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EQRx’s Challenge, And My Challenge to Them

It’s time to talk about a new venture called EQRx. This has made quite a splash in the last few days at the JP Morgan investor conference, and it’s been launched by Alexis Borisy (involved with founding and/or helping run CombinatoRx, Foundation, Blueprint, WarpDrive Bio, Editas, Relay and others) with the aim of generating cheaper medicines. How, you ask, are they going to do that? Are they aiming for cheaper generics? The state of California has been talking about that, but it’s a tough place to work in. The high-volume generic drugs are already competing on price, and the low-volume ones, where some bizarre pricing does indeed take place, don’t have much of an impact (being low-volume and all).

No, EQRx is more ambitious. Their plan is apparently to come up with new competing pharmaceuticals in existing categories and sell them for lower prices than the patented ones. Which immediate makes one ask again, how are they going to do that? I can do no better than to quote Borisy, via this C&E News writeup from Lisa Jarvis:

“The world has fundamentally changed. . .Today, you can do a virtual screen of a billion compounds, do on-demand synthesis of all of those, and you can do it overnight in the cloud”

My challenge here is to write about this in something approaching a measured tone. The temptation is strong to spend the next couple of paragraphs in full Daffy Duck mode, because that quote alone seems to have been designed to send me over the edge. So to buy time, let me refer to this Stat writeup by Matthew Herper, where Borisy assures the world that “This is not fantasy world. This is something that can be done” Here’s exactly what he has in mind, by the numbers:

Over the next 10 years, Borisy said, he’d like for EQRx to start developing somewhere in the ballpark of 50 different experimental medicines. He wants the company to come out with its first medicine in five years, and to have 10 drugs within a decade. 

Must. Not. Lose. It. Let’s buy some more time. I note that Herper’s article focuses on the downstream business uncertainties of this plan. As he says, the idea of a “fast follower” drug is not a new one in the business, but neither have such compounds ever competed on price. The business question is whether physicians and insurance companies are ready to make that part of their decision-making process in the prescription drug world because frankly, they don’t do so much of that now. EQRx is a bet that they’re ready to. Insurance companies are very interested in generic drugs when available, and will often require patients to exhaust the existing lower-priced therapeutic options before they’ll pay for a more expensive one as well, but we really haven’t had that many examples of prescription medicines fighting it out on price alone.

But EQRx is also, of course, a bet that they can discover all these medicines in the first place. And that’s where I have comment to offer. It has not escaped my attention that they are picking up funding from some of the venture capital shops that have traditionally stayed out of biopharma, such as Andreessen Horowitz. Here’s their take, which tiptoes up to this question:

But how? What secret do they have that the multi-billion dollar biopharma industry doesn’t? Often the biggest innovations in technology address the process, not the product. Take Amazon, for example; by building a different retailer from the ground up and infusing tech throughout, they were able to deliver products faster, at a lower price and a higher margin. This simply can’t be done by revamping an existing company, as many retailers and other companies have tried. In much the same way, EQRX is now reimagining how medicines are created, tested, and commercialized by re-engineering the system itself. 

The hallmark of good engineering is where the solution is simple, but not easy; the answer elegant, but not overwrought. EQRx shifts science risk to execution risk by focusing on known biology, where drug targets have been validated and proven valuable for treating a disease. They remove friction within the system through early and deep partnerships across the healthcare value chain. And most importantly, they integrate data science and technology end-to-end throughout the discovery and development process. Engineering a better product is good, but engineering a better process is best.

So we come down to “They’re gonna be like Amazon” and “They have lotsa data science”. That’s unfair of me, but not as unfair as it should be. Let’s get down to it: if a16z and the other backers of EQRx think that they have shifted the science risk here, they are mistaken. You cannot dodge it in this business; science risk is stalking you all the way through the execution of your business plan. It would indeed be dreamy if that were not the case – it’s pretty to think so. But a company like Amazon is a story of pure, world-class execution, coming up with a smoother, cheaper, more convenient way to sell things that you didn’t invent or optimize by yourself, that you don’t manufacture yourself, and that you already know that people are buying constantly (and what’s more, buying with ferocious price discrimination). Coming up with ten new drugs in ten years ain’t none of those things, guys.

Why not? Let’s look at the existing fast-follower “me-too” landscape. As mentioned, the folks developing such compounds are not doing so with an eye to competing on price. They have large profits in mind, certainly. If they were able to come up with ten such drugs in ten years, why wouldn’t they? There is no incentive to move slower – the burst of speed that EQRx is talking about and its desire for lower-priced drugs are two separate things and they are not related. Why hasn’t anyone done the speed part while keeping the high prices part, you wonder?

Is that because, as the Silicon Valley types would have it, the existing drug development system is too stuck in its old ways of thinking and operating and is ready for some disruption? What disruption is EQRx bringing to the R&D process? When I read that Borsiy quote from the C&E News piece, I don’t know whether to laugh or shiver. No, in case you were wondering, you cannot virtually screen a billion compounds overnight. Allow me to refer you to Pat Walters, who knows what he’s talking about in this area. Virtual screening can be quite useful, but the larger and more useful it gets, the less trivial it becomes. A specific problem is the generation of false positives, which can eat you alive. This is the point to note that no, you cannot do “on-demand synthesis of all of those”, either. I know that Borisy is not talking about synthesizing a billion compounds, of course (although who knows what some of the people reading his statements think), but compounds of any real complexity are still kind of a pain to make in quantity.

And let’s remember, EQRx wants patent-breakers. That’s what the company is, at bottom: an attempt at speedy patent-busting, with the disruption-on-price stuff as a separate menu item. The fastest way to come up with a fast-follower is to hew as closely to the existing chemical matter as you can and still get IP. The further away you venture, the greater your chances of surprises – PK surprises, selectivity surprises, toxicology surprises. Mind you, you’re in for those no matter how closely you stick to the known compounds, but you’ll definitely uncover more of them as you move into new chemical space.

Now, it’s true that the existing fast follower drugs generally come along with some advantage over the older compounds – more convenient dosing, fewer side effects, better efficacy and so on, because they’re competing on these and not on price. Not all of these turn out to be real in clinical practice, but they were aimed towards these things during development, because coming to market with “Here’s something that’s pretty much the same as Drug XYZ, which will be going generic soon, and here’s your opportunity to still pay a higher price” is not a winning proposition. But this brings up two other factors. The first is that even in fields where there are several drugs all hitting the same mechanism, it’s usually the case that they behave differently in different people. A true copycat drug that acts exactly the same is very rare – partly because that’s not what people were aiming for during development, but even more so because of the variety of physiology and metabolism found in the human population.

The second factor is timing. If you’re going to introduce a fast follower drug, it kind of does have to be fast. Otherwise, the competition will have gone generic, or will be getting close, by the time you’re hitting the market, and then (as mentioned) you’d really better have a reason for people to pay for your compound. If EQRx is trying to lead a price revolution, it’s got to be in the prescription side of the business, because generic drugs in this country are already pretty cheap. So their ten-drugs-in-ten-years pace, while still frankly nuts, is the sort of thing that they’ll actually have to meet if they’re going to come with less costly alternatives while the expensive stuff is still on patent.

Let’s get real: no matter how spiffy your data science integration is, discovery and development of a new drug – even one that copies an existing one as closely as possible but is still patentable – just takes longer than that. Finding the compound. Setting up and validating the assays. The counterassays. Screening. Analog synthesis and analog screening. Scale-up. Pharmacokinetics. Toxicology. More toxicology. Formulations. GMP scale-up. Design of a trial. Recruiting patients. Running the trial. Sending it all to the FDA. These things take irreducible amounts of time, and not-so-irreducible amounts of cash. I know that I sound like a crusty codger who’s all salty ’cause he’s about to get Amazoned, sure. There are people in the Valley who live for that kind of story and to see the looks on the faces of people once the Mighty Disruption hits them. But let me put my cards out on the table:

I will put up $500 dollars on LongBets.com against the proposition that EQRx will produce ten drugs in the next ten years. Money on these propositions goes to charity – if someone associated with this venture would like to take the other side of this, I will gladly name an organization that my money will go to if I lose. I am easy to contact, by email or Twitter. I am registered on LongBets, and will be happy to work out more detailed terms of the wager in advance on request. Failing that, I will write my own statement and post it there, for all comers to challenge and for the bet to be eventually mediated and recorded. Updates to follow.

Why am I being such a curmudgeon about it? I certainly have nothing against lowering drug costs. I definitely have nothing against speeding up drug development. What rubs me the wrong way is hype. I freely admit that part of this is having devoted the last thirty years of my life to a difficult and complex process, which makes it difficult to be take with equanimity being told about how it could all be done so much faster and easier. But if it can, perhaps such a public bet will spur on the people trying it that much more. If EQRx really can deliver so many new drugs so quickly, I will happily and publicly eat crow. Takers?

 

 

71 comments on “EQRx’s Challenge, And My Challenge to Them”

  1. Emjeff says:

    Derek;

    All excellent points, but it’s even worse than you have laid out. If your new drug X is going to replace the one currently on the market, then you better have data that shows it does the same thing. What does that mean? In most cases, long expensive and multiple clinical outcome trials. Those are not cheap, and neither are they fast. Just because you are close to something on the market does not mean the FDA will let you skate; on the contrary, you WILL be doing those trials, and they WILL be very expensive, no matter how pure your motives are.

    1. NumbNuts says:

      If it sounds too good to be true, it is.

  2. Hap says:

    1) Patents aren’t made to be broken, either (particularly when written by huge profit-seeking entities) – if a drug is close enough to another in chemical matter, the drugs will get fought over in court, which will eat into the profits (or the ability of the drug to eat into other people’s profits).

    2) It seems hard to get around the idea that if companies could find a cheaper way to make equally effective drugs, they would take the money for themselves. Companies have outsourced a lot to smaller businesses who don’t have the bureaucracies of their partners, and so if mass is the problem with developing new methods of making drugs, it seems like a problem that could have been solved. It also seems unrealistic to assume that people would then use the money to make drugs cheaper rather than themselves richer. No one wants to play a low-margin game – the goal of businesses is to get away from competing on price (or anything, if they can). Price wars seem like trade wars – they aren’t really as easy to win as they look.

    3) Biology seems like a pit of “unknown unknowns” and that’s where pharma business plans go to die.

    If someone can come up with a better way to make drugs, then wish them well. Maybe the next frontier would be to come up with a way to do so without the side effect of hype.

  3. Magrinho says:

    It’s not cynical to call out a cynical, trolling-for-suckers approach to raising capital. This lives in a pitch deck, fantasy world. Anybody with a modicum of understanding of drug discovery will laugh at this. And I would assume this includes EQRx. There is too much money sloshing around in biotech right now. Too many marks. Too easy to raise money.

    1. Earl Boebert says:

      I think there’s a possibility that one is one the wrong track when one characterizes these schemes as classical scams designed to relieve the ignorant of their money. There is a lot of money sloshing around everywhere these days, and as the Panama Papers shows, a lot of it is hot.

      An expert in the field once told me (some years ago, so this may be obsolete) that a corrupt politician sitting on a pile of ill-gotten gains would be happy to get ten clean cents for one dirty dollar. I wonder if there is something like that going on in these patently absurd schemes.

    2. Adamantane says:

      So EQRx is the next Theranos?

      1. Adam Grobin says:

        Exactly what I was thinking. Keep an eye on who us investing. If Bio & Pharma veteran’s stay away, it looks even more like Theranos

      2. x says:

        My thought as well. Check to see if Liz Holmes or Chelsea Clinton is involved somehow 😛

        1. anon the II says:

          Would you care to elaborate on this comment? I’ll call out a political dig masquerading as a scientific comment.

          1. aairfccha says:

            https://www.statnews.com/2016/03/21/clinton-fundraiser-theranos/
            “Just last week, emails to potential donors went out inviting them to a “conversation with Chelsea Clinton,” which was to be “hosted by Elizabeth Holmes.” The top ticket price: $2,700.”

            This was when Theranos had already begun its nosedive.

        2. loupgarous says:

          If this is the “Theranos Test”, look for endorsements by George Schultz, James Mattis and Joe Biden, too. Otherwise intelligent folks from all sides of politics can get taken, but good, in biopharma investing.

        3. James Millar says:

          Don’t be too hard on Theranos, they helped public education a great deal by reducing the DeVos family fortune a bit.

  4. James says:

    Also, best of luck getting sufficient people to enroll in studies for a medicine they are told upfront is ‘non inferior’ to one they could already get at the pharmacy.

    1. anon3 says:

      Good point…can you ethically enrol patients when the there’s no claim of potential benefit and only risk?

      1. loupgarous says:

        EQRx’s PR strategy defines the benefit to clinical trial enrollees – at least the same efficacy as existing drugs, at a lower cost. Their answer to “is it ethical…?” is “Is it ethical to treat only those people for this rare condition who can afford the price of the current patented version? Our drug candidate, if it offers only comparable efficacy in treating this disease, would be available to more people…. ”

        This question comes up most often with biologics. The current experience with biosimilar pricing, even after FDA made concessions on the need for safety and efficacy studies, is that the cheapest biosimilars are at least 60% as expensive as the biologic they are similar to.

        Medicaid, Medicare and private insurance all tacitly or explicitly ration expensive drugs such as biologics. It’s unclear whether paying 60% of the price for an expensive but (say) 90% effective cure for an otherwise intractable and deadly disease would end rationing of care, using EQRx’s products, should they pass safety and efficacy testing. That’s where biosimilars are now.

  5. Old says:

    All I can say is look at the other two attempts of Borisy that were launched with similar hype and unrealistic goals focusing on drug discovery-CombinatoRx and WarpDrive. Nuf said..

    1. Biotech fan says:

      WarpDrive actually not only created a novel modality but also used it to build a KRAS inhibitor which it successfully sold to Revolution medicines (who are running with it, hopefully all the way to the clinic).

      1. Hap says:

        CombinatoRx didn’t seem like a ridiculous idea – hard to monetize but not a bad idea. WarpDrive seemed like a name asking for a lightning bolt to the nether regions but not based on a ridiculous idea, either. They didn’t (yet) work but lots of things do that in pharma.

      2. Old says:

        Please…

      3. Old says:

        Dilusional

      4. Laura Sailor says:

        I will take the bet, Derek! Big ideas may fail but they almost always yield new applications and generate new thinking. If I lose $500, it is just the cost of my flight to JPMorgan 2021 ! And my charity of course will be Fibrous Dysplasia.

  6. Paul says:

    I totally agree with the statements presented here about EQRx. It is spot on, along with everything Derek has said about companies using AI to do drug discovery.

    On that note about AI, one of those very companies raised a $40 million Series B last week. This is Deep Genomics, of which Derek also commented a few months ago here: https://blogs.sciencemag.org/pipeline/archives/2019/09/30/an-ai-generated-drug

    After raising this Series B, their revamped website says:
    “Our AI platform rapidly directs us to the best drug candidates. It knows biology, from disease biomarkers all the way down to the level of DNA, RNA and the molecular machinery of the cell. …we’re using our platform to evaluate over 69 billion molecules against 1 million targets, in silico, to generate a library of 1000 compounds that are experimentally verified to manipulate cell biology as intended.”

    Really. They just have a CEO wearing a Hawaiian shirt in his photo, and a set of advisors, with no management team listed on their website. Perhaps their management is also run by AI. How? It works like this:

    “Everyone at Deep Genomics uses the platform to do their work, and everyone participates in improving the platform.”

    I follow these companies and shake my head. Like WeWork, the founders don’t need to succeed to become fabulously wealthy. They just need VC’s unfamiliar with this industry who are unwittingly willing to burn piles of cash.

  7. NotHF says:

    Not going to any of the places that usually VC biotech is a massive warning sign all on its own. Sophisticated biotech investors, or even marginally informed ones, would laugh this out of the room.

  8. Industry Guy says:

    But Derek, they aren’t making “me too’s”, they are making equivelars…….way different. lol
    “A fool and their money….”

  9. notbob says:

    Lets assume they are actually successful in this approach (and I share Derek’s concerns about the practicality). I still have big problems with the morality/social benefit of this kind of work. Identifying and validating (in people) a novel therapeutic approach to human disease is an activity of massive social benefit. Drug companies invest huge amounts of time and money trying to do this incredibly difficult and expensive work because they expect a financial reward at the end of it all. In the end investors get a return and the world gets new therapies.

    These people want to end that. They want other companies to do the hard and expensive science of target validation (in people) and then they want to swoop in, copycat the resultant drug and walk away with the profits. Maybe patients get a discount in the short term, but in the long term it just removes the incentive for real companies with real scientists to work on novel targets and mechanisms. Its just a form of financial engineering that results in a net loss to society at large.

    1. Hap says:

      If they could make drugs more cheaply than other companies wanted to, though, then they would be in effect saying that companies were taking more money for their drugs than they really needed, money that could have been usefully deployed elsewhere to solve other problems. Preserving the profit structure as currently implemented sounds like a version of the “broken window” fallacy to me.

      1. notbob says:

        The only reason they would be able to do it “more cheaply” would be because their R&D costs will be substantially lower. Why? They will never have to eat the cost of having a project fail because of fundamental biology. They want other companies to do the work and pay the cost of target validation for them.

        Think of how many billions drug companies have spent (unsuccessfully) on Alzheimer’s disease. If and when a breakthrough occurs that investment should be rewarded. Otherwise those kind of investments will never happen, to the detriment of us all.

        1. Just another chemist says:

          Many companies try to develop drugs on targets validated by other companies, including mine. While it may lower R&D costs a bit, it is only a drop in the bucket compared with the overall cost when you include clinical trials

        2. Hap says:

          But the people who did that won’t be rewarded, just like all the failed light bulb designs before them needed to find the ones that worked weren’t rewarded, either. The lack of reward for failing hasn’t stopped people from trying to do something better.

          And, as Just Another Chemist said, the main barrier is trials, which are expensive. You can’t get away from biology if you want to be in pharma, no matter how hard you try. You find it whether or not you mean to.

  10. enl says:

    As I am not in drug discovery, but do have some knowledge of data science and some, outdated, experience with computational genetics, I can summarize my expectations here with: garbage in, garbage out.

    I think that full-daffy-duck mode was achieved by the VC crowd. “MINE! MINE! ALL MINE!” being the appropriate quote.

  11. electrochemist says:

    Anyone remember Sepracor? A major part of their corporate strategy was to patent and market individual enantiomers of already approved drugs that were racemic mixtures. This seems to me to be the simplest example of what EQRx is proposing – no change in chemical formula, just selecting the enantiomer.

    In at least one, very high-profile case, Sepracor’s strategy didn’t work too well: R-Fluoxetine. Turned out there were tox issues for the pure enantiomer that weren’t seen (or were manageable) for racemic Fluoxetine (aka, Prozac). [Reference: ACS Chem Neurosci. 2014 Jan 15; 5(1): 14–23.]

    The idea that EQRx will be able to bring variations on other approved drugs to market at lower prices without running into such snags seems highly questionable.

    1. Derek Lowe says:

      That is an excellent example!

    2. milkshake says:

      R-fluoxetine was actually the less potent enantiomer, it just had a nicer PK than the S-enantiomer. So they upped the dose, which means the patients received several times more of R-enantiomer than they would get with a racemic drug

      1. not so fast says:

        Actually, not such a good example.
        For years, many companies survived breaking up racemic versions of drugs into their single enantiomers. That worked, until it didn’t. The prozac example is sort of the “counter-example”.

  12. Fuh Dhge says:

    I definitely agree with your overall take on this, Derek, but the one thing I question is whether or not pricing effects how drugs are prescribed/their sales nowadays. Off the top of my head, I can think of two therapeutic areas where me-too drugs undercut the list price of competitors to the company’s benefit: (a) AbbVie’s Mavyret & Merck’s Zepatier vs. Gilead’s Harvoni in Hep C, and (b) Amgen’s Repatha vs. Sanfoi/Regeneron’s Praluent in cardiovascular disease.

    These may be special circumstances, but it looks like introducing cheaper prices has influenced how those drugs were prescribed and their sales. It’s significant money too: Mavyret sales in 2018 were $3.44B

    1. Just another chemist says:

      While Mavyret came out after Harvoni, it was already in the clinic by the time Harvoni was approved. It also works via a different mechanism.

      1. Fuh Dhge says:

        I totally understand (and agree with) the issue from a timing-before-generic competition perspective. Repatha/Praluent were also approved within a month or two of one another. I’m just listing two examples were pricing looks like it’s affecting how patent-protected drugs are being used.

        And, while Mavyret does work partly by a unique mechanism relative to Harvoni, the two drugs in the combination pill worked by established mechanisms:
        – pibrentasvir is an NS5A inhibitor that’s structurally related to daclatasvir from 2014/2015
        – glecaprevir is NS3/4A protease inhibitor, just like telaprevir from nearly a decade ago

  13. Mad Chemist says:

    Methinks the DEA should raid Borisy’s home. Whatever he’s smoking, it’s powerful stuff indeed.

    1. Dr. Manhattan says:

      Nah, It’s legal now in Mass. But I agree…very potent!

  14. cynical1 says:

    This kind of sounds like the companies that went around replacing hydrogen with deuterium ………….but dumber.

    1. loupgarous says:

      The point everyone else here’s making isn’t that me-too drug structures can’t be designed more efficiently. It’s at least possible that they can. It’s that developing those new chemical entities into new drugs to hit existing targets is more expensive than EQRx’s proponents seem to think.

      AI hits the stumbling block in drug development that the pharmacokinetics and toxicology of new drugs depend largely on new science – developing animal models that show how drugs hit identified drug targets, better tox studies, and other experimental work that costs a lot of money. EQRx has announced they intend to swoop in once other companies have spent that money and shown they have a drug which is safe and effective therapy – but they don’t seem to think they’ll have to repeat all that work, and spend all that money on a new analogue of someone else’s drug. They apparently think animal model studies and clinical trials are either cheap or can be dispensed with.

      AI might shave time from development of new drug structures intended to hit existing targets in the same ways that patented drugs do, but that’s just one process that needs improvement badly. To cite just one example of an expensive process EQRx neglects, AI can’t be used to process clinical data, where tabulation of adverse events and comparison of efficacy of new drugs versus standard of care has to be as transparent as possible.

      John D. Clark’s book Ignition! has an instructive tale for those who think that chemists can be easily be replaced by artificial intelligence:

      ““The Air Force has always had more money than sales resistance, and they bought a one-year program (probably for something in the order of a hundred or a hundred and fifty thousand dollars) and in June of 1961 Hawkins and Summers punched the “start” button and the machine started to shuffle IBM cards. And to print out structures that looked like road maps of a disaster area, since if the compounds depicted could even have been synthesized, they would have, infallibly, detonated instantly and violently. The machine’s prize contribution to the cause of science was the structure, to which it confidently attributed a specific impulse of 363.7 seconds, precisely to the tenth of a second, yet. The Air Force, appalled, cut the program off after a year, belatedly realizing that they could have got the same structure from any experienced propellant man (me, for instance) during half an hour’s conversation, and at a total cost of five dollars or so. (For drinks. I would have been afraid even to draw the structure without at least five Martinis under my belt.)”

      Very possibly, AI could give us a nice list of “me-too” compounds which resemble existing patented drugs. It can’t replace all the other necessary labor which skilled minds and hands must perform to demonstrate how closely the new compound behaves like its existing, patented analogue – specifically, how safe and effective it is in treating the same illnesses. This blog recounts just how complex and difficult a task that is, and that’s why so many people read it.

      1. loupgarous says:

        Whoops. Biosimilars already get a mulligan from repeating some safety and efficacy studies which their original counterparts underwent, as part of PPACA/Obamacare, and FDA does something similar for generic manufacturers (probably why some manufacturers are gaming REMS – to make it harder for generic outfits to test for equivalency to off-patent medications.).

        But prices have been coming down for original biologics after their biosimilars go on the market, so there’s some evidence for EQRx’s theory that they can do the same thing with their “different enough not to infringe” drug candidates.

        As a business plan, it’s still not reassuring. The obvious play for older Big Pharma firms is to let EQRx and similar firms go all in, make the requisite investments – then slash prices on drugs which are being targeted by the upstarts. Experience with biosimilar pricing ought to give plenty of data on how low they’d have to discount to squeeze EQRx out of the market.

    2. Compchem says:

      While it’s possible to generate a zillion molecules that “look like” drugs with AI, it’s not possible to accurately predict their activity even at the most reductionist level (I don’t count interpolating within someone else’s published data set, rather than extrapolating to something genuinely novel, or predicting that adding extraneous junk to an existing molecule will have no effect, as these are both things 30-year old technology can already do). Predicting safety is 100x more difficult.

  15. AM says:

    I wonder how many of these companies could have their leaders indicted for RICO.

    There’s sufficient evidence that this approach will not work (with good intentions) or is literally there to steal IP (with bad intentions). Establishing a company like this is essentially a pyramid scheme and amounts to fraud.

    I mean…they indicted Kapoor and his CEOs in the opioid scheme, so there’s a precedent.

    1. loupgarous says:

      If the results of EQRx’s AI screening run pan out, creating analogues of patented drugs different enough to be new IP unprotected by those patents, where are they? Exactly in the same place all of Big Pharma is now, having to very expensively prove their new drugs are safe and effective.

      Nine of EQRx’s ten new drugs may fail in clinical trials if they’re so different from existing patented drugs that they don’t infringe on those patents. How many times have unexpected toxicity, undesired off-target activity or simply failure to improve on standard of care killed new drugs that are only slightly different from existing ones for the same indication?

      This is not a good business model. The only way it could work would be to change FDA’s governing law to permit less stringent safety and efficacy testing for these new-IP analogues, and that sounds like the worst idea in the land of bad ideas.

  16. Jim Bosley says:

    Also: Not to be unfair, but why do the names “Elizabeth” and “Holmes” keep popping into my head as I read this?

    1. John Wayne says:

      It has a similarity in that, if you assume the company achieves all of its goals, does it matter?

      Theranos: if their devices worked, they could potentially take over all of the medical testing services from other companies if they were cheaper and the other companies couldn’t compete. So what? It’s not like blood is a precious commodity. Also, the existing tests are the standard upon which all medical care is predicated upon; displacing it will not be easy.

      EQRx: if they can make an approved version of most major drug classes, all they will have done is taken all the cheapest and highest risk sections of the drug supply onto themselves. They are welcome to it. Making effectively generic drugs doesn’t look like a way to get rich, it looks like a way to get sued a lot.

    2. Tourettes of Chemistry says:

      Perhaps it has something to do with being needled.

      The initial Stat post immediately brought to mind the significance of quality vs. quantity.

      https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0147215

  17. Eric says:

    If Pfizer said that they were going to emphasize me-to drugs and compete on price, I would believe them. They actually have a track record of second to market drugs better than the first in class competitor. But the sheer naïve lack of development insight that EQRx is projecting further erodes confidence in their success. If someone can do this, it’s not these guys, since they don’t even understand the challenges of drug development enough to pass the red face test.

    1. Try me! says:

      Eric,
      So you are saying the strategy is feasible if you have the right team. Should they need to, they’ll turn around and hire 10 PFE folks… lots talent out there.

      I believe this is entirely feasible. As someone wrote, once someone achieves clinical PoC, a good team of chemists can surely come up with another small molecule with similar target profile.

      Take a kinase inhibitor with several crystal structures reported. Known assays. Some chemistry starting points from prior patents. I think that would be quite a safe bet.

      IMHO, the main difference is the price the drug will have when it comes to market. It will be decent, make the company money, and be affordable by the patients. Not all, but a large portion of Pharma and Biotech have become unaccountable. That leads to humongous waste of resources. And that has got to change.

      Kudos and best of luck to EQRx

      1. Eric says:

        Nope. Not what I said.

        Even a “me too” strategy is a big development effort…with way more than 10 people…

        Ok, maybe you start from targets with POC already established, but If you are many more than 5 years behind the first to market, you miss the window, and are competing against the generics. Derek made that point above.

        1. Try me! says:

          Eric,
          These days, you can perfectly hire “10 folks” who know what they are doing and use CROs to run your clinical project. Especially for a follow-on drug.

          I do not know the exact number, but I understand it’s significantly more than 5 years of patent protection following approval than many drugs benefit from. Who knows, perhaps there will be changes to patent protection duration laws…

          Nobody says this is a done deal. I just think it is an idea worth exploring, as lower prescription drug prices are needed.

          1. Hap says:

            In generic companies, though, there’s an awful lot of experience with small molecule drugs, and some of the big pharma generics have significant experience in biosimilars. Both of them want to make money, and have little reason to spare big pharma their profits. What does EQRx have that they don’t?

            Unless they’re own by Civica or some other group whose reason for being is lower-priced drugs, there is lots of reason to think that their patient centricity will lose to their profit motive. That’s how PBMs got where they are, for example (from being patients’ defenders against big pharma to being the screwer of both patients and big pharma). What will keep them from that temptation?

            This seems like a fantasy. If they can pull it off and do as noted, then good for them and maybe for everyone. I just have strong doubts.

  18. J Severs says:

    I am retired, but otherwise I would swipe the Horowitz quote for my next progress review: “‘The hallmark of good is where the solution is simple, but not easy; the answer elegant, but not overwrought’. This year I accomplished. . . .”

  19. Anon says:

    Not surprised by the a16z hype.
    But, has Alexis lost his mind? Who does he think he’s fooling?

  20. Student V says:

    The hype is nonsense, but it’s a story the media wants to believe, and a goal they desperately want, and so they push it. “Look out big pharma the boogey man is coming for you!” They literally take joy in the idea of burning down the industry they write about professionally. It’s kind of sickening.

    The backers of this venture think they are funding disruption that will takeover an industry and solve a societal problem at the same time, but they don’t realize what they are doing is philanthropy, not disruption.

  21. PhDaft says:

    Mnah, just another Ponzi Scheme for suckers. Amazing that people still fall for all the glitter wrappings and the buzz words ..
    Well, as ol’ S. put it:
    All the world’s a stage.

  22. anon the II says:

    Three comments:
    1. Somehow the lying dogs like Borisy always end up rich and the guys slaving away in the lab trying to discover new drugs always end up middle class.
    2. This drug discovery thing is really complicated and nobody outside of the business, especially the politicians, seem to get it right, thus opening the way for charlatans.
    3. It’s really hard to defend an industry that decided it would be a good idea to kick a quarter-million man-years of experience to the curb. Not that I’m bitter or anything.

    1. NMH says:

      regarding 1, try lower-middle class lifestyle (with a PhD), and yes I am bitter.

      Similar in academia: the people who are the closest to getting the money (grants in this case of academia) do well, while the staff that produces the data that is needed for grant applications are in a lower class. Spend enough time in academia generating data and results and you understand why things like the Bolshevik revolution occurred.

  23. JeffC says:

    I went to a talk some time ago where a very engaging speaker discussed how complexity and complication were different and I’ve been mulling on this ever since. The fundamental premise is that something that is complicated is ultimately solvable; it may be very very hard but it is possible. Whereas something that is complex is far more ambiguous and usually does not have an obvious single solution in every situation or a solution at all. And I think drug discovery fits into the “complex” description. And that’s it why the tech people (typically) come in and think it can be fixed. Their usual problems are hard and complicated (which is not to be underestimated or undervalued) whereas our problems are complex. And so they keep coming back for more expecting to be able to find the magic solution. Whereas I think we all know that all of these tools, approaches and technologies are useful in a specific situation but they tend not to be generalizable across the entire field of drug discovery. I do think that genetics, functional genomics, AI/ML will make a meaningful contribution to improving how we go about discovering drugs, but they are not a silver bullet. There are no silver bullets. Our business is just complex. And sometimes that’s really wonderful and why I do it.

    1. Just saying says:

      Agreed.
      Can we also agree that once a drug has been discovered for a given target, that specific problem moves from complex to difficult?
      If so, for that specific problem, technologies might do the trick…

  24. Maltese Falcon says:

    One possible way “new” therapies could be introduce is to re-purpose approved drugs for new indications. Safety/tox studies already filed with FDA, minimizing time for approval. New trials with the appropriate cohorts could be expedited, if well designed. Issue is IP. But that could be a licensing and business decision with the inventors.

  25. Passerby says:

    I don’t get these VCs: isn’t their job to pick the winners and not the hype-fueled smoke-and-mirrors evangelists? So why are they themselves funding hype-fueled endeavors?

    1. Earl Boebert says:

      At the time I had dealings with them, their job was to get 5x their investment in 5 years. One way or another.

    2. DH says:

      As long as the venture doesn’t crash and burn before the VCs cash out, they don’t care.

    3. MTK says:

      The VC’s are there to pick winners.

      The disconnect here is that your definition of a winner is different from theirs.

      A winner in your mind is to have an idea that actually comes to fruition, meaning new drugs in this case. Their idea of a winner is an investment that bears fruit, meaning a return. The two definitions are not necessarily correlated.

    4. Hap says:

      Why does anyone hype anything? Because hype makes money. Sometimes, the added money from hyping a company gives them more money and better chance of succeeding, while other times, it allows the owners to get a bunch of money and get out before anyone else realizes what’s going on. In either case, the VCs make more money with more hype.

      The company’s selling its future reputation for the possibility of success sooner. If it succeeds, people might not care that its leadership hyped the company. If it doesn’t deliver at all, it won’t matter because it won’t be around (though the leaders might take hits to their reputations). If it delivers something but not what it promised then it will hurt its competitive position and maybe its future ability to get money, but it’ll still be around.

  26. Nick K says:

    I have a strong feeling your $500 is safe.

  27. Richard McHale says:

    Damn, I’ve spent two months trying to find ways to quench a catalyst without blowing the product formation reaction. If I fail the cost of the API doubles — and at Walgreens that will mean a $40 scrip will be $100 – and yet come to find out here that in the time I fiddle the eff around with my reaction problem (aka “on-demand synthesis”) they will roll out of Phase IV with the same API and sell it for less than a pack of Kools and a condom.

    1. John Wayne says:

      First, kudos for using the phrase ‘pack of Kools and a condom.’

      Second, the AI is going to figure out that chemistry stuff. Man, humans are dumb* …

      * I’m being cheeky and sarcastic while simultaneously sucking up to an AI that might not understand context.

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