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Galvani: GSK Goes “Bioelectronic”

You’ll likely have seen the news that GSK is partnering with Verily (a Google startup) to launch a company called Galvani. This will investigate devices that directly modify nerve transmission, which is something that I don’t think any large drug company has ever put money into – certainly not the $700 million that GSK has announced. But it’s not like they’d ever spend $700 million on something that’s not going to work out – oh, OK. But let’s try to assess this deal on its own merits.

First off, I have to give the company credit for trying something new and being willing to put money behind it. But then again, Sirtris (the earlier $700 million dollar investment referred to) was pretty new stuff, too, and doesn’t seem to have worked out in the slightest. Admittedly, that can well happen to these sorts of ideas, but there are a lot of current (and former) GSK people who claim that the company didn’t perform very compelling due diligence on that other deal, and ignored people who did, which will certainly lengthen the odds for you even more. So what about “bioelectronic medicine”, as they’re calling this new field?

I’ll freely confess that it’s mostly out of my expertise – but it’s out of most people’s expertise. GSK has been putting money into the field for three years or so, and they say that they have a list of candidate nerves that directly affect tissues involved with disease, and whose signals they’re planning on either enhancing or blocking. I can certainly how that could work, but I can certainly see how it could not work, too (and there are plenty of disease processes that are not necessarily driven by nerve impulses). The company says that they’re going after diabetes first, so what’s the target?

If I had to guess, I’d say that they’re thinking about slowing or stopping the inappropriate gluconeogenesis in the liver of Type II diabetes patients. Directly trying to stimulate insulin secretion looks like a losing game in comparison – the peripheral tissues are already resistant to insulin in Type II, and the islet cells are already under strain trying to produce enough of it into the blood to get a response. But in the disease state, the liver is (insanely, from our outside perspective) busy making even more new glucose and dumping it into the bloodstream. As I understand it, that may be partly because the elevated free fatty acids in the bloodstream make the hepatic tissue act as if it’s working under fasting/starving starving conditions, which is when it needs to produce glucose for the brain, but I think there’s still a lot that’s unknown about the process.

Here’s an interview at Stat with Moncef Slaoui of GSK about the whole deal. And here’s his answer when Ed Silverman asks him where the whole thing came from:

Well, I became head of R&D (at Glaxo) in 2006 and my mission was to turn around the productivity, which was lagging. And I undertook a deep reorganization and by 2011, we had the early signs that we made a significant turnaround and productivity would go up. But in 2011, early 2012, we realized it took five to six years to turn around R&D asked ourselves whether it will wane away and if the way we discover drugs will it be sustainable in long run. … You know, the way we ensure a drug works is that it has a unique structure to interact with a specific target.

As I recall it, GSK spent the early 2000s telling everyone that productivity was going Great! Just Fine! To be fair, that’s what everyone in the business tends to say most of the time – you only hear that there were problems in retrospect, generally after someone new comes in to clean up all the stuff that was going Just Fine. That “deep reorganization” would be this stuff, more here, and those posts will provide you with another look at the way history gets rewritten a bit during these things.

But now let’s ask ourselves what Slaoui means when he says “we realized it took five to six years to turn around R&D (and) asked ourselves whether it will wane away”. He may be talking about the company’s moves out of oncology and some other areas, and into (so it’s seemed) more high-volume low-margin parts of the business. (As for that “wane away” phrase, there are a lot of ex-GSK people who would be glad to point out that things do indeed wane away pretty quickly when you close down whole research sites!)

Still, I will definitely congratulate the company for having the uh, nerve, to move into nerve transmission as a therapeutic mode. If they can get this to work, they’ll have staked out a huge first-mover position in the field. Now it just has to work, and that brings up the partnership with Verily. As the folks at Stat have been detailing, Verily itself has not been without problems. The optimistic take is that they’re just the sort of people to take on an out-there project like this one, but the pessimistic take is that an out-there project like this one is just the sort of thing that they might convince someone else that they’re terrific at, even if they aren’t. So far, it appears that none of the biggest, most noisy Verily projects actually seem to be going well, if that last link is accurate, so there’s room to wonder about this one.

But then again, GSK has been working on some of this stuff themselves for the last three years, and they presumably have some internal data that they find convincing. This will be a very interesting area to watch, that’s for sure. Slaoui says that “And in the next 18 months, we plan to start clinical trials with a prototype device to establish clinical proof of concept“, so there’s a marker down. Let’s see what happens.

52 comments on “Galvani: GSK Goes “Bioelectronic””

  1. Dr. Manhattan says:

    From your previous post (June 2016) on Verily: “One of these ideas is the so-called “tricorder”, a medical diagnostic device deliberately named after the Star Trek gizmo. That’s inviting trouble right there, if you ask me.”

    Now we have “bioelectronic medicine”.

    Yeah, a lot of this sounds like SciFi ideas in yet another attempt to move computer-based solutions into the messy arena of biology. It may work if you only need approval from Starfleet, it’s another issue altogether with the FDA or EMEA.

  2. biotech scientist says:

    I would not be treating diseases there are already therapies for. Look at inhalable insulin. This is interesting, but I don’t know why they aren’t going after paralysis, and taking a bigger neurological plunge. Maybe they are.

    1. zapper says:

      @biotech scientist

      I talked with some of the GSK folks involved in this a few years ago. They were explicitly *avoiding* the CNS and focusing on peripheral things, where the biology was a bit more tractable.

      I think for some indications (e.g., stimulating muscles directly), the science is pretty clearly worked out, but there needs to be some “engineering” work done to get it into a form factor that patients and doctors can work with. It’s certainly a lot cleaner than trying to alter the middle of a gargantuan regulatory network with some small molecule.

  3. anonymous says:

    Former defence chief Rumsfeld come to my mind. I mean if the the drug companies like GSK missed out on “the known” area how else they can be sure of “the unknown?” Seems crazy to me, but who am I? I am a simple bench chemist and may be the MBA’s with no science degree knows better!

    1. Harrison says:

      Incidentally Donald Rumsfeld was the CEO of Searle (now part of Pfizer):

      Donald Rumsfeld served as CEO, and then as President, of Searle between 1977 and 1985. During his tenure at Searle, Rumsfeld reduced the number of employees in the company by 60%.

  4. Marcin says:

    Would someone educate me but isn’t accupuntcure about the same concept?

    1. anonao says:

      may be by attaching small batteries on the needle 🙂

      1. cynical1 says:

        Actually, my stepson is an acupuncturist and they already do attach batteries to the needles.

        1. just sayin' Durham says:

          But cynical1, we know that GSK is just wasting money the looking for next quarterly numbers.

    2. Mark Thorson says:

      I was thinking chiropractic. The alleged mechanism of chiropractic is stimulating organ function by relieving pressure on nerves (called “subluxations”) that serve these organs.

    3. Tim Shi says:

      Yes or No. Accupuncature is a kind of “device” to stimulate human body “Qi” and meridian. It is based on the body network, not nerve system, not directly targeting either tissue or organ. However, I do realize there are some similarities and hopefully this is the 6th sense of human being. In anyway, go for it!

  5. MALLAM says:

    Looks like another likely “black hole” investment by Slaoui and Witty before they exit next year.

    1. johnnyboy says:

      If you look at the Stat interview, Slaoui will be the CEO of this company when he retires in 2017. So this whole thing might just be him having found a way to continue getting his millions.

      1. Former GSK says:

        Unfortunately no one put in a leading role in this venture knows anything about the science in this area. There are plenty of neuroscientists who understand the science, but Moncef and Famm are not among them. The whole thing is typical GSK flash and talk, kind of like Verily. Which makes sense since the mantra has been to “be more like biotech” – style over substance every time.

  6. Peter Kenny says:

    The name of the new company brings the term ‘sacrificial anode’ to mind.

  7. Wavefunction says:

    “Generally after someone new comes in to clean up all the stuff that was going Just Fine”

    Sometimes it’s also the opposite; the new guy can turn “Reasonably Fine” into “Abysmal” in a heartbeat. History shows ample evidence of this.

  8. luysii says:

    It’s not clear to me just what they’re going after — neurotransmission between neuron and postsynaptic cell, or axonal conduction of the neural impulse itself (action potential). If the latter, we have the example of 3,4 diamino pyridine, a potassium channel blocker. It was hoped that it would improve nerve conduction velocity in the demyelinated axons of multiple sclerosis patients. It has also been used in Lambert Eaton syndrome. The side effects in most were unacceptable (abdominal pain, convulsions etc.)

  9. dearieme says:

    Each company hopes that the other will provide the necessary breakthrough.

  10. Sir Sirtris says:

    I was excited when I saw the news reports about this new direction in therapeutic research however after reading Moncef’s incoherent replies in Derek’s blog, I put the success to failure ratio at 1:1000000. Sounds like the Sirtis debacle repeated. Is Christophe Westphal involved in this venture as well? I do recall that there was a comment about using such devices to cause ovulation for infertile couples. If a device could stimulate the ovaries to replicate the monthly ovulation cycle then that would be pretty cool. If bioelectronics can help with paralysis or other movement disorders then this would be a monumental breakthrough. Let’s get in a new CEO ASAP.

    1. johnnyboy says:

      At one point he says they will get preclinical proof of principle in 3 years, and in the next sentence he says they will be starting clinical trials in 18 months. So his timelines make a lot of sense.

    2. Old says:

      Let’s set the record straight on Sirtris which has been quite bashed here over the years. The main argument was that the fantastic internal scientific diligence was ignored by GSK management who went ahead and did the deal to buy the company. The internal assessment was based on the presumption that the activation of SIRT1 by the Sirtris small molecules was an artifact, dependent on the artificial substrate that was used. As it turns out following the acquisition, Sirtris scientists provided substantial data that this was not the case and in fact the compounds discovered at the company indeed bound to and activated SIRT1 (see: and and What was missed in the pre-acquisition diligence (along with Pfizer and Amgen’s efforts to discredit the effort following the acquisition) was the fact that there is complicated biochemistry involved with this mechanism and that there appeared to be more of a focus on bashing the effort versus doing the hard science to figure it out. After years of bashing, insults and general disdain for the Sirtris effort, it is time to face the fact that the program was on solid footing at least in vitro and that the investment by GSK was not foolhardy or naive (or ever based on the development of resveratrol) but reflects the kind of risk that most breakthrough drug discovery investments need to take. Will anything ever come out of this field of research in terms of a drug, perhaps not but at least an effort was made with real money put at risk which embodies drug discovery.

      1. Sir Sirtris says:

        Wow, in this week of the Olympics you definitely win the Gold Medal in historical revisionism. You are either a former Sitris scientist or one of the GSK wunderkids that ignored the due diligence. I’m sure you were constantly saying, just give us more money and five more years, I promise we’ll have a candidate. GSK tried “candidates” in multiple trials and they were all negative. This was bad science sold to GSK by a pair of hucksters and approved by GSK internal leaders that lacked the intellectual acumen to see through the bad science. Please go away, the readers could care less about you attempting to “set the record straight”

        1. Sir Sirtris says:

          Old. Apologies, the articles you posted are in well respected journal and the science presented appears to be solid. You are correct that one needs to take on risk if breakthroughs are to occur. You are indeed correct that many, including myself, probably fell prey to the external and internal criticism without actually looking at the science. I hope that something emerges out of the $720 spent on this endeavor.

  11. MRTTF says:

    I am a PhD chemist that works in the battery field for medical devices, and can say that this type have activity has been going on for over 15 years. Neurostimulation is used for a whole host of things, typically pain management. There has been a huge drive toward other applications, e.g. weight loss, arthritis, deep brain stimulation, etc., over the past couple of years. Electrical pulses are used to block or stimulate certain nerves to get the desired outcome.

  12. Calling Agilist! says:

    Code blue in the GSK spin room, report immediately Dr. Agilist!

    1. b says:

      Their Google alert hasn’t come in yet

    2. Sir Sirtris says:

      I think Agilist (aka the GSK Spin Doctor) is too busy feather dusting Moncef’s office to reply to this thread. Wow, MRTTF really poured water on this “innovative” technology that has been mined for 15+ years. Sigh, another waste of GSK millions. New CEO STAT!!

      1. MRTTF says:

        @Sir Sirtris–

        Just to clarify, the basic science is not innovative. Several other posters have mentioned other device manufacturers that have been doing this for years. Where innovation is occurring is in the diseases being treated and the neurostimulation method, e.g. current duration, current amplitude, etc.

  13. db180 says:

    Those who can, make antibodies, those who can’t modulate cytokines by sticking electrodes on the vagus nerve.

    May be helpful target validation for others. The feedback-control opportunities are interesting but not unique to this approach.

  14. Me says:

    Deep Brain stimulation in PD is all I can think of that is anything like this and has at least some support for efficacy.

  15. mh says:

    Agree with MRTTF – old news. Aren’t baroreflex stimulators for the control of resistant hypertension and heart failure an example of this type of technology in practice? Cochlear implant for deafness as well. Not sure why this is so surprising or controversial. If you strip away the rhetoric, this is pretty basic and accepted science.

  16. MoMo says:

    Don’t knock the science of neurostimulation and soon you will all be connected to electrodes, if you are not already. GSK will be selling neurostimulators on the QVC channel next to Tagamet.


  17. lynn says:

    This reminds me of the electro-medical quackery of the 1800’s [see Perhaps I’m just too much of a skeptic.

  18. DevicesRus says:

    It is interesting to see the quite large dichotomy between the molecule guys and the device guys. The large device companies (Medtronic, Abbott, Boston, etc.) have built large companies on the basis of electrical therapy, pacemakers, implantable defibrillators, neuro stim for pain, DBS for Parkinson’s etc. When I was at Medtronic we used to joke that we tried electrical stim everywhere you could think of and have been doing this for 30+ years. One big issue that GSK will have to think about is the very real difference between regulatory pathways for devices and drugs. At Lilly they used to say that the loneliest guy in a drug company is the device guy, at Medtronic it was the drug guys trying to use devices to deliver drugs. In any case I don’t think this is really all that “new” but I am skeptical of most of what comes from Verily.

  19. Dr. Manhattan says:

    “Don’t knock the science of neurostimulation and soon you will all be connected to electrodes, if you are not already. GSK will be selling neurostimulators on the QVC channel next to Tagamet.”

    I think William Gibson (Neuromancer) predicted that three decades ago…

    1. MoMo says:

      Sorry Dr. M- don’t read fiction. Its for the weak.

  20. Diver dude says:

    This is interesting. At GW in 1992/3, we were working on using implanted electrodes to allow EEG patterns to be used as predictors of epileptic seizures as part of the therapeutic package for lamotrigine. At that time, we looked at Medtronic as a potential partner or take over target for their expertise in this area. I’m kind of hoping that one of my ex-colleagues has been quietly working away at this all these years and has finally succeeded 🙂

  21. Diver dude says:

    That should be BW (damn you, autocorrect)

  22. Live! LIVE!! LIIIIIIVE!!!!!!!!!!!

  23. Tortoise says:

    Watch out Google, better ask Jensen and Fernando for some due diligence on what’s happened to McLaren in Formula 1 since they started the GSK-McLaren partnership…

    (“working together to help drive innovation and winning performance” …except on the racetrack)

  24. Barry says:

    there was a time in the ’80s when Big Pharma did small molecules (and vaccines) but other biologicals (with the exception of porcine insulin?) were the province of Biotech. Soon however, most Big Pharma companies were trying biologicals in-house and several of the Biotech companies were trying to get into small-molecule therapeutics. Currently, seven of the top-ten earning drugs on the market are biologicals.
    This may be the start of a new blurring, in which GSK gets into devices that had been the province of specialists in pacemakers, defibrillators…

  25. Emjeff says:

    I certainly hope this deal has some milestones built into it, so that GSK only pays for actual results. That was (unbelievably) missing from the Sirtris deal – GSK paid a premium price and got absolutely nothing. In fact, the entire sirtulin research effort at GSK has been stopped for over a year. Incredibly, both Patrick and Moncef still have their jobs after this debacle…

    1. PorkPieHat says:

      Emjeff, GSK did get the IP estate of Sirtris, for what that’s worth (not $720M, for damn sure). Whatever happened to the IP? Guessing GSK is sitting on it.

  26. Dr. Manhattan says:

    “Sorry Dr. M- don’t read fiction. Its for the weak.”

    Sorry you missed out on Moby Dick, Crime & Punishment, Catcher in the Rye, 1984, Brave New World, Heart of Darkness, Tale of Two Cities, The Sun also Rises….etc.,etc. All part of a well rounded education.

    1. FanOMoMo says:

      Reading Catcher in the Rye did John Lennon a lot of good didn’t it? And Moby Dick, a story about ugly New Englanders harpooning poor whales so they can see their ugly mugs in the dark. I was glad the whale won.

  27. Thoryke says:

    Perhaps the people discussing bio-electronics at GSK should chat with the people over here building “neural dust” electronics?–son072916.php

  28. Phil says:

    You make a good point. You don’t have to like the protagonists to be moved.

  29. steve says:

    I’m surprised that no one has mentioned Kevin Tracey’s work. Maybe it’s just easier to bash than do your homework. Kevin heads up the Feinstein Medical Center on Long Island and has very interesting data on neuronal control of immune responses by regulating T cell subsets through acetylcholine receptors. He started a company, SetPoint Medical, that has an implantable device that inhibits inflammatory cytokines production in rheumatoid arthritis patients and have preliminary data on reduced severity of disease. Early days but based on solid preclinical data and some promising early clinical data. Neuromodulation may have some very interesting applications. With apologies to MoMo for quoting fiction, “There are more things in heaven and earth, Horatio, than are dreamt of in your philosophy.”

    1. Kary says:

      To add the reference to the work you’re describing:
      Proc. Natl. Acad. Sci. U.S.A., 2016 vol. 113(29) pp. 8284-9
      Vagus nerve stimulation inhibits cytokine production and attenuates disease severity in rheumatoid arthritis. Koopman, et al.

      Another variation from Daniel Mucida:
      Neuro-immune Interactions Drive Tissue Programming in Intestinal Macrophages, Gabanyi, et al. Cell 2016

      And additional work from Cliff Woolf as well.

      Not sure whether any of these researchers are directly or indirectly connected to Galvani.

      1. MRTTF says:

        Steve & kary–

        As I understand, GSK has invested in some of the early financing of SetPoint.

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