Paul D. Rennert

a (presumably primordial) Ig-like domain regulates the disease relevant SWI/SNF chromatin remodeling complexes that's pretty cool science.org/doi/10.1126/sc…

@Microinteracti1 The United States it is undoubtedly the greatest military power on earth, but that is meaningless because its diplomatic skills are those of a distracted 5 year old. #Witkoff #Kushner #Rubio

@dgermain21 maybe secrete a little IL-18? or the IL of your choice ... or whatever else (add a little mRNA vax?, eat some probiotic mix?, express a TGFBR-dn?)

As sci-fi cool as in vivo CART is and as much as I want it to succeed, I still can't help but think about the fact that we know the "lymphoma microenvironment" plays a huge role in CART efficacy in DLBCL. But we don't know whether it's patients with "TEX" LME who have poor outcomes post-CART because (1) the tumor itself is insensitive to CART, (2) the post-production CART is wimpy, AND/OR (3) the pre-production apheresis product is lame going in. I have some worry that in vivo CART may work great for patients with favorable LME (just as SOC auto CART do) because their circulating T cells are happy, their CART products are potent, and their tumors are sensitive to CART. But the patients in highest need for better therapies will be equally (if not more) resistant to in vivo CART as they are to auto CART because you are asking ALL of the CART process (production AND treatment) to happen in the unfavorable patient milieu... Maybe/hopefully I'm wrong?

no one is focused on allo

pretty cool: IL-33 antibody for the win in COPD astrazeneca.com/media-centre/p… $AZN

From @NatureBiotech: New rules spur cell and gene therapy trials in China “Once proven safe and effective in investigator-initiated trials, therapies [in China] can then be given to patients as treatments, again without requiring national regulatory approval. And the hospital that made the therapy and conducted the trial can charge for the treatment, creating a financial incentive for hospitals to deploy high-quality cell and gene therapies. This situation contrasts with that in individual European Union countries, for example, where regulations enable hospitals to deliver investigational cell therapies when few or no approved alternatives remain. But, unlike in China, national regulatory approval is usually needed to go ahead with testing… In the United States, the process is more onerous. Hospital-developed cell therapies destined for patients require an Investigational New Drug application approved by the US Food and Drug Administration, with some exceptions for compassionate use.” @US_FDA @HHSGov nature.com/articles/s4158…

wtf

@HochstatMichael and I have a different question ... why are the autoimmmune CAR players - $CABA, $RNAC - so beaten down despite strong early data?

@HochstatMichael this guidance has been around informally for a while now... hence Lyell's clin trial design changes.

🚨 CAR‑T Approval Risk Just Jumped The FDA just rewrote the CAR‑T rulebook: ✅ randomized trials required, ✅ must show superiority over SOC, ❌ no more single‑arm shortcuts. Every old‑model program is now repricing risk. ⚠️ Risky / High‑Volatility Stocks •Autolus (AUTL) – early‑stage, trial-dependent 🧬 •Capricor (CAPR) – speculative, small pipeline 💉 (Smaller CAR‑T biotechs with single‑arm data exposure) 🏛️ Safer / Big Players •Gilead (GILD) – Kite Pharma, diversified 💊 •Novartis (NVS) – Kymriah, early mover 🚀 •Bristol Myers (BMY) – CAR‑T + oncology portfolio 🔬 •J&J / Legend Biotech – multiple myeloma CAR‑T 🔹 📌 Investor Takeaways •Trials now cost more 💸, timelines longer ⏳, execution risk higher ⚡ •Smaller biotechs = volatility risk 📉 •Big pharma = more cushion, CAR‑T is just one piece 🛡️ ⸻

Scholar Rock's anti-TGFb1 antibody clinical study with early data in oncology indications... minimal AEs and signs of durable efficacy in checkpoint-refractory patients. $SRRK nature.com/articles/s4159…

ok but yawn... nature.com/articles/s4158…

What happens when the grid fails? Prediction: propane wars will precede water wars... you'll want to keep those emergency generators for AC running until you die of thirst.

The Financial Times covered recent initiatives at Cancer Research UK (CRUK) including a nice piece on the ongoing Aleta Biotherapeutics clinical trial in CD19-CAR-T treated B cell lymphoma patients. ft.com/content/153bf7…

Ante este Rothko puedes sentir primero un temblor; luego, algo parecido al síndrome de Stendhal, un golpe tan fuerte que te deja sin palabras.

@bbu lovely

Robert Mapplethorpe Two Vases and Flower, 1985 .

stunning week in cell and gene therapy: in vivo base editing of PCSK9 delivered via LNP, w clinical data (Nat Med), preclinical POC of CAR-astrocytes engineered w AAV (Science) and of self-amplifying RNA delivered IM (also Science), Japan approves gene therapies using IPSCs

and a timely review ... pros and cons of CAR-T therapy in autoimmunity and inflammation nature.com/articles/s4157…

an interesting follow-on question is what level of sustained efficacy do CAR-Ts need to show in refractory autoimmune disorders like gMG, CIDP, versus anti-FcRn or anti-C1s antibodies, especially if long-term rituximab maintenance is needed to maintain the CAR-T-induced response

interesting and different efficacy outcomes in ASyS and SSc autoimmune patients treated with blinatumomab (CD3/CD19) and teclistamab (CD3/BCMA), respectively, + Rituximab maintenance. Potential for targeting both BCMA and CD19, especially in ASys. nature.com/articles/s4159…

It’s important that you understand what happened last night. Last night, Stephen Colbert interviewed Democratic Texas Senate candidate James Talarico, a candidate who, by all accounts, is on track in the polls to flip Texas blue. In response, Trump’s FCC reportedly threatened CBS if the interview aired. CBS caved and pulled the segment, citing “financial reasons.” In modern American history, no president has been more hostile to free speech than Donald Trump. But censorship always backfires. Here’s the full segment Trump didn’t want you to see.