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Biotech / Medical : Juno Therapeutics Inc. (JUNO) -- Ignore unavailable to you. Want to Upgrade?

To: Biotech Jim who wrote (64)	3/4/2017 4:42:06 PM
From: tuck	Read Replies (1) \| Respond to of 84

Thanks for your thoughts. >>I also note that RBC thinks the JUNO pre-conditioning regimen with fludarabine higher dose than KITE may be in part the ultimate culprit in the cerebral edema/neurotox/patient death issues, and I think this is similar to the JUNO thinking, but they cite other issues as well.<< What other issues? Certainly we kicked the idea of the pre-conditioning regimen being done at too high a dose on the momo/tif thread. I wondered aloud if JUNO might see if the FDA would let them try a lower dose going forward. Seems like it would be faster than trying to re-engineer the drug as we also discussed over there. But in the face of these difficulties, it makes sense to take a next generation compound forward, instead, and that's why I'm buying the weakness along with you. However, if the next gen compound also requires a pre-conditioning regimen - and I'd be pleasantly surprised if it doesn't - there's still that potential problem. I don't know how well that can be modeled in little animals. Or even big ones. So I'll probably stand pat with this size position at these prices (i.e., I might reload if the sold puts expire worthless at these prices, or if they don't, I would simply hold the assigned shares without adding). I'd like to see more color on these issues, and what makes the new constructs/compounds better at avoiding them. Cheers, Tuck

To: Biotech Jim who wrote (64)	6/13/2017 6:00:11 PM
From: tuck	Respond to of 84

how to deal with patient crises and deaths in these fragile patient populations There's the on/off switch concept from Bellicum, Ziopharm/Intrexon, and Kite/Cell Design Labs. Not seeing Juno involved in this, or developing collaborations to address the above issue (though their publications index does point to a Bellicum approach, I don't get the impression Juno is actually interested in using it). Why not avoid the "on target/off tumor" effect altogether? I gather this has been Juno's approach, via bispecific CARs, since targeting one antigen seems to be insufficient. Though you don't see this mentioned on their website, their publications index points to this approach, too, and they have apparently been working on it for a couple of years. This article is a good review: Bispecific antibodies and CARs: generalized immunotherapeutics harnessing T cell redirection I find this effort, from a UCSF lab particularly interesting (and presumably available for licensing; there is a patent and applications): Precision Tumor Recognition by T Cells With Combinatorial Antigen Sensing Circuits Also this one: Versatile strategy for controlling the specificity and activity of engineered T cells But it seems there's no getting around the need for preconditioning, and its associated problems, as doing without it impacts efficacy too much. Unclear if these newer approaches can address this conundrum, but I hope so. Cheers, Tuck

To: Biotech Jim who wrote (64)	11/1/2017 1:49:35 PM
From: tuck	Respond to of 84

ASH abstracts out, and the JCAR017 study called TRANSCEND has produced results Juno can move forward with. I see the preconditioning regime is continued, though specifics are not given. Some CRS and neurotox, but nothing disastrous. JUNO stock is being allowed to keep it recent gains. High Durable CR Rates in Relapsed/Refractory (R/R) Aggressive B-NHL Treated with the CD19-Directed CAR T Cell Product JCAR017 (TRANSCEND NHL 001): Defined Composition Allows for Dose-Finding and Definition of Pivotal Cohort Cheers, Tuck