Nkgen Biotech Inc. · OTC:NKGN
Nkgen Biotech — Allogeneic Cell Therapies Summit 2024
39 slides from Nkgen Biotech's conference presentation, June 2024
Slide 1: SNK02: Cryopreserved Allogeneic Enhanced Natural Killer Cells
SNK02 : Cryopreserved Allogeneic Enhanced Natural Killer Cells June 2024 For Investor Use Only
Slide 2: Natural Killer Cells
Natural Killer Cells Innate Lymphoid Cells: Arundhati Mandal & Chandra Viswanathan • 5-20% of circulating lymphocytes Disease NK Cell Activity and/or Number Surface Phenotype: Viral infection Activity & number • CD3- CD56+ Cancer Activity Rheumatoid Activity & number (blood), number Can Distinguish
Slide 3: NKGen's Differentiated CMC Platform
NKGen’s Differentiated CMC Platform Autologous, Allogeneic, and CAR-NK products Expansion capability demonstrates the potential to produce commercially viable quantities of allogeneic NK cells from a single blood collection –over 100K doses Cryopreservation process that can maintain high viability,
Slide 4: State-Of-The-Art GMP Manufacturing Facility
State-Of-The-Art GMP Manufacturing Facility Licensed cell therapy manufacturing facility • 25,000 sq ft facility (12,000 sq ft for GMP) completed in 2019 • CAP/CLIA Laboratory • Facility owned and operated by NKGen Biotech For Investor Use Only 4
Slide 5: NKGen's Manufacturing (CMC) Process Results
NKGen’s Manufacturing (CMC) Process results in Superior Cell Expansion, Increased Cytotoxicity, and Increased Activating Receptor Expression NKGen can expand NK cells from any donor! Expansion Fold Expansion Fold NK cell 6000 6000 (8 Healthy Donors) (11 Cancer Patients) 5060 Expansion 5022 4000 4000
Slide 6: Increased Cytokine and Death Receptor Expression
Increased Cytokine and Death Receptor Expression CYTOKINE (TNF-Alpha, IFN-Gamma) DEATH LIGANDS (Fas-L, TRAIL) CULTURE PERIOD (DAY) CULTURE PERIOD (DAY) CULTURE PERIOD (DAY) CULTURE PERIOD (DAY) INCREASED EXPRESSION OF CYTOKINES ADDITIONAL AND DEATH RECEPTORS ABILITY TO KILL THAT ARE RELATED TO TUMOR
Slide 7: Product release specifications
Macrographic Observation | Identity Specific Surface Antigen Flow Cytometry Negative Surface Antigen Flow Cytometry GECENNNENGOCOHIGNNNNNNNNEN USP <85> Bacterial Endotoxns Tet Trypan Blue Staining Method (EP <2.7.29>) Trypan Blue Staining Method (EP <2.7.29>) MycoAlert / gPCR method © Myenptnsms Aga
Slide 8: NKGen Can Produce Over 100,000 Doses And Maintain High Viability And Cytotoxicity
NKGen Can Produce Over 100,000 Doses And Maintain High Viability And Cytotoxicity Not All Companies Can Produce Large Numbers of Doses And Preserve Viability and Cytotoxicity With Their Cryopreservation Process Whole Blood Drug Viability Cryopreserved Release to Donor selection Collection Substance
Slide 9: Allogenic Senescence
Allogenic Senescence For Investor Use Only
Slide 10: Allogenic Cytotoxicity
Allogenic Cytotoxicity For Investor Use Only 10
Slide 11: Allogenic Receptor Expression
Allogenic Receptor Expression For Investor Use Only 11
Slide 12: Surface maker expression levels of SNK02
• Surface maker expression levels of SNK02 Surface expression levels (%) of activating receptors on each pre-cryopreserved (Fresh) and post-cryopreserved (Frozen) CD56+ NK cells in SNK01 derived from each donor were analyzed flow cytometrically and depicted with bright gray-colored bars on left side
Slide 13: Expression Level Of Anti-HER2-CAR on NK Cell
Expression Level Of Anti-HER2-CAR on NK Cell CAR Expression 100 89.03 85.67 87.93 86.31 87.16 86.03 90 83.03 81.62 82.74 80 70 % expression 60 50 40 SNK anti-HER2-CAR NK 30 20 10 1.11 1.05 2.3 2.47 2.39 1.89 2.42 1.38 1.64 0 D10 D14 S1 D6 S1 D10 S1 D14 S2 D6 S2 D10 S2 D14 S2 D17 Promoter leader Hing
Slide 14: NK Cell Expansion Rate
NK Cell Expansion Rate Expansion Rate (P1) Expansion Rate (S1) Expansion Rate (S2) 450 1200 3000 SNK SNK SNK 400 1000 2500 Expansion fold 350 Anti-HER2-CAR SNK Anti-HER2-CAR-SNK anti-HER2-CAR SNK 300 800 2000 250 SNK: 427.8-fold SNK: 1012.4-fold SNK: 2489.5-fold 600 1500 200 CAR SNK: 399.1-fold CAR
Slide 15: The Effect Of Freezing/Thawing On CAR Expression & Cytotoxicity
The Effect Of Freezing/Thawing On CAR Expression & Cytotoxicity CAR Expression Cytotoxicity (2 hours) Fresh (SK-OV3) Thawing (SK-OV3) 50 SNK02 SNK02 80 Anti-HER2-CAR 40 Anti-HER2-CAR SK-OV3 SNK02 SNK02 60 30 Persistence 40 20 100 20 10 86.03 83.2 82.84 84.02 90 81.6 0 0 80 10:1 5:1 2.5:1 1.25:1 0.63
Slide 16: SNK01 Has High CXCR3 Expression And Strong Migration Potential to cross the BBB
SNK01 Has High CXCR3 Expression And Strong Migration Potential to cross the BBB • Migratory Potential of SNK01 toward cerebrospinal fluid (CSF) and plasma from Alzheimer disease (AD) patients. (A) The migration of SNK01 cells toward control medium (Con) and medium containing CSF from AD patients (AD
Slide 17: Autoreactive T cells And SNK01 Cross BBB Via CXCR3
Autoreactive T cells And SNK01 Cross BBB (Blood Brain Barrier) Via CXCR3 CXCR3+ T cells migrate to CXCL10 positive astrocytes that frequently are associated with amyloid deposits.1 CXCR3 was highly expressed on a subpopulation of neurons and neuronal processes in the neocortex, hippocampus, striatum
Slide 18: SNK02 Has High CXCR3 Expression And Strong Migration Potential to cross the BBB
SNK02 Has High CXCR3 Expression And Strong Migration Potential to cross the BBB For Investor Use Only 18
Slide 19: Oncology Program
Oncology Program For Investor Use Only 19
Slide 20: NK Cells: The Missing Piece In Cancer Therapeutics?
NK Cells: The Missing Piece In Cancer Therapeutics? Tumor targeting Immune activation Immune effectors We believe that the future of cancer therapies will be in mAbs, ADCs PD-1/L1, CTLA-4, TIGIT Missing piece: Adoptive, combination therapies that enhanced NK effector cells enable precision targeting
Slide 21: Effect Of NK Cells On Cetuximab-mediated ADCC
Effect Of NK Cells On Cetuximab-mediated ADCC Preliminary Phase I data Presented at ASCO 2023 Media IgG EGFR A B * ** *** 100 *** *** *** * 80 *** * ** 80 ** 60 Lysis (%) 60 Lysis (%) 40 40 20 20 0 0 Con GC Con GC Con GC Con GC Con GC Con GC parental PC-9 PC-9/GR PC-9/OR parental HCC827 HCC827/GR HC
Slide 22: ASCO 2023 Poster Presentation SNK01 Phase I/IIa Clinical Trial Results
ASCO 2023 Poster Presentation SNK01 Phase I/IIa Clinical Trial Results ClinicalTrials.gov Identifier: NCT04872634 12 patients with TKI resistant metastatic NSCLC were evaluated Dose-limiting toxicity was not observed, therefore the maximum tolerated dose of SNK01 was determined to be 6×109 cells/dos
Slide 23: Improved Survival Rates Following SNK01 Combination Treatment with a PD-1 Inhibitor
Improved Survival Rates Following SNK01 Combination Treatment with a PD-1 Inhibitor Pembrolizumab Pembrolizumab + SNK Pembrolizumab Pembrolizumab + #5 SNK #5 2-Year PFS 2-Year Survival SNK01 + pembrolizumab 25% 58.3% Pembrolizumab Pembrolizumab + SNK #5 Pembrolizumab monotherapy 0% 16.7% Synergistic
Slide 24: Can SNK Change The TME For PDL1- Tumors?
Can SNK Change The TME For PDL1- Tumors? NK cells can positively affect the TME to help make PD-L1 negative tumors respond to ICIs* Patient Age: 321 • Stage IVB Desmoplastic Small Round Cell Sarcoma • Diagnosed 2017 • Disease included lung, abdomen and pelvis with extensive disease in abdominal/ pel
Slide 25: SNK02 Phase I Trial Overview (NCT05990920)
ACTIVE, NOT RECRUITING @ Study of Allogeneic Blood-derived Natural Killer Cells to Evaluate Safety and Tolerability in Cancer Refractory to Conventional Therapy ClinicalTrials.gov ID @ NCT05990920 Sponsor @ NKGen Biotech, Inc. Information provided by @ NKGen Biotech, Inc. (Responsible Party) Last Up
Slide 26: US01 – SNK02
US01 – SNK02 Stage Dx Dose # Prior Tx Toxicity Total Comments doses 001 IV Angiosarcoma 6B 4 2 SD 18 Stable 4 mos. 003 IV Leiomyosarcoma 6B 7 3 SD 12 Stable for 3 mos. 004 IV Endometrial 6B 1 1 SD 8 Stable for 2 mos. Adenocarcinoma 005 IV Pleomorphic 6B 5 5 PD 4 Patient died of respiratory sarcoma f
Slide 27: Lab Panels and collection timepoint
Lab Panels and collection timepoint Screening Cycle 1 Cycle 2 Cycle 5 Cycle 8 Subsequence EOT Day 1 Day 3 Day 1 Day 3 Day 1 Day 3 Day 1 Day 3 collection once every +3h +3h +3h +3h Day -42 to Pre EOI EOI Pre EOI EOI Pre EOI EOI Pre EOI EOI four cycles Day -1 (e.g. cycle 12, +15 +15 +15 +15 16, 20, 24
Slide 28: SNK02 Persistence - Chimerism by NGS on total NK Cells (%)
SNK02 Persistence - Chimerism by NGS on total NK Cells (%) Time SNK02 Persistence - Chimerism by NGS on total NK Cells (%) Points/Subject 202-103-001 202-103-002 202-103-003 202-103-004 202-103-005 202-104-002 s C1D1-PRE 0 0 0 0 0 0 C1D1-EOI 12.85 4.44 24.49 10.46 15.29 19.09 C1D1-3hEOI 7.75 2.17 5.
Slide 29: Auto-Antibodies
Auto-Antibodies Autoantibodies - HLA Class I, II %CPRA* Subject ID HLA C1D1** C2D1 C5D1 C8D1 EOT Class I NEG NEG NEG POS 202-103-001 Class II NEG NEG NEG POS Class I NEG NEG POS-99 %CPRA POS-100 %CPRA POS-100 %CPRA 202-103-002 Class II NEG NEG POS-89 %CPRA POS-100 %CPRA POS-99 %CPRA Class I NEG NEG
Slide 30: 202-103-001 – 18 total doses
202-103-001 – 18 total doses Percentage of total NK Cell in peripheral blood (%) Subject ID Cycle # Timepoint Patient’s NK Cell Donor SNK02 Pre 100 0 EOI 87.15 12.85 C1 +3 hrs EOI 92.25 7.75 Day 3 98.53 1.47 Pre 100 0 EOI 90.95 9.05 C2 +3 hrs EOI 94.42 5.58 Day 3 100 0 202-103-001 Pre 100 0 EOI 86.8
Slide 31: 202-103-002 – 12 total doses
202-103-002 – 12 total doses Percentage of total NK Cell in peripheral blood (%) Subject ID Cycle # Timepoint Donor Patient’s NK Cell SNK02 Pre 100 0 EOI 95.56 4.44 C1 +3 hrs EOI 97.83 2.17 Day 3 99.48 0.52 Pre 100 0 EOI 77.81 22.19 C2 +3 hrs EOI 95.73 4.27 Day 3 100 0 202-103-002 Pre 100 0 EOI 99.7
Slide 32: 202-103-003 – SNK02 Cell Persistance %
202-103-003 – 10 total doses SNK02 NK cell Persistance (%) Percentage of total NK 25 Cell in peripheral blood Subject ID Cycle # Timepoint (%) SNK02 Cell Persistance % Patient’s NK Donor 20 003 Cell SNK02 Pre 100 0 15 EOI 75.51 24.49 C1 +3 hrs EOI 94.33 5.67 Day 3 99.49 0.51 10 Pre 100 0 EOI 90.93 9
Slide 33: 202-103-004 – SNK02 Cell Persistance %
202-103-004 – 4 total doses Percentage of total NK Cell in peripheral blood SNK02 NK cell Persistance (%) Subject ID Cycle # Timepoint (%) 25 Patient’s NK Donor Cell SNK02 SNK02 Cell Persistance % Pre 100 0 20 EOI 89.54 10.46 004 C1 +3 hrs EOI 92.16 7.84 Day 3 99.77 0.24 15 202-103-004 Pre 100 0 EOI
Slide 34: 202-103-005 – 8 total doses
202-103-005 – 8 total doses Percentage of total NK Cell in peripheral blood (%) Subject ID Cycle # Timepoint Donor Patient’s NK Cell SNK02 Pre 100 0 EOI 84.71 15.29 C1 +3 hrs EOI 96.14 3.84 Day 3 98.49 1.51 Pre 99.92 0.08 EOI 82.61 17.25 C2 +3 hrs EOI 95.07 4.93 Day 3 99.93 0.07 202-103-005 Pre 100
Slide 35: 202-104-002 – 4 total doses
202-104-002 – 4 total doses Percentage of total NK Cell in peripheral blood (%) Subject ID Cycle # Timepoint Patient’s NK Cell Donor SNK02 Pre 100 0 EOI 80.91 19.09 C1 +3 hrs EOI 94.29 5.71 Day 3 99.17 0.83 202-104-002 Pre 100 0 EOI 79.19 20.81 C2 +3 hrs EOI 96.09 3.91 Day 3 99.76 0.24 Cycle AETERM
Slide 36: HLA Matching
HLA Matching For Investor Use Only 36
Slide 37: KIR-Ligand Matching
KIR-Ligand Matching Match/Mismatching Donor/Subject ID Typing Ligand in GvH direction HLA-B*44:03 Bw4-80T • KIR-Ligand Mismatch: SNK02-AL22 HLA-B*46:01 Bw6 HLA-C*01:02 C1 HLA-C*14:03 C1 This occurs when the KIRs on the donor NK cells do not recognize HLA-B*14:02 Bw6 the HLA ligands present on the re
Slide 38: Summary
Summary • SNK02 was given weekly repeatedly for up to 18 consecutive weeks appears to be safe and to have some anti-tumor effects in heavily pretreated solid tumors. • Donor specific antibodies were developed in all subjects after multiple doses (b/w 2 to 8 weeks) • SNK02 persistence decreased after
Slide 39: Thank you
Thank you For Investor Use Only
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