Griz

[Griz @camerons_dayoff]

Elegant preclinical work in HD. Pub was just 6 days ago. Hopeful to see this type of work in the clinic soon.

Utilizing bodies intrinsic machinery to contract the length of CAG repeats is completely differentiated from the current pipeline of $QURE, $ALNY, etc at this time.

[Bench to Bedside @bench2bedside_]

Cas9 Nickase induces single stranded cuts into CAG repeats of R6/1 HD mice. These "nicks" generate single stranded gaps which create imperfect hairpins that are naturally "shortened" by the cellular repair mechanism itself.

Elegant safe correction of CAG repeats, at multiple disease loci, without double stranded breaks to potentially limit off-target effects.

Key findings for translation to humans:
1. Cells transduced with both viruses contracted readily, often down to <36 repeats (fig. S3, P = 0.045), suggesting that repeat sizes at least down to 47 repeats are targets for contraction.

2. CAG repeat contractions translate to shorter polyglutamine stretches (See Figure 3).

3. In vivo results show reduced mHTT inclusions, specifically in the striatum.

Limitations and additional perspective are highlighted by the Cardiff group within the paper.

@cardiffuni @UKDRI @Huntingtons @Alnylam @uniQure_NV

https://t.co/HSVqhlg92g

[plasticnewt3 @plasticnewt3]

Anthropic S1 analysis recap: People who can't read financial statements telling people who can't read financial statements that they can't read financial statements.

Since no one has mentioned it, it's worth reading the convertible loan agreement Anthropic signed with Amazon (link below).

[Griz @camerons_dayoff]

@ValueReporter That is why patients take statins and PCSK9 inhibitors. I may be misunderstanding your point, but I believe you are saying to switch from passive to reactive CVD care? You believe you need 70%+ LDL receptor upreg in severe dyslipidemias?

[Griz @camerons_dayoff]

@BiochemKev Any thoughts on where mRNA vaccine drug delivery is headed?

I’m particularly interested in the lymphatic system. Have some connections with these folks.

https://t.co/ob6KXyapsy

[Griz @camerons_dayoff]

@RNAiAnalyst Just to be clear - the delivery technology is the moat. Could care less about the therapy in this case. I am pessimistic about Tau lowering agents.

[Griz @camerons_dayoff]

@RNAiAnalyst Can argue that if this shows a positive signal that Lilly would buy $ARWR within weeks. Internally, the folks at Lilly are obsessed with pre-clinical alzheimer's disease and are building significant infrastructure around earlier detection and triaging of patients.

[Griz @camerons_dayoff]

@RNAiAnalyst Have some resources that I could share around how they are thinking of AD if interested.

I also may buy ARWR tmmrw pending read through; did not know about this program...

[Griz @camerons_dayoff]

@doctorcfa Totally fair. I made what I believe to be a similar mistake with Moderna. Had 30% of PF allocated in 20s, did not have the patience. Long tail here. Ignoring the noise, selling calls, and I will see you at the beach in 2028.

[Griz @camerons_dayoff]

@doctorcfa Find me a time this stock has not filled its GAP. Always does.

Sitting at massive resistance at 24/25. Should be your long-term entry point from technical perspective too

[Griz @camerons_dayoff]

@doctorcfa Key to this stock is just do the opposite of X biotech sentiment.

I am buying MORE today and hunkering down here. Will sell calls as needed but gotta love it down here.... thesis is completely intact with increased cash pos.

[Griz @camerons_dayoff]

My first takeaway from Dr. May's latest report...

IL-17 blockade of any kind hits a ceiling set by other biology. HS looks similar?

Conflicts with UCB's messaging shaping market narrative of IL-17A + IL-17F. Dislocation.+BAFF orthogonal mechanism call option. $ZURA @A_May_MD

[Griz @camerons_dayoff]

@Biohazard3737 Would also note that the way contracts are structured significantly varies (ICFs, Rands, Monthly subs) and then actual internal targets of CROs do NOT align with company expectations which = delays.

[Griz @camerons_dayoff]

@Biohazard3737 Having provided 100s of RFPs to Lilly, Abbvie, and JNJ among others it really comes down to indication and protocol specificity. Lot of biotech companies come to you with V1 of a protocol to ask for an estimate and that can easily miss by 10s millions....

[Griz @camerons_dayoff]

@OptionsHawk Any thoughts on FMC today? -90% peak to trough. Agrochem cycle bottoming? Any put sellers? Seeing significant insider buys in low teens which are underwater

[Underdog @Underdog]

Phillies fans watching Aaron Nola end their season in the first inning

[Griz @camerons_dayoff]

"You can really tell the quality differences between the two rosters... the bullpen for example when you needed someone... the length of the lineup" - Joey Votto

Schwarber and Harper proceed to go B2B

LOCKEROOM MATERIAL

@NBCSPhilly @PhilliesNation @ah_pod

[Griz @camerons_dayoff]

@ChillBanking Once weekly? 😭

[Griz @camerons_dayoff]

@ChillBanking $NVO is boring… might work in the year+ timeframe but my goodness they hate innovation

[Griz @camerons_dayoff]

Where can I apply to be the CEO of $NVO? Absolute buffoons running this company

[Griz @camerons_dayoff]

@pawcio2009 Might want to buy some thiamine supplements