Forty Seven, a clinical-stage immuno-oncology company, received a $5 million research grant from the California Institute for Regenerative Medicine (CIRM) to continue the development of its CD47 antibody Hu5F9-G4 in an ongoing clinical trial.
The trial is assessing the immunotherapy alone and in combination with Vidaza (azacytidine) in patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS).
Vidaza, a drug developed by Celgene, is a cancer treatment for people who can’t have high-dose chemotherapy with a stem cell transplant. It is indicated for AML and MDS and works by silencing a protein called DNA methyltransferase.
This action switches on genes that stop the cancer cells from growing and dividing, reducing the number of abnormal blood cells and keeping cell growth in control.
CD47 is an immune modulator molecule that has a “don’t eat me” signal on cancer cells, to avoid phagocytosis (ingestion) by macrophages. By binding to CD47, Hu5F9-G4 takes the brakes off of macrophages, allowing them to ingest cancer cells.
In several preclinical studies, Hu5F9-G4 alone has been shown to facilitate phagocytosis and the elimination of cancer cells from multiple human tumor types.
When used in combination therapy, it engaged macrophages as effector cells to enhance the effectiveness of cancer-specific antibodies. Hu5F9-G4 also showed that it could prime an effective anti-tumor T-cell response by having macrophages activate T-cells against certain tumor proteins. This provided anti-tumor protection that prevented tumor recurrence.
“There is an urgent unmet medical need for new therapies for AML patients, particularly those who have failed previous treatment or cannot tolerate conventional chemotherapy due to age or physical condition,” Mark Chao, MD and PhD, co-founder and vice president of clinical research at Forty Seven, said in a press release.
“We are grateful for this CIRM grant, which will help us accelerate the program,” he said. “In addition, we appreciate the support and advice we have received from the CIRM staff and expert advisors which will increase the likelihood of success.”
Researchers who founded Forty Seven found that CD47 is overexpressed on AML leukemic stem cells in 2009, also finding that higher levels of the protein were linked to increased risk of death.
In 2015, a Phase 1 clinical trial was initiated in the U.K. in AML patients who had relapsed or failed to respond to previous therapies. Today, Hu5F9-G4 is being studied in five ongoing monotherapy Phase 1 and combination therapy Phase 1b/2 trials in patients with solid tumors, leukemia, or lymphoma.
The new grant from CIRM will allow Forty Seven to build on this work and assess Hu5F9-G4 in a second trial in the U.S. and the U.K., including treatment-naïve AML and high-risk MDS patients who are unable to receive other available treatments.
