Editas Medicine Eyes First Human Trial for CRISPR Cholesterol Therapy EDIT-401

Key Points

• Editas Medicine plans to begin human testing of EDIT-401 in Australia this year. The single-infusion CRISPR therapy is designed to increase LDL receptor production in the liver for patients with heterozygous familial hypercholesterolemia who remain above cholesterol targets despite standard treatment.
• In non-human primates, EDIT-401 reduced LDL cholesterol, Lp(a), and apolipoprotein B by an average of 90%, while increasing liver LDL receptor expression at least sixfold. Human safety data are expected in the first quarter of 2027, with initial efficacy results later that year.
• Editas ended the third quarter with $212 million in cash and expects funding into the second half of 2028, allowing it to advance EDIT-401 through both Phase 1 parts and pursue human proof of concept.

Editas Medicine NASDAQ: EDIT is preparing to begin a first-in-human study of EDIT-401, an in vivo CRISPR-edited medicine designed to lower LDL cholesterol in patients with heterozygous familial hypercholesterolemia, Chief Executive Officer Gilmore O’Neill said during a Wells Fargo discussion.

O’Neill said the company is focused entirely on in vivo CRISPR-edited medicines and is prioritizing programs that could produce differentiated efficacy, use capabilities unique to gene editing and offer measurable biomarkers for early clinical proof of concept. The company is also emphasizing manufacturing costs and accessibility, he said, noting that Editas no longer develops cell-based therapies.

EDIT-401 Targets LDL Receptor Expression

EDIT-401 is intended to increase production of the LDL receptor in liver cells, allowing the receptor to remove more LDL cholesterol from the bloodstream. The treatment is designed as a single intravenous infusion.

According to O’Neill, EDIT-401 reduced LDL cholesterol, lipoprotein(a), or Lp(a), and apolipoprotein B by a mean of 90% in non-human primates. The company said it has observed at least a sixfold increase in LDL receptor expression in the livers of non-human primates.

The program was informed by naturally occurring gain-of-function variants observed in Icelandic and French families. Those variants involve deletions in the three-prime untranslated region of the LDLR gene, which can stabilize messenger RNA and support increased LDL receptor protein production. Editas selected guide RNAs intended to create a comparable, but not identical, deletion.

O’Neill said the company’s preclinical findings suggest that editing roughly 15% of alleles could produce substantial cholesterol lowering in non-human primates. Company modeling indicates that most of the editing at that level is monoallelic rather than biallelic, meaning the company may not need to edit the entire hepatocyte population to achieve the desired effect.

Clinical Study Planned in Australia

Editas has submitted documents to human research ethics committees in Australia and is in discussions with those committees, O’Neill said. The company remains on track to dose the first patients this year.

The Phase 1 trial is expected to enroll patients with heterozygous familial hypercholesterolemia who remain above LDL cholesterol targets despite intensive standard-of-care treatment. The study will have two parts:

• Part 1 will use serial dose-escalation cohorts under a 3+3 design, with at least three participants per cohort and the option to enroll three additional patients if warranted.
• The company anticipates at least four cohorts in Part 1.
• Part 2 will expand the selected dose into a broader patient population.

O’Neill said Editas expects to share safety data in the first quarter of 2027 and aims to report top-line data from Part 1 later in 2027. The company expects to enter the U.S. in 2027, following what O’Neill described as constructive pre-IND interactions with the Food and Drug Administration. He said the main limiting factor for U.S. entry is preparing manufacturing documentation.

The company expects a roughly three-to-one dose translation from non-human primates to humans, based on available experience across in vivo editing programs. O’Neill said a 1.5 mg/kg non-human primate dose could translate to an approximate 0.5 mg/kg to 0.6 mg/kg human dose, though clinical results will determine the ultimately effective dose.

Safety and Lp(a) Considerations

Editas is working with Genevant on a lipid nanoparticle, or LNP, delivery system for EDIT-401. O’Neill said the LNP is unique to the program, though most of its components have previously been used in humans. In preclinical toxicology studies, the company observed minimal liver-enzyme increases at therapeutically relevant doses, with transaminase changes comparable with saline control animals. At higher doses, liver-enzyme increases resolved within days and returned to normal range within a week or less, he said.

O’Neill said recent results from Novartis’ HORIZON study do not alter Editas’ strategy. He characterized the Lp(a) reduction associated with EDIT-401 as an additional potential benefit, while emphasizing that the company’s primary objective is substantial LDL cholesterol lowering. He also said genetic and clinical evidence supports lowering LDL cholesterol to very low levels in high-risk patients.

Cash Runway and Pipeline

Chief Financial Officer Amy Parison said Editas ended the third quarter with $212 million in cash and expects its cash runway to extend into the second half of 2028. She said the company plans to direct capital toward advancing EDIT-401 through both parts of its Phase 1 study and establishing proof of concept in humans.

Beyond EDIT-401, O’Neill said Editas has an in vivo hematopoietic stem cell program in discovery and other early-stage gain-of-function editing programs. The company chose to prioritize EDIT-401 last summer, he said, while continuing to optimize its earlier programs. O’Neill added that future liver-targeted programs could potentially leverage the LNP, messenger RNA and manufacturing work developed for EDIT-401.

About Editas Medicine (NASDAQ:EDIT)

Editas Medicine is a clinical-stage biotechnology company focused on translating the power of gene editing into a new class of transformative genomic medicines. Founded in 2013 and headquartered in Cambridge, Massachusetts, the company leverages proprietary CRISPR/Cas9 and CRISPR/Cas12a (Cpf1) platforms to develop therapies aimed at correcting disease-causing genetic mutations. Editas Medicine's research and development efforts span multiple therapeutic areas, including inherited retinal diseases, hemoglobinopathies, and oncology.

The company's pipeline includes EDIT-101, a lead candidate designed to treat Leber congenital amaurosis type 10 (LCA10), which has entered early-stage clinical trials, and EDIT-301, targeting sickle cell disease and β-thalassemia using an ex vivo editing approach.

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