Benzinga | Nov 9, 2020 08:24AM EST

Beam Therapeutics Names First CAR-T Base Editing Development Candidate for the Treatment of T-ALL and Presents New Data at SITC 2020

BEAM-201, an Off the Shelf Allogeneic CD7-Targeting CAR-T, Named as Development Candidate for Treatment of T-Cell Acute Lymphoblastic Leukemia



First Cell Therapy Featuring Simultaneous Edits to Four Genes; Demonstrates 96-99% On-target Editing at Clinical Scale and In Vivo Proof of Concept of Tumor Clearance

CAMBRIDGE, Mass., Nov. 09, 2020 (GLOBE NEWSWIRE) -- Beam Therapeutics Inc. (NASDAQ:BEAM), a biotechnology company developing precision genetic medicines through base editing, today announced that the company will advance BEAM-201, a potent and specific anti-CD7, multiplex edited, allogeneic CAR-T therapy, as a development candidate for the treatment of T-cell acute lymphoblastic leukemia (T-ALL). Preclinical data on BEAM-201 are being presented in a poster session during the Society for Immunotherapy of Cancer's 35th Anniversary Annual Meeting & Pre-Conference Programs (SITC 2020), and demonstrate potent, dose-dependent tumor control in vitro and in an in vivo xenograft model.

"BEAM-201 is the third development candidate from our pipeline of base editing programs named this year, an incredible milestone for our company and a testament to the strength of our platform and the dedication of our team," said Giuseppe Ciaramella, Ph.D., president and chief scientific officer of Beam. "BEAM-201 is a highly differentiated editing program designed to provide an 'off-the-shelf' CD7-targeting CAR-T cell therapy that may enable a one-time treatment option for patients with T-ALL. To our knowledge, BEAM-201 is the first cell therapy featuring simultaneous edits to four genes. The preclinical data being presented at SITC 2020 demonstrate 96-99% editing efficiencies across four targets without genomic rearrangements, as well as strong in vivo proof of concept of tumor clearance in a xenograft model. We are actively advancing BEAM-201 to assess its potential impact in treating people living with this devastating disease."

BEAM-201 is a potent and specific anti-CD7, multiplex edited, allogeneic CAR-T development candidate for the treatment of relapsed/refractory T-ALL, a severe disease affecting children and adults with a five-year overall survival of less than 25%. BEAM-201 is produced using a GMP-compliant, clinical-scale process in which T cells derived from healthy donors are simultaneously base edited at four genomic loci then transduced with a lentivirus coding for an anti-CD7 CAR. The resulting cells are universally-compatible, allogeneic ("off the shelf") CD7-targeting CAR-T cells resistant to both fratricide and immunosuppression.

Details of Beam's SITC 2020 presentation of BEAM-201 are as follows:

Title: Highly efficient multiplexed base editing enables the development of investigational universal CD7-targeting CAR-T Cells to treat T-ALL

Publication Number: 111

Category: Cellular Therapies

Data Summary:

* In vitro characterization of the effects of base editing in BEAM-201 demonstrated: Simultaneous base editing by a cytosine base editor (CBE) at four target loci in primary human T cells using a clinical-scale process produced 96-99% on-target editing of each of the four genes as measured by next-generation sequencing and flow cytometry; Simultaneous quad base editing of T cells resulted in no detected genomic rearrangements resulting from the editing process; Multiplex base editing did not negatively affect cell expansion during manufacturing; CBE-edited cells decreased expression of the four target genes with minimal effect on other genes, including key members of the p53 pathway that are upregulated in response to DNA double-stranded breaks produced by multiplex editing with nucleases.

* Further characterization of BEAM-201 in vitro and in a tumor mouse model demonstrated: Beam's GMP-compliant, clinical-scale process resulted in final BEAM-201 CAR-T cell populations with on-target editing efficiencies between 96-99.9% at each of the four target loci, and 85% CAR-expressing cells. As a result, Beam estimates that 91% of cells are bi-allelically quad base edited and 77% of cells have all 5 genetic modifications. The company believes this is the highest level and uniformity of CAR expression and simultaneous editing across four target sites reported at clinical scale to date. BEAM-201 cells demonstrated robust in vitro CD7-dependent cytokine production, and rapid in vitro cytotoxicity. BEAM-201 cells also demonstrated dose-dependent clearance or control, across a 25-fold dose range, of an aggressive disseminated CCRF-CEM T-ALL tumor mouse model.