Validated across mouse, pig, and nonhuman primate models using subcutaneous administration in saline.
Cardiac Rescue After Myocardial Infarction
Study Design: Anti-miR-128 LNA ASO (10 mg/kg weekly SC or single dose 2 hr post-reperfusion) in mouse ischemia-reperfusion MI model. Treatment initiated AFTER injury — not prevention.
LV ejection fraction improved with both single-dose and weekly anti-miR-128 treatment vs scramble control over 28 days post-MI. All P<0.05-0.001. n=8-10/group.Reduced infarct size and fibrotic scarring at 28 days post-MI (Masson trichrome staining). Weekly treatment P=0.014 vs scramble.
Study design, RNA-seq at 14 days post-MI: restoration of oxidative phosphorylation; suppression of TNFα/NF-κB, interferon, and IL-6/JAK-STAT3 inflammatory pathways.
A single SC dose administered 2 hours after reperfusion was sufficient to rescue cardiac function. This is a post-injury therapeutic.
Cardiac Function Rescued in DMD Large Animal Model
Study Design: DMD Y/- pigs, anti-miR-128 LNA ASO 5 mg/kg/week SC for 8 weeks (treatment from 6 to 14 weeks of age). N=4 treated, N=5 scramble control, N=5 wild-type.
Anti-miR-128 decreased miR-128 in pig hearts (P=0.001), restored ejection fraction (P<0.001 at 2 months vs DMD control), and reduced cardiac damage marker troponin I.
8 weeks of SC treatment rescued chronic heart failure in a clinically relevant large-animal DMD model — the same chemistry and dosing route used across all Elenae programs.
24-Week Chronic Dosing Safety in Nonhuman Primates
Study Design: Cynomolgus monkeys, anti-miR-128 LNA ASO 5 mg/kg/week SC. N=4 in 24-week chronic tox study + N=7 in 20-week safety follow-up.
24-week NHP chronic dosing: on-target efficacy (>95% miR-128 knockdown in skeletal muscle, heart, liver), no hepatotoxicity (normal AST/ALT), no nephrotoxicity (normal BUN/creatinine), no treatment-related histological changes in liver or kidney. 5 mg/kg/week SC.
Study
Species
Duration
Dose
Result
Chronic toxicity (N=4)
Cynomolgus NHP
24 weeks
5 mg/kg/wk SC
No hepatotox, nephrotox, immune activation; stable body weight
Safety follow-up (N=7)
Cynomolgus NHP
20 weeks
5 mg/kg/wk SC
Confirmed clean safety
DMD efficacy (N=4)
Pig
8 weeks
5 mg/kg/wk SC
Cardiac function rescued; no adverse effects
Human precedent
—
Phase I-II
Various
Cardior, Santaris, miRagen: clean safety in humans
No injection site reactions observed in ANY study across mouse, pig, or NHP — including 24 weeks of once-weekly SC dosing at 5 mg/kg.
Exon-Skipping LNA ASO Mixmer: Tolerability & PK
Data from oncogene exon-skipping program — different ASO, same LNA mixmer chemistry platform.
Tolerability: Weight gain, ALT, AST, creatinine, BUN — all non-significant vs saline control.
Pharmacokinetics: Measurable serum concentration time-course with confirmed solid tissue drug levels across target organs.
