Drug discovery chemist and blogger
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Articles by Derek Lowe
Merck/Moderna's Melanoma Combination Therapy Delivers Promising Phase 3 Trial Results
Oct 23, 2026, 2:55 PM ET, , Summary Merck and Moderna released clinical trial data on October 22, 2026 for their vaccine (intismeran autogene)/Keytruda combination in melanoma patients after surgery. We had a preview back in August saying that the interim Phase III readout showed "a statistically significant and clinically meaningful improvement", and that the trial had met its primary endpoint (recurrence-free survival).
Now That's An Impurity Story
Here’s a recent paper illustrating an impurity problem that I’ll bet none of us out there have experienced! It describes process work on an antifungal molecule, efinaconazole, which is now available as a generic drug. The authors were checking the purity of various batches of the final product and kept noticing a small peak shouldering the desired one under LC conditions. They estimated it at about 0.06% of the samples (it showed up every time!) and eluted just a bit faster than the real drug.
Time Off
I'll be taking the rest of this week and all of next week off (catching up on some things and recharging my batteries in general) Posting will resume on Monday the 12th, and I'll see everyone then! About the author Derek Lowe Comments
AI Help for Biological or Chemical Weapons
I haven’t been sure what to make of the report that this Science piece is referring to. Anthropic says that it has blocked efforts to use its Claude AI systems for a number of undesirable functions, including possible design of bioweapons. One the one hand, it is unfortunately plausible that sufficiently powerful systems could be used in this manner, and that’s really something that we would want to avoid.
As Close to Carbyne As We're Probably Going to Get
Last year I wrote about the problems in generating carbyne, which is a (hypothetical) allotrope of carbon that is made up of rods of conjugated CC triple bonds, one acetylene stuck end-to-end with another and stretching off into the distance. Smaller versions of these structures have been made, and the outlook from those is not encouraging: as mentioned in that post, these are not very stable and get less stable as the chains get longer.
Safety Warning: Carborane Mixtures
Here’s a paper that I thought deserved a bit more notice than it’s probably getting - there are people who could use to see it who probably don’t read Inorganic Chemistry very often. It’s about carboranes, which are interesting-looking cage-type clusters of boron and carbon atoms. These come in a number of varieties, and they’ve been looked at in several fields of chemistry - inorganic, materials science, but there are even applications in medicinal chemistry.
The Latest On CAR-T: Good and Bad
I’ve written many times about CAR-T cell therapies and some of the variations on this theme. Most recently I wrote back in the spring about some of the more allogenic idea being tried, i.e. ones that concentrate on using more off-the shelf approaches to preparing the modified T cells, as opposed to the usual procedure of taking the patient’s own cells, modifying them ex vivo. That has produced some dramatic successes, but it’s quite difficult and expensive.
I’ve been meaning to write about this paper, which has an unusual variation on the “molecular glue” concept. It’s getting to the point where I’m going to have to stop putting that phrase in quotation marks because it’s become so familiar. But for those outside the field, a glue is a small molecule that (by itself) brings two proteins together that otherwise would not interact in such a way.
The State of AI Antibody Design
I often say that I think that antibody design is one of the better use cases for AI drug discovery at present, because you start with a lot of inherent advantages: antibodies as a class are evolutionarily optimized for long plasma half-lives, and the long list of approved antibody drugs shows you that success is out there to be had.
Phosphorylate and Spare Not
Now here’s a biochemical weapon I hadn’t seen before. This recent paper reports a technique used by a particular bacteriophage (T7) against its bacterial targets. One of the proteins it codes for is a kinase (T7K) whose functions have not been well understood.
More Impossible-to-Ignore Vaccine Effects
I did not enjoy getting my recombinant shingles vaccine (Shingrx). I rarely have strong reaction to vaccinations, but the adjuvant in this one really did give me a sore arm, and the second shot (as one might expect) brought on that symptom even more strongly. But I am very happy indeed that I got that series of shots, because the evidence has continued to pile up that this vaccination is associated with a significantly lower risk of dementia later in life. Read Full Article »
More Impossible-to-Ignore Vaccine Effects
I did not enjoy getting my recombinant shingles vaccine (Shingrx). I rarely have strong reaction to vaccinations, but the adjuvant in this one really did give me a sore arm, and the second shot (as one might expect) brought on that symptom even more strongly. But I am very happy indeed that I got that series of shots, because the evidence has continued to pile up that this vaccination is associated with a significantly lower risk of dementia later in life.
KNOT Offshore Partners LP Earnings Release—Interim Results for the Period Ended June 30, 2026 Original
KNOT Offshore Partners LP Earnings Release—Interim Results for the Period Ended June 30, 2026 ABERDEEN, Scotland--(BUSINESS WIRE)--KNOT Offshore Partners LP (NYSE:KNOP): Financial Highlights For the three months ended June 30, 2026 (“Q2 2026”), KNOT Offshore Partners LP (“KNOT Offshore Partners,” “we” or the “Partnership”; NYSE:KNOP): Generated total revenues of $96.8 million, operating income of $15.6 million and net income of $3.4 million; Generated Adjusted EBITDA1 of $57.6 million; and...
GLP-1 Drugs for Aging?
If you thought that there was a lot of noise and action in the GLP-1 drug area before (medical, financial, societal), just wait. I think that this new paper at Nature is a preview of what’s to come. We’ve already been seeing a good bit of evidence that these compounds have what seem to be beneficial effects well outside of their primary effects on appetite and weight, but this work (building on some previous signals) goes straight for a very big target indeed.
Mutate 'Em All and See If You Can Sort 'Em Out
As much as I love an experiment designed to slice and dice the possible explanations in one smooth motion, I also have always enjoyed the blue-sky “I wonder what would happen if. . .” kinds as well. And the modern era of molecular biology and computation really gives people the tools to do that sort of thing, as this recent preprint illustrates. What If. . .you took a simple virus and mutated every single one of the letters in its genetic code, one by one?
The Alleged Dimethylmercury Incident
We had a weird story develop over the weekend here in the Cambridge area (and among organic chemists in general). I’m glad that I wasn’t trying to blog it as it happened, because it’s taken some turns! This all started last Wednesday night, but most of us only heard something on Thursday when word came of an MIT chemistry building that was being closed off because of a report of someone who had been exposed to hazardous material. Read Full Article »
On vacation until August 31
I’m taking a summer break and will return to posting Monday, August 31. About the author Derek Lowe Comments
The Fault Is Not In Our Trees, But In Ourselves
This is an interesting paper at the intersection of chemistry, botany, and environmental science, and I think it’s probably going to get a fair amount of attention in the press. Unfortunately, it’s also likely that some of the headlines around it are going to mangle the details, so let’s try to straighten those out in advance.
Merck And Moderna's Melanoma Results
Aug 20, 2026, 7:15 AM ET, , Summary Moderna and Merck have been working together for some years now on cancer therapies that would combine Merck’s Keytruda antibody with personalized mRNA immunotherapy from Moderna. Since each cancer patient’s tumor case is indeed somewhat different from any other, the idea is to use biopsy and blood samples to tailor the therapeutic-vaccine effects of the mRNA injections to each patient's profile of neoantigens being produced by their tumors.
Chemistry contains multitudes
Something that I think we should be glad of is that chemistry (as a science and as a profession) can accommodate a wide variety of work styles and personality types. I’m pretty sure that there are several lines of work to which this this does not apply so easily, although I’m willing to hear about counterexamples. But chemists most certainly do occur as several different subspecies. Source: © Sigrid Gombert/Getty Images Which subspecies of chemist do you most strongly identify with?
Merck and Moderna's Melanoma Results
Moderna and Merck have been working together for some years now on cancer therapies that would combine Merck’s Keytruda antibody with personalized mRNA immunotherapy from Moderna. And that “personalized” is no figure of speech: since each cancer patient’s tumor case is indeed somewhat different from any other, the idea is to use biopsy and blood samples to tailor the therapeutic-vaccine effects of the mRNA injections to each patient’s profile of neoantigens being produced by their tumors.
More Potential Alzheimer's Research Fraud
Derek Lowe Science Magazine August 19, 2026 This is a new investigation here at Science that suggests some serious problems in an area of Alzheimer’s work that’s had a lot of attention in recent years. It’s been known for decades that there are mutations in some families and populations that predispose people towards Alzheimer’s-like pathology.
More Alzheimer's Research Trouble
This is a new investigation here at Science that suggests some serious problems in an area of Alzheimer’s work that’s had a lot of attention in recent years. It’s been known for decades that there are mutations in some families and populations that predispose people towards Alzheimer’s-like pathology. I talked about these most recently in this 2023 post, but the subject there was actually on the other side of things: mutations that seemed to be having a protective effect.
A Promising New Alzheimer's Therapy... Maybe
This is an Alzehimer’s therapy idea that will be something to watch, but I must say at the outset that I’m very much in the “Show Me” camp for now. Nature reports on a surgical procedure developed in China that claims to increase the lymphatic flow from the central nervous system and thus allow waste material to be more easily removed. This “deep cervical lymphatic-venous anastomosis” (dcLVA) procedure is the subject of several recent journal articles, but the situation for now is rather murky.
A New Alzheimer's Therapy - Or Is It?
This is an Alzehimer’s therapy idea that will be something to watch, but I must say at the outset that I’m very much in the “Show Me” camp for now. Nature reports on a surgical procedure developed in China that claims to increase the lymphatic flow from the central nervous system and thus allow waste material to be more easily removed. This “deep cervical lymphatic-venous anastomosis” (dcLVA) procedure is the subject of several recent journal articles, but the situation for now is rather murky.
The Proposed Changes in Childhood Vaccination: A Strongly Felt Opinion
Let’s talk a bit about the Executive Order on the administration of childhood vaccines. But let me make it clear up front: I am not going to do the president the favor of taking his arguments seriously and doing any sort of point-by-point refutation. That’s because the premise of the whole thing is that there is something about childhood vaccination - and the MMR shot in particular - that Trump believes has caused an “autism epidemic”.
How Is AI Drug Discovery Doing, Really? Meh.
Derek Lowe Science Magazine August 11, 2026 The deluge of articles, presentations, and press releases on the applications of AI techniques to drug discovery does not make it easy to tell just what those applications are and how useful they might be (at least so far). This is an excellent new article from a number of people who know what they’re talking about in the field and who (importantly) are not trying to sell you anything, either. Read Full Article » Show comments Hide Comments
So How Is AI Drug Discovery Doing, Really?
The deluge of articles, presentations, and press releases on the applications of AI techniques to drug discovery does not make it easy to tell just what those applications are and how useful they might be (at least so far). This is an excellent new article from a number of people who know what they’re talking about in the field and who (importantly) are not trying to sell you anything, either.
This Is Why We Run Trials, Unfortunately
Inflammation is one of those huge topics in medicine that you really can’t seem to escape. The immune system is constantly at work - well, it had better be - monitoring for signs of infection and damage and responding to these through a bewildering number of pathways. It’s become apparent over the decades, though, that the immune response is not only a double-edged sword, but that it might well be larger, sharper, and swinging around more constantly than we realized.
Reassessing Inflammation's Link To Cardiovascular Risk
Aug 07, 2026, 2:30 PM ET, Summary Novo Nordisk was building on a large body of evidence that elevated IL-6 is associated with all kinds of cardiovascular risk. A large trial (ZEUS) just read out a few days ago, and Novo Nordisk's ziltivekimab did lower IL-6 in the treated patients as well as lowered markers of inflammation like C-reactive protein.
Put Your Money Down, They Say
Most people probably don’t realize it, but the prediction/betting market like Kalshi and Polymarket have begun taking bets on things like the success of Phase III drug trials. The New York Times highlighted this recently, and I wanted to weigh in on this idea. Not least because it’s something that I had though about before! That goes back to the early 1990s, when I discussed the idea (with a few colleagues) of what I envisioned as more of a futures market in drug discovery.
Target Practice on the Molecular Scale
I’ve remarked before that one of the big differences in the modern chemical literature versus the “back when I was in grad school” era (which for me is the 1980s, dang it all) is that we now can do a lot more at smaller scales. Detailed pictures of surface and single-molecule phenomena just didn’t exist, for the most part, and we just continue to get better at those things. This new paper is a good illustration. The authors are looking at a reaction on a copper surface, Cu(110) to be precise).
The Gut Microbiome and Cancer Therapy
Here’s some work that ties in with that post I did the other day about bacterial associations with cancer (or the general lack of same). It’s been known for some time that cancer immunotherapy responses are influenced by the human microbiome - for example, antibiotic treatment seems to really dampen the effects of PD-L1-directed antibodies, which is of course not what you want to see.
A Friendlier Fluorination
Let’s do some good ol’ organic synthesis today. Probably not so many of the chemists in the audience will have run the good ol’ Appel reaction (alcohol to alkyl chloride with triphenylphosphine and carbon tetrachloride), because good ol’ carbon tet has been disappearing from the world over the years. You used to see it in the labs more often (it has some interesting solvent properties), and outside of research it used to be common in fire extinguishers and in dry cleaning solvents.
Bacteria and Cancer: The Latest Word
There have been a great number of reports over the years of associations between various bacterial species and human tumor tissue, but the problem is that no one has been sure how many of these associations are real. I last wrote about this in 2023 when a big controversy flared up in this area, and now a recent paper prompts another look.
Bacteria and Cancer: The Latest Word
There have been a great number of reports over the years of associations between various bacterial species and human tumor tissue, but the problem is that no one has been sure how many of these associations are real. I last wrote about this in 2023 when a big controversy flared up in this area, and now a recent paper prompts another look.
Flatworms, Ion Channels, and Burning Mouths
Here’s another one for the “no one ever realized this drug was also doing this” file. And let me tell you, it’s a big file. We develop drugs (for the most part) towards specific biochemical targets, and we assay them against panels of related targets and against common receptors and known toxicology pathways (the few that we know). But there’s a lot more out there, as we are constantly reminded. This new paper is a perfect example.
Preventing Misfolding by Preventing Folding
There are people who will tell you that a cell is just the way that ribosomes make more ribosomes, and I’m not in a position to say that they’re wrong. It’s for sure that these protein-synthesizing factories are extremely ancient, extremely well-optimized, and they’re constantly at work in every living cell reading off sequences from messenger RNA molecules and extruding the corresponding protein sequences.
Taking a Tip From Plants - For the Eyes?
Now this is some futuristic medicine, I have to say (commentary here at Cell). The authors are looking at “dry eye disease” (keratoconjunctivitis sicca), which can have a rather complex biological background. There are quite a few contributing causes (contact lens use, aging, clogged oil glands, decreased tear production overall, and more).
Clinical Failure Rates Over the Decades: Yikes
Derek Lowe Science Magazine July 25, 2026 I’m fond of saying that the most important single statistic about the drug industry is the clinical failure rate, which is (by any reasonable standard) appallingly high. To my mind, everything that is infuriating or inexplicable to outside observers (or patients!) about the biopharma industry traces back to that number, which represents a rate of failure that no other major industry operates under. Read Full Article » Show comments Hide Comments
Clinical Failure Rates Over the Decades: Yikes
I’m fond of saying that the most important single statistic about the drug industry is the clinical failure rate, which is (by any reasonable standard) appallingly high. To my mind, everything that is infuriating or inexplicable to outside observers (or patients!) about the biopharma industry traces back to that number, which represents a rate of failure that no other major industry operates under.
Benchmarking the Benchmarks
For as long as there have been computational models, there have been arguments about how to measure how useful they are. Benchmarking this stuff is a problem all its own, and that problem has just become more fraught as the variety and power of computational chemistry and biology techniques have increased. There have been plenty of calls for standardization over the years, but a persistent problem has been people sort of cooking up their own yardsticks and reference standards.
More Pancreatic Cancer Vaccine Progress - Treatment and Preventative
Let’s talk about pancreatic cancer vaccines, because there are some really interesting long-running projects in that area. I’ve written several times about a therapeutic vaccine for pancreatic ductal adenocarcinomas (the most common type) being developed by Roche and BioNTech, most recently here. This is the one where they make an individual agent for each patient, based on the neoantigen proteins that their PDAC tumors are producing.
More Condensate Secrets Revealed
I have a couple of papers to mention today that (to me, anyway) demonstrate how little we know about what’s going on with biomolecular condensates, the membraneless droplets that appear and disappear in every part of the cell. It’s only been in recent years that these have had the attention that they deserve, and I think it’s fair to say that we have a long way to go in understanding their properties and functions.
The Battle For Sickle Cell
Jul 16, 2026, 7:30 AM ET, Summary Genetix Therapeutics’ (formerly Bluebird Bio) CEO, David Meek, said in an interview with Stat that by 2030, they’ll be treating 1,000 sickle cell patients per year, and that the company is already profitable. Doubt is admissible about both those claims. The other sickle cell gene therapy on the market is Vertex’s Casgevy. The company says they treated 64 people last year, but apparently 30 of those were in Q4.
The Battle For Sickle Cell
I wrote here a couple of years ago about the problems being experienced by Bluebird Bio, pioneers in commercializing human gene therapies. The summary is that despite getting three of these through FDA approval, the company was in desperate conditions and heading for bankruptcy, because none of them were being taken up by potential patients in enough numbers to justify the costs. They went public back in 2013, and at one point their stock was nearly $50/share.
Tau In The Clinic, Again
Jul 15, 2026, 6:20 AM ET, Summary As the evidence has piled up that amyloid by itself is not going to be the answer in Alzheimer's disease, tau has been on the upswing for some years. Now we have another direct test of this idea in human patients: Diranersen, an antisense oligo from Biogen and Ionis directed against tau production itself. Phase II results on this one were reported today.
Tau In the Clinic, Again
As readers will well know, I have been unrestrained in my opinion of the anti-amyloid antibody therapies for Alzheimer’s disease. I think that they show remarkably small levels of efficacy, quite possibly invisible to the untrained eye, at great financial cost. And what’s more, they come with significant risks of cerebral cardiovascular events, and the data are far more clear on that point than on any cognitive benefits.
Amyloidosis Continues To Fight Back
Jul 14, 2026, 9:55 AM ET, , Summary For years, there was one drug that approved to slow progression of transthyretin-mediated amyloidosis, namely tafamidis, which was supposed to stabilize the protein tetramer even in people with the mutation. The various attempts at genetic therapy have used this disease as a proving ground. Back in 2017, Alnylam made some biopharma history with a clinical success in this area using RNA interference.
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