ITMN’s PI for HCV: The VRTX board on InvestorVillage has a few ITMN proponents. You might want to post some questions over there. I don’t know much about it myself.
This NYT article is a bit dated but has some background info on the HCV/PI space: #msg-9595653.
ITMN-Too early to tell about ITMN's PI for HCV. It appears they are going to conduct the first study abroad in Europe, it's unclear if they will dose chronic patients or just dose healthy patients. The verbage in the dated PR below is vague, I assume ITMN will treat chronic patients first as PPHM did in their Phase Ia.
. Wonder if anyone would consider combining PI's if ones are more resistant against certain variants then others? Which PI's are you referring too, the one's in clinical trials? ABT's Kaletra is the only other PI I'm aware of that is being testing in combo with other HCV compounds.
InterMune Presents New Preclinical Data on Its HCV Protease Inhibitor at Digestive Disease Week
Strong Potency and Drug Resistance Profile of ITMN-191 Derived From Its Distinct Structure
LOS ANGELES, May 23, 2006 /PRNewswire-FirstCall via COMTEX News Network/ -- InterMune, Inc. (Nasdaq: ITMN) announced today the presentation of research describing the preclinical characterization of ITMN-191 (previously referred to as ITMN B), its orally available hepatitis C virus (HCV) NS3/4A protease inhibitor. The preclinical findings were presented at the Digestive Disease Week (DDW) meeting in Los Angeles. InterMune expects to submit a European Clinical Trial Authorization for ITMN-191 in the third quarter of 2006.
In an oral presentation and Poster of Distinction at DDW, Scott Seiwert, Ph.D., Vice President of Discovery Research at InterMune, described the characterization of ITMN-191 activity against various HCV N3/4A protease variants. ITMN-191 retains activity against variants that exhibit reduced sensitivity to other experimental HCV protease inhibitors in development. A single variant was identified that shows diminished potency to ITMN-191. However, this variant is distinct from variants that have reduced sensitivity to other HCV protease inhibitors. This demonstrates a favorable cross-resistance profile of ITMN-191 with other HCV protease inhibitors currently in development.
Also at DDW, the chemical structure of ITMN-191 was revealed for the first time, demonstrating the distinguishing characteristics between ITMN-191 and other experimental HCV protease inhibitors. InterMune and its collaborators utilized structure-based drug design to optimize drug-target binding interactions. The researchers credit the tight binding between ITMN-191 and the HCV protease for the experimentally observed high potency of ITMN-191 and activity against variants of the protease that are resistant to other HCV protease inhibitors.
Structural optimization also enabled InterMune to improve compound exposure to the liver in animal models. Given that viral replication of HCV is reported to occur primarily in hepatocytes, achieving high drug concentrations in liver is believed to be critical to the clinical success of target therapies against HCV. Further in vivo studies reveal favorable high liver exposure of ITMN-191 across multiple species at potentially clinically relevant dosing concentrations. The results continue to support exploration of twice-daily, oral dosing in treatment of chronic HCV.
"Our research team's detailed characterization of ITMN-191 provides important insight regarding how our compound is distinct from other experimental HCV protease inhibitors in development and reinforces our confidence that ITMN-191 has the potential to be a superior drug candidate with favorable cross resistance and potency profiles," said Dan Welch, President and CEO of InterMune.
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