On March 21, 2024 Nkarta, Inc. (Nasdaq: NKTX), a clinical-stage biopharmaceutical company developing engineered natural killer (NK) cell therapies, reported financial results for the fourth quarter and year ended December 31, 2023 (Press release, Nkarta, MAR 21, 2024, View Source [SID1234641345]).

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"Patients with severe autoimmune diseases deserve novel, effective treatments," noted Paul J. Hastings, President and CEO of Nkarta. "Recent academic studies have shown that CD19-directed cell therapy has the promise to be truly transformative, and we believe that NKX019 may replicate these early results with superior safety and accessibility. Our approach leverages the potential advantages of NK cells, including fludarabine-free lymphodepletion, deep and rapid B-cell depletion, and the added utility of on-demand dosing. Work with investigators, sites and patients is advancing rapidly, and we remain on track to initiate dosing in our clinical trial of NKX019 in refractory lupus nephritis in the first half of 2024."

Hastings continued, "The potential of NKX019 to transform the treatment landscape in autoimmune disease demands our focus. To support our early-mover advantage and advance this program, Nkarta has deprioritized the development of NKX101. This follows a planned interim evaluation of Phase 1 data from NKX101 that included 14 new patients with AML. While the safety profile remained encouraging, the response rate was meaningfully lower than that from the first 6 previously reported patients. We see promise in NKX101, but before pursuing further development or significant investment, we will evaluate options for optimizing future study design, dosing schedule and manufacturing. We are grateful for the support of the NKX101 investigators as well as their patients for their commitment and trust."

NKX019 in autoimmune disease

In October 2023, Nkarta announced the expansion of its pipeline to include autoimmune disease following the clearance by FDA of the IND application for NKX019 in lupus nephritis (LN).
The multi-center, open label, dose escalation clinical trial will assess the safety and clinical activity of NKX019 in up to 12 patients with refractory LN. Patients will receive a three-dose cycle of NKX019 at 1 billion or 1.5 billion cells per dose following lymphodepletion (LD) with single agent cyclophosphamide (cy), an agent with an established safety profile in systemic lupus erythematosus (SLE) and LN.
Nkarta plans to dose the first patient in the LN study in the first half of 2024.
NKX019 is highly active against B cells from patients with multiple autoimmune diseases, and Nkarta is evaluating additional indications for potential clinical investigation with NKX019.
NKX019 in non-Hodgkin lymphoma (NHL)

In October 2023, Nkarta announced a new cohort in its Phase 1 study of NKX019 in relapsed/refractory (r/r) NHL. The cohort (n=6) introduces a compressed dosing schedule, where patients receive NKX019 doses on Days 0, 3 and 7 following LD with fludarabine (flu) and cy. This regimen is designed to intensify exposure of NKX019 by dosing closer to LD. In addition, patients with ongoing cytopenias have the potential to receive NKX019 following LD with cy alone.
Nkarta expects to announce preliminary data from the NKX019 compressed dosing cohort in mid-2024.
Nkarta is no longer enrolling patients in the cohorts in which NKX019 was being administered on Days 0, 7 and 14 following LD. Future development of NKX019 in the NHL indication will be contingent on favorable outcomes from the compressed dosing cohort.
In June 2023, Nkarta presented preliminary clinical data based on a November 2022 data cut-off from its Phase 1 clinical trial of NKX019 in patients with r/r NHL at the annual meeting of the European Hematology Association (EHA) (Free EHA Whitepaper) and the International Conference on Malignant Lymphoma. 7 of 10 patients achieved complete response (70% CR rate) following treatment with NKX019 monotherapy at highest dose levels.
In January 2024, Nkarta reported that 4 of 4 patients with r/r NHL that relapsed after achieving CR following treatment with NKX019 were again able to achieve CR after re-treatment with NKX019. These outcomes suggest that relapse, when it occurs, may be attributable to mechanisms of NKX019 exposure and not resistance to NKX019.
NKX101 in acute myeloid leukemia (AML)

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. The safety profile of NKX101 was consistent with previously reported data.
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.
In June 2023, Nkarta reported updated clinical data from its Phase 1 clinical trial evaluating NKX101 in patients with relapsed or refractory (r/r) AML. In the first 6 patients that received NKX101 after flu/Ara-C LD, 4 of 6 achieved CR/CRi as of the data cut-off on June 10, 2023. In a follow-up report on these 6 patients presented at the annual meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper), of those patients who achieved CR/CRi, 3 of 4 remained in CR/CRi at 4 months as of the data cut off on October 31, 2023.
Fourth Quarter and Full Year 2023 Financial Highlights

As of December 31, 2023, Nkarta had cash, cash equivalents, and investments of $250.9 million, including restricted cash of $2.7 million.
Research and development (R&D) expenses were $96.8 million for the full year 2023 and $23.3 million for the fourth quarter of 2023. Non-cash stock-based compensation expense included in R&D expense was $8.0 million for the full year 2023 and $1.7 million for the fourth quarter of 2023.
General and administrative (G&A) expenses were $34.9 million for the full year 2023 and $7.9 million for the fourth quarter of 2023. Non-cash stock-based compensation expense included in G&A expense was $9.2 million for the full year 2023 and $1.8 million for the fourth quarter of 2023.
Net loss was $117.5 million, or $2.40 per basic and diluted share, for the full year 2023. This net loss includes non-cash charges of $26.5 million that consisted primarily of share-based compensation, depreciation, and an impairment charge against right-of-use assets that Nkarta plans to sublease. Net loss was $27.8 million, or $0.57 per basic and diluted share, for the fourth quarter of 2023.
Financial Guidance

Nkarta expects its current cash and cash equivalents will be sufficient to fund its current operating plan into 2026.
About NKX019
NKX019 is an allogeneic, cryopreserved, off-the-shelf immunotherapy candidate that uses natural killer (NK) cells derived from the peripheral blood of healthy adult donors. It is engineered with a humanized CD19-directed CAR for enhanced cell targeting and a proprietary, membrane-bound form of interleukin-15 (IL-15) for greater persistence and activity without exogenous cytokine support. CD19 is a biomarker for normal B cells as well as those implicated in autoimmune disease and B cell-derived malignancies.

About NKX101
NKX101 is an allogeneic, cryopreserved, off-the-shelf cancer immunotherapy candidate that uses natural killer (NK) cells derived from the peripheral blood of healthy donors. It is engineered with a chimeric antigen receptor (CAR) targeting NKG2D ligands on tumor cells. NKG2D, a key activating receptor found on naturally occurring NK cells, induces a cell-killing immune response through the detection of stress ligands that are widely expressed on cancer cells. NKX101 is also engineered with a membrane-bound form of interleukin-15 (IL-15) for greater persistence and activity without exogenous cytokine support.