WU-NK-201

The promise of next-gen, “off-the-shelf” cell therapies have thoroughly entranced biopharma with the promise of lowering manufacturing costs and potentially challenging dominant checkpoint inhibitors. But to get there, companies need a potent therapy and one that can be continuously sourced from donors. A new biotech uncloaking from a lengthy development period thinks it may have solved that puzzle. Wugen, a primarily St. Louis, MO-based team with an office in San Diego, closed a whopping $172 million B round Thursday with plans to advance its slate of off-the-shelf “memory-like” natural killer cell therapies, which the biotech thinks offers greater cytotoxicity and durability than standard NK cells. Abingworth and Tybourne Capital Management led the round with an expansive slate of new and existing investors on board. Wugen is built off research from Todd Fehniger’s lab at Washington University in St. Louis on the effect of memory NK cells in blood cancer, melanoma and beyond. In 2016, Fehniger’s team posted data from a Phase I study of lead candidate WU-NK-101, showing a 60% overall response rate and 45% response rate among 15 acute myeloid leukemia patients. Operating in stealth, Wugen used a $36 million A round in early 2020 to build up its pipeline. Now, with even more preclinical data to back up its proof of concept, Wugen is ready for the spotlight. More recently, Fehniger, who has remained at Wugen as a scientific advisor, posted an article in Clinical Cancer Research last month showing that memory-like NK cells — innate immune cells that can pass along “memory” of specific antigens — showed greater cytotoxicity and a more durable response against melanoma tumors than other NK cells. Researchers used a complex of cytokines, including human-derived IL-12, IL-15 and IL-18, to prime and activate those cells ex vivo before infusion, effectively “ supercharging ” the therapies to target and eliminate tumor cells. In advanced melanoma, an indication where immune checkpoint inhibitors dominate but nearly half of patients don’t respond to T cell-directed therapies, a potent NK cell therapy could offer a meaningful option for patients. With WU-NK-101, which is directed at the CD16 antigen, the team is studying the drug solo for AML as well as in combination with Erbitux. They’re also testing it after checkpoint inhibitors in head and neck cancer and melanoma. Meanwhile, a follow-on NK candidate, dubbed WU-NK-201, is currently in early preclinical testing for solid tumors, one of many next-gen cracks at the elusive field. Wugen additionally has an off-the-shelf CAR-T program — the lead candidate is WU-CART-007 for T-cell acute lymphoblastic leukemia — that is also in preclinical development. The 40-person team is helmed by CEO Dan Kemp, who left his role as head of cell therapies business development and operations at Takeda in April to take a crack at building Wugen after being “really blown away” by the Fehniger team’s early data. Now, Wugen is gearing for an open-label Phase II test for WU-NK-101 in AML, which is slated to begin in August and enroll 104 patients, according to clinicaltrials.gov. The study’s primary endpoint is ORR. Secondary endpoints include OS and EFS. The trial is expected to wrap in February 2024. Kemp, who arranged Takeda’s “buy-to-build” pickup of GammaDelta Therapeutics in 2017 — a deal worth up to $100 million — and the Japanese drugmaker’s CAR-NK pact with MD Anderson in 2019, said that experience offered him a trial by fire on the frontier of cell therapy. “We really kicked the tires and learned as the cell therapy field evolved over the last five or so years,” he said. The big difference in Wugen’s platform is the lack of engineering that goes into each therapy. Unlike CAR-NK, for instance, the donor-derived memory NK cells used in Wugen’s technology are simply primed for proliferation and then allowed to do their thing in vivo. A smaller manufacturing profile means a single donation can be used to create hundreds of individual therapies, Kemp said. With the newest round of funds, Wugen expects to keep advancing its pipeline as well as rapidly scaling up its team for the approaching clinical gauntlet. Kemp expects Wugen’s workforce, now at 40, to double in the coming six to eight months to prepare for the future.