Beam's base case under the spotlight

Though investors hope that the clinical hold over Beam’s BEAM-201 will not be protracted, the FDA’s stance, revealed in a regulatory filing yesterday, will remind them of the complexity of the company’s Car-T approach. BEAM-201 uses a C-to-T base editor to introduce not one but four edits to donor-derived T cells, before employing a lentivirus to induce expression of an anti-CD7 Car. The base edits silence the endogenous T-cell receptor (TCR), to yield an allogeneic product; CD7, to eliminate fratricide; PD-1, to boost potency; and CD52, to yield immunity to Campath. Beam argues that base editing is more precise than Crispr, and less prone to causing deleterious chromosome changes – though concerns over this are precisely what prompted the FDA to put BEAM-201’s IND application on hold. The SEC filing reveals that the agency requested data from genomic rearrangement assessments and analyses of off-target editing experiments. A related approach, Gracell’s GC027, knocks out TCR and CD7 using Crispr, and yielded promising early data in 2020. Beam, with its $3.8bn valuation, has yet to do any clinical work: the first trial of its lead asset, BEAM-101 for sickle cell disease, has not started dosing.

Selected clinical-stage Car-T projects targeting CD7
Project Company Approach Status
WU-CART-007 Wugen Allogeneic, TCRα & CD7 knockout by Crispr Ph1/2 started Mar 2022
Anti-CD7 CAR-T Yake Biotechnology Unclear Ph1/2
GC027 Gracell Biotechnology Allogeneic, TCRα & CD7 knockout by Crispr Ph1 data at AACR 2020 & 2021
PA3-17 Persongen Autologous, non-gene edited, "fratricide resistant"  Ph1 started Apr 2022
CD7 CAR-T cells Icell Gene Therapeutics Unclear, non-gene edited Ph1
ThisCART7 Fundamenta Therapeutics Allogeneic Ph1
SENL101/ SenL-T7 Hebei Senlang Biotechnology Autologous Ph1
CD7.CAR/28zeta Car-T cells Baylor College Autologous, CD7 knockout by Crispr Ph1
BEAM-201 Beam Therapeutics Allogeneic, TCRα, CD52, PD-1 & CD7 silencing by C-to-T base editing IND on clinical hold
Source: Evaluate Pharma &

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