Here’s a story from the Telegraph about a small company (Berg Pharmaceuticals), whose headline certainly got my attention: “Cancer drug development time halved thanks to artificial intelligence”. That set off some alarm bells for me, and not because I fear being replaced by a bearded AI quoting mispronounced Latin tags and John Cleese dialogue. (That would be unnerving). No, it’s that I think that (at this point, anyway) that any group claiming great advances due to artificial intelligence is probably hyping their results. So what’s Berg up to?
Their drug is BPM31510, and you can read through the whole newspaper article without encountering the phrase “Warburg effect“. That’s the target, though, and it’s been a popular one in recent years. There are indeed many tumors that have abnormally high rates of glycolysis (followed by lactic acid fermentation, as opposed to the usual pyruvate pathway). There are a lot of compounds that have been looked at (and are being looked at still) to interrupt this process (the famous dichloroacetic acid is one), and metabolic targeting is considered to be a good-sized field all its own in oncology.
Berg is trying to normalize mitochondrial function, in the hopes that this will derail tumor cell metabolism. It should be noted, though, that there’s still an active debate about whether mitochondrial dysfunction causes the high glycolysis rates, or whether those cause mitochondrial dysfunction. By targeting the mitochondrial end of things, rather than the glycolysis itself, you taken a side in that argument whether you realize it or not. So how are they targeting them? With ubidecarenone / ubiquinone, also known as Coenzyme Q10. This, of course, is a naturally occurring compound in the body, and is available at any health food store. It is certainly very important to mitochondrial function, and supplementation with it would seem an obvious thing to try if you’re trying to restore that activity. Such supplementation has been tried across a wide range of conditions, but it’s worth noting that ubiquinone has been studied many times as a potential therapy or adjunct therapy in cancer.
So when a newspaper article refers to a new drug being developed, it might be worth mentioned that it’s actually quite an old drug, an endogenous substance very much like a vitamin, whose safety profile is not in doubt, and which has been studied before in the same therapeutic area. Berg does have a new liposomal formulation of ubiquinone, which may well be helpful (and which does require its own safety evaluation, although you’d go into this expected success). Where’s the artificial intelligence come in?
Berg Health’s team used a specialised form of artificial intelligence to compare samples taken from patients with the most aggressive strains of cancer, including pancreatic, bladder and brain, with those from non-cancerous individuals. The technology highlighted disparities between the corresponding biological profiles, selecting those it predicted would respond best to the drug.
“We’re looking at 14 trillion data points in a single tissue sample. We can’t humanly process that,” said Niven Narain, a clinical oncologist and Berg co-founder. “Because we’re taking this data-driven approach we need a supercomputer capability.”
It’s been a while since I heard a biopharma company talk about having to use a supercomputer, I have to say, and I wasn’t sure that the term was still around. The company is looked at proteomic, metabolomic, lipidomic (etc.) profiles of cells and tissue samples, and trying to build a model of the disease state around them. This Bio-IT World article is the best description I’ve found, and the best look at the company in general (the word “supercomputer” does not appear). They’re specifically targeting endogenous molecules – no screening, no synthesis (and thus, as that article notes, no composition-of-matter patents, either). They are mechanism-agnostic, at least at first, which might explain why the Telegraph article is all about BPM31510 restoring mitrochondrial function, while this recent AACR abstract from the company is about its effects on the fluidity of the cell membrane as a mode of action.
To be sure, no one will care so much about the mechanism if the stuff works. I can see two studies on BPM31510 at clinicaltrials.gov at the moment, both of them Phase I. The company was previously working on a topical formulation for squamous cell carcinoma, but their Phase II on that one completed five years ago, so it presumably isn’t going anywhere. Their approach is ambitious, although certainly not crazy, but they’re going to want to keep an eye on their press coverage. Talking up “artificial intelligence” and “cutting development times in half” may bring them a bit more notoriety than is needed.