CVD-001: Hyperlipidemia (LPA)

The Lp(a) Problem: An Unmet Medical Need

Elevated lipoprotein(a) [Lp(a)] is a genetically determined, causal risk factor for atherosclerotic cardiovascular disease (ASCVD), aortic stenosis, and thrombosis. Unlike LDL cholesterol, Lp(a) levels are minimally responsive to diet or statins, leaving approximately 1.4 billion people worldwide (20% of the global population) with elevated levels and no approved treatment options. Individuals with Lp(a) >50 mg/dL face 2-4× increased risk of myocardial infarction and stroke.

The unique biology of Lp(a)—covalent linkage of apolipoprotein(a) to apoB-100—has complicated traditional drug development approaches. While injectable biologics are in development, the field lacks convenient oral therapies that could address this massive unmet need.

AI-Discovered Small Molecule Target

Our AI analyzed the complete Lp(a) biosynthesis and assembly pathway to identify druggable nodes amenable to small molecule intervention. Rather than targeting the well-characterized apolipoprotein(a) synthesis machinery, the system discovered a novel regulatory mechanism controlling Lp(a) particle assembly in hepatocytes.

This target represents a previously uncharacterized protein-protein interaction essential for the covalent attachment of apo(a) to LDL particles. Importantly, it is structurally distinct from factors involved in LDL metabolism, enabling selective Lp(a) reduction without affecting LDL cholesterol levels.

Oral Small Molecule with Favorable Properties

Using AI-guided structure-based drug design, we screened billions of virtual compounds to identify small molecules that selectively disrupt this protein-protein interaction. Our lead candidates demonstrate high oral bioavailability in computational ADMET models with predicted once-daily dosing.

Simulations in our digital patient platform across diverse LPA genotypes (including rare isoforms) predict robust Lp(a) lowering with favorable selectivity over related lipid pathways. An oral small molecule with these properties would represent a significant advance over injectable therapies, enabling broader patient access and improved adherence.