NKGen Biotech Announces Publication of Phase 1 Troculeucel Clinical Trial Results for the Treatment of Alzheimer’s Disease
NKGen Biotech (NKGN) has published results from its Phase 1 clinical trial of troculeucel, an expanded autologous NK cell therapy for Alzheimer's disease (AD) treatment. The trial, involving 11 subjects with a median age of 79 years, demonstrated stable or improved outcomes in 90% of evaluable subjects.
The study utilized three dose cohorts (1×10⁹, 2×10⁹, and 4×10⁹ cells), with subjects receiving four doses at three-week intervals. Key findings showed that troculeucel was well-tolerated with no drug-related adverse events. The therapy reduced neuroinflammation and positively affected brain protein aggregates, as indicated by CSF biomarker levels.
The treatment showed dose-dependent decreases in pTau181 and GFAP biomarkers. Following these promising results, a larger trial with higher dosing/duration has been initiated in the U.S. The research has been published in the peer-reviewed journal Alzheimer's Research & Therapy.
NKGen Biotech (NKGN) ha pubblicato i risultati del suo trial clinico di Fase 1 su troculeucel, una terapia a base di cellule NK autologhe espanse per il trattamento della malattia di Alzheimer (AD). Lo studio, che ha coinvolto 11 soggetti con un'età mediana di 79 anni, ha dimostrato risultati stabili o migliorati nel 90% dei soggetti valutabili.
Lo studio ha utilizzato tre coorti di dosaggio (1×10⁹, 2×10⁹ e 4×10⁹ cellule), con i soggetti che hanno ricevuto quattro dosi a intervalli di tre settimane. I risultati chiave hanno mostrato che troculeucel è stato ben tollerato, senza eventi avversi correlati al farmaco. La terapia ha ridotto la neuroinfiammazione e ha avuto effetti positivi sugli aggregati proteici cerebrali, come indicato dai livelli di biomarker nel liquido cerebrospinale.
Il trattamento ha mostrato diminuzioni dose-dipendenti nei biomarker pTau181 e GFAP. A seguito di questi risultati promettenti, è stato avviato un trial più ampio con dosaggi/durata superiori negli Stati Uniti. La ricerca è stata pubblicata nella rivista peer-reviewed Alzheimer's Research & Therapy.
NKGen Biotech (NKGN) ha publicado los resultados de su ensayo clínico de Fase 1 sobre troculeucel, una terapia con células NK autólogas expandidas para el tratamiento de la enfermedad de Alzheimer (AD). El ensayo, que involucró a 11 sujetos con una edad mediana de 79 años, demostró resultados estables o mejorados en el 90% de los sujetos evaluables.
El estudio utilizó tres cohortes de dosis (1×10⁹, 2×10⁹ y 4×10⁹ células), con sujetos recibiendo cuatro dosis a intervalos de tres semanas. Los hallazgos clave mostraron que troculeucel fue bien tolerado sin eventos adversos relacionados con el fármaco. La terapia redujo la neuroinflamación y afectó positivamente a los agregados de proteínas cerebrales, como lo indican los niveles de biomarcadores en el líquido cefalorraquídeo.
El tratamiento mostró disminuciones dependientes de la dosis en los biomarcadores pTau181 y GFAP. Tras estos resultados prometedores, se ha iniciado un ensayo más grande con dosis/duración más altas en EE. UU. La investigación ha sido publicada en la revista revisada por pares Alzheimer's Research & Therapy.
NKGen Biotech (NKGN)는 알츠하이머병 (AD) 치료를 위한 확장 자가 NK 세포 요법인 트로클루셀의 1상 임상 시험 결과를 발표했습니다. 이 시험은 중간 연령이 79세인 11명의 피험자가 참여했으며, 평가 가능한 피험자의 90%에서 안정적이거나 개선된 결과를 보여주었습니다.
연구는 세 가지 용량 집단(1×10⁹, 2×10⁹, 4×10⁹ 세포)을 사용하였으며, 피험자들은 3주 간격으로 4회 투여를 받았습니다. 주요 결과는 트로클루셀이 잘 견디며 약물 관련 부작용이 없음을 보여주었습니다. 이 요법은 신경 염증을 줄이고 뇌 단백질 응집체에 긍정적인 영향을 미쳤으며, 이는 뇌척수액 생물표지자 수준으로 나타났습니다.
치료는 pTau181 및 GFAP 생물표지자에서 용량 의존적인 감소를 보였습니다. 이러한 유망한 결과에 따라, 미국에서 더 높은 용량/지속 시간의 대규모 시험이 시작되었습니다. 연구 결과는 동료 검토 저널인 Alzheimer's Research & Therapy에 발표되었습니다.
NKGen Biotech (NKGN) a publié les résultats de son essai clinique de Phase 1 sur le troculeucel, une thérapie à base de cellules NK autologues élargies pour le traitement de la maladie d'Alzheimer (AD). L'essai, impliquant 11 sujets avec un âge médian de 79 ans, a montré des résultats stables ou améliorés chez 90 % des sujets évaluables.
L'étude a utilisé trois cohortes de dosage (1×10⁹, 2×10⁹ et 4×10⁹ cellules), les sujets recevant quatre doses à intervalles de trois semaines. Les résultats clés ont montré que le troculeucel était bien toléré, sans événements indésirables liés au médicament. La thérapie a réduit la neuroinflammation et a eu des effets positifs sur les agrégats protéiques cérébraux, comme l'indiquent les niveaux de biomarqueurs dans le liquide céphalorachidien.
Le traitement a montré des diminutions dépendantes de la dose des biomarqueurs pTau181 et GFAP. Suite à ces résultats prometteurs, un essai plus vaste avec des doses/durée plus élevées a été lancé aux États-Unis. La recherche a été publiée dans la revue à comité de lecture Alzheimer's Research & Therapy.
NKGen Biotech (NKGN) hat die Ergebnisse seiner Phase-1-Studie zu Troculeucel veröffentlicht, einer erweiterten autologen NK-Zelltherapie zur Behandlung von Alzheimer-Krankheit (AD). Die Studie umfasste 11 Probanden mit einem Medianalter von 79 Jahren und zeigte bei 90% der bewertbaren Probanden stabile oder verbesserte Ergebnisse.
Die Studie verwendete drei Dosisgruppen (1×10⁹, 2×10⁹ und 4×10⁹ Zellen), wobei die Probanden vier Dosen in dreiwöchigen Abständen erhielten. Wichtige Ergebnisse zeigten, dass Troculeucel gut vertragen wurde und keine arzneimittelbedingten Nebenwirkungen auftraten. Die Therapie reduzierte die Neuroinflammation und hatte positive Auswirkungen auf die Proteinaggregate im Gehirn, wie durch die Biomarkerwerte im Liquor cerebrospinalis angezeigt.
Die Behandlung zeigte dosisabhängige Abnahmen der Biomarker pTau181 und GFAP. Nach diesen vielversprechenden Ergebnissen wurde in den USA eine größere Studie mit höheren Dosen/Dauer initiiert. Die Forschung wurde in der peer-reviewed Zeitschrift Alzheimer's Research & Therapy veröffentlicht.
- 90% of evaluable subjects showed stable or improved composite ADCOMS scores
- No drug-related adverse events reported
- Demonstrated dose-dependent reduction in key biomarkers (pTau181 and GFAP)
- Successfully advanced to Phase 1/2a trial with higher dosing
- 70% of subjects were treated at relatively low doses
- Small sample size of only 11 subjects in Phase 1
Insights
The publication of NKGen Biotech's Phase 1 trial results for troculeucel represents a significant milestone in Alzheimer's disease treatment development. The trial's 90% success rate in stabilizing or improving cognitive function, measured by ADCOMS (Alzheimer's Disease Composite Score), is particularly noteworthy given that 70% of subjects received relatively low doses.
Several aspects of these results warrant special attention:
- The dose-dependent reduction in pTau181 and GFAP biomarkers suggests a direct therapeutic effect on key AD pathological markers. pTau181 is a critical indicator of tau pathology, while GFAP reflects neuroinflammation - both central to AD progression.
- The therapy's dual mechanism of action - reducing neuroinflammation while potentially degrading protein aggregates - differentiates it from current anti-Aβ antibody treatments like Leqembi and Aduhelm, which primarily target amyloid plaques.
- The clean safety profile, with no drug-related adverse events, is particularly important given the elderly patient population (median age 79) and the current AD treatment landscape where safety concerns often limit therapeutic options.
However, it's important to note the study's limitations: the small sample size (10 evaluable subjects) and relatively short duration. The ongoing Phase 1/2a trial with higher dosing will be critical in validating these initial findings.
The potential for troculeucel as part of a multi-pronged treatment approach could be transformative. Current AD treatments focus primarily on single pathways, while this NK cell therapy's ability to address multiple disease mechanisms (neuroinflammation and protein aggregation) could offer more comprehensive treatment options.
For a micro-cap biotech company (
The results from Phase 1 of the Troculeucel Clinical Trial demonstrated stable/improved outcomes in
Troculeucel therapy was well-tolerated and resulted in beneficial effects on protein aggregate levels and neuroinflammatory biomarkers in the cerebrospinal fluid, with decreases in pTau181 and GFAP appearing to be dose dependent.
A larger trial with a higher dosing/duration has been initiated in the U.S. and is on-going.
SANTA ANA, Calif., Feb. 13, 2025 (GLOBE NEWSWIRE) -- NKGen Biotech, Inc. (Nasdaq: 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 publication of results from the Company’s initial dose escalation Phase 1 clinical trial of troculeucel, an expanded autologous NK cell therapy, for the treatment of Alzheimer’s disease (“AD”) in the journal Alzheimer’s Research & Therapy, an international peer-reviewed journal with a translational research focus in AD and other neurodegenerative diseases.
The publication showcases important context and further validation of the findings from the Company’s Phase 1 clinical study, which evaluated its expanded autologous NK cell therapy, troculeucel, in subjects with either mild, moderate, or severe AD (median CDR-SB 10.0). The clinical trial information in this publication includes comprehensive details on troculeucel preparation, preclinical studies elucidating the mechanism of action, clinical trial design, and trial results (safety assessment, efficacy assessment, and biomarkers). Final Results of the Phase 1 trial were previously disclosed at the Alzheimer’s Association International Conference (AAIC 2024).
“We are excited to have our Phase 1 clinical trial published in Alzheimer’s Research & Therapy,” said Paul Y. Song, MD, Chairman and Chief Executive Officer of NKGen. “Previously presenting our positive findings at major medical conferences has been a great way to share our progress with the medical community, but having these data published in such a respected, peer-reviewed journal certainly elevates the credibility of our work and the importance of having a therapy such as troculeucel. The rigorous peer-review process gives our research further validation, as it has been thoroughly evaluated by experts in the field, which not only strengthens the foundation of our early research but also highlights our potential to shape the future of AD treatment. Additionally, this is an important step towards advancing the scientific understanding of troculeucel as a potential treatment option for AD and other neurodegenerative diseases.”
Publication Highlights:
- 11 subjects (5 males and 6 females) enrolled.
- 10 subjects were evaluable.
- Median age was 79 years (56 to 85 years).
- Using a 3 + 3 design to identify the maximum tolerated dose (“MTD”) and/or the recommended phase 2 dose (“RP2D”), three dose cohorts (1 × 109 cells, 2 × 109 cells, and 4 × 109 cells) were enrolled, each receiving a total of four doses at three-week intervals.
- Despite
70% of subjects being treated at relatively low doses of troculeucel,90% of all evaluable subjects had either stable or improved (±0.1) composite ADCOMS scores at week 11 (one-week after the final dose), as previously disclosed. - The study demonstrated that adoptive NK cell therapy was well-tolerated.
- Treatment with troculeucel reduced neuroinflammation and had a positive effect on brain protein aggregates (as suggested by CSF biomarker levels), which appeared to translate into a stabilization or even an improvement in cognitive function.
- Given the role of the innate immune system in AD pathology, a reduction in neuroinflammation as a therapeutic strategy may complement the current available anti-Aβ antibodies.
- Since AD is a complex disease, it stands to reason that a multi-pronged approach to treatment, which includes NK cell adoptive therapy, and potentially other anti-inflammatory therapeutic agents, may be able to stabilize or even improve this disease beyond the effect on slowing progression seen with the anti-Aβ antibodies.
- The additional ability of NK cell therapy to potentially cause degradation of protein aggregates suggests that this treatment on its own may have therapeutic and/or disease-modifying benefits.
The full publication entitled “Treatment of Alzheimer's Disease subjects with expanded non-genetically modified autologous natural killer cells (SNK01): a phase I study” is available at the following link:
https://alzres.biomedcentral.com/articles/10.1186/s13195-025-01681-2
NKGen’s follow-up Phase 1/2a trial on troculeucel in moderate AD is currently enrolling patients for the Phase 2 cohort. For more information, please visit the ClinicalTrials.gov website at https://clinicaltrials.gov/study/NCT06189963.
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 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 Contacts:
Chris Calabrese
Managing Director
LifeSci Advisors, LLC
ccalabrese@lifesciadvisors.com
Kevin Gardner
Managing Director
LifeSci Advisors, LLC
kgardner@lifesciadvisors.com
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