Cellectis has announced that its board of directors have approved a strategic transformation to become an in vivo gene editing company focused on developing long-lasting treatments for chronic diseases.

The transformation builds on promising preclinical proof-of-concept results for the company's lead candidate programs, .Heal-101 and .Heal-201.¹ .Heal-101 is an in vivo base editing product candidate targeting APOC3 for severe hypertriglyceridemia, while .Heal-201 is an in vivo epigenetic editing product candidate targeting PCSK9 for severe hypercholesterolemia.¹

What comes next?

Cellectis is expected to realign its organization and resources to focus on its in vivo gene editing pipeline and support its existing cell therapy partnerships with AstraZeneca, Allogene, Servier, and Iovance. The company says these combined actions are designed to extend its cash runway into the second half of 2028, giving it financial flexibility to advance it’s in vivo gene editing pipeline through key development milestones.¹

What sets Cellectis' gene editing platform apart?

Cellectis' core competencies span nuclease editing, base editing, epigenetic editing, and transcriptional regulation.¹ While most gene editing companies focus on a single editing modality, Cellectis' broad gene editing toolbox, built over a quarter century, is expected to allow the company to combine therapeutic targets using several gene editing modalities at once.¹

André Choulika, Ph.D., co-founder and chief executive officer of Cellectis, says the strategic shift reflects the progress made with it’s two lead candidates. "Gene surgery has the potential to transform the treatment of high-risk metabolic diseases by delivering long-lasting benefits through a single IV injection. Our decision to focus Cellectis on in vivo Gene Editing reflects the progress we have made with .Heal-101 and .Heal-201 and our assessment of where our gene editing capabilities can be most effectively deployed.”

What is .Heal-101 designed to treat?

.Heal-101 targets the human APOC3 gene, a well-validated target for severe hypertriglyceridemia, using a TALE-base editor specific to the APOC3 gene, known as APOC3 TALEB, formulated in lipid nanoparticles.¹ APOC3 TALEB displayed high on-site base editing activity when transfected as mRNA in a hepatic cell line, with mean base editing above 70%, and that base editing translated into a deep and significant reduction of APOC3 protein secretion, with a mean reduction above 70%.¹ APOC3 TALEB also displayed a highly specific base editing profile using an unbiased, genome-wide off-site identification method.

Intravenous injection of .Heal-101 in a liver-humanized, normolipidemic murine model successfully edited human APOC3, with mean on-site base editing of approximately 55%, and decreased plasmatic APOC3 levels by a mean of approximately 60%, up to 70%, which was associated with a decrease of circulating triglycerides by a mean of approximately 45%, up to 68%, relative to pre-treatment baseline.¹

The treatment did not significantly increase liver ALT levels compared with untreated controls. In a hypertriglyceridemic, humanized APOC3 transgenic murine model, intravenous injection of .Heal-101 significantly decreased plasmatic APOC3 levels by a mean of approximately 70% and triglyceride levels by a mean of approximately 76% compared with pre-treatment baseline, demonstrating the candidate's efficacy in a relevant disease model.¹ Cellectis plans to initiate a Phase I investigator-initiated trial in China and share preliminary clinical data from the program in the second half of 2027.

What is .Heal-201 designed to treat?

.Heal-201 targets the human PCSK9 gene, a well-validated target for severe hypercholesterolemia, using a TALE-epigenetic modulator specific to the promoter of PCSK9, known as PCSK9 TALEM, formulated in lipid nanoparticles.¹

PCSK9 TALEM displayed high on-site epigenome editing activity when transfected as mRNA in a hepatic cell line, with mean base editing above 90%, with the epigenome editing translating into a stable, deep and significant reduction of PCSK9 transcript levels and PCSK9 secretion without evidence of off-site gene and protein modulation.¹

Intravenous injection of PCSK9 TALEM mRNA lipid nanoparticles in a liver-humanized murine model successfully decreased plasmatic levels of PCSK9 by a mean of more than 90%.¹ Cellectis plans to initiate a Phase I investigator-initiated trial in China and share preliminary clinical data from this program in the first half of 2028.

Why is Cellectis exiting lasme-cel and eti-cel?

The company says that despite its continued conviction in the promise of allogeneic CAR T-cell therapies and strong physician interest in lasme-cel and eti-cel, the commercial and clinical landscape for B-ALL and NHL changed materially in 2026.^1,2 Continued and recently accelerated advances in frontline treatment regimens have lowered relapse rates, reducing the number of patients progressing to later lines of therapy, while the rapid emergence of bispecific antibodies and in vivo CAR-T approaches have intensified competition in second- and third-line treatment settings.^1,2

Together, the company says, these dynamics have reduced the addressable patient population for lasme-cel and eti-cel, resulting in slower enrollment, a potentially longer and more costly development pathway, and a delayed timeline to potential registration, trends the company believes are likely to continue.^1,2

After a thorough assessment of the evolving therapeutic landscape and a strategic review, Cellectis determined that the most effective use of its financial and operational resources is to focus on and accelerate its most promising in vivo gene editing assets.

The company will exit development of lasme-cel and eti-cel while seeking strategic partnering opportunities to maximize their value.¹

Sources

1. Cellectis Announces Strategic Transformation To In Vivo Gene Editing Company Cellectis September 14, 2026, https://www.cellectis.com/en/press/cellectis-announces-strategic-transformation-to-in-vivo-gene-editing-company/
2. Cellectis Presents Final Phase 1 Results of Lasme-cel andPreliminary Results on Eti-cel at EHA 2026 Congress Cellectis September 14, 2026, https://www.cellectis.com/en/press/cellectis-presents-final-phase-1-results-of-lasme-cel-and-preliminary-results-on-eti-cel-at-eha-2026-congress