handful of excellent books out there that can get you a long ways down the awesome biotech rabbit/wormhole — working through “Eighth Day of Creation” right now and it’s top 0.1% tier, only detracting factor is that it’s oldish (published 1980), but that’s also one of its best factors because it’s written extremely well, in a way we just don’t / can’t write anymore

Listen in as our CEO and founder @lefkofsky recaps Q3 at Tempus ⬇️ Access the Q3 shareholder letter here: tempus.co/4zmfIdj

Q3 was an incredibly strong quarter for Tempus and these results reinforce the durability of our model as our best-in-class diagnostic platform enhances our data and AI offerings. The flywheel we spent more than decade building is in full motion and we expect it to deliver significant value over time for our employees, customers, shareholders and most importantly - our patients.

There’s a CAPR bid lol

$TGTX several years ago, Mike Weiss was the most reviled CEO in biotech. Today, he walks on water. Amazing how times change. Congrats to him and the team on exceptional execution.

“Contagious Clam Cancer: Learning about biology and cancer in unexpected places” We are thrilled to have @themetzgerm speaking at today’s Current Biology Seminar! For all @FredHutch colleagues, don’t miss a great talk today at noon in Pelton!

Which of these 15 AI challenges for cell biology is most urgent? Hilbert’s 23 problems steered math for a century. Our @CellCellPress paper, led by Andrea Califano, proposes 15 for biology, each with a real-world test of AI predictions. doi.org/10.1016/j.cell.2026.…

Now introducing an $XBI version of the game: aditharun.github.io/guess-ye…

Very cool to be at the @CNS_Update evaluating the newest robotic microsurgery technology with MMI and their Symani robot.

As generalized before, most cancer promoting genes are enriched in embryonic neural/neural stem cells, incl. EZH2. They confer cancer cell with neural stemness, which determines tumorigenicity&pluripotency in cells. frontiersin.org/journals/cel… @CR_AACR

Postmortem genetic testing for sudden cardiac death found a genetic cause in about 1 in 5 cases. Most variants were in ACMG secondary findings genes, but wide variation in testing and reporting shows need for standardized autopsy, testing & family followup bit.ly/4fcyrQn

Pharma’s had a monster year because cheap licensing deals in China are turbocharging its R&D productivity and ROI. But what happens when the Hengruis of the world want a bigger slice of the pie and start taking their drugs further on their own? Does pharma give it all back?

One of the larger and more consequential splits in the history of corporate America brought to you by @FT CVS is splitting up its name-brand drugstore business from Aetna and Caremark. Could be announced as soon as Q3 results tomorrow.

You know his name from Campbell-Walsh Urology and his pioneering nerve-sparing technique, now hear his story. At 88, Prof. Walsh joins Surgquest Voices to share the discoveries and decisions behind his extraordinary career. Watch or listen now on wllw.co/zx71Wgbjp!

As you can see, our lab is desperately in need of a new post doc to replace those who have left us. Interested candidates apply here, please repost and spread the word! nam10.safelinks.protection.o…

Bright Minds ($DRUG): should we buy the dip after FDA hold? Not yet; we're waiting for FDA's letter What happened: On Nov 2, 2026, FDA put a partial clinical hold on BMB-101's planned U.S. Phase 2 study in severe childhood epilepsies (DEE), citing toxicity seen in mice and too little pediatric safety and dosing data. The stock fell about 55%, from $54.98 to roughly $24.50. No patients can enroll in that study until the hold lifts. Trials in Australia continue. What we expect: Holds like this are usually lifted eventually; we estimate about a 65% probability. Fixing it will likely require a new juvenile animal study, which points to a 12–24 month delay. Meanwhile, Lundbeck's competing drug, bexicaserin, reports Phase 3 results around year-end 2026. How it compares: Edges: BMB-101 is dosed twice daily, versus three times daily for Lundbeck's bexicaserin (Phase 3). It has no measurable activity at the 5-HT2B receptor linked to the heart-valve risk of UCB's Fintepla (approved; €427M sales in 2025). In lab tests it is "biased," meaning far less β-arrestin recruitment, which may reduce drug tolerance over time. It also has early data in absence seizures, which competitors lack. Caveats: These edges come from lab work and an 11–17-patient open-label study with no head-to-head data. BMB-101 is now 3+ years behind bexicaserin. Stoke's zorevunersen (Dravet, Phase 3 data mid-2027) adds pressure. Valuation: The company holds about $215M in net cash, or roughly $21 per share. At today's price the market values the drug pipeline at only about $40M. Our scenario-weighted estimate of fair value is about $20 per share, with a range of $10 to $37. The stock is not clearly cheap at current levels. Our stance: We are not buying now. FDA's detailed letter (expected around early December) and the bexicaserin results will set the timeline. A pullback toward cash value (about $19–21 per share) or a favorable FDA letter could justify a small, risk-sized position. No position, not investment advice. #biotech #stocks #investing

Thanks @curenash for posting this. People have short memories in MASH. Resmetirom’s P2 missed stat sig on fibrosis. So did sema’s P2, even at 72 weeks. Then came $IVA. Lani’s P2b delivered a ~19pp fibrosis delta in just 24 weeks. And 35% vs 9% achieved BOTH MASH resolution AND fibrosis improvement. That’s remarkable. Now imagine you’re an F2/F3 patient. You’ve got liver scarring. You want that scarring to regress, not just lose weight. If NATiV3 confirms even that fibrosis signal with acceptable safety, think about the conversation in a hepatologist’s clinic. A GLP-1 for metabolic control, lani to tackle MASH and fibrosis. I genuinely believe $IVA could become a blockbuster. Not because of hype, but because of what doctors and patients actually need. If P3 delivers, watch what comes off the prescription shelf. Note it down.

The theory of evolution lays the foundation of our understanding of why and how cancers change over time and adapt to therapy. But cancer evolution is a bit special: it is incredibly fast, with multiple routes to adaptation explored at the same time under therapy, and goes beyond genetic alterations, leveraging on heritable (and therefore Darwinian) epigenetic alterations to accelerate evolution. Important note: whereas genetic alterations are difficult to revert, chromatin changes are, in principle, “editable”. Hence maybe epigenetic drivers of cancer evolution can be "reverted"? Here’s our take, after more than 10 years working in this field, on the genomic and epigenomic evolution of colorectal cancer. Link below 👇

In March I tried to predict $ELTX's AMPLIFY-7P readout with a Monte Carlo simulation. This obviously failed, the trial missed its primary DFS endpoint (HR 0.85). Nevertheless, some of my assumptions were quite accurate. I estimated the median DFS in the observation arm to be between 16 and 22 months, and it reached 21.2 months, while the trial design assumed 7 months. Now @EileenMOReilly presented an interesting pre-specified subgroup analysis at ESMO in Madrid. It turns out that the vaccine (camupepimut) arm carried more ctDNA positive patients at baseline (20.8% vs. 12.5%), a factor that was associated with a roughly 6-fold higher recurrence risk. Splitting by ctDNA status removes that imbalance and results in HRs of 0.51 and 0.57 for the ctDNA negative and ctDNA positive subgroups. So did the trial fail due to some kind of Simpson’s paradox from an unlucky randomization? I would be cautious here. If we add up those subgroups we get to 119 patients while the study enrolled 144, meaning that 25 of 144 patients have no evaluable baseline ctDNA result and are left out. Please correct me if I made a mistake, but as far as I can reconstruct it from the event counts, that is 14 vaccine patients with 9 events (64%) vs. 11 observation patients with 5 events (45%). So it seems that the share of patients that was dropped is the share where the vaccine did worse. The subgroup p-values come from Wilcoxon tests, which weight early events, where the vaccine looks best, while the primary endpoint used the log-rank test. The 95% confidence intervals of all three subgroup HRs include 1 (ctDNA negative 0.25 to 1.02, ctDNA positive 0.22 to 1.48, no prior radiation 0.33 to 1.03). The ctDNA positive HR rests on 6 observation patients who all had an event, with a median DFS of 1.9 months. At least twelve subgroups were tested without multiplicity adjustment. Wouldn’t applying a Benjamini-Hochberg correction be more rigorous here? Don’t get me wrong, I really like this off-the-shelf 7P KRAS vaccine approach and I really "want it to work". Looking at the results I am even tempted to say that camupepimut has some effect. But that does not change my view that camupepimut was probably not handled in the right way. I think the cardinal mistake was to try camupepimut without a checkpoint inhibitor in the first place. The Nature Medicine paper itself blames the failure of checkpoint inhibitors in PDAC partly on the lack of tumor-specific T cells, which is exactly what an efficient vaccine would supply. In hindsight I cannot understand why such a vaccine was tested as a monotherapy in one of the hardest to treat cancers. Of course this is an easy critique after the fact. This subgroup analysis does not change my mind, the primary readout was a weak signal that there is something at work (the post hoc R0 subgroup, HR 0.65), so nothing new here. What I want is that the management changes course, stops this monotherapy approach and continues camupepimut in combination with checkpoint inhibition in the adjuvant setting, which the paper so far lists only as an option for phase 3. So I would wish for a two-arm phase 3 in the adjuvant setting, camupepimut plus checkpoint inhibition vs. observation. Checkpoint inhibition alone has failed in PDAC, so observation is probably the right comparator. That readout would be years away (especially if the combination works). $ELTX plans a phase 1 of camupepimut plus a RAS inhibitor, with or without anti-PD-1, in metastatic PDAC. The company cites a few complete responses in metastatic patients who received checkpoint inhibition after camupepimut as support, although these responses followed checkpoint inhibition and not a RAS inhibitor. An ORR readout could be a closer catalyst than an adjuvant phase 3, but RAS inhibitors already produce responses on their own, so an uncontrolled ORR may say little about what camupepimut adds. Nevertheless, the cash runway is tight, $ELTX needs to raise money which will likely substantially dilute shareholders. Disclosure: I started a (very small) position in $ELTX again, so I am long. $ELTX has a very short financial runway, meaning the risk of total loss of principal is very high. This is not financial advice. Do your own research. I compiled the data, facts and interpretations in this post to the best of my knowledge, but they may contain errors, and I give no guarantee of their accuracy.

Stock up your watchlist 📊 Early November comes in loaded. Here are BPIQ AI’s Ph2, Ph3 & PDUFA catalysts to watch in the first half of the month: $GALT / Ph2b / Belapectin / MASH cirrhosis $BIVI / Ph2 / Bezisterim / Long COVID $ELTX / Ph2 / ELI-002 7P / Pancreatic cancer $LGVN / Ph2b / Laromestrocel / HLHS $MIRM / Ph3 / Brelovitug / HDV $LSTA / Ph2b / MAR001 / High TG $ARGX / Ph3 / Efgartigimod / Myositis $CYTK / PDUFA / Aficamten / oHCM $SMMT / PDUFA / Ivonescimab + chemo / NSCLC $PHVS / Ph3 / Deucrictibant XR / HAE Free preview: $GALT, $BIVI & $ELTX odds are unlocked. Check the image for more details.

Scientists mining the ‘dark proteome’ are uncovering thousands of previously missed proteins, including promising new targets for cancer immunotherapies nature.com/articles/s41587-0… rdcu.be/YxZrAghhPmsa