This week in medicine 1. The first approved medicine to prevent pancreatitis 2. A positive phase 3 trial for a new mode-of-action (TL1A inhibition) in ulcerative colitis 3. Promising early data for a KRAS G12D inhibitor in pancreatic cancer 4. GDF15 is an early marker – and potentially a targetable driver – of dementia 5. CAR T-cells can induce long term (10 year ) remission in B cell lymphomas And more – full version here! breakingground.substack.com/…

Full dataset for IL-11 inhibition in longevity here: nature.com/articles/s41586-0…

This is cool: inhibition of the pro-inflammatory cytokine, IL-11, slows ovarian aging and preserves fertility (in mice and rats). This is the same mechanism that increases mouse lifespan:

We should pay peer reviewers Paying reviewers led to faster first editorial decisions—an average of 5.5 working days versus 38 days for unpaid reviews, And review quality actually improved (as judged by handling editors on the basis of helpfulness in making an editorial decision) In this six-month experiment, reviewers who delivered a peer review within four working days that their handling editor considered good quality were paid £220 (US$290) nature.com/articles/d41586-0…

Sanofi is taking us straight to the future with this monster in development for osteoarthritis It's a trispecific nanobody that anchors to cartilage (via CAP) and inhibits two cartilage-degrading enzymes, MMP13 and ADAMTS5

Source: Prof. Cutsem today at #ESMOGI26!

Cancer outcomes improve through iterative, stepwise progress that gradually updates the standard of care. A good example here in metastatic colorectal cancer:

How to identify a cancer biologist: show them this chart and see if they get excited

🇺🇸 Happy 4th of July! 🇺🇸 This week in biotech: FDA approvals, Phase 3 catalysts, M&A speculation, obesity pipeline developments, and cell & gene therapy remained the week's key themes. See interesting posts/ppl to check out! 👇 @Franca_ole $SGMO insolvency puts ~$4.6B in potential milestone royalty rights under scrutiny. » x.com/Franca_ole/status/2072… @investseekers $NVO rallied ~40% from March lows, yet was June's most-sold stock among Danish retail investors. » x.com/investseekers/status/2… @adamfeuerstein FDA approves Orca Bio's Tregzi for blood cancers, marking its commercial launch. » x.com/adamfeuerstein/status/… @A_May_MD Reuters: $ABVX was in buyout talks before releasing Phase 2 data, per sources. » x.com/A_May_MD/status/207250… @semodough $VKTX: 3Q26 VK2735 maintenance data could move shares ±10–20%, depending on weight-loss durability. » x.com/semodough/status/20722… @agingroy Researchers built the first synthetic cell from scratch to exhibit aging, via loss of proteostasis after 5–10 divisions. » x.com/agingroy/status/207239… @BioStocks $CANF Ph2a pancreatic cancer study met its primary safety endpoint. » x.com/BioStocks/status/20722… @Andre_AGTC $MANE expects two Phase 3 readouts in H2, with NDA submission planned for early 2027. » x.com/Andre_AGTC/status/2072… @DrSamuelBHume CRISPR-edited T cells take aim at mutant p53, with a 71.4% ORR in pancreatic cancer. » x.com/DrSamuelBHume/status/2… @yaireinhorn $VRTX/$CRSP secure expanded FDA approval for CASGEVY in pediatric SCD and TDT. » x.com/yaireinhorn/status/207… @doepke_michel $PTGX extends gains since October's buyout rumors as $JNJ speculation persists. » x.com/doepke_michel/status/2… @RNAiAnalyst $CAPR faces a major overhang as Nippon Shinyaku still holds 7M shares amid litigation. » x.com/RNAiAnalyst/status/207… @HOThomasWPhelps $NVS/$CRVS? Soquelitinib aligns with Novartis' oncology and I&I focus. » x.com/HOThomasWPhelps/status… @bioinvestor24 Bear case: First liver DILI report for $LLY's orforglipron could come in July/August, if it occurs. » x.com/bioinvestor24/status/2… @Maximus_Holla $TENX confirms August Phase 3 LEVEL readout, with ESC presentation scheduled for Aug. 29. » x.com/Maximus_Holla/status/2…

The medical community has cured a mountain of diseases in the past several decades. Diseases cured thread🧵 In 2013, hepatitis C was cured by direct-acting antivirals.

The main issues with a therapy like this: it requires chemotherapy to deplete the host immune system to make space for the new T cells; it carries a risk of neurotoxicity (ICANS) and cytokine release syndrome; and it targets one very specific p53 mutation, leaving itself open to clear routes of resistance (lose the HLA allele that presents the antigen, degrade p53, or just mutate a different p53 residue). This is from AstraZeneca!

p53 is the most mutated gene in cancer, but we have no therapies to target it - creativity needed! What about this? Patients' T cells were CRISPR-edited to recognise and target the most common p53 mutation (R175H). The best responses were in pancreatic cancer: 71.4% objective response rate in a small group of patients with heavily pre-treated disease:

Thank you to the biotech analysts of X for the stock picks this year — much better than buying the S&P500 😂

In Nature today: nature.com/articles/s41586-0…

Another reason to avoid (or treat) obesity. Colorectal cancer more commonly forms aggressive 'replacement' metastases in fatty livers:

Data sources: Dr. Nilofar Azad / RevMed at #ESMOGI26 today

Daraxonrasib is a multi-specific inhibitor, which also inhibits wildtype KRAS - causing some toxicity. But because Zoldonrasib is specific for G12D mutations (which normal cells do not express), it looks like its addition doesn't add much toxicity - pretty cool!

In human trials, it looks like that replicates. Daraxonrasib already doubles average survival vs. standard care chemotherapy in pancreatic cancer (metastatic, second line) but if Daraxonrasib and Zoldonrasib are used together, responses look (cross trial!) even stronger:

Daraxonrasib and Zoldonrasib are both KRAS inhibitors, but giving them together (in mice) is better than either alone. They bind different parts of KRAS, deepening its inhibition - and they seem to anticipate each other's resistance mechanisms. 🧵

Compelling stuff at #ESMOGI26 today. We (the world) have gone from zero options beyond chemotherapy for pancreas cancer, to now moving towards genuine choice — and even personalized therapies.