CAMBRIDGE, Mass.—Anchor Therapeutics has entered into acollaborative agreement with Kyowa Hakko Kirin Co. Ltd. (KHK) to utilizeAnchor's proprietary pepducin technology to advance KHK's internal Gprotein-coupled receptor (GPCR) drug discovery portfolio.
The agreement with KHK takes advantage of Anchor's recentlyadopted business strategy to offer its pepducin technology for use as in-vitroand in-vivo research tools, in addition to developing pepducintherapeutics on its own. Under the agreement, Anchor and KHK will work jointlyto discover and optimize pepducin research tools to further the molecularunderstanding of certain GPCR targets in the KHK portfolio. KHK will assumeresponsibility for application of the research tools against the targets.Anchor will receive an upfront payment, research funding and downstreammilestones.
Pepducins were first developed at the Tufts Medical Centerlaboratories. They utilize lipidated fragments of intracellular GPCR loops tomodulate GPCR action in targeted cell-signaling pathways. Anchor licensed itsfoundational intellectual property from Tufts Medical Center and commencedoperations in early 2008 to advance pepducin therapeutics and research tools,notes Dr. Thomas J. McMurry, senior vice president of R&D and interimpresident of Anchor.
"Our novel pepducin lipopeptides are designed toallosterically modulate internal cell signaling via specific interactions withintracellular GPCR domains," he says. "We are exploiting the power of thisunique mechanism to develop research tools to help unlock GPCR pharmacology aswell as to discover new therapeutics."
The company's semivirtual operations are based in Cambridge,Mass., and comprise "a core scientific staff of four and a network ofconsultants and CRO partners," McMurry states. He adds that the company has noplan to recruit a full-time president.
"The licensing of pepducin technology is a fundamentalcomponent of our business strategy, and we are actively pursuing othercollaborations with pharmaceutical and biotechnology companies and researchinstitutions," he says.
Pepducins are novel, allosteric modulators for GPCR targets,especially those intractable to current approaches. They are composed of ashort peptide derived from a GPCR intracellular loop linked to a lipid moiety.This structure allows pepducins to anchor in the cell membrane and target theGPCR protein via a unique intracellular allosteric mechanism.
"Drugs can interact with a GPCR target receptor at differentlocations," McMurry observes. "Traditionally, most drugs have been designed tointeract with the same binding site as used by the receptor's naturalactivating ligand. One relevant example is Novo Nordisk's Victoza—an approvedlipopeptide drug that binds the orthosteric GLP-1 binding site."
Allosteric drugs interact with the targeted receptor at adifferent binding site than that used by the natural ligand, he explains.Because allosteric compounds do not directly compete with the endogenous ligandfor the same binding site, a "Negative Allosteric Modulator" (NAM) can blocksignaling even in the presence of high concentrations of the natural ligand. Incase of aberrant natural signaling, the NAM approach provides a safe andeffective mechanism to suppress the undesired signaling. Conversely, intherapeutic situations where one would like to gently enhance the positiveactivity of an endogenous ligand, a "Positive Allosteric Modulator" is the pharmacologyof choice. This mechanism enhances the activity of the natural ligand withoutoverstimulation of the receptor that might lead to undesired side effects.Anchor has also demonstrated that its pepducin modulators are capable of biasedsignaling—the ability to selectively influence certain downstream signalingpathways but not others. Biased ligands represent an additional excitingopportunity for generating therapeutics with improved efficacy and safetyprofiles, McMurry adds.
The Anchor pepducin technology platform represents "anentirely new paradigm for modulating GPCR signal transduction, potentiallyproviding a novel approach to studying the in-vitro and in-vivo biology of GPCRs and screening for small-molecule modulators of thesetargets," McMurry claims. He says he believes the technology may transform thescope of GPCR therapeutics to treat a much wider range of serious illnesses,including inflammatory and metabolic diseases.
KHK is a leading biopharmaceutical company in Japan. It hada new start in October 2008 following the merger of Kyowa Hakko Kogyo Co. Ltd.and Kirin Pharma Company Ltd., with the aim of becoming a global specialtypharmaceutical company that creates innovative new drugs in its core businessareas of oncology, nephrology and immunology.