Benzinga | Aug 19, 2021 07:07AM EDT

Plus Therapeutics Presents Data from Preclinical Study of Rhenium-186 Nanoliposome in Leptomeningeal Metastases and Plans for Further Evaluation with Upcoming Phase 1 Clinical Trial

Plus Therapeutics, Inc. (Nasdaq: PSTV) (the "Company"), a clinical-stage pharmaceutical company developing innovative, targeted radiotherapeutics for rare and difficult-to-treat cancers, today presented data from a preclinical study evaluating its lead investigational drug, Rhenium-186 Nanoliposome (186RNL), in the treatment of leptomeningeal metastases (LM), and presented plans for a Phase 1 clinical trial of 186RNL also in LM. The data and upcoming trial plans were presented in two electronic posters (ePosters) at the Third Annual Conference on Brain Metastases hosted by the Society for Neuro-Oncology (SNO), being held virtually August 19-20, 2021.

"Leptomeningeal metastases are a fatal complication of advanced cancer and despite affecting more than 110,000 people per year in the United States alone, there remains a significant lack of effective therapies to treat this devastating disease," said Andrew J. Brenner, M.D., Ph.D., Professor of Medicine, Neurology, and Neurosurgery at The University of Texas, and presenter of both ePosters. "Given our promising clinical experience thus far using 186RNL in recurrent glioblastoma, we are optimistic about the potential safety and efficacy for 186RNL as a novel treatment option for other central nervous system diseases like leptomeningeal metastases and certain pediatric brain cancers."

Data from the ePoster entitled "Preclinical safety and activity of intraventricular Rhenium-186 Nanoliposome (186RNL) for leptomeningeal metastases" demonstrated that, following five different doses of 186RNL tested in non-tumor bearing rats administered with the highest doses (1.340mCi and 1.15mCi) presented minimal weight loss the first week after surgery, but gained it back in subsequent weeks and showed no overt neurological symptoms through the evaluation.

These results suggest that the maximum tolerable dose of 186RNL was not reached, and given the encouraging efficacy shown in pre-clinical LM models, 186RNL has the potential to provide high therapeutic doses for LM with low rates of toxicity.

Additional key findings include:

* The mean absorbed radioactivity for the 186RNL-treated cohort was 1,094 Gy (+/- 218.59) and was retained at two days after injection.

* 186RNL-treated rats had significantly lower luciferase relative to controls (p=0.0286) based on the bioluminescent imaging that was used to track tumor growth.

* Kaplan-Meier plot showed a statistically significant difference in overall survival with the 186RNL-treated animals outliving the controls (p=0.0377).

"The novel design of 186RNL prolongs CNS exposure when delivered to the brain by convection enhanced delivery and we believe it will perform similarly in the leptomeningeal spaces where cancerous cells circulate and along the membrane linings where metastases are found," stated Marc Hedrick, M.D., President and Chief Executive Officer of Plus Therapeutics. "This encouraging preclinical data from Dr. Brenner and his team supports RNL's potential in this significant unmet medical need and Plus' proposed clinical development program."

In addition, the Company presented trial design plans for its upcoming Phase 1 clinical trial as part of an ePoster entitled, "ReSPECT(tm)-LM: Maximum tolerated dose, safety, and efficacy of intraventricular Rhenium-186 Nanoliposome (186RNL) for leptomeningeal metastases." The multi-center, sequential cohort, open-label, dose escalation study, which will begin patient accrual in the fourth quarter of 2021, pending FDA IND approval, will evaluate the safety, tolerability, and distribution of 186RNL via intrathecal infusion to the ventricle of breast and non-small cell lung cancer patients with LM after standard surgical, radiation, and/or chemotherapy treatment. The starting dose of 186RNL will be 6.6 mCi in a volume of 5 mL followed by an expansion at the maximum tolerated dose to determine efficacy. The primary endpoint of the study is the incidence and severity of adverse events and dose limiting toxicities, and the secondary endpoints are the overall response rate, duration or response, progression free survival, and overall survival.

This ReSPECT(tm)-LM Phase 1 clinical trial follows preclinical studies, in which tolerance to doses of 186RNL as high as 1075 Gy was shown in rat models with LM with no observed significant toxicity and treatment led to marked reduction in tumor burden in both C6 and MDA-231 LM models.

186RNL contains the rhenium-186 isotope which is a beta energy emitter with a short 2 mm average path length in tissue and favorable radiation properties, which allow high specific activity radiotherapy with limited exposure to surrounding tissues. In treating LM, whole body radiation is used as part of a palliative regimen for poor-risk patients while tumor control using focal radiation therapy to treat bulky or symptomatic areas is used for good-risk patients. These approaches carry the risk of significant side effects and have no significant effect on survival, respectively.

Copies of each poster will be made available under the Presentations tab of the Investors section of the Company's website when presentations go live at www.plustherapeutics.com.