Multi-Base–Edited CAR T-Cell Therapy Trial Doses First Patient With R/R T-ALL/T-LL

Beam Therapeutics has dosed the first patient with relapsed/refractory T-cell acute lymphoblastic leukemia/T-cell lymphoblastic lymphoma (T-ALL/T-LL) in its phase 1/2 trial (NCT05885464) of BEAM-201.¹

BEAM-201 is an anti-CD7 allogeneic chimeric antigen receptor (CAR) T-cell therapy and is the first quadruplex-edited, allogeneic CART-cell therapy candidate to enter clinical-stage development. The newsalso marks the first treatment with a base editing CAR T-cell candidate in the United States.

“As the first patient dosed with a Beam therapeutic candidate and the first patient in the US to receive a base editing therapeutic, this represents a major milestone for the company, the scientists that made this possible, and the patients we hope to serve,” John Evans, chief executive officer, Beam, said in a statement.¹ “We believe that the full therapeutic potential of CAR-T therapies, including the ability to utilize an allogeneic source of T cells, will only be unlocked through higher levels of cellular engineering enabled by multiple simultaneous genetic edits. Base editing is especially well-suited to this challenge, as it is designed to deliver highly efficient multiplex edits in cells without the double stranded breaks that can lead to frequent chromosomal rearrangements and loss of cell viability. BEAM-201, to our knowledge the first quadruplex-edited cell therapy candidate in clinical development, is an allogeneic CAR-T cell investigational therapy with the potential to make a substantial impact for patients diagnosed with challenging T-cell cancers who have limited treatment options.”

READ MORE: Multiplex-Base Edited CAR T Therapy Cleared for Trial in T-ALL After Hold

The ongoing Phase 1/2 trial of BEAM-201 is a multicenter, open-label study evaluating safety and efficacy in patients with relapsed/refractory T-ALL/T-LL. It is primarily assessing safety, tolerability, and identification of the recommended Phase 2 dose and lymphodepletion regimen. Key safety endpoints include treatment-emergent and-related adverse events, and key efficacy endpoints include complete or partial responses, eligibilityfor hematopoietic stem cell transplant, minimal residual disease negative status. BEAM-201 is multiplexed base edited to eliminate expression of the CD7, TRAC, PDCD1 and CD52 genesto reduce fratricide, graft-versus-host disease and CAR-T cell exhaustion; to evade anti-CD52 lymphodepleting agents; and enable use of an allogeneic cell source.

Beam’s lead pipeline candidate, BEAM-101, is an autologous, base-edited CD34+ hematopoietic stem cell therapy being investigated in patients with sickle cell disease in the phase 1/2 BEACON trial (NCT05456880). The trial has continued enrolling and dosing participants in pursuit of its total target of 45 treated patients and Beam expects to announce initial data in 2024.²

“The first half of 2023 has been marked by focused execution across the business, with the singular goal of making an impact on the lives of people suffering from serious diseases,” Evans said in a quarterly report.² “We arevery pleased with the continued enrollment progress in the BEACON trial, having now consented enough patients projected to both fill the sentinel cohort andinitiate the expansion cohort... We have also continued to accelerate development of BEAM-302, a potential best-in-class product candidate for patients with alpha-1 anti-trypsindeficiency, and are now prioritizing a BEAM-302 regulatory filing in the first quarter of 2024 as our first in vivo program, with a regulatory filing for BEAM-301 expected to follow shortly thereafter.”

REFERENCES

1. Beam Therapeutics announces first patient dosed in Phase 1/2 trial of BEAM-201 in relapsed, refractory T-ALL/T-LL. News release. Beam Therapeutics. September 5, 2023. https://investors.beamtx.com/news-releases/news-release-details/beam-therapeutics-announces-first-patient-dosed-phase-12-trial
2. Beam Therapeutics reports pipeline updates and second quarter 2023 financial results. News release. Beam Therapeutics. August 8, 2023. https://investors.beamtx.com/news-releases/news-release-details/beam-therapeutics-reports-pipeline-updates-and-second-quarter