Replies to post #185240 on Biotech Values

[ghmm]

Maybe a dumb question since I am not a science guy BUT I'll ask anyway :-). Why don't companies use PEGylation more when developing a protein with potential or even theoretical immunogenicity? Isn't PEG technology fairly advanced that the benefits outway the risks/delays needed to go back and apply it?

[RockRat]

Re: TRIL: >>1) Body creates an immune response towards it and the infused protein gets rapidly cleared.<<

Understand the general concern about this. But wouldn't we see that effect show up as a lack of preclinical efficacy? If the doses were too short lived for the mice to mount an immune response to this unnatural Fc region, would it show/be looked for in GLP tox studies (presumably in the form of antibodies to the Fc region)? I'd imagine this would involve primates and be long enough to see an unwanted immune response comparable to the one you are concerned about in humans. Would I be wrong? Those are slated to begin this coming quarter, and to be completed in support of the IND by the end of the 1st half of '15.

I should amend my statement about induction and combo therapy a bit, as TRIL plans have apparently evolved since that paper was published. TTI- 661 is designed as monotherapy, while TTI-662 will have lower effector function and is designed to work with other targeted therapies. Not sure why it is important to have lower effector function for this purpose, but that's the company's official stance.

TIA & Regards, RockRat