Slide 1: Clinical Program Update: NKX101 for Relapsed or Refractory AML
Clinical Program Update: NKX101 for Relapsed or Refractory AML 27 June 2023 Clinical Data as of 10 Jun 2023 Exhibit 99.2
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: Next generation platform: CAR NK cells driving a revolution in off-the-shelf cell therapy
Next generation platform built for: CAR NK cells driving a revolution in off-the-shelf cell therapy Allogeneic, off-the-shelf, and on demand Industrialized manufacturing Outpatient administration Targeting receptor CAR NK Cell OX40 costimulatory domain CD3ζ signaling moiety CAR membrane bound IL-15
Slide 4: AML is a rapidly progressing leukemia with a poor prognosis
Heterogenous group of blood cancers treated with risk-adapted chemotherapy Most patients will ultimately die from relapse or complications from therapy Outcomes for patients with relapsed or refractory disease are especially poor Low response rates with standard chemotherapy 12-18% CR rate, includin
Slide 5: CAR T cell therapy for AML has been limited by lack of appropriate antigens
CAR T cell therapy for AML has been limited by lack of appropriate antigens Most recent approvals have been targeted therapies using genetic biomarkers Response rates are limited, even among those few with targetable mutations Biomarkers have driven development of recent AML therapies Perl, et al N
Slide 6: NK cells have potential for antigen-independent therapy
NK cells kill malignant cells through a balance of signals No need for prior antigen exposure No GVHD due to lack of T-cell receptor NK cell therapy without HCT has been explored in AML for almost 20 years Well tolerated with limited CRS or ICANS in non-transplant setting CR rate <20% with haploiden
Slide 7: High-risk pre-treated patient population and NKX101 dosing schema
High-risk pre-treated patient population r/r AML ≥1 therapy Must have received approved targeted therapy Pre- and post-BMT NKX101 lymphodepletion with fludarabine/cyclophosphamide Flu/Ara-C Flu/Cy Lymphodepletion NKX101 multi-dosing cycle 2-3 doses of CAR-NK per cycle Day 28 Day 0 Day 7 Day 14 Based
Slide 8: NKX101 patients were multiply-relapsed with poor prognosis
NKX101 patients were multiply-relapsed with poor prognosis Characteristics Total (N=30) Age, median (range) 65 (22 - 81) Baseline ECOG, n (%) 0-1 26 (87%) 2 3 (10%) Baseline marrow blast %, median (range) 18.5 (1 - 85) AML Risk Category, n (%) Favorable 4 (13%) Intermediate 7 (23%) Poor/adverse 17 (
Slide 9: NKX101 with Flu/Cy LD was well-tolerated across dose levels
No DLTs through 1.5B cells/dose Myelosuppression and infection consistent with LD and underlying disease were the most common higher-grade toxicities Limited CAR T-like toxicities 5 (12%) had infusion reactions, all grade 1/2 5 (12%) patients had CRS, all grade 1/2 1 grade 2 ICANS (Cycle 2) No graft
Slide 10: Response to NKX101 after Flu/Cy lymphodepletion – Early cohorts
1 2 3 4 5 6 7 8 9 10 11 12 Response to NKX101 after Flu/Cy lymphodepletion – Early cohorts CNS, central nervous system; CR, complete response; CRi, CR with residual thrombocytopenia; HCT: hematopoietic stem cell transplant; MRD, minimal residual disease; MLFS, morphological leukemia-free state; PD,
Slide 11: Response to NKX101 after Flu/Cy lymphodepletion (≥1B/dose x 3)
13 additional patients with AML 12 at 1.5 B x 3 cell dose 1 at 1 B x 3 cell dose* 4/18 (22%) CR/CRi rate 3 previously reported CR, 1 new CRi (MRD negative) Consolidation with HCT has maintained long-term CR Response to NKX101 after Flu/Cy lymphodepletion (≥1B/dose x 3) CR, complete response; CRi, CR
Slide 12: NKX101 lymphodepletion with Ara-C
Fludarabine/Ara-C with anthracycline (e.g. FLAG-Ida) is a frequent salvage regimen for r/r AML with true CR rate of ~10% and cCR rate of ~20% as a comparator arm Anthracyclines (idarubicin, mitoxantrone, etc) add toxicity and limit addressable population Ara-C (cytarabine) is a DNA damaging agent wi
Slide 13: Demographics for Flu/Ara-C lymphodepletion cohort
Demographics for Flu/Ara-C lymphodepletion cohort Characteristics Total (N = 6) Age, median (range) 61.5 (27 - 70) Baseline ECOG, n (%) 0-1 5 (83%) 2 1 (17%) Baseline blast %, median (range) Marrow 35 (20 - 86) Peripheral blood 19 (8-79) AML Risk Category, n (%) Intermediate 1 (17%) Poor/adverse 5 (
Slide 14: Manageable safety profile for Flu/Ara-C lymphodepletion cohort
No DLTs (all 1.5B cells/dose) Myelosuppression and infection were the most common higher-grade toxicities and consistent with LD and underlying disease No Grade >3 infections No CAR T-like toxicities No CRS of any grade No ICANS/neurotoxicity No graft-versus-host disease Manageable safety profile fo
Slide 15: Deep disease control with NKX101 with Flu/Ara-C lymphodepletion
Deep disease control with NKX101 with Flu/Ara-C lymphodepletion Flu/Ara-C 7+3: Cytarabine + anthracycline; HiDAC: high dose Ara-C; dec: decitabine; ven: venetoclax. Based on interim data from open clinical database as of 24 June 2023 Bejanyan, et al Biol Blood Marrow Transplant. 2015 Mar;21(3):454-9
Slide 16: Exposure consistent with previously published data using haploidentical NK cells
Exposure consistent with previously published data using haploidentical NK cells No need for exogenous IL-2 or other cytokine support Ara-C can replace cyclophosphamide without compromising PK Fludarabine/Cyclophosphamide (n=10) Fludarabine/Ara-C (n=5) Median NK101 copies/ug DNA Median NK101 copies/
Slide 17: NKG2D ligands consistently detected in patient bone marrow samples
Ligand staining via IHC performed on baseline bone marrow samples prior to lymphodepletion and NKX101 MICA/B and ULBP 1/3 H-score combines % positive cells and intensity of expression Ligand expression trends higher among responders at higher doses (≥1B) NKG2D ligands consistently detected in patien
Slide 18: Cytokine elevation is modest and not required for clinical response
Cytokine levels were measured in patients throughout treatment Elevation of IL-15, IL-6, IFNγ, IL-10, and IL-8 are all associated with inflammation & CRS Peak levels were only marginally above baseline for most patients Severe CAR T-cell associated CRS can be associated with ~100-fold increases of t
Slide 19: Summary and Next Steps
Relapsed/refractory AML is a heterogenous disease with limited therapeutic options Response rates to traditional chemotherapy remain unacceptably low Approved targeted therapies provide an option for limited number of patients Incorporating Ara-C into NKX101 lymphodepletion provides encouraging anti