Juno looks like theyre using a TCR approach (i think). Novartis CAR-T. Macrogenics using the CD123 DART.
AML FWIW is a disease I haven't tracked in depth because it is probably the most crowded space in oncology with regards to different technologically novel, but relatively high probability of success treatments. It may be that right now there aren't a lot of good options in rr AML, but I expect that within 3 to 5 years there will be at least 3 or 4 highly effective treatments through trials. Predicting which will come out on top will be very difficult - but my expectation is that whatever comes out on top will be a combo of some form.
But, FWIW, to more specifically answer your questions to the best of my current knowledge (so take it for what it's worth?):
A) JUNO's approach (engineered TCR) is fairly novel. Perhaps most similar to GNCAs - although more personalized?? And targets a completely different protein than CD123. Regardless, because it is new tech I'd expect it to take longer to get through ph 1 and 2.
B) is Novartis still doing CART CD123? I thought someone stopped because of apparent bone marrow tox in a preclinical model? And if I'd had to guess it would have been Novartis?
C) As for whether CD123 is a good target, the only human data of which I am aware is that someone tried a traditional mab anti-cd123. Almost all patients had no benefit, but one got a very durable CR. Lends some credence since it may have been an ADCC effect, but lots(!!) of uncertainty.
D) finally there is boatloads of other CD123 competition. E.g. XNCRs DART, I'd be surprised if Cellectis didn't have something, ... .
Note that If I had to pick an MGNX target that is most undervalued I'd pick MGA271. Especially now that there are two PD1s on the market to try combo ph 1. Risk certainly. But novel and not overcrowded. And I think ADCC is currently undervalued as a relatively low tox way to boost IOs to relatively high rate of long term cure.
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