EMRICASAN



NAME OF DRUG : EMRICASAN

ALSO KNOWN AS : IDN-6556, PF-03491390

LABORATORY : CONATUS

STATUS AND ADVANCEMENT

Type of drug : potent inhibitor of caspase-mediated pro-inflammatory cytokines

Clinical trials advancement : Recruiting Phase 2b

The drug got the Fast Track Status granted by the FDA

Estimated time to market : 71 months.

LABORATORY ABSTRACT ON THE DRUG

Emricasan works by inhibiting caspases, which are a family of related enzymes that play an important role as modulators of critical cellular functions, including functions that result in apoptosis and inflammation. Caspase activation and regulation is tightly controlled through a number of mechanisms.

All caspases are expressed as enzymatically inactive forms known as pro-caspases, which can be activated following a variety of cellular insults or stimuli. Seven caspases are specifically involved in the process of apoptosis while three caspases specifically activate pro-inflammatory cytokines and are not directly involved in apoptosis as shown.

Emricasan is a Potent Inhibitor of Apoptotic and Inflammatory Caspases mechanism.

Caspase mediated apoptosis is driven primarily by the activity of caspases 3 and 7 which, by virtue of their enzymatic activity, cleave a wide variety of cellular proteins and result in dismantling of the cell. Other apoptotic caspase family members are principally involved in sensing and transmitting signals from either outside or inside the cell. These signals converge to activate pro-caspases 3 and 7, enabling them to carry out the process of apoptosis.

CK18 is one key structural protein that is cleaved by caspases 3 and 7 in a highly specific manner. The product of this cleavage is a small protein fragment, cCK18. This fragment is contained within the apoptotic cell fragments and is easily detected in serum using a commercially available monoclonal antibody assay.

This monoclonal antibody, M30, is used routinely in clinical trials as a measure of apoptosis. While healthy individuals have normal levels of apoptosis, excessive levels of apoptosis associated with disease can overwhelm the body's normal clearance mechanisms.

Reducing excessive levels of apoptosis reestablishes balance between apoptotic activity and normal clearance mechanisms and brings inflammation and other drivers of disease progression under control. As a result, we believe targeting caspases that drive both apoptosis and inflammation in disease offers a unique and potentially powerful therapeutic approach for the treatment of both acute and chronic liver disease.

Testing in vitro enzyme assays demonstrated that emricasan efficiently inhibits all human caspases at low nanomolar concentrations. Preclinical studies have demonstrated that emricasan is highly selective for the caspase family of enzymes with little to no activity against other enzyme systems.

These studies have also shown that emricasan potently inhibits the apoptosis of cells regardless of the apoptotic stimuli and that it is a potent inhibitor of caspase-mediated pro-inflammatory cytokines.

Emricasan has been examined in various preclinical models of liver disease. In these models, caspase activity was demonstrated to be inhibited, as determined by histological examination, in liver tissue. Based on our evaluation of emricasan in in vitro systems, cellular assays and disease models, we believe emricasan's mechanism of action has been well characterized.

RECENT NEWS ON EMRICASAN

2017-04-19 : Novartis joins forces with Allergan, pushing a NASH combo into late-stage development

2016-12-19 : Conatus Announces Exclusive Worldwide Option, Collaboration and License Agreement Covering Development and Commercialization of Emricasan

SOME PUBLICATIONS RELATED WITH EMRICASAN

June 2014 : The pan-caspase inhibitor Emricasan (IDN-6556) decreases liver injury and fibrosis in a murine model of non-alcoholic steatohepatitis

SOME NASHBIOTECHS POINTS OF VIEW RELATED WITH EMRICASAN

October 2016 : NASH COMBOs ARE THE WAY

September 2016 : TARGETING FIBROSIS ALONE IS A NONSENSE IN NASH

August 2016 : STATUS REPORT ON NASH (August 2016)

May 2016 : UPDATE ON THE RACE TO NASH MARKET (May 2016)

November 2015 : GILEADs POSSIBLES STRATEGIES IN NASH

September 2015 : NASH ! TREATMENT’S STRATEGIES AND COMPETITION


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