Biotech Values

[DewDiligence]

Re: ATryn, sepsis, and burns

>>A P-value of 0.03 is weak, but significant. It's worth considering that the phenomenon may be real, IMHO.<<

To my knowledge, this outcome has not been replicated in other AT studies in sepsis, so it does appear to me to be an artifact. However, if it turned out that AT really did work in sepsis, that would be good news, not bad news, for GTCB.

I do not expect GTCB to pursue a sepsis indication for ATryn, but data showing that AT worked in sepsis could conceivably generate some off-label sales. The amount would likely be de minimus, however.

>>Increased bleeding? No such interaction was observed when heparin was co-administered with activated protein C (both rAPC and antithrombin III down-regulate the coagulation cascade, albeit by different mechanisms).<<

When AT binds with heparin, it causes a 1,000-fold increase in the anticoagulation inhibition of heparin (http://www.atiii.com/Pages%20folder/AboutHD.html ). Thus, I think it’s reasonable to expect a somewhat higher bleeding rate with AT+heparin treatment than with C+heparin treatment, which is exactly what was found in the trial you cited.

>>As for heparin and burns, it would appear that it is used routinely by some in an effort to prevent deep vein thrombosis, although this use may be controversial.<<

Thanks for the citation on DVT in burns patients. I suspect that GTCB’s ATryn protocol for burns will attempt to preclude heparin—or at least keep its use to a minimum—in order to avoid muddying the waters with another agent. If the protocol allows heparin at all, it will probably be on an “as needed” case-by-case basis at the doctor’s discretion—not as routine prophylaxis. (This would be similar to the way Visudyne was allowed at the doctor’s discretion in the phase-3 Macugen trials in AMD.)

>>I'm not attacking ATryn, by the way. I'm just entertaining arguments against its uses in aquired AT deficiencies, uses suggested by GTCB management. I wouldn't bother if I didn't consider GTCB an attractive potential investment. Perhaps I am nit-picking? The platform is attractive, the valuation is very low (probably because the technology is both novel and controversial), and safety is likely to be superior to human plasma-derived proteins.<<

Understood. I definitely do not think you’re nit-picking in discussing potential issues in the ATryn burns indication because this indication represents a non-trivial component of current shareholder value. When the time comes, investors should pay close attention to the design parameters of the ATryn burns trial, including the rules for co-administration of heparin.

Where I do think you may be nitpicking is in your scrutiny of older AT trials in indications—such as sepsis and CABG—where GTCB is unlikely to pursue clinical studies in the next few years, if ever. The contribution to current shareholder value from these indications is certainly no more than round-off error. Regards, Dew