Candidate Cell Therapy Controls Bleeding in Mouse Model of Hemophilia A

Sigilon Therapeutics’ candidate cell therapy for hemophilia A, called SIG-001, delivers sustained production of factor VIII for over six months and corrects bleeding in a hemophilia A mouse model.

These results were shared at the 2019 American Society of Gene and Cell Therapy (ASGCT) Annual Meeting, in a presentation titled, “Correcting Bleeding Disorders Using Blood Clotting Factors Produced by Shielded Engineered Allogenic Cells” (page 181.)

Currently, the factor-replacement therapies available for hemophilia A require frequent infusions and are unable to prevent generation of inhibitors that reduce their efficacy.

“Current factor-replacement treatments for hemophilia require frequent infusions and still leave patients vulnerable to the harmful effects of therapeutic troughs,” David Moller, MD, chief scientific officer of Sigilon, said in a press release.

Sigilon Therapeutics, along with researchers at the Massachusetts Institute of Technology, developed a potential new therapy for hemophilia A called SIG-001 using Sigilon’s trademarked Shielded Living Therapeutics platform.

SIG-001 consists of human cells modified to incorporate large amounts of synthetic DNA-encoding therapeutic proteins into cells, specifically human FVIII.

Sigilon’s cells are altered to have a shield made of synthetic biomaterial, called Afibromer, that can prevent triggering the immune system of the host.

With this new technology, the cells can be implanted with a reduced risk of potentially damaging immune reactions, such as fibrosis (tissue scarring), while promoting long-term production of therapeutic proteins after a single intervention.

Researchers showed that delivering different doses of SIG-001 to mice in a single intraperitoneal injection (into the abdominal cavity) led to a dose-depend secretion of therapeutic doses of FVIII. The same dose-dependent release of FVIII was seen in a mouse model of hemophilia A, in which SIG-001 controlled bleeding time and blood loss during a bleeding test of the mouse tail. Moreover, the levels of FVIII remained stable for over six months.

Overall, these results show that administering SIG-001 into the abdomen can lead to a sustained production of FVIII, which effectively controls the bleeding in a mouse model of hemophilia A.

“We aim to pursue first clinical studies in patients with hemophilia A, and to develop additional therapeutics using Shielded Living Therapeutics for other serious bleeding disorders,” researchers said.

“These data illustrate the potential of this Shielded Living Therapeutics product to provide consistent, lasting delivery of factor VIII, and they form the basis of our planned regulatory filing for SIG-001 later this year,” Moller said.