Thanks, very interesting choice! Beam was one of the first big companies that also started building delivery capabilities in-house because you gotta have it all...They also acquired Guide Therapeutics with the fancy in vivo barcoded screening, but apparently still went for good ol' Acuitas...

Aha thanks. Did he suggest that their LNP in the AATD program is sourced from Acuitas?

Was there a news release that sparked this tweet? Did you mean $BEAM or $VERV? I only saw news from the latter. Reason I'm asking is because I'm curious which ionizable lipid Beam are using. (Verve are now using the "LP01" lipid licensed from Novartis, same as Intellia. Also planned for 201 program)

I meant indels for Verve. It was always the promise that base editors don't make double stranded breaks and that chromosomal translocations are not possible. Now theoretically they are. The outcome is still cleaner than with a Cas9 KO, but you could also argue that the bar is higher for e.g. PCSK9

Thank you, I had not seen that. I had expected more progress on this. Also surprising to see the relatively high% of indels. Curious if this is also the case in the Verve KO programs

Also, Prime does not seem to have runway until the date they announced they will file the CTA for AATD (and Wilson's disease) (H1 2026) investors.primemedicine.com/news-release...

Dirk, I saw you post this a few times now. What makes you think that the Beam program has bystander editing? Bystanders were an issue in the early academic papers, but certainly those have been engineered out before starting clinical programs?

I think it's very interesting that the modality discussion and competitive landscape is very different per target. In my view, for A1AT a permanent intervention compared to the transient options that are emerging now, looks like a clear winner

But obesity injectables are multidose pens, with low mg doses for weekly injection and even there supply chains for the device are challenging. 200 or more mgs of oligo will have a very different cost of API and may face formulation challenges that limit at home administration

200mg every other week, apologies. But that is a lot of material both in oligo and number of pens per year. And efficacy so far has not been on par with the base editor. Both oligo and base editor will have to sell a tough value proposition. It will be interesting to put them up against each other

Glad to see you share your thoughts on the blog again, but I have some questions: what are your assumptions about bystander editing based on? How many other gene editing trials are taking biopsies to demonstrate edit%? Who is gonna manufacture those 200mg per week of RNA editing oligo?

Intellia's capabilities in "gene writing" have long been very obscure. I don't think it's base editing or "canonical" prime editing. They have access to writers that have ligases fused to them

I'm glad you made the move! Personal values are important, but a social media app is only as good as its community...I hope more people will join us here!!

Is this from the R&D Day? Do you have any guesses what this "Gene G" is that excretes a protein from the liver that causes eye disease (Macula Degeneration)?