snicobio

$DYN $ARWR Fab CNS siRNA delivery

Soufflé getting provocative in its first public data disclosure at MDA Novel target for muscle-directed AOCs, seemingly capable of outperforming TfR1 $DYN $RNA $NVS

$PLRX Pivoting into siRNAs with integrin-targeting platform. NHP data mid-2026.

Had my doubts following the Capsida news, but it does appear $NBIX is taking the $VYGR FA program forward.

@Sifty_Bios @xbiodude Lower cross-reactivity against mouse/NHP receptors would mean the preclinical data should look worse than it should look, so I'd think it would underestimate human performance.

Ups and downs with next-gen AAV capsids recently. $SLDB $VYGR

@drsprs yo not cool dude

My close friend from high school is a pretty good contra and he just went all cash this morning. Screenshot for proof. Backstory: he's the one that got me back into active investing in May 2020 because he was bored during COVID lockdowns and wanted something to discuss.

@plainyogurt21 @LY4101174 FDA essentially made the trial single endpoint

@LY4101174 Is this good or bad? Is the FDA legit just handing them on a silver platter approval or becoming more stringent? Lean towards leniencyy: "Based on improvements to date in LVMI"

$GBIO pivot to siRNAs and autoimmune. $40M market cap, >$150M cash (2H27 runway), seed stage data package.

@xbiodude pmc.ncbi.nlm.nih.gov/articles/PMC39… I think outperformance can be explained by findings in the paper above and lower cross-reactivity of their capsid in mice/NHP compared to capsids discovered by in vivo directed evolution. $SLDB

@snicobio Totally agree success, outperformed my expectations as well to a concerning degreee

@xbiodude It'll be interesting how Kate/Novartis perform in the clinic, but I'd consider this a success for a 2nd-gen capsid, especially compared to how it looked pre-clinically.

@snicobio “Next gen” for $SLDB lol

@auditor112017 @RNAiAnalyst This is skeletal muscle biopsy. No clinical data on cardiac, but pre-clinically $RNA showed better cardiac knockdown than $DYN.

@snicobio @RNAiAnalyst Is this for both skeletal muscle and cardiac muscles? Any diff in kd between them?

$DYN while #RNAi will almost always win out over RNaseH ASO for knockdown... ...for #DMPK, a nuclearly retained target in DM1, I had considered that ASO may come out ahead. The barely -35% target knockdown at the high dose makes me doubt this will be the case. $RNA, and esp $ARWR- $SRPT well positioned to surpass that.

@path1finder @Sports_bios The lack of dose response is clearly linked to baseline vHOT imo.

@Sports_bios how can one explain the missing dose response for vHOT? see eg x.com/Biopharmaddict…

Slowly catching up the JPM webcasts - .. $DYN decent JPM presentation - with new information on trial design, stats powering on the endpts - and the data supporting the use of CASI for the AA path - .. they probably were quite disappointed w/ the extreme mkt rxn w/ the 6.8 mpk data last week - ... based on the timeline - they should have the DM1 registrational cohort 6 mos data a year from now - .. Then the exon 51 DMD side should have the data in 4Q25 for the dystro primary and maybe some additional data on the functional side - ..Am definitely way more +ve on this story given the valuation down here (~900MM EV) - much more likely to attract strategics (if there are any) vs a 4B mktcap case in 3Q24. jmho.

@Sports_bios Baseline characteristics also were likely the main reason they were unable to show dose-response for vHOT endpoint too.

@Sports_bios Yeah, I think their argument for AA is compelling and would close the gap between them and $RNA for DM1. I'm very skeptical about the CNS endpoint though given it correlates with baseline characteristics.

@LNuzhna Isn’t it nice transformation efficiencies are so bad we can easily pick single colonies too? Feature, not a bug.

Early morning. Empty lab. Smell of warm fresh LB. I stare at the shaking incubator, thinking to myself how absolutely fucking incredible cloning of recombinant DNA is. Over the years cloning kinda became this mundane thing that everyone absolutely hates and it’s a chore that you do to get to the fun part of poking biology. Gotta pause and appreciate it more.

$VYGR Currently being priced as a pure play AAV platform, but slowly building out non-viral programs. Mini $DNLI in the making.

@drsprs @adar170 Lots of biology we still don't understand about gene therapies and translational regulation. Wonder if the lackluster protein expression dynamics for Patient 1 are related to this.

If anything its a negative for cardiac AAV9. $RCKT is using AAV9 vector for the Danon program. Meh results for MYBPC3 but prob Danon does not require as much LAMP2 protein to help. MYBPC3 HCM needs much higher protein levels to have fxn benefit. Hence, $TNYA prob a zero. $RCKT using different vector AAVrh74 and higher viral doses for PKP2 program. That dz also needs higher protein levels, but at risk of more SAEs.

$TNYA pain $RCKT gain?