In a bone marrow transplant (BMT) or hematopoietic stem cell transplantation (HSCT), healthy blood stem cells and white blood cells are infused into a patient’s body to replace damaged or diseased bone marrow and in many cases, to clear out the remainder of cancer cells in the patient’s system. The source of cells for a BMT/HSCT may come from the patient’s own body (autologous transplant) or from a donor (allogeneic transplant). An exaggerated immune response accompanied with a cytokine storm occurs when the donated white blood cells register the host body’s tissues and organs as foreign antigens. This may cause post transplantation complications such as Graft-vs-host disease (GvHD), Hepatic veno-occlusive disease, Severe endothelial leakage syndrome, Pneumonitis and organ failure, which are all highly associated with cytokine storms. Patients are typically treated with standard-of-care immunosuppressant’s such as corticosteroids, antibodies, or small-molecules that usually work by suppressing the immune system. Such treatment regimens are known to potentially compromising patients’ ability to respond to immunological challenges and exposing patients to severe side effects, first and foremost severe infections that are responsible for approximately 27% of post­-transplant mortality.

Post transplantation causes of mortality

Post transplantation all cause mortality
Post transplantation all cause mortality

Allocetra™ is being developed to prevent life-threatening post-transplantation complications, without exposing patients to the risk caused by immunosuppressive treatments.

Clinical outlook for prevention of complications post-bone marrow transplant

Enlivex has conducted a Phase IIa clinical study to evaluate the safety, tolerability, and preliminary efficacy profile of Allocetra for preventing post-BMT complications. The study showed that Allocetra has the potential to induce immunotolerance and rebalance the immune system to normal activity levels post-BMT – preventing Cytokine Release Syndrome and BMT-associated complications. Patients who received effective doses of Allocetra experienced no GvHD grade II-IV and were discharged from hospital after an average of 21 days compared to the expected 41-45 days. Allocetra has been well-tolerated, showing no observable, significant adverse side effects.

The Company’s timeline for the continued development of Allocetra™ from either matched-donor cells or off-the-shelf source for the prevention of GvHD in allogeneic HSCT patients has been modified to reflect the Company’s re-prioritization of product development in light of the encouraging results of the Phase Ib of Allocetra™ in patients with severe sepsis. As a result, the planned continuation of additional clinical trials of Allocetra™ from either matched-donor cells or off-the-shelf source for the prevention of GvHD in allogeneic HSCT patients have been rescheduled to 2022, pending the expected results of clinical trials in sepsis and potentially other related indications during 2020-2022.