Forty Seven and Rocket to Collaborate for Fanconi Anemia

Biotechs Forty Seven and Rocket Pharmaceuticals have entered into a research collaboration to pursue clinical proof-of-concept for Forty Seven’s novel antibody-based conditioning regimen with Rocket’s ex vivo lentiviral vector hematopoietic stem cell gene therapy as a treatment regimen in Fanconi Anemia.  

Fanconi Anemia (FA) is a rare, genetic, pediatric disease that affects patient’s capacity to produce blood cells. It is characterized by bone marrow failure, malformations and cancer predisposition. The primary cause of death among patients with FA is bone marrow failure, which typically occurs during the first decade of life.

Allogeneic hematopoietic stem cell transplantation, when available, corrects the hematologic component of FA, but requires myeloablative conditioning. Hematopoietic stem cells give rise to blood cells. Graft-versus-host disease, a known complication of allogeneic hematopoietic stem cell transplantation, is associated with an increased risk of solid tumors, mainly squamous cell carcinomas of the head and neck region.

Gene therapies for monogenic blood disorders have broad potential. One concern associated with these treatments is the toxicity of pre-therapy conditioning regimens that utilize cytotoxic chemotherapy and/or radiation to destroy existing hematopoietic stem cells and facilitate engraftment of gene-corrected hematopoietic stem cells. Approximately 60-70 percent of patients with FA have a FANC-A gene mutation, which encodes for a protein essential for DNA repair. Mutation in the FANC-A gene leads to chromosomal breakage and increased sensitivity to oxidative and environmental stress, including that caused by current conditioning regimens.

Forty Seven’s all-antibody based conditioning regimen is designed to address the limitations of current pre-treatment conditioning therapies, which are often associated with serious side effects, including severe infection, cognitive impairment, infertility, endocrine dysfunction, secondary malignancies, and organ damage. These toxicities are especially difficult for pediatric patients and are particularly severe for patients with FA, who are more sensitive to the DNA-damaging effects of traditional conditioning agents.

Preliminary data demonstrate that Rocket’s gene therapy RP-L102 may confer efficacy without pre-treatment conditioning.  The combination of RP-L102 with Forty Seven’s all-antibody conditioning regimen may provide patients an alternate treatment option in situations where conditioning may be advantageous.

“This collaboration is in line with our strategy to study our anti-cKIT and anti-CD47, all-antibody conditioning regimen in combination with several different gene therapies, and to establish clinical proof-of-concept in a broad range of transplant indications,” said Mukul Agarwal, vice president of corporate development at Forty Seven.

Under the terms of their agreement, Rocket will provide its ex vivo LVV HSC gene therapy platform and Forty Seven will contribute its innovative antibody-based conditioning regimen for the collaboration.

At the beginning of March, Forty Seven announced that it will be acquired by Gilead Sciences for $4.9 billion.

Photo: Mukul Agarwal, vice president of corporate development at Forty Seven

Author: Rare Daily Staff