Eli Lilly and Company / Beam Therapeutics Inc.

Hyperlipidemia / atherosclerotic cardiovascular disease

25M US cases/yr · $35.0B Global lipid-lowering therapy market forecast (2030) · 600 Total Lilly-Beam deal value incl. $200M upfront, $50M equity, $350M milestones (USD MM)

Disease Overview

Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of death in the United States, and LDL cholesterol elevation is its single most modifiable driver. Approximately 86 million US adults have total cholesterol above 200 mg/dL (CDC 2023) and roughly 25 million have clinical ASCVD. Heterozygous familial hypercholesterolemia (HeFH) affects about 1 in 250 Americans (~1.3M patients); homozygous FH (HoFH) is far rarer, affecting approximately 1,300 patients. Despite high-intensity statin therapy, ezetimibe and PCSK9 monoclonal antibodies, LDL-C goals are unmet in 60-80% of high-risk patients because of adherence, cost and residual genetic burden; real-world data suggest less than half of HeFH patients reach guideline LDL-C targets even on combination therapy. Liver-directed base editing of PCSK9 offers a one-time treatment with durable LDL reduction analogous to genetic loss-of-function carriers, who show roughly 88% lifetime reduction in coronary disease risk. VERVE-101 targets PCSK9; VERVE-102 is a follow-on PCSK9 editor with GalNAc-enhanced LNP delivery; VERVE-201 targets ANGPTL3 for HoFH and refractory mixed dyslipidemia. The global lipid-lowering market was approximately $23B in 2023 (EvaluatePharma), with PCSK9 agents Repatha and Praluent generating approximately $2.5B combined and fast-growing siRNA Leqvio adding momentum.

Competitive Landscape

Cardiovascular LDL-lowering is a crowded but durable market with room for a durable one-time therapy. Statins (atorvastatin/Lipitor, rosuvastatin/Crestor, both generic) remain standard of care and cover the bulk of prescribing. Ezetimibe (Zetia, Merck) adds roughly 15-20% LDL reduction as an add-on. PCSK9 monoclonal antibodies: Repatha (evolocumab, Amgen, ~$1.5B 2023) and Praluent (alirocumab, Sanofi/Regeneron, ~$700M). Small-molecule oral PCSK9 inhibitor: enlicitide decanoate (Merck, Phase 3). PCSK9 siRNA: Leqvio (inclisiran, Novartis, twice-yearly injection, ~$350M 2023 and growing rapidly with the Medicare Part B pathway). Bempedoic acid: Nexletol and Nexlizet (Esperion). Lp(a)-targeting pipeline: olpasiran (Amgen, Phase 3) and pelacarsen (Novartis/Ionis, Phase 3). ANGPTL3: Evkeeza (evinacumab, Regeneron, approved for HoFH). Base editing enters this field through Verve's VERVE-101 and VERVE-102 (PCSK9) and VERVE-201 (ANGPTL3), plus preclinical competition from Intellia, Prime Medicine, CRISPR Therapeutics and Beam's own wholly-owned hypertension (BEAM-301 GYS2) and Tay-Sachs programs. Durability of a single edit positions the class against chronic injectables, with ultimate success gated on long-term hepatic safety, off-target editing profile and payer willingness to finance one-time therapies for high-prevalence disease.