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Aging and Lifespan

The Samumed Story

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.


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36 comments on “The Samumed Story”

  1. SP says:

    So if they’re not patenting composition of matter, isn’t anyone who gets their hands on some of the drug free to figure out what it is and patent it themselves, under first-to-file? Assuming it hasn’t been disclosed somewhere else and they just don’t want to admit they’re recycling a known series. Want to use your own compound? I’d like me a chunk of the $6B please…

    1. Sideline Chemist says:

      Take a look at the list of patents in the link Derek provided. They are claiming composition of matter. They’re just being vague in how the compounds (which look a lot like typical kinase inhibitors) modulate the Wnt pathway.

      One could view this as phenotypic drug discovery at its best. Let’s say that Samumed has found some compounds that effect a cellular pathway signaling. Perhaps they know exactly how the compounds are causing the changes in pathway signaling, perhaps they don’t. If the signaling modulation is the real readout that you care about to prove usefulness in a patent, then absolutely no need to include any other molecular mechanism.

      I do agree with Hap. Once a positive signal is seen in the clinic, then the “academics & rivals” will be all over those compounds with a fine tooth comb to determine the underlying molecular mechanism. You’ll get away with being cagey once, but unlikely to work repeatedly in the long term.

  2. Hap says:

    1) How do you keep biological pathways secret? If you can find them, and understand them, then someone else can, too, and if that’s what makes you different, then you’re not going to be different (or paid for being so) for very long.

    2) Most people that promise the moon can’t generally deliver it – sometimes it’s because they tried to deliver it and failed, sometimes it’s because they didn’t understand that they were promising something that they couldn’t deliver, and failed, and sometimes it’s because they never intended to do so. It seems like investing in someone who promises the moon means that it’s time for johnnyboy’s “don’t invest in this with any money you would really mind losing” warning.

  3. Anony-mouse says:

    Do they expect a merge with Valeant ?

  4. aa says:

    Please run for President Derek.

  5. j says:

    In the clinic: this is the real deal:

    serious science REAL. and cheap

    1. John Wayne says:

      Here we go …

    2. small time investor says:

      Wow what a pitch? Do they have any bridges I can buy?

  6. Rich Schwantzweiler says:

    Great writeup. But it won’t work without a great CEO. Unfortunately I can’t think of any available now off the top of my head… Oh wait, word on the street is Elizabeth Holmes may be available soon.

  7. sgcox says:

    from the chemical name in the title of several patents: 2-(1H-INDAZOL-3-YL)-1H-IMIDAZO[4,5-C]PYRIDINE, the magical cure is some primitive nonselective kinase inhibitor

  8. Lane Simonian says:

    The relationship to Alzheimer’s appears to be this: the APOE4 gene binds to low density lipid receptor proteins which activates the Wnt pathway which triggers phospholipase C and the onset of Alzheimer’s disease.

    Several problems, however, with this approach to Alzheimer’s disease. First multiple receptors are involved in the activation of phospholipase C including g protein-coupled receptors, receptor tyrosine kinases, and ionotropic and metabotropic receptors. Inhibiting Wnt signalling is likely to only help those with the APOE4 gene early on and only in those cases where other receptors are only marginally involved (this also helps explain why not everyone with the APOE4 gene gets Alzheimer’s). Secondly, at some point early in the disease, inhibiting these receptors is not likely to make a difference–the process has already been set in motion.

  9. Dr. Manhattan says:

    For additional anti-aging compounds see ascomycin and other anti-agathics, discovered in the 1950’s at J Pfitzner Co. Blish, J. “Cities in Flight”

  10. Me says:

    Are my comments being posted?

  11. watcher says:

    In the world of biotech, the old adage continues to apply, time after time after time.
    “If it seems too good, then it must be” a good way to lose a lot of money in the long run.

  12. The worst that will happen is that some of the 1% will rejoin the 99%. It was far harder in clinical practice to helplessly watch desperate patients try snake venom for ALS, or MS or phony cancer therapies (Laetrile), all for the profit of charlatans.

  13. Old Pump Kicker says:

    “…it believes it has invented medicines that can reverse aging” must be the true philosopher’s stone. If you waive it around, people throw money at you.
    On the other hand, we should reject any actual reversal of aging as unscientific, because “science advances one funeral at a time.”

  14. Mark S, says:

    I’m a software guy, not a chem/bio scientist. So I’m waay out on a limb here. But I do have some experience with patents in software.

    If that patent excerpt Derek posted is typical of Samumed’s work it looks to me about like a software patent for “buying stuff over the internet”. IOW, they’re essentially patenting using the Wnt pathway. Any future success anywhere by anyone in that “wiring junction box” falls under this ridiculously overbroad patent.

    After all, how can I, some later discoverer, prove that my Wnt innovation isn’t the same one that Samumed presciently patented back in 2016? All their details are secret and of course they’re going to claim that my invention is an example of what they were talking about.

    I see this as nothing but patent trollery writ very, very large. With a thin veneer of some chemistry that’ll (eventually) fail in the clinic to hold their patents together long enough for somebody else to succeed and get caught in their web. Even if the whole thing fails, and nobody else ever cracks anything Wnt-ish in our lifetimes, at least the organizers will have successfully bilked some fatcats out of a billion or so. And what if, against Powerball-like odds, they succeed? They can name their price and own the world.

    Heads they win; tails they win; edges they win. It’s how things are done in the snake oil business.

    1. Derek Lowe says:

      No, the claims are directed towards chemical matter. Pathway patenting was tried a while back, and the USPTO basically doesn’t allow you to get away with that. Samumed, in the end, is claiming compounds – their use is in affecting Wnt pathways through some not-very-well-specified mechanisms, but the patents are for specific compounds.

  15. Hap says:

    How many companies have been successful (successful = making useful products or even trying as opposed to successful at fleecing investors) while using the “Shh, we’ve got something, and it’s great, but we can’t tell you what it is.” method? As someone hinted above, Theranos seems to be following this model, with (at best) limited success. Who has done it legitimately?

    1. Anon says:

      Theranos? Limited success? Er, you could say very limited indeed. It’s just flopped. The bubble has burst. $9Bn wiped out in 6 months:

    2. Unlike Theranos, this company is disclosing, presenting, and will be publishing it’s clinical data. I assume that the mechanisms will be public later in the development program. Why disclose more if your investors don’t make you?

      1. Hap says:

        If they’re disclosing their data, that is different (and more honest). You don’t need mechanism of action if you have something that works (though if you have good data, then lots of someones will be looking for a mechanism, and they’ll find it).

  16. Me says:

    Well one comment got in, one didn’t. That comment was that Indazoles are frequent-hitters in my book.

  17. Researcher says:

    The Forbes writer chose not to include that Dr. Dennis Carson, previously the Director of the UCSD Moore’s Cancer Center, was the scientific founder of Samumed. Previously, Dennis is credited with nearly single-handedly, in his own academic lab no less, developing a groundbreaking drug for hairy-cell leukemia – cladribine/leustatin. Years later he co-founded Triangle Pharmaceuticals, which Gilead purchased for $464M in 2003. Emtricitibine is still found in Gilead’s key HIV drugs. It’s worth noting that Raymond Schinazi was a co-founder of Triangle – he founded Pharmasset which Gilead purchased for $11B and whose solvaldi and derivatives have generated $30B in revenue in 2+ years on the market and $100B in market value for Gilead. Back in 2007, Pfizer noticed Carson’s work and offered to fund it, so he co-founded Wintherix, which is now Samumed. Knowing Carson was a co-founder might change a few people’s view on the chances that the science behind Samumed is top-notch.

    1. Hap says:

      “Nullius in verba”, I think. Lots of smart people have made mistakes, and so trusting them because they’re smart is not necessarily a good strategy. A combination of “Trust me” , stringent secrecy, and extravagant promises, particularly when your key development is something (like a biological pathway) that can be found by others, is not going to inspire confidence, because similar promises have been made before, with not generally positive results (for anyone else other than the people starting the business). Intelligence and success don’t necessarily imply honesty, so they aren’t proofs against dishonesty.

      If you care whether people trust you, making your startup sound like a supplement scam is not helpful. If you’re making drugs, though, nothing matters other than products; if Samumed finds them, then how they run things (or what people think of them) won’t matter, and if they don’t, it won’t matter.

  18. DCRogers says:

    Forget Alzheimer’s, the most lucrative condition on their list is Male Pattern Baldness; if they can grow hair on barren men’s heads, they’ll be floating in stacks of money.

  19. Parker Stevenson says:

    I see a Theranos merger in their future.

    Or, if things don’t work out, they can clean out the equipment from their rental space (try for <130 in and outs that time), rename the company and start over. Again.

    Too bad they can't sue anyone else anymore, though.

  20. Craig NYG Morton says:

    The CSO exited company concurrent with the Forbes article with requisite photos of CEO as mad scientist after unspectacular alopecia results, so there’s that.

  21. Dan B says:

    publish my comment

    1. loupgarous says:

      The Global Times article reads like it’s been translated to English through Google Translate. But not from French. Google Translate’s still throwing bricks in French-English/English-French translation, while it does better lately in Spanish (predictably, Spanish is sneaking up on English for “second most-spoken native language on Earth”), German and Russian. I’d say a romance or Asian language, judging from the wild excess of the pronoun “a” in the translation.

  22. loupgarous says:

    I’d say the lines to watch for when they cross are “progress toward a druggable Wnt pathway” versus “rate at which research and drug development activity burn through that $6 billion”.

    Now, if they could come up with a nice, selective way to restore patency to the internal iliac arteries and their collateral circulation with less toxicity than PDE5 inhibitors – a cure to poor circulation “down there” would be nice.. Sanumed would have a drug they could make their investors fat with.

    Never mind baldness. I’d go total Yul Brynner/Telly Savalas if more immediate concerns would never be an issue again.

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