RBD5044 / Suzhou Ribo - LARVOL DELTA

Inhibition of liver ApoC3 by GalNAc-conjugated siRNA RBD5044: first-in-human trial to evaluate the safety, pharmacokinetics (PK), and pharmacodynamic (PD) effects on atherogenic lipid profiles in heal (ESC-WCC 2025) - "Following SC dosing, RBD5044 was rapidly absorbed with median time to reach maximum plasma concentrations ranging from 2-6 hours. Plasma concentrations thereafter declined rapidly with a mean half-life ranging between 3.3 - 6.7 hours, consistent with rapid GalNAc-mediated uptake of the siRNA into the liver (Figure 1). There was a dose dependent and sustained (>6 months) suppression of ApoC3 levels (Figure 1) at higher doses, accompanied by robust reductions in plasma triglycerides and atherogenic lipid particles (LDL, ApoB, calculated remnant Cholesterol[1] & VLDL[2]) in combination with increased HDL (Figure 2)."

Clinical • P1 data • PK/PD data • Cardiovascular • Dyslipidemia • APOB • APOC3

Prediction of Interspecies Translation for Targeting Delivery Coefficients of GalNAc-siRNA Silencing Apolipoprotein C-III Using a Mechanistic Minimal Physiologically Based Pharmacokinetic/Pharmacodynamic Model. (PubMed, Clin Pharmacokinet) - "This study successfully constructed the mPBPK-PD model and conducted interspecies extrapolation for a GalNAc-siRNA targeting APOC3. Promising quantitative insights into a hepatic-targeted GalNAc-siRNA delivery system are provided to characterize the unique temporal disconnection of PK/PD properties and evaluate the key in vivo delivery processes. It will promote model-informed strategies and quantitative mechanistic understanding to support efficient drug development, evaluation, and clinical application of this modality in the future."

Journal • PK/PD data • AGO2

Phase 2 Trial Evaluating the Efficacy and Safety of RBD5044 in Patients With Mixed Dyslipidemia (clinicaltrials.gov) - P2 | N=120 | Recruiting | Sponsor: Ribocure Pharmaceuticals AB | Not yet recruiting ➔ Recruiting

Enrollment open • Dyslipidemia • Metabolic Disorders • Mixed Hyperlipidemia

Phase 2 Trial Evaluating the Efficacy and Safety of RBD5044 in Patients With Mixed Dyslipidemia (clinicaltrials.gov) - P2 | N=120 | Not yet recruiting | Sponsor: Ribocure Pharmaceuticals AB

New P2 trial • Dyslipidemia • Metabolic Disorders • Mixed Hyperlipidemia

A Single and Multiple Ascending Doses Study to Evaluate the Safety and Pharmacokinetics of RBD5044 (clinicaltrials.gov) - P1 | N=72 | Completed | Sponsor: Suzhou Ribo Life Science Co. Ltd. | Trial primary completion date: Aug 2024 ➔ Oct 2024 | Recruiting ➔ Completed

Trial completion • Trial primary completion date

Ribo’s siRNA asset RBD5044 receives Clinical Trial Authorization from Swedish MPA for a Phase II trial in patients with mixed dyslipidemia - "Ribocure Pharmaceuticals AB and Suzhou Ribo Life Science Ltd (Ribo) received authorization from the Swedish Medicinal Product Agency (MPA), to initiate a Phase II clinical trial in Sweden with the lipid-lowering siRNA drug RBD5044 that targets APOC3. The trial will evaluate efficacy and safety in patients with mixed dyslipidemia. A randomized, double-blind, placebo-controlled, multi-center phase II trial evaluating the efficacy and safety of RBD5044 in participants with mixed dyslipidemia will be run. The trial sites include Ribocure Clinic, a specialized phase II unit for high quality functional imaging proof of principle trials, based in GoCo Health Innovation City, Gothenburg, as well as sites in Lund and Uppsala, Sweden."

New P2 trial • Dyslipidemia • Hypertriglyceridemia • Metabolic Disorders • Severe Hypertriglyceridemia

Combination therapy with GalNAc-siRNA drugs targeting both PCSK9 and APOC3 resulted in enhanced lipid lowering in mice (ESC 2024) - "Conclusions- The combination of RBD7022 targeting PCSK9 and RBD5044 targeting APOC3 simultaneously reduce LDL-C and TC levels. The combination of RBD7022 and RBD5044 could be a better therapeutic option to further reduce LDL-C, particularly for mixed hyperlipidemia patients and other high-risk individuals with both high LDL-C and high TG levels."

Combination therapy • Preclinical • Atherosclerosis • Cardiovascular • Dyslipidemia

A Single and Multiple Ascending Doses Study to Evaluate the Safety and Pharmacokinetics of RBD5044 (clinicaltrials.gov) - P1 | N=72 | Recruiting | Sponsor: Suzhou Ribo Life Science Co. Ltd. | Not yet recruiting ➔ Recruiting

Enrollment open • APOC3

RBD5044 - a novel anti-ApoC3 GalNAc-siRNA drug resulted in sustained and profound reduction of triglycerides in mice and Rhesus monkeys (ESC 2023) - "RBD5044 shows high efficacy, long duration and a good safety profile in preclinical studies. The Phase I trial of RBD5044 injection in healthy volunteers has been initiated in Australia."

Preclinical • Atherosclerosis • Cardiovascular • Dyslipidemia • APOC3

A Single and Multiple Ascending Doses Study to Evaluate the Safety and Pharmacokinetics of RBD5044 (clinicaltrials.gov) - P1 | N=72 | Not yet recruiting | Sponsor: Suzhou Ribo Life Science Co. Ltd.

New P1 trial • APOC3