Clinical Trials · Cardiovascular Disease
Sino Biopharmaceutical's experimental siRNA therapy Kylo-11 delivered a near-total, year-long suppression of a key cardiovascular risk factor in a first-in-human trial published in The Lancet — a result that could reshape treatment of lipoprotein(a)-driven heart disease if confirmed in larger studies.
Final data from the Phase I study of Kylo-11, an siRNA targeting lipoprotein(a), or Lp(a), were presented Sunday as a Late-Breaking Clinical Science oral report at the 2026 European Society of Cardiology Congress and published simultaneously in The Lancet, which carries an impact factor of 109. The drug was developed by Hangzhou HEGIA Biopharm, a wholly owned subsidiary of Hong Kong-listed Sino Biopharmaceutical Co., Ltd. (01177.HK).
Lp(a) is a genetically determined lipid particle closely linked to atherosclerotic cardiovascular disease — including heart attack and stroke — and is currently viewed as a causal risk factor with few effective therapeutic options. Lowering it has become one of the most closely watched frontiers in cardiovascular drug development.
A single dose, nearly a year of suppression
The trial was randomized, double-blind, placebo-controlled and single-ascending-dose — the standard first-in-human design — and enrolled 70 subjects who actually received Kylo-11 or placebo. Cohorts 1 through 6 included participants with baseline Lp(a) of 75 to 200 nmol/L, receiving single subcutaneous injections of 9 mg, 30 mg, 75 mg, 225 mg, 450 mg or 600 mg. Cohort 7 enrolled subjects with baseline Lp(a) above 200 nmol/L and received a single 225 mg dose, designed to probe the drug's behavior in patients with the highest baseline levels.
At 48 weeks after a single injection, median Lp(a) reductions in the mid-to-high dose groups were striking:
225 mg (Cohort 4): 94.6% median decline from baseline
225 mg (Cohort 7, higher baseline): 95.6% median decline
450 mg (Cohort 5): 96.3% median decline
600 mg (Cohort 6): 97.0% median decline
In Cohort 7, where the median baseline Lp(a) stood at 217.7 nmol/L, a single 225 mg dose produced a median absolute reduction of 207.7 nmol/L by Week 48, bringing median Lp(a) down to just 10.5 nmol/L — a level that, if sustained, would place most patients well below commonly cited risk thresholds.
Perhaps most notable for the "once-a-year" thesis: in all dose groups of 225 mg and above, Lp(a) had already fallen to near its maximum reduction roughly four weeks after dosing and remained there through the full 48-week follow-up period.
Safety: clean so far
Safety was the study's primary endpoint. Within 24 weeks of dosing, 37 of the 70 subjects reported adverse events, which were predominantly Grade 1 or 2 and, in the investigators' assessment, largely unrelated to the study drug. By Week 48, no clear dose-related increase in adverse-event incidence was observed.
No serious adverse events, injection-site reactions or deaths were reported. No adverse events led to discontinuation of the study drug, withdrawal or subject exit — a tolerability profile that will be closely scrutinized as the program advances into larger, longer trials.
What comes next
The results provide the first clinical evidence that a single subcutaneous dose of an Lp(a)-targeting siRNA can produce deep, durable suppression of the lipid particle — the kind of pharmacology that, if replicated in outcomes trials, could support an annual dosing regimen. Sino Biopharmaceutical said the data lay the groundwork for subsequent studies to further validate a "once-a-year" dosing strategy.
The Lp(a) space is crowded and competitive. Antisense oligonucleotides such as pelacarsen, small interfering RNAs including olpasiran and lepodisiran, and oral small-molecule candidates are all in various stages of development. What distinguishes Kylo-11, if the 48-week durability holds in Phase II and Phase III, is the potential for annual dosing with a single injection — a convenience and adherence advantage that could prove decisive in a chronic preventive therapy aimed at millions of patients worldwide.
Source: Sino Biopharmaceutical Co., Ltd. announcement; The Lancet (IF: 109); ESC 2026 Late-Breaking Clinical Science session.