Cellectis posts UCART22 Phase 1 data, eyes 2028 BLA

Rhea-AI Filing Summary

Cellectis S.A. filed a 6-K reporting new clinical data from the BALLI-01 Phase 1 study of lasme-cel (UCART22) in transplant-ineligible, relapsed/refractory B-ALL (3L+). The company states lasme-cel was generally well-tolerated with manageable cytokine release syndrome and neurotoxicity, and outlined a path to a pivotal Phase 2 study.

Activity signals were strongest with Cellectis-manufactured product (Process 2). In the P2 cohort, the overall response rate was 68% with 83% MRD-negativity among responders. Among 13 patients relapsed after prior CD22 therapy (inotuzumab), 31% achieved CR/CRi with MRD-negativity and all proceeded to HSCT. In a heavily pretreated subgroup that had three prior targeted therapies (n=22), 36% achieved MRD-negative CR/CRi. At the recommended Phase 2 dose (DL3; n=12), 7 had prior inotuzumab and 43% achieved MRD-negative CR/CRi, with all undergoing HSCT. The company plans to enroll the first patient in the pivotal Phase 2 in Q4 2025 and anticipates submitting a BLA in 2028.

Insights

Biotech clinical and regulatory analyst

Pivotal path set; Phase 1 signals support Phase 2 start in Q4 2025.

Cellectis reports Phase 1 safety consistent with CAR-T expectations and signals of activity concentrated in its Cellectis-manufactured product (Process 2). The P2 cohort shows an overall response rate of 68% with MRD-negativity in 83% of responders, including responses after prior CD22 therapy and in heavily pretreated patients.

The outlined plan advances lasme-cel to a pivotal Phase 2 with a recommended dose (DL3) already identified. The filing notes End-of-Phase 1 interactions with FDA and EMA and an anticipated BLA in 2028, anchoring a regulatory path while preserving typical development risks.

Execution now turns to Phase 2 enrollment in Q4 2025 and durability/HSCT-bridge outcomes. Actual impact will depend on reproducibility of response rates at DL3 and safety consistency in a larger, pivotal population.

UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

Washington, D.C. 20549

FORM 6-K

Report of Foreign Private Issuer

Pursuant to Rule 13a-16 or 15d-16

under the Securities Exchange Act of 1934

Date of Report: October 16, 2025

Commission File Number: 001-36891

Cellectis S.A.

(Exact Name of registrant as specified in its charter)

8, rue de la Croix Jarry

75013 Paris, France

+33 1 81 69 16 00

(Address of principal executive office)

Indicate by check mark whether the registrant files or will file annual reports under cover of Form 20-F or Form 40-F.

Form 20-F ☒   Form 40-F ☐

Cellectis S.A.

The information included in this report on Form 6-K under the caption “—BALLI-01 Study” below shall be deemed to be incorporated by reference in the registration statements of Cellectis S.A. (collectively, the “Registration Statements”) on Form F-3 (No. 333-288491 and 333-284302) and Form S-8 (Nos. 333-204205, 333-214884, 333-222482, 333-227717, 333-258514, 333-267760, 333-273777, 333-284301 and 333-290218), to the extent not superseded by documents or reports subsequently filed.

The information under the caption “Investors R&D Day” as well as the information included as “Exhibits” to this Form 6-K shall not be deemed incorporated by reference in any filing of Cellectis S.A. under the Securities Act of 1933 or under the Exchange Act of 1934, except as shall be expressly set forth by specific reference in such a filing.

Investors R&D Day

Cellectis S.A. (the “Company”) hosted an Investors R&D Day on October 16, 2025. In connection with the R&D Day, the Company issued a press release, attached as Exhibit 99.1 hereto. Attached as Exhibit 99.2 hereto is a copy of the presentation deck that accompanied the Investors R&D Day.

BALLI-01 Study

Highlights:

• Efficacy: ORR of 68% with lasme-cel Process 2 (n=22), 83% at RP2D (n=12) and 100% in the target Phase 2 population (n=9)

• Safety: in Phase 1 (n=40), lasme-cel was generally well-tolerated (including 1 case of grade 2 IEC-HS which resolved)

• Durability: in patients who achieved MRD-negative CR/CRi, median OS was 14.8 months

• In the target Phase 2 population, CR/CRi rate of 56% with ~80% of patients achieving MRD-negative status

• In the target Phase 2 population, 100% patients became transplant eligible with 78% proceeding to transplant

• Among 11 subjectspatients previously treated with all 3 targeted therapies (inotuzumab, blinatumomab, and CD19 CAR-T), 8 responded and 7 achieved MRD-negative status

• BALLI-01 pivotal Phase 2 in r/r B-ALL initiated

On October 16, 2025, the Company released promising clinical data from the BALLI-01 Phase 1 study of lasme-cel (UCART22) for transplant ineligible patients with relapsed/refractory B-cell acute lymphoblastic leukemia (r/r B-ALL) in the third line or beyond (3L+).

The BALLI-01 Phase 1 clinical study was designed to evaluate the safety and clinical activity of lasme-cel (UCART22) in patients with r/r B-ALL. The BALLI-01 trial enrolled 40 patients aged 15–70 years expressing >70% CD22 on leukemic blasts. Patients were heavily pretreated with a median of 4 prior lines of therapy: 80% of patients had received prior blinatumomab, approximately half had received prior inotuzumab and prior CD19 autologous CAR-T therapy.

Lasme-cel (UCART22) was given at escalating dose levels following lymphodepletion with either fludarabine and cyclophosphamide (FC) or FC with alemtuzumab (FCA). The addition of alemtuzumab was implemented to sustain host T-cell and Natural Killer (NK)-cell depletion and to support lasme-cel expansion and persistence.

Phase 1 Safety Data: The Phase 1 safety data confirm that lasme-cel was generally well-tolerated, with expectations for CAR-T therapies, with manageable adverse events, including cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome (ICANS).

• Dose-limiting toxicities (DLTs) were uncommon, with only 1 case reported at Dose Level 3 (DL3)

• Adverse event of special interest (AESI) of CRS occurred in 2.5% of patients and ICANS in 5% of patients

• 8 lasme-cel related serious adverse events (SAEs) were reported

Phase 1 Activity Data: In the BALLI-01 Phase 1 study, 40 transplant ineligible 3L+ patients were dosed with lasme-cel (UCART22):18 patients were dosed with product manufactured by an external CDMO (Process 1, or P1) and 22 patients were dosed with Cellectis-manufactured product (Process 2, or P2). In this dataset, P2 was associated with higher response rate than P1:

• Complete Remission (CR) / Complete Remission with complete hematologic Recovery (CRi) rate: 18% for P1 vs 36% for P2

At Dose Level 3, Process 2 (DL3), the recommended Phase 2 dose (RP2D), 12 patients were dosed (n=12):

• The CR/CRi rate was 42%, with 80% of these responders achieving MRD-negative status

For the subset of 9 patients who met the criteria of the pivotal Phase 2 population (Process 2, DL3, age ≤ 50):

• The CR/CRi rate was 56% with 80% of responders MRD-negative

• The ORR was 100% with MRD-negative in 78%

In patients treated with P2, 13 patients had relapsed after prior CD22 targeted therapy (Inotuzumab). Of these 13 patients, 4 (31%) achieved CR/CRi with MRD-negative status and all 4 achieved hematopoietic stem cell transplantation (HSCT). In the overall P2 cohort, the ORR was 68% with MRD-negativity in 83% of responders.

At the RP2D (DL3) subset (n=12), 7 of these 12 patients had prior inotuzumab exposure with 43% achieving MRD-negative CR/CRi, and all of these patients achieved HSCT.

In the P2 cohort (n=22), 11 of 22 patients (50%) received 3 prior targeted therapies-CD19 CAR-T, blinatumumab and inotuzumab. Among these heavily pretreated patients, 36% achieved CR/CRi with MRD-negative status.

The survival curve for this study suggests a clear benefit: patients who proceeded to HSCT after lasme-cel (UCART22) therapy showed a trend to longer overall survival than those who did not undergo transplant.

The Phase 1 data showed that lasme-cel (UCART22) maintained its efficacy regardless of the number or type of previous treatments, including CAR-T (60% of patients), transplant (50% of patients), and blinatumomab (80% of patients).

Following successful End-of-Phase 1 meetings with the U.S Food and Drug Administration (FDA) and the European Medicines Agency (EMA), Cellectis provided a registration path for lasme-cel as a bridge to transplant in r/r ALL. The first patient in pivotal Phase 2 is expected to be enrolled in Q4 2025. Cellectis anticipates submitting a Biologics License Application (BLA) in 2028.

EXHIBITS

Exhibit		Title
99.1		Press release dated October 16, 2025
99.2		Investors R&D Day Presentation dated October 16, 2025

SIGNATURES

Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned, thereunto duly authorized.

				CELLECTIS S.A.
October 16, 2025				By:		/s/ André Choulika
						André Choulika
						Chief Executive Officer

FAQ

What did Cellectis (CLLS) report about UCART22 in the BALLI-01 Phase 1 study?

The company reported lasme-cel (UCART22) was generally well-tolerated and showed activity, with a 68% overall response rate in the Process 2 cohort and 83% MRD-negativity among responders.

How did patients previously treated with inotuzumab respond in Process 2?

Among 13 patients relapsed after prior CD22 therapy (inotuzumab), 31% achieved CR/CRi with MRD-negative status and all four proceeded to HSCT.

What were outcomes for heavily pretreated patients in the Process 2 cohort?

In patients who had CD19 CAR-T, blinatumomab and inotuzumab (n=22), 36% achieved MRD-negative CR/CRi.

What is the recommended Phase 2 dose (RP2D) for UCART22 and how did it perform?

The RP2D is Dose Level 3 (DL3). In the DL3 subset (n=12), 7 had prior inotuzumab and 43% achieved MRD-negative CR/CRi, with all undergoing HSCT.

When will Cellectis start the pivotal Phase 2 trial of UCART22?

The first patient is expected to be enrolled in Q4 2025.

When does Cellectis anticipate submitting a BLA for UCART22?

Cellectis anticipates submitting a Biologics License Application in 2028.

What safety profile was observed for UCART22 in Phase 1?

Safety was generally consistent with CAR-T expectations, including manageable cytokine release syndrome (CRS) and ICANS.