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Pfizer, Karo Bio go nuclear
STOCKHOLM— In an effort to deal yet another blow against autoimmune diseases, Swedish pharmaceutical company Karo Bio AB and Pfizer Inc. have entered into a research collaboration agreement for the discovery and development of novel small-molecule RORgamma modulators for the treatment of autoimmune diseases.
Per the terms of the agreement, Pfizer will be responsible for covering research costs and will also have the exclusive right to market any products that emerge from the collaboration. Karo Bio will be eligible for up to $217 million in upfront and milestone payments as well as potential royalty fees.
"We are delighted to collaborate on RORgamma with Pfizer and with the agreement in total," Per Bengtsson, president and CEO of Karo Bio, said in a press release. "This partnership secures a pole position within this new and rapidly evolving area of autoimmune diseases. It also confirms the commercial value of Karo Bio's leading position in the nuclear receptor drug development field."
Nuclear receptors, proteins located inside cells to which hormones naturally bind, are responsible for regulating key body functions. As Karo Bio notes on its site, "to date, 48 different nuclear receptors have been identified that are assumed to be of relevance for humans. Around 10 percent of today's medicines act through nuclear receptors."
These receptors serve as switches for gene transcription within cells, and "one specific hormone-nuclear receptor complex may have different effects in different tissues." By targeting nuclear receptors, researchers can develop therapies that affect gene expression, and some of the functions nuclear receptors regulate affect diseases such as inflammation, osteoporosis, diabetes, obesity, dyslipidemia and even the growth of some cancers.
RORgamma is a nuclear hormone receptor with potential for the treatment of autoimmune diseases such as multiple sclerosis, rheumatoid arthritis and psoriasis since it directly affects the production and secretion of IL-17, a cytokine known to be a chief offender in inflammation. Karo Bio's first RORgamma project began in 2010, and the company has since then discovered novel, potent and specific RORgamma modulators.
"The central role of RORgt in Th17 cell differentiation, coupled with the increasing clinical validation for the importance of IL-17 and other Th17-derived cytokines in autoimmune diseases, makes RORgt a compelling target," Jose-Carlos Gutierrez-Ramos, senior vice president of Biotherapeutics, Worldwide Research and Development at Pfizer, said in a press release. "Combining Karo Bio's deep expertise in nuclear hormone receptors with the world-class chemistry and cytokine immunology expertise of Pfizer has the potential to accelerate our drug discovery effort in this competitive area."
Bengtsson says that autoimmune diseases represent a growing field of interest for Karo Bio, adding that the company is also working on estrogen-beta agonists "that may have a very interesting role in multiple sclerosis."
"We gradually build up knowledge within certain therapeutic fields defined by projects sprung out from our core competence," says Bengtsson. "We are experts in developing promising drugs that target any of the 48 human nuclear receptors. This includes determining the 3D structure of a ligand- receptor complex, testing, designing, synthesizing lead and candidate drugs and pursuing them through preclinical development.
"If promises hold up, this will be a significant market," Bengtsson says of the modulators. "It has the potential to become first-line treatment for many or most autoimmune diseases."
This collaboration is not the first time the two companies have worked together. Karo Bio and Wyeth LCC, which was acquired by Pfizer in October 2009, initiated a collaboration in 2001. The collaboration targeted development candidates to treat inflammatory diseases and focused on the liver X receptor as a target receptor. As of Sept. 1, 2009, Wyeth took on all research and development activities under the collaboration, though, as noted by Per Olof Wallström, president and CEO of Karo Bio at the time, "the collaboration, research and license agreement between the companies shall remain in effect."