Intellia ending work with Regeneron on gene therapy for hemophilia B

Regeneron to continue with gene-editing treatment, with Phase 1 trial planned

Lindsey Shapiro, PhD avatar

by Lindsey Shapiro, PhD |

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Note: This story was updated March 28, 2024, to clarify the gene therapy delivers the mRNA of the Cas9 enzyme.

Intellia Therapeutics is ending its collaborative agreement with Regeneron, which had the two companies working together in developing hemophilia B gene-editing therapies, according to a securities and exchange commission (SEC) filing.

Intellia’s action, which takes effect in six months, follows a recent U.S. Food and Drug Administration (FDA) decision allowing the companies to launch a first clinical trial of a gene-editing treatment candidate for the disease.

Regeneron with continue developing the hemophilia B program on its own. The two companies’ collaborations in programs for other indications, including hemophilia A and transthyretin amyloidosis, remain active.

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Hemophilia B gene therapy in development uses CRISPR/Cas9 technology

This partnership began in 2016, when the companies entered into an agreement to develop, license, and commercialize gene-editing therapies. Its timeframe for collaborative work was further expanded in 2020.

A codevelopment and cofunding agreement for the hemophilia B program stipulated that Intellia would share 35% of the costs, and be eligible for the same proportion of profits later realized from treatment candidates.

While this will no longer be the case, the original 2016 agreement still holds, the SEC filing noted. Intellia will continue to offer support to Regeneron as needed, and it will be eligible to receive milestone payments and royalties related to the development program.

In most cases, hemophilia is caused by genetic mutations that affect certain proteins important for blood clotting, leaving patients more susceptible to spontaneous or uncontrolled bleeding episodes.

Hemophilia B is specifically caused by mutations in the F9 gene, which encodes a clotting protein called factor IX (FIX).

Intellia and Regeneron developed a gene therapy for hemophilia B patients that uses CRISPR/Cas9 gene-editing technology to insert a healthy copy of the F9 gene into cells.

Briefly, the CRISPR/Cas9 system uses an enzyme called Cas9 to make a cut in a specific part of a gene’s DNA sequence, activating a cell’s natural DNA repair mechanisms. Those mechanisms then can be leveraged to add, remove, or edit parts of the gene. A genetic template for producing the Cas9 enzyme, called messenger RNA, is delivered to the body along with a short piece of genetic material called a guide RNA that directs the enzyme to the exact part of the gene where editing is to take place.

FDA agreed to opening an initial clinical trial of a therapy, possibly this year

These gene-editing components are designed to be packaged into a small nanoparticle carrier, which is infused directly into the bloodstream to deliver the F9 gene to a patient’s cells. The idea is that once a functional F9 gene copy is present in a person’s body, it will be able to make its own FIX protein continuously. A single treatment will offer lifelong control of bleeds.

Preclinical research has shown that this approach led to sustained FIX activity in mice and non-human primates.

A planned Phase 1 clinical trial of the candidate therapy, when announced late last month, was slated to begin by mid-year.

The companies are taking a similar approach in designing a gene-editing therapy for hemophilia A, where mutations in the F8 gene lead to the lack of, or problems with, a clotting protein called factor VIII.