Nkgen Biotech Inc. · OTC:NKGN
Nkgen Biotech — H.C. Wainwright 26th Annual Global Investment Conference 2024
60 slides from Nkgen Biotech's conference presentation, Sep 9, 2024
Slide 1: NKGen Biotech - H.C. Wainwright 26th Annual Global Investment Conference
NKGen Biotech Paul Y. Song , MD Chairman and CEO H.C. Wainwright 26th Annual Global Investment Conference September 9 - 11, 2024
Slide 2: Disclaimer: Forward-Looking Statements
Disclaimer Forward - Looking Statements This Presentation may contain " forward - looking statements " within the meaning of Section 27 A of the Securities Act and Section 21 E of the Securities Exchange Act of 1934 , as amended . NKGen Biotech, Inc . 's ("NKGen" or "the Company") forward - looking
Slide 3: Disclaimer: Forward-Looking Statements
Disclaimer Forward - Looking Statements Important factors that may affect actual results or outcomes include, among others, the risk that regulatory approvals for the Company’s product development are not obtained, are delayed or are subject to unanticipated conditions that could adversely affect NK
Slide 4: Natural Killer Cells
Natural Killer Cells Innate Lymphoid Cells: • 5 - 20% of circulating lymphocytes (CD3 - CD56+) Can Distinguish Healthy Cells (self) from Dangerous Cells (non - self): • Ability to identify and eliminate “dangerous” cells • Mediate antibody - dependent cellular cytotoxicity (“ADCC”) • Immune regulato
Slide 5: NKGen's Differentiated CMC Manufacturing Platform
NKGen's Differentiated CMC 1 Manufacturing Platform 5 1 CMC = Chemistry, Manufacturing and Controls, the term covers procedures used to assess the physical and chemical characterist ics of drug products, and to ensure their quality and consistency during manufacturing Cryopreserved non - genetically
Slide 6: State-Of-The-Art GMP Manufacturing Facility
State - Of - The - Art GMP 1 Manufacturing Facility Licensed cell therapy manufacturing facility • 25,000 sq ft facility (12,000 sq ft for GMP) completed in 2019 • CLIA 2 certified and CAP 3 accredited clinical laboratory • Facility owned and operated by NKGen Biotech 6 1 GMP = Good Manufacturing Pr
Slide 7: NKGen's IP Protected Manufacturing (CMC) Process Results in Super NK Cells
NKGen’s IP Protected Manufacturing (CMC) Process Results in Super NK Cells Cytotoxicity Expansion 7 1100 3915 0 2000 4000 6000 FOLD (X) Culture Day Expansion Fold (11 Cancer Patients) 5022 D0 D6 D10 D14 D17 D0 D6 D10 D14 D17 E:T Ratio E:T Ratio = NK Cell : Cancer Cell Ratio Target Cell = Myelogenous
Slide 8: Autologous Next Gen Manufacturing
Autologous Next Gen Manufacturing NKGen “Off - the - Shelf Autologous” SNK Cell 1 Therapy • Cryopreserved autologous manufacturing process takes ~18 days from NK cell isolation to cryopreserved product packaging and u p t o 30 days from collection to release, including product testing, for patient a
Slide 9: SNK01 Cryopreservation
SNK01 Cryopreservation 9 98.0 98.0 96.5 94.6 94.7 89.8 0.0 20.0 40.0 60.0 80.0 100.0 after thawing in infusion buffer after 4 hours (%) Viability Trypan blue 7AAD 89.8 67.3 42.1 94.5 74.4 52.0 90.9 62.9 44.5 0.0 20.0 40.0 60.0 80.0 100.0 10:1 3:1 1:1 Lysis(%) E:T Ratio Cytotoxicity after thawing in
Slide 10: Surface Marker Expression Levels of Cryopreserved SNK Product
Surface Marker Expression Levels of Cryopreserved SNK Product 10 • Surface expression levels (%) of activating receptors on each pre - cryopreserved (Fresh) and post - cryopreserved (Frozen) CD3 - CD56 + NK cells in SNK product derived from each donor were analyzed flow cytometrically and depicted w
Slide 11: SNK01 – Mechanism of Action in Neurodegenerative Disease
SNK01 – Mechanism of Action in Neurodegenerative Disease 11
Slide 12: Market Opportunity in Neurodegenerative Disease
Market Opportunity in Neurodegenerative Disease NKGen’s SNK01, not yet approved by the U.S. Food and Drug Administration (FDA), will seek to address a multi - billion/year market 12 1. Dementia Statistics published by World Health Organization, Newsroom, Dementia Fact Sheet, on March 15, 2023. 2. "G
Slide 13: Chronic protein deposition leads to an autoinflammatory cascade and damage
Chronic protein deposition leads to an autoinflammatory cascade and damage Removing proteins only addresses one aspect of the underlying pathology Activation of Autoreactive CD4+ and CD8+ T cells 1 - 5 which migrate to the brain via CXCR3 6 13 1. Lindestam Arlehamn - NATURE Communications (2020) 11:
Slide 14: Autoreactive T cells And SNK01 Cross BBB Via CXCR3
Autoreactive T cells And SNK01 Cross BBB Via CXCR3 SNK01 Has High CXCR3 Expression And Strong Migration Potential 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 process
Slide 15: NK Cells Regulate Autoreactive T cells
NK Cells Regulate Autoreactive T cells 1 - 4 SNK01 Has Enhanced NKG2D and DNAM - 1 Expression that helps identify and eliminate autoreactive T - cells and auto - immune neuroinflammation 15 1. Rabinovich - J Immunol (2003) 170 (7): 3572 – 3576. 2. Lu - Immunity. 2007 May ; 26(5): 593 – 604. 3. Niels
Slide 16: Effects of Activated T-cells on Cytokines, Cytotoxic Activity, and IFN-γ in SNK01 Cells
Effects of Activated T - cells on Immunosuppressive Cytokines, Cytotoxic Activity, and IFN - γ Expression in SNK01 Cells 16 The production of IL - 10 (A) and TGF - β 1 (B) by SNK01 cells for 2 days cultivation after stimulation with or without K562 target cells for 3 hours before harvest at a 1:1 E:
Slide 17: SNK01 Can Reduce Amyloid, p-Tau, Alpha-Synuclein, and Neuroinflammation
SNK01 Can Reduce Amyloid, p - Tau, Alpha - Synuclein, and Neuroinflammation NK cells have been found to prevent and reduce protein accumulation 1,2 NK cells have also been found to identify and degenerate intact sensory axons after nerve injury 3 17 1. Earls - PNAS - January 2020 117 (3) 1762 - 1771
Slide 18: Uptake and degradation of Aβ aggregates
18 (A - E) Intracellular levels of A β aggregates in SNK 01 and HMC 3 cells were analyzed by Western blot analysis . (A) SNK 01 cells were treated with varying concentrations of A β aggregates for 1 hour and harvested . (B) SNK 01 cells were treated with 5 µM of A β aggregates and harvested at 1 , 3
Slide 19: Uptake and degradation of aggregated α-synuclein proteins
19 Uptake and degradation of aggregated α - synuclein proteins (A - E) Intracellular levels of α - syn aggregates in SNK01 and HMC3 cells were analyzed by Western blot analysis. (A) SNK01 cells were treated with varying conc en trations of α - syn aggregates for 1 hour and harvested. (B) SNK01 cells
Slide 20: Neurodegenerative Scientific Advisory Board
20 Neurodegenerative Scientific Advisory Board Craig Blackstone, M.D., Ph.D . • Chief of Movement Disorders Division at Massachusetts General Hospital and Harvard Medical School. • Board certified Neurologist and distinguished investigator focused on cellular pathogenesis of neurogenetic disorders •
Slide 21: Case Studies
Case Studies 21
Slide 22: Alzheimer's Compassionate Case Study: PSEN1 Mutation and Advanced Alzheimer's
Alzheimer’s Compassionate Case Study # 1 38 Y.O. With PSEN1 Mutation And Advanced Alzheimer’s Treated With SNK01 THESE REPORTS OF PATIENT EXPERIENCES AND IMAGES HAVE NOT BEEN VALIDATED. ONLY CONTROLLED CLINICAL TRIALS CAN SUPPORT BENEFIT FOR PATIENTS. THESE MAY NOT BE PREDICTIVE OF CLINICAL TRIAL RE
Slide 23: Young-onset Alzheimer's Affects 3.9M People Worldwide
23 Young - onset Alzheimer’s Affects 3.9M People Aged 30 - 64 Worldwide PSEN1 is most common mutation
Slide 24: Alzheimer's Case Study #1 - Patient Baseline
Alzheimer’s Case Study #1 - Patient Baseline 24 Prior to SNK01 treatment, patient was unable to talk, feed himself, hold a pen, or get out of a wheelchair by himself • Daniel is still declining and no longer able to (1) feed himself independently (caregiver helps him eat since he can’t hold his spoo
Slide 25: After Doses of SNK01 – Patient Able To Walk, Talk And Feed Himself
After 3 Doses of SNK01 – Patient Able To Walk, Talk And Feed Himself 25 THESE REPORTS OF PATIENT EXPERIENCES AND IMAGES HAVE NOT BEEN VALIDATED. ONLY CONTROLLED CLINICAL TRIALS CAN SUPPORT BENEFIT FOR PATIENTS. THESE MAY NOT BE PREDICTIVE OF CLINICAL TRIAL RESULTS. 10/13/20 Post - treatment Report
Slide 26: After Doses of SNK01 – Patient Regained Ability To Walk And Run
After 5 Doses of SNK01 – Patient Was Able To Regain Ability To Walk And Run 26 1/5/21 5/19/21 "Hi Dr. Song, it was really nice catching up. Here are some messages I have of Daniel’s Board and Care reporting falls due to balance issues, videos of Daniel having difficulty walking and wearing a helmet
Slide 27: Alzheimer's Compassionate Use Case Study #2
Alzheimer’s Compassionate Use Case Study #2 70 Y.O With Advanced Alzheimer's Treated With SNK01 Clinical response after six treatments (July 2020 – December 2020). Patient had noticeable improvement in her overall cognitive function. But treatment was stopped for 2 years due to Covid. 27 THESE REPOR
Slide 28: After Two-Year Hiatus, Treatment Resumed and Patient Showed Immediate Response
After A Two - Year Hiatus, Treatment Resumed and Patient Showed Immediate Response 28 Week 5 Patient was granted single Compassionate Use Investigational New Drug (“IND”) approval by FDA "By the way. Everyone sees a different Janice recently. Energy. Eye contact. General interaction . Can't wait for
Slide 29: Patient Showed Continued Improvement After Weeks
Patient Showed Continued Improvement After 16 Weeks – Patient Now Able To Walk, Talk, And Feed Herself Week 9 Patient feeding herself which she has not done in years Week 21 Improved memory "This evening, I went from our family room to kitchen to clean things up before heading upstairs. To my surpri
Slide 30: Patient Continues To Show Physical Improvement
Patient Continues To Show Physical Improvement 30 THESE REPORTS OF PATIENT EXPERIENCES AND IMAGES HAVE NOT BEEN VALIDATED. ONLY CONTROLLED CLINICAL TRIALS CAN SUPPORT BENEFIT FOR PATIENTS. THESE MAY NOT BE PREDICTIVE OF CLINICAL TRIAL RESULTS. March and April 2024 Can effectively navigate surroundin
Slide 31: Compassionate Case Study #3
Compassionate Case Study #3 79 Y.O. Female With Advanced Alzheimer’s Treated with SNK01 Legend Stage MMSE Score Severe Dementia ≤12 Moderate Dementia 13 - 21 Mild Dementia 21 - 25 No Cognitive Impairment ≥25 THESE REPORTS OF PATIENT EXPERIENCES AND IMAGES HAVE NOT BEEN VALIDATED. ONLY CONTROLLED CLI
Slide 32: ClinicalTrials.gov: Safety of SNK01 in Alzheimer's Disease (ASK-AD)
Find Studies ~ About Studies ~ Submit Studies * — Resou ClinicalTrials.gov Safety of SNKO1 in Subjects With Alzheimer’s Disease (ASK-AD) (ASK-AD) The safety and sclertitc valisy ofthis study is the responsibilty of Recrutmant Statue @ Reerting st Posted © December 22.2020 at Update Posted Api 14, 2
Slide 33: Biomarker Data From MX04 Phase I Trial
Biomarker Data From MX04 Phase I Trial No observed serious adverse events (SAEs) or dose limiting toxicity Improvements seen in A β 42/40, p - Tau, and alpha - synuclein protein levels Reductions seen in neuroinflammation markers: GFAP, NfL, YKL - 40 SNK 01 ’s ability to reduce all proteins and neur
Slide 34: Inflammatory and Neuronal Damage Markers (CSF)
Inflammatory and Neuronal Damage Markers (CSF) 34 Data From MX04 Phase I Trial
Slide 35: Changes In Cognitive Function Post SNK01 Treatment
Changes In Cognitive Function Post SNK01 Treatment 35 0 1 2 3 4 5 6 7 8 9 10 CDR-SB ADAS-Cog MMSE No. of patients Week 22 - All Patients Declined Compared to Week 11 Stable or Improved Compared to Week 11 0 1 2 3 4 5 6 7 8 9 10 No. of patients Cognitive assessments at week 22 (12 weeks post last dos
Slide 36: Alzheimer's Disease Composite Score (ADCOMS)
Alzheimer’s Disease Composite Score ( “ ADCOMS”) A composite of the Clinical Dementia Rating (CDR) scale in its ‘sum of boxes’ incarnation ( CDR - sb), with the addition of four memory ADAS - cog ( Delayed Word Recall , Orientation , Word Finding Difficulty & Word Recognition ), married to the Drawi
Slide 37: SNK01 Phase I/2a Trial in AD
SNK01 Phase I/2a Trial in AD 37 Randomized Phase II trial launched August 2024
Slide 38: Initial SNK01 Data from Phase I/2a Trial in Alzheimer's
Initial SNK01 Data from Phase 1 Trial in Alzheimer’s First three patients enrolled at 6 x 10 9 Dosing Subject 3 Subject 2 Subject 1 Analysis Timepoint 11 (Moderate) 12 (Moderate) 9.5 (Moderate) Baseline 7 (Mild) 12 (Moderate) 7.5 (Mild) Week 14 (3 months) n/a n/a 7.5 (Mil
Slide 39: SNK01 Reduces p-Tau, NfL, GFAP Biomarkers
p - Tau 181 NfL GFAP GFAP NfL GDF - 15 Ltbp2 SNK01 has been shown to reduce each of these biomarkers Suggesting SNK01 as a possible preventative treatment 39
Slide 40: NKGen Announces FDA Clearance of IND for SNK01 in Parkinson's Disease
Aw.NKGEN NkKGen Biotech Announces FDA Clearance of Investigational New Drug (IND) Application for SNKO1 NK Cell Therapy in Parkinson's Disease Published: Apr 29, 2024 NKGen advances its neurodegenerative disease program with FDA IND clearance for its Phase 1/2a SNKO1 Clinical Trial in patients with
Slide 41: Oncology Program
Oncology Program 41
Slide 42: NK Cells: The Missing Piece In Cancer Therapeutics?
NK Cells: The Missing Piece In Cancer Therapeutics? We believe that the future of cancer therapies will be in combination therapies that enable precision targeting, immune activation and immune effector response simultaneously. SNK cells may provide the “missing” piece for modular treatment approach
Slide 43: Improved Survival Rates Following SNK01 Combination with a PD-1 Inhibitor
Improved Survival Rates Following SNK01 Combination Treatment with a PD - 1 Inhibitor 2 - Year Survival 2 - Year PFS 58.3% 25% SNK01 + pembrolizumab 16.7% 0% Pembrolizumab monotherapy Synergistic improvement in 2 - year survival rates following SNK01 combination with pembrolizumab in NSCLC Pembroliz
Slide 44: 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* . 1 . Erlinda M. Gordon, et al. (2022). Durable Responses Using SNK01 Autologous Enhanced Natural Killer Cells and Pembrolizumab for Chemotherapy - Resistant Advance
Slide 45: Effect Of NK Cells On Cetuximab-mediated ADCC
Effect Of NK Cells On Cetuximab - mediated ADCC Preliminary Phase I data Presented at ASCO 2023 Cetuximab: anti - EGFR antibody. A Study on the Anti - Tumor Activity of SNK01 in EGFR - TKI - Resistant Non - small Cell Lung Cancer, NKMax Co., Ltd., Internal In Vitro Test Report , NKMAX - R20 - 04 , O
Slide 46: ASCO 2023 Poster Presentation SNK01 Phase I/IIa 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 ̩ 10 9 cel
Slide 47: No lymphodepletion required
47 No lymphodepletion required
Slide 48: NKGen Can Produce Over 100,000 Allogeneic Doses
NKGen Can Produce Over 100,000 Allogenic Doses While Maintaining High Viability And Cytotoxicity 48 98.0 98.0 96.5 94.6 94.7 89.8 0.0 20.0 40.0 60.0 80.0 100.0 after thawing in infusion buffer after 4 hours (%) Viability Trypan blue 7AAD 89.8 67.3 42.1 94.5 74.4 52.0 90.9 62.9 44.5 0.0 20.0 40.0 60.
Slide 49: Allogeneic Senescence
Allogeneic Senescence 1, SENESCENCE-ASSOCIATED B-GALACTOSIDASE (SA-B-GAL) STAINING p28 CONTROL - AGED MRCS 2. P16 (CYCLIN-DEPENDENT KINASE INHIBITOR 2A) 3. TELOMERASE ACTIVITY ° ° & i j i” :” 2 2 s ; _ a a ae 49
Slide 50: Allogeneic Cytotoxicity
Allogeneic Cytotoxicity 101 3:1 11 05:1 E:T ratio 10:1 3:1 11 05:1 E:T ratio 101 3:1 11 O51 E:T ratio DAY 14 DAY 28 DAY 42 120 120 120 a 2 2 2 DAY 10:1 3 a1 05:1 Sg Ss 60 S 60 S 60 zs : s Du 1051 4308 595 5 DONOR ° ° ° NOR pws 10109877703 101 3:1 1:1 O51 101 3:20 1:2 O51 101 3:10 1: O51 ET ratio E:T
Slide 51: Allogenic Receptor Expression
Allogenic Receptor Expression 51
Slide 52: SNK02 Phase I Trial in Refractory Cancer
SNK02 Phase I Trial in Refractory Cancer 52
Slide 53: SNK02 Phase I Results Published at ASCO 2024
SNK02 Phase 1 Results Published at ASCO 2024 53 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
Slide 54: 2024 Clinical Milestones Timeline
Q1 Q2 Q3 Q4 2024 ASCO Annual Meeting Phase I Combination with Immune Checkpoint Inhibitor (“ICI”) Phase IIa 3 - Month Interim Data AAIC Annual Meeting Phase I/ IIa IND Submission AAIC Abstract Submission Last Patient, Last Visit Phase I ASCO Abstract Submission Phase I Dose Limiting Toxicity (“DLT”)
Slide 55: Thank you
Thank you
Slide 56: Intellectual Property
Intellectual Property NK Cell Expansion Platform Patents 56 • Highly cytotoxic NK Cells • Consistently large yields (including unhealthy donors) • Granted in key territories -- North America, Asia • Still alive (divisional pending) • Expiry 2038 • Larger yields -- ideal for allogeneic production • E
Slide 57: Corporate Information
Corporate Information NKGen was founded in 2017 – Investment to date is $130M • NKGen merged with Graf Acquisition Corp. IV in October 2023 and listed on NASDAQ under the ticker NKGN • Prior investments funded purchase of facility and GMP build - out, operations, and clinical trials • Principal offi
Slide 58: Executive Team & Board of Directors
Executive Team 58 * Board of Directors of NKGen Biotech Sangwoo Park* Founder & Director Founder of NKMAX [Former Korean Parent Company] Paul Y. Song, MD* Chairman & CEO Ryan Park, CFA EVP, FP&A, Corp. Planning Yong Man Kim, PhD Chief Scientific Officer Denise Chua, MBA, CLS, MT(ASCP) SVP, Corporate
Slide 59: References For Neurodegenerative Disease
References For Neurodegenerative Disease • Zhou, Y - Q, et al. (2019). The role of CXCR3 in Neurological Diseases. Curr Neuropharmacol , 17(2): 142 - 150. • Marsh, S.E., et al. (2016). The adaptive immune system restrains Alzheimer’s disease pathogenesis by modulating microglial fu nct ion. Proc Nat
Slide 60: References Neurodegenerative Disease (Cont.)
References Neurodegenerative Disease (Cont.) • Earls, R.H., et al., (2020). NK cells clear alpha - synuclein and the depletion of NK cells exacerbates synuclein pathology in a m ouse model of alpha - synucleinopathy. Proc Natl Acad Sci U S A, 117(3):1762 - 1771. • Rabinovich , B.A., et al. (2003). A
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