2025 AHA | Dose-Dependent and Sustained Reduction in Lipoprotein(a) Level after a Single Dose of Kylo-11, an LPA-targeted Small Interfering RNA, in Healthy Volunteers: A First-in-Human Phase I Study

Oral presentation at AHA Scientific Sessions 2025

• Median Lp(a) reduction of 77.6% in 30 mg dose group at Week 48, 88.8% in 75 mg dose group at Week 44, 96.7% in 225 mg dose group at Week 40 in participants with Lp(a) level of 75–200 nmol/L
• Median Lp(a) reduction of 98.4% (225 mg) at Week 28 in participants with Lp(a) level over 200 nmol/L
• Kylo-11 was well tolerated in healthy volunteers

HANGZHOU, China – November [11], 2025 – Hygieia Pharmaceuticals (referring to “Hygieia” thereafter), a clinical-stage biotech company dedicated to developing RNAi medicines, today announced that the preliminary results from the first-in-human Phase I study (NCT06363851) of Kylo-11 (an experimental small interfering RNA medicine targeting LPA mRNA) in healthy volunteers with elevated serum Lp(a) level. The data were presented in an oral presentation at the American Heart Association (AHA) Scientific Sessions in New Orleans, Louisiana (Abstract ID: 4390197).

This study is a randomized, double-blind, placebo-controlled, single-ascending dose phase 1 trial to evaluate the safety, tolerability, pharmacokinetic (PK), pharmacodynamics (PD), and immunogenicity of Kylo-11 in Chinese healthy adult volunteers. Ascending dose levels including 9 mg, 30 mg, 75 mg, 225 mg, 450 mg, and 600 mg (Cohorts 1~6) were evaluated in participants with Lp(a) level of 75–200 nmol/L; the dose 225 mg of Kylo-11 was additionally evaluated in participants with Lp(a) level >200 nmol/L in Cohort 7. All participants were followed up for at least 24 weeks post dose and up to 48 weeks in the study. The phase I trial remains ongoing for completion of 48 weeks follow-up in all participants.

Kylo-11 Exhibited Superior Efficacy in Lp(a) Reduction along with Outstanding Sustainable Effect

Data as of June 17, 2025, the results of phase 1 trial showed (median follow-up was 228.5 days):

• After single-dose administration of Kylo-11, median percentage changes (IQR) from baseline in serum Lp(a) levels at 24 weeks post dose were -83.5% (-84.9%,-75.6%), -88.9% (-94.9%, -81.7%), -95.2% (-96.5%, -93.5%), -96.7% (-97.4%, -96.3%), -97.2% (-97.8%, -96.9%), -97.4% (-97.8%, -96.5%), and -98.4% (-98.5%,-98.3%) in Cohort 1–7, respectively.
• Median Lp(a) reduction in participants with baseline Lp(a) concentration of 75–200 nmol/L maintained at 77.6% at Week 48 in 30 mg cohort, 88.8% at Week 44 in 75 mg cohort, and 96.7% at Week 40 in 225 mg cohort, respectively.
• Lp(a) reduction in participants with baseline Lp(a) concentration >200 nmol/L maintained 98.4% at Week 28.
• Serum Lp(a) level remained below 75 nmol/L in all participants receiving ≥30 mg of Kylo-11 from 4 weeks post dose during the follow-up period.
   

Kylo-11 Showed a Favorable and Well-Tolerated Profile with No Unexpected Safety Signals

Kylo-11 was safe and well tolerated across all study cohorts in this study. Most TEAEs were Grade 1–2 and unrelated to study drug. No serious TEAEs, TEAEs leading to study discontinuation, or injection-site reactions occurred in the study. 

Professor Xiaolan Yong, the principal investigator of the study from Chengdu Xinhua Hospital, said: "Lp(a) is an independent risk factor for cardiovascular events, but we still don’t have an effective therapy to reduce Lp(a) level in clinical practice. The emergence of Kylo-11, an siRNA medicine specifically designed to lowering serum Lp(a) in human, is highly promising. Phase I data are compelling, demonstrating superior efficacy and durability compared to other molecules in this class worldwide, along with a favorable safety profile. We’re glad that these results have been selected for an oral presentation at the AHA Scientific Sessions 2025. Due to no approved drugs available, we're thrilled to see the hope for ASCVD patients with elevated Lp(a) and potentially change the journey of cardiovascular disease management."

“These data suggest that Kylo-11 has the potential to re-shape the current management of hyperlipidemia: Poor compliance with daily oral therapies often leads to uncontrollable hyperlipidemia, increasing the risk of heart attack and stroke. A once-a-year injection with sustained, outstanding efficacy could overcome this critical challenge and substantially reduce cardiovascular risk. Based on the promising data of Phase I, the Kylo-11 program is now advancing into a China-US Phase II trial.” said Tao Guan, Chief Executive Officer of Hygieia.

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About Hygieia Pharmaceuticals

Hygieia Pharmaceuticals is committed to building a delivery technology platform and drug development of siRNA and have established a complete end-to-end siRNA drug development platform from target discovery to clinical Proof of Concept (POC). We have developed multiple siRNA delivery platforms with independent intellectual property rights (IIPR) and have a professional team with rich experience covering the entire lifecycle from early research and development to industrialization.

The MVIP delivery platform has been clinically validated for efficient delivery and effective prevention of exonuclease degradation of antisense end fragments, with better stability in vivo and no antisense chain degradation in plasma. It is the first siRNA delivery platform in China that obtained global patent authorization, and the world's first dual site coupled siRNA delivery technology for hepatic diseases. It has unique stability to prevent siRNA degradation, and its high efficiency, safety, and long-term effectiveness have been verified through multiple clinical pipelines of Hygieia Pharmaceuticals

The DDP delivery platform is the second-generation siRNA delivery platform for hepatic diseases developed by Hygieia Pharmaceuticals, which can simultaneously deliver two or more siRNAs and can be used to develop drugs for complex or refractory diseases mediated by multiple targets and mechanisms. Currently, DDP pipelines have entered the IND Enabling Study phase.

NSDP is another siRNA delivery platform we developed specifically for neurological diseases, able to target not only the central nervous system (CNS) but also the peripheral nervous system (PNS). Currently, multiple NSDP pipelines are in the preclinical compound confirmation stage.

Based on the above siRNA delivery platforms, Hygieia Pharmaceuticals focuses on disease areas that are currently urgently needed or have no available drugs in clinical practice. Our pipelines mainly focus on hepatitis B, NASH/MASH, cardio cerebrovascular and metabolic diseases, complement mediated diseases, nervous system diseases, etc.