Plus Therapeutics Presents New Data Highlighting Clinical Benefit and Safety of REYOBIQ in the ReSPECT-LM Clinical Trial for Patients with Leptomeningeal Metastases

Rhea-AI Summary

Plus Therapeutics (PSTV) has released new data from its Phase 1 ReSPECT-LM dose escalation trial for REYOBIQ™ (rhenium Re186 obisbemeda) in treating Leptomeningeal Metastases. The data will be presented at the Nuclear Medicine and Neurooncology conference in Vienna.

Key findings include:

• Dose-dependent increase in absorbed dose to cranial and spinal subarachnoid space, reaching 253Gy in Cohort 5
• 31% of patients (5 out of 16) showed partial response in neuroimaging
• 75% Clinical Benefit Rate through day 112 based on neuroimaging
• 86% Clinical Benefit Rate based on physician evaluation
• No dose limiting toxicity in first four cohorts; grade 4 thrombocytopenia observed in Cohorts 5 and 6

RNA sequencing revealed early induction of apoptosis, followed by innate immune response and increased T cells with adaptive immune response by Day 28.

Positive

• High Clinical Benefit Rate of 75% in neuroimaging and 86% in physician evaluation
• 31% partial response rate in neuroimaging
• Strong safety profile with no dose limiting toxicity in first four cohorts
• Successful dose escalation reaching 253Gy in Cohort 5
• Demonstrated biological efficacy through RNA sequencing

Negative

• Grade 4 dose limiting toxicity (thrombocytopenia) observed in Cohorts 5 and 6

Insights

Oncology Clinical Researcher

The new data from Plus Therapeutics' ReSPECT-LM trial represents a meaningful development for patients with leptomeningeal metastases (LM) - one of the most challenging forms of cancer spread where tumor cells infiltrate the fluid and membranes surrounding the brain and spinal cord, typically carrying a dismal prognosis of weeks to months.

The 75% clinical benefit rate by neuroimaging (including 31% partial responses) is noteworthy for this patient population where disease stabilization alone can be meaningful. The radiation dosimetry data showing successful delivery of high radiation doses (up to 253Gy) to the target area demonstrates the technical feasibility of this approach.

From a safety perspective, the absence of dose-limiting toxicities in the first four cohorts is encouraging, with grade 4 thrombocytopenia (dangerous low platelet counts) emerging only at the highest dose levels. This suggests a potential therapeutic window where efficacy can be achieved with manageable toxicity.

The mechanistic RNA sequencing data provides biological plausibility for REYOBIQ's effects, showing both direct cancer cell death (apoptosis) and stimulation of immune responses. This dual mechanism could be particularly valuable in the immunologically-privileged CNS environment.

While promising, these results come from a small Phase 1 trial, and the predominance of stable disease over partial responses requires careful interpretation. The real test will be whether these signals translate into meaningful survival benefits in larger, later-phase studies.

Biotech Investment Analyst

For Plus Therapeutics, a micro-cap company with $10.8M market capitalization, these REYOBIQ data represent crucial validation for their lead asset and radiotherapeutic platform technology. The positive clinical signals in leptomeningeal metastases create a potential path forward in an indication with significant unmet need.

The 86% clinical benefit rate by physician evaluation and 75% by neuroimaging provide concrete efficacy signals that suggest REYOBIQ is biologically active. For a Phase 1 dose-finding study primarily designed to assess safety, these efficacy signals strengthen the asset's value proposition considerably.

The favorable safety profile at the recommended Phase 2 dose allows the company to move forward with confidence, balancing efficacy with tolerability. The mechanism data showing both direct tumor cell death and immune activation differentiates this approach from conventional radiation therapy.

For a company of this size, success of the lead program is particularly critical. While these results don't guarantee ultimate approval, they reduce some development risk and could support partnership discussions or additional funding rounds. The company will need to carefully balance the cost of future trials against its current resources.

The market for effective LM treatments remains underserved, and REYOBIQ's targeted radiotherapy approach offers a differentiated mechanism that could potentially command premium pricing if eventually approved. However, investors should recognize that several clinical development stages remain before commercialization becomes possible.

New abstract published ahead of the Nuclear Medicine and Neurooncology Conference shows promise for REYOBIQ

HOUSTON, April 15, 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, announces the online availability of new data on its lead compound REYOBIQ™ (rhenium Re¹⁸⁶ obisbemeda) in an abstract for both an oral presentation and a poster to be presented at the Nuclear Medicine and Neurooncology conference to be held May 9-10, 2025 in Vienna, Austria.

The abstract, titled, “Rhenium Obisbemeda (REYOBIQ) in Leptomeningeal Metastases,” highlights additional data from the Company’s completed Phase 1 ReSPECT-LM dose escalation trial demonstrating a dose dependent increase in the average absorbed dose to the cranial and spinal subarachnoid space reaching 253Gy in Cohort 5. Neuroimaging response data was available for 16 patients as of the data cutoff with five of those (31%) showing a partial response. An additional seven patients showed stable disease by neuroimaging through day 112 for a Clinical Benefit Rate (complete response + partial response + stable disease) of 75%. Additionally, a clinical response based on the physician evaluation showed a decrease in disease findings in two of 14 evaluable patients (14%) and 10 patients showed stable findings through day 112 for an 86% Clinical Benefit Rate. Furthermore, there was no dose limiting toxicity (DLT) observed in the first four cohorts, with a grade 4 DLT (thrombocytopenia), one in each of Cohorts 5 and 6.

Finally, RNA sequencing of LM cells showed early induction of apoptosis, with an innate immune response followed by an increase in T cells and an adaptive immune response by Day 28. Further details can be found here; the Company will provide additional data and explanation following the meeting.

"This newly-presented ReSPECT-LM data further reinforces our confidence in the potential utility of REYOBIQ in these critically ill patients with the devastating diagnosis of Leptomeningeal Metastases," said Marc H. Hedrick, M.D., Plus Therapeutics President and Chief Executive Officer. "Reyobiq can be delivered at very high doses of radiation to the cancer at the recommended phase 2 dose and shows promising response data across multiple parameters while simultaneously being well tolerated by normal organs and tissues."

About Leptomeningeal Metastases (LM)
LM is a rare complication of cancer in which the primary cancer spreads to the cerebrospinal fluid (CSF) and leptomeninges surrounding the brain and spinal cord. All malignancies originating from solid tumors, primary brain tumors, or hematological malignancies have this LM complication potential with breast cancer as the most common cancer linked to LM, with 3-5% of breast cancer patients developing LM. Additionally, lung cancer, GI cancers and melanoma can also spread to the CSF and result in LM. LM occurs in approximately 5% of people with cancer and is usually terminal with 1-year and 2-year survival of just 7% and 3%, respectively. The incidence of LM is on the rise, partly because cancer patients are living longer and partly because many standard chemotherapies cannot reach sufficient concentrations in the spinal fluid to kill the tumor cells, yet there are no FDA-approved therapies specifically for LM patients, who often succumb to this complication within weeks to several months, if untreated.

About REYOBIQ™ (rhenium Re¹⁸⁶ obisbemeda)
REYOBIQ™ (rhenium Re¹⁸⁶ obisbemeda) is a novel injectable radiotherapy specifically formulated to deliver direct targeted high dose radiation in CNS tumors in a safe, effective, and convenient manner to optimize patient outcomes. REYOBIQ™ has the potential to reduce off target risks and improve outcomes for CNS cancer patients, versus currently approved therapies, with a more targeted and potent radiation dose. 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. REYOBIQ™ is being evaluated for the treatment of recurrent glioblastoma and leptomeningeal metastases in the ReSPECT-GBM and ReSPECT-LM clinical trials. ReSPECT-GBM is supported by an award from the National Cancer Institute (NCI), part of the U.S. National Institutes of Health (NIH), and ReSPECT-LM is funded by a three-year $17.6M grant by the Cancer Prevention & Research Institute of Texas (CPRIT).

About Plus Therapeutics
Headquartered in Houston, Texas, Plus Therapeutics, Inc. is a clinical-stage pharmaceutical company developing targeted radiotherapeutics for difficult-to-treat cancers of the central nervous system with the potential to enhance clinical outcomes. Combining image-guided local beta radiation and targeted drug delivery approaches, the Company is advancing a pipeline of product candidates with lead programs in leptomeningeal metastases (LM) and recurrent glioblastoma (GBM). The Company has built a supply chain through strategic partnerships that enable the development, manufacturing, and future potential commercialization of its products. For more information, visit https://plustherapeutics.com/.

Cautionary Statement Regarding Forward-Looking Statements
This press release contains statements that may be deemed “forward-looking statements” within the meaning of U.S. securities laws, including statements regarding clinical trials, expected operations and upcoming developments. All statements in this press release other than statements of historical fact are forward-looking statements. These forward-looking statements may be identified by future verbs, as well as terms such as “expect” “potential,” “anticipating,” “planning” and similar expressions or the negatives thereof. Such statements are based upon certain assumptions and assessments made by management in light of their experience and their perception of historical trends, current conditions, expected future developments and other factors they believe to be appropriate.

These statements include, without limitation, statements regarding the potential promise of REYOBIQ™, expectations as to the Company’s future performance, including the next steps in developing the Company’s product candidates; the Company’s clinical trials, including statements regarding the timing and characteristics of the ReSPECT-LM single dose and multi-dose clinical trials; the continued evaluation of rhenium (¹⁸⁶Re) obisbemeda including through evaluations in additional patient cohorts.

The forward-looking statements included in this press release could differ materially from those expressed or implied by these forward-looking statements because of risks, uncertainties, and other factors that include, but are not limited to, the following: the early stage of the Company’s product candidates and therapies; the results of the Company’s research and development activities, including uncertainties relating to the clinical trials of its product candidates and therapies; the Company’s liquidity and capital resources and its ability to raise additional cash; the outcome of the Company’s partnering/licensing efforts, risks associated with laws or regulatory requirements applicable to it; market conditions, product performance, litigation or potential litigation, and competition within the cancer diagnostics and therapeutics field; ability to develop and protect proprietary intellectual property or obtain licenses to intellectual property developed by others on commercially reasonable and competitive terms; challenges associated with radiotherapeutic manufacturing, production and distribution capabilities necessary to support the Company’s clinical trials and any commercial level product demand; and material security breach or cybersecurity attack affecting the Company’s operations or property. This list of risks, uncertainties, and other factors is not complete. Plus Therapeutics discusses some of these matters more fully, as well as certain risk factors that could affect Plus Therapeutics’ business, financial condition, results of operations, and prospects, in its reports filed with the SEC, including Plus Therapeutics’ annual report on Form 10-K for the fiscal year ended December 31, 2024, quarterly reports on Form 10-Q, and current reports on Form 8-K. These filings are available for review through the SEC’s website at www.sec.gov. Any or all forward-looking statements Plus Therapeutics makes may turn out to be wrong and can be affected by inaccurate assumptions Plus Therapeutics might make or by known or unknown risks, uncertainties, and other factors, including those identified in this press release. Accordingly, you should not place undue reliance on the forward-looking statements made in this press release, which speak only as of its date. The Company assumes no responsibility to update or revise any forward-looking statements to reflect events, trends or circumstances after the date they are made unless the Company has an obligation under U.S. federal securities laws to do so.

Investor Contact

CORE IR
investor@plustherapeutics.com

FAQ

What are the clinical results of REYOBIQ in the ReSPECT-LM Phase 1 trial?

The trial showed 31% partial response rate in neuroimaging (5/16 patients) and 75% Clinical Benefit Rate through day 112, with dose-dependent radiation absorption reaching 253Gy in Cohort 5.

How safe is PSTV's REYOBIQ treatment based on the Phase 1 trial data?

REYOBIQ showed no dose limiting toxicity in the first four cohorts, with only grade 4 thrombocytopenia observed in Cohorts 5 and 6.

What is the physician-evaluated response rate for REYOBIQ in treating Leptomeningeal Metastases?

Physician evaluation showed 14% decrease in disease findings (2/14 patients) and 86% Clinical Benefit Rate through day 112.

What biological responses were observed in PSTV's REYOBIQ treatment?

RNA sequencing showed early apoptosis induction, followed by innate immune response and increased T cells with adaptive immune response by Day 28.