ASH24: Beam reports early base editing success in SCD, but patient dies from conditioning

Beam Therapeutics, a year after reducing its workforce by 20% and prioritizing its sickle-cell disease (SCD) base editing program, has announced preliminary findings from its Phase I/II BEACON trial of BEAM-101. This trial focuses on patients suffering from severe vaso-occlusive crises (VOCs). The initial haemoglobin data indicates that Beam's ex vivo haematopoietic cell therapy is performing as expected. However, before receiving the experimental treatment, patients must go through a chemotherapy-based conditioning regimen involving busulfan, which has been linked to a patient death in the BEACON trial.

To address the limitations posed by busulfan, Beam is developing a new solution called engineered stem cell antibody paired evasion (ESCAPE). Although ESCAPE is not yet ready for clinical application, the company shared promising non-human primate data for ESCAPE in an abstract released ahead of the American Society of Hematology (ASH) meeting in December. They also provided efficacy data from four patients in the BEACON trial.

In terms of rapid engraftment, Beam reported that within one month post-treatment, all four evaluable patients experienced over 60% induction of foetal haemoglobin (HbF). By the second month, sickle haemoglobin (HbS) levels in non-transfused blood were reduced to 36% or less. Neutrophil engraftment was achieved at a median of 17 days post-transfusion, and platelet engraftment occurred around 20 days later. Additionally, markers of haemolysis were either normalized or improved in all four patients, with no VOCs reported. Data from seven patients will be presented at the ASH meeting.

However, the trial faced a setback with the death of one patient due to respiratory failure four months after receiving BEAM-101. The investigators determined that the death was "likely related" to busulfan and not to the cell therapy itself. Beam intends to integrate its ESCAPE technology into the BEAM-101 treatment regimen to eliminate the need for busulfan. ESCAPE, designed to selectively deplete diseased cells for non-genotoxic conditioning, includes BEAM-103, an anti-CD117 antibody, and BEAM-104, an engineered CD34 cell product. This regimen allows unmodified cells to be eliminated while base-edited cells "escape" and expand, facilitating engraftment.

In the abstract released on Tuesday, Beam reported that non-human primate data showed proof of concept for long-term engraftment following antibody conditioning with ESCAPE. The company plans to initiate Phase I-enabling toxicity studies by the end of the year.