Cellectis Shifts to In Vivo Gene Editing With .HEAL-101, .HEAL-201

Cellectis has announced a strategic transformation to become an in vivo gene editing company, driven by a deteriorating commercial outlook for its allogeneic chimeric antigen receptor (CAR) T-cell candidates, lasme-cel and eti-cel, which the company will now exit. The company will now prioritize its lead in vivo programs, .HEAL-101 and .HEAL-201, in severe dyslipidemias, according to its September 14, 2026 announcement.¹ Preliminary phase 1 data for .HEAL-101 are planned for the second half of 2027, and for .HEAL-201 in the first half of 2028.

"Gene surgery has the potential to transform the treatment of high-risk metabolic diseases by delivering long-lasting benefits through a single IV injection," said André Choulika, PhD, co-founder and CEO of Cellectis, in a company press release.¹

Why is Cellectis exiting its cell therapy programs?

Cellectis said that despite 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-cell acute lymphoblastic leukemia and non-Hodgkin lymphoma changed materially in 2026.¹ Continued and recently accelerated advances in frontline treatment regimens have lowered relapse rates, reducing the number of patients progressing to later lines of therapy where these candidates were positioned, while the rapid emergence of bispecific antibodies and in vivo CAR-T approaches has intensified competition in second- and third-line treatment settings. These dynamics have reduced the addressable patient population for both product candidates, resulting in slower enrollment, a potentially longer and more costly development pathway, and a delayed timeline to potential registration, the company stated.¹

Cellectis said it believes these trends are likely to continue and further constrain the commercial opportunity for both programs. After a strategic review, the company determined that the most effective use of its financial and operational resources is to exit lasme-cel and eti-cel development and redirect those resources toward its in vivo gene editing pipeline, while seeking strategic partnering opportunities to maximize their value.¹

What are .HEAL-101 and .HEAL-201, and what preclinical data support them?

.HEAL-101 is an in vivo base-editing candidate targeting apolipoprotein C3 (APOC3) for severe hypertriglyceridemia, while .HEAL-201 is an in vivo epigenetic editing candidate targeting the proprotein convertase subtilisin kexin 9 (PCSK9) promoter for severe hypercholesterolemia. Both candidates use transcription activator-like effector-based editors formulated in lipid nanoparticles for intravenous delivery. In mouse models, .HEAL-101 reduced triglycerides by approximately 76% and .HEAL-201 reduced plasma PCSK9 by more than 90%, both compared with baseline.¹ Cellectis plans investigator-initiated phase 1 trials in China for both programs, with preliminary data expected in the second half of 2027 for .HEAL-101 and the first half of 2028 for .HEAL-201.¹

Why are APOC3 and PCSK9 considered validated targets, and how does this approach differ from existing therapies?

APOC3 and PCSK9 are both well-established regulators of lipid metabolism, and several approved or late-stage antisense and siRNA therapies already target APOC3 to reduce triglycerides and pancreatitis risk.² Unlike these therapies, which require repeat dosing, Cellectis said its editing approaches are designed to provide durable modulation through a single IV injection while avoiding the double-strand DNA breaks associated with traditional CRISPR-based nuclease editing.¹

At a past session in the 2025 Cell and Gene Meeting on the Mesa, Allan Reine, MD, CEO of Prime Medicine, discussed how next-generation editing platforms, such as his company’s technology, address genotoxicity risk. "We really don't see any off-target editing with our technology. We don't see any translocations, chromosomal rearrangements."³

How is Cellectis funding the transformation and what are the limits?

The company will continue supporting existing cell therapy partnerships with AstraZeneca, Allogene, Servier, and Iovance, and said its operational realignment is designed to extend its cash runway into the second half of 2028.¹

The efficacy data supporting .HEAL-101 and .HEAL-201 are preclinical, from cell line and mouse models, and have not yet been tested in humans. Clinical trials have not yet begun for either program. Cellectis has not disclosed specific terms or a timeline for a potential partnering transaction involving lasme-cel or eti-cel.

References

1. Cellectis. Cellectis announces strategic transformation to in vivo gene editing company. Press release. Published September 14, 2026. Accessed September 14, 2026. https://www.cellectis.com/en/press/cellectis-announces-strategic-transformation-to-in-vivo-gene-editing-company/
2. Tsimikas S. Anti-apoC-III therapies and implications for treatment of pancreatitis and cardiovascular disease. Curr Atheroscler Rep. 2025;27(1):103. doi:10.1007/s11883-025-01345-4
3. Mirasol F. Analyzing the safety and scope of next-generation gene editing platforms. BioPharm International. Published October 7, 2025. Accessed September 14, 2026. https://www.biopharminternational.com/view/analyzing-the-safety-and-scope-of-next-generation-gene-editing-platforms