Biotech Values

[biotech jim]

Re: IFRX vs CCXI

I follow the work of each company, and my view is that the difference is in the degreee of blockade of the C5aR by each company in the clinic. I think investors in the biopharma field under-appreciate the extent to which a receptor blocker actually achieves, considering that receptor occupancy is sigmoidal and hence complete blockade is difficult to achieve. It is also of interest that the classical neutrophil C5aR (the originally named CD88 protein) is considered to have a 'hair pin trigger'.

The field of C5a small molecule antagonists has been an active one for many years, with a limited amount of chemical matter having drug like properties having been identified. The CCXI compound is considered 'bricky', with relatively poor drug like properties including solubility. The question to ask CCXI management is to what extent they have C5aR blockade, at both peak and trough blood levels. Also whether the drug hits the second C5a receptor (see below).

As to IFRX, they have some fantastic C5aR biologists that had extensive training in Peter Ward's lab in the Dept of Pathology at the University of Michigan. They appear to have in IFX1 a novel C5 mAb that may block cleavage by the convertase, but also by 'rogue' plasma borne proteases. It is not clear to what extent this may be significant. They have shown compelling activity in HS, though much more needs to be done. My view is inflammatory skin disorders are where the action will be for C5 approaches, as in hydradenitis supportiva, lichen planis and the like.

Note also there is a second C5aR, termed in the literature, C5L2. Some have called it a 'decoy' receptor, as finding a function of this R has not been easy. This link shows the role of C5aR in kidney fibrosis, and its complicated biology as related to the 2 C5aRs:

https://www.ncbi.nlm.nih.gov/pubmed/28903945

This link summarizes more broadly the 2 C5aRs:

https://www.ncbi.nlm.nih.gov/pubmed/23239822

Disclosure: I hold a significant position in IFRX, and I may have traded CCXI in the past.