Tessera Therapeutics, a well-funded startup based outside of Boston, announced Friday that it developed a lipid nanoparticle that shuttles a gene editing therapy directly to the bone marrow of mice.
One or two infusions of the treatment corrected enough of their broken hemoglobin genes to be potentially curative.
If the treatment works in people, it could provide a simpler and potentially more affordable alternative to two recently approved therapies for sickle cell disease: Casgevy from CRISPR Therapeutics and Vertex Pharmaceuticals, and Lyfgenia from bluebird bio. Those treatments are medical milestones, but they are also expensive and cumbersome.
Each requires harvesting a patient’s bone marrow cells, editing them in the lab, and giving a patient chemotherapy to make room for the altered cells before they are reinfused. Many scientists believe editing the cells directly inside the body, known as in vivo gene editing, is the only way to make the treatment viable for the roughly six million people with the disease worldwide.
Michael Severino“We are able to deliver to stem cells in the bone marrow, in their native niche, without chemo or toxicity,” Tessera CEO Michael Severino told Endpoints News in an interview. “And we are showing that we can edit those with levels that could be curative in the clinic.”
At the American Society of Gene & Cell Therapy conference this week in Baltimore, the company revealed that a single infusion of its experimental treatment fixed 25% of the broken hemoglobin genes in a mouse model of sickle cell disease. In a second experiment, two injections bumped the editing levels up to 44%.
“The minimum threshold for sickle cell we think is about 20% normal hemoglobin,” Severino said. “We are there with a single dose and well above it with two doses. And we will continue trying to push up as high as possible.”
Increasing competition
Tessera, which was founded in 2018, has raised $580 million from private investors for its gene writing technology. It first disclosed data from several programs at the ASGCT conference last year, focused on editing immune cells and liver cells.
Severino wouldn’t say when Tessera plans to advance its sickle cell therapy into clinical trials.
The startup will face intense competition. CRISPR Therapeutics has a grant from the Bill & Melinda Gates Foundation to develop an in vivo version of Casgevy. Several other companies are in the early stages of working on in vivo programs for blood diseases, including Beam Therapeutics, Editas Medicine, Intellia Therapeutics and Prime Medicine.
Other companies are quietly working on plans to compete in the space, including Shanghai-based YolTech Therapeutics and Boston-based ReNAgade Therapeutics, both of which have told Endpoints in recent interviews that they are developing in vivo CRISPR therapies for sickle cell and beta thalassemia, respectively.
Yuxuan Wu“We can get to a much lower price with the in vivo gene editing,” YolTech CEO Yuxuan Wu said.
Sanofi disclosed updates on its own in vivo sickle cell therapy at the ASGCT conference, revealing that its lipid nanoparticles reached roughly 80% of hematopoietic stem cells in mice. Tessera said in its presentation that its nanoparticles delivered a reporter gene to about 95% of the stem cells in mice and monkeys.
Getting a genetic therapy directly into the bone marrow is fundamentally a delivery challenge, but Severino wouldn’t say exactly how Tessera was able to solve the problem.
“It takes multiple levers,” he said. “We change lipid composition and identity to get to that efficient delivery. There’s no one tool in isolation.”