BREAKING: $vrtx $alpn $xbi Been quiet on the ESMO action because I spent the weekend going through a NEJM article. Before going any further note that I I'm biased, long $vera and loud about it so don't take my word for anything below. Every claim below chained to a public doc you can open yourself (hyperlinked at the end) (also final thread with a layman term summary for generalists new to the story) So two things happening concurrently, me trying to find more news on the CMC issues + trying to get insights from ASN. Through this process I also heard the murmurs coming out of ASN, so I did the boring thing and pulled the full supplementary protocol $vrtx posted alongside the NEJM RAINIER publication on Oct 23. Turns out there is also a 136 page citizen petition landed on the FDA documenting the same machinery from the EU protocol version on CTIS. RAINIER ran an invisible safety scaffold around IgG the entire trial, and it's written in $vrtx own NEJM supplement. Pts with baseline IgG below 700 were excluded before enrolment (appendix p14). On study, central IgG was tested monthly, and every result routed the next dose per Table 15 of the protocol (p98): at 300 or above, continue. Between 150 and 300, the IRT system replaced the next active dose with matching pbo, with the pt, investigator, site AND sponsor all blinded to the swap, resuming only once IgG recovered, again with everyone blinded to the change. Below 150 confirmed, permanent dc, and only at that threshold does the site get told the number. Appendix 2 of the protocol (p98) names hypogammaglobulinemia an expected pharmacodynamic effect of pove and instructs investigators NOT to independently obtain Ig values via local labs (except where medical mgmt requires it), reporting to the sponsor immediately if they become unblinded. Section 4: PK, PD, B cells and all Ig levels blinded to subjects, sites and sponsor. Sit with what that means for every clean safety headline you've read. 0 dc’s for low IgG, balanced serious infections, no IVIG. All of it was generated inside a system that tested monthly, intervened automatically below 300, and kept everyone, sponsor included, blind to the lab driving it. The trial characterizes the safety of a monitored hold and resume strategy. It cannot characterize the safety of dosing through a falling IgG, bc the design intervenes before anyone can observe that. You will never trigger a threshold the protocol prevents from being reached. The petition makes exactly this point and notes the counterfactual was never observed. The Mar 9 interim release reported neither the incidence nor duration of IgG below 300, nor how many active doses the system withheld. What it did show, buried in the AE tables, was URTI at 18.3% on pove vs 11.4% on pbp, an exploratory RR of 1.61, an imbalance that emerged despite the protective holds being live. The NEJM supplement adds the PD reality: Fig S7C shows IgG down roughly 38% by wk 24 and still drifting through wk 48, on an N thinning from 372 to 16 at the late visits. When the petitioner corresponded with the company about hypogam disclosure, a rep described the data as a restricted value in an ongoing trial, per the petition. And we already knew from RUBY 3 that severe hypogam (IgG below 300) hit 5% at 80mg, 12% at 240mg and 10% in pMN, in tiny cohorts, with every case emerging after wk 48. Late, unpredictable, and exactly where a 36 wk interim cannot see. To be fair, and this matters…the petition is not a fraud allegation and neither is this post. The question on the docket is if the trial needed monthly IgG surveillance and automatic holds to produce its safety profile, should the label require the same? FDA has to answer that in writing.

Speaking to my FDO (forward deployed oncologist) right now who is live at $MRNA presentation. Notes so far: - no standing ovation - death imbalance bad - boots on ground are not jacked up about extension to tougher cancers - HR naturally being compared to neoadjuvant key only Doesn’t quite seem like home run so far, obviously excited for the space though to continue to take off. Would be curious if anyone trying to trade Moderna on the weekend on these data points.

Real test of hypocrisy of media and investors. Let’s see! Where are my background rate calculators?

This could put a damper on China pharma deals (and other investments) in an unexpected reversal endpoints.news/treasury-prop… probably will be viewed as positive for $BBC and $XBI

So HR is better than expected. So that's why MRNA was strong lately but I believe that we will see sell the news as MRNA is so expensive till we will see more evidence that cancer vaccine works.

The black rifle coffee alpha male takes a sip from his thermos and looks out from the bunker to the battlefield, it’s hell out there. “Perfect” He thinks He adjusts the sights on his custom-built 16-inch 6mm ARC AR-15 with a Proof Research carbon-fiber barrel, JP Enterprises silent captured spring system, and a Geissele Super Dynamic Enhanced two-stage trigger. He picked it because the trigger felt smooth against his $350 carbon fiber combat gloves, and the alloy magazines were 20 grams lighter against his $2200 Kevlar vest. He mindlessly feels at his tactical pouch, he has a 10 year supply of testosterone cypionate in it, just in case the pharmacies get hit. He smirks, “Daddy needs his combat fuel.” He’s been on TRT for 7 years, his testes have cobwebs on them. He steps out of the bunker, he’s spent years training for this moment, doing weighted carries, getting “don’t tread on me” tattoos, bow hunting, having a beard. “It’s fuckin showtime.” He announces. Just then he feels something lightly tap his leg. He glances down. It’s a 17 dollar drone off temu. It has a decal on it. “Is that… hentai?” His legs are blown smooth off. 12 miles away in a disgusting room illuminated only by the degenerate glow of purple LED strip lighting, a 17 year old leans back in his cum stained gamer chair. He’s grown so frail and sickly his friends and family keep mistaking him for Asmongold. He grabs another 30mg vyvanse and washes it down with a cold chicken nugget. “GG faggot” He’s killed 500 men.

@my_ueg Obefazimod data at #UEGW show that, in its ***100%*** advanced-treatment refractory population (which includes JAK failures), Obefazimod *still* produced a higher absolute AND placebo adjusted maintenance endoscopic remission rate than Rinvoq in its *overall population*, which of course included many AT-naive patients. ...Obefazimod showed a higher absolute and adjusted AT-IR ER rate than any P3 trial of ANY drug has ever shown in its OVERALL population.....versus the 100% advanced-treatment refractory population in Obefazimod's ABTECT trials. Just insane efficacy. All from a safe once-daily pill with a novel MoA...