Editas shifts to in vivo sickle cell therapy

Editas Medicine has decided to shift its focus from ex vivo gene therapies for sickle cell disease and beta thalassemia to developing an in vivo treatment for these conditions. The company announced that it plans to either partner or out-license its leading clinical program, reni-cel. This move represents a significant change in strategy for the gene editing company, which aims to develop an in vivo treatment that has shown promising initial results in mice.

During a recent analyst call, Editas CEO Gilmore O’Neill mentioned that the company is not yet ready to announce a timeline for beginning human trials with the in vivo therapy. So far, no in vivo gene editing treatments for sickle cell disease or beta thalassemia have been tested in clinical trials. CFO Erick Lucera highlighted several financial advantages of in vivo treatments compared to ex vivo autologous cell therapies, including larger market potential, lower costs of goods, and reduced clinical trial expenses.

This strategic pivot comes at a time when other companies that have brought sickle cell gene therapies to market, which involve extracting and reinfusing a patient's blood stem cells, have experienced slow commercial uptake. The broader cell and gene therapy field has also seen diminished interest from investors and pharmaceutical companies. For instance, bluebird bio, which focuses exclusively on gene therapies, has had to renegotiate loans, lay off employees, and cut costs in recent months. Vertex and bluebird bio both acknowledge that commercial launches will take time.

Editas would have faced tough competition as the third player in the market with reni-cel, which modifies blood stem cells to produce fetal hemoglobin and then infuses them back into the patient. Beam Therapeutics is also developing a base-edited ex vivo sickle cell gene therapy. Stifel analyst Dae Gon Ha noted that investors were increasingly skeptical about reni-cel’s commercial prospects.

As a result of this announcement, Editas' shares dropped about 8%. The company's shift to in vivo gene editing marks another significant change since its founding in 2013, when it aimed to develop new therapies based on CRISPR technology. Previously, Editas was working on a treatment for a rare inherited form of blindness and cancer programs. In 2023, the company shifted its focus to ex vivo therapies for sickle cell disease and beta thalassemia, which offered a larger market than the rare form of blindness.

The new in vivo approach involves delivering a gene editor using a fatty acid envelope to target cells outside the liver, inducing fetal hemoglobin expression in blood stem cells directly within the body. Typically, these fatty acid particles, known as lipid nanoparticles (LNPs), tend to accumulate in the liver, making delivery beyond this organ a significant challenge for genetic medicine developers.

In preclinical studies involving mice engrafted with human blood stem cells, Editas reported a 29% editing efficiency with a single dose of therapy. Additionally, about 20% of fetal hemoglobin-expressing red blood cells were observed in the host one month after treatment. Several other companies, including Tessera Therapeutics, are also working on developing in vivo gene editing treatments for sickle cell disease.

Moreover, Editas recently signed a non-exclusive license agreement with Genevant Sciences for LNP technology targeting two undisclosed areas. This deal could potentially provide Genevant up to $238 million in upfront and milestone payments, along with royalties. However, Editas did not disclose the specific upfront payment details of the agreement.

This strategic shift highlights Editas Medicine's commitment to exploring new avenues in gene therapy to address sickle cell disease and beta thalassemia, leveraging its expertise in CRISPR technology and innovative delivery mechanisms.