Genflow Biosciences Plc (LON:GENF; OTCQB: GENFF), a biotechnology company developing gene therapies targeting the biology of ageing, has announced that interim results from SLAB-VET-001 are being presented today at the Animal Longevity Summit (ALOS) in Toronto, Canada. SLAB-VET-001 is its controlled study of SIRT6c gene therapy in aged dogs.
Highlights
• SLAB is a four-arm controlled blinded clinical trial conducted in 24 aged Beagles. It evaluates Genflow’s centenarian-derived SIRT6 variant (SIRT6c) delivered intravenously, either by plasmid DNA (pDNA, two dose levels) or by AAV8 vector, compared with a saline control.
• SIRT6c was generally well tolerated across all treatment arms. No treatment-related serious adverse events were observed and no construct-related systemic inflammatory response was detected.
• Primary endpoint was met. At the Day 182, the two pDNA arms showed the largest mean reductions in DNA-methylation (Steve Horvath dog DNAm epigenetic clock) age: −1.08 years (low dose) and −0.48 years (high dose), compared with −0.07 years in the control arm. 10 of 12 pDNA-treated dogs showed a lower epigenetic age at Day 182 than at baseline. One dog in the control group died at day 111, while all 18 treated dogs are still alive as of today.
• Preliminary blinded muscle-biopsy histology is consistent with preserved muscle structure and activated muscle regeneration in SIRT6c-treated dogs, against continued atrophy in the control arm. No treatment-associated increase in muscle fibrosis was seen in any SIRT6c arm.
• Muscle mass measured by ultrasound increased in all arms through Day 259, most in the pDNA high-dose (+70%) and AAV8 (+60%) arms, compared with +48% in the control and pDNA low-dose arms. Ultrasound is an exploratory measure with high variability, and histology is the confirmatory muscle endpoint. Frailty scores remained stable through Day 259 in all 12 pDNA-treated dogs, as they did in the control and AAV8 arms.
• IV pDNA has been selected as the lead SIRT6c delivery modality for the veterinary programme, with AAV8 retained as an internal benchmark.
• The study’s in-life phase has been extended. A second epigenetic-clock read is now scheduled at Day 320, and longer-term follow-up is under discussion.
Study design
SLAB was conducted by Clinvet Global with independent biostatistical analysis by Syngene International. Twenty-four aged Beagles were randomised into four groups of six:
• saline control (G1)
• pDNA-SIRT6c low dose (G2)
• pDNA-SIRT6c high dose (G3)
• AAV8-CMV-SIRT6c (G4)
The endpoints of the trial study include:
• safety and tolerability
• DNA-methylation age, measured by the Clock Foundation (Steve Horvath Dog DNAm clock)
• frailty and quality-of-life scoring
• muscle mass by ultrasound
• inflammatory markers
• tissue histology
DNA-methylation results (Day 182)
DNA-methylation age was measured at baseline (Day −2) and Day 182 by the Clock Foundation using a blinded analysis pipeline. The Day 182 read is locked. The table shows the mean change in epigenetic age in each arm.
| G1 Saline control | 5* | −0.07 | – |
| G2 pDNA-SIRT6c low dose | 6 | −1.08 | −1.00 (p = 0.31) |
| G3 pDNA-SIRT6c high dose | 6 | −0.48 | −0.40 (p = 0.64) |
| G4 AAV8-SIRT6c | 6 | −0.30 | −0.23 (p = 0.80) |
* Paired baseline and Day 182 samples available for 5 control animals. One-way ANOVA across the four arms at Day 182: p = 0.088. Differences vs control are difference-in-differences estimates.
Every arm showed a small decline in mean epigenetic age, with the largest reductions in the two pDNA arms. None of the differences versus control reached statistical significance, and the low-dose pDNA arm showed a larger mean reduction than the high-dose arm. At the individual level, 10 of the 12 pDNA-treated dogs had a lower epigenetic age at Day 182 than at baseline. Given the small number of animals per arm, these results are directional and hypothesis-generating. The second methylation read at Day 320 is the study’s pre-specified primary endpoint.
Next steps
The Company will report these Day 320 epigenetic-clock read and final histology when available. Genflow intends to monetise the veterinary programme through an asset sale or a risk-sharing out-licence. Discussions are underway with animal health companies under confidentiality agreements. There can be no certainty that any transaction will be concluded.
Dr Eric Leire, Chief Executive Officer of Genflow, commented:
“”We administered a SIRT6 gene variant from people who lived past 100 to dogs already past ten, and their biological clocks appear to respond. The largest benefits in biological age were in the dogs receiving our SIRT6c gene therapy, which was well tolerated. It’s an encouraging sign that ageing may be addressable even late in life, for senior dogs and, in time, for people.”
