Biopharma can be a weird place. Breakthroughs happen, although not as often as the press releases would have everyone believe, and we certainly don’t always see them coming. So when word comes of some amazing new therapy, you can’t dismiss it out of hand, because amazing new therapies do arrive from time to time, and sometimes from unexpected directions. On that famous other hand, though, there is an awful lot of clueless hype in this business, too – people taking advantage of the wild-breakthrough situation to claim that they’ve found one, too, even though they’ve found nothing of the kind. It’s an expensive business, and people are always hustling for money to keep going.
All this is lead-up to this article by Matthew Herper at Forbes. He’s talking about Samumed, a privately-held biopharma company that has been raising money proverbial hand over proverbial fist, and they’re doing it the old-fashioned way: by promising the moon.
Based on investments made by private investors that include IKEA’s private venture firm, anonymous high-net-worth individuals and a single venture capital firm, Samumed has raised $220 million, and the most recent round of financing valued it at $6 billion. It is halfway through raising another $100 million at a $12 billion valuation. Kibar owns a third of the company, which would give him a net worth of $4 billion.
Samumed is finding it easy to raise huge amounts of cash because it believes it has invented medicines that can reverse aging. Its first drugs are targeted at specific organ systems. One aims to regrow hair in bald men. The same drug may also turn gray hair back to its original color, and a cosmetic version could erase wrinkles. A second drug seeks to regenerate cartilage in arthritic knees. Additional medicines in early human studies aim to repair degenerated discs in the spine, remove scarring in the lungs and treat cancer. After that Samumed will attempt to cure a leading cause of blindness and go after Alzheimer’s. The firm’s focus, disease by disease, symptom by symptom, is to make the cells of aging people regenerate as powerfully as those of a developing fetus.
All right, then. Heal the sick, raise the dead, just like it says in the New Testament. How exactly do they propose to do all this? The common mechanism is Wnt signaling, and there’s the tricky part. If you really could get control of all the Wnt signaling machinery, you probably could do some amazing things. That’s a set of signal transduction pathways from cell-surface receptors, that is wildly important for pretty much all multicellular life. It’s definitely one of those wiring boxes that you find in biochemistry, with about four Godzillion wires heading in and out of it, but the problem is that (like most such boxes) it has a big “Do Not Touch” sign on it. Wnt mutations tend to be bad news, and have been implicated in a whole host of disease states. Such mutations are surely responsible for a whole host of nonviable human embryos, too, if they happen during development, because Wnt pathways are crucial for cell migration and differentiation during the whole process. The Wnt proteins themselves tend to be rather highly conserved, as one would expect, and are immediately recognizable in everything from humans down to flatworms, sea anemones, and sponges.
Naturally, this area has had a lot of attention for drug discovery, where it is indeed high-risk, high-reward. Here’s a very good review of the situation, whose very title (“Can We Safely Target the Wnt Pathway?”) is an indicator of what the field is like. All this is to say that Samumed, whatever they have, is in fact working in an area that could theoretically provide breakthroughs. But they’re also working in an area that has been very difficult to target, and is an absolute minefield of things that could go wrong. So what do they have? The article tries to address this, but, well. . .
. . .Samumed isn’t quite saying. Normally a patent explains which chemicals a drug targets. But in 2013 the Supreme Court said that genes aren’t patentable–the case involved a test for a gene variant that causes breast cancer–a ruling Samumed interprets as saying the company can have its patents while keeping those biochemical pathways under wraps. “That is our trade secret,” says Kibar. “That is our bread and butter.”
For scientists, this is a huge problem. “There is always a tradeoff,” says Roel Nusse, a Wnt expert at Stanford. “It is hard to find a molecule that is always going to affect disease but not normal tissues. To calibrate the balance, you have to know what the mechanism is.” Kibar says only academics and rivals care.
OK, I don’t fault Matt Herper for this. He knows what he’s talking about in this business, and he just has to work with what the company gives him. But what exactly does this mean? Chemical matter patents have nothing to do with whether genes are patentable, and stating a mechanism for a drug isn’t the same as trying to claim that pathway (or the genes responsible for it). So what do Samumed’s patents actually say? A search through the USPTO for issued patents with Samumed as assignee gives you a whole list, and they tend to be written like this:
This invention relates to inhibitors of one or more proteins in the Wnt pathway, including inhibitors of one or more Wnt proteins, and compositions comprising the same. More particularly, it concerns the use of an indazole compound or salts or analogs thereof, in the treatment of disorders characterized by the activation of Wnt pathway signaling (e.g., cancer, abnormal cellular proliferation, angiogenesis, Alzheimer’s disease, lung disease and osteoarthritis), the modulation of cellular events mediated by Wnt pathway signaling, as well as genetic diseases and neurological conditions/disorders/diseases due to mutations or dysregulation of the Wnt pathway and/or of one or more of Wnt signaling components. Also provided are methods for treating Wnt-related disease states.
So the level of detail that the company is (apparently) intentionally leaving out is just which Wnt proteins are being targeted. That, in a way, might not be such a big deal, because it’s not like we know the functions of all of them, and since many of them have no small-molecule binding sites per se, there are a lot of tricky, indirect, and bounce-shot ways of targeting their functions, as well as just going for the protein-protein interactions themselves, which is no stroll along the beach, either. There are some actual enzymes involved in Wnt signaling (tankyrase, GSK3), but these have been targeted many, many times in previous drug development projects, and nothing (to the best of my knowledge) has made it through yet. The patents themselves do not describe the assays used in tremendous detail – you can make a reporter-based cell line, using a lentivirus construct, that uses luciferase as a readout for Wnt-responsive signaling, and that’s about all you get.
Fine, they’re being cagy – the proof of these things is not in whatever in vitro assays are used, because we don’t understand enough about the living system to make sure that we’re going to really get what we want, anyway. All you can do is narrow down to active compounds and hope for the best. And that’s where Samumed is going to stand or fall: in the clinic. As Herper’s article shows, though, the clinical data they have on hair regrowth is nothing to go crazy about. An arthritis trial is underway (445 patients), and that could shed some more light – or not, because for arthritis, that’s still not a gigantic trial. As Herper puts it:
Viewed under the microscope, Samumed looks like a company with a pair of drugs that have not been proved and, if trends in drug discovery hold true, will probably not make it to market. But its investors obviously see something far more wonderful, world-changing and potentially lucrative.
Indeed they do, and isn’t that what every small company wants its investors to see? And maybe that vision can become reality. But it’s a long way from doing so, and there are countless ways that none of this can come true. I wish Samumed luck, and their investors luck, but what worries me a bit is that neither of them seem to feel like any luck will be needed. Oh, but it will.