The FDA has granted Plus Therapeutics Inc. fast track designation for its lead candidate, Rhenium Nanoliposomes (RNL), for treating recurrent glioblastoma, propelling it into the sixth cohort of a phase I dose-finding trial.

RNL is designed to deliver a very high dose of radiation, of up to 25 times greater concentration than currently used external beam radiation therapy, directly into the brain tumor for maximum effect. The nanoliposomes are intracranially administered by a convection-enhanced delivery using catheters specifically designed for the brain.

“This is a marriage of a drug that is very unique and delivery technology that’s also very unique,” Marc Hedrick, Plus’ president and CEO, told BioWorld.

The surgical approach is mapped on a computer using images taken from the patient through a CAT scan or an MRI. Then spectroscopic imaging helps doctors get the catheters to the appropriate place in the brain as well as to calculate the actual dose retained within the tumor. It’s a technology largely used for brain biopsies, Hedrick said. The convection-enhanced delivery puts a pressure head behind the drug, pushing it through the catheters to cover essentially just the tumor. The drug stays in the brain for days, delivering radiation to the tumor, while minimizing damage to healthy tissue.

The patients are monitored longitudinally for evidence of toxicity and response by MRI.

The U.S. NIH/National Cancer Institute is a major supporter of the phase I dose-finding trial. The radiotherapy study’s data and safety monitoring board recently approved moving into its sixth cohort, which includes increasing the drug volume and radiation dose to 8.8 mL and 22.3 millicuries, respectively.

“Through imaging we can know at any time where the drug is infused and for maybe up to eight days later we can tell where it is and how much radiation is getting to the tumor,” Hedrick said.

Plus is funded to complete the phase I, with help from the NIH, and has enough capital to complete the CMC drug manufacturing and scale-up work. Hedrick said he hopes the phase I will be enrolled by the end of 2020.

The candidate previously received orphan drug designation for treating glioblastoma.

RNL could also be application for other brain tumors, Hedrick said.

Hedrick, a former surgeon at UCLA, oversaw the acquisition of the Rhenium-186-chelated nanoliposome in May, along with other multiple rare cancer candidates, from Nanotx Therapeutics Inc. Transaction terms included an up-front $400,000 in cash and $300,000 in Plus’ voting stock. Plus may pay up to $136.5 million in development and sales milestone payments and a tiered single-digit royalty on U.S. and European sales.

“We stumbled onto this,” Hedrick said. “We probably looked at 25 to 30 different things to in-license and this sort of fell out of the suitcase a little bit. Somebody we were talking to mentioned it and we were curious, so we pursued it. It checked all our key boxes. It had a great scientific pedigree and it had support from the smart thought leaders like the National Cancer Institute and the NIH.”

Austin, Texas-based Plus also has an albumin-stabilized pegylated liposomal docetaxel I.V.-delivered treatment for relapsed small-cell lung cancer (SCLC) that has completed a phase I trial. The company is preparing for a phase II study as a second-line therapy for relapsed SCLC.

The name Plus came from the idea of taking what the company knows will work, Hedrick said, and then adding something that will make it work better.

Plus has GMP-validated manufacturing facilities in San Antonio, Texas.

In September 2019, Plus closed its underwritten public offering of 3 million units, with each unit consisting of one share of common stock and one series U warrant to purchase one share of common stock at $5. The gross proceeds were approximately $15 million.

Company stock (NASDAQ:PSTV) rallied strongly on Sept. 15, with shares closing 24% higher at $3.03 each.

Newly diagnosed incident cases of glioblastoma, a rare brain cancer with a five-year median survival rate of 5%, will increase by 1.4% annually, according to DRG, which added that treatment options for recurrent glioblastoma to remain severely limited.

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