet its financial obligations.
4. Technological Risks: The successful development and commercialization of the company's platform technologies, including the nanoliposomal delivery system and the CNSide assay, are subject to technological risks and potential setbacks.
5. Commercialization Challenges: Even if Plus Therapeutics' investigational therapies and diagnostic tools receive regulatory approval, the company may face challenges in effectively commercializing and distributing these products, which could impact their commercial success.
Conclusion
Plus Therapeutics is a clinical-stage pharmaceutical company at the forefront of developing innovative targeted radiotherapeutics for the treatment of central nervous system cancers. With its lead investigational drug, Rhenium (186Re) Obisbemeda, showing promising results in clinical trials for conditions like glioblastoma and leptomeningeal metastases, Plus Therapeutics is well-positioned to make a significant impact in this underserved therapeutic area. Additionally, the company's acquisition of the CNSide Cerebrospinal Fluid Assay Platform further strengthens its ability to address the challenges of CNS cancers through improved diagnosis and disease monitoring.
As Plus Therapeutics continues to execute its strategic vision and navigate the regulatory landscape, the company's success will be closely watched by investors and the broader medical community. With a robust pipeline, strong financial management, and a clear focus on addressing unmet medical needs in CNS cancers, Plus Therapeutics is poised to potentially transform the treatment landscape for these devastating diseases in the coming years.