AdventHealth Neuroscience Institute Among First in U.S. to Offer Phase IIa Clinical Trial of Troculeucel for Moderate Alzheimer’s Disease

Under the leadership of principal investigator Anita Fletcher, MD, AdventHealth Neuroscience Institute is the first site on the East Coast and among the first in the nation to offer a new Phase IIa clinical trial to evaluate the safety, tolerability and efficacy of SNK01 (troculeucel) in participants with moderate Alzheimer’s disease.

Troculeucel (SNK01) is a novel cell-based, patient-specific, ex vivo expanded autologous natural killer (NK) cell immunotherapeutic drug candidate. It was originally developed by NKGen Biotech for oncology indications and is also being evaluated for the treatment of Parkinson disease.

This new Phase IIa trial for patients with moderate Alzheimer’s disease aims to answer two primary questions:

• Is SNK01 safe and tolerable when administered every 3 weeks for up to 1 year as an intravenous infusion?
• Can SNK01 administration improve cognitive assessment scores (CDR-SB, MMSE, NPI, ADCS-ADL-Severe, ADAS-Cog) and biomarkers (pTau 181, Aβ42/40, GFAP, NfL)?

Study participants must have positive evidence for a diagnosis of Alzheimer’s disease via amyloid positron emission tomography (amyloid PET) of the brain within the past 6 months as well as a Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) score of ≥ 9.5 and <16.0.

Targeting an Unmet Need in A New Way

While the U.S. Food and Drug Administration (FDA) has recently approved two monoclonal antibody intravenous (IV) infusion therapies for the treatment of mild Alzheimer’s disease — lecanemab (Leqembi®) and donanemab (Kisunla™), roughly 30% of Alzheimer’s patients have moderate stage disease for which there is no approved disease modifying therapy.

“Most studies to date have focused on people with early or mild cognitive impairment,” explains Dr. Fletcher. “As a result, there is a significant unmet need for effective treatments for patients with moderate Alzheimer’s. When someone is diagnosed at the moderate stage, our focus has been symptom management, and there is a point at which these medications are no longer effective.”

A part of the innate immune system, NK cells are a type of white blood cell. They can directly kill virally infected cells and some tumor cells and play a role in regulating other immune responses.

“Recent published research has indicated there is an inflammatory component in neurodegeneration, which is why this clinical trial utilizes natural killer cells to try to target the disease.” shares Dr. Fletcher. “It is an opportunity for an intervention in patients for whom other treatments have not been appropriate or effective.”

Separate from the clinical trial, on July 10, 2025, Dr. Fletcher worked with NKGen Biotech to administer the first dose of troculeucel to a patient with Alzheimer’s disease who exhibited continued cognitive decline despite treatment with lecanemab. The treatment was administered under a single compassionate use Investigational New Drug (IND) authorization cleared by the FDA.

Highlights of the Phase I Dose Escalation Trial for SNK01

Troculeucel (SNK01) was previously evaluated for Alzheimer’s disease in an earlier Phase I clinical trial called ASK-AD (NCT06189963.) It was an open label, 3+3 dose escalation study that administered 4 doses of 1, 2, or 4 billion cells intravenously. The study was terminated early after NKGen gained clearance of an investigational new drug application for a new trial with an improved manufacturing process for the therapy. Key findings of the Phase I study included the following:

• Despite 70% of subjects being treated at relatively low doses of troculeucel for only 4 total doses, 90% of all evaluable subjects had either stable or improved (±0.1) composite Alzheimer's Disease Composite Score (ADCOMS) scores at Week 11 (one-week after the final dose).
• One-week post-final dose, improvement in cerebrospinal fluid (CSF) biomarkers were observed in 70% p-Tau181, 60% AB42/40 ratio, 60% GFAP, 40% GDF-15, 30% LTBP2, and 30% NF-L.
• Despite suboptimal dosing for 2/3 of the subjects, troculeucel was able to positively affect biomarkers that are associated with increased Alzheimer’s disease development.
• No treatment related adverse events were observed.

Data from the Phase I ASK-AD study were presented at the 2024 Alzheimer’s Association International Conference (AAIC) in Philadelphia, and at the recent AD/PD 2025 International Conference on Alzheimer's and Parkinson's Diseases

and Related Neurological Disorders in Vienna.

How the Phase IIa SNK01 Trial Works

Full eligibility criteria for the current Phase IIa study can be viewed here. If patients qualify and enroll, they undergo leukapheresis to harvest the white blood cells needed to isolate the NK cells. Those cells then undergo a process to expand them into the product that will later be infused.

For treatment, the patient will receive their infusion of SNK01 (troculeucel) in an outpatient setting. Based on learnings of the Phase I study, the current randomized Phase IIa trial is utilizing the cryopreserved product delivered at the highest dose of 6 x 109 cells every 3 weeks for 1 full year. After each infusion, the patient will be monitored and will also have a clinic visit.

“Unlike many other cell therapies, there is no pretreatment or conditioning regimen necessary to suppress the immune system before administering SNK01,” comments Dr Fletcher. “Because it uses the patient’s own natural killer cells that are not genetically modified, each treatment is a simple outpatient infusion.”

With a background in cellular therapy research, Dr. Fletcher is excited to lead this new study and believes it embodies the whole-person care and collaborative approach AdventHealth is committed to pioneering and advancing.

“Alzheimer’s disease continues to impact far too many people in our community,” she says. “This trial reflects our commitment to furthering cellular therapeutic interventions and offers new hope for improved quality of life for those affected by neurodegenerative disorders."

Contact the AdventHealth Research Institute to refer a patient for this clinical trial.