Orna, Vertex partner on gene-editing therapies for SCD, TDT
Companies will use Orna's LNP delivery system to develop in vivo therapies
Orna Therapeutics is partnering with Vertex Pharmaceuticals to develop gene-editing therapies for people with sickle cell disease (SCD) and transfusion-dependent beta-thalassemia (TDT).
The three-year collaboration will leverage Orna’s proprietary lipid nanoparticle (LNP) delivery system. LNPs are tiny vesicles made up of fatty molecules that can be used to deliver gene editing machinery to a patient’s hematopoietic stem cells, which can give rise to all types of blood cells.
The agreement “validates our industry leading extra-hepatic LNP delivery chemistries and highlights the importance of delivery to enable the next wave of RNA medicines,” Amit Munshi, Orna’s CEO, said in a company press release.
SCD and TDT are diseases that affect hemoglobin, the protein that red blood cells use to carry oxygen throughout the body. SCD is caused by mutations in the HBB gene that lead to the production of a faulty version of hemoglobin, whereas in TDT hemoglobin levels are low or the protein is missing.
In either case, patients may develop anemia, a condition caused by a shortage of red blood cells in the blood, impairing oxygen delivery throughout the body.
In vivo therapies
Vertex, along with CRISPR Therapeutics, has developed a gene-editing therapy called Casgevy (exagamglogene autotemcel), which is approved by the U.S. Food and Drug Administration to treat SCD and TDT. Casgevy was the first approved therapy to employ the CRISPR/Cas9 gene-editing technology.
Casgevy is a so-called ex vivo therapy, meaning gene editing occurs outside the body after stem cells are harvested from the patient. In contrast, Orna’s LNPs are designed to deliver gene-editing components directly to cells within the patient’s body. This approach could enable the development of in vivo therapies, in which gene editing occurs inside the body without the need for harvesting or transplanting cells.
“We are excited to collaborate with [Vertex] to develop in vivo therapies that leverage our proprietary technologies to achieve unprecedented delivery to [hematopoietic stem cells],” Munshi said.
When undergoing treatment with Casgevy, a patient’s hematopoietic stem cells are collected and modified in the lab to produce high levels of fetal hemoglobin, a form of the protein normally produced during fetal development that is more effective at transporting oxygen than the adult form.
After a round of chemotherapy used to destroy faulty stem cells, the modified stem cells are transplanted back to the patient. They are then expected to give rise to new red blood cells that are capable of producing fetal hemoglobin.
Under the terms of the agreement, Orna will receive an upfront payment of $65 million and is eligible to receive up to $635 million according to the achievement of pre-specified research, preclinical, regulatory, and commercial milestones related to developed therapies.
Orna will also be eligible to receive tiered royalties on future net sales of treatments that may result from this collaboration and may receive up to $365 million in additional milestones per product, if Vertex uses its technology for additional indications.
The agreement “has the potential to deliver large-scale impact to patients,” said Ansbert Gadicke, MD, Orna’s chairman and managing partner of MPM BioImpact, a biotechnology investment company.
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