EX-99.2 3 nktx-ex99_2.htm EX-99.2

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Clinical Program Update: NKX101 for Relapsed or Refractory AML 27 June 2023 Clinical Data as of 10 Jun 2023 Exhibit 99.2


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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 about the industry in which the company operates and the future of our business, future plans and strategies, projections, anticipated trends and events, the economy, and other future conditions, and the beliefs and assumptions of the management of the company. Words such as “address,” “anticipate,” “believe,” “consider,” “continue,” “develop,” “estimate,” “expect,” “further,” “goal,” “intend,” “may,” “plan,” “potential,” “project,” “seek,” “should,” “target,” “will,” variations of such words, and similar expressions are intended to identify such forward-looking statements. Such statements reflect the current views of the company and its management with respect to future events and are subject to inherent risks, uncertainties, and changes in circumstances that are difficult to predict and may be outside our control. Therefore, you should not rely on any of these forward-looking statements. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, the company's actual results, performance, or achievements could differ materially from the results expressed in, or implied by, these forward-looking statements. Please see section entitled “Risk Factors” in our annual, quarterly and other filings with the Securities and Exchange Commission for a description of these risks and uncertainties. This presentation has been prepared by the company based on information it has obtained from sources it believes to be reliable. Summaries of documents contained in this presentation may not be complete. The company does not represent that the information herein is complete. The information in this presentation is current only as of the date on the cover, and the company's business or financial condition and other information in this presentation may change after that date. The company undertakes no obligation to update any forward‐looking statements in order to reflect any event or circumstance occurring after the date of this presentation or currently unknown facts or conditions. Interim data from clinical trials are subject to the risk that one or more of the clinical outcomes may materially change as patient enrollment continues and more data on existing patients become available. The clinical trial program is ongoing, and the final results may be materially different from those reflected in any interim data the company reports. Further, others, including regulatory agencies, may not accept or agree with the company’s assumptions, estimates, calculations, conclusions or analyses or may interpret or weigh the importance of data differently, which could impact the value of the particular program, the approvability or commercialization of the particular product candidate or product and the value of the company in general. In addition, the information the company chooses to publicly disclose regarding a particular study or clinical trial is typically a summary of extensive information, and you or others may not agree with what the company determines is the material or otherwise appropriate information to include in its disclosure, and any information the company determines not to disclose may ultimately be deemed significant with respect to future decisions, conclusions, views, activities or otherwise regarding a particular product, product candidate or business.


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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 Blood cancers and solid tumors


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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, including venetoclax-based regimens Allogeneic HCT is best chance of long-term cure Limited to patients who are fit Pre-transplant CR improves outcomes AML is a rapidly progressing leukemia with a poor prognosis Rowe, et al Blood. 2010 116 (17). Survival (%) Survival of relapsed AML Roboz, et al J Clin Oncol. 2014 Jun 20;32(18):1919-26. AML, acute myeloid leukemia; CR, complete response; HCT, hematopoietic cell transplantation Perl, et al N Engl J Med. 2019 Oct 31;381(18):1728-1740. Years Bewersdorf, J, et al. Haematologica. 2020.105(11), 2659.


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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 Engl J Med. 2019 Oct 31;381(18):1728-1740. AML, acute myeloid leukemia; CR, complete response; CAR, chimeric antigen receptor. DiNardo, et al. N Engl J Med 2018; 378:2386-2398. Stein, et al. Blood. 2017 Aug 10;130(6):722-731. Biomarker FLT3 IDH1 IDH2 Prevalence in AML ~30% 6-10% 9-13% Approved targeted therapy gilteritinib ivosidenib enasidenib CR rate 21% 22% 19% Estimated CR rate in total AML population 6% 1-2% 2-3% Mardiana, et al. Front Oncol. 2020 May 6;10:69.


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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 haploidentical NK cells NK cells have potential for antigen-independent therapy AML, acute myeloid leukemia; CR, complete response; CRS, cytokine release syndrome; HCT, hematopoietic cell transplantation; GVHD, graft-versus-host disease; ICANS, immune effector cell-associated neurotoxicity syndrome; NK cells, natural killer cells Bachier, et al. Blood. 2020. 136, Supp 1. 42-43. Imai, et al. Blood. 2005 Jul 1;106(1):376-83.


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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 on standard criteria Cyclophosphamide Fludarabine Days -5 to -3 Additional cycles to potentially deepen response NCT04623944 Efficacy assessment NKG2D CAR mb IL-15


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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 (57%) Median prior lines of therapy (range) 2 (1 - 12)    Prior allogeneic transplant, n (%) 5 (17%)    Prior venetoclax, n (%) 27 (90%)    Prior fludarabine, n (%) 6 (20%) 90% 2 57% Prior venetoclax Median lines of prior therapy Adverse risk AML ANC, absolute neutrophil count; ECOG, Eastern Cooperative Oncology Group. Based on interim data from open clinical database as of 10 June 2023 Flu/Cy


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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-versus-host disease NKX101 with Flu/Cy LD was well-tolerated across dose levels CRS, cytokine release syndrome; DLT, dose limiting toxicity; ICANS, Immune Effector Cell-Associated Neurotoxicity Syndrome; LD, lymphodepletion * Treatment emergent adverse events regardless of relationship  ^ In the setting of febrile neutropenia/pneumonia  Grade 3+ AEs* in ≥10% of patients Total (n=30)​ Hematologic Events   Thrombocytopenia 18 (60%)​   Anemia 16 (53%)    Neutropenia 13 (43%)    Febrile neutropenia  8 (27%)   White blood cell count decreased 5 (17%)   Leukocytosis 4 (13%) Infections   Pneumonia 3 (10%)​ Other   Hypoxia ​^ 4 (13%)​   Fatigue 3 (10%)   Hypotension 3 (10%) Based on interim data from open clinical database as of 10 June 2023 Flu/Cy


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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, progressive disease; PR, partial response; SD, stable disease. Based on interim data from open clinical database as of 24 June 2023 Koschade, et al. Ann Hematol. 2022 Aug;101(8):1703-1710. Flu/Cy <5% peripheral blasts Previously presented patients with AML treated in cohorts prior to 1B cells/dose x 3 100M / 300M x 3 doses 150M / 1.5B x 2 doses Response appeared more consistent in those patients with <5% blasts in blood Marrow blasts: 3-40%  ~50% of patients with r/r AML Patient


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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 with residual thrombocytopenia; LD, lymphodepletion; MRD, minimal residual disease; MLFS, morphological leukemia-free state; PD, progressive disease; PR, partial response; SD, stable disease. Flu/Cy Based on interim data from open clinical database as of 24 June 2023 * Patient was previously reported as diagnosed with MDS in Apr 2022 update Patient Patient 1.5B x 3 (n=13) 30 29 28 27 26 25 24 23 22 21 20 19 18 1 B x 3 (n=5) 17 16 15 14 13 <5% peripheral blasts 20% blasts  MRD negative 12% blasts  MRD negative Dose


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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 with potent immunosuppressive effects Incorporated across AML treatment landscape, including upfront therapy Exposure upregulates NKG2D ligands, increasing sensitivity to NK killing in vivo NKX101 lymphodepletion with Ara-C Ogbomo, et al. Neoplasia. 2008 Dec; 10(12): 1402–1410. Holubova, et al. Int J Mol Sci. 2019 Jul 15;20(14):3472. Cytarabine USPI Perl, et al N Engl J Med. 2019 Oct 31;381(18):1728-1740. Roboz, et al J Clin Oncol. 2014 Jun 20;32(18):1919-26. Flu/Ara-C CR: complete response; cCR, cumulative CR rate; FLAG-Ida: fludarabine, cytarabine +/- GCSF and idarubicin; NK: natural killer; NKG2D: natural killer group 2, member D Lymphodepletion NKX101 3 doses of CAR-NK per cycle 1.5 B cells/dose Day 0 Day 7 Day 14 Cytarabine (2 g/m2) Fludarabine (30 mg/m2) Days -7 to -3 Additional cycles to potentially deepen response Efficacy assessment Day 28 Based on standard criteria


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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 (83%) Median prior lines of therapy (range) 2 (1 - 3)    Prior venetoclax, n (%) 6 (100%) Prior cytarabine, n (%) 3 (50%) Flu/Ara-C AML: acute myeloid leukemia; ANC, absolute neutrophil count; ECOG, Eastern Cooperative Oncology Group. Flu/Ara-C 100% 2 83% Median prior lines of therapy Adverse risk AML Prior venetoclax Based on interim data from open clinical database as of 10 June 2023


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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 for Flu/Ara-C lymphodepletion cohort Flu/Ara-C DLT, dose limiting toxicity; LD, lymphodepletion; CAR, chimeric antigen receptor; CRS, cytokine release syndrome; ICANS, Immune Effector Cell- Associated Neurotoxicity Syndrome; AE, adverse event; WBC, white blood count. Flu/Ara-C Grade 3+ AEs in >1 subject Total (n=6) Hematologic Events​ ​ ​   Anemia​ 3 (50%)​​   Febrile neutropenia  3 (50%) ​    Neutropenia​ 3 (50%) ​    Thrombocytopenia 2 (33%)​   Lymphocyte count decreased ​ 2 (33%)​   WBC decreased ​2 (33%)​ Infections​     Sepsis 3 (50%)​​ Based on interim data from open clinical database as of 10 June 2023


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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. Stone, et al. Leuk Res. 2019 Jul;82:36-42. Patient Info Marrow Blast 1 70 yo ♂ TP53 AML relapse <6 mo post HCT 30% 2 50 yo ♂ WT1 AML relapse <6 mo post HCT 30% 3 27 yo ♂ AML refractory to 7+3, HiDAC, FLT3 inh 86% 4 70 yo ♂ AML refractory to ven/aza, CD123 ADC 40% 5 63 yo ♀ AML, refractory to dauno/Ara-C, dec/ven 79% 6 60 yo ♀ AML unfit, refractory to dec/ven 20% Deep responses in patients with high-risk clinical features Early relapse post-HCT Chemo-refractory disease Medically unfit 4/6 (67%) CR/CRi rate 3/6 (50%) CR rate NKX101 Response CR (MRD negative) after cycle 1 Consolidated with cycle 2, remains in CR CRi (MRD negative) after 3 cycles Response deepened with each of cycle CR (MRD 0.18%) after 1 cycle Taken to allogeneic HCT, remains in CR Progressive disease Progressive disease CR, flow negative (MRD pending) after 1 cycle Patient


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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/ug DNA Day Day Romee, et al. Sci Transl Med. 2016 Sep 21; 8(357) NKX019 NKX101 dosed on days 0, 7, and 14


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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 patient bone marrow samples All patients at 1B dose and over Non- Responders Responders


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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 these pro-inflammatory cytokines No association was observed between elevated serum cytokines and response to NKX101 Cytokine elevation is modest and not required for clinical response Morris, et al Nat Rev Immunol. 2022 Feb;22(2):85-96. Maude, et al. Cancer J. 2014 Mar-Apr; 20(2): 119–122.


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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 antileukemic activity (67% CR/CRi rate) although follow-up is limited Cytokines remain low throughout treatment with NKX101, differentiating from CAR T cell therapies Safety profile and pharmacokinetics facilitate moving into earlier lines of therapy with standard of care treatment Next update planned for 1H24 Clinical amendment pending to include consolidation and retreatment Additional enrollment planned in fludarabine / Ara-C cohort Summary and Next Steps