NKX101 / Nkarta Therap - LARVOL DELTA

A Phase 1 Study of NKX101, a Chimeric Antigen Receptor Natural Killer (CAR-NK) Cell Therapy, with Fludarabine and Cytarabine in Patients with Acute Myeloid Leukemia (ASH 2023) - "Because Ara-C is known to upregulate NKG2D ligand expression, use of Flu/Ara-C as an alternative to standard Flu/cyclophosphamide (Flu/Cy) for lymphodepletion (LD) was tested for NKX101...Patients had received a median of two prior lines of therapy, with all patients having previous venetoclax exposure (Table 1)...Despite being an allogeneic, non-HLA-matched cell product, NKX101 persisted for up to three weeks in PK testing. Directly comparing the data from patients treated with Flu/Cy with NKX101 versus Flu/Ara-C with NKX101 suggests that Flu/Ara-C can replace the Flu/Cy regimen common to CAR T cell therapy as LD without compromising overall NKX101 exposure."

Clinical • P1 data • Acute Myelogenous Leukemia • Graft versus Host Disease • Hematological Malignancies • Immunology • Infectious Disease • Leukemia • Oncology • CXCL8 • IFNG • IL10 • IL15 • IL6 • NKG2D • RUNX1 • RUNX1T1 • TP53 • ULBP1

NKX101, an Allogeneic Off-the-Shelf CAR NK Therapy Targeting NKG2D-Ls, Has Potent In Vitro Cytotoxicity Against Patient-Derived AML Leukemic Stem Cell (LSC) and Non-Leukemic Stem Cell (Non-LSC) Blasts (ASH 2023) - "Additionally, the ability of NKX101 to potently kill AML LSC blasts suggests that NKG2D-L targeting may be a viable mechanism for eliminating LSC in the blood and bone marrow of patients with r/r AML. Taken together, these data support NKG2D-Ls as promising therapeutic targets for AML and support further investigation of NKX101 CAR NK cell therapy for the treatment of r/r AML."

Preclinical • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • IL15 • NKG2D • ULBP1

NKX101, an Allogeneic Off-the-Shelf CAR NK Cell Therapy Targeting NKG2D-Ls, Has Potent Anti-Leukemic Activity Alone or in Combination with Ara-C (ASH 2023) - "ConclusionsIn summary, we show that NKX101 potently targets and eliminates AML cells expressing NKG2D-Ls further validating NKG2D-Ls as therapeutic targets. Additionally, we show that the combination of Ara-C and NKX101 leads to increased anti-leukemic activity, supporting continued investigation of NKX101 CAR NK cell therapy after lymphodepletion incorporating Ara-C for the treatment of r/r AML."

Combination therapy • Acute Myelogenous Leukemia • IL15 • NKG2D

NKX101-101: NKX101, Intravenous Allogeneic CAR NK Cells, in Adults With AML or MDS (clinicaltrials.gov) - P1 | N=61 | Active, not recruiting | Sponsor: Nkarta, Inc. | Trial primary completion date: Jul 2024 ➔ Oct 2024

Trial primary completion date • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Myelodysplastic Syndrome • Oncology • FLT3

NKX101, an allogeneic off-the-shelf NKG2D CAR-NK cell therapy, has potent in vitro cytotoxicity against patient-derived AML leukemic stem cells and non-leukemic stem cell blasts (AACR 2024) - "In summary, we show that NKG2D-Ls are expressed on the surface of both LSC and non-LSC AML blasts and at levels above those observed in normal hematopoietic cells. Additionally, the ability of NKX101 to potently kill AML LSC blasts suggests that NKG2D-L targeting may be a viable mechanism for eliminating LSCs in the blood and bone marrow of patients with r/r AML. Taken together, these data support NKG2D-Ls as promising therapeutic targets for AML and support further investigation of NKX101 CAR-NK therapy for the treatment of r/r AML."

Preclinical • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • IL15 • NKG2D

NKX101, an allogeneic off-the-shelf CAR NK cell therapy targeting NKG2D-Ls, has potent anti-leukemic activity alone or in combination with Ara-C (AACR 2024) - "Expression of a single NKG2D-L was sufficient to trigger NKX101 cytotoxicity against target cell lines, further validating NKG2D-Ls as therapeutic targets. Flow cytometry analysis revealed that pre-treatment with Ara-C upregulated NKG2D-Ls on AML cell lines in a dose-dependent manner. NKX101 showed enhanced anti-leukemic activity against AML cells pre-treated with Ara-C compared to untreated controls, demonstrating that the combination can enhance NKX101 potency."

Combination therapy • Acute Myelogenous Leukemia • Oncology • IL15 • NKG2D

NKX101-101: NKX101, Intravenous Allogeneic CAR NK Cells, in Adults With AML or MDS (clinicaltrials.gov) - P1 | N=61 | Active, not recruiting | Sponsor: Nkarta Inc. | Recruiting ➔ Active, not recruiting | N=90 ➔ 61

Enrollment change • Enrollment closed • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Myelodysplastic Syndrome • Oncology • FLT3

Nkarta Reports Fourth Quarter and Full Year 2023 Financial Results and Corporate Highlights (GlobeNewswire) - "Nkarta announced today that it has closed patient enrollment in its clinical trial of NKX101 and deprioritized the program as part of a pipeline realignment that directs primary resources to its lead pipeline program, NKX019, for the treatment of autoimmune disease. This follows a recent review of preliminary safety and response data from patients with r/r AML that received NKX101 after LD comprising fludarabine and cytarabine (flu/Ara-C). The aggregate CR/CRi rate (5 of 20 patients) was lower than what had been observed in the first 6 patients in the cohort....This announcement reflects the NKX101 clinical update that Nkarta had planned to report in the first half of 2024. Nkarta plans to present these data at a future medical conference."

Discontinued • Enrollment closed • P1 data • Acute Myelogenous Leukemia

Nkarta Presents NKX101 Clinical Data at the 2023 American Society of Hematology Annual Meeting & Exposition (GlobeNewswire) - P1 | N=90 | NCT04623944 | Sponsor: Nkarta Inc. | "Nkarta, Inc...announced a poster presentation at the 2023 American Society of Hematology (ASH) Annual Meeting and Exposition featuring follow-up data from its Phase 1 clinical trial that evaluates NKX101 in patients with relapsed or refractory acute myeloid leukemia (r/r AML)....As reported in June 2023, of those patients who received NKX101 after a disease-specific lymphodepletion (LD) regimen comprising fludarabine and cytarabine (Flu/Ara-C), four of six achieved CR/CRi. In the follow up presented today, three of those four patients remained in CR/CRi at 4 months from treatment with NKX101....Nkarta plans to provide an update from the NKX101 Flu/Ara-C LD cohort in the first half of 2024 that includes preliminary safety and response data from 12 to 20 additional patients."

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

NKX101, Intravenous Allogeneic CAR NK Cells, in Adults With AML or MDS (clinicaltrials.gov) - P1 | N=90 | Recruiting | Sponsor: Nkarta Inc. | Trial completion date: Jul 2038 ➔ Jul 2039 | Trial primary completion date: Jul 2023 ➔ Jul 2024

Trial completion date • Trial primary completion date • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Myelodysplastic Syndrome • Oncology • FLT3

High Dose NK Cell Therapy Shows Efficacy in AML (CGTLive) - "'Patients with relapsed or refractory AML have few treatment options, and novel approaches are urgently needed. Traditional chemotherapy is often unable to drive deep remissions in this setting, and many patients cannot tolerate it,' Carlos Bachier, MD...said in a statement. 'NKX101 following lymphodepletion with fludarabine and Ara-C had encouraging anti-tumor activity in a small number of patients with difficult to treat relapsed/refractory AML. This activity, together with its tolerable safety profile, merits further study of NKX101.'"

Media quote

Nkarta Updates Clinical Progress of CAR-NK Cell Therapy NKX101 for Patients with Relapsed or Refractory Acute Myeloid Leukemia (GlobeNewswire) - P1 | N=90 | NCT04623944 | Sponsor: Nkarta Inc. | "Four of six patients in one dose expansion cohort achieved a best composite complete response (67% CR/CRi rate) after receiving at least one cycle of NKX101. In this cohort, a cycle consisted of three weekly doses of NKX101 at 1.5 billion cells per dose after treatment with fludarabine (Flu) and Ara-C (cytarabine) for lymphodepletion. Ara-C is an established and important drug in the treatment of AML across treatment lines, including first line therapy. Exposure to Ara-C is also known to upregulate NKG2D ligands, potentially increasing sensitivity of cancerous cells to NK-cell mediated killing....Nkarta expects to enroll 12 to 20 additional patients in the expansion cohort using Flu/Ara-C lymphodepletion of the Phase 1 clinical trial and provide a clinical update in the first half of 2024. Nkarta also plans to introduce protocol changes intended to standardize criteria for retreatment and consolidation and simplify...

Clinical protocol • Enrollment status • P1 data • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

Combination of anti-EGFR antibody cetuximab with NKX101, an allogeneic NKG2D-L targeting NK cell therapy, enhances potency and in vitro cytotoxicity against solid tumors (AACR 2023) - "We demonstrate that cetuximab increases the anti-tumor effect of NKX101 in a dose-dependent manner. Assessment of the interaction between NKX101 and cetuximab in vitro revealed that the two agents can combine to kill cancer cells in a synergistic manner. Blocking CD16 on NKX101 cells with a neutralizing antibody significantly decreased potency of the combination, suggesting that the improvement in potency observed is a direct result of CD16-mediated ADCC activity."

Preclinical • Colorectal Cancer • Head and Neck Cancer • Oncology • Solid Tumor • EGFR • IL15 • NKG2D

Nkarta Presents Preclinical Data Exploring Gene Knockout Strategies and Combination Agents with NK Cell-Based Therapies at the 2023 AACR Annual Meeting (GlobeNewswire) - "This study demonstrates that cetuximab...increases the anti-tumor effect of NKX101 in a dose-dependent manner. Assessment of the interaction between NKX101 and cetuximab in vitro revealed that the two agents can combine to kill cancer cells in a synergistic manner....Blocking CD16 on NKX101 cells with a neutralizing antibody significantly decreases the potency of the combination, suggesting that the improvement in potency observed is a direct result of CD16-mediated ADCC activity."

Preclinical • Oncology • Solid Tumor

Nkarta Reports Fourth Quarter and Full Year 2022 Financial Results and Corporate Highlights (GlobeNewswire) - "Nkarta plans to present updated results from its ongoing clinical trial of NKX019 in 2023....Nkarta plans to present additional results from its ongoing clinical trial of NKX101 in the first half of 2023."

P1 data • Oncology • Solid Tumor

Nkarta Reports Third Quarter 2022 Financial Results and Corporate Highlights (GlobeNewswire) - "Nkarta plans to present additional clinical data from its ongoing Phase 1 clinical trial of NKX019 by year-end 2022 as part of a company-hosted announcement; Nkarta plans to present additional clinical data from its ongoing Phase 1 clinical trial of NKX101 in the first half of 2023; Owing to the recent start of patient enrollment, data from the dose expansion cohorts are not expected to be announced in the NKX019 clinical update planned for 2022."

P1 data • Acute Myelogenous Leukemia • Hematological Malignancies • Myelodysplastic Syndrome • Non-Hodgkin’s Lymphoma • Oncology

Nkarta Reports Second Quarter 2022 Financial Results and Corporate Highlights (GlobeNewswire) - "Nkarta plans to present additional clinical data in the second half of 2022 from its ongoing dose escalation monotherapy clinical trials of NKX101 and NKX019."

Clinical data • Oncology

[VIRTUAL] A PHASE 1 STUDY OF NKX101, AN ALLOGENEIC CAR NATURAL KILLER (NK) CELL THERAPY, IN SUBJECTS WITH RELAPSED/REFRACTORY (R/R) ACUTE MYELOID LEUKEMIA (AML) OR HIGHER RISK MYELODYSPLASTIC SYNDROME (MDS) (EHA 2021) - P1 | "The starting dose of NKX101 is 1×108 CAR NK cells where NKX101 will be administered on Days 0, 7, and 14 of a 28‑day cycle following standard fludarabine/cyclophosphamide lymphodepletion. Results The trial is in progress. Conclusion NKX101 is a novel fourth generation allogeneic CAR NK being evaluated in a Phase 1 trial with R/R AML or higher risk MDS patients at multiple centers (NCT04623944)."

Clinical • P1 data • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Immune Modulation • Inflammation • Leukemia • Myelodysplastic Syndrome • Oncology • IL15 • NKG2D

Nkarta Announces Positive Preliminary Dose Finding Data for Two Lead Engineered Natural Killer Cell Programs (GlobeNewswire) - P 1 | N= 90 | NCT04623944 | Sponsor: Nkarta Inc | "Twenty-one patients who received NKX101 were assessed...In the two highest dose-level cohorts (3 doses of 1 billion cells or 3 doses of 1.5 billion cells), 3 of 5 patients with AML achieved a complete response (60% CR) with hematologic recovery. Two of the 3 reported complete responses were MRD (minimal residual disease) negative. MRD negativity is broadly viewed as an important quantitative measure of disease burden in AML and is associated with increased disease-free survival and decreased risk of recurrence. For all cohorts in the dose finding portion, 8 of 17 patients with AML achieved an overall response (47% ORR) and 3 of 17 achieved a complete response with hematologic recovery (18% CR). Four patients with MDS were treated, with no response observed."

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

"$NKTX NKX101 data in AML/MDS. Story coming $FATE" (@JacobPlieth)

Acute Myelogenous Leukemia

Nkarta to Host Conference Call Highlighting Preliminary Clinical Data from Two Lead NK Cell Therapy Candidates (GlobeNewswire) - "Nkarta...announced that it will host a conference call on Monday, April 25, 2022 at 8:00 a.m. ET to review clinical data from its ongoing Phase 1 clinical trials assessing two lead clinical programs, NKX101 and NKX019. Leading investigators from the two clinical trials will join management for the discussion."

P1 data • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Chronic Lymphocytic Leukemia • Hematological Malignancies • Indolent Lymphoma • Leukemia • Lymphoma • Mantle Cell Lymphoma • Myelodysplastic Syndrome • Non-Hodgkin’s Lymphoma • Oncology • Small Lymphocytic Lymphoma

Development of multiomics approaches to evaluate NKG2D ligand dynamics and anti-tumor immune responses during CAR-NK treatment (AACR 2022) - "Using recombinant NKG2D as a capture reagent, we have developed sandwich ELISA method to detect NKG2D-ligands shed into the culture supernatant or serum. In summary, we describe here the development of IHC and ELISA methods to determine NKG2D-ligand expression and shedding as well as a scRNAseq assay to identify NKX101+ product cells and evaluate the anti-tumor immune response during CAR-NK treatment."

Acute Myelogenous Leukemia • Oncology • Solid Tumor • IL15 • NKG2D

NKX101, Intravenous Allogeneic CAR NK Cells, in Adults With AML or MDS (clinicaltrials.gov) - P1 | N=90 | Recruiting | Sponsor: Nkarta Inc. | N=64 ➔ 90

Enrollment change • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Myelodysplastic Syndrome • Oncology • FLT3

Nkarta Presents New Preclinical Data from Engineered NK Cell Platform at AACR Annual Meeting 2022 (GlobeNewswire) - "NKX101 is an investigational NK cell therapy engineered to overexpress a chimeric receptor consisting of NKG2D ectodomain, costimulatory signaling motifs, and a membrane-bound form of IL-15....Employing multiplex IHC and digital image analysis, we found that membrane bound NKG2D-ligands are upregulated in AML and HCC compared to age-matched normal tissue controls. Lastly, using in-house developed ELISAs, we determined that shed NKG2D-ligands can be successfully detected in serum isolated from patients with MDS. Taken together, these assays provide methods for evaluation of NKG2D-ligand dynamics as well as the detection and phenotypic analysis of CAR-NK and immune cell populations in clinical samples."

Preclinical • Acute Myelogenous Leukemia • Gastrointestinal Cancer • Hematological Malignancies • Hepatocellular Cancer • Oncology

Nkarta Receives U.S. FDA Orphan Drug Designation for NKX101 for Treatment of Patients with AML (GlobeNewswire) - "Nkarta, Inc....announced that the U.S. Food and Drug Administration (FDA) has granted orphan drug designation (ODD) to NKX101 for treatment of acute myeloid leukemia (AML)."

Orphan drug • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology