New Biopharmaceutical Products Pipeline

Innovative, Cholesterol-Lowering Oral Treatment

At CVI Pharmaceuticals, we never cease in discovering and developing new biopharmaceutical products. We are committed to advancing a clinical-stage pipeline to address the unmet medical needs in the hypercholesterolemia and complex medical challenges of patients who suffer from liver and rare metabolic diseases.

Standard-of-care, lipid-lowering statins are effective at lowering LDL-C, leading to well-documented CV benefits. However, not all patients can tolerate statins or reach their LDL-C goal on maximally-tolerated statin-dosing. Patients with atherosclerotic cardiovascular disease (ASCVD) or heterozygous familial hypercholesterolemia (HeFH) who require additional LDL-C lowering on top of maximally tolerated statin therapy represent a high-risk patient population with an unmet medical need. Patients with fatty liver disorders, including NASH and NAFLD, may benefit from reduced liver fat levels. Fatty liver disease is a growing problem globally due to increasing metabolic disease. Patients with NASH and NAFLD often have associated dyslipidemia. As a result, most NAFLD/NASH patients die from cardiovascular diseases.

Pipeline Overview

Our Current Clinical Candidates

CVI-LM001

A Novel Candidate for Cardiometabolic and Liver Diseases

CVI-LM001 is a novel, first-in-class, safe and oral once daily PCSK9 modulator with distinct mechanisms of action in lowering blood atherogenic LDL-cholesterol and reducing liver fat respectively. Working synergistically with statins, CVI-LM001 has the potential to target patients with hypercholesterolemia and NAFLD/NASH patients with elevated LDL-C. Currently, a 12-week Phase 2 POC trial is initiated in China in patients with hypercholesterolemia.

CVI WEB-pipeline_07292020CVI WEB-pipeline_07292020

CVI-LM001 Dual Mechanisms of Action to Combat Hyperlipidemia and Fatty Liver Disease

CVI WEB-pipeline

MOA-1: CVI-LM001 upregulates liver LDLR expression and accelerates blood LDL-cholesterol removal via a unique mechanism of inhibition of PCSK9 transcription and prevention of LDLR mRNA degradation; statin activates LDLR transcription via SREBP2 pathway.

LDLR: LDL receptor, SRE-1: sterol-regulatory element, mRNABP: mRNA binding protein, 3’UTR: 3’untranslated region

CVI WEB-pipeline

MOA-2: CVI-LM001 activates hepatic adenosine monophosphate-activated protein kinase (AMPK), a master regulator of cellular energy, which turns on pathways that reduce the hepatic fat synthesis and boost fatty acids oxidation.

Preclinical Studies

In a hyperlipidemic hamsters model, treatment with CVI-LM001 (40, 80, and 160 mg/kg, QD) for four weeks dose-dependently increased liver LDLR protein levels up to 3.5-fold and decreased circulating PCSK9 levels to 10% of control at the highest dose; this was accompanied by significant reductions in serum LDL-C, total cholesterol (TC), and triglycerides. In a diet-induced NASH hamster model, four weeks treatment with CVI-LM001 substantially reduced hepatic ballooning and improved NASH score.

Clinical Studies

In a double-blind, randomized phase 1a study conducted in healthy volunteers, compared to baseline, serum PCSK9 levels were significantly reduced after 10 days of oral treatment with CVI-LM001 (300 mg, QD). Moreover, in a proof-of-mechanism phase 1b study conducted in subjects with elevated LDL-C, compared with the placebo cohort, treatment with CVI-LM001 for 28 days significantly reduced serum LDL-C, TC, Apo B, and PCSK9 levels. CVI-LM001 had a favorable safety profile and was well tolerated in Phase 1 studies conducted in healthy volunteers and hyperlipidemic subjects.

Altogether, these studies demonstrate that CVI-LM001, a novel PCSK9 modulator, has the potential to be a new oral cholesterol-lowering drug and warrant further clinical development. Currently, a 12-week Phase 2 POC trial is initiated in China in patients with hypercholesterolemia.

CVI-LM002

A Novel, Oral, Best-In-Class Small Molecule Targeting Obesity, NAFLD/NASH, and Rare Metabolic Diseases

CVI Pharmaceuticals Limited has discovered a series of novel small molecules that can significantly improve metabolic disorders in preclinical models. CVI-LM002 is a lead candidate that can induce significant body weight loss and body fat reduction in a diet-induced obese primate model and ameliorate hyperlipidemia and reduce liver fat in HFD-induced hamster models. Based on several diverse pharmacologic properties, including liver and adipose tissue of this compound, CVI Pharmaceuticals Limited believes that CVI-LM002 can potentially treat patients with obesity and NAFLD/NASH as well as rare metabolic diseases. CVI-LM002 is currently at the pre-IND stage.

Ask About Our Biopharmaceutical Product Candidates

If you wish to learn more about the research we’re conducting about new lipid-lowering mechanisms or have any questions about the pharmaceutical products we are developing, get in touch with us. Our team is more than happy to address your inquiries. You may contact us via the phone number or email address featured on this website. We hope to hear from you!