Nkarta, Inc. · NASDAQ:NKTX
Nkarta — Investor Presentation (March 2024)
27 slides from Nkarta's investor presentation, Mar 25, 2024
Slide 1: Engineering Natural Killer Cells for next generation treatment of autoimmune diseases and cancer
March 2024 ENGINEERING Natural Killer Cells for next generation treatment of autoimmune diseases and cancer ON DEMAND CONFIDENTIAL Exhibit 99.1
Slide 2: Forward-looking statements
Forward-looking statements This presentation contains forward‐looking statements, within the meaning of the Private Securities Litigation Reform Act of 1995, regarding future events and the future results of the company that are based on current expectations, estimates, forecasts, and projections ab
Slide 3: Delivering the future of cell therapy by harnessing the killing ability of NK cells
Delivering the future of cell therapy by harnessing the killing ability of natural killer (NK) cells CARs engineered for optimal target cell killing CAR NK Cell CAR membrane bound IL-15 Candidates engineered with a targeting CAR and membrane bound IL-15 Fully allogeneic from healthy, pre-screened do
Slide 4: Pipeline with transformational potential
NKX101 (NKG2D) r/r AML Phase 1 follow-up ongoing Patient enrollment closed NKX101 (NKG2D) Solid Tumors Gated on proof of concept in r/r AML NKX070 (CD70) Heme & Solid Tumors Collaboration NK + T (Undisclosed) Undisclosed Collaboration Pipeline with transformational potential Program (Target) Indicat
Slide 5: NKX019 in Autoimmune Disease
NKX019 in Autoimmune Disease
Slide 6: Autoimmune disease is a major unmet need
Autoimmune disease is a major unmet need Estimated 7 million patients in U.S. with a form of B-cell mediated autoimmune disease1 Pathogenic B cells can drive systemic diseases via combination of intrinsic and extrinsic factors Effectiveness of current therapies is inadequate and often consists of li
Slide 7: Benefit of CD19-directed CAR T in SLE may be via elimination of autoantibody-producing cells
Benefit of CD19-directed CAR T in SLE may be via elimination of autoantibody-producing cells CD19high CD20dim/neg BAFF-Rdim/neg plasmablasts CD19dim/neg CD20neg BAFF-Rneg long-lived plasma cells Current agents that target B cells have inconsistent benefit in SLE Rituximab (CD20 antibody) Belimumab (
Slide 8: Transient persistence is followed by rapid elimination in autoimmune disease
Transient persistence is followed by rapid elimination in autoimmune disease Expansion peaks at ~10 days Less antigen burden may explain differences in persistence and exposure In B cell malignancies, CAR T cells persist long after antigen-dependent expansion CAR T cell kinetics in autoimmune diseas
Slide 9: Immune reset occurs after B cell suppression in as short as 50 days
Immune “reset” occurs after B cell suppression in as short as 50 days in autoimmune disease Persistent B cell aplasia is NOT required for long-term responses Autoantibodies remain negative in most patients and drug-free remissions persist for up to 29 mo1 Prolonged B cell aplasia is common in oncolo
Slide 10: Patient samples from NHL trial show effective elimination of CD19+ cells by NKX019
Patient samples from ongoing NHL trial show effective elimination of CD19+ cells from circulation by NKX019 Normal and malignant cells cleared with a single cycle One cycle includes lymphodepletion and 3 doses of NKX019 Deep suppression achieved by day 30 NKX019 targets and kills C19+ cells from pat
Slide 11: Evaluation of B cell receptor heavy chains can identify naïve B cell phenotypes
Evaluation of B cell receptor (BCR) heavy chains can identify naïve B cell phenotypes Naïve B cells express IgM and IgD (non-class switched isotypes) After activation, B cells undergo class switching and express IgG and IgA antibodies Class switching appears to be required for the generation of auto
Slide 12: B cell subsets identifiable by single cell RNA profiles
Various B cell subsets have expression profiles identifiable by single cell RNA (sc-RNA) Provides additional insight beyond surface expression (e.g. flow cytometry) Recovery after treatment with NKX019 in NHL trial results in a naïve population Naïve B cells and intermediate B cells which are “trans
Slide 13: Early Cmax of NK cells may lessen need for prolonged fludarabine suppression
Early Cmax of NK cells may lessen need for prolonged suppression provided by fludarabine LD is tailored to limit chemotherapy exposure as delayed peak effect offers less benefit for NK cells Elimination of fludarabine also lessens risks of cytopenias, infection, and secondary MDS1 Historical use of
Slide 14: Cy-alone LD results in similar exposure of NKX019
Days Days 0 10 20 30 40 50 60 70 0 10 20 30 40 50 60 70 NKX019 (copies/ug DNA) 106 105 104 103 102 101 106 105 104 103 102 101 Cycle 1 (Flu/Cy) Patient 1 Patient 2 Current trial of NKX019 for NHL allows omission of fludarabine during LD Regardless of LD, patients receive NKX019 on Days 0, 3, and 7 f
Slide 15: Autologous CAR T cells depend on multi-agent LD for elimination of cytokine sink
Despite no immune barrier, autologous CAR T cells depend on multi-agent LD for elimination of “cytokine sink” to facilitate expansion Fludarabine-sparing LD results in limited CAR T expansion and benefit IL-15 levels peak shortly after infusion and correlate with expansion Lower peak IL-15 levels as
Slide 16: Autocrine stimulation by membrane-bound IL-15 provides pro-survival signal
Autocrine stimulation by membrane-bound IL-15 (mbIL-15) provides pro-survival signal mb-IL15 allows NKX019 to survive several weeks without supplemental cytokines like IL-15 or IL-2 Construct causes no secreted IL-15 and has limited cross-cell stimulation Unlike CD19 CAR T, there is no association b
Slide 17: NKX019 has superior killing of CD19+ cells compared to CAR T
NKX019 has superior killing of CD19+ cells compared to CAR T, even with low levels of surface expression NKX019 Low CD19 Expressing Cells High CD19 Expressing Cells NKX019 CD19 CAR-T CD19 CAR-T Effector : Target Effector : Target Nalm6 cells engineered to express varying levels of CD19 were obtained
Slide 18: B cells in autoimmune disease may be more accessible to killing
While CD19 allows effective targeting of cells of B cell lineage, multiple factors may make B cells in autoimmune disease more accessible to killing Widespread antigen escape via downregulation or loss of CD19 by malignant B cells Tumor microenvironment preventing trafficking and infiltration Large
Slide 19: NK cells traffic throughout the body, including privileged sites
NK cells traffic throughout the body, including to traditionally privileged sites Under pathological conditions, including autoimmune diseases, NK cells redistribute between tissues and organs1 NKX019 distributes broadly in animal models Patients with B-cell malignancies have achieved CR with NKX019
Slide 20: CD19 CAR NK cells may be ideally suited for autoimmune disease
NK cells reach peak activity at infusion for rapid target activity Maximal immediate effect without in vivo expansion T cells require expansion and necessitate a different LD approach Allogeneic NK cells are cleared by host immunity Low risk of prolonged B-cell aplasia which is not required for resp
Slide 21: NKX019 for autoimmune diseases: multicenter, open-label, phase 1 study
NKX019 for autoimmune diseases: A multicenter, open-label, phase 1 study NKX019 1B or 1.5B CAR-NK cells/dose Lymphodepletion Cyclophosphamide 1000 mg/m2 once Day -3 Day 0 Day 7 Day 14 First patient dosing expected 1H 2024 CAR: chimeric antigen receptor Endpoints: 3 doses per cycle Opportunity to inv
Slide 22: NKX019 in Oncology
NKX019 in Oncology nkarta
Slide 23: CAR T-cell therapy is not broadly accessible
CAR T-cell therapy is not broadly accessible Only 20-30% of patients with LBCL who could benefit from CAR T receive it Patients often need to change providers and receive bridging chemotherapy Potential toxicity requires proximity to a specialized inpatient treatment center Over 25% of patients requ
Slide 24: NKX019 for B-cell malignancies: phase 1 study in r/r NHL
NKX019 for B-cell malignancies: A multicenter, open-label, phase 1 study in r/r NHL NKX019 3 doses per 28-day cycle Lymphodepletion Cyclophosphamide Fludarabine Efficacy assessment Dose 1 Dose 2 Dose 3 Dickinson, et al. Oral presentation at EHA 2023, program section s347. 4 of 4 CR in retreatment of
Slide 25: NKX019 Amendment: Compressed Dosing as an Outpatient
NKX019 Amendment: Compressed Dosing as an Outpatient Dose compression cohort enrolling patients with large B-cell lymphoma (LBCL), targeting patients who have received prior CD19 CAR-T cell therapy New compressed dosing schedule to intensify exposure to NKX019 in the first week after LD Previous coh
Slide 26: Summary
Summary nkarta
Slide 27: Anticipated 2024 clinical milestones and cash runway
1H 2024 NKX019 in lupus nephritis Dose first patient and program update Autoimmune expansion | 2024 updates | Cash runway Anticipated 2024 clinical milestones in autoimmune Pipeline prioritization focuses on NKX019 development in autoimmune disease Disease-tailored lymphodepletion leverages NK cell