Did some work this week on Scribe Therapeutics $SCTX and its epigenetic editing candidate, STX-1150, that inhibits PCSK9 transcription. Epigenetic editing via histone modifications and DNA methylation has struggled to make it into the clinic due to off-target methylation; Scribe aims to fix this problem by including DNMT3A's ADD domain within the Cas fusion protein. twonaturalcap.com/p/scribe-t…

Anyone have strong opinions on $IONS ION582 candidate? Seems like it's in trouble unless Ultragenyx's Aspire trial had unusually high placebo rates. What am I missing?

It's a shame Hume formulated his epistemology before beyond rule of 5 molecules came about. Would've been a nice illustration of what he was trying to get at

Disappointed the most recent Cheeky Pint episode wasn't able to get into whether Dante or Tennyson's view of Ulysses is more accurate

Very cool stuff, even if RevMed has deprioritized their bitopic inhibitor!

$catx seems quite cheap?

bioPROTACs are fascinating Don't need to worry about E3 ligase expression levels when your fusion protein encodes one

Fascinating paper out of Johns Hopkins on cancer vaccines for FLC Unlike what Moderna is working on for melanoma (and unlike CAR-T) this vaccine can be off-the-shelf, so patients don't need to wait for treatment personalization nature.com/articles/s41591-0…

Seriously interesting stuff from Dialectic Therapeutics. Really cool use of PROTACs. Don't need to worry about thrombocytopenia if MoA is via degradation rather than inhibition.

If Verve-102/STX-1150 get to market, the PCSK9 space will be a fascinating way to watch how patients weigh daily pills vs biweekly subcutaneous biologics vs once every six month biologics vs one-time, more experimental, therapies.

Man.... $crbu

Don't LDL-C lowering figures like this actually limit Scribe's ability to achieve uptake in would be early adopters (those who currently need to be on statins + bempedoic acid + PCSK9s)? That patient pool needs more like a ~90% LDL-C reduction, and is it really an appealing pitch to say with this one-time treatment you can now cut out one of the three medications? Presumably you'd still have adherence issues, and so you're left with the same problem of patients not being at goal. What am I missing?

Anyone know much about Axogen $AXGN?

Aldurazyme is a very good example of ultra-rare disease drug terminal value......lost exclusivity in 2013. Sanofi still recorded ~310mm euros in revenue last year

Wrote this week on @Triana_Bio's work developing a molecular glue degrader to treat ALK-fusion non-small cell lung cancer. Coolest part about TRI-611 is it leverages a novel degron, and signals the field is making some steps forward in getting to rational MGD design. twonaturalcap.com/p/triana-b…

Good to see shareholders reacting well to Telix's ITM acquisition

Think Michael Moritz has to be one of the few Evelyn Waugh fans today who's not also Roman Catholic