Partnering Strategy

Deciphera has built a discovery platform and is investigating drug candidates against high value opportunities across a number of therapeutic areas.  The company has significant capabilities in drug discovery and preclinical development and seeks to strategically partner with pharmaceutical and biotechnology companies as early as the preclinical candidate or IND stage. Deciphera is also open to a discovery collaboration utilizing its Phylomechanics platform to develop lead candidates in targeted kinase areas for development.

Deciphera's discovery engine focuses on small molecule candidates that bind into the kinase switch pocket as opposed to the ATP pocket.

Advantages

Selective or Ensemble Approaches

A distinguishing feature of kinase switch pockets is that each kinase switch has been evolutionarily conserved only to regulate its own conformational shape and biological activity. Thus unlike the classical ATP pocket (which is relatively conserved in all kinases), kinase switch pockets provide unique regions of amino acids amenable to development of highly selective drug candidates.

Deciphera's pipeline contains important examples of inhibitors which have been developed to provide exceptional kinase selectivity:

• p38-alpha kinase
• BRAF kinase
• FLT3 kinase

Alternatively, switch pockets also provide opportunities to hone inhibitors which uniquely inhibit a desired ensemble of kinases not readily accomplished by classical ATP competitive inhibitors

• BCR-ABL multi-targeted inhibitors
• BRAF multi-targeted inhibitors
• AXL multi-targeted inhibitors
• JAK2 multi-targeted inhibitors

Sensitivity to Gatekeeper Mutations

Another distinguishing feature of switch pocket inhibitors is their retained sensitivity toward kinase gatekeeper mutations. The gatekeeper is an amino acid located proximal to the ATP pocket. Many ATP competitive inhibitors of kinases lose potency versus gatekeeper mutations. Mutations at this key amino acid locus occur with a high frequency in the clinical setting because a Single Nucleotide Polymorphism (SNP) change in a single DNA base is sufficient to cause selective pressure mediated drug resistance. Clinical manifestations of gatekeeper mutation drug resistance include:

• T315I BCR-ABL mutation - chronic myelogenous leukemia (resistance to Gleevec, Sprycel, Tasigna)
• T670I KIT mutation - gastrointestinal stromal cancers (resistance to Gleevec)
• T790M HER1 mutation - non-small cell lung cancer; solid tumors (resistance to Tarceva, Iressa)

Deciphera switch pocket inhibitors retain sensitivity to gatekeeper mutations:

• T315I BCR-ABL mutation (DCC-2036 IC50 = 4 nM)
• T529I BRAF mutation (DP-2693 IC50 = 5 nM)
• T529I BRAF mutation (DP-2807 IC50 = 33 nM)

Deciphera Contact

For further information on partnering opportunities, contact:

Diane Thompson, PhD (Primary Contact) or Christine de los Reyes

busdev@deciphera.com

(785) 838-3767

Deciphera Pharmaceuticals, LLC
4950 Research Park Way
Lawrence, KS 66047

785-838-3767 phone
785-838-3747 fax
info@deciphera.com

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