UCART 20x22

Cellectis may have kicked off the year promising “huge momentum” in the allogeneic CAR-T space over the course of 2026, but even the French biotech has been unable to resist the dominance of in vivo options. The Paris-based company had been expecting to read out a pivotal phase 2 trial of lasme-cel, the biotech’s lead candidate for B-cell acute lymphoblastic leukemia (B-ALL), by the end of the year. Around the same time, Cellectis was due to produce a full phase 1 dataset for its other allogeneic CAR-T, eti-cel, in non-Hodgkin lymphoma (NHL). But the biotech revealed on Monday morning that both those clinical-stage programs have been scrapped. “In 2026, despite our 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,” the company explained in a Sept. 14 release. “Continued and recently accelerated advances in frontline treatment regimens have lowered relapse rates, reducing the number of patients progressing to later lines of therapy,” the company continued. “Concurrently, the rapid emergence of bispecific antibodies and in vivo CAR-T approaches has intensified competition in second and third-line treatment settings.” “Together, 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 therefore a delayed timeline to potential registration,” Cellectis added. “We believe these trends are likely to continue and further constrain the commercial opportunity for both product candidates.” It marks a stark turnaround from February, when Cellectis CEO André Choulika, Ph.D., insisted to Fierce that “2026 is our year,” pointing to “huge momentum” in the allogeneic CAR-T space. But the momentum has been draining out of allogeneic cell therapies for a while, with companies shifting their allegiance to in vivo CAR-T , where gene editing is used to generate CAR-T cells within a patient’s body. One of the most notable signs was when leading cell therapy organization Kite Pharma, a subsidiary of Gilead Sciences, scrapped a $2.3 billion allogeneic deal with Shoreline Biosciences last year and instead started pumping money into in vivo, purchasing Interius BioTherapeutics for $350 million and inking a deal with Pregene Biopharma worth as much as $1.6 billion. A wider Big Pharma shopping spree in the space has also seen AbbVie buy Capstan Therapeutics for $2.1 billion, Bristol Myers Squibb acquire Orbital Therapeutics for $1.5 billion, AstraZeneca pick up EsoBiotec for $1 billion, and Eli Lilly scoop up both Kelonia Therapeutics and Orna Therapeutics . Cellectis is also switching over to in vivo, channelling its resources to two preclinical candidates: HEAL-101, an in vivo base editing product candidate targeting APOC3 for severe hypertriglyceridemia, and HEAL-201, an in vivo epigenetic editing product candidate targeting PCSK9 for severe hypercholesterolemia. The plan is to take both candidates into phase 1 studies in China, with preliminary readouts pencilled in for the second half of 2027 and the first half of 2028, respectively. While the programs span “two distinct approaches” of base editing and epigenetic editing, Cellectis CEO Choulika said HEAL-101 and HEAL-201 are both “designed to provide highly specific genomic or epigenomic modulation with the goal of avoiding double-strand DNA breaks.” “Gene surgery has the potential to transform the treatment of high-risk metabolic diseases by delivering long-lasting benefits through a single IV injection,” he added in this morning’s release. “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.” As part of this strategic shift, Cellectis said it will “realign its organization and resources” to focus on the in vivo programs as well as continuing to support its partnerships with AstraZeneca , Allogene, Servier and Iovance. Fierce has asked Cellectis if this restructuring is likely to involve layoffs. The realignment is intended to stretch the company’s cash runway into the second half of 2028. The biotech ended June with $169 million in the bank.

Dive Brief:Cellectis is giving up on donor-derived cell therapies and shifting its focus to gene editing medicines, stating in a Monday announcement that the commercial and clinical landscape for combatting blood cancers with so-called CAR-T treatments has changed materially.The decision dramatically lengthens Cellectis road to a marketed medicine, as the company is ending work on treatments that were in clinical development and turning to therapies that havent been tested in humans. One CAR-T program it discovered and out-licensed has advanced as far as Phase 2 testing.Cellectis claimed that its new strategy represents the most effective use of its financial and operational resources. Investors expressed disappointment, however, as company shares fell as much as 43% in morning trading and, at around $2 apiece, trade just above all-time lows.Dive Insight:Founded around the turn of the century with gene editing technology developed by Institut Pasteur, Cellectis has long been a frontrunner in advancing allogeneic therapies built from the cells of donors. It raised $228 million in an initial public offering in 2015 and, since then, has worked to prove its treatments could become a simpler alternative to the complicated, personalized CAR-T therapies now available for multiple blood cancers.Yet like many of its peers, Cellectis has struggled. Individualized, autologous cell therapies have set a high bar for winning approvals in malignancies like leukemia, lymphoma and multiple myeloma. Their allogeneic counterparts have had difficulty matching those results, leading many developers in recent years to shift resources to other areas, such as autoimmune disease research.As recently as early August, Cellectis was touting data for two clinical-stage cell therapies called lasme-cel and eti-cel in leukemia and lymphoma. But treatment protocols in many blood cancers have changed drastically as new types of medicines from cell therapies to bispecific antibodies and more have been approved. Those developments have heightened Cellectis competition, reduced the addressable patient populations for each therapy and slowed study enrollment. We believe these trends are likely to continue and further constrain the commercial opportunity for both product candidates, the company said in a statement.Cellectis will seek strategic partnering opportunities to maximize the value of lasme-cel and eti-cel. The company will also realign its organization and support existing partnerships with Allogene, Servier, AstraZeneca and Iovance Biotherapeutics, the company said.The new drugs itll work on, meanwhile, are prospective cardiovascular disease treatments that are still in preclinical development. One, called HEAL-101, uses base editing technology to target a gene, APOC3, linked to high triglycerides. Another known as HEAL-201 harnesses an epigenetic editing approach to lower levels of the cholesterol-regulating protein PCSK9. Cellectis will face an uphill battle in both cases, as multiple medications aimed at APOC3 and PCSK9 are already available.Cellectis strategic shift comes in the wake of multiple recent high-profile failures in cardiovascular disease studies. The latest setback happened just over a week ago, when a therapy from Novartis and Ionis Pharmaceuticals fell short in a major study that had widely been expected to succeed. '