Editas Medicine Plans Human Trial After Gene Therapy Slashed LDL 90% in Primate Study

Key Points

• Editas plans to begin dosing patients this year in a Phase I/II trial of EDIT-401, an in vivo gene-editing therapy initially targeting people with heterozygous familial hypercholesterolemia.
• In nonhuman primates, EDIT-401 was associated with a 90% LDL reduction that persisted through 10 months, along with reductions in Lp(a) and apolipoprotein B. These effects have not yet been demonstrated in humans; the company is targeting an LDL reduction above 60% while prioritizing safety.
• Editas expects to report first-cohort safety and tolerability data in the first quarter and data from later cohorts in the second half of 2027. Its $125 million raise is expected to fund dose escalation and most of the trial’s expansion enrollment, extending its cash runway into the second half of 2028.

Editas Medicine NASDAQ: EDIT expects to dose the first patients this year in a Phase I/II study of its lead gene-editing candidate, EDIT-401, as the company focuses its development strategy on in vivo CRISPR therapies.

Speaking at Guggenheim’s 3rd Annual Healthcare Innovations Conference, President and CEO Gilmore O’Neill said EDIT-401 is designed to increase production of the LDL receptor, which helps remove LDL cholesterol from the blood. In nonhuman primate testing, the treatment was associated with a 90% reduction in LDL cholesterol, alongside comparable reductions in lipoprotein(a), or Lp(a), and apolipoprotein B.

O’Neill said data presented at the American Heart Association meeting showed the effects remained durable through 10 months in the animals. The results have not yet been established in humans.

Clinical Trial and Data Plans

The first part of the Phase I/II study is a dose-escalation trial starting at a nontherapeutic dose to prioritize patient safety, O’Neill said. The protocol calls for at least four cohorts with at least three patients per cohort, with the potential to expand cohorts as needed. A second part will enroll an expansion population after a dose is selected.

Editas is initially targeting patients with heterozygous familial hypercholesterolemia, or HeFH, an inherited condition associated with high cholesterol. O’Neill said the company could also expand to other very high-risk patients with atherosclerotic cardiovascular disease who cannot reach their LDL cholesterol targets with current treatment.

The company plans to report safety and tolerability data from the first cohort in the first quarter. It has guided to top-line data from subsequent cohorts, including LDL cholesterol reductions, efficacy, safety and tolerability, in the second half of 2027.

O’Neill said Editas is aiming for a reduction in LDL cholesterol greater than 60% in humans, while emphasizing that a best-case outcome would also require a good safety and tolerability profile.

Delivery and Safety Considerations

EDIT-401 uses a lipid nanoparticle equipped with GalNAc, which O’Neill said enables entry into liver cells through a receptor other than the LDL receptor. He said preclinical testing showed similar efficacy in normal animals and mice with one impaired copy of the LDL receptor gene.

Asked about potential risks from increased LDL receptor expression, O’Neill pointed to people with naturally occurring genetic variants and very low LDL levels, as well as findings from cardiovascular studies. He also said the company had examined a hypothetical risk involving stress in cells and was reassured in part because LDL receptor is a low-abundance protein.

O’Neill said Editas would monitor a potential diabetes risk. He also said the company had conducted computational, laboratory and biochemical work to assess unintended edits and had found a “very clean profile.”

Funding and Potential Approval Path

Chief Financial Officer Amy Parison said Editas raised $125 million earlier this year, extending its cash runway into the second half of 2028. The funding is expected to support completion of the dose-escalation portion of the trial and most enrollment in the expansion portion, she said.

O’Neill said he believes LDL cholesterol reduction could provide a path to approval, subject to regulatory agreement. He added that prior HeFH approvals have involved safety databases of a few hundred patients, though the Food and Drug Administration’s requirements for a gene-editing therapy remain to be determined.

About Editas Medicine (NASDAQ:EDIT)

Editas Medicine, Inc. is a biotechnology company focused on developing genomic medicines using CRISPR-based gene-editing technologies. The company's research platforms include CRISPR/Cas9 and CRISPR/Cas12a, which are designed to make precise changes to DNA and potentially treat diseases caused by genetic abnormalities. Editas Medicine's lead investigational program is reni-cel, formerly known as EDIT-301. Reni-cel is an ex vivo gene-editing therapy intended to treat sickle cell disease and transfusion-dependent beta thalassemia by modifying a patient's blood-forming stem cells before they are returned to the body.

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