Enlivex defends sepsis data that sank stock, shifting focus from mortality to subgroup analysis

Enlivex Therapeutics had a message Friday for investors who halved its share price: You’re misreading our data. The cell therapy developer blamed imbalances between cohorts for the mixed results—and contended the effect on a small subgroup of sepsis patients suggests the candidate has a future.

The phase 2 clinical trial compared Allocetra, an off-the-shelf cell therapy that is designed to reprogram macrophages, to placebo in the treatment of organ failure in adult sepsis patients. Enlivex takes cells from healthy donors and makes them express an “eat me” signal. After administration, macrophages duly eat the cells and homeostasis is restored. That’s the idea, anyway. 

Whether the phase 2 trial supports the efficacy of the mechanism is a point of disagreement between Enlivex and its investors. The biotech’s stock plummeted 54% to $1.83 in the wake of the release Thursday. Enlivex CEO Oren Hershkovitz, Ph.D., put his side across on a conference call with investors this morning. 

“Definitely we saw the market reaction, and we found that probably the market didn't understand well the results, in our interpretation of the data,” Hershkovitz said. “This is a complicated study, and maybe people don't read it the way we do. We're pleased with the data and the results that we see. The market [reaction] is something that's difficult to explain and understand for us. That came as a surprise.”

The case against Enlivex includes the mortality rate, which was 13.3% in the Allocetra arm compared to 2.2% in the control group. None of the deaths were deemed related to Allocetra. Enlivex noted that the mortality in both cohorts was lower than in historical studies and pointed to an imbalance between the control and treatment arms, which had a higher rate of septic shock and invasive ventilation at baseline.

Hershkovitz said the imbalance “made it challenging to deduce the relative effect” of Allocetra in the overall population. However, the CEO was willing to claim a “very good potential indication of effect” in a 15-patient subpopulation in which Allocetra appeared to have an advantage over placebo. The patients in the subpopulation had urinary tract infections.

Asked whether the results support plans to file for approval in Europe, Hershkovitz said Enlivex needs to collect more data. “Once we get all of the data and the interaction between the expression biomarkers and all that, we’ll probably consider to go and discuss that with the regulator,” Hershkovitz said.

The CEO later added he expects another trial will be needed “even if the results from all the other subgroups are good.”