Artery Therapeutics is developing CS6253, a first-in-class ABCA1 agonist designed to correct a lipid transport defect implicated in Alzheimer's pathology in APOE4 carriers. In Phase 1, CS6253 showed a favorable safety profile, pharmacokinetics supporting weekly subcutaneous dosing, and evidence of mechanism, including rapid high-density lipoprotein (HDL) formation and exploratory signals of amyloid-β mobilization.
APOE4 is the strongest common genetic risk factor for Alzheimer's disease (AD). Approximately 25% of people carry one copy, while the 2% carrying two copies face substantially higher lifetime risk. APOE4 impairs lipid transport in the brain, producing poorly lipidated ApoE particles and a distinct biological pathway that may be therapeutically addressable.
Artery Therapeutics is a clinical-stage biotechnology company pioneering first-in-class peptide therapies targeting the ATP-binding cassette transporter A1 (ABCA1), a master regulator of cellular lipid biology with profound therapeutic implications across neurodegenerative, metabolic, and cardiovascular diseases.
Our lead pipeline program targets a core biological mechanism of APOE4-associated Alzheimer's disease. By activating ABCA1 to correct impaired ApoE4 lipidation and lipid transport, we aim to intercept the disease at its source rather than managing its downstream consequences. The greatest need is among APOE4 homozygotes: roughly 2% of the population but an estimated 15% of Alzheimer's cases.
Headquartered in San Ramon, California, and supported by investors, the National Institutes of Health — National Institute on Aging (NIH-NIA), and the Alzheimer's Association Part the Cloud initiative, Artery is advancing CS6253, the first ABCA1 agonist to successfully complete Phase 1 clinical trials, into Phase 2A development for APOE4 homozygous carriers with MCI-Alzheimer's Disease (mild cognitive impairment due to Alzheimer's disease).
ABCA1 is the body's master cholesterol efflux transporter and the brain's primary lipidator of ApoE. When ABCA1 function is impaired, as it is in APOE4 carriers, lipid deficits lead to amyloid accumulation, neuroinflammation, and cellular degeneration. CS6253 activates ABCA1 to correct this transport failure at its source, unlocking a versatile therapeutic platform beginning with Alzheimer's disease.
ABCA1 & HDL Biogenesis. The figure shows how the ABCA1 transporter helps build small, "good cholesterol" (HDL) particles known to cross the blood-brain barrier.
ABCA1 governs cellular membrane health, lipid transport, and reverse cholesterol transport. ABCA1 and nascent HDL are directly linked: ABCA1 loads cellular cholesterol and phospholipid into its extracellular cavity, then transfers the payload to lipid-free ApoA-I, forming nascent HDL. When this process falters, cholesterol accumulates inside cells and lipid-poor particles circulate, a single mechanism underlying multiple diseases.
In the central nervous system, ABCA1 is the primary lipidator of ApoE. In APOE4 carriers, the ApoE4 protein interacts poorly with ABCA1, producing poorly lipidated particles that impair cellular cholesterol balance and amyloid-β clearance. CS6253 is designed to correct this specific lipid deficit upstream.
Derived from the carboxyl terminus of ApoE, CS6253 stabilizes and enhances ABCA1 function, generating nascent HDL, restoring ApoE lipidation and reactivating lipid transport. CS6253 is the first ABCA1 agonist to complete Phase 1 clinical development.
In a humanized APOE4 Drosophila model, an ABCA1 agonist peptide fully restored the protective glial lipid-droplet formation that APOE4 blocks. In human APOE4 target-replacement mice, CS6253 prevented cognitive decline, reduced amyloid-β and tau hyperphosphorylation, and preserved synaptic density. In non-human primates, CS6253 demonstrated rapid small HDL formation and amyloid-β42/40 mobilization.
Phase 1 human trials showed CS6253 to be well tolerated, with linear pharmacokinetics supporting weekly subcutaneous dosing. Within minutes of intravenous dosing, CS6253 induced the formation of functional nascent HDL particles, providing evidence of ABCA1 target engagement.
ApoE Structural Transition & Maturation. ApoE undergoes a fundamental shape change as it acquires lipids, shifting from an unstable, folded protein into a fully functional, particle-bound structure:
By accelerating ABCA1-mediated lipid transfer, CS6253 is designed to shift ApoE out of this vulnerable, lipid-poor state and into stable, lipid-rich particles that support healthy lipid transport and cellular clearance.
NCT05965414 was the first-ever human trial of a direct ABCA1 agonist. It was a double-blind, placebo-controlled Phase 1 study in 66 healthy adults, the majority aged 50 and older, with and without APOE4, testing both single and repeated dosing by intravenous (IV) and subcutaneous (SC) administration.
| Program | Candidate | Target | Indication | Status |
|---|---|---|---|---|
| CNS | CS6253 |
ABCA1 Agonist | APOE4-associated dementia | Phase 2A Ready |
| PNS | CS6253 |
ABCA1 Agonist | Orphan peripheral nerve disease | Phase 2A Ready |
| Discovery | Undisclosed |
ABCA1 Agonist | Undisclosed | Preclinical |
APOE4 homozygotes with mild cognitive impairment due to Alzheimer's disease (MCI-Alzheimer's Disease), the highest-risk and most underserved patient group.
Cerebrospinal fluid (CSF) and plasma biomarker dynamics; safety and tolerability.
Chemistry, Manufacturing & Controls activities currently ongoing in preparation for Phase 2A.
The Phase 2A study is fully funded by the NIH-NIA. Dosing is scheduled to begin in 2027.
Dr. Johansson is a cardiovascular scientist and serial biotech entrepreneur who has founded or co-led companies raising more than $500M in private and public markets, including taking three companies to public listing on North-American exchanges. He practiced cardiovascular medicine for 18 years and has led Phase 1 through Phase 3 development programs across cardiometabolic and CNS disease.
He was responsible for the NDA and FDA registration of Omacor/Lovaza, the first pharmaceutical-grade omega-3 product and a major cardiovascular therapy. Dr. Johansson has authored more than 75 peer-reviewed publications, generated more than 15 patents, and conceived the ABCA1 agonist strategy for Alzheimer's disease. He has led Artery Therapeutics since its founding.
Co-founder since inception. Jonas leads investor relations, business development, and financial management, translating scientific progress into partnering strategy with disciplined capital allocation.
Directs overall operations, project management, and vendor oversight. He is also responsible for Artery's grants compliance, enabling Artery to effectively scale operational capacity and meet key milestones.
Previously CFO and Chief Executive of SBC Pacific Bell subsidiaries. 30+ years of senior executive experience in finance, operations, and corporate governance. Has provided strategic guidance since inception.
World-class expertise spanning APOE4 biology, CNS lipid metabolism, Alzheimer's biomarkers, and clinical trial design.
Joy Chambers-Grundy Professor of Brain Science and director of the Chambers-Grundy Center for Transformative Neuroscience at UNLV. Author of over 1,000 peer-reviewed papers and 43 books, he leads the Clinical Trials Observatory tracking the global AD pipeline. Guides Phase 2A protocol design and FDA engagement.
The world's foremost authority on ApoE4 as a driver of Alzheimer's pathology. Over five decades at Tel Aviv University he built the foundational science explaining how ApoE4 causes neurodegeneration. He independently validated CS6253 in APOE4 target-replacement mouse models. He is profoundly missed.
Founding figure in clinical lipoprotein research and cardiovascular pharmacology at Linköping University and the Stockholm Heart Center. Decades of statin and HDL trial leadership. Bridges CS6253's CNS and cardiovascular programs through HDL biology and ApoE metabolism expertise.
One of the world's most cited Alzheimer's researchers and former Chair of the Department of Neurobiology, Care Sciences and Society at Karolinska, where he founded the Center for Alzheimer Research. A central figure in European AD drug development. Guides clinical endpoints and regulatory strategy for Phase 2A.
Leading researcher at the intersection of brain lipid metabolism, ApoE4 biology, and Alzheimer's risk at the Keck School of Medicine, USC. Senior author on the cynomolgus primate study of CS6253 and on work showing how ApoE4 alters ABCA1 trafficking in astrocytes. Provides critical context for the mechanism and its endpoints.
Global leader in fluid biomarkers for neurodegeneration at the University of Gothenburg. His CSF and plasma assays for amyloid-β, tau, NfL, and GFAP are used in virtually every major AD trial worldwide. Guides Phase 2A biomarker strategy and interpretation of CSF and plasma endpoints.
Twenty-one peer-reviewed publications spanning foundational peptide chemistry, CNS and cardiovascular pharmacology, primate studies, and first-in-human clinical trials, in Alzheimer's & Dementia, Nature Communications, PNAS, Journal of Neuroscience, PLoS ONE, and others.
Artery Therapeutics is advancing CS6253 for APOE4-driven Alzheimer's disease, with Phase 1 complete and Phase 2A fully funded. Strategic capital accelerates our trajectory toward late-stage clinical trials.
Accredited investors are invited to request additional program materials or speak directly with management about equity investment opportunities.
This page is for information only. It is not an offer to sell or a solicitation of an offer to buy any security. Any offering would be made only to verified accredited investors through definitive documentation.
Whether you are a potential investor, scientist, physician, or someone personally affected by APOE4-associated dementia, including Alzheimer's disease, we welcome your message.
Artery Therapeutics welcomes collaboration with academic and industry researchers investigating ABCA1 biology, ApoE lipidation, and related lipid transport pathways. Because CS6253 is a proprietary investigational compound not yet approved for use outside our sponsored studies, we ask that investigators contact us before initiating independent research involving CS6253 — so we can provide validated material, share current safety and pharmacology data, and explore opportunities for formal collaboration, including material transfer agreements and co-sponsored research.