NotGenentech
2.7K posts
$NVS paying $2bn for Synnovation's SNV4818, after $LLY paid $1.5bn for Scorpion's STX-478. Mechanistically, seems like good news for $RLAY, bad for $OKUR & $COGT
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I’d rather look at the full dataset once all patients are evaluable (n=96). So yeah, agree with the market reaction and secondary pricing $CTMX
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NotGenentech retuiteado
When the investigators are trying to describe grade 2-3 toxicity
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Could be why pembro might work better than others in its class - this unintended off-target activity is against a legitimate fetal-origin target!
Aaron Ring@aaronmring
One striking example is pembrolizumab (anti-PD-1), the top-grossing mAb and overall best-selling pharmaceutical in the world. In addition to PD-1, we found that it also bound TDGF1/Cripto, and we confirmed that interaction with orthogonal assays.
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Late line CRC therapies in development following $CTMX's data this week (from Guggenheim).
A lot is riding on $CTMX's 10 mg/kg cohort which had just 19 evaluable patients (3 patients were excluded so ITT response rate is lower) so this needs to be corroborated in the dose optimization stage.
Temab-A's ORR is probably in the 15-20% range in the broad CRC population (data in the table are for MET amplified CRC), making $CTMX's ORR superior for now.
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NotGenentech retuiteado
The same western blot image used 23 times in 14 different papers by one Japanese team. The image has been labelled as representing a range of experiments and proteins. This is the most I have ever seen. Perhaps it is a record?
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@spontonic Thx for this. This is what I mean, the synergy thesis in preclinical model seems very weak.
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I have been looking for murine cancer models for PD-1xVEGF bispecifics. Surprisingly, I have not found clear preclinical data of synergy that compares
- aPD-1xVEGF
- aPD-1 alone
- aPD-1 + aVEGF
Am I not looking at the right places? The early work of ivonescimab was comparing to aVEGF.
Would appreciate it if you can point me to more compelling preclinical data.
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@HartungIngo Low efflux pump clearance...lots of normal tissue tox.
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Let me translate this into an actionable statement: We need designer payloads for 2nd generation ADCs. Optimized for low efflux pump recognition & high systemic clearance (to minimize off-antibody tox) with orthogonal cell killing mode-of-actions. MedChems: Now work your magic!
Antonio Giordano, MD PhD@antgiorda
Over expression of efflux pump ABCC1 as mechanism of resistance to ADCs with a TOP1i payload.
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@JacobPlieth The effect size is so small they need to increase the N. I am sure irAE for this asset is a mess.
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Obv we're still desperate for more data on CCR8, but this $BMY imzokitug ph1/2 trial expansion is barely credible. 185 -> 949 patients?! #version-content-panel" target="_blank" rel="nofollow noopener">clinicaltrials.gov/study/NCT04895…
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Is CCR8 the new Claudin18.2? @ApexOnco analysis of an I-O mechanism that's quietly become hot:
oncologypipeline.com/apexonco/ccr8-…
$CHRS $BMY $ABBV $RHHBY $AMGN $GILD $BGNE $FGEN
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$CTMX against the competition
Jacob Plieth@JacobPlieth
My $CTMX expectations, from earlier this month
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@DickMedChem PFS/OS signal unimpressive. Likely to dilute away. I am dubious of this assets ability to move into earlier lines with that GI safety profile.
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The latest dataset from $CTMX is to be considered extremely promising, primarily due to the patients having undergone extensive pre-treatment. The ADC player is highly likely to raise new money. ir.cytomx.com/static-files/f…
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NotGenentech retuiteado
Who knew $REGN was developing an anti-GPRC5D T-cell engager? clinicaltrials.gov/study/NCT07455… $JNJ $PFE $BMY
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Just a hypothetical calculation!
$ABBV $IMGN paid ~ 5x Elahere peak sales projection, but the drug was approved. $TERN-701 could generate $2B peak sales (conservative) - 25% discount (development risks) would imply a valuation of $7.5B = $69 per share.
fiercepharma.com/pharma/abbvie-…
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So when will VCs start microdosing pan-KRASi?
Eric Topol@EricTopol
🆕 @ScienceMagazine An exciting new approach vs pancreatic cancer: "cancer interception" Considered ubiquitous, the pancreas in healthy adults has hundreds of PanINs of microscopic premalignant cancer that can be regressed in the experimental model science.org/doi/10.1126/sc… science.org/doi/10.1126/sc…
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I think it is going to be a cdc7 inh with very high selectivity over cdk9, cdk4/6, cdk1/2.
JLeonard@jeromeleonard5
I think the third mtap small molecule $idya will push in '25 will be a cdkn2A/B inhibitor.
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NotGenentech retuiteado
we actually beat back the fatness
Reddit Lies@reddit_lies
@art_is_found It's basically overnight too
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