Nkgen Biotech Inc. · OTC:NKGN
Nkgen Biotech — AD/PD Drug Development Summit 2024
39 slides from Nkgen Biotech's conference presentation, Apr 25, 2024
Slide 1: SNK01 for Neurodegenerative Disease
SNK01 for Neurodegenerative Disease Paul Y. Song, MD April 2024
Slide 2: 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 regulatory capabilities,
Slide 3: 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 3
Slide 4: NKGen's Manufacturing (CMC) Process results in Super NK cells
NKGen’s Manufacturing (CMC) Process results in Super NK cells Superior Cell Expansion, Increased Cytotoxicity, and Increased Activating Receptor Expression NKGen can expand NK cells from any donor! NKGen increases receptor expression! Expansion Fold Expansion Fold 6000 6000 (8 Healthy Donors) (11 Ca
Slide 5: Autologous Next Gen Manufacturing
Autologous Next Gen Manufacturing NKGen “Off-the-Shelf Autologous” SNK Cell Therapy Superior Cell Our Expansion and Cryoprocess Activation preserves cell features Auto-SNK No Lymphodepletion 1 2 3 5 4 5 Collect Isolate Activate & Expand Cryopreserve Deliver to Clinic Thaw and Administer Leukapheresi
Slide 6: SNK01 – Mechanism of Action in Neurodegenerative Disease
SNK01 – Mechanism of Action in Neurodegenerative Disease 6
Slide 7: Market Opportunity in Neurodegenerative Disease
Market Opportunity in Neurodegenerative Disease NKGen’s SNK01, not yet FDA approved, will seek to address a multi-billion/year market Over 55 million people Alzheimer’s We are aware of no therapies worldwide had dementia in and Parkinson’s currently 2023, with a new case patients are estimated to on
Slide 8: Autoreactive T cells Cause Neuroinflammation And Damage
Autoreactive T cells Cause Neuroinflammation 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 cells1-5 which migrate to the brain via CXCR36 1. Lind
Slide 9: Autoreactive T cells And SNK01 Cross BBB Via CXCR3
Autoreactive T cells And SNK01 Cross BBB (Blood Brain Barrier) Via CXCR3 SNK01 Has High CXCR3 Expression And Strong Migration Potential to cross the BBB CXCR3 Expression CXCR3+ T cells migrate to CXCL10 positive astrocytes that frequently are associated with amyloid deposits.1 CXCR3 was highly expre
Slide 10: NK Cells Regulate Autoreactive T cells
NK Cells Regulate Autoreactive T cells1-4 SNK01 Has Enhanced NKG2D and DNAM-1 Expression that helps identify and eliminate autoreactive T cells to reduce auto-immune inflammation. DNAM-1 M Tube_007 P1 5 UL UR 10 0.49 99.40 4 10 CD56 3 10 FITC A 2 10 LL LR 0 2 0.03 0.08 -10 -10 2 0 10 2 10 3 10 4 10
Slide 11: Level of immunosuppressive cytokines in conditioned media of SNK01 cells
Level of immunosuppressive cytokines in conditioned media of SNK01 cells Level of interleukin 10 (IL-10) and TGF-β1 in conditioned media (CM) of SNK01 cells. The production of IL-10 (A) and TGF-β1 (B) by SNK01 cells for 2 days cultivation after stimulation with or without K562 target cells for 3 hou
Slide 12: Weak or Deficient NK cells common in Active Autoimmune Disease
Weak or Deficient NK cells common in Active Autoimmune Disease Schleinitz - Immunology, 131, 451–458 12
Slide 13: 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 reduce protein accumulation1,2 NK cells have also been found to identify and degenerate intact sensory axons after nerve injury3 1. Earls - PNAS - January 2020 117 (3) 1762-1771. 2. Marsh et al. PNAS
Slide 14: NK Cells Play a Protective Role in Protein Deposition
NK Cells Play a Protective Role in Protein Deposition Knockout/Depletion of NK cells in both models caused rapid acceleration of protein deposition 1. Earls RH, Menees KB, Chung J, et al. NK cells clear α-synuclein and the depletion of NK cells exacerbates synuclein pathology in a mouse model of α-s
Slide 15: Functional Characteristics of SNK01 Cells for Alzheimer's Disease (AD)
Functional Characteristics of SNK01 Cells for Alzheimer’s Disease (AD) Uptake and degradation of aggregated amyloid-β (Αβ) proteins (A-E) Intracellular levels of Aβ aggregates in SNK01 and HMC3 cells were analyzed by Western blot analysis. (A) SNK01 cells were treated with varying concentrations of
Slide 16: Uptake and degradation of aggregated α-synuclein proteins
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 concentrations of α-syn aggregates for 1 hour and harvested. (B) SNK01 cells were treated
Slide 17: Case Studies
Case Studies 17
Slide 18: Alzheimer's Compassionate Case Study #1: 38 Y.O. With PSEN1 Mutation
Alzheimer’s Compassionate Case Study # 1 38 Y.O. With PSEN1 Mutation And Advanced Alzheimer’s Treated With SNK01 IMPRESSION: Striking decreased parietal activity with moderate diffuse temporal, occipital and posterior fossa activity. RESULTS AND INTERPRETATIONS: This patient is heterozygous in the P
Slide 19: Alzheimer's Case Study #1 - Patient Baseline
Alzheimer’s Case Study #1 - Patient Baseline 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 spoon),
Slide 20: After 3 Doses of SNK01 – Patient Able To Walk, Talk And Feed Himself
After 3 Doses of SNK01 – Patient Able To Walk, Talk And Feed Himself Post-treatment Report 10/13/20 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. 20
Slide 21: After 5 Doses of SNK01 – Patient Was Able To Regain Ability To Walk
After 5 Doses of SNK01 – Patient Was Able To Regain Ability To Walk And Run "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 as the Board and C
Slide 22: Alzheimer's Compassionate Use Case Study #2: 70 Y.O. Treated With SNK01
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. THESE REPORTS
Slide 23: After A Two-Year Hiatus, Treatment Resumed and Patient Showed Immediate Response
After A Two-Year Hiatus, Treatment Resumed and Patient Showed Immediate Response "By the way. Everyone sees a different Janice recently. Energy. Eye contact. General interaction. Can't wait for you to see. This morning I said each day of the week and she repeated each day after I said it. Sounds sma
Slide 24: Patient Showed Continued Improvement After 16 Weeks
Patient Showed Continued Improvement After 16 Weeks – Patient Now Able To Walk, Talk, And Feed Herself "This evening, I went from our family room to kitchen to clean things up before heading upstairs. To my surprise Janice got up and walked thru two rooms and arrived to my surprise in the kitchen. T
Slide 25: Patient Continues to Show Improvement…
Patient Continues to Show Improvement… 25 Actively engaged in conversation Able to get up out of a chair Can effectively navigate surroundings March and April 2024 THESE REPORTS OF PATIENT EXPERIENCES AND IMAGES HAVE NOT BEEN VALIDATED. ONLY CONTROLLED CLINICAL TRIALS 25 CAN SUPPORT BENEFIT FOR PATI
Slide 26: Parkinson's Compassionate Use Case Study: Qualitative Evaluation Of 47 Y.O.
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) 60% Mental sharpness/reaction Fatigue/energy Percent Improvement from Baseline 50% Speech 40% Left Leg Mov
Slide 27: Phase I Data
[DD ws. national Lisrary of Medicine =a Find Studles + About Studios ¥ Submit Studies ¥ Resources ¥ About Shey PRS Login ClinicalTrials.gov Search Results Save this study Safety of SNKO1 in Subjects With Alzheimer's Disease (ASK-AD) (ASK-AD) ‘Ginicarrrals gov Identiner: NCTO4678453 The safety and sc
Slide 28: Dose Response Observed for Several Biomarkers in CSF
Data From MX04 Phase I Trial No observed SAEs or dose limiting toxicity Dose Response Observed for Several Biomarkers in CSF Improvements seen in AB42/40, p-Tau, and alpha-synuclein protein levels Reductions seen in neuroinflammation YKL-40, NF-L were reduced or stable in 50-60% of patients but not
Slide 29: Changes In Cognitive Function Post SNK01 Treatment
Changes In Cognitive Function Post SNK01 Treatment Data From MX04 Phase I Trial Cognitive assessments at week 22 (12 weeks post last dose) Week 22 - All Patients compared to week 11; By dose cohort 10 9 CDR-SB ADAS-Cog MMSE 8 7 10 No. of patients 9 6 8 No. of patients 5 7 6 4 5 3 4 2 3 2 1 1 0 0 CDR
Slide 30: Results
Results 90% had either stable or improved ADCOMS scores, at one-week *MCIDs used to determine post-treatment (week 11). stable or improved cognition: ADCOMS -0.1 78% had either stable or improved Dotted lines are subjects in ADCOMS scores, at 3 months Cohort 1 (1x109 cells), Dashed lines are subject
Slide 31: Phase I Clinical Trial Patient #15 85 Y.O. With Alzheimer's Disease
Phase I Clinical Trial Patient #15 85 Y.O. With Alzheimer's Disease Treated With SNK01 Patient MMSE Score Increased From 14 to 22 Subject 015. His walk was unsteady, and he couldn't dance prior to treatment. He was much more coordinated, could now dance, and was mentally sharper after treatment. See
Slide 32: ClinicalTrials.gov: SNK01 in Moderate Alzheimer's Disease
ClinicalTrials.gov RECRUITING @ Cli ical Study of SNKO1 in Participants With Moderate Alzheimer's Disease ClinicalTrials.gov ID @ NCT06189963 Sponsor @ NKGen Biotech, Inc. Information provided by @ NKGen Biotech, Inc. (Responsible Party) Last Update Posted @ 2024-01-08 Study Overview Brief Summary T
Slide 33: Phase 1/2a SNK01 in Moderate Alzheimer's Clinical Trial Patient
Phase 1/2a SNK01 in Moderate Alzheimer’s Clinical Trial Patient “ She has been doing great. No side effects… She is improving a little bit at a time…” Patient’s husband 33
Slide 34: Product Testing of Cryopreserved SNK01 Products in Clinical Trial
1-3. Product Testing of Cryopreserved SNK01 Products in Clinical Trial (from 3 patients in AD trial) Test Method Specifications Batch 1 Batch 2 Batch 3 Light-yellow cell suspension without cell Appearance Macrographic Observation Pass Pass Pass aggregation or clumping BacT/Alert No microorganism det
Slide 35: Dementia risk biomarkers: GFAP, NfL, GDF-15, LTBP2
Fibrillary Acid Protein (GFAP) Neurofilament-light (NfL) Growth/Differentiation Factor-15 (GDF-15) Latent Transforming Growth Factor beta binding protein 2 (ltbp2) 35
Slide 36: Dementia Risk Panel – MX04 CSF Analysis
Dementia Risk Panel – MX04 CSF Analysis Subject AD Stage GFAP - cfb Week 11 Week 22 NFL - cfb Week 11 Week 22 GDF-15- cfb Week 11 Week 22 LTBP2 - cfb Week 11 Week 22 MX04-201-002 Moderate ↑ ↑ ↑ ↑ ↑ ↑ ↑ ↑ MX04-201-003 Moderate ↑ ↑ ↑ ↑ ↓ ↓ ↑ ↓ MX04-201-004 Mild ↑ ↓ ↑ ↑ ↑ ↑ ↑ ↑ MX04-201-005 Mild ↓ ↓ ↓
Slide 37: Thank you
Thank you
Slide 38: 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 function. Proc Natl Acad
Slide 39: 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 mouse model of alpha- synucleinopathy. Proc Natl Acad Sci U S A, 117(3):1762-1771. • Rabinovich, B.A., et al. (2003). Activate