Slide 1: SNK01 (Enhanced Natural Killer Cells) for Alzheimer's Disease
SNK01 (Enhanced Natural Killer Cells) for Alzheimer’s Disease March 2024
Slide 2: Natural Killer Cells
Natural Killer Cells Innate Immune System - 5-20% of circulating lymphocytes Unlike T cells that have only one receptor, NK cells have 40+ receptors that allow them to distinguish Self (Healthy Cells/Tissue) from Non- Self (cancer, virally infected cells, autoreactive immune cells, etc.). Immune reg
Slide 3: NKGen's Manufacturing (CMC) Process
NKGen’s Manufacturing (CMC) Process NKGen can expand NK cells from any donor! NKGen increases receptor expression! Expansion Fold Expansion Fold 6000 6000 (8 Healthy Donors) (11 Cancer Patients) 5060 5022 Expansion 4000 4000 3915 FOLD (X) FOLD (X) 3140 2000 2000 1096 1100 Receptor 0 0 Expression Lev
Slide 4: SNK01 Can Reduce Protein Accumulation and Clear Damaged Neurons
SNK01 Can Reduce Protein Accumulation and Clear Damaged Neurons NK cells have been found to prevent and reduce protein accumulation1,2 in alpha- synuclein and amyloid mouse models. SNK01 has been found to phagocytose and digest proteins in vitro. NK cells have also been found to identify and elimina
Slide 5: Chronic protein deposition leads to Activation of Autoreactive T cells
Chronic protein deposition leads to Activation of Autoreactive CD4+ and CD8+ T cells1-5 which migrate to the brain via CXCR36 and cause neuroinflammation and damage. 1. Lindestam Arlehamn - NATURE Communications (2020) 11:1875 1-11. 2. Stojić-Vukanić Z - Front Immunol (2020) 11: 566225. 3. Monsonego
Slide 6: Autoreactive T cells And SNK01 Cross BBB Via CXCR3
Autoreactive T cells And SNK01 Cross BBB Via CXCR3 CXCR3 Expression 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, cer
Slide 7: NK Cells Identify and Regulate Autoreactive T cells
NK Cells Identify and Regulate Autoreactive T cells1-4 (via NKG2D and DNAM-1) 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 5 PerCP-Cy5.5-A DNAM-1 NKG2D 1. Rabinovich - J Immunol (2003) 170 (7): 3572–3576. 2. Lu - Immunity. 20
Slide 8: Phase I Study
Phase I Study Proof of concept – safety study 3+3 dose escalation design - 1, 2, & 4x109 cells. SNK01 given via simple IV Q3W for 4 doses Mild, moderate and severe AD patients (median MMSE score 14) Cognitive Assessments and CSF & Plasma biomarkers collected: Day 0 1 week post-tx 3 months post-tx 8
Slide 9: Data From MX04 Phase I Trial
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-Tau181, and alpha-synuclein protein levels Reductions seen in neuroinflammation GFAP YKL-40, NF-L were reduced or stable in 50-60% of patients
Slide 10: Results
Results Week 11 22 Tau181 80% 56% pTau217 50% 67% Total Tau 40% 56% Week 11 22 Tau181 40% 33% pTau217 30% 56% Total Tau 30% 22% Dotted lines are subjects in Cohort 1 (1x109 cells), dashed lines are subjects in Cohort 2 (2x109 cells) and solid lines are subjects in Cohort 3 (4x109 cells). 10
Slide 11: Results
Results Majority of patients showed stable or improved CDR-SB, ADAS-Cog, and MMSE at week 11 and week 22 One patient improved from MMSE score of 14 to 22 11
Slide 12: Results
Results 90% had either stable or improved ADCOMS scores, at one-week post-treatment (week 11). 78% had either stable or improved ADCOMS scores, at 6 months (week 22). *MCIDs used to determine stable or improved cognition: CDR-SB -2 (mild, moderate and severe); Week 11 22 ADAS-Cog -3 (mild) or -4 (mo
Slide 13: Conclusions
Conclusions • SNK01 was very safe well tolerated. • SNK01 was able to cross the BBB via a simple IV to reduce proteins and neuroinflammation. • Results suggest that SNK01 may have clinical activity in AD. • A randomized Phase Il trial is now under way using higher doses (6 x 109 cells) and one year