Editas Medicine is prioritizing in-vivo gene editing and advancing the clinical development of EDIT-301 for severe sickle cell disease and transfusion-dependent beta thalassemia. The company's strategic shift follows promising initial data from the RUBY Phase 1/2 clinical study of EDIT-301 in sickle cell disease.
EDIT-301 Clinical Progress
Initial data from the RUBY trial demonstrated human proof-of-concept, showing that EDIT-301 could safely drive expression of fetal hemoglobin to clinically meaningful levels and correct anemia in sickle cell disease patients. In the first patient with five months of follow-up, fetal hemoglobin fraction increased to 45.4%, exceeding the 30% threshold where sickle cell patients may have no symptoms. Total hemoglobin increased by more than 4 g/dL to 16.4 g/dL, well within the normal range. 96% F-cells and the Mean Corpuscular fetal hemoglobin increased to 13.8 pg gram per red cells, exceeding 10 pg gram threshold considered clinically meaningful.
Baisong Mei, Chief Medical Officer of Editas Medicine, stated that the data suggests EDIT-301 has the potential to give robust clinical benefit to patients with severe sickle cell disease and has the potential for clinical differentiation in the long-term. The company has completed a safety review of sentinel patients from the RUBY trial and has commenced parallel patient dosing, remaining on track to dose 20 total patients by year-end.
Strategic Shift to In Vivo Gene Editing
Editas Medicine is sharpening its discovery focus to in-vivo administered genome editing medicines. This strategic pillar involves selecting therapeutic targets that will allow their genome managing approach to differentiate maximally from the current standard of care for serious diseases. The goal is to build a robust pipeline of assets that maximize the probability of technical, regulatory, and commercial success.
Gilmore O'Neill, CEO of Editas Medicine, explained that the company is strengthening its discovery engine and technological capabilities by splitting its research division into separate technology and drug discovery groups. The technology group will focus on targeted delivery and enhancing the gene editing toolbox to enable targeted gene repair, while the drug discovery group has begun lead discovery work on in-vivo therapeutic targets in hematopoietic stem cells (HSCs) and other tissues.
Financial Outlook
Editas Medicine's cash, cash equivalents, and marketable securities as of December 31st were $437 million. The company expects these resources to fund operating expenses and capital investments into 2025. This provides ample resources to support continued trials of EDIT-301, as well as advancing research ethics in Hemoglobinopathy and other in-vivo discovery.
EDIT-301 Mechanism of Action
EDIT-301 utilizes a unique mechanism of action that edits the promoter sequence of the gamma-globin genes to disrupt binding of BCL11A suppressor, mimicking the nature mechanism of hereditary persistence of fetal hemoglobin. The editing is done by a high fidelity, highly specific engineered AsCas12a enzyme. In turn, this provides a high sustained level of fetal hemoglobin in a manner that can be independent of every through periodic stress, residing in reduced, sickle, and the vessel occlusive events in sickle cell patients, and resolving anemia and transfusion dependence in beta thalassemia patients.
Future Plans
Editas Medicine plans to provide clinical updates from the EDIT-301 RUBY study in mid-2023 and the end of 2023, which will include longer-term data from the initial two patients that were dosed last year, as well as data from additional patients from the ongoing RUBY trial. In addition, the company plans to dose the first patient in the EDIT-301 EDIT trial for TDT this quarter and provide early data in the EDIT-301 EDITHAL trial for TDT by year-end.
