Hulskof schreef op 19 november 2020 05:21:
Zeer interessante reeks tweets op Twitter over Fate in vergelijking met Affimed en Gamida Cell. In het kort: waarom wordt Fate 10x hoger gewaardeerd dan Affimed terwijl het nog geen enkele proof of concept heeft? Een mogelijke verklaring is dat Affimed zelf geen NK cellen bezit en Fate wel. Hoe krijg je dan ooit een gedefinieerd eindproduct?
Hier te lezen:
twitter.com/brendan_49/status/1329087...Samenvatting zonder plaatjes...
Some random facts about $FATE (engineered NK cells) that might be interesting to my $AFMD (mabs w/ affinity to preload NK cells) and $GMDA (proprietary NK cell expansion combined w/ established antibodies) people.
t.co/M6xrBO58LDSurprising to me - $FATE has only dosed 35 patients so far, across all their trials. 150+ doses, since re-dosing is what you do with NK cells. Safety w/ NK cells is excellent as usual.
t.co/HhXtcNL6uONK cells + antibodies - where should each piece of functionality go? In particular, where should the targeting be? Build a receptor into the NK cell? Or pre-load NK cell w/ very sticky antibody? Both concepts can be off-the-shelf.
t.co/rljwSbMY3i$FATE first clinical dataset - no responses in 15 solid tumors. Not surprising since it was monotherapy w/ an untargeted NK cell product. NK cells w/ out a targeting mechanism aren't promising.
t.co/gTlbCcnMMmFT596 embeds a CD19 CAR and is combined with CD20 mab in b cell lymphoma. Great concept. So far, 1 PD, 1 PR.
$GMDA plain-vanilla NK + rituxin has 10 CRs in 15 tries in similar population.
So $FATE has to leap a high bar, here.
t.co/CgDGaSBhBL$FATE has a CAR-NK for BCMA/MM construct, IND-ready. Recall that Genentech is already dose-escalating BCMA $AFMD antibody, which, I'd speculate, will be combined with NK cells once safety is established.
t.co/gOVGSuqaKcIn 2021 $FATE will IND an NK cell designed to enhance antibody cytotoxicity in solid tumors.
Again, $AFMD is dose-escalating an EGFR targeted antibody right now, which is planned for NK cell combos.
t.co/jJvABFZsZASome takeaways:
1) Why is $FATE valued at $4.5b w/ out any proof of concept? Belief that engineered NK cells - CAR-NK or NK + antibodies - will work. And in particular that the engineering enabled by induced pluripotency will be big advantage vs. NK cells from other sources.
2) I don't think we know whether CAR-NK is better than engineered NK + extremely sticky pre-loaded antibodies ( $AFMD ), nor whether NK cells need to be improved in fancy ways. $GMDA 10/15 CRs in lymphoma suggests vanilla NKs + targeting is pretty good.
3) If you're agnostic about CAR-NK vs NK+sticky antibodies you ought to like $AFMD. AFMD/ $FATE have overlapping product concepts in lymphoma, BCMA, solids, etc. AFMD is 1/10th as expensive, and will have more clinical data sooner.
4) Big picture - pointing NK cells (via antibodies or CARs) at targets validated by monoclonal antibodies looks like a GREAT idea. Clinical data so far is promising, concept is straightforward, costs tolerable, safety is pristine. $AFMD fave play - but would like to find more.