Pfizer, Karo Bio go nuclear

Collaboration to target RORgamma modulators for autoimmune therapies

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STOCKHOLM— In an effort to deal yet another blow againstautoimmune diseases, Swedish pharmaceutical company Karo Bio AB and Pfizer Inc.have entered into a research collaboration agreement for the discovery anddevelopment of novel small-molecule RORgamma modulators for the treatment ofautoimmune diseases.
Per the terms of the agreement, Pfizer will be responsiblefor covering research costs and will also have the exclusive right to marketany products that emerge from the collaboration. Karo Bio will be eligible forup to $217 million in upfront and milestone payments as well as potentialroyalty fees.
"We are delighted to collaborate on RORgamma with Pfizer andwith the agreement in total," Per Bengtsson, president and CEO of Karo Bio,said in a press release. "This partnership secures a pole position within thisnew and rapidly evolving area of autoimmune diseases. It also confirms thecommercial value of Karo Bio's leading position in the nuclear receptor drugdevelopment field."
Nuclear receptors, proteins located inside cells to whichhormones naturally bind, are responsible for regulating key body functions. AsKaro Bio notes on its site, "to date, 48 different nuclear receptors have beenidentified that are assumed to be of relevance for humans. Around 10 percent oftoday's medicines act through nuclear receptors."
These receptors serve asswitches for gene transcription within cells, and "one specific hormone-nuclearreceptor complex may have different effects in different tissues." By targetingnuclear receptors, researchers can develop therapies that affect geneexpression, and some of the functions nuclear receptors regulate affectdiseases such as inflammation, osteoporosis, diabetes, obesity, dyslipidemiaand even the growth of some cancers.
RORgamma is a nuclear hormone receptor with potential forthe treatment of autoimmune diseases such as multiple sclerosis, rheumatoidarthritis and psoriasis since it directly affects the production and secretionof IL-17, a cytokine known to be a chief offender in inflammation. Karo Bio'sfirst RORgamma project began in 2010, and the company has since then discoverednovel, 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 andother Th17-derived cytokines in autoimmune diseases, makes RORgt a compellingtarget," 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 theworld-class chemistry and cytokine immunology expertise of Pfizer has thepotential to accelerate our drug discovery effort in this competitive area."
Bengtsson says that autoimmune diseases represent a growingfield of interest for Karo Bio, adding that the company is also working onestrogen-beta agonists "that may have a very interesting role in multiplesclerosis."
"We gradually build up knowledge within certain therapeuticfields defined by projects sprung out from our core competence," saysBengtsson. "We are experts in developing promising drugs that target any of the48 human nuclear receptors. This includes determining the 3D structure of aligand-receptor complex, testing, designing, synthesizing lead and candidatedrugs 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-linetreatment for many or most autoimmune diseases."
This collaboration is not the first time the two companieshave worked together. Karo Bio and Wyeth LCC, which was acquired by Pfizer inOctober 2009, initiated a collaboration in 2001. The collaboration targeteddevelopment candidates to treat inflammatory diseases and focused on the liverX receptor as a target receptor. As of Sept. 1, 2009, Wyeth took on allresearch and development activities under the collaboration, though, as notedby Per Olof Wallström, president and CEO of Karo Bio at the time, "thecollaboration, research and license agreement between the companies shallremain in effect."

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