Here are some notes from the call. Excuse any misspellings some of the terminology was above my level of knowledge
. Encouraged by anti-viral activity even at lowest dose significant anti-viral activity. Validates unique mechanism, inhibiting protein NS4A.
. Does have dose limiting toxicity that would limit dose escalation.
. Early signs of elevation of serum creatinine, reversable after dosing completed.
. Next generation some in preclinical development. No date set on when next would move into the clinic. Think can get IND filing in Q1/Q2 2008 if get lead candidate soon.
. Talked about other programs, broad pipeline, etc.
[JS-Cowen] What promotion increased creatinine? See it preclinically? Route of elimination for drug (through Kidney?)
Roughly 6 of 8.
Did not see any sign in preclinical tox. Difference in that there is multiple dosing. Elevation about .4 - .5 mg / deciliter.
Primarily metabolized in liver, exact answer not 100% known how much through urine appears most through liver.
[BH-CIBC] 1095 and backup hemotypes, how close? Efficacy of 1095 vs. 806?
Different pharmacore. EC-50 of 9132 14 nM (Genotype 1) vs. 1095 and related compounds EC-50 20-30 nM
[JC-Susq] Mechanism of Action for elevated creatinine level? How proceed with GILD? Lost about a year?
Point to it being causing some damage to renal tubule. Don't see signs of interstitial nephritises. Trying to elicit exact mechanism still. Most likely not related to target of mechanism of action. Believe effect most related to structure of 9132 then mechanism. [JC]as passing through kidney believe some binding their [ACHN] we believe so.
No substantive change. Achieve proof of concept with backup compound, defined by clearing 3 hurdles (>= 1 log Viral log reduction, acceptable safety profile, movement into Phase 2).
Think so maybe conservative since learned things and may do things different such as go directly into patients. No one else as far as we know with advanced program against this target.
[GF-Wachovia] Why tox not observed in Phase 1A. Talk about doses examined? Backup compounds Achillion through Phase 1, Gilead Phase 2 on?
Phase 1A 10mg up to 2400 mg as single dose. Didn’t see tubular issue that saw in multiple dose. In multiple dose 300mg BID.
Not quite we will do whats best for drug. Far more collaborative effort “more then likely with Gilead in the drivers seat”
[JF-Morgan Stanley] Any other side effects that saw to see mechanism of toxicity outside kidney? Anything that can do differently?
No didn’t see anything else that would go along with this.
Data is pretty recent. Starting to look in other models to see what is predictive of what we saw. Not mechanism related but more hematite related.
[TW-Piper] Viral load on trajectory comparable efficacy to class? Any non-responders? Did meet the first criteria (positive efficacy data)?
806 clearly demonstrated anti-viral activity. Probably more so then expected at low dose activity. Didn’t see signs of viral rebound.
Depends on how you define it. All patients who received drug had greater viral load drop then 2 who received placebo. 4 above 1 log, 4 below but higher then placebo. Believe higher dosing would see much stronger activity.
Till finish analysis no answer.
[MS-R Capital] Novel mechanism of action, NS3? telaprevir also 4a? Financials Shares/Cash?
GS-9132 binds non structural protein NS4A co factor for NS3 protease. Shown after our compound binds to it, disrupt formation of replicate complex.
No active site inhibitor of NS3 protease.
15.5 million [preferred convertible soon?] converted at IPO. Cash low 60 million range.
[DK-Credit Swiss] Gilead experience, did they see why and how to fix it?
No net yet. Working quite closely with them reviewing data.
