June 13, 2024
Barry Bunin, PhD
Founder & CEO
Collaborative Drug Discovery
“Advisory Panel of Experts Endorses F.D.A. Approval of New Alzheimer’s Drug” That’s the headline for a recent article in The New York Times about a committee of independent advisers to the FDA voting unanimously that the benefits outweigh the risks of the newest experimental drug for Alzheimer’s disease—Eli Lilly’s donanemab. The drug, which works through clearing amyloid from the brain, has been shown to modestly slow cognitive decline in patients in the early stages of the disease. While it also has significant safety risks, including swelling and bleeding in the brain, the committee concluded, though, that the consequences of Alzheimer’s are so dire that even a modest benefit can be worthwhile. The article notes that two similar amyloid-fighting drugs were approved recently: Leqembi, made by Eisai and Biogen, was approved last year. That drug’s risks and modest benefits are similar to those of donanemab. Aduhelm, made by Biogen, is the other drug and was approved in 2021 but was discontinued because there was insufficient evidence that it could benefit patients. On top of mounjaro (https://app.pharmakb.com/drugs/Tirzepatide), this is additional excellent financial news for Eli. Lilly
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“A New Synthetic Antibiotic Tightly Binds Bacterial Ribosomes.” That’s the headline in a Drug Discovery News article about researchers at Harvard University using a fully synthetic approach to expand the repertoire of possible antimicrobials to overcome existing antibiotic resistance mechanisms. The synthetic antibiotic, called cresomycin, binds to the bacterial ribosome, surmounting existing antimicrobial resistance mechanisms that have plagued current ribosome-binding antibiotics by being perfectly preconfigured to bind the ribosome tightly. The work, performed in the lab of Harvard’s Andrew G. Myers, and recently published in Science, found that cresomycin inhibits a variety of microorganisms, including ESKAPE pathogens that
are multidrug resistant, in both in vitro experiments and in a mouse model. “Being able to do total synthesis of the antibiotic from building blocks, as opposed to taking the original antibiotic and then doing chemical derivatives of it — that in itself is already a very interesting accomplishment,” said Axel Innis, a structural biologist at the European Institute of Chemistry and Biology who was not involved in the study. “It looks like a really good compound, and we'll have to see how it comes out in clinical trials."
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"Weight Loss Drug Could Reduce Heart Attack Risk by 20%, Study Finds." That’s the headline from a recent article in The Guardian that reports: “A weight loss injection could reduce the risk of heart attacks and benefit the cardiovascular health of millions of adults across the UK, in what could be the largest medical breakthrough since statins, according to a study.” Researchers found that participants taking the medication semaglutide, the active ingredient inbrands including Wegovy and Ozempic, had a 20% lower risk of heart attack, stroke, or death due to cardiovascular disease. The study, presented at the European Congress of Obesity (ECO) and led by researchers at University College London, also found that semaglutide brought about cardiovascular benefits for its participants, regardless of their starting weight or the amount of weight that they had lost. It suggests that those with mild obesity or who have lost only a small amount of weight could have an improved cardiovascular outcome. Prof John Deanfield, Director of the National Institute for Cardiovascular Outcomes Research and the lead author of the study, said “This fantastic drug really is a gamechanger. The study suggests that there are potentially alternative mechanisms for improved cardiovascular outcomes with semaglutide beyond weight loss … Quite clearly, something else is going on that benefits the cardiovascular system.”
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“How Successful are AI-Discovered Drugs in Clinical Trials?" Derek Lowe, in his blog for Science, explores this question posed in a new paper, and finds that, at least so far, humans continue to play a major role in identifying the best targets in the drug discovery process. After reviewing each drug candidate listed in the AI article, he concludes: “What you will see is that in almost every case, these targets were already known to be implicated in the disease under investigation. In some of these examples, in fact there are several drugs already in the clinic targeting the same proteins, or even therapies that are already on the market working through the same mechanisms (C. diff toxin B, e.g.) I don't think any of these are bad targets, let me make that clear.” CDD has taken a similar approach with a new AI module directly within CDD Vault which does not promise a hole in one for drug discovery, but rather uses chemical rich vectors to rapidly and securely identify similar or exact match compounds in ChEMBL and SureChEMBL (for patent novelty), as well as generative bioisosteres.
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Barry A. Bunin, PhD, is the Founder & CEO of Collaborative Drug Discovery, which provides a modern approach to drug discovery research informatics trusted globally by thousands of leading researchers. The CDD Vault is a hosted biological and chemical database that securely manages your private and external data.