Stock Price Plummets 75%! This Biotech Halts Main CAR-T Project and Lays Off Employees

Recently, Cargo Therapeutics has been lightening its load, abandoning 50% of its workforce and its lead candidate for CAR-T therapy after weak durability and severe side effects. The drug, known as firicabtagene autoleucel or firi-cel, is an autologous CD22 CAR-T cell therapy that has been undergoing Phase 2 trials in patients with large B-cell lymphoma who experienced disease relapse or did not respond to CD19 CAR-T therapy.

Just three weeks ago, the prospects for firi-cel seemed positive, with Cargo reporting that 71 patients had been treated in the trial. The biotech company had "hoped" to report a mid-study analysis of the data in the first half of this year, calling it a "potentially pivotal" study. Yesterday, the company announced that it had conducted a "temporary analysis" of the trial, triggered by recent safety events. Although the review of data from 51 patients showed an overall response (OR) rate of 77% and a complete response (CR) rate of 43%, the durability of the CR rate at three months was only 18%.

More importantly, 18% of patients experienced immune effector cell-associated hemophagocytic lymphohistiocytosis-like syndrome (IEC-HS), a toxicity associated with CAR-T cell therapy, reaching Grade 3 or higher. This included Grade 4 and 5 serious adverse events, with Grade 5 indicating death, though Cargo did not specify how many patients experienced this outcome.

Cargo went public in 2022 with a $200 million listing, and the following year raised $281 million in an IPO. After the news about firi-cel, the company's stock price plummeted, with its market value dropping by 75% in Thursday's pre-market trading to $3.31, compared to Wednesday's closing price of $13.19.

After concluding that the data "did not support a competitive risk-benefit profile for patients," Cargo decided to cancel the firi-cel program. The company's new focus will be on advancing its trispecific CAR-T, CRG-023, into a Phase 1 dose-escalation trial.

With $368.1 million in hand entering the new year, the biotech company announced it will halve its workforce to extend its cash runway through mid-2028, while continuing to "evaluate its strategic options."

"We are disappointed by the unexpected results of the Phase 2 study," said Cargo CEO Gina Chapman in a press release. "The durability of complete response is a key clinical goal for R/R LBCL patients undergoing CD19 CAR-T therapy. Combined with the incidence and severity of IEC-HS being higher than expected, the data generated so far has not met our expectations for offering a competitive risk-benefit profile for patients in the context of available treatment options."

William Blair analysts expressed disappointment that firi-cel failed to deliver on the promise shown in the Phase 1 trial, where 20 patients who achieved CR had median PFS and OS that were not met.

In a report on January 30, analysts wrote, "Additionally, we recognize this is a severely ill patient population who had previously received CAR-T therapy, so their CAR-T products may contain a higher proportion of terminal effector memory cells or immunosuppressive T regulatory cells, which may explain the lack of durability." They also expressed surprise at the high level of Grade 3 or higher IEC-HS, noting that this has only been observed previously in products produced at higher doses or with different potency parameters.

Reference

https://www.fiercebiotech.com/biotech/cargo-offloads-car-t-along-half-its-workforce-wake-efficacy-toxic-side-effects

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