Among 10 patients evaluated, compared with their baseline at 1 week after receiving their final dose in the trial, 30% demonstrated clinical improvement on the Alzheimer’s disease composite score.
This article first appeared on CGTLive™. This version has been lightly edited.
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Patients with Alzheimer disease (AD) treated with NKGen’s autologous natural killer (NK) cell therapy SNK01 in the phase 1 ASK-AD clinical trial (NCT04678453) showed clinical improvement, according to a recent company announcement summarizing data presented at the Clinical Trials on Alzheimer’s Disease Annual Meeting, held October 24-27, 2023, in Boston, Massachusetts.1
Among 10 patients evaluated, compared with their baseline at 1 week after receiving their final dose in the trial, 30% demonstrated clinical improvement on the Alzheimer’s disease composite score (ADCOMS), 60% of patients demonstrated a stable ADCOMS score, and 1 patient who previously had an ADCOMS score classified as moderate achieved an ADCOMS score classified as mild. Furthermore, 50% to 70% of the 10 patients showed scores that were stable or improved compared with baseline on the Clinical Dementia Rating-Sum of Boxes (CDR-SB), the Alzheimer’s Disease Assessment Scale-Cognitive Subscale, and the Mini-Mental State Examination (MMSE).
At 12 weeks after receiving their final dose, 44% to 89% of 9 patients evaluable for efficacy at this point either showed improvement or maintained stability on all cognitive scores compared with their results at 1 week after the final dose. Additionally, 50% of the patients who had a stable ADCOMS score at 1 week after the final dose remained stable at 12 weeks after the final dose. In terms of safety, no treatment-related adverse events were reported. The company also noted that SNK01 showed activation and expansion in all patients.
The single-center, dose-escalation study divided patients into 3 cohorts, and they received doses of SNK01 at either 1x109 cells, 2x109 cells, or 4x109 cells. Patients received the therapy intravenously in 4 administrations every 3 weeks. At baseline, 5 patients had AD classified as mild, 3 patients had AD classified as moderate, and 2 patients had AD classified as severe. Their CDR-SB scores at baseline ranged from 4 to 18 (median, 9).
“We are pleased to present the final data from our phase 1 AD study further demonstrating that SNK01 is well tolerated and appears to reduce both proteins (pTau181 and Aβ42/40) and neuroinflammation (GFAP [glial fibrillary acidic protein]) among trial patients,” Paul Y. Song, MD, CEO of NKGen Biotech, said in a statement.1 “Remarkably, despite a median baseline MMSE score of 14 and the fact that two-thirds of our patients received what we believe to be suboptimal dosing, using the ADCOMS score, 90% of patients demonstrated improvement or maintained stable cognitive function following 11 weeks, suggesting that SNK01 may do more than simply slow disease progression.”
SNK01 is also being evaluated in clinical trials as a monotherapy and as part of combination therapies with other treatments, such as checkpoint inhibitors and cell engagers, for the treatment of patients with advanced refractory solid tumors.2 In February of this year, SNK01 was approved by the FDA for compassionate use in a patient with Parkinson disease.3
“When we first proposed the use of our enhanced NK cells for neurodegenerative diseases, we were met with skepticism,” Song continued.1 “But thanks to the clinical team at Hospital Angeles, who worked with us to get full Comisión Federal para la Protección contra Riesgos Sanitarios and Research Ethics Board approval, we were able to conduct this groundbreaking trial, which has provided us with invaluable clinical and biomarker data that undoubtedly helped us receive US investigational new drug (IND) clearance for a phase 1/2a study in patients with moderate-stage AD. Whereas this phase 1 trial was a dose-escalation trial that only gave 4 total doses over 11 weeks, our new IND approval calls for using a higher dose and a prolonged dosing regimen. We are very excited to begin this next phase in hopes of establishing an entirely new treatment paradigm for more advanced patients.”
Nadezhda Omelchenko, MD, a research associate at Cancer Center of Southern California in Santa Monica, spoke about case studies for SNK01 in sarcomas that she presented at the American Society of Gene and Cell Therapy 2023 Annual Meeting, held May 16-20, in Los Angeles, California.4 Omelchenko went over the key results from each of the 3 patients, who had different forms of chemotherapy-resistant soft tissue sarcoma. The cases were unique in terms of dosing and other factors, but some positive results were observed in each.
“The rationale of the study was to use people’s own innate immune system in a manner of anticancer activity,” Omelchenko said. “In this case, NK cells were used as the essential innate immune system cells. They were first taken from the peripheral blood, then enhanced and amplified in the laboratory ex vivo, and then administered back to the patients in an increased therapeutic dose. We used it in combination with immune checkpoint inhibitors, which not only inhibit immunosuppressive activity of T cells, but also uncloak in the tumor microenvironment, which allows it to evade the immune system. It is believed the combination of these 2 immunotherapy drugs could lead to better and more effective increased activity in a person's own innate immune system, which has a crucial role in anticancer activity.”
References
1. NKGen Biotech presented phase I clinical trial data at the 16th Annual Clinical Trials on Alzheimer’s Disease (CTAD) conference. News release. NKGen Biotech Inc. October 26, 2023. Accessed November 21, 2023. https://nkgenbiotech.com/nkgen-biotech-presented-phase-i-clinical-trial-data-at-the-16th-annual-clinical-trials-on-alzheimers-disease-ctad-conference/
2. NKGen Biotech announces collaboration with the Parkinson’s Foundation to bring its novel natural killer cell therapy to the clinic for advanced Parkinson’s disease. News release. NKGen Biotech. November 4, 2022. Accessed August 28, 2023. https://nkgenbiotech.com/nkgen-biotech-announces-collaboration-with-the-parkinsons-foundation-to-bring-its-novel-natural-killer-cell-therapy-to-the-clinic-for-advanced-parkinsons-disease/
3. NKMAX's NK cell therapy for Parkinson’s scores FDA compassionate use approval. News release. NKMAX. February 23, 2023. Accessed August 28, 2023. https://www.koreabiomed.com/news/articleView.html?idxno=20514
4. Omelchenko N, Chawla N, Chua-Alcala V, et al. SNK-01 autologous enhanced natural killer cells and an immune checkpoint inhibitor control tumor growth in rare chemotherapy-resistant advanced soft tissue sarcomas. Presented at: American Society of Gene and Cell Therapy 2023 Annual Meeting; May 16-20, 2023; Los Angeles, California. Abstract #1136.
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