EXECUTIVE INTERVIEW - Plus Therapeutics: Advanced Drug Delivery Solutions

Radiation has been a primary treatment in oncology for over 100 years. With advancing technology, cancer clinical research and treatment options have continued to evolve. Targeted radiotherapeutics, a class of drugs that combines a radioactive isotope with a targeting molecule and a novel delivery technique to directly irradiate cancer cells, are one example of a new and advanced approach to drug delivery in oncology. Plus Therapeutics is a US clinical-stage pharmaceutical company developing targeted radiotherapeutics designed to deliver a safe and effective dose of radiation directly to the tumor of adults and children with rare and difficult-to-treat cancers. Plus’ lead drug candidate, REYOBIQ™ (rhenium re186 obisbemeda), is based on the radioactive isotope rhenium-186.

Drug Development & Delivery recently interviewed Dr. Marc Hedrick, CEO of Plus Therapeutics, to discuss the company’s targeted radiotherapeutic platform for central nervous system and solid tumor cancers and why internal radiation therapy offers patients a more advanced drug delivery solution compared to traditional external radiation therapy.

Q: Can you tell us a little bit about Plus Therapeutics and how your targeted radiotherapeutics work?

A: Plus Therapeutics is a Houston-based clinical-stage pharmaceutical company developing targeted radiotherapeutics designed to deliver a safe and effective dose of radiation directly to the tumor of adults and children with rare and difficult-to-treat cancers. Plus Therapeutics has developed a promising lead radiotherapeutic, REYOBIQ (rhenium Re186 obisbemeda), which is designed to treat central nervous system (CNS) cancers by leveraging a rhenium radioisotope used to both image and shrink the cancer patient’s tumor.

Q: Why radiotherapeutics?

A: Radiation therapy is an important and effective treatment for cancer and the gold standard for CNS cancers. However, traditional external radiation beam therapy (EBRT) is limited by low doses to minimize potential damage to healthy tissues and organs and the need for frequent treatment sessions, which are inconvenient and time-consuming for the patient. Plus Therapeutics has developed a targeted radiotherapeutic that addresses the limitations of EBRT, utilizing a delivery system designed to maximize toxicity to cancer cells while minimizing radiation exposure to healthy cells.

Q: How can Plus Therapeutics’ solution change patient care and management of diseases like glioblastoma, solid tumor cancers, and other cancers of the central nervous system?

A: The key difference with our radiotherapeutics is the precision with which they target cancer cells. We believe that by delivering our radiotherapeutic directly to the tumor with extreme precision using a catheter, we can mitigate the risk of damage to other healthy cells in a patient’s body. Most people are aware of the side effects of external beam radiation therapy, like hair and appetite loss, and other complications that stem from toxic radiation levels in the body. By limiting exposure to radiation to sites directly within or adjacent to the solid tumor, we aim to enhance patient care overall by shielding the body from unnecessary radiation exposure.

Q: What is REYOBIQ and what makes it different from existing treatments?

A: REYOBIQ (rhenium Re186 obisbemeda) is a novel injectable radiotherapy specifically formulated to deliver direct, targeted high-dose radiation to CNS tumors in a safe, effective, and convenient manner to optimize patient outcomes. With this radiotherapeutic drug, the goal is to inject high doses of radiation into or adjacent to brain and CNS cancers, which act on the tumor, break down slowly to sufficiently destroy tumor tissue, and stay localized while sparing healthy tissues until fully cleared.

We believe that REYOBIQ has the potential to improve outcomes for CNS cancer patients, compared to 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 (GBM), leptomeningeal metastases (LM), and pediatric brain cancer (Ependymoma and High Grade Glioma) in the ReSPECT-GBM, ReSPECT-LM, and ReSPECT-PBC clinical trials, respectively. These cancers are aggressive and challenging cancers occurring throughout the central nervous system with limited treatment options.

Q: Can you further discuss the ReSPECT clinical trials?

A: The ReSPECT-GBM trial is supported by an award from the National Cancer Institute (NCI), part of the U.S. National Institutes of Health (NIH); ReSPECT-LM is funded by a three-year $17.6M grant by the Cancer Prevention & Research Institute of Texas (CPRIT), and ReSPECT-PBC was awarded a $3M grant from the U.S. Department of Defense (DoD). We recently shared positive trial data for the now complete Phase 1 ReSPECT-LM dose escalation trial. The data showed it was well tolerated and demonstrated high radiation doses effectively delivered to tumors, with no significant safety issues. The findings provided evidence of prolonged survival and improved patient outcomes. Future enrollment will be available through the ReSPECT-LM dose optimization trial. Our ReSPECT-GBM trial is currently enrolling in Phase 2, and our ReSPECT-PBC will soon be enrolling for Phase 1.

Q: Can you share some background on Plus Therapeutics’ subsidiary diagnostic company, CNSide?

A: Plus Therapeutics’ subsidiary, CNSide Diagnostics, has developed the CNSide^® Cerebrospinal Fluid (CSF) Assay Platform, which is a groundbreaking tool that offers highly sensitive, CSF-based, laboratory-developed tests (LDTs) for patients with LM from carcinomas and melanomas. This proprietary test platform is designed to assess tumor cells that have spread from a primary carcinoma or melanoma to the central nervous system (CNS) by collecting a patient’s CSF. The CNSide CSF Assay Platform is the leading precision oncology product emerging from CNSide Diagnostics, offering an advancement in clinician understanding of LM by assisting diagnosis, identifying biomarkers, supporting treatment decisions, and monitoring the disease and effects of LM treatment. CNSide empowers physicians to “Achieve Clarity and Act with Certainty.”