NKGen Biotech's Troculeucel Shows Dose-Dependent Cognitive Benefits in Phase 1 Alzheimer's Disease Trials
核心洞察
NKGen Biotech reported encouraging Phase 1 results for troculeucel, an autologous NK cell therapy, showing 100% of moderate Alzheimer's disease patients achieved cognitive stability or improvement at three-month assessment.
Higher cell doses (4-6 billion cells) demonstrated greater directional cognitive improvement and more frequent achievement of clinically meaningful change thresholds across standardized measures.
Plasma GFAP (搜索) emerged as a potential non-invasive biomarker, showing strong correlations with cognitive status that strengthened in patients receiving higher troculeucel doses.
NKGen Biotech has reported promising dose-dependent cognitive benefits from troculeucel, a novel autologous natural killer (NK) cell therapy, in patients with moderate Alzheimer's disease. The pooled analysis of two Phase 1 studies (NCT04678453; NCT06189963) demonstrated that all six moderate Alzheimer's disease patients showed cognitive stability or improvement at three months, with higher doses associated with greater therapeutic benefit.
Dose-Responsive Cognitive Improvements
The combined Phase 1 data revealed encouraging signs of biological activity across dose levels ranging from 1 to 6 billion cells. At the three-month assessment, 100% of patients achieved stability or improvement across all established minimal clinically important difference (MCID) thresholds, including the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog; ±4 points), Clinical Dementia Rating-Sum of Boxes (CDR-SB; ±2 points), and Alzheimer's Disease Composite Score (ADCOMS; ±0.1 points).
Notably, no cognitive decline was observed in any patient, and higher doses (4-6 billion cells) were associated with greater directional improvement and more frequent MCID exceedance. Half of the patients improved from the moderate to mild range on CDR-SB at three months, suggesting potential disease modification effects.
Early Durability Signals
In the two patients who remained on therapy for 12 months, improvements across cognitive measures were maintained throughout treatment, suggesting early durability of effect. This extended follow-up data provides preliminary evidence that troculeucel's cognitive benefits may be sustained over time.
Favorable Safety Profile
Troculeucel demonstrated a very well-tolerated safety profile, with no treatment-related adverse events reported across both Phase 1 studies. This safety data supports the continued clinical development of the autologous NK cell therapy approach for neurodegenerative disorders.
Plasma GFAP as Biomarker
In complementary biomarker analyses, NKGen reported that plasma glial fibrillary acidic protein (GFAP (搜索)) demonstrated strong and statistically significant correlations with cognitive status. Baseline plasma GFAP levels correlated with CDR-SB (r=0.60, p=0.044) and ADCOMS (r=0.64, p=0.030), supporting its role as a biomarker of disease severity in Alzheimer's disease.
The GFAP (搜索)-cognition correlations remained robust following troculeucel treatment, with plasma GFAP continuing to correlate with CDR-SB (r=0.57, p=0.056) and ADCOMS (r=0.66, p=0.022) after three months of therapy. In moderate Alzheimer's disease patients receiving ≥4 billion cells, correlations strengthened further, with statistically significant associations observed for CDR-SB (r=0.76, p=0.009) and ADCOMS (r=0.71, p=0.018).
Clinical Development Path
Troculeucel is a patient-specific, ex vivo expanded autologous NK cell immunotherapeutic drug candidate that has received International Nonproprietary Name (INN) designation from the World Health Organization. NKGen is developing troculeucel for both neurodegenerative disorders and a broad range of cancers.
The company plans to present these integrated Phase 1 analyses at the International Conference on Alzheimer's and Parkinson's Diseases and Related Neurological Disorders (AD/PD™ 2026) in Copenhagen, Denmark. The presentations will include an oral session titled "First-in-Class NK Cell Therapy Troculeucel Shows Cognitive Benefit in Moderate Alzheimer's: Dose Dependent Phase 1 Findings" and a poster on "Plasma GFAP (搜索) as a Biomarker for Anti-inflammatory Response and Cognitive Improvement."
These Phase 1 results do not include data from NKGen's ongoing Phase 2 trial, which is actively enrolling patients. The encouraging dose-response relationship and biomarker correlations provide important translational support as the company advances troculeucel's clinical development in Alzheimer's disease.