etivelcabtagene erigedleucel (UCART20x22) / Cellectis - LARVOL DELTA

Pipeline Highlights (GlobeNewswire) - "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; 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."

P1 data • B Acute Lymphoblastic Leukemia • Non-Hodgkin’s Lymphoma

Cellectis Reports Financial Results for the Fourth Quarter and Full Year 2024 and Provides a Business Update (GlobeNewswire) - "Pipeline Highlights:...(i) BALLI-01 study evaluating UCART22 in relapsed or refractory B-cell acute lymphoblastic leukemia (r/r B-ALL):...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 UCART22 in relapsed or refractory ALL in the third quarter of 2025; (ii) NATHALI-01 study evaluating 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 the Phase 1 dataset and late-stage development strategy for UCART20x22 in relapsed or refractory NHL in late 2025."

Enrollment status • P1 data • Pipeline update • Acute Lymphocytic Leukemia • Non-Hodgkin’s Lymphoma

Cellectis announces the drawdown of the third tranche of €5 million under the credit facility agreement entered with the European Investment Bank (EIB) (GlobeNewswire) - "Cellectis...today announced that it has drawn down the final tranche of €5 million ('Tranche C') under the credit facility agreement for up to €40 million entered into with the European Investment Bank...With the drawdown of Tranche C, the Company has drawn down the full €40 million available under the Finance Contract. Tranche C is expected to be disbursed by the EIB by December 18, 2024. The Company plans to use the proceeds of Tranche C towards the development of its pipeline of allogeneic CAR T-cell product candidates: UCART22 and UCART20x22."

Financing • Oncology

Cellectis Provides Business Updates and Financial Results for Third Quarter 2024 (GlobeNewswire) - "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."

Pipeline update • Trial status • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Cellectis Reports Financial Results for First Quarter 2024 (GlobeNewswire) - "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)...[and] in the NATHALI-01 study (evaluating UCART20x22) in relapsed or refractory B-cell non-Hodgkin lymphoma (r/r B-NHL)....We expect to provide updates in the advancements of BALLI-01 and NATHALI-01 by year-end 2024."

Enrollment status • P1/2 data • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Non-Hodgkin’s Lymphoma

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) (ASH 2023) - P1/2 | "TALEN® gene editing technology is used to inactivate the TRAC and CD52 genes to minimize graft-versus-host disease (GvHD) and allow for the use of alemtuzumab (CLLS52, an anti-CD52 monoclonal antibody) in the lymphodepletion (LD) regimen, respectively...After LD with FCA (fludarabine 30 mg/m2 × 3d, cyclophosphamide 0.5g/m2 × 3d, CLLS52 12 mg on D1, 24 mg on D2, D3), a single infusion of UCART20x22 is administered at a flat dose level ([DL1] 50 x 106 cells; [DL2] 150 x 106 cells; and [DL3] 450 x 106 cells)...Pt 3 is an 18yo female with R/R DLBCL transformed from marginal zone lymphoma who previously received chemoimmunotherapy, venetoclax, ibrutinib, BR, CAR19, obinutuzumab, glofitamab, tafasitamab, lenalidomide, and an experimental epigenetic modifier...Pt 1 had G1 CRS and received tocilizumab (toci) x3 and dexamethasone (dex) x1... As of 01 July 2023, 3 pts were enrolled and treated at DL1. Pt 1 is a 76yo female with double-expressor diffuse large..."

CAR T-Cell Therapy • IO biomarker • P1/2 data • Aplastic Anemia • Bone Marrow Transplantation • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Immunology • Lymphoma • Marginal Zone Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Transplantation • CD22 • CD8 • IFNG • IL2 • IL6 • TNFA

Cellectis announces the drawdown of the second tranche of €15 million under the credit facility agreement entered with the European Investment Bank (EIB) (GlobeNewswire) - "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."

Financing • Hematological Malignancies • Oncology

Cellectis to Present Preliminary Results of NATHALI_01 and Updated Results of the BALLI_01 Phases I Trials at the American Society of Hematology (ASH) 65th Annual Meeting (GlobeNewswire) - P1/2 | N=80 | NatHaLi-01 (NCT05607420) | Sponsor: Cellectis S.A. | "Cellectis...announced today that preliminary results of the Phase I NATHALI-01 clinical trial evaluating UCART20x22 in patients with relapsed or refractory non-Hodgkin lymphoma (r/r NHL)...will be presented at the American Society of Hematology 65th Annual Meeting (ASH 2023)....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....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."

P1 data • Non-Hodgkin’s Lymphoma

NATHALI-01: A PHASE 1/2A TRIAL OF UCART20X22, AN ALLOGENEIC DUAL CAR T-CELL THERAPY FOR PATIENTS WITH RELAPSED/REFRACTORY B-CELL NON-HODGKIN LYMPHOMA (NHL) (ICML 2023) - P1/2 | "After lymphodepletion with FCA (fludarabine 30 mg/m2 × 3d, cyclophosphamide 0.5g/m2 × 3d, alemtuzumab 12 mg on D1, 24 mg on D2, D3), patients will receive a single infusion of UCART20x22 at a flat dose level ([DL]; DL1-50 × 106 cells, DL2-150 × 106 cells, and DL3-450x106 cells). The trial is currently open for enrollment."

CAR T-Cell Therapy • Clinical • P1/2 data • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD22 • IFNG

Cellectis Showcased Preclinical Data at an Oral Presentation and Two Poster Presentations at the 29th International Society for Cell & Gene Therapy (ISCT 2023) Annual Event (GlobeNewswire) - "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."

Preclinical • Hematological Malignancies • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor

Cellectis Publishes an Article in Cancer Immunology Research Demonstrating Preclinical Evidence of UCART20x22 Product Candidate to Target a Broad Spectrum of Patients with B-cell Malignancies (GlobeNewswire) - "Cellectis...publishes an article in Cancer Immunology Research demonstrating pre-clinical proof-of-concept data of UCART20x22 product candidate, Cellectis’ first allogeneic dual CAR T-cell targeting the CD20 and CD22 antigens, to overcome current mechanisms of resistance to CAR T-cell therapies in B-cell Non-Hodgkin lymphoma (B-NHL), while providing a potential alternative to CD19 directed therapy."

Preclinical • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Non-Hodgkin’s Lymphoma • Oncology

Cellectis Implements CLLS52 for the First Time in the Clinic with Sanofi’s Alemtuzumab (GlobeNewswire) - "Cellectis...announced it has implemented the use of alemtuzumab as a Cellectis Investigational Medicinal Product (IMP), coded as CLLS52, as part of the lymphodepletion regimen for UCART22 in the BALLI-01 clinical trial in relapsed/refractory B-cell ALL, for UCART123 in the AMELI-01 clinical trial in relapsed/refractory AML, and for UCART20x22 in the NatHaLi-01 clinical trial in relapsed/refractory B-cell NHL....Under the agreements, Sanofi is supplying alemtuzumab to support Cellectis’ clinical trials and the parties agreed to enter into discussions to execute a commercial supply of alemtuzumab under pre-agreed financial conditions."

Clinical protocol • Commercial • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Cellectis enters into warrant agreement with the European Investment Bank related to credit facility agreement and announces the drawdown of the first tranche of €20 million (GlobeNewswire) - "The Company plans to use the proceeds of Tranche A towards the development of its pipeline of allogeneic CAR T-cell product candidates: UCART22, UCART20x22, UCART123 and UCARTCS1."

Commercial • Oncology

Cellectis Announces Closing of Global Offering and Exercise of Underwriters’ Option to Purchase Additional Shares (GlobeNewswire) - "The Company plans to use (i) approximately $17.0 million (€15.6 million) of the net proceeds of the Global Offering to fund the continued clinical development of UCART 123, UCART22, UCART20x22, and UCARTCS1, and (ii) any remainder for working capital and other general corporate purposes."

Commercial • Oncology

Cellectis Announces Pricing of Follow-On Offering (Cellectis Press Release) - "Cellectis plans to use (i) approximately $17.0 million (€15.6 million) of the net proceeds of the Global Offering to fund the continued clinical development of UCART 123, UCART22, UCART20x22, and UCARTCS1, and (ii) any remainder for working capital and other general corporate purposes."

Commercial • Oncology

Cellectis secures a €40 million credit facility from the European Investment Bank to support its Research, Development and Innovation activities (GlobeNewswire) - "The credit facility will enable Cellectis to support the development of its UCART product candidates pipeline. The credit facility consists of three tranches of €20 million, €15 million, and €5 million respectively, each redeemable in fine in 6 years. The credit facility is part of the European Investment Bank’s strategy to support biotech companies developing a high-level of expertise in various therapeutic areas with significant unmet medical need. Cellectis...announced that it has entered into a €40 million credit facility agreement with the European Investment Bank ('EIB') (the 'Finance Contract'). The Company plans to use the facility toward the development of its pipeline in the field of allogeneic CAR T-cell product candidates, UCART22, UCART20x22, UCART123 and UCARTCS1."

Financing • Oncology

Cellectis Announces Positive Preliminary Clinical Data for UCART22 in ALL and UCART123 in AML (GlobeNewswire) - "Cellectis is enrolling patients at dose level 1 (50x106 cells) with a fludarabine, cyclophosphamide, and alemtuzumab lymphodepletion regimen in the NATHALI-01 Phase 1 dose-escalation clinical study of UCART20x22. UCART20x22 is Cellectis’ first allogeneic dual CAR T-cell product candidate being developed for patients with relapsed or refractory non-Hodgkin lymphoma and fully designed, developed and manufactured in-house."

Trial status • Hematological Malignancies • Non-Hodgkin’s Lymphoma • Oncology

NatHaLi-01: Study Evaluating UCART20x22 in B-Cell Non-Hodgkin Lymphoma (clinicaltrials.gov) - P1/2 | N=80 | Recruiting | Sponsor: Cellectis S.A. | Not yet recruiting ➔ Recruiting

Enrollment open • Chronic Lymphocytic Leukemia • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • BCL2 • BCL6 • CD22

NatHaLi-01: Study Evaluating UCART20x22 in B-Cell Non-Hodgkin Lymphoma (clinicaltrials.gov) - P1/2 | N=80 | Not yet recruiting | Sponsor: Cellectis S.A.

New P1/2 trial • Chronic Lymphocytic Leukemia • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • BCL2 • BCL6 • CD22

Cellectis Receives IND clearance for UCART20x22, its First in-house Manufactured Product Candidate for the Treatment of B-cell Malignancies (GlobeNewswire) - "Cellectis...announced that the U.S. Food and Drug Administration (FDA) has cleared Cellectis’ Investigational New Drug (IND) application to initiate a Phase 1/2a clinical trial of UCART20x22 for patients with relapsed or refractory Non-Hodgkin Lymphoma (r/r NHL). The Company plans to begin enrolling patients in the NatHaLi-01 study in the second half of the year."

IND • New P1/2 trial • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

PRE-CLINICAL PROOF OF CONCEPT DEMONSTRATES ROBUST ACTIVITY OF UCART20X22 DUAL CAR T-CELLS FOR THE TREATMENT OF B-CELL MALIGNANCIES (EHA 2022) - "TALEN® gene editing technology was used to mediate inactivation of the TRAC and CD52 genes : TRAC KO is used to prevent Graft-vs-Host Disease , and CD52 KO to allow deepe r host lymphocyte depletion by confer ring resistance to lymphodepletion regimens including an anti-CD52 monoclonal antibody, such as alemtuzumab . Furthermore , in vitro assays against primary cells from Non-Hodgkin Lymphoma patient s with diverse CD22 and CD20 antigen levels demonstrate that UCART20x22 has potent and specific cytotoxic activity as well as IFN g release against these panel of samples . Conclusion W e present a robust pre-clinical proof of concept of a potent allogeneic dual CAR T-cell product candidate , UCART20x22, with the potential to 1) overcome common mechanisms of resistance in B- NHL, 2) enable the development of allogeneic CART option for B-NHL patients, 3) reduce the time from treatment decision to infusion."

CAR T-Cell Therapy • Preclinical • Graft versus Host Disease • Hematological Malignancies • Immunology • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD19 • CD22 • IFNG

UCART20x22: First allogeneic dual CAR T-cell therapy for the treatment of B-cell malignancies (AACR 2022) - "Besides efficiently targeting two commonly expressed antigens in B-cell malignancies, UCART20x22 incorporates TALEN® mediated TRAC and CD52 specific gene editing to prevent Graft-vs-Host Disease and improve persistence in the presence of alemtuzumab (an anti-CD52 monoclonal antibody that can be used as part of a lymphodepleting regimen). These attributes allow the production of allogeneic CAR T-cells from healthy individuals that can be administered at the time of treatment decision. In summary, we show an efficient first in class allogeneic dual CAR T-cell product candidate with demonstrated in vitro and in vivo properties to overcome antigen escape in B-cell malignancies."

CAR T-Cell Therapy • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD22 • IFNG

Cellectis Presents Preclinical Data from its First Allogeneic Dual CAR T-cell Product Candidate UCART20x22 for Patients with Relapsed or Refractory Non-Hodgkin Lymphoma at the American Association for Cancer Research (AACR) 2022 Annual Meeting (GlobeNewswire) - "Cellectis...released preclinical data on its product candidate UCART20x22 at the American Association for Cancer Research (AACR) Annual Meeting....In vivo pre-clinical models demonstrate that UCART20x22 efficiently eradicates tumors expressing both or either antigen, and sustained presence of UCART20x22 cells was observed in the bone marrow after tumor clearance....An Investigational New Drug application (IND) for UCART20x22 is expected to be filed this year."

IND • Preclinical • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Cellectis Provides Business Objectives for 2022 and Updates its Corporate Presentation (GlobeNewswire) - "Cellectis 2022 expected milestones: UCART Preclinical Programs - UCART20x22: Cellectis targets to file an IND for UCART20x22 and to initiate a Phase 1 trial in 2022."

IND • New P1 trial • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Cellectis Provides Business Update and Reports Financial Results for Second Quarter and First Six Months 2021 (GlobeNewswire) - “Cellectis continues to build its UCART pipeline and advance product candidates with industry leading partners. Cellectis anticipates the filing of two investigational new drug (IND) applications for UCART20x22 and UCARTMESO in 2022.”

IND • Hematological Malignancies • Oncology • Solid Tumor