NKGen Biotech Presents Troculeucel Mechanism of Action with Corresponding Phase 1 Biomarker Data at the Alzheimer’s Association International Conference 2025

Rhea-AI Summary

NKGen Biotech (OTC:NKGN) presented groundbreaking Phase 1 data for troculeucel, their innovative NK cell therapy for Alzheimer's disease, at AAIC 2025. The therapy demonstrated remarkable efficacy with 92% of patients (12 out of 13) showing stable or improved cognitive function after three months.

Key findings revealed that troculeucel can cross the blood-brain barrier and exhibits multiple mechanisms of action, including reduction of neuroinflammation and ability to degrade both amyloid and α-synuclein proteins. Notably, two out of three moderate AD patients receiving the highest dose improved to mild-stage AD, maintaining improvement through one year of treatment.

The treatment showed dose-dependent improvements in CSF biomarkers, with 100% of high-dose patients showing improvements in CSF α-synuclein levels after six months, while maintaining stable Aβ42/40 ratio and p-Tau 181 levels.

Positive

• 92% of patients showed stable or improved cognitive function (ADCOMS) after 3 months
• Two out of three moderate AD patients improved to mild-stage AD at highest dose
• 100% of high-dose patients showed improvements in CSF α-synuclein after 6 months
• Therapy demonstrates multiple mechanisms of action including protein degradation and neuroinflammation reduction
• Treatment shows ability to cross blood-brain barrier via CXCR3

Negative

• 70% of patients were treated at relatively low doses
• Limited patient sample size (n=13) in Phase 1 trials
• Only 3 patients received the highest dose treatment

Insights

Neuroscience Researcher

NKGen's Troculeucel shows promising Phase 1 results in Alzheimer's patients, addressing multiple disease pathways with significant cognitive improvements.

The mechanism of action data for Troculeucel represents a potentially significant advancement in Alzheimer's disease treatment. Unlike current therapies that target single proteins, this non-genetically modified NK cell therapy appears to address multiple pathological processes simultaneously. The data shows Troculeucel crosses the blood-brain barrier via CXCR3 receptors (expressed at 91.25%), allowing it to target central nervous system inflammation through simple IV administration—a major advantage over invasive delivery methods.

What's particularly notable is Troculeucel's apparent ability to recognize and eliminate autoreactive T cells while preserving normal T cell function, essentially providing targeted neuroinflammation reduction. The cell therapy demonstrated capacity to internalize and degrade both amyloid and α-synuclein aggregates in vitro, mimicking microglial function. This translates to clinical improvements in CSF biomarkers in a largely dose-dependent manner, with 60% of patients showing stabilized/improved Aβ42/40 ratio, 90% improving p-Tau181, and 70% improving α-synuclein levels.

The cognitive function data is especially compelling—92% of patients showed stable or improved ADCOMS scores after just three months. Most remarkably, two of three moderate-stage patients receiving the highest dose improved to mild-stage AD and maintained this improvement through one year of treatment. This suggests Troculeucel may not just slow decline but potentially reverse symptoms in some patients, which would represent a paradigm shift in Alzheimer's treatment outcomes compared to current therapies that merely delay progression.

Biotechnology Investment Analyst

NKGen's Troculeucel shows strong Phase 1 results in Alzheimer's, addressing multiple disease pathways with potential broader applications.

NKGen Biotech's Phase 1 data for Troculeucel reveals a differentiated therapeutic approach in the competitive Alzheimer's treatment landscape. The multi-modal mechanism—targeting amyloid, tau, and α-synuclein while reducing neuroinflammation—positions this therapy uniquely against single-target competitors. Most approved Alzheimer's treatments show modest cognitive decline slowing, while Troculeucel demonstrates potential disease stabilization and even improvement in cognitive function in 92% of patients.

The dose-dependent biomarker responses suggest a clear biological effect, with the highest dose (6 x 10^9 cells) showing consistent improvements across all measured parameters. Particularly noteworthy is the improvement from moderate to mild AD in two patients receiving the highest dose, maintained through one year of treatment. This suggests durable therapeutic effect, a critical factor for chronic neurodegenerative conditions.

From a commercial perspective, Troculeucel's autologous nature presents manufacturing complexities but offers a personalized approach that may command premium pricing. The technology platform's potential application beyond Alzheimer's to other neurodegenerative diseases significantly expands the addressable market opportunity. The data consistency across multiple biomarkers (amyloid, tau, α-synuclein, GFAP) strengthens the scientific validity of NKGen's approach, potentially derisking future clinical development. The company's OTC listing status means successful clinical progression could trigger significant valuation reappraisal, especially if the technology demonstrates continued efficacy in larger trials.

• Troculeucel, a cryopreserved autologous, non-genetically modified NK cell product, appears to cross the blood brain barrier (BBB) via CXCR3, to reduce neuroinflammation via a simple IV administration.

• Troculeucel was shown to internalize and digest amyloid and α-synuclein proteins in vitro and to improve CSF levels of amyloid, α-synuclein, and p-tau in Phase 1 patients in a largely dose-dependent manner.

• Troculeucel identifies and eliminates auto-activated T cells without disrupting resting T cells in vitro; and improves neuroinflammation in patients, as measured by CSF levels of GFAP.
• As measured by ADCOMS, 92% of patients (combined data of n=13) had stable or improved cognitive function at 3 months.

SANTA ANA, Calif., July 28, 2025 (GLOBE NEWSWIRE) -- NKGen Biotech, Inc. (OTC: NKGN) (“NKGen” or the “Company”), a clinical-stage biotechnology company focused on the development and commercialization of innovative autologous and allogeneic natural killer (“NK”) cell therapeutics, today announced the presentation of a poster entitled, “Mechanism of Action of Troculeucel (Non-genetically Modified Natural Killer Cells with Enhanced Cytotoxicity) in Alzheimer's Disease Confirmed by Corresponding Phase I Biomarker Data” at the Alzheimer’s Association International Conference 2025 (“AAIC 2025”) held in Toronto, Canada and online from July 27-31, 2025.

Troculeucel is a first-in-kind, autologous, non-genetically modified NK cell product with significantly increased cytotoxicity and over 90% activating receptor expression that can be consistently produced from any donor. Preclinical and clinical trial data on the effect of troculeucel from two Phase 1 studies (NCT04678453 and NCT06189963) were presented to highlight the mechanism of action and confirmatory biomarker data from 13 patients with Alzheimer’s disease (“AD”).

Elevated levels of chemokine CXCL9, CXCL10, and CXCL11 have been detected in cerebrospinal fluid (“CSF”) during neuroinflammatory conditions. These ligands bind to the chemokine receptor CXCR3 and are believed to be locally produced by CNS-resident cells, including astrocytes and microglia, in response to inflammatory signals associated with protein deposition. In AD, the accumulation of misfolded proteins elicits a cascade of autoreactive T-cell mediated neuroinflammation and neuronal damage. These T cells have been shown to exhibit high CXCR3 chemokine receptor expression enabling them to cross the BBB. Troculeucel is a highly enhanced activated NK cell therapy with 91.25% CXCR3 expression and demonstrating strong chemotactic migration potential toward CSF from AD patients.

Troculeucel was found to exhibit over 99% DNAM-1 and NKG2D expression, by which NK cells recognize and engage autoreactive T cells while sparing resting T cells, which do not express these ligands. In vitro studies demonstrated that troculeucel was selectively activated in the presence of activated T cells, as evidenced by increased interferon-gamma production, elevated cytotoxicity, and enhanced CD107a expression. These findings suggest that troculeucel may reduce neuroinflammation by preferentially eliminating autoreactive T cells while preserving non-pathogenic resting T cells.

NKGen’s in vitro data demonstrated that troculeucel had, similarly to microglial (HMC3) cells, the ability to internalize and degrade both amyloid and α-syn aggregates. In patients (n=10) treated for three months only, and, despite 70% of patients being treated at relatively low doses of troculeucel, CSF biomarker levels were stabilized or improved: Aβ42/40, p-Tau181, and α-synuclein in 60%, 90%, and 70% of patients, respectively, which was largely observed in a dose-dependent manner. In patients treated with the highest dose of 6 x 10⁹ cells for six months, 100% (n=3) had improvements in CSF α-synuclein while Aβ42/40 ratio and p-Tau 181 remained stable.

With respect to a surrogate neuroinflammatory biomarker, Glial Fibrillary Acid Protein (“GFAP”), 6/10 patients showed decreased levels after 3 months, despite administration of relatively low doses of troculeucel. Remarkably, after 6 months all three patients treated at the highest dose level of 6 x 10⁹ cells per infusion had improved CSF and plasma levels of GFAP.

Twelve out of 13 patients (92%), with a median Clinical Dementia Rating – Sum of Boxes (“CDR-SB”) score of 10 at enrollment, exhibited either stable or improved Alzheimer’s Disease Composite Score (“ADCOMS”) after three months of treatment. Notably, after just three months of treatment, two of the three patients with moderate AD who received the highest dose of troculeucel improved to mild-stage AD. Both patients maintained this improvement through the one-year treatment period, as measured by CDR-SB and ADCOMS scores.

“As we collect more clinical and biomarker data, we continue to gain even more insight into troculeucel’s mechanism of action (“MOA”),” said Paul Y. Song, M.D., Chairman and Chief Executive Officer of NKGen. “Unlike therapies that solely target a specific protein, we have shown that troculeucel can safely improve CSF levels of amyloid, α-synuclein, and tau proteins while also identifying and eliminating autoreactive T cells while sparing resting T cells, to reduce neuroinflammation. We believe this unique ability of our enhanced NK cells which appear to cross the BBB to affect multiple disease pathways, is why we are seeing such encouraging clinical results as well. Rather than slowing the rate of cognitive decline, we are demonstrating potential cessation of decline and real cognitive improvement in the vast majority of patients treated to date. We believe based on the MOA, that troculeucel has promise for several other neurodegenerative diseases beyond Alzheimer’s disease.”

Data Highlights from the Poster Presentation:

• Troculeucel shows high expression of receptors involved in modulating neuroinflammation and cell migration, shows increased cytotoxicity against activated T cells, migrates towards the CSF, and degrades Aβ42/40 and
  α-synuclein aggregates in vitro.
• Twelve out of 13 patients (92%), with a median CDR-SB score of 10 at enrollment, had either stable or improved ADCOMS scores after three months of treatment.
• Notably, two of the three patients with moderate AD who received the highest dose of troculeucel improved to mild-stage AD after just three months of treatment. Both patients maintained improvement through the one-year treatment period, as measured by CDR-SB and ADCOMS scores.
• We propose that troculeucel crosses the BBB via CXCR3 expression and modulates neuroinflammation caused by autoreactive T cells as well as protein aggregation in patients.
• Our results are supported by high NKG2D, DNAM-1 and CXCR3 expression, and consistently decreased CSF GFAP and α-synuclein levels at 3 and 6 months of treatment and while Aβ42/40 ratio and p-Tau 181 remained stable.
  

A copy of the poster, along with previously disclosed Phase 1 data demonstrating the positive effects of troculeucel (SNK01) on amyloid, tau, and neuroinflammation biomarkers in Alzheimer’s patients, can be accessed on the Company’s website Scientific Publications page: https://nkgenbiotech.com/scientific-publications/.

About NKGen Biotech

NKGen is a clinical-stage biotechnology company focused on the development and commercialization of innovative autologous and allogeneic NK cell therapeutics. NKGen is headquartered in Santa Ana, California, USA. For more information, please visit www.nkgenbiotech.com.

About Troculeucel

Troculeucel is a novel cell-based, patient specific, ex vivo expanded autologous NK cell immunotherapeutic drug candidate. NKGen is developing troculeucel for the treatment of neurodegenerative disorders and a broad range of cancers. Troculeucel is the International Nonproprietary Name (“INN”) for SNK01 assigned by the World Health Organization (“WHO”). The WHO INN approval of troculeucel establishes a universally recognized nonproprietary drug name for SNK01 and marks a significant step on NKGen’s journey toward bringing this therapy to market.

Forward-Looking Statements 

Statements contained in this press release may contain “forward-looking statements” within the meaning of Section 27A of the Securities Act and Section 21E of the Securities Exchange Act of 1934, as amended. Forward-looking statements may be identified by the use of words such as “anticipate”, “believe”, “could”, “continue”, “expect”, “estimate”, “may”, “plan”, “outlook”, “future” and “project” and other similar expressions that predict or indicate future events or trends or that are not statements of historical matters. Because such statements are subject to risks and uncertainties, many of which are outside of the Company’s control, actual results may differ materially from those expressed or implied by such forward-looking statements. Such statements include, but are not limited to, statements regarding the Company’s plans and expected timing for developing troculeucel and SNK02, including the expected timing of completing and announcing further results from its ongoing clinical studies; and the Company’s expected timing for developing its product candidates and potential benefits of its product candidates. Risks that contribute to the uncertain nature of the forward-looking statements include: the Company’s ability to execute its plans and strategies; risks related to performing clinical studies; the risk that initial and interim results of a clinical study do not necessarily predict final results and that one or more of the clinical outcomes may materially change as patient enrollment continues, following more comprehensive reviews of the data, and as more patient data become available; potential delays in the commencement, enrollment and completion of clinical studies and the reporting of data therefrom; the risk that studies will not be completed as planned; the risk that the abstract will not be published as planned including delays in timing, format, or accessibility; and NKGen’s ability to raise additional funding to complete the development of its product candidates. These and other risks and uncertainties are described more fully under the caption “Risk Factors” and elsewhere in the Company’s filings and reports, which may be accessed for free by visiting the Securities and Exchange Commission’s website at www.sec.gov and on the Company’s website under the subheading “Investors—Financial and Filings”. Investors should take such risks into account and should not rely on forward-looking statements when making investment decisions. All forward-looking statements contained in this press release speak only as of the date on which they were made. The Company undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made, except as required by law.

Internal Contact:

Denise Chua, MBA, CLS, MLS (ASCP)
SVP, Corporate Affairs
949-396-6830
dchua@nkgenbiotech.com

External Contact:

Kevin Gardner
Managing Director
LifeSci Advisors, LLC
kgardner@lifesciadvisors.com 

FAQ

What are the key results from NKGen Biotech's Phase 1 trial of troculeucel for Alzheimer's?

The trial showed 92% of patients (12 out of 13) had stable or improved cognitive function after 3 months. Two out of three moderate AD patients receiving the highest dose improved to mild-stage AD and maintained improvement for one year.

How does NKGen Biotech's troculeucel work in treating Alzheimer's disease?

Troculeucel crosses the blood-brain barrier via CXCR3, reduces neuroinflammation, eliminates auto-activated T cells, and can internalize and digest amyloid and α-synuclein proteins. It shows 91.25% CXCR3 expression and over 99% DNAM-1 and NKG2D expression.

What biomarker improvements were seen in NKGN's Alzheimer's treatment?

After 3 months, 60% of patients showed improved Aβ42/40, 90% improved p-Tau181, and 70% improved α-synuclein levels. At 6 months, all high-dose patients showed improvements in CSF α-synuclein while maintaining stable Aβ42/40 and p-Tau 181 levels.

What distinguishes troculeucel from other Alzheimer's treatments?

Troculeucel is a first-in-kind, autologous, non-genetically modified NK cell product that targets multiple disease pathways simultaneously, including protein aggregation and neuroinflammation, rather than targeting a single protein.

What is the safety profile of NKGN's troculeucel in Alzheimer's treatment?

The treatment demonstrated safety while effectively crossing the blood-brain barrier and selectively eliminating autoreactive T cells while preserving non-pathogenic resting T cells.