Unum Therapeutics’ cell therapy tech is getting one last lease on life after a Czech biotech was able to pick up the core of a once-ballyhooed company for the cost of spare parts.
For $8.1 million upfront and just $3.4 million in milestones, Prague-based cell therapy startup Sotio bought out the preclinical “BOXR” CAR-T platform that Unum said they would turn to in March, after a third round of safety issues in as many years proved the final straw for their lead program.
That never quite happened. Instead, with their reserves dwindling, their CSO departing and the stock struggling to stay above $0.50 cents, chairman Bruce Booth and the board orchestrated a deal to effectively empty out Unum and replace its core with kinase-targeting tech from a small Cambridge biotech called Kiq. It was an admission of defeat for a company that had A-list investors and sought to bring the “next-generation” of CAR-T. They started actively looking to sell-off BOXR.
Sotio CEO Radek Špíšek acknowledged he paid a relatively meager price for BOXR, but he says that reflected Unum’s reputation more than the merits of the new approach. He noted that the pre-clinical platform is distinct from the ACTR approach that led to multiple patient deaths and clinical holds.
“I think they were very much punished by the market,” he told Endpoints News, adding of the BOXR platform: “It’s very much different — it’s actually totally conceptually different than the pre-existing programs that had the regulatory problems.”
The platform remains preclinical, so the odds of failure are naturally high. Still, one independent cell therapy expert who reviewed their preclinical work said the approach made mechanistic sense and looked promising. Essentially, it involves taking T cells, adding CARs to direct them toward tumors and then also adding other transgenes that will allow the cells to enter and persist in the micro-environment around solid tumors.
The idea is one of many now being tested to bring CAR-T’s benefits to solid tumors. The lead program within BOXR involves CARs that target GCPR3, a gene often over-expressed in liver and other cancers. In addition to the CAR, researchers add to the T cells a gene that regulates cell metabolism called GOT2.
Christopher Rudd“It could be effective to all tumors, not just those who are resistant to CAR therapy,” Christopher Rudd, director of immuno-oncology at the University of Montreal, told Endpoints . For “those that are affected by CAR therapy, it could make [the therapy] even more efficient.”
He added there were still questions about how it would prevent T cells from exhausting and promoting cytokines — immune signals — within the tumor. Safety is always a concern with immuno-oncology, he said, but nothing stood out with this approach.
Sotio is hoping to file an IND for hepatocellular carcinoma before the end of next year, but Špíšek said the company had larger goals with the old Unum outfit than a single program.
Over the last decade, they’ve built up a cell therapy logistics and manufacturing base in the Czech Republic, while expanding into China and Basel. Now, they’ll try to turn the new acquisition into a research base inside Cambridge, which they’re calling “A T cell therapy R&D Center of Excellence.” It will be led at first with a man intimately acquainted with the BOXR platform and the promise and pitfalls of cell therapy: longtime Unum CTO Geoff Hodge, whose cell therapy expertise likely became extraneous when Unum pivoted to kinases.
Geoff HodgeŠpíšek is hoping their GMP cell therapy facilities will let them progress the platform faster than others could. They will also look to combine the BOXR CAR-Ts with their pre-existing drugs, including an engineered IL-15 that might stimulate the T cells further.
So far, he said, there have been no safety signals. But he added it was still quite early.
“Of course, this needs to be developed very cautiously in the clinic,” he said.
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August 31, 2020 at 08:35PM
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Sold for pennies, Unum gets one last shot at redemption - Endpoints News
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