Newly analyzed biomarker data from the initial dose-escalation Phase 1 AD trial found that troculeucel reduces GFAP, NfL, p-tau181, GDF-15, and LTBP2 levels, which are detectable up to 10 years before dementia symptoms appear according to recent reports. This suggests a potential role for the use of troculeucel in delaying or preventing dementia onset in asymptomatic individuals with detectable biomarkers.

Preliminary analysis from the Phase 1/2a AD trial administering the highest dose of cryopreserved troculeucel given to date (6 billion cells) showed troculeucel to be very safe with no adverse reactions. Of the first three subjects treated at this highest dose, 100% had stable or improved cognitive function, and two of the three showed significant improvement from moderate stage disease to mild cognitive impairment after only three months of treatment.

SANTA ANA, Calif., Oct. 29, 2024 (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 cell therapeutics, today announced the presentation of two posters, on its first-in-kind, autologous, non-genetically modified NK cell product, troculeucel, in Alzheimer’s Disease (“AD”). The posters entitled, “Use of Non-genetically Modified Natural Killer Cells (SNK01) With Enhanced Activity in Subjects with Active Alzheimer’s Disease. Further Biomarker Analysis and Implications for Use in Prevention” and “Treatment of Moderate Alzheimer’s Disease Subjects with Expanded Non-genetically Modified Natural Killer Cells (troculeucel; SNK01) with Enhanced Activity – Report of the Phase 1 results of the Phase 1/2a Study” were presented at the 17th Clinical Trials on Alzheimer’s Disease Annual Meeting (“CTAD”) on October 29, 2024.

NKGen previously showed, in a dose-escalation Phase 1 pilot trial, that four treatments with suboptimal doses of troculeucel in AD subjects were well-tolerated and had preliminary ability to impact cognition and improve protein and neuroinflammation biomarkers. Based on recent publications by Guo et. al., and Johansson et. al., which both reported the detection of several biomarkers a full decade before patients developed clinical symptoms of dementia, NKGen reanalyzed its biobank to determine if troculeucel effected specific biomarkers (e.g., GFAP, NfL, p-tau181, GDF-15, and LTBP2) implicated with increased AD risk.

“Despite the majority of subjects receiving suboptimal dosing and only four total doses in the Phase 1 pilot trial, we found that our autologous NK cell treatment was safe and that 90% of evaluable subjects experienced stable or improved cognitive function,” said Paul Y. Song, MD, Chairman and CEO of NKGen. “We also revealed that several subjects demonstrated reductions in several neuroinflammation biomarkers, such as GFAP, NfL, p-tau181, GDF-15, and LTBP2. We believe that increased screening for these biomarkers in asymptomatic individuals may reveal that troculeucel, which potentially reduces the associated biomarkers, could be a safe intervention to either delay, or prevent the onset of, dementia. However, further studies are needed to confirm these initial findings.”

For the follow-up Phase 1/2a trial on moderate Alzheimer’s patients, the Company hypothesized that troculeucel, given at the highest dose to date of 6 billion cells, could be safely infused and hopes to confirm an even greater impact on cognition and biomarkers.

Dr. Song added, “While 35% of all Alzheimer’s patients have moderate-stage disease, there is currently no approved therapy to improve cognitive function, let alone stop and/or slow cognitive decline, in this patient population. We have since initiated a Phase 1/2a trial using our highest dose of cryopreserved troculeucel in moderate AD subjects. We observed stable or improved cognitive function and no treatment-related adverse events after just three months of treatment. Notably, two of the three enrolled subjects in the Phase 1 cohort showed clinical improvement from moderate to mild AD based on ADCOMS and CDR-SB scores. Based on our promising data to date, we have already dosed the first two subjects in our double-blind, randomized Phase 2 cohort; and, look forward to sharing data updates when available. We are excited about the potential of troculeucel as a treatment for AD as well as the potential utility for it across other tau- and synuclein-related neurodegenerative diseases.”

Data Highlights from the Poster Presentations:

Poster entitled “Use of Non-genetically Modified Natural Killer Cells (SNK01) With Enhanced Activity in Subjects with Active Alzheimer’s Disease. Further Biomarker Analysis and Implications for Use in Prevention”:

• Eleven subjects (5 males and 6 females) enrolled.
  • 10 subjects were evaluable.
  • Median age was 79 years (56 to 85 years).
• 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.
• One-week post-final dose, improvement in 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 two/thirds of the subjects, troculeucel was able to positively affect biomarkers that are associated with increased AD development.
• No treatment related adverse events were observed.
• Results from this study suggest troculeucel could potentially be a safe preventative intervention for individuals at high-risk for AD.
• Further evaluation of neuroinflammation biomarkers related to predicting risk of AD and dementia would be beneficial to support the investigation.
  

Poster entitled “Treatment of Moderate Alzheimer’s Disease Subjects with Expanded Non-genetically Modified Natural Killer Cells (troculeucel; SNK01) with Enhanced Activity – Report of the Phase 1 results of the Phase 1/2a Study”:

• Three (3) subjects were enrolled in the Phase 1 cohort.
• Early review of the data shows that after three months’ treatment with a dose of 6 x 10⁹ cells every 3 weeks:
  • Clinical improvement was seen in two/thirds of the subjects, who went from a moderate to a mild AD rating on the CDR-SB scale.
  • All three subjects had either a stable or improved ADCOMS score.
• No treatment-related clinical or laboratory adverse reactions were seen; and, well tolerated in moderate AD subjects. Findings are similar to the SNK01-MX04 Phase 1 AD study (NCT04678453), where troculeucel was well-tolerated, and the one moderate AD subject who received a dose of 4 x 10⁹ cells also went from a moderate to a mild rating on the CDR-SB.
• This study aims to confirm previous preliminary efficacy seen on both cognitive and biomarker changes in AD subjects.
• Troculeucel will be evaluated for safety and efficacy in the randomized, placebo-controlled Phase 2a part of the study.
  

Copies of the posters are available on the Scientific Publications page of the Company’s website at https://nkgenbiotech.com/. Previously disclosed Phase 1 data on the positive effects of troculeucel on amyloid, tau, and neuroinflammation biomarkers in Alzheimer’s patients can also be found on the Scientific Publications webpage.

About Troculeucel

Troculeucel is a novel cell-based, patient specific ex vivo expanded autologous natural killer (“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 our 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)
Vice President, Investor Relations and Corporate Communications
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