Jiankui they/them

@augurbio Imo the messaging has been while skin fxn can be used, its not strong enough to stand on its own, ie clear efficacy needs to be there. 1yr 10 patients who cant even deteriorate on upright stability, the only metric where there is no placebo effect isn't all that compelling.

I don’t disagree that it isn’t a very stable means of measurement, but I’m not really seeing why the skin FXN would become an issue now. They’ve done other trials, they’ve always been in deep correspondence with the FDA. They have Breakthrough, START, etc. Just seems like if it was a dealbreaker, FDA would’ve said that long ago.

btw $LRMR almost has no shot at AA. Skin fxn is not surrogate for CNS fxn, mFARS improvements in nonamb patients likely just placebo/noise, wont have 30 patients at 6m at filing because 36% discon rate in OLE, modified dosing regimen will only have data in handful of patients..

@augurbio Open to considering is not strong language imo. Besides even that is contingent on demonstrating evidence of exposure-response. On the relevant tissue they leave out cns which should be highly relevant to derisking a confirmatory with upright stability as endpoint.

They’ve been using skin frataxin this entire time and continue to be awarded regulatory designations, including Breakthrough Therapy earlier this year. Not saying you’re wrong, but I’m curious why the FDA would suddenly flip on it when we have this: “FDA stated in written correspondence for a START pilot program meeting that it is open to considering skin FXN concentration as a reasonably likely surrogate endpoint in support of an accelerated approval FDA recommended measuring skin FXN concentrations to support evidence of effectiveness for accelerated approval pathway and acknowledged submitted data appear sufficient to support relationship between increased skin FXN concentrations and relevant tissues such as heart, dorsal root ganglia and skeletal muscle” Unless of course we believe Larimar is lying.

@RNAiAnalyst READ THE CRL -> THE COMPANY LIED

@IC50_cent This study design want agreed on last year.

$repl let's also remember the (old) FDA signed off on the registrational trial design. Also how do you show 'contribution of components' for what should be a synergistic combo? 3 cohorts? RP1 mono, (unethical) PD1 mono (=send patients home to die), combo.

Straight up lying that fda rugpulled them when they said trial would be unapprovable in 2021. Making 4m a year. What an asshole. At what point do these guys start getting prosecuted for securities fraud?

$REPL CRL is WILD...these guys lied for fucking years. Also FDA is absolutely correct here, management story never made sense, cant comp Gr3 to Gr4 population. Also censoring PD in retreated patients is dirty. V little chance this beats opdualag on OS imo this company should die.

Looks like @DrPatrick blocked me like he did Cynviloq. Too bad anktiva can’t enhance the body’s ability to not be a massive pussy.

@WillSpagnoli I mean he adopted a dog with a treatable cancer to do a short bus science experiment on and then has some fluff piece written about it leaving out dog was given a separate immunotherapy inciting a circle jerk for techbio chads

@IC50_cent Oh noooo that would mean he got a dog with cancer from a shelter to prove he could cure it, not just cured it bc he was sad, this crushes the whole story now Who cares it’s a sick accomplishment either way

Turns out the dog guys vaccine was given concomitant with pd1 and looking for investors…so basically the classic single arm io combo grift has now come to n=1 dog studies. Probably wasn’t even his dog tbh

Fade chalamet tonight. No position.

@LizHighleyman My point was he did all this sequencing and protein modeling to pinpoint the tumor driver in an unbiased manner (supposedly) which is already identified for mast cell cancer. Sure enough all this 'work' led him to the target that could've been ID'd w 5 minutes of googling.

@IC50_cent UNSW news release says he tried to get a KIT inhibitor that’s available in the US, but <unnamed company> wouldn’t allow compassionate use for a dog in Australia. cancerhealth.com/article/man-cu…

Very techbro of the dog guy to sequence and use alphafold to find a bespoke therapy for a cancer that is almost unilaterally driven by KIT which has multiple approved inhibitors

@pemulisking 50% chance this guy tries to raise money for a AI platform mRNA startup and this all some publicity stunt

@IC50_cent Hope the dog does well but Christ what a dumb story

IMO $CRVS drug looks inert on cytokine/T cell compartment (data slice & dice). Even if you don’t agree why did the first 2 cohorts with no action on biomarkers show efficacy on EASI? Company unblinded, CEO says last cut TARC doesn’t matter/il4 can’t be measured but have it now…

This is a masterclass in misinterpreting data

@Biotech2k1 @semodough This is incorrect

@IC50_cent @semodough Still better.

$COGT Stifel At first glance, bezuclastinib appears to dominate across endpoints, but when you strip out the placebo effect and control for baseline variability, the two drugs look similar on numerous critical metrics (e.g. TSS % change from baseline, ≥50% reduction in TSS from baseline, skin symptom improvement). Bezuclastinib showed superiority on biomarker endpoints (e.g. bone marrow mast cell burden), suggesting bezuclastinib will be a great option for patients who require a harder hit to mast cells than currently offered with AYVAKIT. We view bezuclastinib as non- differentiating on skin symptoms (e.g. itching/spots), but potentially differentiating on symptoms like fatigue and brain fog.

@Biotech2k1 @semodough Given different absolute placebo effect sizes you should probably think about these things in terms of %s…should rerun the math

@semodough I did the Placebo adjusted endpoints and that statement by them isn't correct. The TSS score alone was about 8 for $COGT placebo adjusted vs 5 for Blueprint. That is a huge difference. That is why they have Breakthrough therapy for this indication.

Like your effectively betting on this blue curve indicating that drug is active in enough patients to beat a non-active control. I just don't know man. CR doesn't matter as primary is PFS. Also if drug wins with a 6m PFS what is the peak revs here? Vor not the right analog...

$NUVB What is PoS in HGG? In Natsume 2022 DS-1001 put up a 10.4wk PFS in enhancing tumors with 7wks time on drug (8/35 pts were low grade). $TNGX TNG908 put up < 8wks time on drug in gbm and terminated. Most of these HGGs no longer addicted to IDH1. Does this beat placebo on PFS?