SAR445419 / Sanofi - LARVOL DELTA

Trial Testing Safety of IL-21 NK Cells for Induction of R/R AML (clinicaltrials.gov) - P1 | N=19 | Active, not recruiting | Sponsor: Sumithira Vasu | Recruiting ➔ Active, not recruiting | Trial completion date: Dec 2024 ➔ Dec 2025

Enrollment closed • Trial completion date • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Oncology • Transplantation • IL21

Phase II Clinical Trial of "Off-the-Shelf" NK Cells with Allogeneic Stem Cell Transplantation in Patients with High-Risk Myeloid Malignancies (ASH 2024) - P1/2 | "Starting on day -7 patients received melphalan 100 or 140 mg/m2, fludarabine, and on day -3, total body radiation (2Gy) as the preparative regimen, with bone marrow or peripheral blood progenitor cells on day 0. Cyclophosphamide, tacrolimus and mycophenolate was given as GVHD prophylaxis. Patients received KDS-1001 cells 3 x107/kg on day -2, +7 and +28...The post stem cell transplant course for those treated thus far seems to be similar to the reported literature. Longer follow up is needed to assess the impact on disease relapse and relapse free survival."

Clinical • P2 data • Acute Graft versus Host Disease • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Chronic Graft versus Host Disease • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Immunology • Infectious Disease • Leukemia • Myelodysplastic Syndrome • Oncology • Septic Shock • Transplant Rejection • Transplantation • KIR2DS2

IIT PH1 KDS-1001 in Patients With CML (clinicaltrials.gov) - P1 | N=0 | Withdrawn | Sponsor: Duke University | N=12 ➔ 0 | Trial completion date: Sep 2027 ➔ Dec 2029 | Not yet recruiting ➔ Withdrawn | Trial primary completion date: Sep 2025 ➔ Dec 2027

Enrollment change • Trial completion date • Trial primary completion date • Trial withdrawal • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology • ABL1 • BCR

Trial Testing Safety of IL-21 NK Cells for Induction of R/R AML (clinicaltrials.gov) - P1 | N=21 | Recruiting | Sponsor: Sumithira Vasu | Trial completion date: Dec 2023 ➔ Dec 2024 | Trial primary completion date: Dec 2023 ➔ Dec 2024

Trial completion date • Trial primary completion date • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Oncology • Transplantation • IL21

Evaluation of NK cell combination therapies in mouse models of cancer (AACR 2024) - "SAR445419 is a universal off-the-shelf allogeneic human NK cell (hNK) product made using Sanofi's proprietary platform with potential broad application across hematologic and solid tumor indications...We also reported prolonged lifespan of leukemia-bearing animals treated with NK cells and pegenzileukin, a PEGylated non-alpha rhIL‑2 variant engineered to preferentially bind to the IL-2 βγ receptors and promote NK cell function...Obtained results suggest that CD38KO NK cells are resistant to anti-CD38 mAb-mediated fratricide and provide a rationale for the combination of CD38KO NK cells with anti-an CD38 mAb against MM. Overall, these preclinical in vivo studies have a pivotal role in the evaluation of NK cell combination therapies against cancer and reveal their therapeutic potential."

Combination therapy • Preclinical • Hematological Malignancies • Leukemia • Lymphoma • Multiple Myeloma • Oncology • Solid Tumor • IL2

A Study to Investigate Use of Off-the-shelf Natural Killer (NK) Cells (SAR445419) in Relapsed/Refractory Acute Myeloid Leukemia (clinicaltrials.gov) - P1 | N=7 | Terminated | Sponsor: Sanofi | Trial completion date: Jan 2025 ➔ Mar 2024 | Active, not recruiting ➔ Terminated; Sponsor's decision

Trial completion date • Trial termination • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

Sanofi discontinues development of NK cell therapy… Kiadis closes [Google translation] (News The Voice Healthcare) - "Sanofi will discontinue the development of 'SAR445419', an allogeneic natural killer (NK) cell therapy candidate acquired through a merger and acquisition three years ago...In addition, it was decided to close Kiadis Sciences, located in the Netherlands, which was merged through an acquisition proposal in November 2020....Endpoint, a medical media company, reported this news in Clinical Trials on the 10th based on the suspension of the phase 1 clinical trial related to SAR445419 updated on the 8th and the announcement of Kiadis' closure as the reason for the suspension."

Discontinued • M&A • Trial termination • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

A Study to Investigate Use of Off-the-shelf Natural Killer (NK) Cells (SAR445419) in Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) (clinicaltrials.gov) - P2 | N=0 | Withdrawn | Sponsor: Sanofi | N=107 ➔ 0 | Trial completion date: Feb 2027 ➔ Oct 2027 | Not yet recruiting ➔ Withdrawn

Enrollment change • Trial completion date • Trial withdrawal • Bone Marrow Transplantation • Hematological Malignancies • Oncology • Transplantation

A Study to Investigate Use of Off-the-shelf Natural Killer (NK) Cells (SAR445419) in Relapsed/Refractory Acute Myeloid Leukemia (clinicaltrials.gov) - P1 | N=7 | Active, not recruiting | Sponsor: Sanofi | Recruiting ➔ Active, not recruiting | N=12 ➔ 7

Enrollment change • Enrollment closed • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

SAR445419 Off-the-Shelf Natural Killer Cells Are Safe and Show Efficacy Signal in Relapsed/Refractory Acute Myeloid Leukemia. (TCT-ASTCT-CIBMTR 2024) - P1 | "Patients were treated at two dose levels of SAR'419 (DL1: 1x10e7 cells/kg; DL2: 3x10e7 cells/kg) following administration of Fludarabine 30 mg/m2/day & Cytarabine 2 g/m2/day on days -6 to -2. Cryopreserved, third-party, donor-derived NK cells (SAR'419) are well tolerated and feasible in relapsed/refractory AML patients as induction and maintenance treatments. Completely HLA-mismatched NK cells can persist and expand to high levels in vivo with an efficacy signal noted at 1x10e7 cells/kg."

Clinical • IO biomarker • Acute Myelogenous Leukemia • Graft versus Host Disease • Hematological Malignancies • Immunology • Leukemia • Oncology • Transplantation • IL21

A Phase 2, Single-Arm, Multicohort, Open Label, Multicenter Trial of Off-the-Shelf Natural Killer Cells (SAR445419) in Patients with High-Risk Myeloid Malignancies Undergoing Allogeneic HSCT (ASH 2023) - P2 | "Prophylaxis for Graft-versus-host disease (GVHD) using cyclophosphamide, mycophenolate mofetil, and tacrolimus will start on Day +3. RFS will be reported as the percentage of patients who are relapse free and alive at 12 months from the date of HSCT and who received at least the first 2 planned doses of SAR'419. Adverse events will be graded by the National Cancer Institute Common Terminology Criteria for Adverse Events v5.0 and will be summarized using descriptive statistics."

Clinical • P2 data • Acute Graft versus Host Disease • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Cytomegalovirus Infection • Graft versus Host Disease • Hematological Malignancies • Immunology • Infectious Disease • Leukemia • Myelodysplastic Syndrome • Oncology • Transplantation • IL21

A Phase I, Single-Arm, Open Label, Dose Escalation, Multicenter Study of Off-the-Shelf Natural Killer (NK) Cells (SAR445419) in Patients with Relapsed/Refractory Acute Myeloid Leukemia (R/R AML) (ASH 2023) - P1, P1/2 | "Eligible patients will be administered fludarabine, 30 mg/m 2/day and cytarabine, 2 g/m 2/day (Day -6 to Day -2) for 5 days followed by 6 doses of SAR'419 (intravenous) given thrice weekly over 2 weeks beginning on Day 1...Key exclusion criteria are participants with a second primary malignancy requiring active therapy (adjuvant hormonal therapy is allowed); with known acquired immunodeficiency syndrome or human immunodeficiency virus disease requiring antiretroviral treatment or having active hepatitis B or C infection, or symptomatic severe acute respiratory syndrome coronavirus 2 infection; and who are receiving >10 mg/day of oral prednisone or equivalent...All other safety analyses will be performed on the safety population using descriptive statistics. This study is actively recruiting at this time and is being conducted in the United States."

Clinical • IO biomarker • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Hepatitis B • Hepatology • Human Immunodeficiency Virus • Infectious Disease • Leukemia • Novel Coronavirus Disease • Oncology • Respiratory Diseases • Transplantation • IL21

A Study to Investigate Use of Off-the-shelf Natural Killer (NK) Cells (SAR445419) in Relapsed/Refractory Acute Myeloid Leukemia (clinicaltrials.gov) - P1 | N=12 | Recruiting | Sponsor: Sanofi | Trial primary completion date: Oct 2023 ➔ Mar 2024

Trial primary completion date • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

Trial Testing Safety of IL-21 NK Cells for Induction of R/R AML (clinicaltrials.gov) - P1 | N=21 | Recruiting | Sponsor: Sumithira Vasu | N=30 ➔ 21 | Trial completion date: Dec 2022 ➔ Dec 2023 | Trial primary completion date: Dec 2022 ➔ Dec 2023

Enrollment change • Trial completion date • Trial primary completion date • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Oncology • Transplantation • IL21

A Study to Investigate Use of Off-the-shelf Natural Killer (NK) Cells (SAR445419) in Relapsed/Refractory Acute Myeloid Leukemia (clinicaltrials.gov) - P1 | N=12 | Recruiting | Sponsor: Sanofi | Not yet recruiting ➔ Recruiting

Enrollment open • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

A Study to Investigate Use of Off-the-shelf Natural Killer (NK) Cells (SAR445419) in Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) (clinicaltrials.gov) - P2 | N=107 | Not yet recruiting | Sponsor: Sanofi | Initiation date: May 2023 ➔ Feb 2024

Trial initiation date • Bone Marrow Transplantation • Hematological Malignancies • Oncology • Transplantation

A Phase II Clinical Trial of "Off-the-Shelf" NK Cells with Allogeneic Stem Cell Transplantation to Decrease Disease Relapse in Patients with High-Risk Myeloid Malignancies (ASH 2022) - P1/2 | "We will also exclude any patient requiring systemic corticosteroids with prednisone dose >10 mg or equivalent or who has KDS-1001 Donor specific antibodies (dsa) >5000 MFI units, or has KDS-1001 Donor anti-C1q positive. Exploratory analyses with immunophenotyping for NK cell chimerism and persistence will be done as feasible. Immune reconstitution studies or additional future research may be performed."

Clinical • P2 data • Acute Myelogenous Leukemia • Allergy • Bone Marrow Transplantation • Chronic Myeloid Leukemia • Fibrosis • Gastroenterology • Graft versus Host Disease • Hematological Malignancies • Hepatitis B • Hepatology • Human Immunodeficiency Virus • Immunology • Infectious Disease • Inflammation • Leukemia • Liver Cirrhosis • Myelodysplastic Syndrome • Oncology • Transplantation • KIR2DS2

A Study to Investigate Use of Off-the-shelf Natural Killer (NK) Cells (SAR445419) in Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) (clinicaltrials.gov) - P2 | N=107 | Not yet recruiting | Sponsor: Sanofi

New P2 trial • Bone Marrow Transplantation • Hematological Malignancies • Oncology • Transplantation

A Study to Investigate Use of Off-the-shelf Natural Killer (NK) Cells (SAR445419) in Relapsed/Refractory Acute Myeloid Leukemia (clinicaltrials.gov) - P1 | N=12 | Not yet recruiting | Sponsor: Sanofi

New P1 trial • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

IIT PH1 KDS-1001 in Patients With CML (clinicaltrials.gov) - P1 | N=12 | Not yet recruiting | Sponsor: Lindsay Rein, MD | Trial completion date: Sep 2026 ➔ Sep 2027 | Trial primary completion date: Sep 2024 ➔ Sep 2025

Trial completion date • Trial primary completion date • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology • ABL1 • BCR

Ph1 Trial Test Safety of IL-21 NK Cells for Induction of R/R AML (clinicaltrials.gov) - P1 | N=30 | Recruiting | Sponsor: Sumithira Vasu | N=44 ➔ 30 | Trial completion date: Dec 2021 ➔ Dec 2022 | Trial primary completion date: Dec 2021 ➔ Dec 2022

Enrollment change • Trial completion date • Trial primary completion date • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Oncology • Transplantation • IL21

[VIRTUAL] A Phase I Trial of Incorporating Natural Killer (K-NK) Cells for Patients with Chronic Myeloid Leukemia (CML) and Molecular Residual Disease after Tyrosine Kinase Inhibitor (TKI) Therapy (ASH 2020) - "Kiadis K-NK003 cells are off-the-shelf NK cells from a universal donor expanded using PM21, proprietary membrane particles modified to express membrane bound IL-21 and 4-1bb ligand...Patients must have been on their most recent TKI consistently for at least 6 months prior to enrollment on study and must be expected to remain on current TKI for the duration of the study. Patients with current accelerated or blast crisis phase disease will be excluded."

Clinical • P1 data • Residual disease • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology • GZMB • IFNG • IL2 • IL21 • TNFA

[VIRTUAL] A Phase I Trial of Incorporating Natural Killer (K-NK) Cells for Patients with Chronic Myeloid Leukemia (CML) and Molecular Residual Disease after Tyrosine Kinase Inhibitor (TKI) Therapy (TCT-ASTCT-CIBMTR 2021) - "Kiadis K-NK003 cells are off-the-shelf NK cells from an universal donor expanded using PM21, proprietary membrane particles modified to express membrane bound IL-21 and 4-1bb ligand...Adult patients with chronic phase CML who have been on TKI therapy for at least 1 year prior to enrollment in the study will be eligible. Patients must have been on their most recent TKI consistently for at least 6 months prior to enrollment on study and must be expected to remain on current TKI for the duration of the study."

Clinical • P1 data • Residual disease • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology • GZMB • IFNG • IL2 • IL21 • TNFA

[VIRTUAL] A Phase I Trial of Incorporating Natural Killer (K-NK) Cells for Patients with Chronic Myeloid Leukemia (CML) and Molecular Residual Disease after Tyrosine Kinase Inhibitor (TKI) Therapy (TCT-ASTCT-CIBMTR 2021) - "Kiadis K-NK003 cells are off-the-shelf NK cells from an universal donor expanded using PM21, proprietary membrane particles modified to express membrane bound IL-21 and 4-1bb ligand...Adult patients with chronic phase CML who have been on TKI therapy for at least 1 year prior to enrollment in the study will be eligible. Patients must have been on their most recent TKI consistently for at least 6 months prior to enrollment on study and must be expected to remain on current TKI for the duration of the study."

Clinical • P1 data • Residual disease • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology • GZMB • IFNG • IL2 • IL21 • TNFA

[VIRTUAL] A Phase I Trial of Incorporating Natural Killer (K-NK) Cells for Patients with Chronic Myeloid Leukemia (CML) and Molecular Residual Disease after Tyrosine Kinase Inhibitor (TKI) Therapy (TCT-ASTCT-CIBMTR 2021) - "Kiadis K-NK003 cells are off-the-shelf NK cells from an universal donor expanded using PM21, proprietary membrane particles modified to express membrane bound IL-21 and 4-1bb ligand...Adult patients with chronic phase CML who have been on TKI therapy for at least 1 year prior to enrollment in the study will be eligible. Patients must have been on their most recent TKI consistently for at least 6 months prior to enrollment on study and must be expected to remain on current TKI for the duration of the study."

Clinical • P1 data • Residual disease • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology • GZMB • IFNG • IL2 • IL21 • TNFA