Cellectis S.a. · EURONEXT:ALCLS
Cellectis — Investor Presentation (May 2024)
36 slides from Cellectis's investor presentation, May 2024
Slide 1: Commitment to a Cure
Commitment to a Cure Corporate Presentation May 2024 NASDAQ: CLLS EURONEXT GROWTH: ALCLS.PA
Slide 2: Forward-Looking Statements
Forward-Looking Statements This presentation contains “forward-looking” statements within These forward-looking statements are made in light of the meaning of applicable securities laws, including the Private information currently available to us and are subject to Securities Litigation Reform Act o
Slide 3: Cellectis at a Glance
Cellectis at a Glance 3 Clinical Trials Global GMP Facilities Near-Term Clinical Catalysts $143M *as of March 31, 2024 70+ patients dosed End-to-end manufacturing Multiple near-term UCART autonomy clinical data updates Cash Runway into 2026** in Cellectis-sponsored trials Diversified Partnerships wi
Slide 4: A Highly-Experienced Executive Committee
A Highly-Experienced Executive Committee André Choulika, Ph.D. Steven Doares, Ph.D. Phillippe Duchateau, Ph.D. Mark Frattini, M.D., Ph.D. Kyung Nam-Wortman Founder & CEO SVP, US Manufacturing Chief Scientific Officer Chief Medical Officer EVP, Chief Human & Site Head Resources Officer Stephan Reynie
Slide 5: UCARTs are Designed to be Off-The-Shelf
UCARTs are Designed to be “Off-The-Shelf” Scalable Robustness Market Access Manufacturing Reduced cost The goal is to provide Immediately available Scalable manufacturing: potency and consistency to all eligible patients 1 batch = 100s doses to each patient Control Production, Minimize Costs and Imp
Slide 6: Strategic Partnership with AstraZeneca
Strategic Partnership with AstraZeneca Cell & Gene Therapy R&D Collaboration Investment Agreements • Develop up to 10 novel products in oncology, • $220M equity investment (subscribed for 16 immunology and rare diseases million ordinary shares and 28 million convertible preferred shares at $5.00 per
Slide 7: Experts in Gene-Editing Use TALEN
Experts in Gene-Editing Use TALEN® High rates of gene editing for knock outs and knock ins Efficient In clinic since 2015 Protein / DNA interaction with Mature Safe ~220 patients dosed 32 base pairs recognition WHY TALEN®? Euchromatin & Genome Targets desired site with a Precise maximum 7 bps range
Slide 8: Cellectis' UCART Candidate Platform
Cellectis’ UCART Candidate Platform TALEN® Powered CAR-T cell CD52 KO TRAC KO Resistance to Minimizes risk of CAR alemtuzumab GvHD CAR20+CAR22 Targeting CD20 & CD22 For B-cell Malignancies CAR22 Targeting CD22 For B-cell ALL CAR123 Targeting CD123 CD52 TCR For AML ALL: acute lymphoblastic leukemia;
Slide 9: Differentiated Targets & Near-Term Catalysts
Differentiated Targets & Near-Term Catalysts Phase 1 Dose Phase 1 Dose Phase 2 Candidate / Target Indication Study Preclinical Escalation Expansion Pivotal2 Upcoming Expected Milestones UCART22 BALLI-01 Data update with Recommended ALL Phase 2 Dose (RP2D) Fully Owned CD22 NCT04150497 UCART123 AML AM
Slide 10: Cellectis' UCART Platform
Cellectis’ UCART Platform 10
Slide 11: BALLI-01 Study Design
11 BALLI-01 Study Design Key inclusion criteria: Dose-escalation mTPI design • 2-4 pts/cohort • Age 15–70 years, adequate organ DL 3-P1 DL 3-P2 function, ECOG PS ≤1 FCA 5 × 106 cells/kg FCA • B-ALL blast CD22 expression ≥70% • Received ≥1 standard chemotherapy DL 2i-P1 DL 2i-P2 2.5 × 106 cells/kg FC
Slide 12: UCART22-P1 Administration Shows Promising Tolerable Safety Profile
UCART22-P1 Administration Shows Promising Tolerable Safety Profile Patient Characteristics (N=19) Safety: FCA Cohorts (N=13) Median age: 28 (17-61) 0 Dose limiting toxicity WHO classification: 0 ICANS (immune effector cell • B-ALL with recurrent genetic associated neurotoxicity) abnormalities: 8 (42
Slide 13: Promising Clinical Responses with UCART22-P1 and FCA Lymphodepletion
Promising Clinical Responses with UCART22-P1 and FCA Lymphodepletion FC LD (n=5) FCA LD (n=6) • Host lymphocytes remained suppressed using FCA lymphodepletion • 2/7 patients in DL2 and DL2i achieved blast reductions to < 5% by day 28 using FCA lymphodepletion • 1 patient in DL2: MRD negative CRi • 1
Slide 14: Baseline Characteristics of UCART22-P2 Patients Treated at DL2
Baseline Characteristics of UCART22-P2 Patients Treated at DL2 3 patients were enrolled into the first UCART22-P2 cohort at DL2 Patient 1 Patient 2 Patient 3 17-year-old female with 68-year-old female with 27-year-old male with Ph-negative B-ALL with a Ph-negative B-ALL B-ALL with an ABL2 fusion hyp
Slide 15: UCART22-P2 Expansion Correlates with Changes in Ferritin Levels
UCART22-P2 Expansion Correlates with Changes in Ferritin Levels Patient 1 Patient 2 Patient 3 100 8000 100 4000 1.0 1500 80 80 UCART22 cells/μl UCART22 cells/μl 0.8 UCART22 cells/μl 6000 3000 Ferritin (ng/ml) Ferritin (ng/ml) 1000 Ferritin (ng/ml) 60 60 0.6 4000 2000 40 40 0.4 500 2000 1000 20 20 0.
Slide 16: Summary of UCART22-P2 Patients Treated at DL2
Summary of UCART22-P2 Patients Treated at DL2 Safety • No dose-limiting toxicities (DLT) • No immune effector cell-associated neurotoxicity syndrome (ICANS) • No GvHD • CRS in 2/3 (67%) patients with one G1 that resolved without treatment and one G2 that resolved after tocilizumab x1 • Patient 1 had
Slide 17: NatHaLi-01 Study Design
17 NatHaLi-01 Study Design Key inclusion criteria: • Age 18–80 years Dose-escalation Dose Expansion • Mature B-cell NHL except CLL/SLL, BOIN design • 2-4 pts/cohort Richter’s from CLL/SLL, Burkitt’s lymphoma, or Waldenstrom’s macroglobulinemia 450 × 106 cells DL 3 • Tumor positive for CD20 and/or CD
Slide 18: Baseline Characteristics
Baseline Characteristics As of 28 July 2023, 3 patients received LD and were treated with UCART20x22 at Dose Level 1 (50 × 106 cells) Pt 1 Pt 2 Pt 3 Age 76 65 18 Sex Female Female Female NHL Subtype DLBCL Transformed FL Transformed MZL Genetic/Molecular Double expressor (BCL2, MYC) Triple-hit NOTCH1
Slide 19: Safety Summary
19 Safety Summary • No UCART20x22-related DLTs • No ICANS or GVHD was observed • One CLLS52-related DLT of bone marrow aplasia after Day 42 thought to be due to cumulative chemotherapy exposure in a patient with baseline Grade 1/2 cytopenias and bone marrow hypocellularity at screening • All patient
Slide 20: UCART20x22 Treatment Response
20 UCART20x22 Treatment Response As of July 28, 2023, 3 patients were treated at dose level 1 (50 × 106 cells) and were evaluable for response: Patient 1 Patient 2 Patient 3 76-year-old female with 65-year-old female with 18-year-old female with double-expressor DLBCL relapsed triple-hit transformed
Slide 21: Robust Expansion of UCART20x22 Cells in Peripheral Blood
Robust Expansion of UCART20x22 Cells in Peripheral Blood Correlates with an Increase in Serum Ferritin Levels Patient 1 Patient 2 Patient 3 800 3000 500 2000 15 15000 UCART20x22 cells/μl UCART20x22 cells/μl UCART20x22 cells/μl 600 400 1500 2000 10 10000 Ferritin ng/ml Ferritin ng/ml Ferritin ng/ml 3
Slide 22: UCART20x22 Cells Detected in Post-Treatment Biopsy for Patient 3
UCART20x22 Cells Detected in Day 9 Post-Treatment Biopsy for Patient 3 Negative Control Positive Control UCART20x22 Baseline UCART20x22 Day 9 UCART20x22 cells were measured by RNAscope using a probe set specific for the UCART22 targeted sequence, at 20X magnification. No staining was observed with t
Slide 23: UCART123 – AMELI-01 Trial Design
UCART123 – AMELI-01 Trial Design Phase I, Open Label Dose-escalation and Dose-expansion Study to Evaluate the Safety, Expansion, Persistence and Clinical Activity of UCART123 in Patients with Relapsed or Refractory Acute Myeloid Leukemia Key Eligibility Criteria Dose-Escalation UCART123 • Relapsed o
Slide 24: Addition of Alemtuzumab Results in Prolonged Host Lymphodepletion
Addition of Alemtuzumab Results in Prolonged Host Lymphodepletion Absolute Lymphocyte Counts FC Arm FCA Arm Data Source: ASH 2022 Conference Presentation ALC: absolute lymphocyte counts ; FC: Fludarabine + Cyclophosphamide; FCA: Fludarabine + Cyclophosphamide + Alemtuzumab; DL1: Dose Level 1; DL2: D
Slide 25: Anti-Leukemic Activity and Robust CAR T-Cell Expansion Observed using FCA
Anti-Leukemic Activity and Robust CAR T-Cell Expansion Observed using FCA Lymphodepletion VCN AUC(0-28days) 2 responses observed in FC arm Patient 101-219 (DL2i): SD p = 0.04 Patient 103-223 (DL2i): MLFS 2 responses observed in FCA arm Patient 114-229 (DL2): SD • Achieved greater than 90% BM blast r
Slide 26: Patient 104-226 Achieved a Durable MRD Negative Complete Response
Patient 104-226 Achieved a Durable MRD Negative Complete Response at Day 56 that Was Maintained for Over One Year Clinical Characteristics Age, Race, Sex 64-year-old white female ECOG PS 1 ELN 2017 Classification; WHO Classification Adverse risk; AML with myelodysplasia-related changes Cytogenetic a
Slide 27: Translational Data Supports Use of a Two-Dose Regimen of UCART123
Translational Data Supports Use of a Two-Dose Regimen of UCART123 • UCART123 expansion correlates with reduction in AMELI-01 Amended Protocol with Two-Dose Regimen Design tumor burden at DL2 (6.25 x 105 cells/kg) but at this Dose-Escalation UCART123 dose, UCART123 cell function is not sufficient for
Slide 28: UCART Platform Takeaways from ~290 Patients
UCART Platform Takeaways from ~290 Patients* GvHD TRAC KO results in safe, non-alloreactive UCART cells Expansion CD52 KO + alemtuzumab use in LD has the potential to provide a safe, effective & controllable therapeutic window Persistence Encouraging clinical activity in ALL, AML, and NHL Safety Pro
Slide 29: Discover, Create, Develop, Produce and Test
Discover, Create, Develop, Produce and Test ALPHA Study Paris New York, New York Paris, France Raleigh, North Carolina Innovation, Clinical Development HQ, PD/AD, Starting Materials UCART – Clinical & potential for Commercial 25,000 sq ft. facility 55,000 sq ft. facility 82,000 sq ft. facility ü Gen
Slide 30: Expected Milestones in 2024
Expected Milestones in 2024 UCART22 UCART123 UCART20x22 r/r B-ALL r/r AML r/r B-NHL Data update with Data update with Data update with Recommended Phase 2-dose regimen Recommended Phase 2 Dose (RP2D) 2 Dose (RP2D) Partnerships Updates from licensed partners (AstraZeneca, Servier, Allogene, Iovance,
Slide 31: Key Takeaways – Why Cellectis?
Key Takeaways – Why Cellectis? Innovative Allogeneic Breaking Paradigms with Life-Saving Therapies CAR T End-to-End In-House Owning Manufacturing is Owning the Product Manufacturing Best-In-Class Gene Designed to be Safe, Precise & Efficient, Backed by Editing Platform Strong IP Strong Partnerships
Slide 32: Thank You
Thank You Reach us at: investors@cellectis.com Cellectis Paris Cellectis New York Cellectis Raleigh 8, rue de la Croix Jarry 75013 430 East 29th Street 2500 Sumner Boulevard Paris – France New York, NY, 10016 – USA Raleigh, NC, 27616 – USA 32 Cellectis®, TALEN® and our corporate logos are registered
Slide 33: Appendix
Appendix 33
Slide 34: Powerful and Comprehensive Gene Editing Platform
Powerful and Comprehensive Gene Editing Platform Gene Knockout Gene Repair Gene Replacement Gene Insertion Nucleases Experts in Gene Editing: Proprietary ü 30+ years for Cellectis’ electroporation technology founders Base editors ü 24 years doing gene editing ü 10 years developing TALEN® Gene Knocko
Slide 35: Why TALEN?
Why TALEN®? Maturity Genome Recognition Chromotrypsis Precision Vectorization IP Outreach Site # base pairs In clinic since Euchromatin & Every 7 Strong for TALEN® 32 Not reported mRNA 2015 heterochromatin base pairs CLLS Every 64 In clinic since Euchromatin ~20 RNP Scattered CRISPR 2018 only Yes ba
Slide 36: Diversified Partnerships with Industry Leaders
Diversified Partnerships with Industry Leaders CAR-T CAR-T Mitochondrial Cell and gene BCMA, CD70 + 13 TILs CD19 DNA editing therapies targets Exclusive worldwide U.S. rights Exclusive worldwide Research Collaboration Joint Research and license to CD19- sublicensed to license to 15 collaboration and