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Wednesday, January 5, 2011

New Class Of Drug Might Improve Herceptin (trastuzumab) Capability In Treating Aggressive Form Of Breast Cancer

The Breakthrough Breast Cancer-funded team at the University of Oxford showed that combining Herceptin with pan-HER inhibitors kills cancer cells much more effectively than Herceptin on its own. The drug combination does this by knocking out the activity of HER2 and, crucially, its related proteins, too. These results were then confirmed in mouse models.
Dr Anthony Kong, the Breakthrough Breast Cancer clinician scientist who led the study, said: “It was incredible to see how much more potent Herceptin becomes when combined with a new type of drug. We think this could have a big impact in improving survival rates for patients with HER2 positive breast cancer. “We are hoping to set up a clinical trial in the near future to test this treatment combination in patients.”

Source

pan-HER
SAN DIEGO, Dec. 20, 2010 /PRNewswire/ -- Ambit Biosciences (Ambit), today announced that it has initiated separate Phase I trials for two products AC430, a selective Janus Kinase 2 (JAK2) inhibitor, and AC480, a pan-HER inhibitor.
The Phase I trial for AC430 is a two part, placebo-controlled, single ascending, and multiple ascending dose trial in healthy volunteers.  AC430 will be administered orally once-daily and doses escalated until a maximum tolerated or maximum feasible dose is established.  In addition to evaluating the safety, tolerability, and pharmacokinetics of AC430, the study will also assess cytokine signal transduction.  
The Phase I trial for AC480 is a multi-center, dose escalation study with AC480 administered by intravenous infusion on days one and two of a 21 day cycle, either alone or in combination with docetaxel.  The trial will assess safety, pharmacokinetics and anti-tumor activity of AC480 in patients with advanced solid tumors.
"The initiations of these studies are important milestones," said Alan Lewis, President and CEO Ambit Biosciences. "AC430 has demonstrated convincing efficacy in pre-clinical models of autoimmune and inflammatory diseases, and AC480 IV was developed to assess whether pulsatile doses of a pan-HER inhibitor administered in combination with a taxane such as docetaxal would produce synergistic anti-tumor activity."
About AC430
AC430 was specifically developed to be a best-in-class JAK2 inhibitor.  In preclinical studies, AC430 has exhibited potency against JAK2 in cell-based models that is at least equivalent, and in most cases superior to, competing JAK2 inhibitors, and also has excellent oral pharmacokinetic properties.  In preclinical oncology and autoimmune models, AC430 is well tolerated and has significant efficacy at oral doses as low as 10 mg/kg/day.  JAK2 has been implicated as a target for therapy in both oncology and autoimmune disease.
About AC480
AC480 is a small molecule kinase inhibitor that selectively inhibits the HER family of receptors, HER1, HER2, HER3 and HER4.  Excessive HER signaling has been associated with the development of a wide variety of types of solid tumors, including those found in lung, breast, head and neck and brain cancers.  Currently marketed HER inhibitors inhibit only one or two of the HER family members and a pan-HER inhibitor that inhibits all of the HER receptors may be effective in more cancer types.  Published data with oral HER inhibitors administered in combination with taxanes, such as docetaxel, demonstrate activity in clinical studies and these clinical data are supported by preclinical data demonstrating that combining HER inhibitors with taxanes produces synergistic anti-tumor activity.  An intravenous formulation of a pan-HER inhibitor such AC480 enables high pulsatile doses to be administered in combination with taxanes.
About Ambit Biosciences
Ambit Biosciences Corporation is a biotechnology company engaged in discovering, developing and commercializing targeted small molecule therapeutics for the treatment of cancer.
Ambit contacts:
Alan Fuhrman, Chief Financial Officer, Ambit Biosciences (858) 334-2133, afuhrman@ambitbio.com
Christopher Morl, Chief Operating Officer, Ambit Biosciences (858) 334-2134, cmorl@ambitbio.com

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