Preliminary Safety, Antitumor Activity, and ctDNA Changes with Zoldonrasib (RMC-9805), an Oral, RAS(ON) G12D-Selective, Tri-Complex Inhibitor in Patients with #KRAS G12D PDAC from a Phase 1 in Advanced Solid Tumors $RVMD #GI25 #ASCOGI25

DCO same as prev. presented @ #ENA24 (2 Sept 2024)
revmed.com/wp-content/upl…
on the other hand, the ctDNA data are new $RVMD #GI25 #ASCOGI25

rate of 100% reduction in #KRAS G12D VAF a bit lower with 9805/zoldon (G12D inh) than in G12X/RAS with 6236/darax (RAS-multi inh)

now let's see how it'll translate in larger n in terms of ORR / DoR / PFS in G12D

nothing on mechanisms of resistance to either agents

incremental updates overall imo

It would be interesting to look at the ctDNA data of other RAS(OFF) inh in PDAC, to assess any predictability on efficacy outcomes of VAF reduction (no time to do that right now but that's what I'd do).

nice #thread by @Atelfo

the dual view of oncology being the top area for BD/M&A is that it's also probably the top area in terms of absolute wasted money

peak nb of running onco clinical trials in 2021 likely reflecting somewhat of an age of disillusionment of IO ("somewhat of"

https://twitter.com/Atelfo/status/1653006693515624451

b/c when you see 40 IL-2's are still in the pipe, it seems there's no such thing as disillusionment for some)

tgted onco = challenges in actionable mutation testing (e.g. I saw a chart last week -unfo I lost the link- showing that a tgt like RET was tested in <50% of NSCLC pts

Roche $ROG $RHHBY reports strong sales growth in base business of both divisions in the first quarter; Group sales decline due to expected drop in demand for COVID-19 tests

rev -7% (-3% cc), Pharma +5% (+9% cc)
globenewswire.com/news-release/2… rev 15.3bn vs ~14.8bn in CHF so seemingly a beat on top line

guidance confirmed: low single digit decline in group rev at cc, core EPS to decline consistently at cc, but dividend to increase in CHF

The #AACR23 abstracts will be accessible from here (not all sessions populated yet at the time of this tweet)
abstractsonline.com/pp8/#!/10828/ "new drugs on the horizon":

ND03 - Discovery of ARV-766, an androgen receptor degrading PROTAC for the treatment of men with metastatic castration resistant prostate cancer $ARVN #PROTAC
abstractsonline.com/pp8/#!/10828/p…

#ASH22 abstracts are live
ash.confex.com/ash/2022/webpr… first data of $GMAB CD38-heaxoby not really great

3254 Preliminary Dose-Escalation Results from a Phase 1/2 Study of GEN3014 (HexaBody®-CD38) in Patients (pts) with Relapsed or Refractory Multiple Myeloma (RRMM)
ash.confex.com/ash/2022/webpr…

$GSK +1.4% in London, apparently beating both top & bottom lines, rev guidance upgraded but not EPS

GSK delivers strong Q3 2022 sales of £7.8 billion +18% AER, +9% CER and Total EPS 255.9p +>100% AER, +>100% CER; Adjusted EPS of 46.9p +25% AER, +11% CER
investegate.co.uk/gsk-plc--gsk-/… Obviously, Shingrix is the main driver, but Menveo also did well (+ve policy in FR), and immuno-inflammation/respiratory/others thanks to Benlysta & Benlysta. Onco also but that's such a small franchise at GSK.

$NOVOB +5% this morning, strong Ozempic/Rybelsus. 2nd weak quarter in a row for Wegovy.

Novo Nordisk's sales increased by 26% in Danish kroner and by 16% at CER to DKK 128.9 billion in the first 9 months of 2022 globenewswire.com/news-release/2… $NOVO Q3'22 slides
novonordisk.com/content/dam/nn…

PFIZER $PFE REPORTS STRONG THIRD-QUARTER 2022 RESULTS AND RAISES 2022 OUTLOOK

double top/bottom-line beat
rev lower end/margin/EPS guidance slightly upgraded

businesswire.com/news/home/2022… $PFE Q3'22 slides
s28.q4cdn.com/781576035/file…

$NVS R&D day slides
novartis.com/sites/novartis…

$SAN $SNY Vaccine day slides from yesterday
Part 1
sanofi.com/-/media/Projec…
Part 2
sanofi.com/-/media/Projec… $NVS featured multi-b$ products

$SAN $SNY sees limited opportunity for flu/COVID vaccine combo as fo now "mRNA safety profile unfit for flu market", I think I agree with that, except maybe for the elderlies?

EMA status on last Friday: 142 cases in April out of 17m doses w/ $AZN vaccine➡️316 at the end of May = 174 new cases out of 19m add. -first- doses of 1st doses in the EEA, i.e. stable

Thrombotic Thrombocytopenia after ChAdOx1 nCov-19 Vaccination $AZN
nejm.org/doi/full/10.10… rate, but↘️in fatal events (deemed related to the awareness work of the agency)

A lot of focus on transfection or gene-editing of haematopoietic (& progenitor) stem cells in just one week:

$MRNA a week ago $ALCLS $CLLS on last Friday with their TALEN gene editing tech for HSCs (lead program in Sickle Cell Disease)

$MOR finally pulling the trigger on M&A, putting cash from Bonds to work on this $CNST acquisition, with the assist of Royalty Pharma to increase the range of accessible M&A targets. BET & EZH2 inhibitors indeed seem to be relevant target to $MOR positioning. Had to do tradeoffs

https://twitter.com/BertrandBio/status/1326910113496649729

for main runners in the partnered pipeline though (Tremfya $JNJ royalties, pot. royalties from $GSK for otilimab & from $RHHBY $ROG for gantenerumab).

Debate on potential for single dose in the UK. Which is aligned with a thought I previously shared. You cannot do it just like that but at least it deserves some second thoughts.

More data needed before giving just one vaccine dose, says Covid adviser theguardian.com/world/2020/dec… There's also this mention of the rigid "by age" strategy for vaccination, which I agree with. After the most vulnerable and the 60-65+, I also thought at vaccinating the population of potential super-spreaders, i.e. 18-25y or 18-30y (or 16-25y/16-30y), then going downwards from

$LYS +32% in Paris trading this morning, with a press release worded like the "highly stat. sig." mean change in CSF HS concentration was saying it all, but unfortunately that's not really the case.
Directionally the variation seems OK, but 1/ p-values don't provide any magnitude of an effect by themselves (unless you reverse some other data), and 2/ one also needs to take into account where the bar is ideally.
On point #1, Abeona already provided data with "highly stat. sig." (assuming this measn "p-val in the range of ~0.001 vs baseline") according to