Agios Pharmaceuticals and Celgene agreed, ahead of schedule, to extend the initial period of exclusivity of the companies’ April 2010 agreement from three to four years. During this period Celgene has an exclusive option to drug candidates generated by Agios’ cancer metabolism research platform.
“This alliance has enabled Agios to identify and advance a broad portfolio of cancer metabolism discovery programs,” remarks David Schenkein, M.D., CEO of Agios. Under terms of the new deal, Agios will now receive a $20 million payment. Celgene also has the right to extend the exclusive period still further for additional payments.
Agios received $130 million up front when the original agreement was inked, including an equity investment. Agios leads discovery and early translational development for all programs. Celgene has an exclusive option to license candidates at the end of Phase I and will lead and fund global development and commercialization of some of the licensed programs. Agios retains development and commercialization rights for certain products in the U.S. On all programs, Agios may receive up to $120 million in milestones as well as royalties on sales.
“In the first 18 months of our collaboration, we have made significant progress and have been extremely impressed by the caliber of the team, the science, and the unique research capabilities that Agios brings to this alliance,” comments Thomas Daniel, M.D., president of research for Celgene. “As this early extension decision demonstrates, we are enthusiastic about the potential of Agios’ industry-leading approach targeting cancer metabolism to drive the development of multiple innovative, first-in-class cancer therapies.”
Cancer cell metabolism is marked by major changes in nutrient requirements and usage to ensure cell proliferation and survival. Research in the field has demonstrated that cancer cells become addicted to certain fuel sources and metabolic pathways, Agios explains. In cancer, this metabolic reprogramming is coordinated with proliferative signaling and regulated by the same oncogenes and tumor suppressor genes to ensure efficient proliferation.
Glycolysis, fatty acid metabolism, and autophagy are three pathways shown to play a critical role in cancer metabolism. Identifying and disrupting certain enzymes in these, and perhaps other, metabolic pathways provides an intervention point for discovery and development of cancer therapeutics.
Agios built a platform that integrates cancer biology, metabolomics, biochemistry, and informatics to enable target and biomarker identification. Currently disclosed discovery programs include two cellular targets: M2 form of pyruvate kinase (PKM2) and IDH1/2.
The company has found that while multiple forms of pyruvate kinase can be found in most normal adult tissues, PKM2 (normally found in fetal cells) was the only isoform of pyruvate kinase found in cancerous tissue. Only cells expressing PKM2 enable the unique glucose metabolism seen in cancer cells, thereby allowing these cells to make tumors in vivo, Agios adds. By re-expressing PKM2, cancer cells acquire the ability to grow in vivo, according to the firm.
With regard to IDH1/2, Agios' scientists have established that the mutated gene has novel enzyme activity consistent with an oncogene. This discovery shows that the mutated form of IDH1 produces a metabolite, 2-hydroxyglutarate (2HG), which may contribute to the formation and malignant progression of gliomas as well as other forms of cancer.
Agios believes that its capabilities to interrogate differential cellular metabolism of diseased cells relative to normal cells may also be applicable to other therapeutics areas including autoimmune, inflammatory, and neurological diseases.