Forty Seven Inc., a developer of immuno-oncology treatments spun out of Stanford University, has launched a pair of collaborations with pharma giants Merck KGaA and Genentech, a member of the Roche Group, to develop its lead candidate as part of combination therapies for a trio of cancer indications.
The collaborations—whose values were not disclosed—are both intended to advance Hu5F9-G4, a monoclonal antibody targeting the CD47 receptor, which Forty Seven describes as a “don't eat me” signal that cancer cells commandeer to avoid being ingested by macrophages.
Forty Seven said it will partner with Merck KGaA to conduct a Phase Ib clinical trial combining Hu5F9-G4 with the Merck/Pfizer-partnered marketed checkpoint inhibitor Bavencio® (avelumab) in patients with ovarian cancer.
Bavencio is an anti-programmed death ligand-1 (PD-L1) antibody that won FDA approval in March 2017 for its first indication, treating metastatic Merkel cell carcinoma (mMCC) in adults and children aged 12 years and over. Two months later, Bavencio won its second FDA authorization as a treatment for patients with locally advanced or metastatic urothelial carcinoma (UC) who have disease progression during or following platinum-containing chemotherapy, or have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.
Forty Seven reasons that just as binding of avelumab to PD-L1 takes the brakes off T cells, binding of Hu5F9-G4 to CD47 will similarly take the brakes off macrophages. PD-L1 and CD47 are immunosuppressant molecules overexpressed on cancer cells that send inhibitory signals to T cells and macrophages, respectively.
“Not all patients however, respond to checkpoint inhibitors, so additional scientifically driven combination approaches are required,” Forty Seven CMO Chris Takimoto, M.D., Ph.D., said in a statement.
Added Alise Reicin, M.D., head of global clinical development at the biopharma business of Merck KGaA: “This collaboration enhances our strategic approach to novel immuno-oncology combinations in this disease setting. We are hopeful that through these efforts we will discover viable options to help patients with this hard-to-treat cancer.”
Dr. Reicin added that Merck KGaA—which operates as EMD Serono in the U.S. and Canada—has two ongoing registrational studies exploring avelumab’s potential role against ovarian cancer, both as a monotherapy and in combinations.
Merck KGaA and Pfizer are developing Bavencio through an up-to-$2.85 billion strategic alliance launched in November 2014.
The Merck KGaA/Forty Seven collaboration will add to the five ongoing clinical studies of Hu5F9-G4, which is being assessed in patients with solid tumors, acute myeloid leukemia, non-Hodgkin's lymphoma, and colorectal carcinoma.
In several preclinical studies, Forty Seven said, Hu5F9-G4 had been shown to facilitate phagocytosis and elimination of cancer cells from multiple human tumor types as a monotherapy.
When used in combination therapy, the company added, Hu5F9-G4 engaged macrophages as effector cells to enhance the efficacy of cancer-specific antibodies like rituximab and cetuximab via antibody-dependent cellular phagocytosis (ADCP).
Combination with Tecentriq
Separately, Forty Seven said it will team up with Genentech to sponsor two clinical trials combining Hu5F9-G4 with the Roche subsidiary’s PD-L1 antibody Tecentriq® (atezolizumab) in patients with acute myeloid leukemia (AML) and with urothelial (bladder) cancer.
“There is a large unmet medical need for new therapies for AML and bladder cancer patients, particularly those who are elderly or have compromised organ function and are not able to withstand the side-effects of chemotherapy,” stated Forty Seven’s chief business officer Craig Gibbs, Ph.D., MBA. “We are excited to evaluate these novel combinations in collaboration with a global leader in oncology.”
Tecentriq is an anti-PD-L1 monoclonal antibody granted accelerated approval by the FDA in April 2017 for patients with locally advanced or metastatic urothelial cancer who are not eligible for cisplatin chemotherapy, or have disease progression during or following any platinum-containing chemotherapy, or within 12 months of neoadjuvant or adjuvant chemotherapy.
That approval was the agency’s second for Tecentriq. In October 2016, the FDA authorized the treatment for metastatic non-small-cell lung cancer (NSCLC) in patients demonstrating disease progression during or following platinum-containing chemotherapy and whose disease progressed on an appropriate FDA-approved targeted therapy if their tumor had epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) gene abnormalities.
Forty Seven was established in 2015 by a team of cancer biology and immunology researchers at Stanford University who partnered with experts in drug development, production, and distribution, as well as venture capital firms to launch the company.
In October 2017, Forty Seven closed on a $75 million Series B financing, saying it would use the proceeds to support continued development of Hu5F9-G4. New investor Wellington Management Company led the financing, which featured participation from GV (Google Ventures) and three other existing investors—Clarus, Lightspeed Venture Partners, and Sutter Hill Ventures.
Last month, Forty Seven won a $5 million grant from the California Institute for Regenerative Medicine toward an ongoing clinical trial assessing Hu5F9-G4 alone and in combination with azacytidine in patients with AML and myelodysplastic syndrome (MDS).