taniraleucel (CYNK-001) / Celularity, United Therapeutics Corp - LARVOL DELTA

Conditioning Impacts on Regulatory T-Cells (Tregs) in the Microenvironment of AML: Observations from the Phase 1 Cynk-001-AML-001 Trial (ASH 2023) - P1 | "CYNK-001 proliferation and persistence was not enhanced with rhIL-2 infusion. Based on these data, rIL-2 was excluded from subsequent cohorts in this study."

P1 data • Acute Myelogenous Leukemia • Febrile Neutropenia • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Immunology • Leukemia • Neutropenia • Oncology • CD34 • CD8 • NCAM1

Results of Cynk-001-AML-001: A Phase I Multi-Dose Study Evaluating the Safety, Tolerability, and Persistence of Cynk-001 in Adults with De Novo or Secondary Acute Myeloid Leukemia in Morphologic Complete Remission with Minimal Residual Disease or Relapsed/Refractory AML (ASH 2023) - P1 | "Patients in cohorts 1-3 underwent standard lymphodepletion with fludarabine (25 mg/m2/day) and cyclophosphamide (300 mg/m2/day) on days -5, -4 and -3. This trial yielded important insights into the optimal approach to lymphodepletion and the potential clinical efficacy of allogeneic NK cells in R/R AML. Based on these results, this trial is now closed to further enrollment and future development activities will focus on next generation NK cell therapies edited to optimize persistence and efficacy and limit the requirement for enhanced lymphodepletion."

Clinical • Minimal residual disease • P1 data • Residual disease • Acute Myelogenous Leukemia • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Immunology • Leukemia • Oncology • Thrombocytopenia • CD34 • IL2 • NCAM1

CYNK001AML01: Natural Killer Cell (CYNK-001) Infusions in Adults with AML (clinicaltrials.gov) - P1 | N=27 | Terminated | Sponsor: Celularity Incorporated | N=94 ➔ 27 | Recruiting ➔ Terminated; Business reasons

Enrollment change • Minimal residual disease • Trial termination • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • Pain

Human Placental Hematopoietic Stem Cell Derived Natural Killer Cells Preferentially Eliminate Senescent Cells Derived from a Tumor Model (ASGCT 2024) - "Celularity is developing human placental CD34+-derived, cryopreserved, off-the-shelf, allogeneic NK cell products non-modified (CYNK-001), or genetically modified to optimize persistence and efficacy (CYNK-201) for the treatment of tumors and age-related diseases...With CYNK-001, there was significantly increased cytolysis of etoposide or doxorubicin treated cells vs. cytolysis of control non-treated A549 cells...Consistently, significantly increased secretion of inflammatory cytokines GM-CSF, G-CSF, IFN-γ, and TNF-α was also observed following CYNK co-culture with chemo-induced senescent A549 cells compared to non-treated cells, further confirming the preferential senolysis.Our preclinical data indicates that CYNK cells could serve as potent and selective senolytic agent for age-related diseases and also following conventional cancer treatment, CYNK may improve overall therapeutic outcomes and delay disease recurrence. Further investigation of CYNK cells in this regard,..."

Preclinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CD34 • CD58 • CSF2 • CXCL8 • IFNG • IL15 • IL6 • NCAM1 • NKG2D • TNFA

Celularity to Present Data Showing Senescent Cell Elimination by Off-the-Shelf Natural Killer Cells Derived from Human Placental Cells (GlobeNewswire) - "The preclinical data, which suggest that Celularity’s placenta-derived unmodified natural killer (NK) cells (CYNK-001) and genetically modified NK cells (CYNK-201) may serve as potent and selective senolytic agents for use in addressing age-related diseases, will be presented on May 9, 2024....Celularity believes these preclinical data demonstrate the potential of its assets to target and selectively remove damaged and abnormal cells expressing stress ligands, such as senescent, virally infected and cancer cells."

Preclinical • Oncology

Celularity Announces Clinical Data on Human Placental-Derived Unmodified Allogeneic Natural Killer Cell Therapy Candidate Cynk-001 in Adult Patients With Relapsed Refractory and Measurable Residual Disease-Positive Acute Myeloid Leukemia (GlobeNewswire) - P1 | N=91 | CYNK001AML01 (NCT04310592) | Sponsor: Celularity Incorporated | "Celularity...announced preliminary results from its Phase 1 trial of CYNK-001....In patients with relapsed refractory acute myeloid leukemia (R/R AML) treated with a four-dose regimen consisting of 1.8 billion CYNK-001 cells per dose, two of four patients achieved an objective response at Day 28. In patients with measurable residual disease-positive (MRD positive) AML treated with a three-dose regimen consisting of 1.8 billion CYNK-001 cells per dose, one of three patients achieved MRD negativity....Based on preliminary analysis of the Phase 1 trial data, this trial will now be closed to further enrollment as Celularity refines the trial design for subsequent studies with a next-generation NK product candidate....Data from the CYNK-001 Phase 1 trial will be submitted for inclusion at an upcoming scientific conference."

P1 data • Trial status • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

Developing CYNK-001-derived exosomes to deliver TGF-β siRNA for GBM immunotherapy enhancement (AACR 2023) - "Our results demonstrated anti-tumor activity of CYNK-Exo against GBM cells; efficient TGF-β knockdown in GBM cells by siCYNK-Exo; and synergistic anti-tumor activity ofTGF-β siCYNK-Exo in combination with CYNK-001 against GBM cells. Our data support a potential combination therapy using CYNK-001 and TGF-β siCYNK-Exo for GBM treatment."

IO biomarker • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor • CD34 • CD81 • CD9 • CSF2 • GZMA • GZMB • IFNG • NCAM1 • TGFB1 • TNFA

[VIRTUAL] A Phase 1 Multi-Dose Study of Human Placental Hematopoietic Stem Cell Derived Natural Killer Cells (CYNK‑001) in Adults with Primary or Secondary Acute Myeloid Leukemia (AML) in Morphologic Complete Remission with Minimal Residual Disease (MRD) (NCT04310592) (TCT-ASTCT-CIBMTR 2021) - P1 | "In this study (NCT02781467), a single infusion of PNK-007 up to 10e6 cells/kg was administered following cyclophosphamide (Cy)-fludarabine (Flu) Lymphodepletion (LD)... To date, 1 MRD+ pt with intermediate risk AML in morphologic CR received 3 doses of CYNK-001 at 600M cell dose following induction/consolidation with venetoclax and azacitidine... CYNK-001 is a cryopreserved allogeneic, off-the-shelf NK cell investigational product derived from human placental CD34+ cells. CYNK-001 is being evaluated in patients with AML who are in CR and are MRD+. Pt enrollment under CYNK-001-AML-001 is ongoing."

Clinical • P1 data • Residual disease • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • Transplantation • CD34

[VIRTUAL] A Phase 1 Multi-Dose Study of Human Placental Hematopoietic Stem Cell Derived Natural Killer Cells (CYNK‑001) in Adults with Primary or Secondary Acute Myeloid Leukemia (AML) in Morphologic Complete Remission with Minimal Residual Disease (MRD) (NCT04310592) (TCT-ASTCT-CIBMTR 2021) - P1 | "In this study (NCT02781467), a single infusion of PNK-007 up to 10e6 cells/kg was administered following cyclophosphamide (Cy)-fludarabine (Flu) Lymphodepletion (LD)... To date, 1 MRD+ pt with intermediate risk AML in morphologic CR received 3 doses of CYNK-001 at 600M cell dose following induction/consolidation with venetoclax and azacitidine... CYNK-001 is a cryopreserved allogeneic, off-the-shelf NK cell investigational product derived from human placental CD34+ cells. CYNK-001 is being evaluated in patients with AML who are in CR and are MRD+. Pt enrollment under CYNK-001-AML-001 is ongoing."

Clinical • P1 data • Residual disease • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • Transplantation • CD34

[VIRTUAL] A Phase 1 Multi-Dose Study of Human Placental Hematopoietic Stem Cell Derived Natural Killer Cells (CYNK‑001) in Adults with Primary or Secondary Acute Myeloid Leukemia (AML) in Morphologic Complete Remission with Minimal Residual Disease (MRD) (NCT04310592) (TCT-ASTCT-CIBMTR 2021) - P1 | "In this study (NCT02781467), a single infusion of PNK-007 up to 10e6 cells/kg was administered following cyclophosphamide (Cy)-fludarabine (Flu) Lymphodepletion (LD)... To date, 1 MRD+ pt with intermediate risk AML in morphologic CR received 3 doses of CYNK-001 at 600M cell dose following induction/consolidation with venetoclax and azacitidine... CYNK-001 is a cryopreserved allogeneic, off-the-shelf NK cell investigational product derived from human placental CD34+ cells. CYNK-001 is being evaluated in patients with AML who are in CR and are MRD+. Pt enrollment under CYNK-001-AML-001 is ongoing."

Clinical • P1 data • Residual disease • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • Transplantation • CD34

[VIRTUAL] A Phase 1 Multi-Dose Study of Human Placental Hematopoietic Stem Cell Derived Natural Killer Cells (CYNK‑001) in Adults with Primary or Secondary Acute Myeloid Leukemia (AML) in Morphologic Complete Remission with Minimal Residual Disease (MRD) (NCT04310592) (TCT-ASTCT-CIBMTR 2021) - P1 | "In this study (NCT02781467), a single infusion of PNK-007 up to 10e6 cells/kg was administered following cyclophosphamide (Cy)-fludarabine (Flu) Lymphodepletion (LD)... To date, 1 MRD+ pt with intermediate risk AML in morphologic CR received 3 doses of CYNK-001 at 600M cell dose following induction/consolidation with venetoclax and azacitidine... CYNK-001 is a cryopreserved allogeneic, off-the-shelf NK cell investigational product derived from human placental CD34+ cells. CYNK-001 is being evaluated in patients with AML who are in CR and are MRD+. Pt enrollment under CYNK-001-AML-001 is ongoing."

Clinical • P1 data • Residual disease • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • Transplantation • CD34

[VIRTUAL] Early report of a phase I/II study of human placental hematopoietic stem cell derived natural killer cells (CYNK-001) for the treatment of adults with COVID-19 (NCT04365101) (AACR 2021) - P1/2 | "Early efficacy has been seen in 3 of 4 pts with improvement of oxygenation, inflammatory markers, and radiographic findings. Once Phase 1 is completed, the Phase 2 portion of the study will test this approach in a randomized fashion compared to best available therapy to confirm efficacy of this approach."

Clinical • P1/2 data • Hematological Malignancies • Oncology • Solid Tumor • CD34

Natural Killer Cell (CYNK-001) Infusions in Adults With Multiple Myeloma (clinicaltrials.gov) - P1 | N=29 | Active, not recruiting | Sponsor: Celularity Incorporated | Trial completion date: Nov 2022 ➔ Apr 2023

Trial completion date • Bone Marrow Transplantation • Cardiovascular • Hematological Disorders • Hematological Malignancies • Monoclonal Gammopathy • Multiple Myeloma • Oncology • Pain • Plasmacytoma • Transplantation

CYNK001GBM02: CYNK-001 IV and IC in Combination With IL2 in Surgical Eligible Recurrent GBM With IDH-1 Wild Type (clinicaltrials.gov) - P1/2 | N=0 | Withdrawn | Sponsor: Celularity Incorporated | N=66 ➔ 0 | Recruiting ➔ Withdrawn

Combination therapy • Enrollment change • Trial withdrawal • Anaplastic Astrocytoma • Astrocytoma • Brain Cancer • CNS Tumor • Glioblastoma • Immunology • Oncology • Solid Tumor • IDH1

Celularity Reports Third Quarter 2022 Financial Results and Provides Corporate Update (GlobeNewswire) - "Third Quarter Clinical and Regulatory Highlights: CYNK-001 is currently being investigated in a Phase 1 clinical trial in AML and a Phase 1/2a clinical trial in GBM, with preliminary data readouts In AML expected in December 2022."

P1 data • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

A phase I/IIa, open-label, multicenter, non-randomized clinical trial to assess the safety and efficacy of CYNK-001 in combination with recombinant human interleukin 2 in adults with recurrent resection eligible IDH1 wild-type glioblastoma (GBM). (ASCO 2022) - P1/2 | "Screening MRI scans for inclusion are performed within 14 days prior to Day -5 lymphodepletion with Cyclophosphamide 900mg/m2 and fludarabine 30mg/m2 plus mesna. Approximately 66 patients are planned for this Phase I/IIa study. Approximately 66 patients are planned for this Phase I/IIa study."

Clinical • Combination therapy • P1/2 data • Brain Cancer • Glioblastoma • Immunology • Oncology • Solid Tumor • CD34 • IDH1 • IL2 • NCAM1

CYNK001AML01: Natural Killer Cell (CYNK-001) Infusions in Adults With AML (clinicaltrials.gov) - P1 | N=94 | Recruiting | Sponsor: Celularity Incorporated | N=56 ➔ 94 | Trial completion date: May 2024 ➔ Dec 2024 | Trial primary completion date: Dec 2023 ➔ Jun 2024

Enrollment change • Minimal residual disease • Trial completion date • Trial primary completion date • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Immunology • Leukemia • Oncology • Pain

CYNK001GBM02: CYNK-001 IV and IC in Combination With IL2 in Surgical Eligible Recurrent GBM With IDH-1 Wild Type (clinicaltrials.gov) - P1/2 | N=66 | Recruiting | Sponsor: Celularity Incorporated | Not yet recruiting ➔ Recruiting

Combination therapy • Enrollment open • Anaplastic Astrocytoma • Astrocytoma • Brain Cancer • Glioblastoma • Immunology • Oncology • Solid Tumor • IDH1

Celularity Reports First Quarter 2022 Financial Results and Provides Corporate Update (GlobeNewswire) - "CYNK-001 for the Treatment of AML and GBM: CYNK-001 is currently being investigated in two Phase 1 clinical trials, in AML and in GBM, with data readouts expected in the second half of 2022. Celularity continues to enroll new cohorts in both arms of the Phase 1 AML study with clinical trial protocol adjustments communicated in December 2021, which include an addition of interleukin-2 (IL-2) to the treatment regimen; a fourth dose on day 21; and an increase in the dose of NK cells."

Clinical protocol • Enrollment status • P1 data • Acute Myelogenous Leukemia • Brain Cancer • CNS Tumor • Hematological Malignancies • Leukemia • Oncology • Solid Tumor

Human placental hematopoietic stem cell derived natural killer cells (CYNK-001) mediate protection against influenza a viral infection. (PubMed, Hum Vaccin Immunother) - "Our results demonstrate that CYNK-001 displays protective functions against IAV via its anti-inflammatory and immunomodulating activities, which leads to alleviation of disease burden and progression in a severe IAV-infected mice model. The potential of adoptive NK therapy for IAV infections warrants clinical investigation."

Journal • Acute Lung Injury • Immune Modulation • Immunology • Infectious Disease • Inflammation • Respiratory Diseases • CD8

CYNK001GBM02: CYNK-001 IV and IC in Combination With IL2 in Surgical Eligible Recurrent GBM With IDH-1 Wild Type (clinicaltrials.gov) - P1/2 | N=66 | Not yet recruiting | Sponsor: Celularity Incorporated

Combination therapy • New P1/2 trial • Anaplastic Astrocytoma • Astrocytoma • Brain Cancer • Glioblastoma • Immunology • Oncology • Solid Tumor • IDH1 • MRI

CYNK001GBM01: Natural Killer Cell (CYNK-001) IV Infusion or IT Administration in Adults With Recurrent GBM (clinicaltrials.gov) - P1 | N=3 | Terminated | Sponsor: Celularity Incorporated | N=36 ➔ 3 | Trial completion date: Feb 2024 ➔ Aug 2021 | Active, not recruiting ➔ Terminated | Trial primary completion date: Sep 2023 ➔ Aug 2021; Business decision.

Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Anaplastic Astrocytoma • Astrocytoma • Brain Cancer • Glioblastoma • Immunology • Oncology • Pain • Solid Tumor

FDA Grants Fast Track Status to CYNK-001 for AML (OncLive) - "'The majority of patients with AML continue to have poor long-term outcomes, particularly those who suffer relapse or have measurable residual disease, necessitating development of novel therapies, including CYNK-001,' Andrew Pecora, MD...said in a press release."

Grant • Media quote

Celularity Receives Fast Track Designation from U.S. FDA for its NK Cell Therapy CYNK-001 in Development for the Treatment of AML (GlobeNewswire) - "Celularity Inc....announced the U.S. Food and Drug Administration (FDA) has granted Fast Track Designation for its non-genetically modified cryopreserved human placental hematopoietic stem cell-derived natural killer (NK) cell therapy, CYNK-001, in development for the treatment of acute myeloid leukemia (AML)."

Fast track designation • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

Celularity Reports Third Quarter 2021 Financial Results and Corporate Update (GlobeNewswire) - "Third Quarter Corporate Highlights:...Entered into a research collaboration with Oncternal Therapeutics...to evaluate placental derived-cellular therapies targeting receptor-tyrosine kinase-like Orphan Receptor 1 (ROR1) in preclinical studies. The collaboration will initially explore the use of Oncternal’s ROR1-targeted chimeric antigen receptor (CAR) gene modification as part of Celularity’s CYNK natural killer cell and CyCART platforms. The partnership will also explore the use of monoclonal antibody, cirmtuzumab, in combination with Celularity’s CYNK natural killer cells."

Licensing / partnership • Oncology