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1 CORPORATE UPDATE September 14 th, 2026
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2 Forward Looking Statements This press release contains “forward-looking” statements within the meaning of applicable securities laws, including the Private Securities Litigation Reform Act of 1995. Forward-looking statements may be identified by words such as “design”, “expect”, “initiate”, “into”, “moving forward”, “plan”, “potential”, “promising”, “target”, “will”, or similar expressions and/or the negative of these. These forward-looking statements are based on our management's current expectations and assumptions and on information currently available to management. Forward-looking statements in this press release include statements regarding the Company's transition into an in vivo gene editing company, the ability of the Company to initiate an IIT in China; the planned timing for the release preliminary clinical data for the Company's lead programs, the potential for success of the Company's in vivo gene editing programs, the expected design of the clinical development of the Company's lead programs, the ability to continue advancement of cell therapy activities through existing partnerships, the anticipated impact, including potential cost savings, of the Company's decision to cease development of lasme-cel and eti-cel and to initiate a restructuring plan, the contemplated implementation of headcount reductions and other cost-savings initiatives and their planned timeframe, and the targeted extension of the Company's cash runway. Actual results, performance or events may differ materially from those projected in any forward-looking statement. Many important factors may adversely affect such forward-looking statements and cause actual results to differ from those in any forward-looking statement, including, without limitation, uncertainties inherent in the initiation and completion of preclinical and clinical studies; the performance of the IIT in China; the availability and timing of results from studies, once initiated; the acceptance by global regulatory agencies of data generated from IITs in China; the potential that pre-clinical animal model data may not translate into further preclinical development or clinical setting; promising preclinical data not yielding positive further preclinicial data or clinical results; changes in the competitive landscape for in vivo gene editing products; expectations for regulatory approvals to conduct clinical trials; availability of funding sufficient for the Company's foreseeable and unforeseeable operating expenses and capital expenditure requirements; and impacts of the Company's headcount reductions and other cost savings initiatives, which may include operational and strategic challenges. With respect to our cash runway, our operating plans, including product development plans, may change as a result of various factors, including factors currently unknown to us. Furthermore, many other important factors, including those described in our Annual Report on Form 20-F as amended and in our annual financial report (including the management report) for the year ended December 31, 2025 and subsequent filings Cellectis makes with the Securities Exchange Commission from time to time, which are available on the SEC's website at www.sec.gov, as well as other known and unknown risks and uncertainties may adversely affect such forward-looking statements and cause our actual results, performance or achievements to be materially different from those expressed or implied by the forward-looking statements. Except as required by law, we assume no obligation to update these forward-looking statements publicly, or to update the reasons why actual results could differ materially from those anticipated in the forward-looking statements, even if new information becomes available in the future.
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3 Agenda and Speakers Speakers André Choulika, PhD Chief Executive Officer Adrian Kilcoyne, MD, MPH,MBA Chief Medical Officer Welcome Cellectis, A Gene Editing Company In vivo Gene Editing Strategic Transformation Q&A
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Gene Editing
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5 Cellectis is a Gene Editing Company Silencing Gene Editing has transformed science in numerous ways and many experts agree that it will be a major paradigm shift in medicine Cellectis since its inception over 25 years ago is a pioneer in Gene Editing Activating Repairing targeted gene(s) Gene Editing intervenes in cells at genome level to change gene expression by:
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6 Gene Editing in Medicine Genetics drive disease: Cancer, diabetes, obesity, neurological disorders, immunity, longevity… all diseases are rooted in genetics: polymorphisms and aberrant gene expression. The basic logic of gene editing: fix the gene, fix the disease. Building on our ex vivo leadership to advance the next frontier: in vivo gene editing Collect cells → edit them under GMP conditions → infuse (example of CAR -T cells) EX VIVO Deliver the editor to the target tissue → silence, activate, repair IN VIVO Two pathways for gene editing Cellectis main focus so far Cellectis new focus from now
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in vivo Gene Editing
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8 A single IV injection for a long-lasting effect In vivo delivered is made by intravenous injection (IV) liver cells product How does In Vivo Gene Editing work
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9 A One-Time Treatment With a Long-Lasting Effect Product: mRNA coding for a gene editor in a lipid nanoparticle (LNP) What is The in vivo Gene Editing Product? AAAAAA 3′ AAAAAA 3′
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10 Two Promising Preclinical In Vivo Assets Decision to advance 2 preclinical candidate products in dyslipidemia: .HEAL-101 (mRNA+LNP) TargetingAPOC3 in severe hypertriglyceridemia (sHTG) .HEAL-201 (mRNA+LNP) Targeting PCSK9 in severe hypercholesterolemia ✓ Well validated targets ✓ Single IV injection offering potentially long -lasting effect IV: intravenous
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.HEAL-101 GENE SURGERY
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12 Severe Hypertriglyceridemia ( sHTG): A Major Unmet Medical Need High risk of acute pancreatitis Associated with cardiovascular disease Poor quality of life and limited treatment options High Clinical Burden High Risk sHTG (TGs ≥ 880 mg/dL or ≥ 500 mg/dL With Prior AP History) Total: ~1-2 million patients US/EU .HEAL-101 Target Patient Population
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13ASO: Antisense Oligonucleotides; RNAi: interfering RNA Indication: Severe Hypertriglyceridemia (sHTG) with high risk of acute pancreatitis Target: APOC3 gene is well-validated with ASO and RNAi Tech: TALE-Base Editor disables the APOC3 gene Goal: One-time treatment for durable lowering of triglycerides to reduce risk of acute pancreatitis Status: Promising preclinical data supporting transition to clinic .HEAL-101
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14 .HEAL-101: TALE -Base Editor Targeting APOC3 .HEAL-101 No DNA break offering potential of improved safety profile .HEAL-101 is a base editor It modifies one base in DNA C to T conversion
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15 .HEAL-101: Disable APOC3 Expression .HEAL-101 editing location A stop codon is generated APOC3 protein is disabled APOC3 gene expression
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16 No modification of top putative off-sites 0 20 40 60 80 Frequency of editing (%) Indels Editing ONsite ONsite OFFsite 1 OFFsite 2 OFFsite 3 OFFsite 4 OFFsite 5 OFFsite 6 OFFsite 7 OFFsite 8 OFFsite 9 OFFsite 10 OFFsite 11 OFFsite 12 OFFsite 13 0 2 4 6 8 10 40 50 60 70 80 Frequency of base edting (%) Edited Mock Efficient on-site modification with no DNA alteration Feola et al, FASEB 2026 .HEAL-101 Elicits Efficient and Specific Editing of APOC3 Gene .HEAL-101 mRNA is introduced in hepatic cell lines
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17 .HEAL-101 Stops APOC3 Expression In Vitro Frequency of APOC3 editing Quantification of APOC3 secretion 0 20 40 60 80 100 Frequency of Stop codon (%) 0 20 40 60 80 100 Normalized decrease of APOC3 secretion (%) .HEAL-101 Mock .HEAL-101 Mock
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18 .HEAL-101 Decreases Triglycerides in Humanized Mice .HEAL-101 Precise APOC3 editing Decrease of APOC3 Drop of triglycerides Indels Base editing 0 20 40 60 80 100 Frequency of editing (%) Control .HEAL-101 -100 -80 -60 -40 -20 0 20 Change Before/After treatment (%) Control .HEAL 101 -100 -80 -60 -40 -20 0 20 Change from baseline (%)
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19 .HEAL-101 Induces 76% Decrease of Triglycerides in Affected Mice 76% decrease 70% decrease .HEAL-101 Control .HEAL-101 -100 -80 -60 -40 -20 0 20 50 100 APOC3 Change from baseline (%) Control .HEAL-101 -100 -80 -60 -40 -20 0 20 50 100 Triglycerides Change from baseline (%)
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.HEAL-201 GENE SURGERY
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21 Hypercholesterolemia: A Major Unmet Medical Need LDL-C: Low-Density Lipoprotein Cholesterol • Leading driver of atherosclerotic cardiovascular disease • Lowering LDL-C reduces risk of cardiovascular event (CVE) • Many patients remain above LDL-C goals despite maximally tolerated therapy High Clinical Burden • Younger high risk patients • Premature Cardiovascular disease • Persistent elevated LDL- C despite maximal therapy • Total: ~1-2 million patients (US + EU) .HEAL-201 Target Patient Population
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22CVE: cardiovascular event Indication: Severe Hypercholesterolemia Target: PCSK9 gene is a well validated target Tech: TALE-Modulator silences the PCSK9 gene Goal: One-time treatment for durable lowering of LDL -C to reduce CVE risk Status: Promising preclinical data supporting transition to clinic .HEAL -201
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23 .HEAL -201: TALE -Epigenetic Modulator Targeting PCSK9 .HEAL-201 is an Epigenetic modulator Epigenetically modulates the PCSK9 gene without altering the DNA sequence PCSK9 is active PCSK9 is silenced No DNA Sequence Change .HEAL-201 binds target
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24 .HEAL -201 Promotes Efficient and Specific Knockdown of PCSK9 Epigenetic change in the DNA without sequence modification PCSK9 transcription is shut down Efficient PCSK9 mRNA transcription reduction Control .HEAL-201 0.0 0.2 0.4 0.6 0.8 1.0 Fold Change
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25 .HEAL -201 Promotes Efficient and Specific Knockdown of PCSK9 Efficient PCSK9 protein reduction Epigenetic change in the DNA without sequence modification PCSK9 protein is turned off 0 7 14 21 28 35 42 49 0 10 20 30 40 50 60 70 80 90 100 Day # (Post-Transfection) Normalized PCSK9 secretion (%) Mock .HEAL-201
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26 .HEAL -201 Promotes Efficient and Specific Knockdown of PCSK9 Transcriptome post .HEAL-201 treatment shows a precise modification PCSK9 Other genes Downregulated →Up-regulated Magnitude of change vs baseline .HEAL-201: high specificity on PCSK9 only
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27 .HEAL -201 Epigenetic Modification is Stable Over Time .HEAL-201 promotes rapid and durable decrease of PCSK9 .HEAL-201 -1 0 1 2 3 4 5 -100 -80 -60 -40 -20 0 20 Time (week) Decrease of PCSK9 with respect to W-1 (%) .HEAL-201 treated
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Clinical Development Plan
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29 .HEAL-101 Clinical Development Plan No cardiovascular outcomes trial required for commercialization Phase 1b/2 StudyPhase 1 Study1 • Patient population: severe hypertriglyceridemia (sHTG) • First-in-Human for safety and tolerability • Establish dose efficacy in triglyceride reduction in a broader sHTG population 2 • Expand to global populations • Dose optimization and regimen exploration • Confirm activity and inform Phase 3 pathway
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30 Phase 1b/2 StudyPhase 1 Study .HEAL -201 Clinical Development Plan ASCVD: atherosclerosis cardiovascular disease 1 • Patient Population: Severe hypercholesterolemia ≥190 mg/dL • First-in-Human for safety and tolerability • Establish dose efficacy in LDL-C reduction in a broader population 2 • Younger high risk patients • Severe genetic hypercholesterolemia — LDL-C ≥190 mg/dL • Early ASCVD — premature cardiovascular disease Persistent elevated LDL-C despite maximal therapy Surrogate markers accepted by FDA / EMA for approval
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31 Advancing Toward First -In-Human Proof of Concept • Plan to start an IIT in China • GMP manufacturing starting • Phase 1 designed to be optimized for rapid dose selection Getting to first human data • FDA / EMA preparation initiated • Manufacturing scope broadened toward global supply IND/CTA enabling activities Potential Path to clinical value creation In vivo POC 2026 IIT enabling activities Q4-26 Dose escalation initiation Q1-27 Interact / Pre IND Global readiness IND/CTA End-27 Dose escalation initiation H2-27 .HEAL-101 APOC3 .HEAL-201 PCSK9 IIT enabling activities Q1-27 1st read out H2-27 1st read out H1-28
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A Differentiated Gene Editing Platform
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33 Nuclease Base Editor Epigenetic Transcription ✓ ✓ .HEAL-101 ✓ .HEAL-201 ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓ Cellectis’ Core Competencies
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34 Cellectis’ Unique Advantages • Nuclease editing • Base editing • Epigenetic editing • Transcriptional regulation Broad Gene Editing Toolbox • TALE editors • Binding does not nick DNA • Precision to the base pair • 32 base pairs recognition site Strong Differentiation • Any Gene Editing modality • Hybrid tools combinations Unique Advantages
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Cellectis’ Strategic Decision to Pivot to in vivo Gene Editing
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36 ADC: antibody-drug conjugate; MRD: Minimal Residual Disease; LBCL: Large B-cell Lymphomia; B-ALL: B-cell acute lymphoblastic leukemia; NHL: Non-Hodgkin lymphoma B-ALL: • Frontline Blinatumumab consolidation reduces relapses to 15-25% (vs 45-55% before its introduction), substantially reducing 3 rd line+ B-ALL patients • New 2nd and 3rd line+ pipeline drugs with novel bispecifics and ADCs • Focus shifts from salvage therapy to earlier intervention and long -term disease control NHL: • Cema-cel in frontline consolidation has demonstrated higher MRD -conversation rate • New 2nd and 3rd line+ pipeline drugs with bispecific, ADCs and other novel combos • In vivo CAR-T rush in LBCL Earlier interventions and novel therapies are improving depth of response, durability and survival in B-ALL and NHL Changes in the Heme -Onc Landscape in 2026
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37 Cellectis Pivot Lasme-cel in Pivotal Phase 2 Eti-cel Phase 1 Completed Promising Preclinical in vivo Gene Editing Assets Cash runway expected into Q4 2027 Exiting internal programs Continuing existing collaborations Cash runway expected into H2 2028 Cellectis Today Advancing .HEAL-101 & .HEAL-201 with FIH in 2027 IN VIVO GENE EDITING EX VIVO CELL THERAPY IN VIVO GENE EDITING EX VIVO CELL THERAPY Cellectis Tomorrow FIH: First in Human Cell therapy Partnered programs
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38 Cellectis Targeted Roadmap Continuing Existing Partnerships Targeting Cash Runway into H2 2028* Exiting internal cell therapy development (lasme-cel & eti-cel), seeking partnership Re-aligning our organization** to our new priorities Advancing 2 Lead Assets FIH Data disclosure .HEAL-101 targeting APOC3 in severe hypertriglyceridemia H1-27 H2-27 .HEAL-201 targeting PCSK9 in severe hypercholesterolemia H2-27 H1-28 *Excluding potential proceed from new partnership **Subject to the completion of the relevant works council consultation process and applicable French & US labor law requirements FIH : First in Human
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39 HEAL By GENE SURGERY EDITING LIFE
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40 Questions & Discussion André Choulika, PhD Chief Executive Officer Arthur Stril Chief Business Officer & Chief Financial Officer Adrian Kilcoyne, MD, MPH,MBA Chief Medical Officer David Sourdive, PhD Executive Vice President CMC and Manufacturing