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Cellectis exits CAR-T development to focus on in vivo gene editing for metabolic diseases

Cellectis exits CAR-T development to focus on in vivo gene editing for metabolic diseases

Cellectis (Euronext Growth: ALCLS / Nasdaq: CLLS), the Paris-based gene editing company, is ending internal development of its allogeneic CAR-T programs and repositioning around in vivo gene editing for chronic metabolic diseases. The shift follows slower enrollment and rising development costs in its late-line blood cancer programs, alongside increasing competition from bispecific antibodies and emerging in vivo CAR-T approaches.

The board approved the transformation on September 11, 2026. Cellectis will exit development of lasme-cel and eti-cel, its CAR-T candidates targeting B-cell acute lymphoblastic leukemia (B-ALL) and non-Hodgkin lymphoma (NHL) respectively, while advancing two in vivo programs — .HEAL-101 and .HEAL-201 — in severe dyslipidemias. The company said it will seek partnering opportunities for the discontinued CAR-T assets.

The strategic rationale for exiting lasme-cel and eti-cel centers on structural changes in the oncology landscape rather than clinical failure. Cellectis cited improved frontline treatment regimens that have lowered relapse rates, reducing the pool of patients reaching later lines of therapy where its allogeneic products were positioned. The simultaneous rise of bispecific antibodies and in vivo CAR-T approaches has intensified competition in second- and third-line settings. Together, the company said, these dynamics have slowed enrollment and extended the development timeline and cost to a potential registration — trends it expects to continue.

.HEAL-101 uses a TALE-base editor delivered via lipid nanoparticles (LNP) to edit the APOC3 gene in the liver, aiming to reduce triglyceride levels in patients with severe hypertriglyceridemia (sHTG). .HEAL-201 uses a TALE-epigenetic modulator, also LNP-delivered, to silence PCSK9 expression and lower LDL cholesterol in severe hypercholesterolemia. Cellectis said both programs have generated preclinical proof-of-concept, with in vivo editing efficiency and lipid reductions reported in murine models. Both programs plan to initiate Phase I investigator-initiated trials in China, with preliminary clinical data from .HEAL-101 expected in H2 2027 and from .HEAL-201 in H1 2028.

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The company said it will maintain its existing cell therapy partnerships with AstraZeneca, Allogene Therapeutics, Servier, and Iovance Biotherapeutics while restructuring operations around the in vivo pipeline. The operational realignment — subject to works council consultation under applicable French labor law — is designed to extend the cash runway into H2 2028, providing runway to reach those first clinical readouts.

Cellectis is entering an increasingly active field of liver-directed gene editing for cardiovascular and metabolic disease. Eli Lilly, through its 2025 acquisition of Verve Therapeutics, is developing in vivo editing programs targeting PCSK9 and ANGPTL3, while CRISPR Therapeutics has already reported Phase I human data for its ANGPTL3-directed CTX310. Cellectis' use of TALE-based base and epigenetic editors differentiates its technical approach from these CRISPR-derived systems, although neither .HEAL program has yet generated human clinical data.

Chief Executive Officer André Choulika said the decision reflects both the progress made with the two in vivo candidates and the company's assessment of where its editing capabilities can be most effectively deployed, describing the goal as delivering long-lasting benefit through a single intravenous injection.


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