Replies to post #185535 on Biotech Values

[poorgradstudent]

TRIL:

Would a study of a mouse SIRPaFc in mice really convince you that the human drug would be equivalent?

Given that they seem to have data from the primate, then mouse SIRPaFc in mice wouldn't be all that meaningful for me.

They collected immunogenicity data during the initial primate studies, and will do so during the upcoming GLP tox studies. But the human drug is expected to be more immunogenic to mice and monkeys, so the usefulness of the data is questionable, and is likely one reason they don't intend to publish it.

If I'm reading between the lines there, the use of the protein in primates appears to have raised an immune response of unknown magnitude?

That could be a little worrying. The likelihood of immunogenicity isn't specifically related to injecting a human protein into a primate, or vice versa. Rather, the amino acid sequence of the protein is important. In other words, if the human SIRPa/Fc sequences that TRIL uses (omit the linker for now) are identical to those generated from the genome of the primate, then there's a good chance that the response in humans will be similar to that seen in primates. Often, the amino acid sequence of a select protein in many primates will have high identity (>90% identical) to the sequence present in humans. So if there are no sequence mismatches in the SIRPa/Fc between humans and the primate species used, then the immune response may be similar.

Second point: if they saw an immune response from the primate, they could easily do a series of epitope mapping to determine which region of the SIRPaFc generated the response. If they map it to the junction, then I think there is a >50% chance that this will carry over to humans. The reason being that the junction region is usually no more "human" than "primate" since it can include amino acids squeezed in there by the protein engineers to make the two protein halves connect.

[DewDiligence]

[TRIL]…the example of Enbrel being considered less immunogenic than Humira.

Your use of the word, considered makes it sound as though this a matter of opinion rather than something that can be measured empirically. Is this the inference you intended?