The data will be presented in a poster: 

Title: TALE-based epigenetic modulators show sustained knock-down of target genes in T-cells and HEPG2 via a high-throughput multiplex screening platform

Transcription activator-like effector-based epigenetic modulators (TALEM) are engineered fusion proteins consisting of a TALE DNA-binding domain with functional domains that mediate epigenetic modifications. These proteins can be precisely guided to a target location in the genome to switch genes on or off through a process known as epigenetic editing.

Unlike traditional gene editing tools, this approach does not induce DNA breaks and DNA sequence modifications, making it a potentially safer alternative for genome editing.

In this work, Cellectis developed a high-throughput screening system capable of rapidly assembling and testing hundreds of these TALEM, identifying which combinations are most effective at regulating a given gene.

The results:

This strategy was used for two distinct genes: one highly expressed in hepatocytes (active in liver cells) and another implicated in T-cell dysfunction and exhaustion, a key challenge in cancer immunotherapy. In both cases, the approach achieved >90% reduction in gene activity, which remained stable throughout the study.

“We are excited to present these results at ASGCT, which demonstrate Cellectis’ ability to apply its gene editing platform into the emerging field of epigenetic editing” said Louisa Mayer, Ph.D., Scientist II and Supervisor - Innovation & Gene Editing at Cellectis. “This work shows our ability to design and identify highly potent epigenetic editors across different cell types, thereby enriching our gene‑editing toolbox.”

The abstract is published on the ASGCT website. The poster will be available on Cellectis’ website on the presentation day, Wednesday May 13, 2026 at 5 pm ET.  

Allogene announced the futility analysis, which was triggered by the protocol-defined data cutoff of the 24th patient completing Day 45 minimal residual disease (“MRD”) assessment, showed that 58.3% (7/12) of patients in the cema-cel arm achieved MRD negativity compared to 16.7% (2/12) in the observation arm, representing a 41.6% absolute difference in MRD clearance between the arms. Allogene reported that based on specific benchmark literature, a difference of 25-30% in the MRD clearance could translate into meaningful clinical benefit at study completion. Allogene further announced that the cema-cel treatment was generally well-tolerated as of the cutoff, with most patients (10/12) managed in the outpatient setting post-infusion, no cases of cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), graft-versus-host disease (GvHD) or treatment-related Serious Adverse Events, and no hospitalizations for treatment-related Adverse Events. For more details on the data announced by Allogene, please refer to Allogene’s press release click here.  

"Seeing cema-cel advance in a pivotal trial is a great moment. Cema-cel derives from the first allogeneic CAR-T ever made, UCART19, as Cellectis has pioneered the concept of allogeneic “off-the-shelf" cell therapy, a concept many considered impossible. The data disclosed by Allogene is a testament to that vision, as we believe our allogeneic platform will replace autologous CAR-T therapies and expand their use in more indications. We warmly congratulate Servier and Allogene on this milestone and look forward to the continued development of cema-cel" said André Choulika, Ph.D., Co-Founder and Chief Executive Officer of Cellectis.  

Cema-cel, which is derived from the UCART19 product initially developed by Cellectis, is an anti-CD19 allogeneic CAR-T cell therapy. Unlike autologous CAR-T therapies, which are manufactured from each patient's own T-cells, cema-cel is derived from healthy donor T-cells. We believe that allogeneic treatment have the potential to overcome many of the challenges of autologous cell therapies including speed, accessibility, and product consistency, while offering a path to make cell therapies mainstream pharmaceutical products. 

Allogene announced that study accrual is anticipated to be complete by the end of 2027 and that it anticipates an interim Event-Free Survival (EFS) analysis in mid-2027 and the primary EFS analysis in mid-2028. If positive, Allogene announced that these results could support a Biologics License Application (BLA) submission. Under the Servier Agreement, Cellectis is eligible to receive payments up to $340 million in development and sales milestones, as well as low double-digit royalties on net sales of licensed CD19 products, including cema-cel developed in LBCL. 

• Phase 1: 83% ORR at RP2D and 100% ORR in the target Phase 2 population
• In target Phase 2 population: 100% of patients became eligible to transplant
• Pivotal Phase 2 first interim analysis expected in Q4 2026
• BLA submission anticipated in 2028

Phase 1 with eti-cel in r/r NHL (NATHALI-01 trial) ongoing

• Best-in-class dual allogeneic CAR-T cell product targeting CD20 & CD22
• At current dose level, 88% ORR; 63% CR rate after 2+ prior lines of therapy
• 93% of subjects had prior CD19 CAR-T
• Low-dose IL-2 cohort to be included in; Full Phase 1 dataset expected in Q4 2026

Partnerships

• Servier (through Allogene): Pivotal randomized Phase 2 ALPHA3 trial with cema-cel in 1L consolidation in LBCL: interim futility analysis evaluating MRD clearance and early safety results planned for April 2026
• AstraZeneca: Activities progressing under the Joint Research and Collaboration Agreement

• Cash, cash equivalents and fixed-term deposits of $211 million as of December 31, 2025[1] provides runway into H2 2027
• Conference call scheduled on March 20, 2026 at 8:00 am ET / 1:00 pm CET

New York, NY – March 19, 2026 - Cellectis (the “Company”) (Euronext Growth: ALCLS - NASDAQ: CLLS), a clinical-stage biotechnology company using its pioneering gene editing platform to develop life-saving cell and gene therapies, today provided financial results for the fourth quarter and full year 2025, ending December 31, 2025 and provided a business update.

“Lasme-cel demonstrated a potentially transformative efficacy profile in one of oncology’s most challenging settings, achieving 100% overall response rate in the target Phase 2 population. Critically, lasme-cel converted all patients in the target population into transplant-eligible candidates. The pivotal Phase 2 is now enrolling, and with a BLA submission anticipated in 2028, lasme-cel is on a clear regulatory path to potentially becoming the first off-the-shelf CAR-T therapy to address this high unmet medical need” said André Choulika, Ph.D., Co-Founder and Chief Executive Officer of Cellectis. “With interim Phase 2 data for lasme-cel in r/r B-ALL, and full Phase 1 data for eti-cel in r/r NHL, both expected in Q4 2026, we are entering an important year for Cellectis, as we advance our ambition to bring life-saving off-the-shelf CAR-T therapies to patients who have run out of options”.

Allogeneic CAR-T Pipeline

Lasme-cel in relapsed or refractory B-cell acute lymphoblastic leukemia (r/r B-ALL) - BALLI-01

• In October 2025, Cellectis presented full Phase 1 lasme-cel clinical data at the Cellectis’ R&D Day. The presented data position lasme-cel as a potentially game-changing therapy for patients with r/r B-ALL. Data highlighted:

Strong efficacy:

• 68% overall response rate (ORR) with lasme-cel Process 2, manufactured internally (n=22)
• 83% ORR at the recommended Phase 2 dose (RP2D) (n=12)
• 100% ORR in the target Phase 2 population (n=9)

In the target Phase 2 population, the complete response or complete remission with incomplete hematology recovery (CR/Cri) rate was 56%, with approximately 80% of these patients achieving minimum residual disease (MRD)-negative status

Favorable safety profile:

• Low rates of ≥ grade 3 cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) at 2.5% and 5% respectively

Transplant eligibility in target Phase 2 population:

• All patients became eligible for transplant

Strong survival benefit:

• 14.8 months median overall survival (OS) in patients who achieved MRD-negative CR/CRi

The first interim analysis for the pivotal Phase 2 of the BALLI-01 trial is expected in Q4 2026 (n=40). Cellectis anticipates submitting a Biologics License Application (BLA) in 2028.

Eti-cel in relapsed or refractory non-Hodgkin lymphoma (r/r NHL) – NATHALI-01

• In December 2025, Cellectis presented encouraging Phase 1 preliminary data of eti-cel at the American Society of Hematology (ASH) annual meeting. The data showcased the potential of eti-cel in r/r NHL patients who have relapsed following multiple lines of therapy including, for 93% of patients, an autologous CD19 CAR-T, with an 88% ORR and 63% CR at the current dose level (n=8).
• Cellectis is initiating patient enrollment in the cohort with low dose interleukin-2 (IL-2) support to evaluate the potential to further enhance the already high response rates and durability of response in patients with r/r NHL.
• Cellectis expects to present the full Phase 1 dataset in 2026, including results from the IL-2 combination.

Circular single-stranded DNA (cssDNA) as a non-viral template for gene therapy

• In November 2025, Cellectis published a Nature Communications article establishing cssDNA as a highly efficient non-viral DNA donor template, for gene insertion in hematopoietic stem and progenitor cells (HSPCs).

While viral vectors such as AAV6 are commonly used for gene insertion, they raise safety and efficacy concerns. Over the past decade, non-viral DNA templates delivery has emerged as promising alternatives.

Cellectis’ research results mark a pivotal advance toward next-generation non-viral cell and gene therapies.

Key findings:

• Superior efficiency: cssDNA achieved over 40% knock-in efficiency, outperforming linear DNA by 3-5 times.
• Versatility: the process successfully targets multiple loci in HSPCs and primary T cells.
• Better persistence: in murine models, cssDNA-edited cells showed superior engraftment and edit maintenance compared to AAV6-edited cells.

TALE base editors (TALEB) safety and precision

• At ESGCT 2025, Cellectis presented a comprehensive safety study on TALE base editors (TALEB), which enable precise C-to-T DNA editing without causing double-strand breaks.

Key study highlights:

• Safety assessment: researchers used advanced bioinformatics and experimental models to track potential off-target effects in the nuclear genome of primary T cells.
• No bias detected: the study found no evidence of unintended editing at CTCF binding sites, which are critical for genome organization and gene expression.

These research results provide a strong framework for the safe development of TALEB in therapeutic cell engineering, supporting their potential for future nuclear and mitochondrial applications.

Partnerships

AstraZeneca – Joint Research and Collaboration Agreement

• Activities are progressing under the Joint Research and Collaboration Agreement with AstraZeneca, which leverages Cellectis’ gene editing expertise and manufacturing capabilities to develop up to 10 novel cell and gene therapy products for areas of high unmet medical need, including oncology, immunology and rare genetic disorders.

Servier (through its sublicensee Allogene) – Anti-CD19 CAR-T

• Under the Servier Agreement, Cellectis is eligible to up to $340 million in development and sales milestones as well as low double-digit royalties on sales.
• In December 2025, an arbitral tribunal has issued its decision in the arbitration proceedings against Les Laboratoires Servier and Institut de Recherches Internationales Servier IRIS SARL (“Servier”), relating to the License, Development and Commercialization Agreement entered into between Servier and Cellectis on March 6, 2019, as amended (the “Servier Agreement”). The Tribunal ruled on a partial termination of the License Agreement with respect to product UCART19 V1 (also referred to as “ALLO-501” by Allogene) and provided that Cellectis shall, at Allogene’s request, engage in good-faith discussions regarding the granting of a direct license to product UCART19 V1. All other claims brought by the parties were dismissed.

Allogene – Anti-CD70 CAR-T

• According to Allogene, the TRAVERSE trial in renal cell carcinoma has completed enrollment in its Phase 1b cohort, and Allogene is currently exploring partnering opportunities to advance the asset.

Iovance

• According to Iovance, new data across several pipeline programs is anticipated throughout 2026, including a Phase 1/2 trial investigating IOV-4001, a PD-1 inactivated TIL therapy, in previously treated advanced melanoma and NSCLC.

Corporate

Annual Shareholders Meeting

• On June 26, 2025, Cellectis held a Shareholders General Meeting. At the meeting, during which approximately 57% of voting rights were exercised, resolutions 1 through 23 and resolutions 25 and 26 were adopted, while resolution 24 was rejected, consistent with the recommendations of the Board of Directors. The detailed results of the vote and the resolutions are available on Cellectis’ website: https://www.cellectis.com/en/investors/general-meetings/

Board composition

• The Cellectis Shareholders' Meeting appointed Mr. André Muller as a director of the Company's Board of Directors. At the close of this meeting, the term of Mr. Axel-Sven Malkomes expired, and the previously announced resignation of Mr. Pierre Bastid became effective. In connection with these changes to the Board of Directors, the Board of Directors appointed Mr. André Muller, Dr. Donald Bergstrom, and Dr. Rainer Boehm as the members of the Company’s Audit Committee.

The publication will be followed by an investor conference call and webcast on Friday, March 20, 2026, at 8:00 AM ET / 1:00 PM CET. The call will include the Company’s fourth quarter and full year 2025 results and an update on business activities. Details for the call are as follows:

Dial in information:

Domestic: +1-800-579-2543

International: +1-785-424-1789

Conference ID: CLLSFY

Webcast Link: https://viavid.webcasts.com/starthere.jsp?ei=1747993&tp_key=8aa72cea7f

“2025 was a transformational year for Cellectis, as we transitioned to a late-stage development allogeneic CAR-T company with the initiation of a pivotal Phase 2 trial for lasme-cel.” said André Choulika, Ph.D., Chief Executive Officer of Cellectis. “As we enter 2026, we remain fully committed to executing our pivotal Phase 2 BALLI-01 trial for lasme-cel in ALL, with interim data expected in Q4, presenting the full Phase 1 data of the NATHALI-01 trial for eti-cel in NHL, and leveraging the momentum of our strategic partnership with AstraZeneca.”

Allogeneic CAR-T Pipeline

Lasme-cel in r/r B-ALL (BALLI-01)

Following the initiation of the pivotal Phase 2 BALLI-01 clinical trial in October 2025, Cellectis expects to complete the first interim analysis in Q4 2026. This upcoming milestone (n=40) builds upon the encouraging Phase 1 clinical data presented at the Cellectis’ R&D Day, which highlighted:

• Strong Efficacy: 68% overall response rate (ORR) with lasme-cel Process 2 (n=22), 83% at the recommended Phase 2 dose (RP2D) (n=12) and 100% in the target Phase 2 population (n=9). 56% complete remission or complete remission with incomplete hematologic recovery (CR/CRi) rate with ~80% of these patients achieving minimal residual disease (MRD)-negative status in the target Phase 2 population. 60% MRD- negative CR/CRi rate achieved in patients who relapsed following a prior CD22 targeted therapy.
• Strong Survival Benefit: 14.8 months median overall survival (OS) in patients who achieved MRD-negative CR/CRi.
• Favorable Safety Profile: lasme-cel was generally well tolerated, with a single case of grade 2 immune effector cell–associated hemophagocytic syndrome (IEC-HS), which resolved.

Eti-cel in r/r NHL (NATHALI-01)

Building on the preliminary Phase 1 data presented at the American Society of Hematology (ASH) Annual Meeting in December 2025, Cellectis is focused on maximizing the clinical impact of its dual-target CAR-T candidate:

• Phase 1 interim Results: The NATHALI-01 clinical trial demonstrated an encouraging ORR of 88% and a CR rate of 63% at the current dose level, showcasing the potential of eti-cel in r/r NHL patients who have relapsed following multiple lines of therapy including, for most patients, an autologous CD19 CAR-T.
• Q1 2026: Initiation of patient enrollment in the cohort with low dose interleukin-2 (IL-2) support to evaluate the potential to further enhance the already high response rates and durability of response in patients with r/r NHL.
• Q4 2026: The Company expects to report the full Phase 1 dataset, including results from the IL-2 combination.

Strategic Partnerships

AstraZeneca

• Activities are progressing under the Joint Research and Collaboration Agreement with AstraZeneca, which leverages Cellectis’ gene editing expertise and manufacturing capabilities to develop up to 10 novel cell and gene therapy products for areas of high unmet medical need, including oncology, immunology and rare genetic disorders.

Servier / Allogene

• CD19: Servier’s sublicensee Allogene announced that the H1 2026 interim futility analysis from the pivotal Phase 2 ALPHA3 Trial with cema-cel in first-line consolidation large B-cell lymphoma remains on track. Under the Servier agreement, Cellectis is eligible to up to $340 million in development and sales milestones as well as low double-digit royalties on sales.
• CD70: Allogene announced that the TRAVERSE trial in renal cell carcinoma has completed enrollment in its Phase 1b cohort, evaluating ALLO-316 in heavily pretreated patients, and that plans are ongoing to determine the next phase of the program.

Iovance

• Iovance announced that clinical results for IOV-4001, a PD-1 inactivated tumor- infiltrating lymphocyte (TIL) cell therapy, in previously treated advanced melanoma patients are anticipated in the first quarter of 2026, and that other potential indications for IOV-4001 are also in development.

Cash Runway

• Cellectis believes its cash, cash equivalents, and fixed-term deposits will be sufficient to fund its operations into H2 2027.

J.P. Morgan Healthcare Conference

Cellectis management will participate in the 44th Annual J.P. Morgan Healthcare Conference from January 12-15, 2026, and will be available for one-on-one investor meetings. To schedule a meeting, please contact Cellectis Investor Relations at investors@cellectis.com

The Tribunal ruled on a partial termination of the License Agreement with respect to product UCART19 V1 (also referred to as “ALLO-501” by Allogene) and provided that Cellectis shall, at Allogene’s request, engage in good-faith discussions regarding the granting of a direct license to product UCART19 V1. All other claims brought by the parties were dismissed.

New York, NY – December 8, 2025 – Cellectis (the “Company”) (Euronext Growth: ALCLS – NASDAQ: CLLS), a clinical-stage biotechnology company using its pioneering gene-editing platform to develop life-saving cell and gene therapies, announced the presentation of   encouraging updated data of patients treated in the Phase 1 NATHALI-01 clinical trial with eti-cel, at the 67^th Annual Meeting of the American Society of Hematology (ASH) in Orlando, FL.

Eti-cel product candidate is the first allogeneic dual CAR-T targeting CD20 and CD22 simultaneously, being developed in Phase 1 of the NATHALI-01 clinical trial, for patients with relapsed/refractory non-Hodgkin lymphoma (r/r NHL), following at least two lines of therapy.

Cellectis presented preliminary results on eti-cel, which demonstrated an encouraging overall response rate (ORR) of 88% and a complete response (CR) rate of 63% (n=8) at the current dose level.

Additional in vivo data presented suggest that exogenous low dose Interleukin-2 (IL-2) support can significantly enhance the expansion and persistence of CAR-T cells to boost CAR-T efficacy without exacerbating toxicity.  

“Cellectis believes that, with the addition of low dose IL-2 support, it is possible to further deepen the already high response rates seen with eti-cel in these patients who have relapsed following multiple prior lines of therapy including, in most cases, a CD19 CAR-T” said Adrian Kilcoyne, MD, MPH, MBA, Chief Medical Officer at Cellectis. “The trial will now investigate any potential impact of low dose IL-2 support in these difficult to treat patients. We look forward to sharing the full Phase 1 dataset expected in 2026.” 

Next Steps

Overall, these preliminary data underscore the potential of this innovative approach to transform outcomes for r/r NHL patients. The Company will now investigate the potential impact of low dose IL-2 support and will start recruitment of patients in the IL-2 support cohort in Q1 2026. Cellectis expects to present the full Phase 1 dataset in 2026.

The poster presentation will be available on Cellectis’ website.

Gene editing of HSPCs offers the potential for long-term therapeutic benefit. While viral vectors such as AAV6 are commonly used for gene insertion, they raise safety and efficacy concerns. Over the past decade, non-viral DNA templates delivery has emerged as promising alternatives and have been used with nucleases to target short single-stranded linear DNA corrective template in HSPCs.

Although non-viral approaches were initially limited to making only small corrections within defective genes, Cellectis harnessed its TALEN^® technology and CssDNA donor templates, to develop a robust gene insertion process. This process enables precise and efficient integration of large genetic sequences within therapeutically relevant subpopulations of HSPCs, significantly expanding the potential of non-viral gene therapy.

The results show that:

• CssDNA achieved 3-5 times higher knock-in efficiency than linear single stranded DNA (LssDNA), with values surpassing 40%.
• CssDNA can be used to insert genes at multiple loci in HSPCs and is applicable to other cell types of therapeutic interest, including primary T cells.
• Comparative studies also showed that CssDNA-edited HSPCs demonstrate a higher propensity to engraft and maintain gene edits in a murine model compared to AAV6-edited HSPCs.

“These results establish the CssDNA process as an efficient non-viral gene insertion strategy, and mark a pivotal advance towards the development of next-generation cell and gene therapies” said Julien Valton, Vice President of Gene Therapy of Cellectis.

The article is available on Nature Communications website here.

Lasme-cel in r/r B-ALL (BALLI-01)

• 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)
• Median OS of 14.8 months in patients who achieved MRD-negative CR/CRi
• First interim analysis for the BALLI-01 trial expected in Q4 2026

Eti-cel in r/r NHL (NATHALI-01)

• ORR of 86% and 57% CR rate (n=7)
• Development update to be presented at the ASH 2025 annual meeting
• Full Phase 1 dataset expected to be shared in 2026

• Servier arbitration: arbitral decision expected to be rendered on or before December 15, 2025
• Cash, cash equivalents and fixed-term deposits of $225 million as of September 30, 2025[1]provides runway into H2 2027

New York, NY – November 7, 2025 - Cellectis (the “Company”) (Euronext Growth: ALCLS - NASDAQ: CLLS), a clinical-stage biotechnology company using its pioneering gene editing platform to develop life-saving cell and gene therapies, today provided financial results for the third quarter 2025 ending September 30, 2025 and business updates.

“We are proud of the promising data from our core clinical product candidates. Our lasme-cel program for r/r B-ALL and eti-cel program for r/r NHL demonstrated their ability to induce deep and meaningful responses, underscoring their potential to improve outcomes in diseases with high unmet medical needs” said André Choulika, Ph.D., Chief Executive Officer at Cellectis. “We look forward to sharing an additional development update on eti-cel at the ASH 2025 Annual Meeting and to provide the first interim analysis for the pivotal Phase 2 BALLI-01 trial in Q4 2026. Together, these milestones strengthen our leadership in allogeneic CAR-T innovation and position Cellectis for a transformative year ahead."

Pipeline Highlights

UCART Clinical Programs

BALLI-01 study evaluating lasme-cel (UCART22)

• Clinical data from the Phase 1 BALLI-01 study with lasme-cel for the treatment of relapsed or refractory B-cell acute lymphoblastic leukemia (r/r B-ALL), were presented at the Cellectis’ R&D Day that took place on October 16, 2025. The presented data position lasme-cel as a potentially game-changing therapy for patients with r/r B-ALL.

In the Phase 1 of BALLI-01 study, 40 transplant ineligible third line or beyond (3L+) patients were dosed with lasme-cel: 18 patients (n=18) were dosed with product manufactured by an external CDMO (Process 1, or P1) and 22 patients (n=22) were dosed with Cellectis-manufactured product (Process 2, or P2).

Highlights include:

• • Efficacy: lasme-cel demonstrated an overall response rate (ORR) of 68% with Process 2 product (n=22), and an ORR of 83% at the recommended Phase 2 dose (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; there was one case of grade 2 immune effector cell–associated hemophagocytic syndrome (IEC-HS), which resolved.
• • Durability: among patients who achieved minimal residual disease (MRD)-negative complete remission or complete remission with incomplete hematologic recovery (CR/CRi), median overall survival was 14.8 months.
• • Depth of response in target Phase 2 population: the CR/CRi rate was 56%, with approximately 80% of these patients achieving MRD-negative status.
• • Transplant eligibility in target Phase 2 population: all patients (100%) became eligible for transplant, and 78% proceeded to transplantation.

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

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

• 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 in r/r ALL. The first interim analysis for the Phase 2 of the BALLI-01 trial is expected in Q4 2026. Cellectis anticipates submitting a Biologics License Application (BLA) in 2028.

Commercial Opportunity for Lasme-cel

• As part of the R&D Day presentation, the Company discussed the potential commercial opportunity for lasme-cel in r/r B-ALL.

If approved for commercialization, Cellectis estimates that lasme-cel could achieve up to approximately $700 million in potential peak gross sales across the U.S., EU4 (France, Germany, Italy, Spain) and UK in 2035, corresponding to an estimation of about 1,100 patients treated annually. Furthermore, gross peak sales could increase to up to approximately $1.3 billion with potential label expansion to second line and first line MRD+ consolidation. These estimates highlight that lasme-cel has the potential to drive meaningful growth of the CAR-T market in B-ALL, leading to a robust peak sales potential with attractive margins stemming from the allogeneic approach.

American Society of Hematology (ASH) 2025 annual meeting poster presentation

• On November 3, 2025, Cellectis announced the acceptance of an abstract for lasme-cel for poster presentation at the American Society of Hematology (ASH) 2025 annual congress, that will take place on December 6-9, 2025.
• The poster highlights the correlation between alemtuzumab exposure and depth of response in the difficult-to-treat r/r ALL patients who have received lasme-cel. Additionally, the data identifies a threshold exposure level of alemtuzumab above which achieving a complete response/complete response with incomplete hematologic recovery (CR/CRi) is more likely without any increase in toxicities.

The poster presentation will occur on December 8, 2025, 6:00 PM - 8:00 PM ET, in Room OCCC - West Halls B3-B4.

NatHaLi-01 study evaluating eti-cel (UCART20x22)

• At the R&D Day, Cellectis unveiled preliminary data on eti-cel, its allogeneic CAR-T product candidate for relapsed or refractory non-Hodgkin lymphoma (r/r NHL), demonstrating an encouraging ORR of 86% and CR rate of 57% at the current dose level (n=7), with 4 out of 7 patients achieving a complete response. The preliminary high rate of complete responses underscores the potential of this innovative approach to transform outcomes for r/r NHL patients. Cellectis expects to present the full Phase 1 dataset for eti-cel, including low-dose IL-2 combination cohorts, in 2026.
• On November 3, 2025, Cellectis announced the acceptance of an abstract for poster presentation at ASH 2025.

The poster provides a development update on eti-cel for patients with r/r NHL and outlines the addition of low dose interleukin-2 (IL-2) to further deepen and extend anti-tumor activity of eti-cel in patients with r/r NHL, supported by compelling preclinical data.

The poster presentation will occur on December 7, 2025 at 6:00 PM – 8:00 PM ET, in Room OCCC – West Halls B3-B4.

Innovation

Circular single-stranded DNA (CssDNA) as a non-viral template for gene therapy

• In October 2025, Cellectis presented findings in a poster, highlighting the strong potential of circular single-stranded DNA (CssDNA) as a universal, efficient non-viral template for gene therapy, at the European Society of Gene and Cell Therapy (ESGCT) annual congress.

Over the past decade, non-viral DNA template delivery has been used with engineered nucleases to target single-stranded DNA sequences in hematopoietic stem and progenitor cells (HSPCs).

While developed for gene therapy purposes, so far this method has been restricted to gene corrections. To expand this scope, Cellectis developed an editing process using its gene editing technology and kilobase-long circular single-stranded DNA donor templates.

The data presented show that:

• CssDNA editing process achieved high gene insertion frequency in viable HSPCs.
• CssDNA-edited HSPCs show a higher propensity to engraft and maintain gene edits in a murine model than adeno-associated viruses (AAV)-edited HSPCs.

TALE base editors (TALEB) off-targets in the nuclear genome

• At ESGCT 2025, the Company presented in a poster a comprehensive study of TALE base editors (TALEB) off-targets in the nuclear genome.

TALE base editors (TALEB) are fusions of a transcription activator-like effector domain (TALE), split-DddA deaminase halves, and an uracil glycosylase inhibitor (UGI).

These recent additions to the genome editing toolbox can directly edit double strand DNA, converting a cytosine (C) to a thymine (T) through the formation of an uracil (U) intermediate without the need of DNA break. Base editing has great potential in therapeutic applications. However, being able to avoid potential off-target effects is key toward this goal.

To evaluate TALEB safety, Cellectis combined advanced bioinformatic predictions with multiple experimental approaches to investigate potential off-target effects in the nuclear genome of primary T cells.

The study found no evidence of biases towards off-site C-to-T editing at sites flanked by CTCF binding sites, a key DNA-binding protein that regulates genome organization and gene expression at genome wide level.

These results provide a strong framework for the safe development of TALEB in therapeutic cell engineering, supporting their potential for future nuclear and mitochondrial applications.

AstraZeneca – Joint Research and Collaboration Agreement

• In its presentation during the Cellectis’ R&D Day held in October, AstraZeneca highlighted the significance of its strategic investment and research collaboration with Cellectis to accelerate its cell therapy and genomic medicine ambitions. The collaboration leverages Cellectis’ gene editing expertise and manufacturing capabilities to develop up to 10 novel cell and gene therapy products for areas of high unmet medical need, including oncology, immunology and rare genetic disorders.

Servier arbitration

• With respect to the ongoing arbitration proceeding through the Centre de Médiation et d’Arbitrage de Paris, the arbitral decision is expected to be rendered on or before December 15, 2025.

Iovance

• In November 2025, Iovance reported that clinical results for IOV-4001, a PD-1 inactivated TIL cell therapy, in previously treated advanced melanoma patients are anticipated in the first quarter of 2026. Other potential indications for IOV-4001 are also in development.

• Preclinical data demonstrated that combining eti-cel with low-dose IL-2 may deepen and extend anti-tumor activity in patients with r/r NHL

• Eti-cel full Phase 1 dataset, including low-dose IL-2 combination cohorts, expected to be presented in 2026

• Correlation between alemtuzumab exposure and response with lasme-cel (UCART22) allows optimization of efficacy without an increase in toxicities

New York, NY – November 3, 2025 - Cellectis (the “Company”) (Euronext Growth: ALCLS - NASDAQ: CLLS), a clinical-stage biotechnology company using its pioneering gene-editing platform to develop life-saving cell and gene therapies, announced today the acceptance of two abstracts for poster presentation at the American Society of Hematology (ASH) 2025  annual meeting taking place from December 6 to 9, 2025, in Orlando, FL.

First poster – Development update on eti-cel

The first poster provides a development update on eti-cel product candidate (UCART20x22), an allogeneic dual CAR-T targeting CD20 and CD22 being developed in Phase 1 of the NATHALI-01 clinical trial, for patients with relapsed/refractory non Hodgkin lymphoma (r/r NHL). In addition, the poster outlines the addition of low dose interleukin-2 (IL-2) to further deepen and extend anti-tumor activity of eti-cel in patients with r/r NHL, supported by compelling preclinical data.

Cellectis unveiled preliminary results on eti-cel, which demonstrate an encouraging overall response rate (ORR) of 86% and a complete response (CR) rate of 57% at the current dose level (n=7), with 4 out of 7 patients achieving a complete response. The preliminary high rate of complete responses underscores the potential of this innovative approach to transform outcomes for r/r NHL patients. Cellectis expects to present the full Phase 1 dataset for eti-cel, including low-dose IL-2 combination cohorts, in 2026.

“We are excited by the progress and evolution of the eti-cel program with the addition of IL-2, which promises to build on the encouraging preliminary response rates observed in the Phase 1 program,” said Adrian Kilcoyne, MD, MPH, MBA, Chief Medical Officer at Cellectis.  “We look forward to sharing the full Phase 1 dataset including the IL-2 cohorts expected in 2026.”

Poster title: Trial in progress: Open-label dose-finding and dose-expansion study to evaluate the safety, expansion, persistence, and clinical activity of UCART20x22 in subjects with relapsed or refractory B-cell non-Hodgkin lymphoma (B-NHL) NATHALI-01

Presenter: Vivian Dai, Senior Director, Clinical Research Scientist at Cellectis

Date/Time: December 7, 2025 at 6:00 PM – 8:00 PM ET

Room: OCCC – West Halls B3-B4

Second poster – Correlation between alemtuzumab exposure and response with lasme-cel

The second poster highlights the correlation between alemtuzumab exposure and depth of response in the difficult-to-treat patients who have received lasme-cel (UCART22) in the course of the Phase 1 of BALLI-01, a clinical trial testing this allogeneic CAR-T product candidate targeting CD22 in relapsed/refractory acute lymphoblastic leukemia (ALL). Additionally, the data identifies a threshold exposure level of alemtuzumab above which achieving a complete response/complete response with incomplete hematologic recovery (CR/CRi) is more likely without any increase in toxicities.

“We strongly believe in the critical role of alemtuzumab in optimizing responses in these heavily pretreated patients,” said Adrian Kilcoyne, MD, MPH, MBA, Chief Medical Officer at Cellectis.  “These data have confirmed this and demonstrated that we could further enhance the high CR/CRi and minimal residual disease (MRD)-negative rates observed in our Phase 1 program. We look forward to starting enrollment in our pivotal Phase 2 program in Q4 2025.”

Poster title: Increased alemtuzumab exposure correlates with improved responses in heavily pretreated R/R ALL patients: Analysis of the BALLI-01 trial

Presenter: Xenia Naj, Ph.D., Director Translational Sciences at Cellectis

Date/Time: December 8, 2025, 6:00 PM - 8:00 PM

Room: OCCC - West Halls B3-B4

These abstracts can now be accessed here

The press release will be available in the Investors section of Cellectis’ website: https://www.cellectis.com/en/investors/press-releases/

Cellectis will not host a conference call to discuss these results. Our investors relations team remains available for questions at investors@cellectis.com

• 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 patients 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

• Potential peak gross sales of up to ~$700 million across the U.S., EU4, UK

New York, NY – October 16, 2025 - Cellectis (the “Company”) (Euronext Growth: ALCLS - NASDAQ: CLLS), a clinical-stage biotechnology company using its pioneering gene editing platform to develop life-saving cell and gene therapies, today hosted an R&D Day providing promising clinical data from the Phase 1 BALLI-01 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 Company unveiled the design of the pivotal Phase 2, its planned registration path for lasme-cel's initial indication, as well as the commercial opportunity. The event also included panel discussions with global hematology experts on the potential of lasme-cel to address the significant unmet need for heavily pretreated patients.

“We are encouraged by the Phase 1 results of the BALLI-01 study in a population that had largely exhausted treatment options and faced a poor prognosis. The depth of response we observed, enabling a high percentage of patients in the study to proceed to transplant, with the potential for durable remission, is clinically meaningful. We are focused on rapidly advancing our pivotal Phase 2 program and bringing lasme-cel to patients with this significant unmet need”, said Adrian Kilcoyne, MD, MPH, MBA, Chief Medical Officer of Cellectis.

“Today, Cellectis’ has reached a tipping point as we move lasme-cel into a pivotal Phase 2 trial. The need in refractory or relapsed B-ALL, especially for adult patients for whom every day counts, is significant. Our strategy is to achieve minimal residual disease-negative (MRD-negative) complete remission to create a window for hematopoietic stem cell transplantation and meaningfully improve overall survival. Cellectis is pioneering allogeneic CAR-T therapies that aim to be safer, faster, and more scalable and accessible therapy. Lasme-cel is designed to be off-the-shelf, ready when the patient is ready, so it may enable rapid disease control instead of waiting, potentially bringing more patients to the point where transplant becomes possible”, said André Choulika, Ph.D., Chief Executive Officer of Cellectis. “That is why an allogeneic CD22 approach is not just another CD19 program, it is potential solution for a broader patient population facing r/r B-ALL.”

BALLI-01 Phase 1 Study Evaluating lasme-cel

The Phase 1 of BALLI-01 clinical study was designed to evaluate the safety and clinical activity of lasme-cel in patients with r/r B-ALL.

The BALLI-01 trial enrolled 40 patients aged 15–70 years expressing >70% CD22 on leukemic blasts. Subjects were heavily pretreated with a median of 4 prior lines of therapy: 80% of subjects had received prior blinatumomab, approximately half had received prior inotuzumab and prior CD19 autologous CAR-T therapy.

Lasme-cel 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 Phase 1 of BALLI-01 study, 40 transplant ineligible 3L+ patients were dosed with lasme-cel: 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 P2 (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 69% with MRD-negativity in 83% of responders. 

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

In the P2 cohort, 11 of 22 patients 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 therapy showed a trend to longer overall survival than those who did not undergo transplant.

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

Taken together, these findings position lasme-cel as a potentially game-changing therapy for patients with r/r B-ALL.

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.

B-ALL Panel

Cellectis’ R&D Day also included a panel discussion on the potential of lasme-cel to address the significant unmet need for r/r B-ALL patients. Panelists included:

Pr. Nitin Jain, Professor of Medicine Department of Leukemia at MD Anderson Cancer Center

Pr. Nicolas Boissel, Head of the Adolescents and Young Adults Unit of the Hematology Department of Hôpital Saint-Louis AP-HP

Dr. Aravind Ramakrishnan, Leading Oncologist and Program medical Director for the Sarah Cannon Transplant & Cellular Therapy Program

Commercial Opportunity for Lasme-cel

As part of the R&D Day presentation, the Company discussed the potential commercial opportunity for lasme-cel in r/r B-ALL.

If approved for commercialization, Cellectis estimates that lasme-cel has the potential to reach up to approximately 1,900 addressable 3L+ B-ALL patients annually in 2035 across the U.S., EU4 (Germany, France, Spain, Italy) and UK. Of the projected incident 1L treated B-ALL population of approximately 9,200 patients, about 45% are expected to progress to 2L (mostly adolescents and adults given better outcomes for children) and two-thirds of patients treated in the 2L setting are expected to go on to require further therapeutic intervention. Finally, approximately 70% of patients treated in the 3L setting are considered for clinical allogeneic CAR-T eligibility based on patient fitness and comorbidities.

Lasme-cel is positioned to potentially capture a majority of such addressable market given that it provides an alternative target to CD19, one-time dosing, off-the-shelf availability and deep, MRD-responses in the 3L+ setting. Interviewed physician key opinion leaders indicated an expectation to use lasme-cel in a majority of 3L+ patients if available, and oncology analogs suggest an illustrative lasme-cel preference share of about 65% among eligible patients.

Finally, lasme-cel has high pricing potential across the U.S., EU4 and UK. For the EU4 and UK, Cellectis triangulated an illustrative lasme-cel 2025 anchor price of approximately $365,000 from the averaged CAR-T price range, with a projected list price in 2035 assumed to remain constant with 2025. For the U.S., Cellectis triangulated an illustrative lasme-cel 2025 anchor price of approximately $515,000 from the averaged CAR-T price range, with a projected 2035 list price, assumed to grow at a ~5% CAGR (Compound Annual Growth Rate) based on the 2021-2025 price growth.[2]

With the above assumptions, lasme-cel could achieve up to approximately $700 million in potential peak gross sales across the U.S., EU4 and UK in 2035, corresponding to an estimation of about 1,100 patients treated annually. Furthermore, gross peak sales could increase to up to approximately $1.3 billion with potential label expansion to second line and first line MRD+ consolidation. These estimates highlight that lasme-cel has the potential to drive meaningful growth of the CAR-T market in B-ALL, leading to a robust peak sales potential with highly attractive margins stemming from the allogeneic approach.

NatHaLi-01 study evaluating eti-cel (UCART20x22)

Cellectis unveiled preliminary data on eti-cel, its allogeneic CAR-T product candidate for relapsed or refractory non-Hodgkin lymphora (r/r NHL). These preliminary results demonstrate an encouraging overall response rate (ORR) of 86% and a complete response (CR) rate of 57% at the current dose level (n=7), with 4 out of 7 patients achieving a complete response.

The preliminary high rate of complete responses underscores the potential of this innovative approach to transform outcomes for r/r NHL patients. Further updates on the program are expected at the end of the year 2025.

Strategic Partnership with AstraZeneca

In its presentation during the R&D Day, AstraZeneca highlighted the significance of its strategic investment and research collaboration with Cellectis to accelerate its cell therapy and genomic medicine ambitions. The collaboration leverages Cellectis’ gene editing expertise and manufacturing capabilities to develop up to 10 novel cell and gene therapy products for areas of high unmet medical need, including oncology, immunology and rare genetic disorders.

Webcast details

A replay of today’s event and copy of the presentation will be published on Cellectis’ website.

New York, NY – October 16, 2025 – Cellectis (the “Company”) (Euronext Growth: ALCLS - NASDAQ: CLLS), a clinical-stage biotechnology company using its pioneering gene editing platform to develop life-saving cell and gene therapies, today hosts a R&D Day in New York City. The Company’s leadership team and key opinion leaders will present the full Phase 1 dataset and outline the pivotal Phase 2 trial design and commercial opportunity for lasme-cel in r/r B-ALL.

Details of the Event:

• Date: Today, October 16, 2025
• Time: 08:30 – 10:30 a.m. ET
• Format: In-person and live webcast
• Webcast: Join live via https://us06web.zoom.us/j/84630848404

A replay will be available after the event on the Cellectis website

Poster presentation:

Title: Circularization of Single-Stranded DNA Donor Template Unleashes the Power of Non-Viral Gene Delivery for Long-Term HSCs editing

Presenter: Julien Valton, Ph.D., Vice President Gene Therapy at Cellectis

Date/Time: Wednesday, October 8, 2025 from 2:00 p.m. to 3:30 p.m. CET

Poster number: P0439

Over the past decade, non-viral DNA template delivery has been used with engineered nucleases to target single-stranded DNA sequences in hematopoietic stem and progenitor cells (HSPCs).

While developed for gene therapy purposes, so far this method has been restricting to gene corrections. To expand this scope, Cellectis developed an editing process using its gene editing technology and kilobase-long circular single-stranded DNA donor templates.

Research data show that:

· CssDNA editing process achieved high gene insertion frequency in viable HSPCs.

· CssDNA-edited HSPCs show a higher propensity to engraft and maintain gene edits in a murine model than adeno-associated viruses (AAV)-edited HSPCs.

These data highlight the strong potential of CssDNA as a universal and efficient non-viral DNA template for gene therapy applications.

The research was also presented as an oral presentation at the Homology-Directed Repair: The Path Forward Workshop in Sevilla on October 6, 2025.

Poster presentation:

Title: Comprehensive analysis of TALEB off-target editing  

Presenter: Maria Feola, Ph.D., Senior Scientist, Team Leader Gene Editing at Cellectis

Date/Time: Thursday, October 9, 2025 from 2:00 p.m. to 3:30 p.m. CET

Poster number: P0506

TALE base editors (TALEB) are fusions of a transcription activator-like effector domain (TALE), split-DddA deaminase halves, and an uracil glycosylase inhibitor (UGI).

These recent additions to the genome editing toolbox can directly edit double strand DNA, converting a cytosine (C) to a thymine (T) through the formation of an uracil (U) intermediate without the need of DNA break. Base editing has great potential in therapeutic applications. However, being able to avoid potential off-target effects is key toward this goal.

To evaluate TALEB safety, Cellectis combined advanced bioinformatic predictions with multiple experimental approaches to investigate potential off-target effects in the nuclear genome of primary T cells.

The study found no evidence of biases towards off-site C-to-T editing at sites flanked by CTCF binding sites, a key DNA-binding protein that regulates genome organization and gene expression at genome wide level.

These results provide a strong framework for the safe development of TALEB in therapeutic cell engineering, supporting their potential for future nuclear and mitochondrial applications.

The poster presentations are now published on Cellectis’ website.

• Cellectis to host an Investor R&D Day in New York City on October 16, 2025: Phase 1 dataset and late-stage development strategy for lasme-cel (UCART22) in r/r B-ALL to be presented
• End-of-Phase 1 meetings with FDA & EMA for lasme-cel (UCART22) in r/r B-ALL completed in July 2025; on track to launch pivotal Phase 2 in H2 2025
• Servier arbitration: arbitral decision expected to be rendered on or before December 15, 2025
• eti-cel (UCART20x22): Phase 1 study in r/r NHL ongoing with readout expected in late 2025
• AstraZeneca partnership: R&D activities are continuing to advance for the three programs initiated
• Appointment of Mr. André Muller as Director to Cellectis’ Board of Directors
• Cash, cash equivalents and fixed-term deposits of $230 million as of June 30, 2025[1] provides runway into H2 2027
• Conference call and webcast scheduled for tomorrow, August 5, 2025 at 8:00AM ET / 2:00PM CET

New York, NY – August 4, 2025 - Cellectis (the “Company”) (Euronext Growth: ALCLS - NASDAQ: CLLS), a clinical-stage biotechnology company using its pioneering gene editing platform to develop life-saving cell and gene therapies, today provided financial results for the second quarter 2025 ending June 30, 2025 and business updates.

“I am pleased to announce that Cellectis will host an Investor R&D Day in New York City on October 16, 2025. The Company’s leadership team and key opinion leaders will present the Phase 1 dataset and outline the late-stage development strategy for lasme-cel (UCART22) in r/r B-ALL and will share insights on the Company’s vision and differentiated capabilities,” said André Choulika, Ph.D., Chief Executive Officer at Cellectis.

“Our teams have remained focused on advancing research and developing solutions for patients with unmet medical needs. In July 2025, we completed the end-of-Phase 1 multidisciplinary meetings with both the FDA and EMA for lasme-cel in r/r B-ALL. We are excited about a pivotal Phase 2 which we expect to initiate in the second half of this year.”

Pipeline Highlights

UCART Clinical Programs

BALLI-01 study evaluating lasme-cel (UCART22) in relapsed or refractory B-cell acute lymphoblastic leukemia (r/r B-ALL)

• In July 2025, Cellectis completed the multidisciplinary end-of-Phase 1 regulatory interactions with both the Food and Drug Administration (FDA) and the European Medicines Agency (EMA). Preparations are currently underway in anticipation for an amendment to initiate a pivotal Phase 2 of lasme-cel in r/r B-ALL, which is expected in H2 2025.

• Cellectis will present the Phase 1 dataset and late-stage development strategy for lasme-cel in r/r B-ALL at an Investor R&D Day that will take place on October 16, 2025 in New York City.

NatHaLi-01 study evaluating eti-cel (UCART20x22) in relapsed or refractory B-cell non-Hodgkin lymphoma (r/r NHL)

• Cellectis continues to focus on the enrollment of patients in the NatHaLi-01 study and expects to present a Phase 1 readout for eti-cel in r/r NHL in late 2025.

Partnerships

Servier – Anti-CD19 CAR-T

• In May 2025, Allogene Therapeutics, Inc. (“Allogene”), Servier’ sublicensee, announced that, as part of the ALPHA3 clinical trial evaluating cemacabtagene ansegedleucel (cema-cel) in first-line consolidation for large B-cell lymphoma, the milestone for lymphodepletion regimen selection and futility analysis has been shifted by approximately two quarters and is now expected by Allogene in the first half of 2026.

• On August 1, 2025, Allogene announced that it has selected standard fludarabine and cyclophosphamide (FC) as the lymphodepletion regimen to be used in its ALPHA3 study. The arm testing FC plus ALLO-647, an anti-CD52 mAb (FCA), is now closed to further enrollment. According to Allogene, this decision, made ahead of the scheduled futility analysis, was prompted by a Grade 5 adverse event in the FC plus ALLO-647 arm that has been attributed to the use of ALLO-647. According to Allogene, this event was deemed unrelated to cema-cel. Allogene further announced that the amended ALPHA3 trial now proceeds as a randomized study with two arms, comparing cema-cel after standard FC lymphodepletion to observation, the current standard of care. Statistical design of the trial and the prespecified study conduct remain the same. The next milestone will be the futility analysis comparing MRD conversion and is expected by Allogene to occur 1H 2026.

Allogene – Anti-CD70 CAR-T

• In June 2025, Allogene presented updated data from the Phase 1 TRAVERSE study of ALLO-316 in renal cell carcinoma during an oral presentation at the 2025 ASCO Annual Meeting. The presentation focused on the Phase 1b expansion cohort from the Phase 1 TRAVERSE study in which patients were treated with a standard regimen of cyclophosphamide and fludarabine following by a single dose of 80 million CAR-T cells.

AstraZeneca – Joint Research and Collaboration Agreement

• Research and development activities are continuing to advance for the three cell and gene therapy programs under our Joint Research and Collaboration Agreement with AstraZeneca in November 2023 (the “AZ JRCA”): one allogeneic CAR-T for hematological malignancies, one allogeneic CAR-T for solid tumors, and one in vivo gene therapy for a genetic disorder.

Servier arbitration

• With respect to the ongoing arbitration proceeding through the Centre de Médiation et d’Arbitrage de Paris, the arbitral decision is expected to be rendered on or before December 15, 2025.

Corporate Updates

Annual Shareholders’ Meeting

• On June 26, 2025, Cellectis held a Shareholders General Meeting at the Biopark auditorium in Paris, France. At the meeting, during which approximately 57% of voting rights were exercised, resolutions 1 through 23 and resolutions 25 and 26 were adopted, while resolution 24 was rejected, consistent with the recommendations of the Board of Directors. The detailed results of the vote and the resolutions are available on Cellectis’ website: https://www.cellectis.com/en/investors/general-meetings/

• The Cellectis Shareholders' Meeting appointed Mr. André Muller as a director of the Company's Board of Directors, with immediate effect. In addition, at the close of this meeting, the term of Mr. Axel-Sven Malkomes expired, and the previously announced resignation of Mr. Pierre Bastid became effective. In connection with these changes to the Board of Directors, the Board of Directors appointed André Muller, Donald Bergstrom, and Rainer Boehm as the members of the Company’s Audit Committee.

The publication will be followed by an investor conference call and webcast on Tuesday August 5, 2025 at 8:00 AM ET / 2:00 PM CET. The call will include the Company’s second quarter results and an update on business activities.

Details for the call are as follows:

Dial in information:

Domestic: +1-800-343-5172

International: +1-203-518-9856

Conference ID: CLLSQ2

Webcast Link: https://viavid.webcasts.com/starthere.jsp?ei=1727030&tp_key=10a62ee950

At the meeting, during which approximately 57% of voting rights were exercised, resolutions 1 through 23 and resolutions 25 and 26 were adopted, while resolution 24 was rejected, consistent with the recommendations of the board of directors.

The Cellectis shareholders' meeting appointed Mr. André Muller as a member of the Company's Board of Directors, with immediate effect. In addition, at the close of the AGM, the term of Mr Axel-Sven Malkomes expired, and the previously announced resignation of Mr. Pierre Bastid became effective.

Mr. Muller serves currently (and this until July 1^st, 2025) as Chief Executive Officer of Idorsia Pharmaceuticals, Ltd. a listed Swiss biotech company. Previously, Mr. Muller served as Chief Financial Officer of Idorsia Pharmaceuticals, Ltd. and Actelion Pharmaceuticals, Ltd. He held various financial positions at Pierre Fabre SA, an international pharmaceutical and dermo-cosmetics company. Mr. Muller holds a Master's degree in Business Administration from the EMLYON Business School in Lyon.

"We are honored to welcome Mr. André Muller to the Cellectis’ Board of Directors as a director. His extensive experience will be an invaluable asset to the Company. We would also like to express our gratitude to Mr. Pierre Bastid and Mr. Axel Sven-Malkomes, whose directorships terminated at the end of this meeting. Their contribution over the last few years has been exceptional, and their precious support has greatly contributed to the advancement of the Company's strategy," said Jean-Pierre Garnier, Chairman of the Board of Directors of Cellectis.

The detailed results of the vote and the resolutions are available on Cellectis’ website: https://www.cellectis.com/en/investors/general-meetings/

The notice convening the annual general meeting stating the detailed agenda and modalities of participation in the meeting and the report of the board of directors to the shareholders meeting are available on the Cellectis website: https://www.cellectis.com/en/investors/general-meetings/

New York, NY – May 12, 2025 - Cellectis (the “Company”) (Euronext Growth: ALCLS - NASDAQ: CLLS), a clinical-stage biotechnology company using its pioneering gene editing platform to develop life-saving cell and gene therapies, today provided financial results for the first quarter 2025, ending March 31, 2025, and provided a business update.

« We are making progress in our wholly-owned clinical studies and in the three programs under our strategic partnership with AstraZeneca. We will continue to focus our efforts and resources on advancing these core programs and are looking forward to the results expected over the next few months » said André Choulika, Ph.D., Chief Executive Officer at Cellectis.

Pipeline Highlights

UCART Clinical Programs

BALLI-01 study evaluating lasme-cel (UCART22) in relapsed or refractory B-cell acute lymphoblastic leukemia (r/r B-ALL)

• On April 15, 2025, the International Nonproprietary Names (INN) Expert Committee of the World Health Organization (WHO) selected lasmecabtagene timgedleucel (lasme-cel) as recommended international non-proprietary name of UCART22 drug substance.
• Cellectis continues to focus on the enrollment of patients in the BALLI-01 study and expects to present the Phase 1 dataset and late-stage development strategy for lasme-cel in r/r B-ALL in the third quarter of 2025.

NATHALI-01 study evaluating eti-cel (UCART20x22) in relapsed or refractory B-cell non-Hodgkin lymphoma (r/r NHL)

• On April 15, 2025, the INN Expert Committee of the WHO selected etivelcabtagene erigedleucel (eti-cel) as recommended international non-proprietary name of UCART20x22 drug substance.
• Cellectis continues to focus on the enrollment of patients in the NATHALI-01 study and expects to present a Phase 1 readout for eti-cel in r/r NHL in late 2025.

Research Data & Preclinical Programs

Novel Non-Viral Gene Editing and Base Editing Research

• On April 28, 2025, Cellectis announced the presentation of research data on TALEN®-mediated non-viral transgene insertion for advancing cellular and gene therapies, and advancements in genetic editing using TALE base editors (TALEB), at the American Society of Gene and Cell Therapy (ASGCT) annual meeting that will be held on May 13-17, 2025 in New Orleans. The data will be presented in two posters:

TALEN®- Mediated non-viral Transgene Insertion for the Advancement of Cellular and Gene Therapies

• In this work, Cellectis combines TALEN®-mediated gene editing with non-viral transgene insertion for advancing cellular and gene therapies and explores gene insertion-efficacy and cellular health using single-stranded DNA (ssDNA) for payload delivery in different cell types.
• This innovative approach has the potential to address the challenges associated with traditional lentiviral viral methods or AAV-mediated transgene insertion such as manufacturing constraints, potential genomic toxicities or limited payload size.

High fidelity C-to-T editing with TALE base editors

• TALE base editors (TALEB) are fusions of a transcription activator-like effector domain (TALE), split-DddA deaminase halves, and an uracil glycosylase inhibitor (UGI). The C-to-T class of TALEB edits double-stranded DNA by converting a cytosine (C) to a thymine (T) and does not involve a DNA strand nick. Cellectis has developed a method to evaluate TALEB activity, analyzing factors affecting its efficiency. Using precise ssODN knock-in in primary T cells, the method assesses how target sequence composition and spacer variations impact TALEB performance.
• Overall, the results of this study enhance the control and use of TALEB, allowing for the design of highly efficient and specific TALEB compatible with future potential therapeutic applications.

The abstracts are live on the ASGCT website. The posters will be available on Cellectis’ website the first day of the event.

Partnerships

AstraZeneca Joint Research and Collaboration Agreement

Research and development activities are ongoing under three cell and gene therapy programs under the joint research and collaboration agreement entered into by Cellectis and AstraZeneca in November 2023: one allogeneic CAR T for hematological malignancies, one allogeneic CAR T for solid tumors, and one in vivo gene therapy for a genetic disorder.

The press release will be available in the Investors section of Cellectis’ website: https://www.cellectis.com/en/investors/press-releases/

Cellectis will not host a conference call to discuss these results. Our investors relations team remains available for questions at investors@cellectis.com

The data are presented in two posters:

Title: TALEN®- Mediated non-viral Transgene Insertion for the Advancement of Cellular and Gene Therapies.

Cell and gene therapy approaches can use gene-editing tools and introduce transgenes to modify disease-associated genes, thus providing a potential therapeutic solution for a wide array of diseases.

In this work, Cellectis combines TALEN®-mediated gene editing with non-viral delivery of transgene for advancing cellular and gene therapies, and explores gene insertion-efficacy and cellular health using single-stranded DNA (ssDNA) for payload delivery in different cell types.

This innovative approach has the potential to address the challenges associated with traditional lentiviral viral methods or AAV-mediated transgene insertion such as manufacturing constraints, potential genomic toxicities or limited payload size.

Research data show:

• Non-viral methods for gene editing: TALEN® mediated gene editing combined with non-viral templates (linear and circular ssDNA) can be used for highly efficient gene insertion in T-cells as well as hematopoietic stem and progenitor cells (HSPCs) promoting viability and insertion specificity
• Advantages of Circular ssDNA over viral vectors: Transcriptomic analysis and in vivo data demonstrate that CssDNA-mediated cell engineering allows better maintenance of HSPC fitness as well as more stable gene editing, compared to traditional viral donor template-mediated transgene delivery.

« The implementation of these gene-editing techniques holds significant potential for the development of next-generation therapies, aiming to provide alternative efficient, and safe therapeutic options for patients with cancer, autoimmune diseases, monogenic disorders, and various other conditions. » said Beatriz Aranda Orgilles, Ph.D., Associate Director – IO and business development analyst at Cellectis.

Title: High fidelity C-to-T editing with base editors

TALE base editors (TALEB) are fusions of a transcription activator-like effector domain (TALE), split-DddA deaminase halves, and a uracil glycosylase inhibitor (UGI). The C-to-T class of TALEB edits double-stranded DNA by converting a cytosine (C) to a thymine (T) and does not involve DNA strand nick.

Cellectis has developed a method to characterize the efficiency of this conversion and examined various factors influencing TALEB activity. This method also takes advantage of a highly precise and efficient knock-in of ssODN in primary T cells to develop an assay to assess how the composition and spacer variations of target sequences affect TALEB activity/efficiency.

Research data show:

• Efficiency of C-to-T editing: TALEB enables efficient conversion of C to T. Variations in target sequences and surrounding bases affecting editing efficiency. An educated choice of the TALEB architecture further allows to control the editing outcome.
• Assessment of off-target editing risks: Studies have been conducted to evaluate off-target editing, showing no detectable editing in primary cells at previously described sites, highlighting the specificity of TALEB for potential therapeutic applications.

«It is inspiring to see the advancement of Cellectis’ TALE technology into a new tool that is available in our gene editing toolbox. Our ability to understand and fine-tune the editing capacity of TALE base editors has equipped us with another efficient and specific approach that can be used to support novel gene editing and gene therapy applications. » said Louisa Mayer, Ph.D., Scientist II and Supervisor – Innovation & Gene Editing at Cellectis.

Overall, the results of this study enhance the control and use of TALEB, allowing for the design of highly efficient and specific TALEB compatible with future therapeutic applications.

The abstracts are live on the ASGCT website. The posters will be available on Cellectis’ website the first day of the event.

• UCART22 Phase 1 dataset and late-stage development strategy expected in the third quarter of 2025; Orphan Drug Designation (ODD) and Rare Pediatric Disease Designation (RPDD) granted by FDA and ODD granted by the European Commission to UCART22 for the treatment of ALL.
• UCART20x22 Phase 1 study in relapsed or refractory B-cell non-Hodgkin lymphoma (r/r NHL) ongoing with readout expected in late 2025.
• AstraZeneca partnership: R&D activities ongoing on three programs – one allogeneic CAR T for hematological malignancies, one allogeneic CAR T for solid tumors, and one in vivo gene therapy for a genetic disorder.
• Cash position of $264 million as of December 31, 2024[1] provides runway into mid-2027.
• Conference call March 14, 2025 at 8:00 am ET / 1:00 pm CET.

The publication will be followed by an investor conference call and webcast on Friday, March 14, 2025, at 8:00 AM ET / 1:00 PM CET. The call will include the Company’s fourth quarter and full year 2024 results and an update on business activities. Details for the call are as follows:

Dial in information:

Domestic: +1-800-225-9448

International: +1-203-518-9708

Conference ID: CLLS24

Webcast Link: https://viavid.webcasts.com/starthere.jsp?ei=1706599&tp_key=4524940f8f

The data are presented in a poster:

CAR induced expression of synthetically engineered FAP-IL2v immunocytokine boosts persistent anti-tumor activity of TALEN-edited allogeneic CAR T-cells without associated IL-2 toxicity

Presenter: Shipra Das, Ph.D., Associate Director Immuno-Oncology, at Cellectis.

Date/Time: February 25, 2025, 1:45-4:45 p.m. PT

Session: Poster Session B

• CAR T-cell therapies have transformed the treatment landscape for specific hematological malignancies and have shown promising preliminary efficacy in solid tumors.

• Recent studies suggest a link between the in vivo expansion and persistence of CAR-T cells and enhanced therapeutic outcomes in patients. The co-administration of interleukin-2 (IL-2) has been demonstrated to improve CAR T-cell engraftment, expansion, and functionality in preclinical models but poses toxicity risks at high doses.

• Using Cellectis’ TALEN^® gene editing technology, we developed ‘Smart CAR T cells’ with the ability to express a CAR-inducible IL-2 variant (IL-2v) immunocytokine, potentiated by tumor-specific cues for localized activity within the solid tumor microenvironment (TME).

• CAR-inducible expression of this recombinant FAP_scFv-IL2v boosts anti-tumor activity of engineered CAR T-cells both in vitro and in vivo. Notably, the enhancement of CAR T-cell activity mediated by IL-2v relies on its anchoring to the FAP protein, which is uniquely present in the TME, thus minimizing the systemic toxicity typically associated with circulating free IL-2 cytokines.

• This proposed cellular engineering strategy would represent an effective and safe method to substantially improve CAR T cell expansion and anti-tumor activity, while confining IL-2 activity to the tumor microenvironment.

The poster is published on Cellectis’ website.

As a condition to the disbursement of Tranche C the Company issued 611,426 warrants to the benefit of the EIB, in accordance with the terms of the 14^th resolution of the shareholders’ meeting held on June 28, 2024 and articles L. 228-91 and seq. of the French Commercial Code (the “Tranche C Warrants”).

Each Tranche C Warrant allows the EIB to subscribe for one ordinary share of the Company, at a price of €1.70, corresponding to 99% of the volume-weighted average price of the Company’s ordinary shares over the last 3 trading days preceding the decision of the board of directors of the Company to issue the Tranche C Warrants. The total number of shares issuable upon exercise of the Tranche C Warrants represent circa 0.6% of the Company’s outstanding share capital as at their issuance date.

Tranche C will mature six years from its disbursement date and will accrue interest at a rate of 6% per annum capitalized annually and payable at maturity.

The other terms of the Tranche C Warrants and prepayment events of Tranche C under the Finance Contract are as set forth in the Company’s press release of April 4, 2023 and Form 6-K filed with the U.S. Securities and Exchange Commission on such date.

The data will be presented in a poster:

Title: Breaking barriers in solid tumors with SMART allogeneic CAR T-cells

Date / Time: November 9^th, 2024 from 9:00am to 8:30pm ET

Presenter: Beatriz Aranda-Orgilles, Associate Director, Immuno Oncology at Cellectis

Poster number: 254

Despite the success of CAR T-cell therapies treating blood cancers, these cutting-edge technologies continue to face obstacles in solid tumors. A main barrier is the hostile tumor microenvironment (TME), which forms an immunosuppressive barrier and restricts T-cell infiltration into the tumor. Other contributing causes such as tumor antigen diversity or low expression of CAR-targeted tumor-associated antigens (TAA) in normal tissues can lead to antigen escape or on-target off-tumor toxicity, respectively. These factors can lead to relapse and pose a challenge for therapeutic safety.

Cellectis presents several strategies using TALEN®-mediated gene editing to generate allogeneic CAR T-cells while repurposing PD-1 function with tightly regulated functionalities, with the objective to increase efficacy and avoid potential toxicities in solid tumors.

Using in vitro and in vivo techniques, we show that TME-induced FAP-dependent expression of CAR tethers cytotoxic activity to the tumor area and can minimize potential "on-target off-tumor" toxicities. In a parallel approach, we integrate IL-12 into PD-1 regulatory elements to confine IL-12 to the TME and inactivate TGFBR2 to overcome TGFB1-mediated resistance. This strategy enhances proliferation and infiltration of CAR T-cells, while reducing tumor burden and limiting side effects.

Overall, our  data show the potential of repurposing immune pathways to create armored allogeneic CAR T-cells with enhanced activity in immunosuppressive microenvironments while minimizing potential safety issues. These approaches have the potential to provide a therapeutic option for patients with solid malignancies.

The poster is available on Cellectis website

• AstraZeneca partnership: R&D activities are ongoing on three programs – one allogeneic CAR T for hematological malignancies, one allogeneic CAR T for solid tumors, and one in vivo gene therapy for a genetic disorder

• Appointed Adrian Kilcoyne, M.D., MPH, MBA, an industry leader in the advancement of cell therapy treatment, as Chief Medical Officer

• Cash position of $264 million as of September 30, 2024[1]; cash runway projection into 2027

• Conference call scheduled for 8:00 am ET / 2:00 pm CET on November 5, 2024

New York, NY – November 4, 2024 - Cellectis (the “Company”) (Euronext Growth: ALCLS - NASDAQ: CLLS), a clinical-stage biotechnology company using its pioneering gene editing platform to develop life-saving cell and gene therapies, today provided business updates and reported financial results for the nine-month period ending September 30, 2024.

“This quarter, we were thrilled to welcome Dr. Kilcoyne to Cellectis as Chief Medical Officer. Dr. Kilcoyne joins us at a pivotal time for the Company, bringing extensive experience in drug development as we are progressing in our clinical programs. We expect to present Phase 1 dataset and late-stage development strategy in 2025 for UCART22 in ALL and UCART20x22 for NHL” said André Choulika, Ph.D., Chief Executive Officer at Cellectis. 

“Additionally, we are excited to announce that research and development activities have started for three programs under our collaboration and research agreement with AstraZeneca: one allogeneic CAR T for hematological malignancies, one allogeneic CAR T for solid tumors, and one in vivo gene therapy for a genetic disorder.  

Cellectis is confident about the continued progress of its ongoing clinical trials in hematological malignancies and is excited about our strategic collaboration with AstraZeneca, with whom we continue to advance our ambition in cell and gene therapy to bring potentially lifesaving therapies to patients with unmet medical needs."

Pipeline Highlights

UCART Clinical Programs

• Cellectis continues to focus on the enrollment of patients in the BALLI-01 study, evaluating UCART22 in relapsed or refractory B-cell acute lymphoblastic leukemia. We expect to present the Phase 1 dataset and late-stage development strategy in 2025.
• Cellectis continues to focus on the enrollment of patients in the NATHALI-01 study, evaluating UCART20x22 in relapsed or refractory B-cell non-Hodgkin lymphoma. We expect to present the Phase 1 dataset and late-stage development strategy in 2025.
• The Company decided to focus its current development efforts on the BALLI-01 and NATHALI-01 studies and therefore to deprioritize the development of UCART123, currently evaluated in relapsed or refractory acute myeloid leukemia. Up to now, this study has provided important insights into the role of CD123-targeted allogeneic CAR-T therapy in relapsed refractory acute myeloid leukemia and the future development of our allogeneic CAR-T platform.

MUC1 CAR T-cells for treating Triple-Negative Breast Cancer

• On September 3, 2024, Cellectis published a scientific article in Science Advances suggesting that TALEN®-edited MUC1 CAR T-cells could be a potential treatment option for advance-stage triple negative breast cancer (TNBC) patients with limited therapeutic options. In this article, Cellectis described its CAR T-cell engineering strategy using TALEN® and synthetic biology to multi-armor CAR T-cells with synergistic functionalities to overcome the immunosuppressive tumor microenvironment of solid tumors.

Partnerships

Servier and Allogene – Allogeneic CAR-T

Allogene’s investigational oncology products utilize Cellectis technologies.

• Allogene announced that the pivotal Phase 2 ALPHA3 trial was initiated in June 2024. This study is evaluating the use of cemacabtagene ansegedleucel (cema-cel) as part of the first line (1L) treatment regimen for patients with LBCL who are likely to relapse after standard 1L treatment. Allogene announced that ALPHA3 is the first pivotal trial to offer CAR T as part of 1L treatment consolidation.
• Allogene announced that enrollment is ongoing in the relapsed/refractory (r/r) CLL cohort of the Phase 1 ALPHA2 trial of cema-cel, and that initial data readout from the CLL cohort is projected by early 2025.
• Allogene announced that a Phase 1 data update of the TRAVERSE trial of ALLO-316 from approximately 20 patients with CD70 positive RCC is planned by YE 2024. In October 2024, Allogene announced that the U.S. Food and Drug Administration (FDA) granted Regenerative Medicine Advanced Therapy (RMAT) designation to ALLO-316 for the treatment of adult patients with CD70 positive advanced or metastatic renal cell carcinoma (RCC).

AstraZeneca – Joint Research and Collaboration Agreement

• Under the terms of the joint research and collaboration agreement entered into by Cellectis and AstraZeneca Ireland Limited (“AstraZeneca”) on November 1, 2023 (the “AZ JRCA”), AstraZeneca is leveraging Cellectis’ proprietary gene editing technologies and manufacturing capabilities to design novel cell and gene therapy candidate products. As part of the AZ JRCA, 25 genetic targets have been exclusively reserved for AstraZeneca, from which up to 10 candidate products could be explored for development. AstraZeneca has an option for a worldwide exclusive license on the candidate products, to be exercised before IND filing.
• Research and development activities under three cell and gene therapy programs have already started under the AZ JRCA: one allogeneic CAR T for hematological malignancies, one allogeneic CAR T for solid tumors, and one in vivo gene therapy for a genetic disorder.
• Under the AZ JRCA, $47m have been triggered so far (of which $25m upfront and $22m reached development milestones for the three initial projects), in addition to reimbursement of research costs incurred under the AZ JRCA.

Appointment

• On August 7, 2024, Cellectis announced the appointment of Adrian Kilcoyne, M.D., MPH, MBA as its Chief Medical Officer.
• Before joining Cellectis, Dr. Kilcoyne was Chief Medical Officer and Head of Research and Development at Celularity, advancing their oncology allogeneic CAR-T and NK Cell therapy programs. Prior to this, he was Chief Medical Officer at Humanigen. He has held numerous Oncology leadership roles across Research and Development, Medical Affairs, Commercial, Health Economic Outcome Research and Evidence Generation in both large pharmaceutical and biotechnology companies such as AstraZeneca and Celgene. Dr. Kilcoyne graduated from Trinity College, Dublin Medical School. He initially trained in Gynecological Oncology at the Hammersmith Hospital in London and subsequently in Public Health Medicine at Oxford during which time he completed a Master’s in Public Health. Dr. Kilcoyne then trained in pharmaceutical medicine and completed his MBA.

The publication will be followed by an investor conference call and webcast on Tuesday, November 5, 2024 at 8:00 AM ET / 2:00 PM CET. The call will include the Company’s third quarter results and an update on business activities. Details for the call are as follows:

Dial in information:

Domestic: +1-800-225-9448

International: +1-203-518-9708

Conference ID: CLLSQ3

Webcast Link: https://viavid.webcasts.com/starthere.jsp?ei=1688144&tp_key=affca25222

The data will be presented in two posters:

Controlling C-to-T editing with TALE base editors

Presenter: Alexandre Juillerat, Ph.D., Vice-President Gene Editing & NY Lab Head at Cellectis

Date/Time: Thursday, October 24 from 2:00pm to 3:30pm CET

Poster number: P0666

• TALE base editors (TALEB) are fusions of a transcription activator-like effector domain (TALE), split-DddA deaminase halves, and an uracil glycosylase inhibitor (UGI). The C-to-T class of TALEB edits double strand DNA by converting a cytosine (C) to a thymine (T) via the formation of an uracil intermediate.
• Cellectis recently developed a strategy that allows the comprehensive characterization of C-to-T conversion efficiencies within the editing window. This method also takes advantage of a highly precise and efficient TALEN®-mediated ssODN knock-in in primary T cells to assess how target composition and spacer variations affect TALEB activity/efficiency.
• The datasets obtained in this study enhanced our understanding of TALEB and permitted the design of efficient and specific tools that could be compatible with the potential development of therapeutic applications.

Circular Single-Stranded DNA Enables Efficient TALEN-Mediated Gene Insertion in Long Term HSC

Presenter: Julien Valton, Ph.D., Vice-President Gene Therapy at Cellectis

Date/Time: Thursday, October 24 from 2:00pm to 3:30pm CET

Poster number: P0585

• Non-viral alternatives such as linear single-stranded DNA (LssDNA) and circular single-stranded DNA (CssDNA) are emerging as promising options to vectorized DNA donor template for nuclease-mediated gene insertion in hematopoietic stem and progenitor cells (HSPCs) used for gene therapy applications.
• Capitalizing on its TALEN® technology, Cellectis has devised a gene editing process that incorporates non-viral DNA donor template delivery (LssDNA or CssDNA) to enhance gene insertion in HSPCs.
• The circularization of ssDNA increases gene insertion rates in long term HSCs and has the potential to enhance their engraftment capacity in preclinical murine model, thereby to facilitate the advancement of next-generation cell therapies. This research marks a crucial step towards enhancing the efficacy of non-viral gene therapy.

The posters will be published on Cellectis’ website after the presentations.

Globally, breast cancer continues to be the most prevalent malignancy in women. Among all subtypes, triple-negative breast cancer (TNBC) stands out as the most aggressive form with high metastatic potential and poor survival rates.

Despite a few emerging targeted therapies under investigation, surgery, chemotherapy and radiation therapy continue to be the standard of care, and their success remains limited. As an alternative, Chimeric Antigen Receptor (CAR) T-cell therapies could hold promise for advance-stage TNBC patients as tumor-associated MUC1 antigen is overexpressed in a large number of patients thus offering a distinct target for treatment.

In this article, Cellectis described its multi-layered CAR T-cell engineering strategy using TALEN® and synthetic biology to multi-armor CAR T-cells with synergistic functionalities to overcome the immunosuppressive tumor microenvironment (TME) of solid tumors. With this strategy, Cellectis demonstrates enhanced cytotoxic activity of MUC1 CAR T-cells armored with PD1KO, tumor-specific IL12 release and TGFBR2KO attributes, all of them catered towards the TNBC TME, in intravenous and intratumoral mouse models.

“Complexity of solid tumors decreases the efficacy of CAR T-cell therapies. With this pre-clinical study, we showed that TALEN®-mediated multiplex editing can support CAR T-cells in effectively mounting an anti-tumor response to clear breast tumors, and that we can further decrease the dose of the treatment by injecting the CAR T cells intratumorally while still treating distant tumors. This innovative approach also allowed us to discover an unexpected cooperation between the edits in increasing safety, highlighting the potential capabilities of multiplex editing” said Piril Erler, PhD, Scientist II at Cellectis.

Importantly, intratumoral treatment effectively reduced local and distant tumors of large size using low doses of multi-armored MUC1 CAR T-cells. This pre-clinical data suggests that the benefits of antigen recognition are maintained at distant sites and highlights the potential to address metastasis with local administration.

The article is available on Science Advances’ website by clicking on this link: https://www.science.org/doi/10.1126/sciadv.adn9857

Adoptive cell therapy based on CAR T cells has proven to be lifesaving for many cancer patients. However, its therapeutic efficacy has so far been restricted to only a few malignancies, with solid tumors proving to be especially recalcitrant to efficient therapy.

One key factor for this are cancer-associated fibroblasts (CAFs), that modulate the tumor microenvironment (TME) to inhibit T cell infiltration and induce T cell dysfunction. Additionally, the sparsity of tumor-specific antigens (TSA) and expression of CAR-directed tumor-associated antigens (TAA) on normal tissues often results in on-target off-tumor cytotoxicity, raising safety concerns.

Using TALEN® gene editing technology, Cellectis presents an innovative CAR T cell engineering strategy designed to overcome these challenges. Our allogeneic SMART CAR T-cells are designed to express a constitutive CAR, targeting FAP⁺ CAFs in solid tumors, and a second inducible CAR, expressed only in the presence of FAP+ CAFs and targeting the tumor associated antigen (TAA) named mesothelin. The resultant SMART Dual CAR T-cells efficiently infiltrate and efficiently target triple-negative breast tumors in physiologically relevant mice models, with no observable on-target, off-tumor toxicity.

“The adaptations of this approach could resolve several key challenges for CAR T-cell therapy against solid tumor-low CAR T-cell infiltration, immuno-suppressive microenvironment, antigen heterogeneity as well as on target, off-tumor toxicity. This strategy thus has significant implications for successful therapeutic development of CAR T-cells against solid tumors” said Shipra Das, Ph.D., Associate Director Immuno-Oncology and Innovation Program Management at Cellectis.

The article is available on Molecular Therapy website by clicking on this link : https://www.sciencedirect.com/science/article/pii/S1525001624005409?utm_campaign=STMJ_219742_AUTH_SERV_PA&utm_medium=email&utm_acid=300123771&SIS_ID=&dgcid=STMJ_219742_AUTH_SERV_PA&CMX_ID=&utm_in=DM500444&utm_source=AC_

“We’re thrilled to welcome Dr. Kilcoyne to Cellectis. He is a strategic, forward-thinking drug developer who is passionate about delivering life-saving therapies to patients. His clinical vision and proven leadership, as well as his extensive experience, will strengthen our clinical development efforts as we advance our product pipeline of next-generation CAR T-cell therapies” said André Choulika, Ph.D., Chief Executive Officer at Cellectis.

Before joining Cellectis, Dr. Kilcoyne was Chief Medical Officer and Head of Research and Development at Celularity, advancing their oncology allogeneic CAR-T and NK Cell therapy programs. Prior to this, he was Chief Medical Officer at Humanigen. He has held numerous Oncology leadership roles across Research and Development, Medical Affairs, Commercial, Health Economic Outcome Research and Evidence Generation in both large pharmaceutical and biotechnology companies such as AstraZeneca and Celgene. Dr. Kilcoyne graduated from Trinity College, Dublin Medical School. He initially trained in Gynecological Oncology at the Hammersmith Hospital in London and subsequently in Public Health Medicine at Oxford during which time he completed a Master’s in Public Health. Dr. Kilcoyne then trained in pharmaceutical medicine and completed his MBA.

“I am excited to join Cellectis at this pivotal time for the company as it is poised to deliver on its mission to provide transformative UCART therapies to patients with significant unmet medical need,” said Dr. Adrian Kilcoyne. “I believe that Cellectis’ world-class capabilities in gene editing and cell therapy manufacturing, promising pipeline and experienced leadership team will enable us to accelerate our current clinical pipeline and drive future innovation as we strive to deliver first-in-class and best-in-class allogeneic cell and gene therapies.”

Dr. Mark Frattini departs Cellectis effective immediately to pursue other opportunities. We thank Dr. Frattini for his contributions and wish him well in his new endeavors.

• ODD granted by the FDA to CLLS52 (alemtuzumab) for ALL treatment

• Cash position of $273 million as of June 30, 2024[1]; cash runway projection into 2026

New York, NY – August 6, 2024 - Cellectis (the “Company”) (Euronext Growth: ALCLS - NASDAQ: CLLS), a clinical-stage biotechnology company using its pioneering gene editing platform to develop life-saving cell and gene therapies, today provided business updates and reported financial results for the six-month period ending June 30, 2024.

"Over the past months, we have achieved a significant milestone with the granting of ODD designations by the Food and Drug Administration and the European Commission, complemented by the FDA’S Rare Pediatric Disease Designation. We have overcome major challenges, which reflects our ongoing commitment to innovation. Driven by an unwavering belief in our ability to revolutionize the healthcare field, we continue our pursuit of advancement with the confidence that our work will lead to the launch of a life-saving drug product. Our determination is the engine of our future success” said André Choulika, Ph.D., Chief Executive Officer at Cellectis.

Pipeline Highlights

UCART Clinical Programs

• On June 4, 2024, Cellectis received Orphan Drug Designation (ODD) from the European Commission (EC) for UCART22, for the treatment of acute lymphoblastic leukemia (ALL). The Orphan Drug Designation in the European Union is granted by the EC based on a positive opinion issued by the European Medicines Agency (EMA) Committee for Orphan Medicinal Products. This designation may allow certain regulatory, financial, and commercial incentives to develop medicines for rare diseases where there are no satisfactory treatment options.
• On July 25, 2024, the FDA designated UCART22 as a drug for a Rare Pediatric Disease (RPDD). This designation may allow to obtain a “Priority Review Voucher” at the time of Biologics License Application (BLA). The FDA also granted ODD to UCART22 product candidate for ALL treatment. Receiving ODD by the FDA may help to expedite and reduce the cost of development, approval, and commercialization of a therapeutic agent.
• Patients with relapsed/refractory ALL have limited, if any, treatment options, especially for those who have failed prior CD19 directed CAR T-cell therapy and allogeneic stem cell transplant. These designations for UCART22 mark an important step towards developing allogeneic CAR T products that would be readily available for all patients.
• On August 1, 2024, the FDA granted ODD to Cellectis’ CLLS52 (alemtuzumab), an Investigational Medicinal Product (IMP) used as part of the lymphodepletion regimen associated with UCART22, evaluated in the BALLI-01 clinical trial. The importance of adding alemtuzumab to the lymphodepletion regimen has been demonstrated in Cellectis’ BALLI-01 study, where the addition of this lymphodepletion agent to the fludarabine and cyclophosphamide regimen was associated with sustained lymphodepletion and significantly higher UCART22 cell expansion allowing for greater clinical activity.
• Cellectis continues to focus on the enrollment of patients in the BALLI-01 study, evaluating UCART22 in relapsed or refractory B-cell acute lymphoblastic leukemia, in the NatHaLi-01 study, evaluating UCART20x22 in relapsed or refractory B-cell non-Hodgkin lymphoma, and in the AMELI-01 study, evaluating UCART123 in relapsed or refractory acute myeloid leukemia. We expect to provide updates in the advancements of BALLI-01 til the end of the year 2024.

Research Data & Preclinical Programs

Non-viral Gene Therapy Approach for Sickle Cell Disease

• On June 12, 2024, Cellectis announces the publication of a scientific article in Nature Communications.
• Cellectis leverages TALEN® technology and a non-viral gene repair template delivery to develop a clinically relevant gene editing process in hematopoietic stem and progenitor cells (HSPCs). This process enables efficient HBB gene correction with high precision, specificity and minimal genomic adverse events.
• Applying this HBB gene correction process to SCD patient-HSPCs results in over 50% expression of normal adult hemoglobin in mature red blood cells and in the correction of sickle phenotype, without inducing β-thalassemic phenotype. Edited HSPCs engraft efficiently in an immunodeficient murine model and maintain clinically relevant levels of HBB gene correction events. This comprehensive preclinical data package sets the stage for the therapeutic application of autologous gene corrected HSPCs to address SCD.

Partnerships

Licensed Allogeneic CAR T-cell Development Programs

Anti-CD19 Programs

Allogene’s investigational oncology products utilize Cellectis technologies.

We have initiated an arbitration proceeding through the Centre de Médiation et d'Arbitrage de Paris. We are requesting that the arbitral tribunal issue a decision (i) terminating the Servier License Agreement, and (ii) requiring Servier to pay us fair financial compensation for losses incurred due to the lack of development of the licensed products and for non-payment of milestone payments for milestones that have been achieved under the Servier License Agreement.

In May 2024, Allogene announced the execution of an Amendment and Settlement Agreement (the "Servier Amendment"), which amended the license agreement between Servier and Allogene, under which Servier exclusively sublicensed to Allogene its rights under the License Agreement between Cellectis and Servier (the "Servier License"), for the development and commercialization of allogeneic anti-CD19 CAR T cell product candidates in the U.S. (the "Allogene Sublicense"). Allogene disclosed that, pursuant to the Servier Amendment to the Allogene Sublicense, the licensed territory was expanded to include the European Union and the United Kingdom, and Allogene was granted an option to further extend its licensed territory to include China and Japan subject to certain conditions.

Corporate Updates

Collaboration and Investment Agreements with AstraZeneca

• On May 6, 2024, Cellectis announced the completion of the subsequent investment of $140M in Cellectis by AstraZeneca (LSE/STO/Nasdaq: AZN) (the “Additional Investment”).
• AstraZeneca subscribed for 10,000,000 “class A” convertible preferred shares and 18,000,000 “class B” convertible preferred shares, in each case at a price of $5.00 per convertible preferred share, issued by the Board of Directors of Cellectis.
• On the completion date of the Additional Investment, AstraZeneca owned approximately 44% of the share capital and 30% of the voting rights of the Company (based on the number of voting rights outstanding at the time).
• Following the Additional Investment, Mr. Marc Dunoyer and Dr. Tyrell Rivers have been nominated members of the board of directors of Cellectis, designated by AstraZeneca.

Annual Shareholders Meeting

• On June 28, 2024, Cellectis held a shareholders’ general meeting at the Biopark auditorium in Paris, France
• At the meeting, during which approximately 40% of shares were exercised, resolutions 1 through 28 were adopted and resolution 29 was rejected, consistent with the recommendations of the management. The detailed results of the vote and the resolutions are available on Cellectis’ website: https://www.cellectis.com/en/investors/general-meetings/

“We are excited that the FDA granted CLLS52 (alemtuzumab) ODD designation status. The importance of adding alemtuzumab to the lymphodepletion regimen has been demonstrated in Cellectis’ BALLI-01 study, where the addition of this lymphodepletion agent to the fludarabine and cyclophosphamide regimen was associated with sustained lymphodepletion and significantly higher UCART22 cell expansion allowing for greater clinical activity”, said Mark Frattini, M.D., Ph.D. Chief Medical Officer at Cellectis.

Cellectis is the inventor of the combination of CD52 knockout UCART cells with a lymphodepleting regimen containing an anti-CD52 antibody such as alemtuzumab. The CD52 knockout aims to render the UCART product candidates resistant to alemtuzumab as part of the lymphodepleting regimen. Cellectis’ UCART22 product candidate has the CD52 gene inactivated by TALEN® gene editing technology.

The FDA grants ODD status to medicines intended for the treatment, diagnosis or prevention of rare diseases or disorders that affect fewer than 200,000 people in the US. Receiving ODD may help to expedite and reduce the cost of development, approval, and commercialization of a therapeutic agent.

• There is an urgent need to develop new therapies for ALL for patients who are not candidates for hematopoietic stem cell transplantation (HSCT) or relapse after

• FDA ODD and RPDD designations for UCART22 marks an important step towards developing allogeneic CAR T products that would be readily available for all patients

New York, NY – July 25, 2024 – Cellectis (the “Company”) (Euronext Growth: ALCLS - NASDAQ: CLLS), a clinical-stage biotechnology company using its pioneering gene-editing platform to develop life-saving cell and gene therapies, today announced that the U.S. Food and Drug Administration (FDA) has granted Orphan Drug (ODD) and Rare Pediatric Disease Designation (RPDD) Status to UCART22 product candidate for the treatment of Acute Lymphoblastic Leukemia (ALL).

ALL represents about 10% of all leukemia cases in the United States, progresses rapidly, and is typically fatal within weeks or months if left untreated. It is estimated that 6,660 new cases of ALL and 1,560 deaths related to the disease occurred in the US in 2022[2].

Mark Frattini, M.D., Ph.D., Chief Medical Officer at Cellectis said: “We are excited that the FDA granted UCART22 both ODD and RPDD Status in the treatment of acute lymphoblastic leukemia. This decision represents additional evidence of the potential of UCART22 to bring a much-needed therapeutic option to these patients with ALL. There is an urgent need to develop new therapies for ALL for patients who are not candidates for HSCT or relapse after CD19 directed CAR T-cell therapies and/or HSCT.”

UCART22 is an allogeneic CAR T-cell product candidate targeting CD22 and evaluated in BALLI-01, a Phase 1/2 open-label dose-escalation and dose-expansion study, designed to evaluate the safety, expansion, persistence and clinical activity of UCART22 in patients with relapse/refractory ALL.

The last clinical data presented by Cellectis at the American Society of Hematology in December 2023 were encouraging and suggested that UCART22-P2 (fully manufactured at Cellectis) is more potent with a preliminary response rate of 67% at Dose Level 2, compared to a 50% response rate at Dose Level 3 with UCART22-P1 (manufactured by an external CDMO). Cellectis expects to provide updates on the progress of BALLI-01 by year-end 2024.

The FDA grants ODD status to medicines intended for the treatment, diagnosis or prevention of rare diseases or disorders that affect fewer than 200,000 people in the US, an RPDD is granted for serious or life-threatening disease in which the serious or life-threatening manifestations, such as mortality with relapsed and/or refractory disease, primarily affect individuals aged from birth to 18 years. Receiving ODD may help to expedite and reduce the cost of development, approval, and commercialization of a therapeutic agent. Receiving RPDD may lead to receiving a rare pediatric disease priority review voucher at the time of marketing approval.

At the meeting, during which approximately 40% of shares were exercised, resolutions 1 through 28 were adopted and resolution 29 was rejected, consistent with the recommendations of the management.

The detailed results of the vote and the resolutions are available on Cellectis’ website:

https://www.cellectis.com/en/investors/general-meetings/

TALE base editors are a recent and important addition to the gene editing landscape. By design, TALE base editors do not create break within DNA strands as does CRISPR/Cas9, or other engineered nucleases, and is a promising therapeutic strategy for genetic diseases. A key aspect to broaden the scope of possible applications is our comprehension of design rules.

TALE base editors rely on the deamination of cytidines within double strand DNA, leading to the formation of an uracil (U) intermediate. These molecular tools are fusions of transcription activator-like effector domains (TALE) for specific DNA sequence binding, split-DddA deaminase halves that will, upon catalytic domain reconstitution, initiate the conversion of a cytosine (C) to a thymine (T), and an uracil glycosylase inhibitor (UGI).

Previous works have pointed towards the positioning of targeted cytosine to be a key determinant for efficient editing.

To extend the understanding of key determining factors allowing efficient TALE base editing (C-to-T conversion), Cellectis investigated whether the nature (length and composition) of the linker that connects the TALE array with the split deaminase catalytic heads could impact C-to-T conversion within the editing window.

The datasets presented in this paper highlight how three key factors, spacer length, TALEB architecture and composition of the surrounding bases, can impact editing outcomes and further improve our understanding of TALE base editors' activity and specificity, leading to the possibility to tune and control editing using educated designs.

“This experimental strategy used by Cellectis to characterize editing profiles in depth and in a high throughput format could easily be applied to any new editors to continue expanding this platform for potential therapeutic applications” said Maria Feola, Scientist III, Manager, Gene Editing at Cellectis.

Research data specifically underlines the primordial importance of the positions preceding the targeted TC, which markedly increases editing efficiency. 

The article is available on Scientific Reports website by clicking on this link: https://www.nature.com/articles/s41598-024-63203-8

Sickle cell disease (SCD) is one of the most common inherited diseases worldwide. SCD is caused by a single point mutation in the HBB gene, which encodes the β subunit of hemoglobin (Hb). Normally, red blood cells adopt a disc-like shape that allows them to move easily through the blood vessels and deliver oxygen throughout the body. In sickle cell disease, red blood cells become crescent or “sickle”-shaped, a dysfunctional state that impairs blood flow, oxygen delivery and triggers multiple debilitating symptoms including intense pain crisis.  

Cellectis leverages TALEN® technology and a non-viral gene repair template delivery to develop a clinically relevant gene editing process in hematopoietic stem and progenitor cells (HSPCs). This process enables efficient HBB gene correction with high precision, specificity and minimal genomic adverse events. 

Applying this HBB gene correction process to SCD patient-HSPCs results in over 50% expression of normal adult hemoglobin in mature red blood cells and in the correction of sickle phenotype, without inducing β-thalassemic phenotype. Edited HSPCs engraft efficiently in an immunodeficient murine model and maintain clinically relevant levels of HBB gene correction events. This comprehensive preclinical data package sets the stage for the therapeutic application of autologous gene corrected HSPCs to address SCD. 

“The unique combination of TALEN® technology, non-viral DNA repair template design and Cellectis’ PulseAgile proprietary electroporation system enabled us to set up a precise, efficient and clinically relevant HBB gene correction process in long term hematopoietic stem and progenitor cells from SCD patients” said Julien Valton, Ph.D., Vice President Gene Therapy at Cellectis. “SCD is a devastating blood disorder affecting millions of individuals worldwide. The TALEN® gene therapy approach could represent a new alternative treatment, especially for patients with limited therapeutic options. This gene editing process bears a strong therapeutic potential as it could be easily used to correct point mutations associated to many other genetic diseases.”  

Research data showed that: 

• TALEN® technology, coupled to non-viral DNA correction template delivery, achieves high HBB gene correction efficiencies in healthy donor - and SCD patient - HSPCs in vitro. 
• HBB gene correction translates into an efficient rescue of functional Adult Hemoglobin (HbA) and a significant decrease of dysfunctional Sickle Hemoglobin (HbS) and Sickle red blood cells.  
• TALEN® nuclease activity is highly specific with only one off-target site detected at the HBD locus. 
• Corrected HSPCs display long-term in vivo engraftment capacity in murine animal model, indicating their strong potential for therapeutic applications towards SCD.  

The article is available on Nature Communications website by clicking on this link: https://doi.org/10.1038/s41467-024-49353-3 

UCART22 is an allogeneic CAR T-cell product candidate targeting CD22 and evaluated in BALLI-01, a Phase 1/2 open-label dose-escalation and dose-expansion study, designed to evaluate the safety, expansion, persistence and clinical activity of UCART22 in patients with relapse/refractory ALL.

ALL represents 12% of all leukemia cases, progresses rapidly, and is typically fatal within weeks or months if left untreated[1]. In 2024, the 10-year prevalence is estimated at 1.9 in 100,000 persons in the European Union (EU). Based on the preliminary clinical data generated with UCART22 in heavily pretreated patients who were relapsed or refractory to approved medicinal products, the European Medicines Agency (EMA) considered that the significant benefit of UCART22 has been demonstrated.

“Patients with relapsed/refractory ALL have limited, if any, treatment options, especially for those who have failed prior CD19 directed CAR T-cell therapy and allogeneic stem cell transplant” said Mark Frattini, M.D., Ph.D., Chief Medical Officer at Cellectis. “The Orphan Drug Designation for UCART22 marks an important step towards developing allogeneic CAR T products that would be readily available for all patients.”  

The last clinical data presented by Cellectis at the American Society of Hematology in December 2023 were encouraging and suggested that UCART22-P2 (fully manufactured in-house) is more potent with a preliminary response rate of 67% at Dose Level 2, compared to a 50% response rate at Dose Level 3 with UCART22-P1 (manufactured by an external CDMO). Cellectis expects to provide updates on the progress of BALLI-01 by year-end 2024.

The Orphan Drug Designation in the EU is granted by the EC based on a positive opinion issued by the EMA Committee for Orphan Medicinal Products. Medicines intended for the treatment, diagnosis or prevention of seriously debilitating or life-threatening conditions that affect fewer than five in 10,000 people in the EU are eligible for the designation. The Orphan Drug Designation allows companies certain regulatory, financial, and commercial incentives to develop medicines for rare diseases where there are no satisfactory treatment options.

The notice convening the annual general meeting stating the detailed agenda and modalities of participation in the meeting is available on the Cellectis website: https://www.cellectis.com/en/investors/general-meetings/

New York, NY – May 28, 2024 - Cellectis (the “Company”) (Euronext Growth: ALCLS - NASDAQ: CLLS), a clinical-stage biotechnology company using its pioneering gene editing platform to develop life-saving cell and gene therapies, today provided business updates and reported financial results for the three-month period ending March 31, 2024.

“We are thrilled to have announced the closing of the additional equity investment of $140 million by AstraZeneca. This followed AstraZeneca’s initial payment of $105 million, composed of a $80 million equity investment and a $25 million upfront payment under our research collaboration.

Following AstraZeneca’s additional investment, we expect our cash runway to fund operations into 2026. We will continue to focus our efforts and expenses on advancing its core clinical trials BALLI-01, NATHALI-01 and AMELI-01, which remain wholly owned assets, while building, within our owned preclinical pipeline and in collaboration with AstraZeneca, the next generation of medicines to address areas of high unmet patient needs.

We strongly believe that gene edited cell and gene therapy products are revolutionizing medicine across a number of therapeutic areas and will become a large part of molecular medicine of the future.” said André Choulika, Ph.D., Chief Executive Officer at Cellectis.

Pipeline Highlights

UCART Clinical Programs

• Cellectis continues to focus on the enrollment of patients in the BALLI-01 study (evaluating UCART22) in relapsed or refractory B-cell acute lymphoblastic leukemia (r/r B-ALL), in the NATHALI-01 study (evaluating UCART20x22) in relapsed or refractory B-cell non-Hodgkin lymphoma (r/r B-NHL), and in the AMELI-01 study (evaluating UCART123) in relapsed or refractory acute myeloid leukemia (r/r AML).

• We expect to provide updates in the advancements of BALLI-01 and NATHALI-01 by year-end 2024.

Partnerships

Licensed Allogeneic CAR T-cell Development Programs

Anti-CD19 program

Allogene’s investigational oncology products utilize Cellectis technologies. Servier, which has an exclusive license to the anti-CD19 investigational products from Cellectis, has granted Allogene an exclusive sublicense to these products in the U.S., European Union and the United Kingdom.

• Allogene announced the execution with Servier of an amendment to the sublicense to expand the licensed territory to the European Union and the United Kingdom.
• Allogene announced that it continues to focus on the development of its investigational product cemacabtagene ansegedleucel, or cema-cel (previously known as ALLO-501A), as part of the first line (1L) treatment plan for LBCL patients who are at risk of relapse following 1L chemoimmunotherapy. Allogene announced that start-up activities for the ALPHA3 trial are ongoing with a planned study initiation in mid-2024.
• Allogene further announced that enrollment is ongoing in the relapsed/refractory (r/r) CLL cohort of the Phase 1 ALPHA2 trial of cema-cel.

Anti-CD70 program

The anti-CD70 program is licensed exclusively from Cellectis by Allogene and Allogene holds global development and commercial rights to this program.

• Allogene announced that a Phase 1 data update of the ongoing TRAVERSE trial with ALLO-316 in RCC from approximately 20 patients with CD70 positive RCC is planned by YE 2024.

Corporate Updates

Collaboration and Investment Agreements with AstraZeneca

• On May 6, 2024, Cellectis announced the completion of the subsequent investment of $140M in Cellectis by AstraZeneca (LSE/STO/Nasdaq: AZN).
• AstraZeneca subscribed for 10,000,000 “class A” convertible preferred shares and 18,000,000 “class B” convertible preferred shares, in each case at a price of $5.00 per convertible preferred share, issued by the board of directors of Cellectis.
• AstraZeneca owns approximately 44% of the share capital and 30% of the voting rights of the Company (based on the number of voting rights currently outstanding).

Appointment

• On May 2, 2024, Cellectis announced the appointment of Mr. Arthur Stril as Interim Chief Financial Officer, following the resignation of Bing Wang, Ph.D.
• The appointment of Mr. Marc Dunoyer and Dr. Tyrell Rivers as members of the board of directors of Cellectis, decided by the extraordinary general meeting of the shareholders of Cellectis held on December 22, 2023, is effective as from May 3, 2024.

The publication will be followed by an investor conference call and webcast on Wednesday, May 29, 2024 at 8:00 AM ET / 2:00 PM CET. The call will include the Company’s first quarter results and an update on business activities. Details for the call are as follows:

Dial in information:

Domestic: 1-877-451-6152

International: 1-201-389-0879

Conference ID: 13746795

Webcast Link: https://viavid.webcasts.com/starthere.jsp?ei=1672725&tp_key=f83e7ab481

New York, NY – May 6, 2024 - Cellectis (Euronext Growth: ALCLS – NASDAQ: CLLS)  a clinical-stage biotechnology company using its pioneering gene-editing platform to develop life-saving cell and gene therapies, today announced that, following clearance from the French Ministry of Economy and satisfaction of all other closing conditions, AstraZeneca (LSE/STO/Nasdaq: AZN) completed the additional equity investment of $140M in Cellectis, as previously announced by Cellectis on November 1 and 15, 2023 (the “Additional Investment”).

As part of the Additional Investment, AstraZeneca subscribed today for 10,000,000 “class A” convertible preferred shares and 18,000,000 “class B” convertible preferred shares, in each case at a price of $5.00 per convertible preferred share, issued by the board of directors of Cellectis pursuant to the authorizations granted by the extraordinary general meeting of the shareholders of Cellectis held on December 22, 2023.

Prior to their conversion into ordinary shares, the “class A" convertible preferred shares have single voting rights and will not be eligible for double voting rights under any circumstances, and the “class B” convertible preferred shares have no voting rights except with respect to any distribution of dividends or reserves. Both classes of preferred shares enjoy a liquidation preference (if any liquidation surplus remains after repayment of Cellectis’ creditors and of par value to all shareholders) and are convertible, at AstraZeneca’s direction, into the same number of ordinary shares with the same rights as the outstanding ordinary shares.

Immediately after the Additional Investment, AstraZeneca owns approximately 44% of the share capital and 30% of the voting rights of the Company (based on the number of voting rights currently outstanding).

In addition, the appointment of Mr. Marc Dunoyer and Dr. Tyrell Rivers as members of the board of directors of Cellectis, decided by the extraordinary general meeting of the shareholders of Cellectis held on December 22, 2023 and conditioned upon the completion of the Additional Investment, is now effective.

In the absence of a public offering, no prospectus will be established in France or outside of France in connection with the Additional Investment.

Mr. Stril joined Cellectis in 2018 as Vice President, Corporate Development, and was appointed Chief Business Officer in 2020. He has been managing Cellectis’ business development and portfolio management teams and most recently led the execution of the Company’s strategic collaboration and investment agreements with AstraZeneca. As interim Chief Financial Officer, Mr. Stril will oversee the finance and investor relations functions, and continue to oversee the business development functions. He will remain based in Cellectis’ New York office.

“On behalf of Cellectis’ Board and team, I would like to warmly thank Bing for his contribution to the Company during his tenure, he was a key member of our leadership team during important corporate moments. We wish only the best for Bing and his family,” said André Choulika, PhD., Chief Executive Officer and Founder of Cellectis.

“While I will undoubtedly miss Bing, we are extremely excited about our next phases of growth and the nomination of Arthur as the interim CFO. Arthur has a deep knowledge and understanding of Cellectis. He will be of tremendous value to Cellectis as interim CFO as we advance our critical pipeline of assets into expansion and pivotal trials and explore new opportunities. Arthur’s commitment to excellence aligns perfectly with Cellectis’ values and vision for the future. As for the past years, he will be instrumental as we progress in the development of therapies for hard-to-treat cancer patients.”

“I am very excited to step into the role of interim CFO and contine to work with Cellectis’ teams, shareholders and partners at such an important moment for the company,” said Arthur Stril. “I look forward to continuing to build on the momentum of the recent years, as Cellectis keeps executing on its clinical trials, internal manufacturing, groundbreaking innovation, and strategic partnerships with leaders in the cell and gene therapy space.”

Mr. Stril began his career at the European Commission’s Directorate-General for Competition, controlling global pharmaceutical mergers. He later became head of the Hospital Financing Unit at the French Ministry of Health. Since 2023, Mr. Stril serves on the board of directors of Primera Therapeutics as a director designated by Cellectis. Mr. Stril graduated with a Master of Mathematics from Cambridge University and a Master of Physics from the École Normale Supérieure and holds immunotherapy and immuno-oncology diplomas from the University of Paris. Mr. Stril is also a member of the French Corps des Mines and is on the Board of Advisors of non-profit Life Science Cares.

• Execution of strategic collaboration and investment agreements with AstraZeneca

• Cécile Chartier, Ph.D., appointed as a director of the Cellectis’ Board of Directors

• Drawdown of the second tranche of €15 million under the credit facility agreement entered into with the European Investment Bank (EIB)

• Cash position of $156 million as of December 31, 2023[1]

New York, NY – April 29, 2024 - Cellectis (the “Company”) (Euronext Growth: ALCLS - NASDAQ: CLLS), a clinical-stage biotechnology company using its pioneering gene editing platform to develop life-saving cell and gene therapies, today provided business updates and reports preliminary financial results for the fourth quarter and full year 2023, ending December 31, 2023.

“Cellectis remains deeply focused on advancing its ongoing Phase 1 clinical trials BALLI-01, NaThaLi-01 and AMELI-01. The clinical data presented at ASH last December, regarding our product candidates UCART22 and UCART20x22, both manufactured in-house, are very encouraging and show high expansion potency and a high preliminary response rate. UCART22 manufactured in-house, compared to UCART22 manufactured by an external CDMO, shows meaningful superiority at a lower dose. These results show the major advantage we have in the market: the control of our production from A to Z to deliver highly potent reproducible product candidates.

Regarding UCART20x22, preliminary results presented at ASH showed one partial and two complete metabolic responses in patients who have failed prior autologous CD19 CAR T-cell therapies. These data support the continued study of UCART20x22 in r/r B-cell NHL,” said André Choulika, Ph.D., CEO of Cellectis.

“In Q4 2023, Cellectis entered into strategic collaboration and investment agreements with AstraZeneca. We are very proud of our partnership to design and develop the next generation of cell and gene therapy medicines with one of the most respected pharmaceutical companies. This collaboration will allow Cellectis and AstraZeneca to join forces and advance potentially breakthrough innovations in the cell and gene therapy space.

This year, Cellectis will continue to break new ground in the field of allogeneic cell therapy and we will provide regular updates in the advancements of our programs.”

Pipeline Highlights

UCART Clinical Programs

BALLI-01 (evaluating UCART22) in relapsed or refractory B-cell acute lymphoblastic leukemia (r/r B-ALL)

• On April 11, 2023, Cellectis announced that a patient was dosed in France with its first in-house manufactured product candidate UCART22 and completed the 28-day dose limiting toxicity (DLT) period.

• On June 8, 2023, at the European Hematology Association (EHA) Cellectis presented updated clinical and translational data supporting the preliminary safety and efficacy profile of UCART22 in a heavily pretreated r/r B-ALL population.
• On December 11, 2023, Cellectis presented a poster at the American Society of Hematology (ASH) Annual Meeting with updated results of the Phase I BALLI-01 trial. The poster presentation highlights the following data:

• In vitro comparability studies suggested that the new process used by Cellectis to manufacture in-house UCART22 (“UCART22 P2”) resulted in a more potent product than the process used by the external CDMO to manufacture UCART22 (“UCART22 P1”).
• As of July 1^st, 2023, 3 patients were enrolled into the first UCART22 P2 cohort at dose level 2 (1 million cells/kg). UCART22 P2 was administered after fludarabine, cyclophosphamide, and alemtuzumab (FCA) lymphodepletion and was well tolerated. No DLTs or ICANS were observed, and the CRS observed was Grade 1 or 2.
• There was a higher preliminary response rate (67%) at dose level 2 for UCART22 P2 compared to a 50% response rate with a dose 5 times higher of UCART22 P1 (dose level 3).
• UCART22 expansion was observed in the responding patients and correlated with response and increases in serum cytokines and inflammatory markers.

• The study continues to enroll patients with UCART22 P2.

NaThaLi-01 (evaluating UCART20x22) in relapsed or refractory B-cell non-Hodgkin lymphoma (r/r B-NHL)

On December 9, 2023, Cellectis presented a poster at the ASH Annual Meeting with the initial first-in-human preliminary results from the NatHaLi-01 trial, a Phase 1/2a dose-finding and expansion study evaluating UCART20x22 in r/r B-cell NHL. The poster presentation highlights the following data:

• As of July 1^st, 2023, 3 patients were enrolled and treated at dose level 1 (50 million cells flat dose). Cytokine release syndrome (CRS) Grade 1 or 2 occurred in all patients, and all CRS resolved with treatment. No immune effector cell associated neurotoxicity (ICANS) or graft versus host disease (GvHD) was observed. There were no UCART20x22 DLTs, and there was 1 DLT related to CLLS52 (alemtuzumab).
• All patients responded at Day 28, with 1 partial metabolic response and 2 complete metabolic responses in patients who had failed prior autologous CD19 CAR T-cell therapies.
• UCART20x22 expansion correlated with response and increases in serum cytokine and inflammatory marker levels as well as with CRS.
• These initial data support the continued study of UCART20x22 in r/r B-cell NHL and the study continues to enroll patients.

AMELI-01 (evaluating UCART123) in relapsed or refractory acute myeloid leukemia (r/r AML)

• On May 17, 2023, Cellectis presented an oral presentation at the American Society of Gene and Cell Therapy (ASGCT) 2023 Annual Meeting that was an encore of the clinical data on the AMELI-01 clinical trial that were unveiled at an oral presentation at the ASH 2022 Annual Meeting. These preliminary data supported the continued administration of UCART123 after FCA lymphodepletion in patients with r/r AML. The study continues to enroll patients.

MELANI-01 (evaluating UCARTCS1) in relapsed or refractory multiple myeloma (r/r MM)

• In April 2023, we announced our decision to stop enrollment and treatment of patients with UCARTCS1 under the MELANI-01 Study.

Research Data & Preclinical Programs

TALEN^® Editing Process for Gene Correction and Gene Insertion in HSPCs

• On April 10, 2024, Cellectis published a scientific article in Molecular Therapy, demonstrating that TALEN-mediated intron editing of hematopoietic stem and progenitor cells (HSPCs) enables transgene expression restricted to the myeloid lineage. This approach could unlock new therapeutic avenues for the treatment of inborn metabolic diseases as well as neurological diseases that require delivery of therapeutics to the brain.
• On April 22, 2024, Cellectis revealed two posters' presentations on novel TALEN® editing process for gene correction and gene insertion in hematopoietic stem and progenitor cells (HSPCs), at the American Society of Gene and Cell Therapy (ASGCT) annual meeting that will be held in Baltimore, Maryland on May 7-11, 2024.
• Full abstracts and presentations will be available on Cellectis’ website following the event.

TALEN^®-edited MUC1 CAR T-cells

• On April 17, 2023, Cellectis released preclinical data on TALEN^®-edited MUC1 CAR T-cells at the American Association for Cancer Research (AACR) Annual Meeting. The preclinical data presented in a poster showed the capability of armored allogeneic MUC1 CAR T-cells to excel in the immune suppressive tumor micro-environment suggesting that they could be an effective option in treating relapsed and refractory triple negative breast cancer (TNBC) patients with limited therapeutic options.

• On October 31, 2023, Cellectis presented preclinical data on MUC1-CAR T-cells to overcome key challenges of targeting solid tumors in a poster session at the Society for Immunotherapy of Cancer’s 38^th Annual Meeting (SITC). The preclinical data presented highlight the capability of multi-armored allogeneic CAR T-cells to preserve their activity despite the immunosuppressive microenvironment, while mitigating potential safety concerns.

Multiplex engineering for superior generation of efficient CAR T-cells

• On May 17, 2023, Cellectis presented preclinical data in a poster on multiplex engineering for superior generation of CAR T-cells, at the ASGCT Annual Meeting. In the presentation, Cellectis shows that we can use the state-of-the-art TALEN® technology to precisely edit up to four loci simultaneously while delivering several additional payloads to increase the efficacy and persistence of CAR T-cells.

HBB gene correction of sickle cell mutation

• On June 5, 2023, preclinical data on gene editing process using Cellectis TALEN® technology to develop highly efficient HBB gene correction of sickle cell mutation, were presented in a poster at the International Society for Cell and Gene Therapy (ISCT) 2023 Annual Meeting. These results showed that non-viral DNA delivery associated with TALEN® gene editing reduces the toxicity usually observed with viral DNA delivery and allows high levels of HBB gene correction in long-term repopulating hematopoietic stem cells.

TALE Base Editors (TALE-BE)

• On June 5, 2023, a comprehensive analysis to better design efficient TALE Base Editors (TALE-BE) using Cellectis’ TALEN® technology was presented in a poster at ISCT 2023 Annual Meeting. Cellectis developed a strategy that allowed to comprehensively characterize editing efficiencies in function of the TC position within the TALE-BE editing windows. This method is specifically taking advantage of the highly precise and efficient TALEN® mediated ssODN knock-in in primary T cells, allowing to focus on how target composition and spacer variations can affect TALE-BE activity/efficiency.

On October 25, 2023, Cellectis presented a comprehensive analysis of TALE-BE editing determinants at the European Society of Gene and Cell Therapy (ESGCT) 30^th annual congress. Cellectis believes that the knowledge presented will help ensure that genome editing-based strategies are skillfully designed to minimize the risk of potential genotoxic events, overall expanding the potential of TALE-BE for nuclear and mitochondrial therapeutic cell engineering.

TALEN-mediated HBB gene correction strategy

• On October 24, 2023, Cellectis presented preclinical data on its program of gene therapy for HSPC at the European Society of Gene and Cell Therapy (ESGCT) 30th annual congress.
• Intronic editing enables lineage specific expression of therapeutics relevant for HSPC gene therapy.
• TALEN®-mediated intron editing of the CD11b locus results in the lineage-specific expression of a reporter transgene in myeloid cells, with negligible expression in HSPC or other cellular subsets in vitro and in vivo.
• Cellectis believes this intron editing approach could be disruptive in HSPC gene therapy and brain delivery of multiple therapeutics.

Article published in Frontiers Bioengineering

• On May 12, 2023, Cellectis published an article in Frontiers Bioengineering demonstrating the efficacy of its TALEN® engineered FAP UCART-cells in cancer-associated fibroblast (CAF) depletion, reduction of desmoplasia and tumor infiltration. Over 90% of epithelial cancers including breast, colorectal, pancreatic and lung adenocarcinomas express the CAF-specific surface marker, fibroblast activation protein α (FAP), which makes it a promising CAR T-cell target. In this study, Cellectis proposed a novel and versatile approach of combination CAR T-cell therapy that can be extended to most stroma-rich cold tumors with relevant tumor-antigen targeting CAR T-cells which otherwise are recalcitrant to cell therapy.

Article published in Molecular Therapy – Methods & Clinical Development

• On October 12, 2023, Cellectis announced the publication of a new research paper in Molecular Therapy – Methods & Clinical Development, demonstrating the efficacy of its TALEN-mediated gene correction of mutated PIK3CD gene in Activated phosphoinositide 3-kinase delta syndrome 1 (APDS1) T-cells.

The study aims at exploring an alternative therapeutic strategy by correcting the mutated PIK3CD gene associated to APDS1 by gene editing. This article describes a TALEN®-mediated gene insertion strategy that allows targeted correction of the dominant gain-of-function mutation of the PIK3CD gene by insertion of a functional sequence in a precise manner. Results show efficient gene insertion in APDS1 patients’ T-cells, normalization of PI3K signaling and rescue of T-cell cytotoxic functions.

Partnerships

Collaboration and Investment Agreements with AstraZeneca

• In November 2023, Cellectis announced it has entered into (i) a joint research collaboration agreement (the “Collaboration Agreement”), (ii) an investment agreement relating to an initial equity investment of $80 million (the “Initial Investment Agreement”), and (iii) a subsequent investment agreement relating to an additional equity investment of $140 million, with AstraZeneca (the “Subsequent Investment Agreement”).
• Under the Collaboration Agreement, AstraZeneca Ireland (“AZ Ireland”) will leverage Cellectis’ proprietary gene editing technologies and manufacturing capabilities to design novel cell and gene therapy candidate products. As part of the Collaboration Agreement, 25 genetic targets have been exclusively reserved for AZ Ireland, from which up to 10 candidate products could be explored for development. AstraZeneca will have an option for a worldwide exclusive license on the candidate products, to be exercised before IND filing. Cellectis’ clinical-stage assets, UCART22, UCART123 and UCART20x22 will remain under Cellectis’ ownership and control.
• Under the Initial Investment Agreement, AstraZeneca Holdings (“AZ Holdings”) made an initial equity investment of $80 million in Cellectis by subscribing for 16,000,000 ordinary shares, at a price of $5.00 per share (the “Initial Investment”). Following settlement and delivery of the new shares, AZ Holdings owned approximately 22% of the share capital, and 21% of the voting rights of the Company.
• In addition to the Collaboration Agreement and the Initial Investment Agreement, on November 14, 2023, the Company and AZ Holdings entered into the Subsequent Investment Agreement. Under the Subsequent Investment Agreement, AZ Holdings will make a further equity investment in Cellectis of $140 million by subscribing for two newly created classes of convertible preferred shares of Cellectis: 10,000,000 “class A” convertible preferred shares and 18,000,000 “class B” convertible preferred shares, in each case at a price of $5.00 per share (the “Additional Investment”). Until they convert into ordinary shares, the “class A" convertible preferred shares would have single voting rights and would not carry any double voting rights, and the “class B” would carry no voting rights except on any distribution of dividends or reserves. Both classes of preferred shares would enjoy a liquidation preference (if any liquidation surplus remains after repayment of Cellectis’ creditors and of par value to all shareholders) and would be convertible into the same number of ordinary shares with the same rights as the outstanding ordinary shares. All the conditions precedents to the closing are met and the closing should occur on the earlier of (i) the third business day following the approval by the Cellectis' board of directors of the Company's annual and consolidated account for the financial year ended on December 31, 2023, and (ii) May 7, 2024 or such other date as may be agreed in writing by the parties.
• Immediately following the Additional Investment, it is anticipated that AZ Holdings would own approximately 44% of the share capital of the Company and 30% of the voting rights of the Company (based on the number of voting rights outstanding immediately after the completion of the Initial Investment) and as per the Company's shareholders decision dated December 22, 2023, Mr. Marc Dunoyer and Dr. Tyrell Rivers will serve on the Company's board of directors as members designated by AZ Holdings. Further, certain business decisions are subject to AZ Holdings’ approval, including, in particular, winding up any company of the Cellectis group, issuing securities senior to or pari passu with the convertible preferred shares or any shares without offering AstraZeneca the option to purchase its pro rata share of such securities (subject to customary exceptions, including issuances under employee equity incentive plans), declaring or paying dividends, prepaying indebtedness before due, and disposing of any material assets concerning gene editing tools or manufacturing facilities and selling, assigning, licensing, encumbering or otherwise disposing of certain material IP rights.

Licensed Allogeneic CAR T-cell Development Programs

Anti-CD19 programs

Allogene’s AlloCAR T™ oncology programs utilize Cellectis technologies. ALLO-501 and cemacabtagene ansegedleucel are anti-CD19 products being developed under a collaboration agreement between Servier and Allogene based on an exclusive license granted by Cellectis to Servier. Servier grants to Allogene exclusive rights to ALLO-501 and cemacabtagene ansegedleucel in the U.S.

• Allogene announced it continues to focus on the development of its investigational product cemacabtagene ansegedleucel, or cema-cel (previously known as ALLO-501A) as part of the first line (1L) treatment plan for LBCL patients who are likely to relapse following 1L chemoimmunotherapy, in the ALPHA3 1L consolidation trial. Allogene announced start-up activities for the ALPHA3 trial are underway and the trial is expected to begin in mid-2024.
• In the first quarter, Allogene further announced it began enrollment in the ALPHA2 trial of the investigational product cema-cel in patients with relapsed/refractory (r/r) Chronic Lymphocytic Leukemia (CLL).

Allogene: anti-CD70 program

The anti-CD70 program is licensed exclusively from Cellectis by Allogene and Allogene holds global development and commercial rights to this program.

· Allogene announced it has developed and implemented a diagnostic and treatment algorithm that may mitigate the treatment-associated hyperinflammatory response without compromising the CAR T function needed to eradicate solid tumors in its solid tumor trial with ALLO-316 in renal cell carcinoma (RCC).

Corporate Updates

Financing

• On January 4, 2023, we entered into an amendment to the sales agreement, dated as of March 29, 2021, with Jefferies LLC with respect to an equity offering program under which we may offer and sell ADS having an aggregate offering price of up to $60.0 million from time-to-time following January 4, 2023, through Jefferies as our sales agent. As of the date of this Annual Report, we have not sold any ADS under the amended program subsequent to such date. We decided to discontinue the ATM.
• In February 2023, Cellectis announced (i) the completion of its offering by way of a capital increase, of 8,800,000 American Depository Shares (ADS), each representing one ordinary share with a par value of 0.05 euro each (the “Offering”), which had been launched on February 2, 2023 and (ii) the exercise by the underwriting banks, Jefferies LLC and Barclays Capital Inc., of their option (the “Option”) to purchase an additional 1,107,800 ordinary shares (the “Additional Ordinary Shares”) of the Company to be delivered in the form of 1,107,800 ADSs. Following the Offering and the Option exercise, the total number of ordinary shares issued in the form of ADSs amounts to 9,907,800, bringing the gross proceeds of the Offering and Option to approximately $24,769,500 (€22,695,162.18) and the aggregate net proceeds, after deducting underwriting commissions and estimated offering expenses, to approximately $22,783,330 (€20,875,325.27). 

Calyxt and Cibus Merger Agreement

• On May 31, 2023, Calyxt, Inc. (“Calyxt”) completed its all-stock, reverse merger business combination with Cibus Global, LLC (“Cibus”). Following the closing of this merger, effective on June 1, 2023, the combined company operates under the name of Cibus, Inc.. Cellectis’ equity interest in Calyxt was reduced to 2.9% after the closing of the Merger, which resulted in Cellectis losing control of Calyxt.

Drawdown of 2 first tranches of the European Investment Bank financing

• On April 4, 2023, Cellectis announced it entered into the warrant agreement (the “Warrant Agreement”) and finalized the related ancillary documents required under the credit facility with the European Investment Bank (“EIB”) for up to €40 million previously announced on December 28, 2022. The Company also announced the drawdown of the first tranche of €20 million (“Tranche A”) under the Finance Contract, that has been disbursed by the EIB in early April 2023. Cellectis plans to use the proceeds of Tranche A towards the development of its pipeline of allogeneic CAR T-cell product candidates: UCART22, UCART20x22, UCART123.

· On January 16, 2024, Cellectis announced the drawdown of the second tranche of €15 million (“Tranche B”) under the credit facility agreement for up to €40 million entered into with the European Investment Bank (the “EIB”) on December 28, 2022 (the “Finance Contract”). The Company plans to use the proceeds of Tranche B towards the development of its pipeline of allogeneic CAR T-cell product candidates: UCART22, UCART20x22, and UCART123.

Shareholders General Meeting

• During its meeting held on June 27, 2023, the shareholders of the Company appointed Mrs. Cécile Chartier as director of the Company’s board of directors. At the end of the meeting, the terms of office of Ms. Annick Schwebig and Mr. Hervé Hoppenot ended and Ms. Annick Schwebig and Mr. Hervé Hoppenot departed the board of directors as of such date.  
• During its meeting held on December 22, 2023, the shareholders of the Company approved the Additional Investment of AstraZeneca. 

Non-viral circular ssDNA delivery associated to TALEN® gene editing allows high levels of gene insertion in long-term repopulating HSPCs

New York, NY – April 22, 2024 – Cellectis (the “Company”) (Euronext Growth: ALCLS - NASDAQ: CLLS), a clinical-stage biotechnology company using its pioneering gene-editing platform to develop life-saving cell and gene therapies, will present first data exploring novel TALEN® editing processes in hematopoietic stem and progenitor cells (HSPCs) at the American Society of Gene and Cell Therapy (ASGCT) being held on May 7-11, 2024.

“These two posters showcase the potential and versatility of the TALEN® technology to promote efficient gene insertion in HSPCs. We show that circular single strand DNA templates can be efficiently delivered to HSPCs and enable unprecedented efficiency of gene insertion without compromising the viability, fitness and differentiation capacity of edited cells” commented Julien Valton, Ph.D., Vice President of Gene Therapy at Cellectis.

“We also illustrate a novel TALEN® mediated-DNA template insertion approach that rewires the natural ability of myeloid cells to cross the blood brain barrier to efficiently vectorize a genetically encoded-therapeutic protein to the brain. This approach is, by essence, versatile and could be used to vectorize an array of therapeutic proteins to the brain and potentially address multiple neurological disorders.”

Poster presentation: Intron Editing of HSPC Enables Lineage-Specific Expression of Therapeutics

Gene therapy using edited hematopoietic and progenitor stem cells (HSPCs) has the potential to provide a lifelong supply of genetically encoded therapeutics.

Today, most therapies are impacted with the difficulty to cross the blood-brain barrier (BBB). The BBB is a continuous endothelial membrane that, along with pericytes and other components of the neurovascular unit, limits the entry of toxins, pathogens, protein and small molecules to the brain.

Cellectis has developed a TALEN® mediated promoter-less intron editing technology that enables the expression of a therapeutic transgene exclusively by monocyte derived from edited HSPCs.

The edited cells containing genetically encoded therapeutic proteins have the capacity to cross the blood-brain barrier and secrete the corresponding therapeutic within the brain.

This novel editing approach is an important addition to the HSPC gene editing toolbox that might unlock new strategies for the treatment of metabolic and neurological diseases.

Research data showed that:

o Intron editing can be performed within B-cell, T-cell, Monocyte-specific endogenous genes (CD20, CD4 and CD11b, respectively)

o Intron editing allows expression of transgenes in a lineage-specific manner without markedly impacting the expression of the endogenous gene targeted

o Editing of CD11b intron using a therapeutic transgene encoding IDUA (the enzyme missing in Type-1 Mucopolysaccharidosis patients) enables to restrict the expression of IDUA to the myeloid lineage.

o Edited HSPCs efficiently engraft in the bone-marrow of immunodeficient mice and differentiate into edited myeloid cells that can cross the BBB and populate the brain.

o The intron editing strategy described in this work is versatile and could be potentially used to vectorize multiple genetically encoded-therapeutic proteins to the brain and thus address multiple metabolic and neurological disorders.

Title: Intron Editing of HSPC Enables Lineage-Specific Expression of Therapeutics

Presenter: Julien Valton, Ph.D., Vice President Gene Therapy at Cellectis

Session Date/Time: May 8, 2024 at 12PM ET
Session Title: Gene Targeting and Gene Correction New Technologies
Presentation Room: Exhibit Hall
Final Abstract Number: 721

Poster presentation: Circularization of Non-Viral Single-Strand DNA Template for Gene Correction and Gene Insertion Improves Editing Outcomes in HSPCs

Today, most of the gene insertion approaches used to edit HSPCs ex vivo are hampered by the low efficiency of DNA template delivery into their nucleus.

Cellectis has developed and optimized a novel gene editing process, leveraging the TALEN® technology and circular single strand DNA template delivery, enabling highly efficient gene insertion in HSPCs.

Research data showed that:

o Non-viral single strand DNA delivery associated to TALEN® technology allows gene insertion in long-term repopulating hematopoietic stem cells

o Circularization of the single strand DNA further increases the rates of gene insertion without impacting cellular viability and fitness of HSPCs, facilitating the development of next generation of ex vivo cell therapies

Title: Circularization of Non-Viral Single-Strand DNA Template for Gene Correction and Gene Insertion Improves Editing Outcomes in HSPCs

Presenter: Alex Boyne, Gene Editing Platform Manager at Cellectis

Session Date/Time: May 9, 2024 at 12PM ET
Session Title: Nonviral Therapeutic Gene Delivery and Synthetic/Molecular Conjugates
Presentation Room: Exhibit Hall
Final Abstract Number: 1235

Full abstracts and poster presentations will be available on Cellectis’ website following the event: https://www.cellectis.com/en/investors/scientific-presentations/

New York, NY – April 10, 2024 – Cellectis (the “Company”) (Euronext Growth: ALCLS - NASDAQ: CLLS), a clinical-stage biotechnology company using its pioneering gene-editing platform to develop life-saving cell and gene therapies, announced today the publication of a new research paper in Molecular Therapy, demonstrating that TALEN-mediated intron editing of hematopoietic stem and progenitor cells (HSPCs) enables transgene expression restricted to the myeloid lineage. This approach could unlock new therapeutic avenues for the treatment of inborn metabolic diseases as well as neurological diseases that require delivery of therapeutics to the brain.

About HSPCs

Gene editing in hematopoietic stem and progenitor cells (HSPCs) has enabled the treatment of multiple previously uncurable genetic diseases. Edited therapeutic HSPCs can engraft in the patient’s bone marrow, self-replicate, differentiate and populate other organs, propagating the therapeutic effects systemically and indefinitely after a single intervention.

In this paper, Cellectis developed an intron-specific gene insertion strategy for HSPC, that restricts the expression of a therapeutic protein named IDUA to the myeloid lineage. Edited myeloid cells then act as a Trojan horse to vectorize IDUA across the blood brain barrier and thus, its delivery to the brain. This gene insertion strategy displays minimal genomic footprint and prevents the expression of IDUA by stem cells or other non-myeloid differentiated cells. It could potentially enable the development of efficient therapies for both metabolic and neurological disorders.

“This novel TALEN^® mediated-intron editing approach rewires the natural ability of myeloid cells to cross the blood brain barrier to efficiently vectorize a genetically encoded-therapeutic protein to the brain. In addition, by inserting the therapeutic transgene in an intronic region of the targeted gene, this approach preserves endogenous gene expression and thus, mitigates the common adverse events observed after gene insertion. This approach is, by essence, versatile and could be used to vectorize an array of therapeutic proteins to the brain and potentially address multiple neurological disorders” commented Julien Valton, Ph.D., Vice President of Gene Therapy at Cellectis.

Research data showed that:

• The CD11b intronspecific gene insertion approach efficiently restricts the expression of a desired transgene to the myeloid lineage, preventing its overexpression by stem cells or by other differentiated lineages.
• The insertion of an IDUA transgene in the first intron of the CD11b gene enables to express IDUA (the enzyme missing in Mucopolysaccharidosis type I patients), in a myeloidspecific manner without affecting CD11b endogenous expression.
• Edited HSPC exhibited robust engraftment in the bone marrow of immunodeficient mice, displayed multi-lineage differentiation in various hematopoietic tissues and showed significant presence in the brain as myeloid cells.

The article is available on Molecular Therapy website by clicking on this link:

https://doi.org/10.1016/j.ymthe.2024.04.001

Poster presentations:

Title: Circularization of Non-Viral Single-Strand DNA Template for Gene Correction and Gene Insertion Improves Editing Outcomes in HSPCs

Presenter: Alex Boyne, Gene Editing Platform Manager at Cellectis

Session Date/Time: May 9, 2024 at 12PM ET
Session Title: Nonviral Therapeutic Gene Delivery and Synthetic/Molecular Conjugates
Presentation Room: Exhibit Hall
Final Abstract Number: 1235

Cellectis presents the development of a novel gene editing process, leveraging the TALEN^® technology and non-viral DNA template delivery, enabling highly efficient gene correction and gene insertion in hematopoietic stem and progenitor cells (HSPCs).

Title: Intron Editing of HSPC Enables Lineage-Specific Expression of Therapeutics

Presenter: Julien Valton, Ph.D., Vice President Gene Therapy at Cellectis

Session Date/Time: May 8, 2024 at 12PM ET
Session Title: Gene Targeting and Gene Correction New Technologies
Presentation Room: Exhibit Hall
Final Abstract Number: 721

Gene therapy using hematopoietic and progenitor stem cells (HSPC) has the potential to provide a lifelong supply of genetically encoded therapeutics. Gene editing strategies enabling supra-endogenous expression of therapeutics often rely on constitutive promoters resulting in transgene overexpression irrespective of cellular differentiation, which could be detrimental for HSPC function. Cellectis presents the development of a TALEN^® mediated promoter-less intron editing strategy that relies on the endogenous cellular RNA splicing machinery to induce lineage-specific transgene expression exclusively after HSPC differentiation.

Full abstracts and presentations will be available on Cellectis’ website following the event:

https://www.cellectis.com/en/investors/scientific-presentations/

As a condition to the disbursement of Tranche B the Company issued 1,460,053 warrants to the benefit of the EIB, in accordance with the terms of the 14^th resolution of the shareholders’ meeting held on June 27, 2023 and articles L. 228-91 and seq. of the French Commercial Code (the “Tranche B Warrants”).

Each Tranche B Warrant allows the EIB to subscribe for one ordinary share of the Company, at a price of €2.53, corresponding to 99% of the volume-weighted average price of the Company’s ordinary shares over the last 3 trading days preceding the decision of the board of directors of the Company to issue the Tranche B Warrants. The total number of shares issuable upon exercise of the Tranche B Warrants represents circa 2% of the Company’s outstanding share capital as at their issuance date.

Tranche B will mature six years from its disbursement date and will accrue interest at a rate of 7% per annum capitalized annually and payable at maturity.

The other terms of the Tranche B Warrants and prepayment events of Tranche B under the Finance Contract are as set forth in the Company’s press release of April 4, 2023 and Form 6-K filed with the U.S. Securities and Exchange Commission on such date.

The Finance Agreement allows the Company to drawdown a third tranche, of a maximum amount of €5 million, subject to certain conditions, including issuance of a specified number of additional warrants to the benefit of the EIB.

At the meeting, resolutions 1 through 5 as well as resolutions 7 and 8 were adopted and resolution 6 was rejected, consistent with the recommendations of the board of directors.

Cellectis’ shareholders supported the contemplated $140M additional investment by AstraZeneca in the Company, to be effected by way of subscription of 10,000,000 newly created “class A” convertible preferred shares and 18,000,000 newly created “class B” convertible preferred shares, in each case at a price of $5.00 per share (the “Additional Investment”).

The completion of the Additional Investment remains subject to the clearance of such investment from the French Ministry of Economy pursuant to applicable foreign direct investment regulations, and other customary closing conditions.

The Company’s shareholders also approved the appointments of Mr. Marc Dunoyer and Dr. Tyrell Rivers as directors of the Cellectis board of directors, which appointment remains subject to the completion of the Additional Investment.

“We are grateful to our shareholders for supporting the Additional Investment and we are looking forward to welcoming Mr. Dunoyer and Dr. Rivers to our board of directors. Their extensive experience in the pharma industry will be an additional asset for the Company. This Additional Investment would provide meaningful and valued perspectives to our common ambition of bringing potentially life-saving therapies to patients with unmet medical needs” said Jean Pierre Garnier, Chairman of the Board of Directors at Cellectis.

Mr. Marc Dunoyer is Chief Strategy Officer of AstraZeneca and Chief Executive Officer of Alexion, AstraZeneca Rare Disease. He had previously served as an Executive Director and AstraZeneca’s Chief Financial Officer from November 2013. Mr. Marc Dunoyer’s career in pharmaceuticals, which has included periods with Roussel Uclaf, Hoechst Marion Roussel and GSK, has given him extensive industry experience. He is a qualified accountant and joined AstraZeneca in 2013, serving as Executive Vice-President, Global Product and Portfolio Strategy from June to October 2013. Prior to that, he served as Global Head of Rare Diseases at GSK and (concurrently) Chairman, GSK Japan. Mr. Dunoyer is a member of the Boards of Orchard Therapeutics Plc and JCR Pharmaceuticals. He holds an MBA from HEC Paris and a Bachelor of Law degree from Paris University.

Dr. Tyrell Rivers is Executive Director of Corporate Ventures at AstraZeneca, where he is responsible for creating and executing innovative, value-enhancing business strategies. Prior to assuming this role in 2014, he worked at MedImmune Ventures, specializing in life science investing. Earlier in his career, Dr. Rivers held various positions at Merck & Co., where he led technical support for commercial vaccines and directed global business initiatives for accessing key technologies for research and development. He currently serves as a Board member of ADC Therapeutics, Cerapedics, and Quell Therapeutics. Dr. Rivers holds his B.S. in Chemical Engineering from the Massachusetts Institute of Technology, a Ph.D. in Chemical Engineering from the University of Texas at Austin, and an M.B.A. from the New York University Stern School of Business.

The detailed results of the vote and the resolutions are available on Cellectis’ website: https://www.cellectis.com/en/investors/general-meetings/

The notice of meeting as published today in the BALO (Bulletin des Annonces Legales Obligatoires), including the agenda, the text of the resolutions and the terms of participation, is online on the Cellectis website at the following address:

https://www.cellectis.com/en/investors/general-meetings/

New York, NY – November 15,  2023 - Cellectis (Euronext Growth: ALCLS – NASDAQ: CLLS) today anounced that, following the consultation of its works council, it has now signed a binding Subsequent Investment Agreement with AstraZeneca (LSE/STO/Nasdaq: AZN) regarding the contemplated additional equity investment of $140M by AstraZeneca, which was previously announced on November 1, 2023. The additional investment will be made by way of subscription of 10,000,000 “class A” convertible preferred shares and 18,000,000 “class B” convertible preferred shares, in each case at a price of $5.00 per share (the “Additional Investment”).

The closing of the Additional Investment remains subject to (i) the approval of the extraordinary general meeting of the shareholders of Cellectis to be called in the coming days and expected to be held on or around December 22, 2023, (ii) clearance of such investment from the French Ministry of Economy according to the foreign direct investment French regulations, and (iii) other customary closing conditions. Immediately following the Additional Investment, it is anticipated that AstraZeneca would own approximately 44% of the share capital of the Company and 30% of the voting rights of the Company (based on the number of voting rights currently outstanding).

In the absence of a public offering, no prospectus will be established in France or outside of France in connection with the Additional Investment.

• Updated results of the Phase I BALLI-01 Trial evaluating UCART22 in r/r B-cell ALL and preliminary results of the Phase I NATHALI-01 Trial evaluating UCART20x22 in r/r B-cell NHL to be presented at ASH 65^th Annual meeting.

• Clinical trials ongoing: BALLI-01 (evaluating UCART22), NATHALI-01 (evaluating UCART20x22) and AMELI-01 (evaluating UCART123) studies for patients with r/r B-cell ALL, r/r B-cell NHL and r/r AML, respectively.

• Preclinical data on HSPC gene therapy and a comprehensive analysis of TALE-BE editing determinants presented at ESGCT 2023 30^th annual congress.

• Preclinical data on Multi-armored Allogeneic MUC1-CAR T-cells targeting Triple-Negative Breast at SITC 2023 annual event.

• Cash position of $72[1] million as of September 30, 2023. Cash runway into 2026 including Initial AstraZeneca Investment and Potential Additional AstraZeneca Investment.

• Conference call scheduled for 8.00am ET / 2.00 pm CET on November 7, 2023

These data will be presented in two poster sessions:

Poster Presentation (P2110)

Title: Preliminary Results of Nathali-01: A First-in-Human Phase I/IIa Study of UCART20x22, a Dual Allogeneic CAR-T Cell Product Targeting CD20 and CD22, in Relapsed or Refractory (R/R) Non-Hodgkin Lymphoma (NHL)

Session Name: 704. Cellular Immunotherapies: Early Phase and Investigational Therapies: Poster I

Presenter: Dr. Jeremy Abramson (Massachusetts General Hospital Cancer Center)

Date/Time: Saturday, December 9, 2023 at 5:30 - 7:30 PM PT at San Diego Convention Center, Halls G-H

The poster presentation highlights the following data:

• as of July 1, 2023, 3 patients were enrolled and treated at dose level 1 (50 million cells) with product manufactured in-house by Cellectis. Cytokine release syndrome (CRS) Grade 1 or 2 occurred in all patients, and all CRS resolved with treatment.
• No immune effector cell associated neurotoxicity (ICANS) or graft versus host disease (GvHD) was observed. There were no UCART20x22 dose limiting toxicities (DLTs), and there was 1 DLT in connection with CLLS52 (alemtuzumab).
• All patients responded at Day 28, with 1 partial metabolic response and 2 complete metabolic responses in patients who had failed prior autologous CD19 CAR T-cell therapies.
• UCART20x22 expansion correlated with increases in serum cytokine and inflammatory marker levels as well as with CRS.
• These initial data support the continued clinical trial evaluating UCART20x22 in R/R NHL.

Poster Presentation (P4847)

Title: Updated Results of the Phase I BALLI-01 Trial of UCART22 Process 2 (P2), an Anti-CD22 Allogeneic CAR-T Cell Product Manufactured By Cellectis Biologics, in Patients with Relapsed or Refractory (R/R) CD22+ B-Cell Acute Lymphoblastic Leukemia (B-ALL)

Session Name: 704. Cellular Immunotherapies: Early Phase and Investigational Therapies: Poster III

Presenter: Dr. Nitin Jain (University of Texas MD Anderson Cancer Center)

Date/Time: Monday, December 11, 2023 at 6:00 - 8:00 PM PT at San Diego Convention Center, Halls G-H

The poster presentation highlights the following data:

• in vitro comparability studies suggested that UCART22 Process 2 (P2) (manufactured in-house by Cellectis) is more potent than UCART22 Process 1 (P1) (manufactured by an external CDMO), and as of July 1, 2023, 3 patients were enrolled into the first UCART22 P2 cohort at dose level 2 (1 million cells/kg).
• UCART22 P2 was administered after fludarabine, cyclophosphamide, and alemtuzumab (FCA) lymphodepletion regimen and was well tolerated. No DLTs or ICANS was observed, and the CRS observed was Grade 1 or 2.
• There was a higher preliminary response rate (67%) at dose level 2 (1 million cells/kg) with UCART22 P2 (manufactured in-house by Cellectis) compared to 50% at dose level 3 (5 million cells/kg) with UCART22 P1 (manufactured by an external CDMO).
• UCART22 expansion was observed in the responding patients and correlated with increases in serum cytokines and inflammatory markers.
• The study continues to enroll patients at dose level 2i (2.5 million cells/kg) with UCART22 P2.

The announcement will be followed by an investor conference call and webcast on Tuesday, November 7, 2023 at 8:00 AM ET / 2:00 PM CET. The call will include the Company’s third quarter results and an update on business activities. Details for the call are as follows:

Dial in information:

Domestic: 1-877-451-6152

International: 1-201-389-0879

Conference ID: 13741035

Webcast Link: https://viavid.webcasts.com/starthere.jsp?ei=1632799&tp_key=bff99741ab

New York, NY – November 1, 2023 - Cellectis (Euronext Growth: ALCLS – NASDAQ: CLLS) today announced it has entered into (i) a Joint Research Collaboration Agreement (the “Collaboration Agreement”, (ii) an investment agreement relating to an initial equity investment of $80M, and (iii) a memorandum of understanding (the “MOU”) relating to an additional equity investment of $140M, with AstraZeneca (LSE/STO/Nasdaq: AZN). The Collaboration Agreement aims to accelerate the development of next generation therapeutics in areas of high unmet need, including oncology, immunology and rare diseases.

Under the terms of the Collaboration Agreement, AstraZeneca will leverage Cellectis’ proprietary gene editing technologies and manufacturing capabilities to design novel cell and gene therapy candidate products. As part of the Collaboration Agreement, 25 genetic targets have been exclusively reserved for AstraZeneca, from which up to 10 candidate products could be explored for development. AstraZeneca will have an option for a worldwide exclusive license on the candidate products, to be exercised before IND filing.

Pursuant to the Collaboration Agreement, Cellectis’ research costs under the collaboration will be funded by AstraZeneca and Cellectis will receive an upfront payment of $25M. Under the terms of the Collaboration Agreement, Cellectis is also eligible to receive an investigational new drug (IND) option fee and development, regulatory and sales-related milestone payments, ranging from $70M up to $220M, per each of the 10 candidate products, plus tiered royalties.

As a condition to the signing of the Collaboration Agreement, AstraZeneca has agreed to make an initial equity investment of $80M in Cellectis by subscribing for 16,000,000 ordinary shares, at a price of $5.00 per share (the “Initial Investment”). The new shares are issued to AstraZeneca by the board of directors of Cellectis pursuant to the 17^th resolution of Cellectis’ shareholders meeting held on June 27, 2023. Following settlement and delivery of the new shares (expected to be on November 6, 2023), AstraZeneca will own approximately 22% of the share capital, and 21% of the voting rights of the Company, will have the right to nominate a non-voting observer on the board of directors of Cellectis, and will have the right to participate pro rata in Cellectis’s future share offerings.

Additionally, the MOU contemplates that AstraZeneca will make a potential further equity investment in Cellectis of $140M by subscribing for two newly created classes of convertible preferred shares of Cellectis: 10,000,000 “class A” convertible preferred shares and 18,000,000 “class B” convertible preferred shares, in each case at a price of $5.00 per share (the “Additional Investment”). Until they convert into ordinary shares, the “class A" convertible preferred shares would have single voting rights and would not carry any double voting right at any moment, and the “class B” would carry no voting rights except on any distribution of dividends or reserves. Both class of preferred shares would enjoy a liquidation preference (if any liquidation surplus remains after repayment of Cellectis’ creditors and of par value to all shareholders) and would be convertible into the same number of ordinary shares with the same rights as the outstanding ordinary shares. The MOU is non-binding and the Additional Investment remains to be confirmed by both parties following a consultation process with Cellectis’ works council. If confirmed, the closing of the Additional Investment will remain subject to (i) Cellectis’ shareholders’ approval at a two-thirds majority of the votes cast by voting shareholders, (ii) clearance of such investment from the French Ministry of Economy according to the foreign direct investment French regulations, and (iii) other customary closing conditions. Immediately following the Additional Investment, it is anticipated that AstraZeneca would own approximately 44% of the share capital of the Company and 30% of the voting rights of the Company (based on the number of voting rights outstanding immediately after the completion of the Initial Investment) and would have the right to nominate two directors to the board of directors of Cellectis. Further, certain business decisions are subject to AstraZeneca’s approval, including, in particular, winding up any company of the Cellectis group, issuing securities senior to or pari passu with the convertible preferred shares or any shares without offering AstraZeneca the option to purchase its pro rata share of such securities (subject to customary exceptions, including issuances under employee equity incentive plans), declaring or paying dividends, prepaying indebtedness before due, and disposing of any material assets concerning gene editing tools or manufacturing facilities and selling, assigning, licensing, encumbering or otherwise disposing of certain material IP rights.

Cellectis will use the proceeds received from the Collaboration Agreement and the proposed equity investments to develop gene editing tools, for research and development expenses incurred in developing its programs, and other general corporate purposes. Cellectis’ clinical-stage assets, UCART22, UCART123 and UCART20x22 will remain under Cellectis’ ownership and control.

André Choulika, PhD, Chief Executive Officer of Cellectis, said: “We believe AstraZeneca is the perfect match to Cellectis by providing world-class expertise in the development and the commercialization of innovative medicines. This collaboration will allow us to leverage our pioneering research in gene editing and cell therapies, as well as our cutting-edge capabilities in manufacturing with the ambition to bring potentially life-saving therapies to patients with unmet medical need.”

Marc Dunoyer, Chief Strategy Officer, AstraZeneca, and Chief Executive Officer, Alexion, AstraZeneca Rare Disease, said: “The differentiated capabilities Cellectis has in gene editing and manufacturing complement our in-house expertise and investments made in the past year. AstraZeneca continues to advance our ambition in cell therapy for oncology and autoimmune diseases as well as in genomic medicine, which has potential to be transformative for patients with rare diseases.”

In the absence of a public offering, no prospectus will be established in France or outside of France in connection with the Initial Investment or Additional Investment.

The data will be presented by Laurent Poirot, Ph.D., SVP Immunology of Cellectis, in a poster session that will be held November 4^th 2023 from 9:00 a.m. to 8:30 p.m. PDT, at San Diego Convention Center, Hall A.

The poster is number 254 and it is entitled “TGF-Beta Blockade Combined with Activation-Induced IL12 Secretion Synergize to Optimize Potency of MUC1-CAR T-cells in Preclinical Targeting of Triple-Negative Breast Cancer”.

While during SITC 2022 Cellectis presented how TALEN®-mediated gene editing allows programming of various functions addressing both safety and potency aspects of allogenic CAR T-cell therapy, this year the company’s presentation will focus on the synergistic benefits of ΔPD1-IL12 and TGFBR2-KO attributes in preclinical models of triple negative breast cancer.

“We demonstrate that combination of the ΔPD1-IL12 with TGFBR2 KO not only enhanced CAR-T cell activity but surprisingly limit their accumulation outside the tumor, therefore reducing the risks of off-tumor toxicity. These cells also show strong anti-tumor activity against distal tumors when infused intratumorally.”, said Laurent Poirot, Ph.D., SVP Immunology at Cellectis.

These pre-clinical data highlight the capability of multi-armored allogeneic CAR T-cells to preserve their activity despite the immunosuppressive microenvironment, while mitigating potential safety concerns.

The data will be presented in three posters:

Intronic editing enables lineage specific expression of therapeutics relevant for HSPC gene therapy (Poster N°646)

Presenter: Eduardo Seclen, Senior Scientist & Team Leader, Gene Editing

Date/Time: Wednesday October 25^th from 18:15 to 19:30 and Thursday October 26^th from 19:30 to 20:30

• Intronic editing enables lineage specific expression of therapeutics relevant for HSPC gene therapy.
• TALEN®-mediated intron editing of the CD11b locus results in the lineage-specific expression of a reporter transgene in myeloid cells, with negligible expression in HSPC or other cellular subsets in vitro and in vivo.
• We believe this intron editing approach could be disruptive in HSPC gene therapy and brain delivery of multiple therapeutics.

TALEN editing coupled to non-viral DNA delivery enables efficient correction of sickle cell mutation with minimal transcriptional changes and low level of HBB KO (Poster N°380)

Presenter: Julien Valton, VP, Gene Therapy

Date/Time: Wednesday October 25^th from 18:15 to 19:30 and Thursday October 26^th from 19:30 to 20:30

• Using a combination of scRNA sequencing and multiple genomic read out methodologies, we demonstrate that the mutant HBB gene can be efficiently corrected in HSPCs by TALEN®-mediated gene editing coupled to non-viral gene delivery (ssODN) with a low risk of generating β-thalassemic RBCs.
• TALEN®-mediated HBB editing coupled to non-viral gene delivery (ssODN) in SCD patients’ HSPCs led to a lower activation of p53 response compared to viral gene delivery (AAV), preserves the transcriptomic profile of edited HSPCs in vitro and their engraftment capacity in vivo.

Comprehensive analysis of TALE-BE editing determinant (Poster N°667)

Presenter: Maria Feola, Scientist III, Manager, Gene Editing

Date/Time: Wednesday October 25^th from 17:00 to 18:15 and Thursday October 26^th from 20:30 to 21:30

• The robustness and versatility of genome engineering strategies we developed allowed us to gain in-depth insight of TALE-BE editing rules in cellulo and further highlighted that the composition surrounding the TC to be edited could strongly impact editing efficiencies. Therefore, educated choice of the TALE-BE architecture and positioning on DNA could either prevent target sequence limitations (increasing targetable sequence space) or decrease, if not eliminate, bystander editing within the editing window, allowing for more precise genome editing outcomes.
• We believe that the knowledge presented will help ensure that genome editing-based strategies are skillfully designed to minimize the risk of potential genotoxic events, overall expanding the potential of TALE-BE for nuclear and mitochondrial therapeutic cell engineering.

The research work described in this article was jointly conducted by Imagine Institute and Cellectis teams.

About APDS1:

Activated phosphoinositide 3-kinase δ syndrome (also known as APDS type 1 or APDS1) is a rare but devastating disease caused by gain-of-function mutations in the PIK3CD gene and resulting in a combined immunodeficiency.

Approved treatments for APDS1 consist in prophylactic measures including long term antibiotics and Ig (immunoglobulin) replacement therapy.

Allogeneic hematopoietic stem/progenitor cell (HSPC) transplantation has been proposed as a definitive treatment for APDS1. However, the lack of compatible donor as well as graft failure, graft instability, and poor graft function are still major challenges that must be overcome to reach a positive therapeutic outcome. Thus, so far there are neither optimal nor long-term therapeutic solutions for APDS1 patients and new alternative treatments are highly regarded.

The study published here aims at exploring an alternative therapeutic strategy by correcting the mutated PIK3CD gene associated to APDS1 by gene editing. This article describes a TALEN®-mediated gene insertion strategy that allows targeted correction of the dominant gain-of-function mutation of the PIK3CD gene by insertion of a functional sequence in a precise manner. Results show efficient gene insertion in APDS1 patients’ T-cells, normalization of PI3K signaling and rescue of T-cell cytotoxic functions.

Preclinical results demonstrated that:

• The PIK3CD gene can be efficiently corrected by TALEN®-mediated gene insertion of the functional PIK3CD DNA sequence vectorized by AAV, in healthy donor and APDS1 patient T-cells.
• TALEN®-mediated PIK3CD gene correction rescues PI3K signaling in APDS1 patient T-cells.
• TALEN®-mediated PIK3CD gene correction normalizes the transcriptomic status of APDS1 patient CD8+ T-cells and rescues their cytolytic activity.

In summary, we demonstrate that the PIK3CD dominant gain of function mutation associated to APDS1 can be successfully corrected in APDS1 patient T-cells using TALEN® gene editing and AAV-based DNA repair matrix. This correction rescues the cytolytic function of APDS1 T-cells, normalizes their intracellular phospho-AKT levels found at basal and at activated states as well as the transcriptomic signature of certain genes involve in T-cells’ cytolytic function, activation, and fitness.

“This successful demonstration of PIK3CD gene correction warrants the development of a gene therapy approach to treat p110δ dysregulations in a long-term fashion. This proof-of-concept study paves the way for the future development of a bona fide gene surgery candidate to potentially cure APDS1” said Julien Valton, Ph.D., Vice President Gene Therapy at Cellectis.

Rescuing the Cytolytic Function of APDS1 Patient T-cells via TALEN-mediated PIK3CD Gene Correction

Poggi L.^1,2, Chentout L.^1,2, Lizot S.³, Boyne A. ⁴, Juillerat A.⁴, Moiani A.³, Luka M.^5,6, Carbone. F ^5,6, Ménager M M. ^5,6, Cavazzana M.^1,7, Duchateau P.⁴, Valton J.³*, Kracker S.^1,2*

¹ Université de Paris Cité, Imagine Institute, Paris, France

² Laboratory of Human Lymphohematopoiesis, INSERM UMR 1163, Paris, France

³ Cellectis, 8 rue de la Croix Jarry, 75013 Paris, France

⁴ Cellectis, Inc., 430 East 29th Street, New York, NY 10016, USA.

⁵ Université de Paris Cité, Imagine Institute, Laboratory of Inflammatory Responses and Transcriptomic Networks in Diseases, Atip-Avenir Team, INSERM UMR 1163, F-75015 Paris, France

⁶ Labtech Single-Cell@Imagine, Imagine Institute, INSERM UMR 1163, F-75015 Paris, France.

⁷ Biotherapy Clinical Investigation Center, Groupe Hospitalier Universitaire Ouest, Assistance Publique-Hôpitaux de Paris, INSERM, Paris, France

* Corresponding authors Julien Valton and Sven Kracker (julien.valton@cellectis.com and sven.kracker@inserm.fr, respectively)

Poster Presentation:

Laurent Poirot, SVP Immunology of Cellectis, will present a poster on the benefits of combining potency attributes for TALEN®-edited smart CAR T-cells targeting MUC1 in preclinical models of triple-negative breast cancer.

Title: TGF-Beta Blockade Combined with Activation-Induced IL12 Secretion Synergize to Optimize Potency of MUC1-CAR T-cells in Preclinical Targeting of Triple-Negative Breast Cancer.

Poster Number: 254

Presenter: Laurent Poirot, Ph.D., SVP Immunology, Cellectis.

Date/Time: Poster will be on display Saturday, November 4^th, 2023 from 9:00 a.m. to 8:30 p.m. PDT, at San Diego Convention Center, Hall A.

Full text of the abstract will be made public on October 31, 2023 at 9:00 a.m. EDT on the SITC website and in a Journal for ImmunoTherapy of Cancer (JITC) supplement published on Oct. 31^st, 2023 at 6 a.m. PDT/9 a.m. EDT.

Financial Results

The interim condensed consolidated financial statements of Cellectis, have been prepared in accordance with International Financial Reporting Standards, as issued by the International Accounting Standards Board (“IFRS”).

We present certain financial metrics broken out between our two reportable segments – Therapeutics and Plants – in the appendices of this Q2 2023 financial results press release.

On January 13, 2023, Calyxt, Cibus Global LLC (Cibus) and certain other parties named therein, entered into an Agreement and Plan of Merger (the “Merger Agreement”), pursuant to which, subject to the terms and conditions thereof, Calyxt and Cibus will merge in an all-stock transaction (the “Calyxt Merger”). As a consequence of the foregoing, Calyxt met the “held-for-sale” criteria specified in IFRS 5 and was classified as a discontinued operation until May 31, 2023.

On June 1, 2023, Calyxt and Cibus closed the merger transaction and now operate under the name Cibus, Inc. Consequently, Calyxt was deconsolidated and Calyxt's cash, cash equivalent and restricted cash are no longer included in the Group's cash, cash equivalent and restricted cash since June 1, 2023.

Cash: As of June 30, 2023, Cellectis, had $89 million in consolidated cash, cash equivalents, and restricted cash. This compares to $95 million in consolidated cash, cash equivalents and restricted cash as of December 31, 2022. This $6 million difference mainly reflects $55 million of cash out, which include $15 million for R&D suppliers, $7 million for SG&A suppliers, $23 million for staff costs, $7 million for rents and taxes, $3 millions of reimbursement of the “PGE” loan, and a $1 million unfavorable impact on Forex partially offset by a $23 million net cash inflow from the capital raise closed in February, a $21 million net cash inflow from EIB loan, a $1 million cash inflow related to the grant and refundable advance from BPI, $2 millions of financial investments’ capital gain and interests, a $1 million reimbursement of social charges paid on stock options, and a $2 million net cash inflow from licenses and other cash receipts.

Based on the current operating plan, Cellectis anticipates that the cash, cash equivalents, and restricted cash as of June 30, 2023 will fund Cellectis’ operations into the third quarter of 2024.

Revenues and Other Income: Consolidated revenues and other income were $5.6 million for the six months ended June 30, 2023 compared to $6.5 million for the six months ended June 30, 2022. The decrease of $1.0 million reflects the recognition of two milestones related to Cellectis’ agreement with Cytovia for $1.5 million in 2022 and a milestone of $1.0 million with another partner while recognition of revenues in 2023 is not material, and partially offset by the increase of the research tax credit for $0.8 million and the partial recognition of a grant signed with “BPI” of $0.8 million.

R&D Expenses: Consolidated R&D expenses were $43.2 million for the six months ended June 30, 2023, compared to $52.2 million for the six months ended June 30, 2022. The $9.0 million decrease was primarily attributable to (i) a $3.4 million decrease in personal expenses due to departures not replaced (ii) a $4.7 million decrease in purchases, external expenses and other (from $28.0 million in 2022 to $23.2 million in 2023) mainly explained by internalization of our manufacturing and quality activities to support our R&D pipeline and (iii) a $0.8 million decrease of non-cash stock-based compensation expenses (from $3.1 million to $2.3 million).

SG&A Expenses: Consolidated SG&A expenses were $8.9 million for the six months ended June 30, 2023, compared to $10.9 million for the six months ended June 30, 2022. The $2.0 million decrease primarily reflects (i) a $1.6 million decrease in purchases, external expenses and other (from $6.4 million in 2022 to $4.9 million in 2023) mainly explained by the implementation of our ERP in 2022 (ii) a $0.2 million decrease in personal expenses and non-cash stock-based compensation expenses.

Net financial gain (loss): Consolidated net financial gain was $11.6 million for the six months ended June 30, 2023, compared to $9.2 million for the six months ended June 30, 2022. The $2.4 million increase primarily reflects (i) a $20.8 million increase of financial income, mainly attributable to the profit from Calyxt’s deconsolidation, partially offset by (ii) the loss in fair value on our retained investment in Calyxt since deconsolidation for $10.2 million, (iii) a $6.8 million decrease in the fair value of Cytovia’s note receivable.

Net income (loss) from discontinued operations: Pursuant to Calyxt deconsolidation income from discontinued operation for the six-month period ended June 30, 2023, 2023 only include five months of activity. The $3.5 million increase of net loss from discontinued operations between the six-month period ended June 30, 2022 and 2023 is primarily driven by (i) the increase of $9.2 million of net financial loss and (ii) the increase of $1.5 million of other operating expenses partially offset by (i) the decrease of $2.8 million of R&D expenses (from $6.3 million in 2022 to $3.5 in 2023) and (ii) the decrease of $4.5 million of SG&A expenses (from $6.8 million in 2022 to $2.3 million in 2023).

Net Income (loss) Attributable to Shareholders of Cellectis: The consolidated net loss attributable to shareholders of Cellectis was $40.7 million (or $0.76 per share) for the six months ended June 30, 2023, of which $35.7 million was attributed to Cellectis continuing operations, compared to $50.9 million (or $1.12 per share) for the six months ended June 30, 2022, of which $47.3 million was attributed to Cellectis continuing operations. This $10.1 million decrease in net loss between the first six months of 2023 and 2022 was primarily driven by (i) a $9.0 million decrease of R&D expenses, (ii) a $2.0 million decrease of SG&A expenses and (iii) an increase of $2.4 million of the financial gain due to the deconsolidation of Calyxt compensated in part by the decrease of fair value of Cytovia’s note receivable. These downward impacts on the net loss were partially offset by (i) a decrease of $1.0 million of revenues and other income, (ii) an increase of $1.5 million of loss from discontinued operations attributable to Shareholders of Cellectis.

Adjusted Net Income (Loss) Attributable to Shareholders of Cellectis: The consolidated adjusted net loss attributable to shareholders of Cellectis was $36.7 million (or $0.68 per share) for the six months ended June 30, 2023, compared to a net loss of $45.5 million (or $1.00 per share) for the six months ended June 30, 2022.

Please see "Note Regarding Use of Non-IFRS Financial Measures" for reconciliation of GAAP net income (loss) attributable to shareholders of Cellectis to adjusted net income (loss) attributable to shareholders of Cellectis.

We currently foresee focusing our cash spending at Cellectis for 2023 in the following areas:

• Supporting the development of our pipeline of product candidates, including the manufacturing and clinical trial expenses of UCART123, UCART22, UCART 20x22 and potential new product candidates;
• Operating our state-of-the-art manufacturing capabilities in Paris (France), and Raleigh (North Carolina, USA); and
• Continuing to strengthen our manufacturing and clinical departments.

* Clinical trials ongoing: BALLI-01 (evaluating UCART22), NATHALI-01 (evaluating UCART20x22) and AMELI-01 (evaluating UCART123) studies for patients with r/r B-cell ALL, r/r B-cell NHL and r/r AML, respectively

* Preclinical data presented on HBB gene correction of sickle cell mutation & TALE Base Editors (TALE-BE) at ISCT 2023 annual event

* Appointment of Cécile Chartier, Ph.D., as Director to Cellectis’ Board of Directors

* Cash position^[1] of $89 million as of June 30, 2023. Cash runway into Q3 2024

* Full financial statements for the second quarter of 2023 will be released in the coming days

* Conference call scheduled for 8AM ET/2PM CET on August 4, 2023

 New York, NY – August 3, 2023 - Cellectis (the “Company”) (Euronext Growth: ALCLS - NASDAQ: CLLS), a clinical-stage biotechnology company using its pioneering gene-editing platform to develop life-saving cell and gene therapies, today provided business updates and preliminary financial results for the six-month period ending June 30, 2023. Full report of the financial results for the second quarter of 2023 will be released in the coming days.

“We are proud of our team and the strong execution this quarter. Our clinical data presented for UCART22 at the European Hematology Association (EHA) were positive for patients with r/r B-ALL who have failed multiple lines of treatment including multi-agent chemoimmunotherapy, CD19 directed CAR T-cell therapy, and allogeneic stem cell transplant. We are looking forward to releasing new data later this year on our UCART22 product candidate manufactured in-house,” said André Choulika, Ph.D., Chief Executive Officer at Cellectis.

“In addition, we have made progress with our pipeline in 2023 and continue to focus on our core clinical trials BALLI-01 (evaluating UCART22), NATHALI-01 (evaluating UCART20x22) and AMELI-01 (evaluating UCART123). This quarter, Cellectis presented an encore of the clinical data on the AMELI-01 clinical trial at the American Society of Gene and Cell Therapy (ASGCT) 2023 annual meeting. These preliminary data support the continued administration of UCART123 after FCA lymphodepletion in patients with r/r AML.

Cellectis’ innovation team also presented preclinical data on a gene editing process to develop a bona fide HBB gene correction of sickle cell mutation, and a comprehensive analysis to better design efficient TALE Base Editors (TALE-BE) at the International Society for Cell and Gene Therapy (ISCT) 2023 annual meeting. These achievements showcase once more the power of our gene-editing platform and our TALEN®, the technology of choice for therapeutic gene editing, and that we are continuing to deliver constant breakthrough innovation to treat diseases with unmet medical needs.

Despite an unprecedented challenging market environment for cell and gene therapy companies, Cellectis remains focused in its mission to develop innovative cancer therapy product candidates.”

Pipeline Highlights

UCART Clinical Development Programs

BALLI-01 (evaluating UCART22) in relapsed or refractory B-cell acute lymphoblastic leukemia (r/r B-ALL)

• UCART22 is an allogeneic CAR T-cell product candidate targeting CD22 and is being evaluated in patients with r/r B-ALL in the BALLI-01 Phase 1/2a clinical study.

• On June 9, Cellectis presented updated clinical and translational data at the European Hematology Association (EHA). These data support the preliminary safety and efficacy of UCART22 in a heavily pretreated r/r B-ALL population. UCART22 is currently the most advanced allogeneic CAR T-cell product in development for r/r B-ALL.

• In the poster presented at EHA, Cellectis included data from patients who received UCART22 after fludarabine, cyclophosphamide (FC) and FC with alemtuzumab (FCA) lymphodepletion (LD). Compared to the clinical update on BALLI-01 at ASH 2021, we have included data from six additional patients who received UCART22 at dose level 3 (DL3), as of the December 31, 2022 data cutoff.

• UCART22 administered after FC or FCA LD regimen was well tolerated. No dose limiting toxicities (DLTs) nor immune effector cell-associated neurotoxicity syndrome (ICANS) were observed.

• For FCA-dose level 3, 50% of the six patients responded. Host lymphocytes remained suppressed through Day 28 for all patients who received FCA LD. Peak ferritin levels correlated with UCART22 cell expansion and cytokine release syndrome (CRS). UCART22 continues to be well tolerated, with no treatment emergent serious adverse events (TESAEs) or DLTs reported. UCART22 cell expansion was detected in 9 of 13 patients in the FCA LD arm and associated with clinical activity.

• The BALLI-01 study is currently enrolling patients after FCA LD with Cellectis’ in-house manufactured product. The next data set is expected to be released later this year.

NATHALI-01 (evaluating UCART20x22) in relapsed or refractory B-cell non-Hodgkin lymphoma (r/r B-NHL)

• UCART20x22 is Cellectis’ first dual allogeneic CAR T-cell product candidate targeting both CD20 and CD22 and is being evaluated in patients with r/r B-NHL in the NATHALI-01 Phase 1/2a clinical study[2].

• The NATHALI-01 clinical study is ongoing. Cellectis expects to provide first-in-human data later this year.

AMELI-01 (evaluating UCART123) in relapsed or refractory acute myeloid leukemia (r/r AML)

• UCART123 is an allogeneic CAR T-cell product candidate targeting CD123 and is being evaluated in patients with r/r AML in the AMELI-01 Phase 1 dose-escalation clinical study.

• On May 17, Cellectis presented an encore of the clinical data on the AMELI-01 clinical trial that were unveiled at the ASH 2022 annual meeting, at the American Society of Gene and Cell Therapy (ASGCT) 2023 annual meeting. These preliminary data support the continued administration of UCART123 after FCA lymphodepletion in patients with r/r AML.

• The oral presentation reviewed preliminary data from patients who received UCART123 at one of the following dose levels: dose level 1 (DL1) 2.5x10⁵ cells/kg; dose level 2 (DL2) 6.25x10⁵ cells/kg; intermediate dose level 2 (DL2i) 1.5x10⁶ cells/kg; or dose level 3 (DL3) 3.30x10⁶ cells/kg after lymphodepletion with FC ([n=8], DL1 – DL3) or FCA ([n=9], DL2 & DL2i).

• The data presented showed that adding alemtuzumab to the FC LD regimen was associated with sustained host lymphodepletion and significantly higher UCART123 cell expansion, that correlated with improved anti-tumor activity.

• 25% (n=2) of patients at DL2 in the FCA arm achieved meaningful response; one patient who failed five prior lines of therapy including allogeneic stem cell transplant experienced a durable minimal residual disease (MRD)-negative complete response that continued beyond 12 months, as of December 2022.

• The AMELI-01 study is currently enrolling patients after FCA lymphodepletion in a two-dose regimen arm.

Research Data & Preclinical Programs

UCART20x22

• On June 5, 2023, Cellectis presented preclinical data on its product candidate UCART20x22, at the International Society for Cell & Gene Therapy (ISCT) 2023 annual event.

• Cellectis provided pre-clinical proof-of-concept data for UCART20x22 to overcome current mechanisms of resistance to CAR T-cell therapies in B-NHL, while providing a potential therapeutic alternative to CD19 targeting and allowing a reduction in the time from treatment decision to infusion.

• Cellectis demonstrated that UCART20x22 displays robust activity in vitro and in vivo, against targets expressing heterogeneous levels of CD22 and CD20. We have used in vitro cytotoxicity assays against different tumor cell lines, showing strong activity whether these cells express a single antigen (CD20 or CD22) or both antigens simultaneously, as well as IFNg release in response to antigen specific stimulation.

Article published in Cancer Immunology Research

• On May 31, 2023, Cellectis published an article in Cancer Immunology Research demonstrating pre-clinical proof-of-concept data of UCART20x22 product candidate, to overcome current mechanisms of resistance to CAR T-cell therapies in B-NHL.

• In this study, we demonstrated that allogeneic CD20x22 CAR T-cells exhibit robust, sustained and dose-dependent activity in vitro and in vivo, while efficiently targeting primary Non-Hodgkin Lymphoma samples with heterogeneous levels of CD20 and CD22.

HBB gene correction of sickle cell mutation

• Encouraging preclinical data on gene editing process using Cellectis TALEN® technology to develop highly efficient HBB gene correction of sickle cell mutation, were presented in a poster presentation at the ISCT 2023 annual event.

• These results showed that non-viral DNA delivery associated with TALEN® gene editing reduces the toxicity usually observed with viral DNA delivery and allows high levels of HBB gene correction in long-term repopulating hematopoietic stem cells.

• Cellectis leveraged TALEN® technology to develop a gene editing process leading to highly efficient HBB gene correction via homology directed repair, while mitigating potential risks associated to HBB gene knock-out. Furthermore, we compared viral (TALEN-V) and non-viral (TALEN-NV) DNA template delivery strategies in mobilized healthy donor (HD) or non-mobilized homozygous sickle patient (HbSS) hematopoietic stem and progenitor cells (HSPCs).

• Both strategies led to high and comparable efficiencies of HBB gene correction in vitro in HD and HbSS, without affecting viability, purity or clonogenic potential of corrected HSPCs.

The poster presentation highlighted the following data:

• TALEN®-mediated engineering efficiently corrects the mutated HBB gene in clinically relevant HSPCs and promote phenotype correction in fully mature RBCs.
• Cellectis optimized TALEN® gene editing process mitigates potential safety challenges by reducing the frequency of HBB gene inactivation (<10% β-thal cells).
• Non-viral DNA template-mediated HBB repair mitigates p53 DNA damage response activation, preserves edited LT-HSCs fitness and enables their efficient engraftment in vivo using an immunodeficient murine model.

TALE Base Editors (TALE-BE)

• A comprehensive analysis to better design efficient TALE Base Editors (TALE-BE) using Cellectis’ TALEN® technology was presented in a poster at ISCT annual meeting.

• Cellectis developed a strategy that allowed to comprehensively characterize editing efficiencies in function of the TC position within the TALE-BE editing windows. This method is specifically taking advantage of the highly precise and efficient TALEN® mediated ssODN knock-in in primary T cells, allowing to focus on how target composition and spacer variations can affect TALE-BE activity/efficiency.

The poster presentation highlighted the following data:

• Determined optimal spacer length (13/15 bp) for highly efficient TALE-BE for both C40/C40 and C11/C11 scaffolds.
• Determined optimal common sequence context for high editing rates.
• Determined that editing efficiency of the C11/C11 scaffold is highly dependent on Cytosine position requirements, resulting in more stringent activity in a context of 15 bp spacer size and decreasing the effects of bystander editing.

We believe that the knowledge obtained will allow to better design efficient TALE-BE while improving the specificity profiles of this innovative editing platform.

Novel treatment paradigm for successful CAR T immunotherapy against stroma-rich solid tumors

• On May 12, 2023, Cellectis published an article in Frontiers Bioengineering demonstrating the efficacy of its TALEN® engineered FAP UCART-cells in cancer-associated fibroblast (CAF) depletion, reduction of desmoplasia and tumor infiltration.

• Over 90% of epithelial cancers including breast, colorectal, pancreatic and lung adenocarcinomas express the CAF-specific surface marker, fibroblast activation protein α (FAP), which makes it a promising CAR T-cell target. In this study, Cellectis proposed a novel and versatile approach of combination CAR T-cell therapy that can be extended to most stroma-rich cold tumors with relevant tumor-antigen targeting CAR T-cells which otherwise are recalcitrant to cell therapy.

Preclinical data showed that:

• In a mouse xenograft model, successful implantation of injected CAFs in the tumors was confirmed by positive staining of spindle-like cells with human-specific FAP antibody, recapitulating a physiologically relevant TNBC tumor with tumor and stromal compartments.
• FAP UCART-cells alone significantly reduced tumor growth.
• In vitro and in vivo results show that FAP UCART-cells enable the reprogramming of the cold, stroma-rich triple negative breast cancer (TNBC) TME, making the tumor susceptible to subsequent Meso UCART infiltration and cytotoxicity and improving the overall antitumor activity of the treatment.
• In the context of combination therapy with anti-PD1 checkpoint inhibitor, maximal anti-tumor activity and survival benefits were observed upon FAP UCART-cell treatment followed by Meso UCART-cell treatment.

Licensed Allogeneic CAR T-cell Development Programs

Servier and Allogene: anti-CD19 programs

• Allogene announced that it is enrolling patients “in the industry’s first potentially pivotal Phase 2 allogeneic CAR T clinical trial with ALLO-501A across sites in the United States and Canada”. The European Medicines Agency (EMA) recently approved the ALPHA2 Clinical Trial Application (CTA).

• Allogene’s single-arm ALPHA2 trial in relapsed/refractory (R/R) large B cell lymphoma (LBCL) will enroll approximately 100 patients who have received at least two prior lines of therapy and have not received prior anti-CD19 therapy. Allogene has announced that it expects to complete enrollment in 1H 2024 with the first data readout by the end of 2024.

• Long-term follow up data from the Phase 1 of Allogene’s ALPHA/ALPHA2 trials in LBCL was presented at both the American Society of Clinical Oncology (ASCO) Annual Meeting with an encore presentation at the European Hematology Association Congress and International Conference on Malignant Lymphoma (ICML) Lugano in June 2023. The Phase 1 trials enrolled heavily pre-treated patients with a median of three prior lines of therapy. Data from 33 CAR T-naïve LBCL patients receiving Alloy™ cell product including 12 patients treated with the Phase 2 regimen, are the first to demonstrate the potential for an allogeneic CAR T product to induce complete responses at rates and durability similar to approved autologous therapies. 

Allogene: anti-BCMA and anti-CD70 program

• The ongoing Phase 1 dose escalation of Allogene’s TRAVERSE study is enrolling patients with advanced or metastatic renal cell carcinoma (RCC) who have progressed on standard therapies including an immune checkpoint inhibitor and a VEGF-targeting therapy.

• Allogene’s TRAVERSE trial is now deploying an investigational in vitro companion diagnostic (IVD) assay designed to prospectively assess CD70 expression levels in patients. Allogene has announced that dose escalation in the TRAVERSE trial is expected to be completed in 2023.

Corporate Updates        

• On June 28, 2023, Cellectis reported results from the annual shareholders’ general meeting held on June 27, 2023, at the Company’s Paris headquarters. At the meeting, during which more than 72% of shares were exercised, Resolutions 1 through 28 were adopted and resolution 29 was rejected, according to the management recommendations. The detailed results of the vote and the resolutions are available on the company’s website: https://www.cellectis.com/en/investors/general-meetings/

At the end of the meeting, the terms of office of Ms. Annick Schwebig and Mr. Hervé Hoppenot ended and Ms. Annick Schwebig and Mr. Hervé Hoppenot departed the board of directors as of such date.

During the annual shareholders meeting, Cécile Chartier, Ph.D., was appointed as a director of the Cellectis’ Board of Directors, with immediate effect.

Cécile Chartier currently serves as Chief Scientific Officer at NextVivo, Inc. Prior to her tenure at NextVivo, Dr. Chartier was Vice President of Research at Iovance Biotherapeutics, Inc. where she led the development of next generation tumor-infiltrating lymphocytes (TIL) therapies through research to early-stage clinical trials. Cécile’s extensive experience in the development of next generation cell and gene therapies coupled with her deep knowledge of the U.S. biotechnology industry will be a huge asset to Cellectis.

The announcement will be followed by an investor conference call and webcast on Friday, August 4, 2023 at 8:00 am ET / 2:00 pm CET. The call will include the Company’s second quarter results and an update on business activities. Details for the call are as follows:

Dial in information:

Domestic: 1-877-451-6152

International: 1-201-389-0879

Conference ID: 13739252

Webcast Link: https://viavid.webcasts.com/starthere.jsp?ei=1619596&tp_key=40e9fac8fc

“We are very excited to welcome Dr. Chartier as a director of Cellectis’ Board of Directors. Cécile’s extensive experience in the development of next generation cell and gene therapies coupled with her deep knowledge of the U.S. biotechnology industry will be a huge asset to the Company” said André Choulika, Ph.D., Chief Executive Officer at Cellectis. “We look forward to her contribution and insights as we continue advancing the development of our product candidates.”

“I am honored to have the opportunity to contribute to the development of truly breakthrough gene editing therapies. I am keen to lend my insights to the Cellectis’ Board of Directors to serve a patient population with severe unmet medical needs, where a successful allogeneic CAR T-cell product candidate could be a major breakthrough” said Cécile Chartier, Ph.D., Cellectis newest Board member.

Cécile Chartier currently serves as Chief Scientific Officer at NextVivo, Inc. Prior to her tenure at NextVivo, Dr. Chartier was Vice President of Research at Iovance Biotherapeutics, Inc. where she led the development of next generation tumor-infiltrating lymphocytes (TIL) therapies through research to early-stage clinical trials.

Prior to this, she spent 12 years at OncoMed Pharmaceuticals, where she served as Senior Director of Target Validation and led multiple antibody therapeutics project teams through Research and Development to IND filing. She also worked at Shering (US Berlex) and Transgene (France), where she focused on gene therapy.

Dr. Chartier obtained her Ph.D. in molecular biology from the Université Louis Pasteur in Strasbourg, France and pursued a post-doctoral training at Harvard Medical School.

At the meeting, during which more than 72% of shares were exercised, Resolutions 1 through 28 were adopted and resolution 29 was rejected, according to the management recommendations.

The detailed results of the vote and the resolutions are available on the company’s website:

https://www.cellectis.com/en/investors/general-meetings/

“These clinical data are very positive for patients with r/r B-ALL who have failed multiple lines of treatment options including chemotherapy, CD19 directed CAR T-cell therapy and allogeneic stem cell transplant and encourage further enrollment into the BALLI-01 clinical study” said Nicolas Boissel, M.D., Ph.D., Head of Hematology Adolescent and Young Adult Unit at Hôpital Saint-Louis, Paris, France.

The poster presentation at EHA highlights the following data:

BALLI-01 is a Phase 1/2a open-label study, evaluating the safety and clinical activity of UCART22 in patients with relapsed/refractory B-cell acute lymphoblastic leukemia (r/r B-ALL).

The poster presentation reviewed clinical and translational data from patients who received UCART22 after lymphodepletion (LD) with fludarabine and cyclophosphamide (FC) (F : 30 mg/m2 × 3d, C : 1.0 g/m2 × 3d) or fludarabine, cyclophosphamide and alemtuzumab (FCA) (F: 30 mg/m2 × 3d, C : 0.5g/m2 × 3d, A : 20 mg/d × 3d) in patients with r/r B-ALL.

Compared to the clinical update on BALLI-01 at ASH 2021, the poster presents data from six additional patients who received UCART22 at dose level 3 (DL3), 5 x 106 cells/kg, as of the December 31, 2022 data cutoff.

Preliminary safety data

UCART22 administered after FC or FCA LD regimen was well tolerated. No dose limiting toxicities (DLTs) nor immune effector cell-associated neurotoxicity syndrome (ICANS) were observed; 61% of patients reported cytokine release syndrome (CRS) (Grade 1 [N=9] or Grade 2 [N=2]). One serious adverse event of special interest (AESI) of Grade 2 graft-versus-host disease (GvHD) (skin) was reported in the setting of reactivation of prior allogeneic hematopoietic stem cell transplantation (HSCT) donor stem cells. Serious adverse events (SAEs) (G≥3) reported in 72% of patients included infections (39%) and febrile neutropenia (28%), and all were not related to UCART22.

Preliminary efficacy data

Responses were assessed beginning on Day 28.

Up to FC/FCA-Intermediate Dose Level 2 (DL2i): 3 complete remissions with incomplete count recovery (CRi) and 1 morphologic leukemia-free state (MLFS) were observed and previously reported at the American Society of Hematology (ASH) 2021 conference.

For FCA-Dose Level 3 (DL3), 50% of the six patients responded:

- 1 patient who failed 4 prior lines, including multiagent chemotherapy, blinatumomab, inotuzumab, autologous CAR19, and allogeneic HSCT, achieved a minimal residual disease (MRD) negative complete response (CR) lasting over 90 days after UCART22 infusion as of the December 31, 2022 data cutoff.

- 1 patient who failed 4 prior lines, including multiagent chemotherapy, venetoclax, autologous CAR19, and allogeneic HSCT, achieved an MRD negative complete response with incomplete count recovery (CRi) consolidated with donor lymphocyte infusion (DLI) after Day 90 and remains in an MRD negative CRi past 7 months as of the December 31, 2022 data cutoff.

- 1 patient who failed 3 prior lines, including multiagent chemotherapy, venetoclax, autologous CAR19, and allogeneic HSCT, achieved an MRD negative MLFS up to Day 114.

Host lymphocytes remained suppressed (mean ALC <0.1 x103 cells/mL) through Day 28 for all patients who received FCA LD. Peak ferritin levels correlated with UCART22 cell expansion and cytokine release syndrome (CRS). UCART22 continues to be safe and tolerable, with no treatment emergent serious adverse events (TEAEs) or DLTs reported. UCART22 cell expansion was detected in 9 of 13 patients in the FCA LD arm and associated with clinical activity.

Overall, these data support the preliminary safety and efficacy of UCART22 in this heavily pretreated r/r B-ALL population.

The BALLI-01 study is currently enrolling patients after FCA lymphodepletion. UCART22 is currently the most advanced allogeneic CAR T-cell product in development for r/r B-ALL. The next data set is expected to be released later this year.

The poster presentation is available on Cellectis’ website: https://www.cellectis.com/en/investors/scientific-presentations/

June 5, 2023 – New York (NY) – Cellectis (the “Company”) (Euronext Growth: ALCLS - NASDAQ: CLLS), a clinical-stage biotechnology company using its pioneering gene-editing platform to develop life-saving cell and gene therapies, showcased preclinical data at an oral presentation and two poster presentations at the International Society for Cell & Gene Therapy (ISCT) 29th annual event that took place at the Paris Convention Center in Paris, France on May 31 - June 3, 2023.

“Our breadth of scientific presence at the 29th ISCT annual event reflects the type of cutting-edge research our teams undertake, which we believe is essential to address patients’ unmet medical need. We are proud of the pre-clinical results presented and remain deeply focused on the development of our product candidates to deliver breakthrough treatments that could benefit thousands of patients worldwide” said André Choulika, Ph.D., Chief Executive Officer at Cellectis.

Oral Presentation

UCART20x22: allogeneic dual CAR T-cells for the treatment of B-cell malignancies

Autologous CAR T-cell therapies have shown outstanding responses in the treatment of selected blood cancers, predominantly B-cell malignancies. Nevertheless, long term studies revealed that some patients treated with CD19 or CD22 CAR T-cells can relapse due to low target antigen expression in tumor cells or to antigen loss. The therapeutic options after CAR T-cell relapses are limited, emphasizing the need to develop novel therapies to improve current survival rates. There is also need for allogeneic “off-the-shelf” therapies that could be readily available at the time of treatment decision and overcome limitations of current autologous approaches.

UCART20x22 is Cellectis’ first dual-targeting, allogeneic cell therapy product candidate targeting CD20 and CD22, to address the current challenges in the treatment of B-cell malignancies.

UCART20x22 features TALEN®-mediated disruptions of the TRAC gene (to minimize the risk of graft-versus-host disease) and of the CD52 gene (to permit use of a CD52-directed monoclonal antibody in patients’ lymphodepletion regimen) to enhance CAR T engraftment, expansion, and persistence.

Cellectis demonstrates that UCART20x22 displays robust activity in vitro and in vivo, against targets expressing heterogeneous levels of CD22 and CD20. We have used in vitro cytotoxicity assays against different tumor cell lines, showing strong activity whether these cells express a single antigen (CD20 or CD22) or both antigens simultaneously, as well as IFNg release in response to antigen specific stimulation.

The oral presentation highlighted the following preclinical data:

• Robust in vitro and in vivo cytolytic activity against tumors expressing different antigen combinations.
• Efficient in vitro targeting of primary B-cell Non-Hodgkin Lymphoma (B-NHL) samples harboring different CD20 and CD22 expression levels, suggesting that UCART20x22 has the potential to reach a large patient population.
• Dose dependent tumor control in vivo, using batches manufactured internally, harboring a tumor cell line as well as in a Patient Derived Xenograft (PDX) model of B-NHL.