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Bertrand Delsuc Profile picture
@BertrandBio
Dec 2, 2021 • 20 tweets • 13 min read • Read on X
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$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
$NVS Strategy to 2026
main approvals by mkt potential & current "strength of evidence"
earlier stage pipe in pharmaceuticals & oncology
on LP(a) & $NVS antisense
on IgAN: correlates vs proteinuria & LT outcome $NVS $CALT $CALTX & others
on peanut allergy: $NVS launching a ph3 with its anti-IgE mAb ligelizumab
on Sjögren & other AI dzz: $NVS lanalumab/VAY736 (anti-BAFF-R mAb) from $MOR
I skip the neuroscience & jump straight to $NVS onco
only 1 $NVS slide on anti-IL-1B canakinumab in lung cancer, also mentioning gevokizumab backup or in // (different binding mode to IL-1B, more an allosteric modulator than an inhibitor like canak)
More slides on #KRAS obviously, with JDQ443 anti-KRAS G12C
$NVS JDQ443 con't: ph1 in mono & combos with SHP2i, anti-PD-1, SHP2i & anti-PD-1
$NVS SHP2i TNO155: some PC combo data w/ anti-KRAS showing pot. synergy, pot. interest with other TKIs (EGFR, ALK)
$NVS SHP2i TNO155 (cont'd): ph1 summary, broad combo program (incl with $MRTX KRAS G12C inh)

Summary of $NVS agents on the KRAS-MAPK
Of note, the recent FIH of YAD/TEAD inh IAG933 (lots of publication on this pathway in past 2/3y or so)
Now the turn of CAR-Ts w/ $NVS new rapid manuf T-Charge platform, to be featured at #ASH21

<2d manuf (assumedly excl. quality control), aimed to retain naive & stem cell memory T cells in the final soup (same idea than $GRCL Fast-CARs) vs prior process leading to more
differentiated central memory T cells

2 inital programs: CD19 & BCMA
among the $NVS wild card: anti-TGF-Beta (under active form) mAb NIS973, tested in PDAC
$NVS betting on new modalities, also incl. protein degradation with many early stage programs, and through collaborations
$NVS misc: #radiopharmaceuticals pipeline, collab & pie in GT, approach in RNA tx
relevant for $MOR: new ph2a in COPD for CSJ117
fund fact: spartalizumab in still in the submission schedule

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More from @BertrandBio

Bertrand Delsuc Profile picture
Jan 25
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…Image
Image
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).Image
Image
Safety, Efficacy, and On-Treatment Circulating Tumor DNA (ctDNA) Changes from a Phase 1 of Daraxonrasib (RMC-6236), a RAS(ON) Multi-Selective, Tri-Complex Inhibitor, in Patients with RAS Mutant PDAC $RVMD #GI25 #ASCOGI25 #KRAS #NRAS #HRAS

DCO 23 Jul 2024 as prev. presented @ #ENA24 as well, only the ctDNA data are new if I'm mistaken
revmed.com/wp-content/upl…Image
Image
Image
Image
Read 4 tweets
Bertrand Delsuc Profile picture
May 1, 2023
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"
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
in some big EU countries)

1st gen KRAS G12C: druggable but DoR too short due to acquired resistance

actual clinical trial feasibility: some indications / settings are so crowded that it becomes increasing challenging to recruit even for big pharma, yet you need to select sites,
Read 5 tweets
Bertrand Delsuc Profile picture
Apr 26, 2023
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… Image
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
Ocrevus flattish sequentially
Tecentriq sales down ~9-10% QoQ
Polivy stable as well vs Q4
Lunsumio starting to ramp up at 14mCHF

Vabysmo / Evrysdi / Phesgo progressing well YoY, Ronapreve still selling in COVID in JP
Read 8 tweets
Bertrand Delsuc Profile picture
Mar 14, 2023
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…
ND01 - ABBV-319: A first-in-class Glucocorticoid Receptor Modulator (GRM) agonist #ADC for the treatment of B-cell malignancies $ABBV
abstractsonline.com/pp8/#!/10828/p…
Read 42 tweets
Bertrand Delsuc Profile picture
Nov 3, 2022
#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…
IASO BCMA CAR-T update of CN trial ORR 95%, CR+ 74%

3311 Updated Results of Fumanba-1: A Phase 1b/2 Study of a Novel Fully Human B-Cell Maturation Antigen-Specific CAR T Cells (CT103A) in Patients with Relapsed and/or Refractory Multiple Myeloma
ash.confex.com/ash/2022/webpr…
Read 39 tweets
Bertrand Delsuc Profile picture
Nov 2, 2022
$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-/… Image
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.
Benlysta & *Nucava
Read 7 tweets

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