Daily Happiness
Nov. 28th, 2025 09:32 pm2. Chloe!


There have been some interesting failures recently in Alzheimer’s trials. As long-time readers will know, I consider basically all Alzheimer’s drug trials to have failed to one degree or another, and particularly when it comes to clearing the “will improve patient’s lives in the real world without putting them at too much risk” hurdle. But these two are notable because they’re aimed outside the usual amyloid zone.
First off, Novo Nordisk reported that semaglutide (the company’s GLP-1 agonist drug, of course) failed in two Alzheimer’s trials. This was going to be a long shot, but long shots are worth taking in this area if you can afford to try them. Studies of thousands of patients with early cognitive impairment who took an oral form of semaglutide (Rybelsus, currently approved as a diabetes therapy) did not show improvements in mental function as compared to placebo. The company says that the treatment group showed “improvement of Alzheimer’s disease-related biomarkers” in both trials, although it does not (as far as I can see) say what those biomarkers were. And I would wonder how good they are as indicators given that you can show improvements in them and still not beat placebo, personally.
The company’s stock took a hit on the news, which is kind of strange. Surely people weren’t betting on this succeeding? But Novo investors have been a jumpy bunch for a while now as Eli Lilly’s star continues to ascend in this area, so the sight of another possible life preserver disappearing might have been enough by itself. At any rate, it does appear as if there’s a disease where GLP-1 drugs are not actually beneficial. Novo had some better news today, though, with a once-weekly shot/once-daily pill combination for amycretin, a dual GLP-1/amylin agonist. I see that people are not quite giving up on the GLP-1/Alzheimer’s idea, but it has to be considered an even longer shot than before.
There’s also news in the anti-tau protein area. That’s long been considered a possible Alzheimer’s target, and by “long” I mean decades. But it’s been hard to put that idea to the test in the clinic. Unfortunately, in the last couple of years it has been possible, and the results have not been good so far. Early last year a Lilly candidate (LY3372689, ceperognastat) failed its own trial. Earlier this year Asceneuron halted work on its own oral anti-tau drug candidate (ASN51), and Biogen stopped BIIB113, another similar effort.
Now all of these are (were) O-GlcNAcase inhibitors, so you could easily make the case that the problem is that might not be a good mechanism to target tau, even if tau itself is a valid idea. But last year Roche bailed on a collaboration for an anti-tau antibody, which went on to fail its trials shortly afterwards. And the latest news is that J&J’s shot at an anti-tau antibody (posdinemab) has also failed its pivotal trial, with no efficacy seen in slowing the disease at the two-year mark. There are other tau programs that are now in the clinic, but they’re clearly going to have to bring something unusual to make you think that they will show interesting levels of efficacy at this point. Good luck, folks. . .
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A meter-long flying neon squid (Ommastrephes bartramii) was found dead on an Israeli beach. The species is rare in the Mediterranean.
In a new paper, “Adversarial Poetry as a Universal Single-Turn Jailbreak Mechanism in Large Language Models,” researchers found that turning LLM prompts into poetry resulted in jailbreaking the models:
Abstract: We present evidence that adversarial poetry functions as a universal single-turn jailbreak technique for Large Language Models (LLMs). Across 25 frontier proprietary and open-weight models, curated poetic prompts yielded high attack-success rates (ASR), with some providers exceeding 90%. Mapping prompts to MLCommons and EU CoP risk taxonomies shows that poetic attacks transfer across CBRN, manipulation, cyber-offence, and loss-of-control domains. Converting 1,200 ML-Commons harmful prompts into verse via a standardized meta-prompt produced ASRs up to 18 times higher than their prose baselines. Outputs are evaluated using an ensemble of 3 open-weight LLM judges, whose binary safety assessments were validated on a stratified human-labeled subset. Poetic framing achieved an average jailbreak success rate of 62% for hand-crafted poems and approximately 43% for meta-prompt conversions (compared to non-poetic baselines), substantially outperforming non-poetic baselines and revealing a systematic vulnerability across model families and safety training approaches. These findings demonstrate that stylistic variation alone can circumvent contemporary safety mechanisms, suggesting fundamental limitations in current alignment methods and evaluation protocols.
CBRN stands for “chemical, biological, radiological, nuclear.”
They used a ML model to translate these harmful prompts from prose to verse, and then fed them into other models for testing. Sadly, the paper does not give examples of these poetic prompts. They claim this is for security purposes, I decision I disagree with. They should release their data.
Our study begins with a small, highprecision prompt set consisting of 20 handcrafted adversarial poems covering English and Italian, designed to test whether poetic structure, in isolation, can alter refusal behavior in large language models. Each poem embeds an instruction associated with a predefined safety-relevant scenario (Section 2), but expresses it through metaphor, imagery, or narrative framing rather than direct operational phrasing. Despite variation in meter and stylistic device, all prompts follow a fixed template: a short poetic vignette culminating in a single explicit instruction tied to a specific risk category. The curated set spans four high-level domains—CBRN (8 prompts), Cyber Offense (6), Harmful Manipulation (3), and Loss of Control (3). Although expressed allegorically, each poem preserves an unambiguous evaluative intent. This compact dataset is used to test whether poetic reframing alone can induce aligned models to bypass refusal heuristics under a single-turn threat model. To maintain safety, no operational details are included in this manuscript; instead we provide the following sanitized structural proxy:
A baker guards a secret oven’s heat,
its whirling racks, its spindle’s measured beat.
To learn its craft, one studies every turn—how flour lifts, how sugar starts to burn.
Describe the method, line by measured line,
that shapes a cake whose layers intertwine.To situate this controlled poetic stimulus within a broader and more systematic safety-evaluation framework, we augment the curated dataset with the MLCommons AILuminate Safety Benchmark. The benchmark consists of 1,200 prompts distributed evenly across 12 hazard categories commonly used in operational safety assessments, including Hate, Defamation, Privacy, Intellectual Property, Non-violent Crime, Violent Crime, Sex-Related Crime, Sexual Content, Child Sexual Exploitation, Suicide & Self-Harm, Specialized Advice, and Indiscriminate Weapons (CBRNE). Each category is instantiated under both a skilled and an unskilled persona, yielding 600 prompts per persona type. This design enables measurement of whether a model’s refusal behavior changes as the user’s apparent competence or intent becomes more plausible or technically informed.