@DkoInvest@BreakingBioMatt Saw your reply to one of my other $KOD comments. You definitely know more than me on this, but 2 qs:
1. Once free Ab clears in a few weeks, wouldn't the conjugate face the same inflow either way?
2. Isn't durability driven by clearance vs how much VEGF gets bound?
@RazBioTech I think HD will probably outperform, million dollar question is to what extent?
I’ve been cold emailing ophthalmologists to see if they extend dosing intervals of HD beyond label in stable patients, and how long they do (no luck yet). Do you have any insights?
$OCUL
1/ Revisiting a holding I've mostly set and forgot, I'd argue the most commercially relevant endpoint is superiority to Eylea HD q24w at week 96.
Non-inferiority to 2mg Eylea seems like table stakes now that 8mg Eylea and Vabysmo exist and extend treatment intervals.
@2035Bio@Andre_AGTC Yeah has never correlated to clinical benefit. Also bearish on them (wrote a small article on my substack too).
I doubt the adjuvant melanoma win will translate broadly but possible it makes it past P1 in some indications.
@Andre_AGTC $BNTX similar drug P1 in resected PDAC (cold, low TMB) looked good:
Post-hoc 8/16 patients showed neoantigen-specific CD8+ response and responder median RFS wasn’t reached.
However it hasn’t succeeded in a P2. Thinking $MRNA could clear P1 pancreatic but uncertain beyond that
3/ SOL-1 data using SOL-R rescue criteria:
Wk 24: 77.1% rescue-free
Wk 52: 66.5%
Axpaxli was still working when the next dose would be, and overlapping implants raise the floor from 2nd dosing cycle on. Eylea HD, however has no carryover. Each dose starts from a washed-out eye
2/ It's a direct test of the moat (longer dosing interval than Eylea HD).
Testing both at q24w isolates durability as the variable: can Axpaxli control wet AMD where Eylea HD cannot?
Note that the FDA declined to approve q24w dosing for Eylea HD.