Finally getting back to responding to your comments. I have a bit of further insight.
1. I was aware of one company a while back developing a recombinant C5a inactive protein (desArg?) as a receptor antagonist, and it was discontinued due to batch to batch variability and cost of goods. I know know detail of the stopped ALXN program with a C5a antibody. There can be significant commercial concerns of an antibody candidate if insufficient half life or other issue, though it may be useful for proof of concept. I do not read much into stopped C5a approaches. So my view is that stopped programs were due to drug specific issues.
2. Thanks for pointing out the Innate Pharma asset. I am aware of a complex literature of C5a biology in myeloid cells that have been suggested to play a role in specific oncologies. I view this aspect of C5a and is receptor(s) function as speculative and insufficiently compelling at the current time. Is there a candidate in search of a disease here, or a disease in search of a target? I see that the Innate obtained this C5a antibody asset from Novo, FWIW. One question here (for myeloid derived suppressor cells) is whether C5a is sufficiently upstream to have a major effect.
3.Concerning avacopan to IFX-1 in AAV, the initial IFX-1 data needs to be longer term. The intriguing thing to me about IFX-1 is the apparent longer term effect at reducing C5a levels. I am sure blockade is quick, as avacopan may take a few days to come to steady-state. Is that really all that important? I think not. That is why I go back to the extent of blockade by each approach. The degree of blockade is important tor true remission as it appears that IFRX sees in HS. Speed is only somewhat important. As to indirect off target effects of avacopan, it is true that generally only some 50-500 molecular targets are evaluated in any in vitro drug specificity test. So with any small molecule there is always that theoretical possibility. But animal tox and human work to date should be sufficient, unless some idiosyncratic tox shows up in man. I would be more concerned with low level liver function tests enzyme elevations or phospholipidosis, for that matter. But overall, I am most concerned about the mediocre drug-like physical properties of the CCXI molecule including solubility.
I will just add that this remission issue is of interest with these complement companies. OMS721 from OMER has apparently shown remission in IgA nephropathy patients kidney function (insufficient data for proof IMO). I wonder if these remission statements are for real, or if management (OMER?, or IFRX?, or both) is just simply messing with my head
