Thread by @sciencescanner

Interesting reading some of the reaction to $NGM - despite the superficially sensible MoA, it never seemed likely an anti-C3 would work in GA...

Why not? After all, genetic variation that reduces function of the C3 inhibitor CFH is a causative factor in GA…

1/n

And the $APLS C3 inhibitor Empaveli pegcetacoplan had its NDA accepted by FDA earlier this year, although it wasnt as effective as some had hoped

The devil is in the detail: complement activation in GA occurs predominantly in Bruch’s Membrane - a tough place to get access

2/n

It is well-known that antibodies cannot penetrate Bruch’s Membrane, surely casting into doubt the primary hypothesis for NGM621 efficacy in GA

So the CATALINA #fail today seemed predictable

3/n

Empaveli, being a smaller molecule, may have greater access but likely is still inefficient as a C3 inhibitor in the eye. The real prize is still up for grabs in GA - small molecules? Anti-CFB acting systemically? Recombinant CFHs?

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