NKGen Biotech Presents Data from Phase 1/2a Clinical Trial of Troculeucel in Moderate Alzheimer’s Disease at the International Conference on Alzheimer’s and Parkinson’s Diseases (AD/PD™ 2025)

Rhea-AI Summary

NKGen Biotech (OTC: NKGN) presented updated Phase 1 clinical data for troculeucel, their NK cell therapy for moderate Alzheimer's disease (AD), at AD/PD™ 2025. The trial administered the highest dose of 6 billion cells every three weeks to three patients with moderate AD.

Key findings after 12 months: Two patients completed all 17 doses, showing improvement from moderate to mild AD within 3 months. One patient achieved a CDR-SB score of 4.5, near the mild cognitive impairment threshold. No drug-related adverse reactions were reported. All patients showed decreased GFAP levels in CSF and plasma at 6 months, while the two completing patients demonstrated improved Amyloid Beta 42/40 ratios at 12 months.

The company is now proceeding with the randomized, placebo-controlled Phase 2a portion of the study, expecting significant cognitive and biomarker differences between treatment and placebo groups within 6 months.

Positive

• 100% of patients showed stable or improved cognitive function
• Two out of three patients improved from moderate to mild AD within 3 months
• No drug-related adverse reactions reported after 12 months
• Positive biomarker results with decreased GFAP levels and improved Amyloid Beta ratios

Negative

• Small patient sample size of only three participants
• One patient withdrew before completing all doses (though unrelated to treatment)

Insights

Biotechnology Research Scientist

NKGen Biotech's data presentation from their Phase 1/2a clinical trial for troculeucel in Alzheimer's disease shows remarkably promising early signals. The trial, despite its small sample size (3 patients), delivered intriguing results that warrant attention.

The most significant finding is that two patients who completed the full treatment regimen (17 doses over 12 months) improved from moderate to mild Alzheimer's within just three months of treatment initiation. One patient even reached a CDR-SB score of 4.5, approaching the boundary between mild AD and mild cognitive impairment.

The biomarker data provides biological plausibility for these clinical improvements. Decreases in GFAP (a marker of neuroinflammation) in both CSF and plasma correlate with the cognitive improvements observed. The improvements in Aβ 42/40 ratios further support a disease-modifying mechanism.

However, we must interpret these results with appropriate caution. This is an extremely small sample (just 3 patients with only 2 completing the full treatment course). While the safety profile appears excellent with no drug-related adverse events reported, the efficacy signals, though promising, require validation in the larger randomized Phase 2a portion.

The mechanism of action—using natural killer cells to potentially cross the blood-brain barrier and affect protein aggregates—represents an innovative approach in the Alzheimer's field, which has seen numerous failures with traditional approaches targeting amyloid and tau.

Investment Analyst

NKGen's trial results represent a potentially significant development for this micro-cap biotech ($8.6M market cap). The presentation of positive early clinical data in Alzheimer's disease—one of medicine's most challenging indications—could catalyze increased investor interest.

What stands out is the reported improvement from moderate to mild Alzheimer's disease within just three months. This rapid response timeframe compares favorably to recently approved AD therapies that typically take much longer to show effects and generally only slow decline rather than improve cognitive function.

The OTC-listed company is advancing to the randomized portion of its Phase 2a trial, which represents the next critical value inflection point. Positive blinded data there would substantially de-risk the program and likely drive significant valuation reassessment.

Investors should note several factors: First, the current extremely low valuation provides substantial upside potential if later-stage trials succeed. Second, the treatment involves autologous (patient's own) NK cells, which may present manufacturing and scalability considerations that impact ultimate commercial potential. Third, the dosing regimen requires treatments every three weeks, potentially for extended periods, which has cost and compliance implications.

While extremely early, these results position troculeucel as a potentially differentiated approach in the massive Alzheimer's market, which could represent significant shareholder value if confirmed in larger studies.

Moderate Alzheimer’s disease (AD) patients in the trial received the highest dose of troculeucel to date at 6 billion cells per treatment.

After 12 months of treatment, both patients who completed 17 doses improved from moderate to mild AD within just 3 months. One patient stabilized at their improved score, while the other patient continued to show ongoing improvement.

Clinical development of troculeucel is ongoing and will be evaluated for safety and efficacy in the randomized, placebo-controlled Phase 2a part of the study.

SANTA ANA, Calif., April 07, 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 oral presentation of updated Phase 1 clinical data from the Phase 1/2a trial evaluating troculeucel, cryopreserved expanded autologous NK cell therapy, in patients with moderate AD at the International Conference on Alzheimer’s and Parkinson’s Diseases and Related Neurological Disorders (AD/PD™ 2025) in Vienna, Austria.

Dr. Paul Y. Song, Chairman and Chief Executive Officer of NKGen Biotech, delivered an oral presentation to conference attendees which was focused on the six and twelve-month cognitive and biomarker results from the Phase 1 cohort of the Phase 1/2a clinical trial for troculeucel NK cell therapy in moderate Alzheimer’s disease (NCT06189963).

Highlights from the presentation:

• Troculeucel was administered intravenously at a dose of 6 x 10⁹ cells to three patients with moderate AD [median Clinical Dementia Rating – Sum of Boxes (CDR-SB) score of 11].
• Primary endpoint was safety, monitored for 21 days after the first dose for each patient.
• Patients were treated every three weeks. Two patients completed 17 doses while one patient completed 10 doses.
• Preliminary efficacy was measured using cognitive scales CDR-SB, Mini Mental State Examination (MMSE), Activities of Daily Living Scale (ADCS-ADL-Severe) and Alzheimer’s Disease Assessment Scale-Cognitive (ADAS-Cog-11), with the calculated Alzheimer’s Disease Composite Score (ADCOMS) score as an additional measure.
• Secondary endpoints included changes in protein aggregate and neuroinflammation biomarker levels in the CSF and blood at 6 and 12 months.
• After up to 12 months of treatment, with a dose of 6 x 10⁹ cells every three weeks, the three patients had no drug-related adverse reactions.
• At 3 months, preliminary efficacy analyses for the three patients showed stable or improved cognitive scores on CDR-SB and ADCOMS; two of the three patients improved on all cognitive scales and ADCOMS score and downgraded their AD stage from moderate to mild (based on CDR-SB score).
• At 6 months, all three patients were stable/improved on CDR-SB, ADAS-Cog-11 and ADCOMS with two of the three patients stable/improved on all cognitive scales and ADCOMS score.
• At 12 months, the two patients completing the 17 doses continued to show stable or improved CDR-SB, ADAS-Cog-11, ADCS-ADL-Severe and ADCOMS scores, with one patient reaching a CDR-SB of 4.5 (considered the cutoff between mild cognitive impairment [MCI] and mild AD). While the initial cohort consisted of three patients, the third patient withdrew from the trial prior to reaching 12 months. This withdrawal was not related to any adverse effects or drug related issues.
• At 6 months, all three patients showed decreased levels in both CSF and plasma for Glial Fibrillary Acidic Protein (GFAP) while at 12 months, the remaining two patients in the study continue to show decreased levels in plasma.
• At 12 months, the CSF and plasma Amyloid Beta (Aβ) 42/40 ratio improved in both patients, while the CSF p-Tau 181 and p-Tau 217 levels remained relatively stable.  
• Troculeucel at the highest dose given to moderate AD patients was well tolerated and in 2/3 patients showed clinical improvements after only 3 months on therapy; cognitive scores continued to show stability or improvement through the end of study period at 12 months. Troculeucel will be evaluated for safety and efficacy in the randomized, placebo-controlled Phase 2a part of the study.

“In our prior proof-of-concept Phase 1 dose escalation trial (NCT04678453) we were able to demonstrate that troculeucel was well tolerated and appears to cross the blood brain barrier to improve CSF levels of amyloid, p-tau, and alpha-synuclein proteins,” said Paul Y. Song, M.D., Chairman and Chief Executive Officer of NKGen. “Despite the fact that 2/3 of the patients were sub-optimally dosed, 90% of patients had stable or improved cognitive functions (ADCOMS) after 11 weeks of treatment (4 doses).”

Dr. Song continued, “In this new Phase 1/2a trial, we are only treating moderate stage patients and at our highest dose of 6 x 10⁹ cells given every three weeks for one full year. We are pleased again to see no drug related adverse events, and more importantly 100% stable or improved cognitive function using CDR-SB and ADCOMS scores. In fact, two of the first three patients treated at our highest dose have improved from moderate to mild disease including one patient who improved from a CDR-SB baseline score of 11 to 4.5. As GFAP has been shown by others to be a very strong independent biomarker, which correlates well with dementia severity and progression, we observed reductions in GFAP in CSF and plasma which appeared to correlate with cognitive improvement in our patients. We also found improvements in levels of Aβ 42/40. As we begin to rapidly enroll patients in our double-blind randomized Phase 2a trial, we expect to see significant cognitive and biomarker differences between the treatment arm and placebo group within as little as 6 months. We are very excited that troculeucel continues to be well tolerated and shows promising disease modifying activity.”

A copy of the presentation will be added to the Scientific Publications page of the Company’s website https://nkgenbiotech.com/ after the conference has concluded.

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.

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.

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

FAQ

What were the key results of NKGN's troculeucel Phase 1 trial in Alzheimer's patients?

Two out of three moderate AD patients improved to mild AD within 3 months, with one patient reaching a near-MCI level CDR-SB score of 4.5. No drug-related adverse reactions were reported after 12 months of treatment.

How many doses of troculeucel did patients receive in NKGN's Alzheimer's trial?

Patients received 6 billion cells every three weeks. Two patients completed all 17 doses over 12 months, while one patient completed 10 doses before withdrawing (unrelated to adverse effects).

What biomarker improvements did NKGN's troculeucel show in Alzheimer's patients?

All patients showed decreased GFAP levels in CSF and plasma at 6 months. At 12 months, the two remaining patients showed improved Amyloid Beta 42/40 ratios and stable CSF p-Tau levels.

What is the next step for NKGN's troculeucel Alzheimer's treatment?

NKGN is proceeding with the randomized, placebo-controlled Phase 2a portion of the study, expecting significant cognitive and biomarker differences within 6 months.