Fludarabine Phosphate

Five months after raising $300 million, securing FDA alignment on a pivotal trial and reporting encouraging early results for its lead off-the-shelf NK cell therapy AlloNK (AB-101), Artiva Biotherapeutics is abandoning the programme and letting go of nearly its entire workforce.The reversal, announced on Tuesday, follows two patient deaths during clinical testing and longer-term efficacy data that fell short of expectations. Company shares fell 32% on the news.Artiva was developing AlloNK across B-cell–driven autoimmune diseases including refractory rheumatoid arthritis, Sjögren disease, systemic sclerosis and myositis.According to the company, one patient in its Phase IIa autoimmune basket trial died after developing leukoencephalopathy following treatment with AlloNK that included lymphodepletion with cyclophosphamide and fludarabine. Investigators and an independent safety review determined the event was "likely related to fludarabine-associated neurotoxicity."The FDA requested a pause in enrollment and dosing in the study after this event, while the company also halted a planned Phase III study. "Given the widespread use of fludarabine-containing lymphodepletion regimens in cell therapy development, Artiva intends to share additional details of this case in a scientific publication," it said.A second patient died suddenly approximately two months after starting therapy, though the cause remains unknown and study investigators assessed the event as being unrelated to treatment.Lack of durable responsesMeanwhile, on the clinical efficacy front, updated results for AlloNK combined with rituximab continued to show "deep B-cell depletion and clinical activity," but Artiva said longer-term follow-up revealed that treatment responses weren't durable enough to justify further development.The company didn't disclose updated efficacy figures, but said in May that five of seven rheumatoid arthritis patients with at least six months of follow-up had achieved an ACR50 response, representing a 71% response rate. There were also no relapses or need for additional immunomodulatory therapies.Artiva said Tuesday that its decision to end the programme followed "an assessment of the risk-benefit of the therapy, likely enrollment delays and the overall development and potential commercial outlook."The decision also ends plans for the roughly 150-patient Phase III CONCERT-RA trial in refractory rheumatoid arthritis, which had been expected to begin in the second half of 2026 and yield top-line results in 2028.The San Diego-based biotech is now slashing its workforce by about 94% and exploring strategic alternatives, including a possible merger, licensing of assets or dissolution. The company had 115 full-time employees as of the end of last year, according to a recent regulatory filing, and reported approximately $319.1 million in cash, cash equivalents and investments as of Sept. 30.

Artiva Biotherapeutics will lay off most of its staff and stop developing an experimental natural killer cell therapy for autoimmune conditions after reporting the deaths of two participants in a clinical trial.Artiva made clear in a Tuesday statement that both of the deaths appear unrelated to its therapy, which is known as AlloNK and was being tested in inflammatory diseases like rheumatoid arthritis. One participant developed leukoencephalopathy a potentially deadly neurological reaction that a study investigator linked to a chemotherapy, fludarabine, used to prepare patients for treatment.The other patient experienced sudden death roughly two months after starting treatment and, while the cause hasnt been determined, a trial researcher again concluded that neither AlloNK nor any other component of the treatment regimen was to blame.Artiva reported the first event to the Food and Drug Administration, which then asked Artiva to pause its ongoing Phase 2a trial. The biotech stopped planned enrollment and dosing in a Phase 3 trial, too.AlloNK didnt appear as long-lasting as the company had hoped, either. The effects seen in testing did not reflect the level of durability of clinical response the company believes is needed to support continued development, according to the Tuesday announcement.Artiva now plans to lay off 94% of its staff and has hired a financial adviser to begin a strategic review a process that often ends in a reverse merger or asset sale. As of the end of September, Artiva held $319.1 million in cash and cash equivalents, according to a federal securities filing.Artiva is one of many companies that had been pursuing cell therapies relying on natural killer, or NK cells. These cells have different characteristics than the T cells used in CAR-T therapies for cancer and have been seen as potentially more convenient, off-the-shelf alternatives. Artivas treatments, for instance, were derived from donor cells rather than cells collected from individual patients.Like many others working on these therapies, though, Artiva has changed course.The company canceled plans for an initial public offering in 2022 before pivoting to autoimmune conditions and eventually joining the public markets two years later.The company had been running a mid-stage basket trial in multiple inflammatory diseases, among them systemic sclerosis and myositis. Artiva disclosed some study results earlier this year, and planned to report additional findings at a medical meeting this month.Those presentations have now been canceled, along with a planned Nov. 9 investor call, Artiva said. Artiva also plans to share findings from the fludarabine-associated death in a scientific publication given the treatments widespread use in cell therapy conditioning regimens, said CEO Fred Aslan, in a statement.Artiva could sell or license its technology or merge with another company given its sizable cash balance, wrote TD Cowen analyst Tyler Van Buren. But regardless of the outcome, we do not expect meaningful appreciation in share value, he added.The news represents the latest setback for a company pursuing cell therapy for autoimmune disease. In August, Novartis and Bristol Myers Squibb paused multiple trials of their cellular medicines rap-cel and zola-cel due to safety concerns. Novartis reported three deaths from a serious immune reaction, while Bristol Myers disclosed transient and reversible inflammatory events.Last week, Bristol Myers Squibb revealed that a patient had died 44 days after receiving a dose of zola-cel. Unlike Artivas AlloNK, Bristol Myers and Novartis treatments are autologous therapies harvested from a patients body, re-engineered and reinfused. Those therapies were also made with the help of a speedy manufacturing process Wall Street analysts have flagged as a possible culprit. '