Nkgen Biotech Inc. · OTC:NKGN
Nkgen Biotech — Graf Acquisition Corp. IV — SPAC Merger (July 2023)
59 slides from Nkgen Biotech's SPAC merger presentation, Jul 17, 2023
Slide 1: Maximizing Immune Integrity Investor Event Presentation
For Investor Use Only For Investor Use Only Maximizing Immune Integrity Investor Event Presentation July 2023
Slide 2: Disclaimer: Disclosures
For Investor Use Only Disclaimer Disclosures This investor presentation (this “Presentation”) has been prepared by NKGen Biotech, Inc . (“ NKGen ,” “ NKGen Biotech” or the “Company”) for informational purposes only and to assist interested parties in making their own evaluation with respect to the b
Slide 3: Important Information About the Business Combination and Where to Find It
For Investor Use Only Disclaimer Important Information About the Business Combination and Where to Find It The proposed Business Combination will be submitted to stockholders of Graf for their consideration . Graf has filed a registration statement on Form S - 4 , dated May 15 , 2023 , and amended o
Slide 4: Forward-Looking Statements
For Investor Use Only Disclaimer Forward - Looking Statements This Presentation includes forward - looking statements regarding, among other things, the plans, strategies and prospects, both business and financial, of Graf and the Company . These statements are based on the beliefs and assumptions o
Slide 5: NKGen Biotech Is A Clinical Stage Company Focused On Neurodegenerative and Oncological Diseases
For Investor Use Only NKGen Biotech Is A Clinical Stage Company Focused On Neurodegenerative and Oncological Diseases With Innovative Natural Killer (NK) Cells • Large expansion capacity, enhanced cytotoxicity, minimal degradation with cryopreservation • Ready - to - scale manufacturing capabilities
Slide 6: Executive Team
For Investor Use Only Executive Team 6 *Board of Directors of NKGen Biotech Sangwoo Park* Founder & Executive Chairman Founder of NKMAX, Korean Parent Company Pierre Gagnon Chief Operating Officer NKMAX, Korean Parent Company Paul Y. Song, MD* CEO and Vice Chairman Jack Tsai, MD, MBA SVP, Business D
Slide 7: Natural Killer Cells
For Investor Use Only Natural Killer Cells Innate Lymphoid Cells: • 5 - 15% of circulating lymphocytes Surface Phenotype: • CD3 - CD56+ Can Distinguish Non - Self/Dangerous Cells From Healthy Cells: • Ability to kill a broad range of “dangerous” cells • Mediate antibody - dependent cellular cytotoxi
Slide 8: NK Cells Remain Challenging To Grow And Freeze
For Investor Use Only NK Cells Remain Challenging To Grow And Freeze NK cells expansion limitations Low activity Inability to scale up production Problem #2 Problem #4 SNK ΠSolution: Consistent >95% pure NK cells with robust expansion from healthy and diseased patients Promote high activity during
Slide 9: State-Of-The-Art GMP Manufacturing Facility
For Investor Use Only 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 9
Slide 10: SNK01 Superior Expansion, Cytotoxicity, And Activating Receptor Expression
For Investor Use Only SNK01 (Autologous) Superior Expansion, Cytotoxicity, And Activating Receptor Expression Cytotoxicity Expansion NK cell activating receptors and ligands Receptor Expression Levels 10 1100 3915 0 2000 4000 6000 FOLD (X) Culture Day Expansion Fold (11 Cancer Patients) 5022 D0 D6 D
Slide 11: NKGen Can Produce Over 100,000 Doses And Maintain High Viability And Cytotoxicity
For Investor Use Only NKGen Can Produce Over 100,000 Doses And Maintain High Viability And Cytotoxicity 11 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 4
Slide 12: NKGen's Differentiated CMC Platform
For Investor Use Only NKGen’s Differentiated CMC Platform Company with 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 proc
Slide 13: NKGen Biotech Pipeline
For Investor Use Only NKGen Biotech Pipeline Product IND Enabling Pre - Clinical Phase I Clinical Phase II Clinical Phase III Clinical Anticipated Milestones Autologous SNK01 Monotherapy • US IND Submission for AD – 2H2023 • US IND submission for PD – 1H2024 avelumab or pembrolizumab • Final CSR Q3
Slide 14: Scientific/Clinical Advisors And Collaborators
For Investor Use Only Scientific/Clinical Advisors And Collaborators Neurology Oncology Craig Blackstone, MD, PhD Advisor Ming Guo, MD, PhD Advisor Anthony T. Reder, MD Advisor Yong Ben, MD, MBA Advisor Evren Alici , MD, PhD Advisor Sant Chawla, MD Collaborator 14
Slide 15: Neuro Program: Alzheimer's and Parkinson's Diseases
For Investor Use Only Neuro Program Alzheimer’s and Parkinson’s Diseases 15
Slide 16: Market Opportunity in Neurodegenerative Disease
For Investor Use Only Market Opportunity in Neurodegenerative Disease NKGen’s SNK01, not yet FDA approved, will seek to address a multi - billion/year market 16 1. Dementia Statistics published by Alzheimer’s Disease International, last accessed July 6, 2023 2. "Global Alzheimer’s Disease Market $6.
Slide 17: Autoreactive T cells Cause Neuroinflammation And Damage
For Investor Use Only Chronic protein deposition leads to an autoinflammatory cascade and damage Activation of Autoreactive CD4+ and CD8+ T cells 1 - 5 which migrate to the brain via CXCR3 6 17 1. Lindestam Arlehamn - NATURE Communications (2020) 11:1875 1 - 11. 2. Stojić - Vukanić Z - Front Immunol
Slide 18: NK Cells Regulate Autoreactive T cells
For Investor Use Only NK Cells Regulate Autoreactive T cells 1 - 4 18 1. Rabinovich - J Immunol (2003) 170 (7): 3572 – 3576. 2. Lu - Immunity. 2007 May ; 26(5): 593 – 604. 3. Nielsen - PLoS ONE 7(2): e31959. 4. Ardolino - Blood (2011) 117 (18): 4778 – 4786. DNAM - 1 NKG2D CD56 DNAM - 1
Slide 19: Autoreactive T cells And SNK01 Cross BBB Via CXCR3
For Investor Use Only Autoreactive T cells And SNK01 Cross BBB 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, striatu
Slide 20: NK cells prevent and reduce protein accumulation
For Investor Use Only Proteins And Damaged Neurons 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 20 1. Earls - PNAS - January 2020 117 (3) 1762 - 1771. 2. Marsh et al. PNAS Fe
Slide 21: Compassionate Case Study: Advanced Alzheimer's With PSEN1 Mutation Treated With SNK01
For Investor Use Only 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 VERIFIED OR VALIDATED. ONLY CONTROLLED CLINICAL TRIALS CAN SUPP ORT BENEFIT FOR PATIENTS. THESE MAY NOT BE PREDIC
Slide 22: Compassionate Use Case Study: Advanced Alzheimer's Treated With SNK01
For Investor Use Only Compassionate Use Case Study # 2 – 70 Y.O. With Advanced Alzheimer’s Treated With SNK01 22 Patient was originally diagnosed in 2016 at Columbia University Medical Center with Advanced Alzheimer’s Disease. Patient received 6 monthly SNK01 treatments in 2020 under compassionate u
Slide 23: Patient Granted Single Compassionate Use IND Approval By US FDA
For Investor Use Only Patient Was Granted Single Compassionate Use IND Approval By US FDA To Resume SNK01 Treatment 23 THESE REPORTS OF PATIENT EXPERIENCES AND IMAGES HAVE NOT BEEN VERIFIED OR VALIDATED. ONLY CONTROLLED CLINICAL TRIALS CAN SUPP ORT BENEFIT FOR PATIENTS. THESE MAY NOT BE PREDICTIVE O
Slide 24: Compassionate Case Study: Advanced Alzheimer's Treated With SNK01
For Investor Use Only Compassionate Case Study # 3 - Age: 79 Y.O. With Advanced Alzheimer’s Treated With SNK01 Legend MMSE Score Stage ≤12 Severe Dementia 13 - 20 Moderate Dementia 20 - 25 Mild Dementia ≥25 No Cognitive Impairment THESE REPORTS OF PATIENT EXPERIENCES AND IMAGES HAVE NOT BEEN VERIFIE
Slide 25: Phase I Study Abstract Accepted for 2023 AAIC
For Investor Use Only Phase I Study Abstract Accepted for the 2023 Alzheimer’s Association International Conference in July 2023 Phase I Study Abstract Accepted For The 2023 Alzheimer’s Association International Conference (AAIC) In July 2023 25 No observed SAEs or dose limiting toxicity in this ong
Slide 26: Decreases in Alzheimer's-Related Protein Biomarkers Following SNK01 Treatment
For Investor Use Only Decreases in Alzheimer’s - Related Protein Biomarkers Following SNK01 Treatment Biomarker Interim Data 1 From MX04 Phase I Trial 2 26 • Following SNK01 treatment, decreases were observed across several protein biomarkers related to Alzheimer’s pathology • 12 weeks after the las
Slide 27: Dose Response From Baseline Following SNK01 Treatment
For Investor Use Only Dose Response From Baseline Following SNK01 Treatment Biomarker Interim Data From MX04 Phase I Trial 27 Worsening Worsening 1 WEEK AFTER THE LAST DOSE 1 WEEK AFTER THE LAST DOSE 12 WEEKS AFTER THE LAST DOSE 12 WEEKS AFTER THE LAST DOSE
Slide 28: Tau > Amyloid?
For Investor Use Only Tau > Amyloid? 1. Rapoport - PNAS (2002) 99:9 6365 – 6372. 2. Brier – Sci. Trans. Med. (2016) 8:338 p. 338ra66. 3. LaJoie - Sci. Transl. Med. eaau5732 (2020) 12:1. 4. Kametani - Frontiers in Neuroscience (2018) 12:25 1 - 11. 28 Clinical pathological studies have linked tau path
Slide 29: Decreases In Alzheimer's-Related Inflammatory Markers Following SNK01 Treatment
For Investor Use Only Decreases In Alzheimer’s - Related Inflammatory Markers Following SNK01 Treatment Biomarker Interim Data From MX04 Phase I Trial 29 • Following SNK01 treatment, reductions were observed across several neuroinflammatory markers related to Alzheimer’s pathology • 12 weeks after t
Slide 30: Dose Response From Baseline Following SNK01 Treatment: Neuroinflammation
For Investor Use Only Dose Response From Baseline Following SNK01 Treatment Biomarker Interim Data From MX04 Phase I Trial 30 Neuroinflammation Decrease in AD Patient 1 WEEK AFTER THE LAST DOSE 12 WEEKS AFTER THE LAST DOSE 1 WEEK AFTER THE LAST DOSE 12 WEEKS AFTER THE LAST DOSE
Slide 31: Changes In Cognitive Function Following SNK01 Treatment
For Investor Use Only Changes In Cognitive Function Following SNK01 Treatment Interim Data From MX04 Phase I Trial 31 were stable or improved one week after final dose remained stable or improved 12 weeks after last dose were stable or improved one week after final dose remained stable or improved 1
Slide 32: Dose Response From Baseline: Cognitive Function
For Investor Use Only 32 Dose Response From Baseline Following SNK01 Treatment Cognitive Function Interim Data From MX04 Phase I Trial Worsening Worsening Worsening 1 WEEK AFTER THE LAST DOSE 1 WEEK AFTER THE LAST DOSE 1 WEEK AFTER THE LAST DOSE 12 WEEKS AFTER THE LAST DOSE 12 WEEKS AFTER THE LAST D
Slide 33: Parkinson's Compassionate Use Case Study: Qualitative Evaluation After SNK01
For Investor Use Only Parkinson’s Compassionate Use Case Study # 1 : Qualitative Evaluation Of 47 Y.O. After Treatment with SNK01 Patient was independently seen and evaluated by Dr. Ming Guo (at UCLA Medical Center) 33 SNK dose dates THESE REPORTS OF PATIENT EXPERIENCES AND IMAGES HAVE NOT BEEN VERI
Slide 34: Oncology Program
For Investor Use Only Oncology Program 34
Slide 35: Improved Survival Rates Following SNK01 Combination Treatment with a PD-1 Inhibitor
For Investor Use Only Improved Survival Rates Following SNK01 Combination Treatment with a PD - 1 Inhibitor 2 - Year PFS 2 - Year Survival SNK01 + pembrolizumab 25% 58.3% Pembrolizumab monotherapy 0% 16.7% Synergistic improvement in 2 - year survival rates following SNK01 combination with pembrolizu
Slide 36: Can SNK Change The TME For PDL1- Tumors?
For Investor Use Only 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 Chemothera
Slide 37: Effect Of NK Cells On Cetuximab-mediated ADCC
For Investor Use Only 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
Slide 38: ASCO 2023 Poster Presentation SNK01 Phase I/IIa Clinical Trial Results
For Investor Use Only 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 determi
Slide 39: NK Cells: The Missing Piece In Cancer Therapeutics?
For Investor Use Only 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 modu
Slide 40: Why NKGen?
For Investor Use Only Why NKGen? 40 NK Cell Expansion Cytotoxicity Cryopreservation Persistence and lymphodepletion Solid tumor penetration Blood brain barrier (BBB) Product Flexibility Overcoming industry challenges with NK cell therapy Limited ex - vivo expansion >100K doses from single peripheral
Slide 41: Transaction Overview
For Investor Use Only Transaction Overview 1 Key transaction Terms • ~$161M transaction equity value 2 • 100% equity rollover • $50M minimum net cash closing condition 3 • Proceeds expected to fund trials and operations into 2025 4 • $25M backstop commitment from majority shareholder 5 • Expected cl
Slide 42: Thank you
For Investor Use Only For Investor Use Only Thank you
Slide 43: Appendix
For Investor Use Only Appendix 43
Slide 44: Allogeneic NK cell product that does not require lymphodepletion
For Investor Use Only Allogeneic NK cell product that does not require lymphodepletion. US Phase I Allogeneic Trial Expected To Begin In 2H2023 44 Confidential
Slide 45: Autologous Next Gen Manufacturing
For Investor Use Only Autologous Next Gen Manufacturing NKGen “Off - the - Shelf Autologous” SNK Cell Therapy • Cryopreserved autologous manufacturing process takes ~18 days from NK cell isolation to cryopreserved product release • One - time production for all the doses; SNK cells are frozen and st
Slide 46: Intellectual Property
For Investor Use Only Intellectual Property NK Cell Expansion Platform Patents 46 • Highly cytotoxic NK Cells • Consistently large yields (including unhealthy donors) • Granted in key territories -- North America, • Still alive (continuing application pending) • Expiry 2033 • Larger yields -- ideal
Slide 47: Cash Used in Operating Activities
For Investor Use Only Cash Used in Operating Activities 47 NKGen expenses 2020 2021 2022 Total cash burn 1 $17.3M $19.9M $22.5M RND - only cash expenses 2 $10.6M $14.0M $15.7M 1. Total cash burn amount equals net cash used in operating activities, which is a GAAP financial measure. 2. R&D - only cas
Slide 48: Significant Opportunity With Funding Potential From Partnering Our Platform And In Oncology
For Investor Use Only Significant Opportunity With Funding Potential From Partnering Our Platform And In Oncology 48 1. Total market sales US, EU5, JPN, according to Global Data. Parkinson’s (2029) and Alzheimer’s (2028). 2. Total NK market sales WW by 2026, according to Allied Market Research. 3. B
Slide 49: Allogeneic Anti-HER2-CAR SNK02
For Investor Use Only Allogeneic Anti - HER2 - CAR SNK02 49 (US IND submission anticipated in 2025) CONFIDENTIAL
Slide 50: NKGen Engineering, Expansion, And Cryopreservation
For Investor Use Only NKGen – Engineering, Expansion, And Cryopreservation 50 Analysis / Final product and cell banking Collection NK cell stimulation Engineering Expansion & Enrichment Collection D0 D3 - 6 D10 - 11 D14 D45 IL - 2 IL - 21 Feeder
Slide 51: Expression Level Of Anti-HER2-CAR on NK Cell
For Investor Use Only Expression Level Of Anti - HER2 - CAR on NK Cell 51 51 Anti - HER2 scFv Co - stimulatory CD3 ζ Cytokine leader Hinge TM Promoter P2A 1.11 1.05 2.3 2.47 2.39 1.89 2.42 1.38 1.64 85.67 89.03 87.93 86.31 87.16 86.03 83.03 81.62 82.74 0 10 20 30 40 50 60 70 80 90 100 D10 D14 S1 D6
Slide 52: NK Cell Expansion Rate
For Investor Use Only NK Cell Expansion Rate 0 50 100 150 200 250 300 350 400 450 D0 D4 D10 D14 D17 Expansion Rate (P1) SNK Anti-HER2-CAR-SNK 0 200 400 600 800 1000 1200 S1 D0 S1 D6 S1 D10 S1 D14 S1 D17 Expansion Rate (S1) SNK Anti-HER2-CAR SNK 0 500 1000 1500 2000 2500 3000 S2 D0 S2 D6 S2 D10 S2 D1
Slide 53: The Effect Of Freezing/Thawing On CAR Expression & Cytotoxicity
For Investor Use Only 1.89 2.42 1.38 1.65 1.29 86.03 83.2 81.6 82.84 84.02 0 10 20 30 40 50 60 70 80 90 100 S2 D6 S2 D10 S2 D14 S2 D17 THAWING Persistence 0 20 40 60 80 10:1 5:1 2.5:1 1.25:1 0.63:1 0.3:1 Thawing (SK - BR3) 0 10 20 30 40 50 10:1 5:1 2.5:1 1.25:1 0.63:1 0.3:1 Thawing (SK - OV3) 0 20 4
Slide 54: Partnerships With Merck And Pfizer
For Investor Use Only Partnerships With Merck And Pfizer In September 2020, NKGen (formerly NKMax America) entered into a clinical trial collaboration and supply agreement with Germany - based Merck KGaA to evaluate the safety and tolerability of SNK01, NKGen's autologous NK cell therapy in combinat
Slide 55: SNK01 MX04 Phase I Trial
For Investor Use Only SNK01 – MX04 Phase I Trial Dosing and Administration: To identify the Maximum Tolerated Dose (MTD), the subjects were given SNK01 in an open - label setting per the following treatment plan, using a 3 + 3 design: • Cohort 1 - 1.0 x 10 9 cells; infusions Q3W, total of four doses
Slide 56: References For NK Cells And PD-1/PD-L1
For Investor Use Only References For NK Cells And PD - 1/PD - L1 • Hasim, M., et al. (2022). When killers become thieves: trogocytosed PD - 1 inhibits NK cells in cancer. ScienceAdvances , 8(15). • Hsu, J., et al. (2018). Contribution of NK cells to immunotherapy mediated by PD - 1/PD - L1 blockade.
Slide 57: References For CI Tolerability
For Investor Use Only References For CI Tolerability • Trinh, S., et al. (2019). Management of Immune - Related Adverse Events Associated with Immune Checkpoint Inhibitor Therapy: a Min ireview of Current Clinical Guidelines. Asia Pac J Oncol Nurs , 6(2):154 - 160. • Berti , A., et al. (2021). Meta
Slide 58: References For Neurodegenerative Disease
For Investor Use Only 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 microglia
Slide 59: References Neurodegenerative Disease (Cont.)
For Investor Use Only 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 ,