On December 31, 2009, we posted an article on this blog about Agios Pharmaceuticals (Cambridge, MA). Agios is a private research-stage biotech company that is developing a pipeline of oncology drugs based on targeting metabolic pathways in cancer cells. In our article, we focused on Agios’ research on mutations in the metabolic enzyme cytosolic isocitrate dehydrogenase (IDH1) as a causative factor in gliomas and glioblastomas. We also mentioned Agios’ research on pyruvate kinase M2 (PKM2) and aerobic glycolysis in cancer.
On April 15, 2010, it was announced that Agios and Celgene Corporation (Summit, NJ), a public biotechnology company with marketed products, had formed a strategic collaboration in the area of cancer metabolism.
Celgene markets Thalomid (thalidomide), which is approved by the FDA for treatment of multiple myeloma (MM). Thalidomide was notorious for causing birth defects in the late 1950s and early 1960s. However, beginning in the late 1990s, this drug has undergone a rehabilitation, provided that proper precautions are maintained to prevent its use in pregnant women and women who may become pregnant. Celgene has also been developing a class of thalidomide-derivative immunomodulatory drugs (IMiDs), which are designed to have greater efficacy against cancer and lesser toxicity than thalidomide. Of these drugs, Revlimid (lenalidomide) is approved by the FDA for treatment of MM and myelodysplastic syndromes (MDS) (life-threatening diseases of the bone marrow in which abnormally functioning immature hematopoietic cells are made; MDS can progress to acute myeloid leukemia in a substantial percentage of patients.) Celgene is researching additional indications for lenalidomide, and is also developing other IMiDs for various indications in cancer and inflammatory and neurodegenerative diseases.
Celgene’s Vidaza (azacitidine), a nucleoside metabolic inhibitor, is also indicated for the treatment of MDS. Celgene acquired Vidaza via its 2007 acquisition of Pharmion (Boulder, CO), which had developed the drug. Vidaza is an inhibitor of DNA methyltransferases (DNMT), which are enzymes that methylate DNA at specific sites and are important in epigenetic regulation. It was the first approved drug that works via an epigenetic mechanism. (Epigenetics is the study of heritable changes in gene function that do not involve changes in the nucleotide sequence of DNA. Major epigenetic processes include DNA methylation, modification of histones in chromatin, and RNA interference.)
Since Vidaza’s approval in 2004, two histone deacetylase (HDAC) inhibitors, which also modulate epigenetic regulation, have been approved. In late 2009, Celgene acquired the HDAC inhibitor romidepsin (Istodax) [approved in 2009 for the treatment of cutaneous T-cell lymphoma (CTCL)], via its acquisition of Gloucester Pharmaceuticals (Cambridge MA).
Celgene is also developing several other anti-inflammatory drugs and kinase inhibitors.
The goal of the Agios/Celgene collaboration is to discover, develop, and commercialize novel oncology therapeutics based on Agios’ innovative cancer metabolism platform. Celgene sees the potential for early drug development opportunities in Agios’ IDH1 and PKM2 programs, as well as future opportunities based on new targets expected from Agios research programs. Celgene also sees opportunities to harness Agios’ R&D to expand its own pipeline in cancer and other diseases.
Under the terms of the agreement, Agios will receive a $130 million upfront payment, including equity. In return, Celgene will receives an initial period during which it will have the exclusive option to develop any drugs resulting from the Agios cancer metabolism platform. Celgene may also extend this exclusivity period through additional funding. Agios will lead discovery and early development for all cancer metabolism programs. During the period of exclusivity, Celgene will have an exclusive option to license any clinical candidates at the end of Phase I, and will lead and fund global development and commercialization of licensed programs. On each program, Agios may receive up to $120 million in milestones as well as royalties, and may also participate in the development and commercialization of certain products in the United States.
The Celgene collaboration continues Agios’ record of success in fundraising, and in gaining the recognition of the scientific and corporate communities. Despite the generally unfavorable financial environment for young biotech companies, Agios has raised, through alliances and investments, over $163 million in less than two years. This is despite the fact that the company has not one drug in the clinic. Agios expects to have a lead compound in the clinic some time in 2010, however. As is always the case, the validation of Agios’ innovative biology-driven platform awaits the results of human clinical trials and the attainment of regulatory approval.