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12:46 PM
 | 
Dec 15, 2016
 |  BC Innovations  |  Targets & Mechanisms

Keeping the Gas off AXL

Aravive has developed an AXL inhibitor with unprecedented affinity

With its development of an AXL decoy able to trap and sequester the native receptor’s ligand with femtomolar affinity, Aravive Biologics Inc. believes it has a biologic that can bypass the potency and selectivity issues of the small molecule AXL inhibitors already in the clinic for cancer. The company plans to submit an IND in 2017 for its lead candidate, Aravive-S6, in leukemia.

Last month, Aravive changed its name from Ruga Corp., and moved from Palo Alto to Houston to accept a $20 million grant from the Cancer Prevention & Research Institute of Texas (CPRIT) to help bring the compound to the clinic.

AXL is a receptor tyrosine kinase (RTK) on the surface of cells that binds the ligand GAS6 to trigger a survival response. Cancers co-opt the pathway to metastasize and become drug resistant, and overactivity is associated with poor survival.

There are no drugs on the market targeting the pathway, but at least 10 products are in preclinical or clinical development. The most advanced are small molecules, but four, including Aravive-S6, are biologics (see “Putting the Brakes on AXL”).

Table: Putting the brakes on AXL

Select AXL receptor tyrosine kinase (AXL; UFO)-targeted therapeutics in clinical and preclinical development. At least three AXL inhibitors are in clinical development and seven others are in preclinical development, including Aravive-S6 from Aravive Biologics Inc. Aravive-S6 is an Fc fusion protein containing a mutant extracellular AXL domain that binds its ligand, growth arrest-specific 6 (GAS6), with high affinity. By binding GAS6, Aravive-S6 inhibits ligand-mediated activation of AXL. Source: BCIQ: BioCentury Online Intelligence

ModalityCompanyProductDescriptionIndicationPhase of development
Small moleculesAstellas Pharma Inc. (Tokyo:4503); Kotobuki Pharmaceutical Co.Gilteritinib (ASP2215)AXL and FMS-like tyrosine kinase 3 (FLT3; CD135) inhibitorAcute myelogenous leukemia (AML); non-small cell lung cancer (NSCLC)Phase III; Phase I
Mirati Therapeutics Inc. (NASDAQ:MRTX)Glesatinib (MGCD265)Dual inhibitor of AXL and c-Met receptor tyrosine kinase (c-MET; MET; HGFR; c-Met proto-oncogene)Solid tumors; NSCLCPhase II
BerGenBio A/S; Rigel Pharmaceuticals Inc. (NASDAQ:RIGL)BGB324AXL inhibitorNSCLC; AMLPhase I
Qurient Co. Ltd. (KOSDAQ:115180)Q-4AXL inhibitorCancerPreclinical
Tolero Pharmaceuticals Inc.TP-0903AXL inhibitorLeukemia; pancreatic cancerPreclinical
Ignyta Inc. (NASDAQ:RXDX)RXDX-106Selective, pseudo-irreversible inhibitor of AXL and...

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