NIA Small Business Showcase: Artery Therapeutics, Inc.

Alzheimer’s disease (AD) affects more than 6 million people in the United States. Apolipoprotein E (APOE) transports cholesterol in the brain, and its genetic variants can increase a person’s likelihood of developing AD. APOE4 (as opposed to APOE3 or APOE2) is a genetic risk factor for developing Alzheimer’s that is found in 65% of all AD patients. Inheriting APOE4 from one parent increases the risk of AD threefold; inheriting it from both parents means a 15-fold increase. There are currently no treatments for APOE4-driven AD, so understanding causality of APOE4-associated dementia presents an opportunity to address an unmet medical need.

Artery Therapeutics is developing CS6253, a new first-in-class chemical entity that could address the lack of treatments for APOE4-driven AD. It is an ABCA1-stabilizing molecule with a novel mechanism of action that has been shown to correct the cholesterol transport that is impaired in APOE4-driven AD. CS6253 addresses the medical need in the homozygous APOE4 patient population, which currently has no good treatment options, and could possibly benefit other AD populations. In human studies, CS6253 has shown favorable safety and pharmacokinetics with long plasma, half-life and, in addition, prototypical lipid changes and signals of amyloid-clearance to cerebrospinal fluid (CSF) and plasma. In animal studies, it has shown potential as a therapeutic for APOE4-associated dementia. In a recent clinical trial, CS6253 showed favorable safety, tolerance, and pharmacokinetics: bioavailability of subcutaneous (SC) injection was high compared to intravenous (IV) injection in 10 subjects, and no local side effects were seen. That indicates a high potential for convenient, once-weekly SC self-administration of CS6253. This entity is made up of natural amino acids and easy to produce, which will ensure consistent manufacturing.

AD affects 1 out of 9 people in this country older than age 65, and two-thirds of those people have APOE4-driven AD. In the United States alone, the cost of caring for people with Alzheimer’s and other dementias is estimated to reach more than $350 billion in 2025, and by 2050, to more than $1.1 trillion. Current AD therapies reduce disease progression by approximately 25%, but can have the side effect of brain swelling/amyloid-related imaging abnormalities (ARIA) — particularly in the homozygous APOE4 carriers. In the clinical trial, there was no increase in treatment-emergent adverse events (TEAEs) or safety chemistry out of range, compared with a placebo; additionally, a single CS6253 dose increased amyloid in CSF, which suggests brain clearance. CS6253 has the potential to be a safe, long-lasting, and easy-to-administer therapeutic for APOE4-driven AD.

Company Milestones

Scientific and Clinical

2010-2013: ABCA1 peptide discovery to lead optimization (including CS6253)
2013-2019: Lead selection, including pharmacology studies in central nervous system (CNS) mouse models
April 2022: Cleared investigational new drug application (IND) with U.S. Food and Drug Administration (FDA)
October 2023: Approved clinical trial application in European Union (EU)
November 2023: Phase 1 — First human dosed with CS6253, followed by single ascending dose
April 2024-July 2024: Phase 1 — Multiple ascending dose
July 2024: Phase 1 — Bioequivalence study with subcutaneous injection
July 2024: Phase 1 — End of study/final patient visit
2024: Phase 1 — Ongoing pharmacodynamics assessment
2025: Planning for chronic toxicology studies and Phase 2a in APOE4 — mild cognitive impairment (MCI)/AD patients

Business

May 2019: Award of NIH grant for IND-enabling program
September 2021: Award of NIH grant for Phase 1 single ascending dose (SAD)
December 2021: Pre-Series A financing of $1.5+ million
July 2022: Alzheimer’s Association — Part the Cloud, funding Phase 1 multiple ascending dose (MAD)
2025: Intention to raise Series A funding of $40 million

Financial Overview

ATI has raised $52 million in funding from friends and family investments, income, grants, pharma-company collaborations, and transactions. The company is seeking $40 million in funding to complete an adaptive Phase 2-3 cognition trial, which will lay the groundwork for a subsequent Phase 3 study. Getting FDA approval and registration will require an additional $200 million, according to the company’s projections.

Intellectual Property (IP)

ATI has licensed IP from the Lawrence Berkeley National Laboratory (LBNL), the University of California, and the U.S. Department of Energy (DOE), which comprise a total of five patent cases: four issued and one pending prosecution. There are now 17 national, international, and divisional patents in all, each of which includes the composition of matter. ATI takes an active role in patent writing and patent prosecution, and is filing additional patents as needed.

Product Development and Regulatory Strategy

ATI’s interaction with the FDA Office of Neuroscience — Division of Neurology during pre-IND and IND filings has provided consensus for key aspects of the development program. Because of the unique potential to address the absolute unmet medical need with ABCA1 agonist CS6253 ATI has flagged CS6253 for breakthrough designation.

Commercialization Strategy

The management group includes a network of experts who have the knowledge and experience to build the company and develop medical therapeutics, from concept to proof of concept to, if required, registration. These exceptional advisors are experts in neurology, AD, and vascular-metabolic disease, and they have performed successful AD trials worldwide. With the completion of the Phase 1 SAD-MAD bioequivalence study, ATI is now exploring the optimal path to Phase 2 and 3 studies, registration, and commercialization.

Company Details

Artery Therapeutics
San Ramon, California

Industry: Biotechnology — Therapeutics — Drug Development

Management Team:

Jan O. Johansson, M.D., Ph.D., Founder and Chief Executive Officer
Johannes Johansson, B.A., PMP, Co-Founder and Chief Operating Officer
Jonas Johansson, B.A., Co-Founder and Chief Financial Officer

Point of Contact:
Jonas Johansson
info@arterytx.com
415-669-4821

SBIR