Nkgen Biotech Inc. · OTC:NKGN
Nkgen Biotech — ASGCT 28th Annual Meeting 2025
41 slides from Nkgen Biotech's conference presentation, May 14, 2025
Slide 1: Troculeucel (SNK01) for Neurodegenerative Disease
Troculeucel (SNK01) for Neurodegenerative Disease Paul Y. Song, MD ASGCT 28th Annual Meeting May 14, 2025
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: 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 4: 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 5: Worldwide Problem
Worldwide Problem www.worldalzreport2015.org 5
Slide 6: Global cases of Parkinson's predicted to rise to 25 million by 2050
Global cases of 1990 2021 2030 2040 Parkinson’s Not POOLE oR (eC RRE Sears predicted to rise No2 USA to 25 million by No3 India 2050. No git Nos Italy [Ero 4 413000 524000 [ee ES? 1376000 1961000 252000) 690000 716000 852000 893.000 USA No3 Germany No4 No6 Germany CA EE indonesia Noo No7 iq 124000 O
Slide 7: Troculeucel (SNK01) Mechanism of Action in Neurodegenerative Disease
Troculeucel (SNK01) Mechanism of Action in Neurodegenerative Disease 7
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 Expansion process increases CXCR3 expression in SNK01 CXCR3+ T cells migrate to CXCL10 positive astrocytes that frequently are ass
Slide 10: NK Cell Involvement in Immune-mediated Diseases
NK Cell Involvement in Immune-mediated Diseases Gross - Proceedings of the National Academy of Sciences Schleinitz - Immunology, 131, 451–458 113(21):201524924 10
Slide 11: NK Cells Regulate Autoreactive T cells
NK Cells Regulate Autoreactive T cells SNKOI Has Enhanced NKG2D and DNAM-1 Expression that helps identify and eliminate autoreactive T cells to reduce auto-immune neuroinflammation. SNKOI has high expression of NKG2D and DNAM-1 rc > CD56+_NKG2D 98.67 na 1/¢086 CD56 +_CXCRE 97.15 9125 CD56 DNAM-1/CD2
Slide 12: 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 13: 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-b (Ab) 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 14: Uptake and degradation of aggregated a-synuclein proteins
Uptake and degradation of aggregated a-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 15: NK Cells can help eliminate damaged neurons and axons
NK Cells can help eliminate damaged neurons and axons Davies et al., 2019, Cell 176, 716–728 15
Slide 16: SNK01 Reduces Amyloid, p-Tau, Alpha-Synuclein, and Neuroinflammation
SNK01 Reduces Amyloid, p-Tau, Alpha-Synuclein, and Neuroinflammation (CSF biomarker data) NK cells have been found to identify and eliminate autoreactive T–cells. NK cells have been found to reduce protein accumulation1,2 NK cells have also been found to identify and degenerate intact sensory axons
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: Young onset Alzheimer's Affects 3.9M People Aged 30-64 Worldwide
Young onset Alzheimer’s Affects 3.9M People Aged 30 -64 Worldwide PSEN1 is most common mutation 19
Slide 20: 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 21: 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. 21
Slide 22: 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. 22
Slide 23: 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 24: Alzheimer's Compassionate Use Case Study #2: 70 Y.O. With Advanced Alzheimer's
Alzheimer’s Compassionate Use Case Study # 2 70 Y.O With Advanced Alzheimer's Treated With SNK01 THESE REPORTS OF PATIENT EXPERIENCES AND IMAGES HAVE NOT BEEN VALIDATED. ONLY CONTROLLED CLINICAL TRIALS 24 CAN SUPPORT BENEFIT FOR PATIENTS. THESE MAY NOT BE PREDICTIVE OF CLINICAL TRIAL RESULTS.
Slide 25: Week 5
"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 small but big from where we were for sure." - Janice's husband Week 5 Patient was g
Slide 26: 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 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: Data From MX04 Phase I Trial
Data From MX04 Phase I Trial No observed SAEs or dose limiting toxicity Improvements seen in AB42/40, p-Tau, and alpha-synuclein protein levels Reductions seen in neuroinflammation markers: GFAP, Nf-L, YKL-40 SNK01 ability to reduce all proteins and neuroinflammation suggests it could be used in num
Slide 29: Alzheimer's Disease Composite Score (ADCOMS)
Alzheimer’s Disease Composite Score (ADCOMS) A composite of the Clinical Dementia SNK01 Alzheimer’s Phase I Trial 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), ma
Slide 30: Phase I trial design: Troculeucel IV Q3W, 17 doses
• Troculeucel IV Q3W, (3+3 dose escalation design - 6x109 cells), 17 doses • Moderate AD patients • Phase I followed by Randomized 2a (underway) 30
Slide 31: Results - Safety (Primary outcome)
Results - Safety (Primary outcome) • Three patients enrolled at highest dose of 6 x 109 cells given every three weeks via IV for 17 treatments. • Three women – All with Moderate Stage Disease (CDR-SB score – 10.8, MMSE-20) • No drug-related adverse reactions for the 12-month study duration 31
Slide 32: Results – Cognitive Tests Change From Baseline
Results – Cognitive Tests Change From Baseline *MCID used to determine stable or improved cognition for CDR-SB = -2 32
Slide 33: Results – Cognitive Tests Change From Baseline
Results – Cognitive Tests Change From Baseline *MCIDs used to determine stable or improved cognition for ADAS-Cog = -3; ADCOMS = -0.1 33
Slide 34: Plasma Biomarker Data for Phase I patients treated at 6 x 10^9 dose
Plasma Biomarker Data for Phase I patients treated at 6 x 109 dose. 34
Slide 35: Results – Neuroinflammation biomarkers
Results – Neuroinflammation biomarkers 35
Slide 36: Results – Protein biomarkers
Results – Protein biomarkers 36
Slide 37: Results – Protein biomarkers
Results – Protein biomarkers 37
Slide 38: NKGen Receives FDA Fast Track Designation for Troculeucel in Moderate Alzheimer's
<J BioSpace’ NEWS v INSIGHTS JOBS CAREER ADVICE COMPANIES Press Releases NKGen Biotech Receives U.S. FDA Fast Track Designation for Troculeucel for the Treatment of Moderate Alzheimer’s Disease February 13, 2025 | 5 min read
Slide 39: NKGen Announces FDA Clearance of IND for SNK01 in Parkinson's Disease
NKGen 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 Parkinson'
Slide 40: Thank you
Thank you
Slide 41: Conclusions
Conclusions • Troculeucel (SNK01) was very well tolerated at the highest dose given to moderate AD subjects for 12 months • Preliminary efficacy evaluation • At 3 months, • 3 subjects showed stable or improved cognitive scores on CDR-SB and ADCOMS; • 2 of 3 subjects improved on all cognitive scales