PNK-007 / Celularity, BMS - LARVOL DELTA

Evaluation of LL-37 resistance mechanics among uropathogenic Escherichia coli strains and antibiotic cross-resistance (AUA 2024) - "Transposon sequencing of an LL-37-resistant UPEC strain, EcPNK007, identified genes essential for EcPNK007 resistance to LL-37. Cross-resistance to colistin and PMB was not observed among LL-37-resistant UPEC strains suggesting that an LL-37-specific resistance mechanism is utilized."

Infectious Disease • Nephrology

[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

SAFETY AND TOLERABILITY OF ALLOGENEIC, OFF-THE SHELF PLACENTAL NATURAL KILLER CELLS (PNK 007) IN PHASE 1 MULTIPLE MYELOMA AND ACUTE MYELOID LEUKEMIA STUDIES (NCT02955550 AND NCT02781467) (EHA 2019) - P1; "This related event was noted as a DLT of cytokine release syndrome (CRS) which occurred 14 days after PNK-007 infusion and was managed with tocilizumab. All noted Infections SOC events were unrelated to PNK-007. The safety profile of PNK-007 merits evaluation for therapeutic use in hematological malignancies and solid tumors. "

Clinical • P1 data • Acute Myelogenous Leukemia • Cardiovascular • Cytomegalovirus Infection • Gastrointestinal Disorder • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Immunology • Leukemia • Multiple Myeloma • Nephrology • Oncology • Renal Disease • Respiratory Diseases

A Phase I study of PNK-007, allogeneic, off the shelf NK cell in relapsed/refractory AML (NCT02781467) (AACR 2019) - P1; "One pt treated with 10M cells/kg PNK-007 developed Cytokine Release Syndrome (CRS) 14 days after infusion and was effectively managed with tocilizumab. PNK-007 is a fully allogeneic, off the shelf CD34+ derived NK cell product. A single infusion of PNK-007 up to 10M cells/kg with rhIL-2 following Cy-Flu conditioning was safe and well tolerated, with one treatable CRS event observed. Two of 10 pts treated achieved clinical response, assessed by the investigators as CRp and MLFS."

P1 data • Acute Myelogenous Leukemia • Myelodysplastic Syndrome • Oncology

[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

Immune Monitoring of CD34+ Placental Cell Derived Natural Killer Cell Therapy (PNK-007) in Phase I Study of Multiple Myeloma (ASH 2019) - P1; "Translational data from a Phase I study of PNK-007 in post-ASCT MM established that dosing up to 3x107 cells/kg at 14 or 7 days post-transplant did not impair engraftment or immune reconstitution. EuroFlow MRD assessment of the bone marrow showed conversion of 6/11 patients from MRD(+) to MRD(-) by day 90 post transplant. The administration of IL-2 in this clinical study did not appear to benefit NK cell reconstitution but instead favored soluble IL2RA antagonism and increased systemic levels of Treg."

P1 data • Hematological Disorders • Hematological Malignancies • Immunology • Multiple Myeloma • Oncology • CD34 • CD8 • IFNG • IL15 • IL2RA

Results of a Phase I Study of Pnk-007, Allogeneic, Off the Shelf NK Cell, Post Autologous Transplant in Multiple Myeloma (NCT02955550) (ASH 2019) - P1; "PNK-007 is the first fully allogeneic, off the shelf CD34+ derived NK cell product in MM clinical trials. A single infusion of PNK-007 up to 30M cells/kg with and without rhIL-2 was well tolerated in the post-ASCT setting. We established the feasibility of infusing PNK-007 as early as 7 days post-ASCT without negative impact on blood count recovery or successful engraftment."

P1 data • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Immune Modulation • Inflammation • Multiple Myeloma • Oncology • CD34 • IL2 • NCAM1

A Phase I study of PNK-007, allogeneic, off the shelf NK cell, post autologous transplant in multiple myeloma (NCT02955550) (AACR 2019) - P1; "PNK-007 is the first fully allogeneic, off the shelf CD34+ derived NK cell product in MM clinical trials. A single infusion of PNK-007 up to 30M cells/kg with and without rhIL-2 was well tolerated in the post-ASCT setting. We established the feasibility of infusing PNK-007 as early as 7 days post-ASCT without negative impact on blood count recovery."

P1 data • Hematological Malignancies • Multiple Myeloma • Oncology

[VIRTUAL] Resistance in Uropathogenic E. coli Strains Isolated from Postmenopausal Women with Recurrent Urinary Tract Infections to the Antimicrobial Peptide Ll-37 (WMF 2021) - "Multiple sequence alignment revealed homology of EcPNK007 fluA1 and fluA2 to CFT073 fluA and UTI89 ag43, respectively. Future work will determine the role of the three fluA alleles in EcPNK007 LL-37 resistance using targeted mutagenesis."

Clinical • Infectious Disease • Nephrology

TCT 2021: Natural Killer Cell Therapy Under Study in Selected Patients With AML (JNCCN 360) - "James McCloskey, MD...and colleagues evaluated the use of CYNK-001—a cryopreserved allogeneic, off-the-shelf natural killer cell investigational product derived from placental CD34-positive cells—in select patients with acute myeloid leukemia (AML). At the 2021 Transplantation & Cellular Therapy Meetings (TCT), these investigators presented their overview of the ongoing CYNK-001-AML-001 trial (Abstract 173)....At the time of abstract presentation, one MRD-positive patient with intermediate-risk AML in morphologic complete remission had received three doses of 600 million cells following consolidation/induction with azacitidine and venetoclax. This patient is currently in follow-up and is reported to have tolerated CYNK-001 well, without dose-limiting toxicities."

PNK-007: allogeneic NK-cell product post-ASCT in MM (YouTube) - "Ravi Vij, MD, MBA...discusses the phase I study (NCT02955550) of single infusion PNK-007, an allogeneic cell therapy product enriched for CD56+/CD3- NK-cells expanded from placental CD34+ cells, after autologous stem cell transplant (ASCT) in multiple myeloma (MM). Prof. Vij reveals PNK-007 with and without recombinant human IL-2 was well tolerated in the post-ASCT setting. Data from this phase I study are encouraging and warrant further evaluation."

Interview • Video

A Safety Study of Human Cord Blood Derived, Culture-expanded, Natural Killer Cell (PNK-007) Infusion With or Without Subcutaneous Recombinant Human Interleukin-2 (rhIL-2) Following Autologous Stem Cell Transplant for Multiple Myeloma (MM) (clinicaltrials.gov) - P1; N=15; Completed; Sponsor: Celularity Incorporated; Active, not recruiting ➔ Completed

Trial completion • Hematological Malignancies • Multiple Myeloma • Oncology • Transplantation

Celularity presents pre-clinical and clinical data from its allogeneic, placental-derived, off-the-shelf cell therapy platform at the 2019 ASH Annual Meeting (Businesswire) - P1, N=15; NCT02955550; Sponsor: Celularity Incorporated; "Results from a Phase 1 clinical study evaluating PNK-007 in patients with multiple myeloma demonstrated a single infusion of PNK-007 was well tolerated after autologous stem cell transplant (ASCT) for up to one year. PNK-007 is a first-generation investigational allogeneic off-the-shelf NK cell therapy. No serious adverse events (AEs) were attributable to PNK-007, and no dose-limiting toxicity, graft-verse-host disease (GvHD), cytokine release syndrome (CRS), graft failure or graft rejection was observed."

P1 data

Development of CD38 CAR Engineered Human Placental Hematopoietic Stem Cell Derived Natural Killer Cells (PNK-CAR38) As Allogeneic Cancer Immunotherapy (ASH 2019) - "Celularity has developed a GMP process for generating off-the-shelf and allogeneic human Placental Hematopoietic Stem Cell derived Natural Killer (PNK-007) cells... The novel PNK-CAR38 demonstrated enhanced in vitro cytotoxic potential against lymphoma and MM lines and showed no on-target off-tumor cytotoxicity against healthy donor-derived cells in vitro. In vivo anti-tumor activity of PNK-CAR38 was shown in a lymphoma disseminated NSG model. Further development of PNK-CAR38 for hematological malignancies is warranted."

IO Biomarker • CD34 • CD38 • FLT3 • IL15 • IL2 • IL7 • NCAM1

A Phase I study of PNK-007, allogeneic, off the shelf NK cell, post autologous transplant in multiple myeloma (NCT02955550) (IMW 2019) - P1; "PNK-007 is the first fully allogeneic, off the shelf CD34+ derived NK cell product in MM clinical trials. A single infusion of PNK-007 up to 30M cells/kg with and without rhIL-2 was well tolerated in the post-ASCT setting. We established the feasibility of infusing PNK-007 as early as 7 days post-ASCT without negative impact on blood count recovery or successful engraftment."

P1 data

Immune monitoring of PNK-007, an allogeneic, off the shelf NK cell in a Phase I study of acute myeloid leukemia (AACR 2019) - "In a 10 patient relapsed/refractory AML phase I study, PNK-007 infusion was evaluated following Cyclophosphamide-Fludarabine (Cy-Flu) conditioning treatment. We further show in this patient population that immune reconstitution appears compromised following Cy-Flu conditioning. Our data identify kinetics of PNK-007 persistence alongside hematopoietic recovery and AML disease."

IO Biomarker • Late-breaking abstract • P1 data • PD(L)-1 Biomarker

Celularity announces results of phase 1 studies of PNK-007, an allogeneic, off-the-shelf, placental-derived cell therapy, at AACR Annual Meeting 2019 (Businesswire) - "Celularity...announced results from two Phase 1 studies of PNK-007, an investigational allogeneic off-the-shelf natural killer (NK) cell therapy, in patients with acute myeloid leukemia (AML) and in patients with multiple myeloma (MM)....The Company plans to initiate a Phase 1b/2a study in AML patients and a Phase 2 study in MM patients during the second half of 2019. These studies will investigate the safety and efficacy of CYNK-001, the cryopreserved successor product to PNK-007."

New P1/2 trial • New P2 trial • P1 data

First clinical results evaluating allogeneic, off-the-shelf, placental-derived cells to be presented by Celularity at 2019 AACR Annual Meeting (Businesswire) - "Celularity...announced it will present first-ever clinical and pre-clinical results from its comprehensive placental hematopoietic stem cell derived natural killer (PNK) cells oncology program at the 2019 American Association for Cancer Research (AACR) Annual Meeting being held from March 29 – April 3, 2019 in Atlanta, Georgia...[Presentations include] first in-human clinical presentation of company’s PNK allogeneic cell therapy in patients with acute myeloid leukemia, clinical presentation of company’s PNK allogeneic cell therapy in patients with multiple myeloma [and] late-breaking presentation of translational research from phase 1 acute myeloid leukemia immunotherapy study."

P1 data

A Safety Study of Human Cord Blood Derived, Culture-expanded, Natural Killer Cell (PNK-007) Infusion With or Without Subcutaneous Recombinant Human Interleukin-2 (rhIL-2) Following Autologous Stem Cell Transplant for Multiple Myeloma (MM) (clinicaltrials.gov) - P1; N=15; Active, not recruiting; Sponsor: Celularity Incorporated; Recruiting ➔ Active, not recruiting; N=46 ➔ 15; Trial completion date: Apr 2020 ➔ Jul 2019; Trial primary completion date: Apr 2020 ➔ Jul 2019

Enrollment change • Enrollment closed • Trial completion date • Trial primary completion date