LA JOLLA, Calif.—In late 2016, Bird Rock Bio Inc., a clinical-stage biopharmaceutical company, reported that it had received approval to start a two-part Phase 1 clinical trial for namacizumab, a therapeutic antibody to the cannabinoid 1 (CB1) receptor. The company has also entered into an agreement with GE Healthcare for process development, formulation and manufacture of namacizumab in preparation for Phase 2 studies, as well as a collaboration and option agreement with Janssen Pharmaceuticals Inc. to fund the Phase 1 trial, process development and Phase 2 preparation.
Namacizumab, a negative allosteric modulating antibody (NAMA) that stabilizes the CB1 receptor in an inactive conformation, is being developed to treat large unmet medical needs in fibrotic and metabolic disease, including non-alcoholic steatohepatitis (NASH) and diabetic nephropathy.
Paul Grayson, CEO of Bird Rock Bio, expects that namacizumab, which he described as a “very unusual antibody” will demonstrate safety, tolerability and biomarker efficacy data in the clinical trial to support differentiated clinical potential in fibrotic and metabolic disease, including NASH, the largest contributor to liver failure and the need for liver transplant. As a first-in-class and only-in-class NAMA that stabilizes the inactive conformation of CB1, namacizumab has the potential to build on the significant mechanistic and clinical data on the modulation of CB1 in disease, according to Grayson.
Namacizumab’s ability to target fibrotic, inflammatory and metabolic cell activities hold potential to treat a broad range of diseases. The double-blind, placebo-controlled, dose-ranging Phase 1 clinical trial will include a single ascending dose (SAD) study in healthy volunteers and a multiple ascending dose (MAD) study in non-alcoholic fatty liver disease patients, assessing outcomes of key biomarkers.
"Namacizumab binds to the CB1 receptor, and binds to it very selectively,” Grayson explained. “In addition, namacizumab has a very specific function—when it binds to the CB1 receptor, it stabilizes the protein target in a non-active conformation. This negative allosteric activity, independent of ligand binding and very different than classic receptor antagonism, is important for a number of therapeutic reasons."
Founded in 2008, Bird Rock Bio was pursuing large molecules, according to Grayson. By 2011, the company had pivoted to its iCAPS platform, a proprietary G-protein-coupled receptor (GPCR) allosteric antibody drug discovery platform that can isolate and present functional GPCRs in the correct confirmation to identify selective monoclonal antibody allosteric modulators. While GPCRs are a valuable class of drug targets, they have been largely unexplored in antibody discovery because of the difficulty in isolating them in the correct conformation and functional form, Grayson said. Namacizumab was discovered internally through Bird Rock Bio’s iCAPS platform.
According to the terms of Bird Rock Bio’s collaboration and option agreement, Janssen has an exclusive option to acquire Bird Rock following the Phase 1 data readout. According to Grayson, “Janssen and Johnson & Johnson in general have had the longest history of large-molecule therapeutics, especially biologics. We believe that Janssen’s expertise in the development, manufacture and commercialization of biologic therapeutics will allow Bird Rock to accelerate the development of namacizumab.”
Grayson added, “Similarly, the process of manufacturing an antibody should be simple, but it’s really very complex. GE Healthcare has done a great job with state-of-the-art systems. As we prepare for future phases of development, we will be working with GE on downstream process development, subcutaneous formulation and clinical scale manufacturing. While we are conducting the SAD and MAD clinical trial, we will also be completing supportive chronic toxicology and bioequivalence studies to be fully prepared for the next phases of clinical development.”
Grayson believes that namacizumab has great commercial potential, saying, “There is a substantial medical need for fibrotic and metabolic diseases, so we’re very optimistic. We also have great partners in the process and commercialization programs, which will take us to the next phase of the company.”
In more recent news, Bird Rock Bio announced early this year that it had received approval for the initiation of a 200-patient, Phase 2 rheumatoid arthritis clinical trial for gerilimzumab, a novel therapeutic antibody to the IL-6 cytokine, to be conducted solely in Brazil. The trial is designed to evaluate three dose regiments—a 20 mg subcutaneous (SC) loading dose followed by a 10 mg maintenance dose after 8 weeks, a 10 mg SC loading dose followed by a 5 mg maintenance dose after 8 weeks and a low 5 mg SC loading dose followed by a 2 mg maintenance dose after 8 weeks, all in combination with methotrexate, compared to methotrexate control.