Replies to post #14101 on Biotech Values

[DewDiligence]

Re: Comments on ATryn in sepsis

At this time, I attribute no underlying shareholder value to the sepsis indication for ATryn. Here’s why:

1. The investigator-led trial reported today was not a true sepsis trial, but rather a simulation of sepsis in healthy volunteers.

2. Plasma-derived antithrombin has not shown an unambiguous clinical benefit in treating sepsis.

3. If GTC has any interest in pursuing a sepsis indication for ATryn—which I rather doubt—it is way down on the list of indications for label expansion.

[DewDiligence]

Other news from ISTH conference in Sydney:

http://biz.yahoo.com/pz/050809/83601.html

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Trigen Announces the Successful Completion of a Phase II Study of TGN 255 for Anticoagulation in Haemodialysis

Tuesday August 9, 7:22 pm ET

Preliminary results presented at XXth Congress of the International Society of Thrombosis and Haemostasis (ISTH), Sydney, Australia, August 6-12, 2005

MUNICH and LONDON, Aug. 9, 2005 (PRIMEZONE) -- Trigen Holdings AG today announced the preliminary results of its Phase II study of anticoagulation in haemodialysis for its novel intravenous anticoagulant, TGN 255, at the XXth Congress of the ISTH in Sydney, Australia. The results are presented in a presentation entitled 'Effect of TGN 255, a Novel Intravenous Direct Thrombin Inhibitor, on the Prolongation of ACT in Patients Undergoing Haemodialysis.'

Trigen conducted the study in 28 patients undergoing haemodialysis at several sites in Europe to assess whether TGN 255 would adequately anticoagulate the extra corporeal circuit in haemodialysis in patients with end-stage renal failure and to evaluate the pharmacokinetics and pharmacodynamics of the drug in this setting. Each patient underwent at least three dialysis sessions with TGN 255 following a baseline session with unfractionated heparin. The results suggest that TGN 255 provided effective and convenient anticoagulant cover in this setting with a high level of control and with no increase in bleeding risk. Final results are expected during the autumn of 2005. However, these preliminary data support the progression of TGN 255 into late-stage clinical trials in this indication as planned.

Trigen is presenting a total of nine scientific presentations at ISTH, highlighting developments in its intravenous (TGN 255) and oral (TGN 167) small molecule Direct Thrombin Inhibitor (DTI) programmes. Full details are listed at the end of this press release.

TGN 255 is a novel intravenous small-molecule DTI being developed as a predictable and safer alternative for anticoagulation in hospital settings. Anticoagulation in haemodialysis is the lead indication for TGN 255. Trigen is also planning to develop TGN 255 in cardiovascular indications.

Trigen Holdings AG is a biotechnology company, with operations in London and Munich and is a leader in cardiovascular drug discovery and development, focussing on thrombosis and vascular dysfunction. The company's expanded product pipeline includes the existing clinical stage candidates, TGN 255 and TGN 167, and PR-15, which is expected to enter the clinic early in 2006. The company also has an extensive portfolio of exciting pre-clinical and discovery stage programmes targeting thrombosis, atherosclerosis and other cardiovascular pathologies. In addition, Trigen benefits from two established discovery platforms, SIGSCREEN(R) and THROMSCAN(R) which have been applied in collaborations with a number of multinational pharmaceutical companies.
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[DewDiligence]

New abstract on antithrombin treatment in DIC / sepsis:

[DIC/sepsis is supposedly one the candidate indications of *acquired* AT deficiency that GTCB is considering for its non-HD ATryn program. The selection of the indication to be pursued will be made next year, but I think burns is the frontrunner; I’ll be surprised if DIC/sepsis gets the nod.

This is the second published study out of Austria on this subject—the other one is in #msg-7268415.]

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_...

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Crit Care. 2005 Sep 19;9(6):R596-R600 [Epub ahead of print]

Reduction of D-dimer levels after therapeutic administration of antithrombin in acquired antithrombin deficiency of severe sepsis.

Kountchev J, Bijuklic K, Bellmann R, Wiedermann CJ, Joannidis M.

Resident, Medical Intensive Care Unit, Division of General Internal Medicine, Department of Internal Medicine, Medical University Innsbruck, Austria.

INTRODUCTION: In acute disseminated intravascular coagulation, the effect of antithrombin (AT) administration on elevated levels of D-dimer is not well established. In the present study, we report on changes in circulating levels of D-dimer in response to administration of AT in a series of patients with acquired AT deficiency due to severe sepsis.

METHODS: Eight consecutive critically ill medical patients presenting with acute disseminated intravascular coagulation associated with severe sepsis/septic shock received a single bolus infusion of AT over 30 minutes, aiming to achieve physiological AT levels. Haemostatic parameters including D-dimer were assessed prior to, 6 and 24 h after AT administration. An average of 42 +/- 9 U/kg body weight was infused.

RESULTS: Following AT substitution, elevated levels of D-dimer fell whereas AT levels rose.

CONCLUSION: These observations support the notion that AT can favourably affect fibrin degradation accompanying disseminated intravascular coagulation of severe sepsis.
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