David de Gruijl, Anto: Founder @ Anto (YC F25) | Pharmacology x Gastroenterology

And I'm gonna try not to butcher your name, by the way. That's That's David and Charles for another YC wasn't pod. David the Grou.

[laughter] >> Nice try. >> Yeah. How is it again?

>> Oh my god, I was like so far. Um, my subconscious brain didn't even like digest the pronunciation last time, so shame on it. Uh, Dave is founder at Anton.

So YC F25 company it's pharmarmacology meets uh gastro anterology me and him were talking about the gut brain axis last time we spoke and uh just a fascinating field so David's also a fellow at Sigma squared societies a founder of anx company we'll talk about that one graduate research at Harvard Medical School you're a bunch of things give a quick intro about yourself Dave >> yeah sure my name is Dave David. I'm originally from the Netherlands. I'm currently founding a company in the space of the gut microbiome and how the gut microbiome influences how we respond to drugs and foods that we ingest.

Um, we predict that using our own uh trained foundation models. Uh I've been in the space for about six years now. Originally in Zurich uh and then later at the gastroenterenterology department of Harvard Medical School and started this company together with a labmate that I met uh in Boston.

And when we first spoke, I was like, "This is so obvious, right?" Like, uh, from a guy like me that's been studying the gut, that's been a biohacker for quite some time. It's just obvious that your gut's health will help the absorption of drug and and make them more efficient in many cases. Why do you think that no one else have been starting something in that space before or have they?

So there has been a wave of companies in this space about 10 years ago. I think one of the main barriers around the gut microbiome was that we didn't really understand what was going on at all. Like we didn't have the tools to actually study the microbiome in depth.

So essentially we knew oh yeah there's some kind of correlation between gut microbes and the way that we respond to food and drugs but we don't know what like the correlation exactly is and if you don't know what the correlation is what can you actually do about it and then about 10 years ago we started developing better tools in terms of like sequencing so understanding the DNA of those gut microbes and other chemistry tools to understand how these microbes function. And that kind of landed the first wave of companies um that for example tried to do microbiota transplants. I'm not sure if you've ever heard of this >> disgusting [ __ ] pill that you swallow.

But yeah, do describe to release so that we can have a couple of listeners vomit. >> Yes. So, so essentially it was clear that there's this kind of correlation between like how we respond to drugs and like your microbiome.

So there were some people like that maybe you knew that to a certain medicine or whatever they're super responders like once they took the medicine their tumor shrank like incredible. >> Basically their ancestors were poop eaters. [laughter] >> I think so.

Yeah. Yeah. >> To Dave Asprey.

>> Yeah. Like it's not really clear exactly why those people have like a quote unquote good microbiome and other stuff. >> The reason I just said dude though don't >> but what people started doing is like okay let's just give the people who are not responding very well uh antibiotics.

So like destroy their own microbiome, then take the poop of those super respponders and just give it to them in a pill with the hope that there are like the super responders microbiome will will last in the digestive tract and that that will like turn like someone who doesn't respond well to the drug uh into someone who does respond well. and the science dude that the level because again to me it's obvious for some reason but I mean you've researched that way more than I did >> but when you eat something in the gut microbiome these bacteras digest the food they break it down >> and then they have it enter your bloodstream right >> yeah correct >> so the the same thing happens when you swallow a pill no >> it will actually digest some components of the pill and put it into your bloodstream so Okay. Why is that still not obvious?

I'm >> It is obvious. It's just not so obvious what to do about it. >> So, if it's obvious that it exists, but like you cannot predict it, nor can you like change anything about it, you might as well just ignore it.

>> And why is it not obvious? Is it that it's not scientifically researched or that reaction has not been studied enough like taking that component of the pill you just took and the digestion actually helping it or is it because there's other mechanisms and there's like so much at play and we haven't isolated that specific mechanism. >> We have yeah we haven't isolated any specific mechanism.

So like because we don't really know what the mechanism is, the best action you can take is just like replacing someone's entire microbiome. If you knew what like the mechanism exactly was, you could take more targeted interventions >> and the poop pills, is it the best way to do it? Because there's tons of um gut microbiome supplements out there.

There's even prebiotics nowadays. These are not as effective. Why Why does poop like literally replace my full gut microbiome?

Wouldn't like some of my existing microbiome stay there? Tell me a bit more about that. Theoretically that would work you know like giving people prebiotics or some other kinds of supplements which kind of [snorts] shift your microbiome in such a way that it's more like a super responder or like someone who responds well to like medicine or in that case food.

That would like actually work. But again like we we don't really know how to do that precisely. So like we just take like the most coarse grain like solution that is like kind of the first generation of companies in this space.

Now like our company and like the next generation of companies, we figure out like in more detail we have the tools to find those mechanisms and then like propose more targeted uh solutions to these kind of problems. >> I'm watching your video on the website. What will be you guys first product?

Yes. So our first product is actually just predicting mechanisms uh of like what the gut microbiome does and how it influences like the way we break down compounds. So we work with companies that essentially have some issues with them with like a clinical trial and they have no idea what the issue exactly is.

They they saw that the trial didn't work as expected, but they don't know why exactly and they start hypothesizing that it might be the gut microbiome. And then we kind of help them more as like a tech enabled service to figure out whether the microbiome was involved in in like the unexpected results and what they can still do about it. now that they have a trial that has like terrible results.

>> What is sparification? >> Yes. So, essentially like modeling the gut microbiome is incredibly hard.

So just building like kind of uh large AI models in the way that we do with text doesn't result in great u great models. Um, it's like as if every word has a spelling mistake in microbiome data, you know, and you just feed like these these these words with huge amounts of spelling mistakes to an LLM >> and you train the LLM and then you expect it to understand language. Uh, it's usually just garbage in, garbage out.

So what our company actually has developed is certain like pre-processing type of algorithms that deal with these spelling mistakes. So we filter out all the words with spelling mistakes and we only keep the words that uh likely don't have any spelling mistakes and we only feed those words to our language models. And if we do that, um, then these models perform much better because they're not trained on noisy data.

>> Why couldn't Fiser or any big company do that themselves without you? >> That's a great question. Like I think eventually they would be able to do that and that is like kind of the golden lining of every single foundation model in in biology is like any big pharma company could do anything that you are doing.

I think I have two like responses to that. I used to work at a pharma company. I worked at Johnson and Johnson and we started a project in 2019 and as far as I understand they're still trying to implement this project seven years later.

So these companies they innovate a lot by acquisition and a lot like by by internal >> innovation. Yeah. Yeah.

Yeah. That's the key, right? Like one employee one YC founders were a hundred employees or something like that.

And I'm not joking and that might sound very arrogant, but >> these guys are just paid to just take things. Everything's slow. They're not super creative.

They're just like 9 to5s. Um >> Exactly. And it just takes super long to get alignment in these companies.

Yeah. >> So for from my perspective during that project >> um there was like every single team like was solving within this company was solving the problem in a totally different way. >> They were solving how to meet on Zoom.

[laughter] >> Yeah. Exactly. like they they essentially like to get them all all these different teams together and say like no no we're gonna from now on we're going to do it this way and we've built this tool.

It was like almost impossible to get them all together. Agree to that, pilot it. >> Um, >> it's crazy.

>> And then >> don't get me started on corporations, right? Like corporations are just over bloated financial instruments. They're not >> productive for very productive for society.

Startups would be more productive for for most of society. Um, and it's not just the FDA, right? It's not just like compliance.

It's the companies themselves that move so slow. Like deploying a drug in 15 years is [ __ ] ridiculous. It should take days and weeks, right?

And I I think we can move at this space nowadays. What do you think? >> It's true.

But I think like one of the things you see in this space is like part of that like speed comes from the companies that might be like very bloated and have a hard time moving fast. But part of it also comes from all the other stakeholders and institutions that play a part in this. So especially in clinical developments if you have governments uh that you need to interact with you're dependent on how quickly governments move which you for example see in China right now is that one of the uh big advantages that China seems to develop in in biotech is that the government simply moves faster.

Um and then essentially you also have these limitations around if you for example try and cure a rare disease, you have to find a significant enough sample of people with this rare disease to test your drug on for a clinical trial. It's not so straightforward to find all these people and have them all together, make sure they don't drop out of the trial for whatever reason. Uh so this logistics part is is like complicated too.

>> Is rare disease as a vertical attractive as a business model and aren't what are rare diseases? Aren't they micro branches of a macro disease? >> Yeah, usually usually it's micro branches of a a macro disease.

That's right. as far as I understand. Um I think like it depends also on the government uh whether that is like an attractive market.

So you see for example in the US there's certain regulation don't quote me on this like please do fact check there's certain regulation as far as I understand that um basically doesn't put price caps on drugs with like that are for rare diseases so that like pharma companies can charge a lot more for these rare disease drugs than um for like other kind of drugs that they would develop >> and this makes it in the current environment. >> Yeah, it is evil and it makes it in the current environment very attractive for pharmaceutical companies to go after rare diseases because like you can even though there's not that many people with the disease maybe you can charge like half a million dollars per per treatment, right? Oh boy.

And on the clinical trial side of things, do you see an efficiency? There's been innovation on that side as well. Lots of companies uh many YC companies have been using AI to do in vitro uh clinical trials, right?

Like what have you seen on is it promising because that could 10x the drug research. Um uh speak from uh inception to market, right? like it could go from five years to two years but of course we need the to accept that so what's the latest development in that space of things >> I think it's incredibly valuable because I think like one of the limitations that you have in drug development is that it's so expensive that expense partially comes from time like the longer things run the more money is put into it obviously So with like any kind of technology or innovation that reduces that time component or resource efficiency in a way um that improves the amount of shots on goal you can do.

So how many drugs you can try that actually um like how many drugs you can try and and see if it actually works. So you have this one side of like being more efficient and making sure that you have more shots on goal, so less cost per drug, and you have this one side where you're trying to make sure that more shots on goal actually hit the goal. >> For us, a bit more on the other side.

So like we try and make sure that more shots hit the goal, >> right? by giving companies uh an algorithm that filters the crappy data and gets them to where they want faster, which is pretty genius. I'm going to come back on that in a second, but [snorts] um AIs can reliably have a human AI avatar models now that is reacting the same as my body would in a clinical trial.

Is that like said and done? Is that like uh applied right now? >> It's definitely not really applied right now.

And it turns out that >> uh I know companies are working on it. Um I'm not sure how validated some of these technologies are and uh one of the things you run into is that the body is really incredibly complex, right? So if you have this model that is sort of like a digital twin or a digital avatar of you and you take into account only human genetics, so like the differences between you and me in terms of what kind of genes we have, but you don't take into account for example the microbiome, you might miss like a crucial part as to why people are gonna respond to that drug and others don't.

And and I think like that is like kind of the the issue with with like figuring out whether things work or not is that human biology is incredibly complex. So many dependencies, >> right? Because you need to reproduce like my full biology, right?

And what biochemicals are you tracking? There's like thousands, right? The before, the after, and then then have a reliable timeline of that data.

O take a patient that has done tens of clinical trial if they survive [laughter] the all >> yes >> um and yeah that is complex in itself right but technically from the first principles right take all the data uh well align on I don't know like hundreds hundreds of biomarker markers >> before and after if you put that in a database you could create some kind of avatar um and you could start from there Right. But um where am I wrong in in that thinking? >> Theoretically that's true and I think even practically it can be very helpful and it would like potentially increase the amount of like or the hit rate or the success rate that you have in in clinical trials.

It's just like practically speaking, I think one of the issues we have is that like there's always something that we didn't take into account that just pops off. Let's say like and because like essentially what we use right now is like our digital avatar of a human is an animal, right? Like we we test on uh medicine first on mice then on like maybe rabbits then on on pigs and then on >> that be removed all together if we have AI humans avatars just to make a decision on where to focus their time money and energy on what drug right I'm pretty sure that's smarter than yeah >> illegally you need to do it on mouses as well or >> the regulations are kind of changing around that so a lot of like even the the FDA put out a call I think last year to reduce animal models in clinical trials and use more like human relevant data which kind of includes the microbiome right like an animal that has a diet of corn doesn't have like the same microbiome as a human but like >> archaic Yeah.

So like there there is some initiatives on that but the question is always like is the AI actually more accurate than the animal model that first has to be like kind of true in order to for like a company to be confident >> if that is constantly improved. Yes. Uh would be my my theoretical uh shot at it, right?

Um especially if there's a recursive loop in between. Oh, okay. We did the the virtual AI avatar test first.

We focus on that drug. We make the human trials and oh, was it a good decision made by the AI and then you do that enough times and you reduce the cost in the meanwhile and so you increase the test so the AI gets exponentially better is what my gut feeling tests. And it seems so [ __ ] archaic.

The mouses, you know, like when I did my neutropic uh like 10 12 years ago, we did studies on it and it was like the the mice swimming test which was like so [ __ ] up. Like give the mice some supplementation and then it would find its way like that's cruelty, man. That's so [ __ ] up.

>> It's crazy. That's actually a little bit on how um how Ento our company initially started like so we were dependent in our lab on pig studies because pigs they have a similar size stomach and >> Yeah. Yeah.

And like even the lab's logo, it used to be a logo of a pig, you know, like and we actually were thinking like, okay, >> animals of, you know, like domestic animals, right? They're pretty nice creatures. They're smart.

And >> incredibly smart. Yeah. And if you could reduce the amount of studies that you can do on pigs by just computation or even like uh experimental studies that be great.

What we realized over the span of like years is like the reason why people still use pigs is because recreating someone's digestive tract in the lab is like not very accurate and not very scalable. So you might as well use a pick because it's like basically your most accurate model. Well, for us like the scalability it can be solved by computation and if the if if you can also make it more accurate than a pig because like essentially the microbiome of a pig is different than that for a human.

So if you simulate a human microbiome then you solve both that scalability problem and the accuracy problem at once. Isn't like the human gut like so different by design because we're vertical creatures >> to some degree? Yes.

But uh when it comes to like basically [snorts] um like for example size if you're trying to test like some kind of let's say like we used to have these tubes that you could put through someone's nose and then it ends up in someone's stomach. They use those kind of tubes in the intensive care units. It's called nasogastric tubes.

>> And like you cannot test a nasogastric tube if you have like if you're building a new one for whatever reason on a mouse because obviously the tube is not going to fit into a mouse's nose, right? And not into a mouse's stomach. So if you want to do it in like a human realistic way, you want to test that on on animals.

Got it. Billion dollar market seems small, right? Because if all the drugs are influenced by that, that would be trillion dollars, wouldn't it?

>> Correct. Correct. Like essentially, you see it with those uh feal transplants is that for the most sold drug in the world right now, it's called Gatoruda.

You could double the response rate to that drug by just changing people's microbiome. >> That's insane. >> Yeah.

And this is like >> what's the science behind that? Is that a guess or >> the science is actually doesn't necessarily have to do with breaking down the drug? It's like an indirect interaction between your microbiome and the drug.

So what happens is that the microbes in your gut they change your immune system and this drug works on your immune system and as far as we understand it's like if you have your guts constantly work or the gut microbes constantly working against this drug. It's a competition between the microbes and your drug. Um and the only way to change is by changing the microbes at this point.

Uh so that is like one of the reasons that we think this is the case. There's other theories behind it too where like this drug acts on a certain target. So you have like the molecule and it has to bind to a certain protein.

But the microbes seem to produce molecules that bind to exactly the same protein. So the drug cannot bind to it anymore. The protein is already like occupied.

Let's just say it that way. [laughter] >> That's insane, man. Imagine because if you you said like uh 50%.

>> Yeah. Yeah. So it's like a $30 billion revenue drug, right?

So if you >> or in terms of like saved, right? How crazy is this? This is like couple million's life saved.

>> It's real difference. Yeah. Yeah.

>> So why don't why aren't all of these patients having a feal transplant then while taking the drug? >> So it's still going like people are working on this and I think recently uh phase 2 clinical trial was um was released that showed like this kind of difference. I think the overall response rate so whether the tumor was shrinking or not was 77% whereas normally if you give the drug randomly to people it's 35%.

>> Oh my god. >> So it's like a huge difference. >> Peer reviewed and great methodology.

That was a study done by this big company right that does the drug. I forgot who it was or >> Merc. >> Okay.

So that was a study done by Merc or >> it's a study I think it's done by >> I'm not sure if a I think a company was also involved but it's actually an hospital that >> that does it. >> So >> the the study is called FMT Luminate. >> It's crazy.

But also it assumes I'm not what was the sample size? How many patients? I think it's like it's a small sample size.

I think it's like in the tens >> in the US >> like not the like the thousands >> and it's I think it was based in in France. [snorts] >> Okay. in France.

Do because my next question is like do all of us have shitty microbiomes uh or already have good microbiomes and are already taking the drug and for us is like incredibly more efficient. >> Um so I think >> these treatments I'm pretty sure it destroys your gut as well, right? like some of these >> I think like in that sense like so there's still more research that needs to be done right like on such a small sample size look super promising but the question is like does this hold up at a large scale I think for some of the companies that tried to do FMTS they had a hard time uh proving that early on like for other conditions [snorts] >> my gut feeling saying super positive on that one also like that I'd be bullish about that.

Now coming back to your business model right as a VC like what is what do you sell for how much is it like Palanteer style uh software deployment in which you work uh with the company you do have a software that's already built but you do adapt it to them multi-million dollar contract a year what does the business model look like >> yeah so that is the initial business model exactly like you describe it's like forward deployed it's helping deploying these kind of models into their their clinical trials. Um, but at the long term, we actually want to capture way more of the value and not just be like involved in in helping other companies understand the microbiome and making sure that they can make drugs that where more people respond to this drug. uh but we want to like actually design some of those drugs ourselves.

So like one of the things that's open when you help other companies is that they can for example take the action of like these feal transplants. What we really believe is that there's an opportunity in this space to be more proactive. So if you have a drug for example that's broken down by microbes in different ways and because of that maybe two out of 10 people respond to the drug.

What if you like take that molecule and you redesign it in such a way like the molecule itself or like the formulation that the microbes that normally would break down this drug they can suddenly not touch it anymore. Then suddenly maybe you can have a drug that is very similar to the original drug but it works in four out of 10 people instead of two out of 10 people and that would have a huge influence on like I mean patient outcomes obviously because it's a tragedy that we prescribe so many drugs to people that just simply doesn't work with their biology and quite honestly we're too lazy to test for it. That is like a bit like sad.

But >> yeah, it's ironic, right? Because there's all these uh health tests nowadays that we take to optimize their health, but there's no such test when we prescribe drugs to people, it seems. >> Yeah, it's very uncommon, right?

Like even >> why not go that step, dude? Like >> wouldn't that be the starter? I think like what we observed was so for genetics there's quite a bit more known on how like for example certain enzymes that your liver produces how that influences the way we respond to medicine.

But quite interestingly, even for the medicine of which we know that those issues exist, a doctor would rarely test for your genetics before they prescribe this drug. So like I I never experienced that. I never had a blood test before a doctor prescribed me a drug.

>> That is so crazy, man. >> And I never thought The craziest thing is I never thought about that thing. >> Yeah.

But it's so obvious, right? It's like >> so what like most pharmaceutical companies have done in this space is if they found out that a certain drug, let's say one common drug is warerin has like these huge issues depending on your genetics and because of that people get many side effects and like they get the wrong dosing. Instead of then um like doing a genetic test before prescribing warerin, they just try and design a new drug that doesn't have the issues that warerin has and then they kind of try and convince doctors to prescribe this new drug instead of warerin.

>> So why not launch company doing that is my question to you. >> That seems more logical. >> What do you mean?

Well, you start designing tests for big pharma that obviously doctors would be in charge, right? But you would target big pharma. People would do tests and that would double the efficiency of their medicines almost overnight and you wouldn't have that many FDA hurdles.

>> So that's more economically sound and like a lower hanging fruit to save more lives. The issue that you have is that like I said like this adoption doesn't exist or at least it didn't exist for genetics. >> Why would indoctrin not want to double the efficiency of what they're prescribing and the patient wouldn't want that too?

>> I think like there's several several hurdles to it. I think like one of them is I guess like doctors like see it as like kind of a um like an extra step. So maybe not everyone wants to take that extra step.

>> Well, please [laughter] >> Yeah. Yeah. Yeah.

And like >> but it's true. I I know I had a guy on my pod by the way that guy could be an investor for you. James Bates uh he runs Adv Med or something like that and as a problem he's solving like clinics are so inefficient.

Uh but go on. >> Yeah. And the second comes actually from um from the pharmaceutical companies too where like maybe the incentives there are not entirely aligned because if you can sell a drug and then you have this kind of test that uh like essentially cuts like the amount of prescriptions down.

Maybe you would not want that test to be there because the guy for you as well there. Um, shout out to my client Barry Patel of Gul Pharma. [snorts] Uh, that guy would implement your stuff.

Maybe. Yeah, I would fund you for that. Like if you want to go on a side quest.

Uh, and that seems so obvious to me. I'm going to do some research. I'm pretty sure there's already people.

I think like one of the issues that we see just in this like space and that's just generally the case for diagnostics and uh building diagnostics that decide whether you should take a certain therapy or not. Um is that like healthcare incentives are just so incredibly complex and >> or biased or corrupt and evil? >> Yeah.

Yeah. Yes, that like I didn't want to say it that way but yes [laughter] >> creating at this stage but yeah go on >> and like uh essentially like because of those those incentives whether it's like the doctor, the patient, the pharmaceutical company that tries to convince doctors to prescribe their medicine or even the insurance and like whether insurance covers certain things. If you add all of those things up together, >> it's really like a lot of companies get stuck in this like alignment uh problem.

>> Let's change that. You should have a manifest on your website or something, but al also you probably shouldn't because the guys you work with are are guilty of that to some degree. And by the way, they're not fully evil, right?

Like these guys are saving lives and they're doing their best, right? But there is some of that and that's that's when people call you start calling them big pharma right and I'm not one of these guys right I'm not a very serious guy still think that [ __ ] needs to change um coming back to your model right like let's bring the pod to close how do you get in touch with these guys how you close sales with them like very long sales very long as [ __ ] so how do you make it Yeah. So I think you always have to be quite patient in this case.

Like you cannot just just with like your average B2B >> S yourself >> just like in the after the first meeting just send a contract and like the contract is signed. I think >> start the process and go on a world tour that lasts at least two or three years and then come back and then find a answer in your mailbox three years later after you contacted them. [laughter] I think like one of the things that we've done as a company is like first of all if you build a company in this space credibility towards like for the customers is incredibly important.

So you cannot just show up and say like hey our model does XYZ it has to be sort of grounded in for example peer-reviewed research. So if you can show like oh yeah we published a paper on this and independent researchers agreed that whatever we were doing was legit that really works. I think the second thing is like a lot of it comes from warm relationships.

So if you don't have the warm relationships yourself, um you need to find like a team or build a team around you of people who've worked with these pharmaceutical companies for longer and where like the people in those companies really trust uh that person because for them their career hinges on sometimes on these kind of deals. If they make the wrong decision, their career can collapse. >> Yes, good point.

>> So, >> so they like want to like only make those decisions if it's with [snorts] people that they've dealt with to some degree before and they know that these people will deliver. >> Yeah, >> I love it, dude. Uh, thanks for being so upfront today.

Uh, where can people find out more about you and the company? So you can find us at www.anto.bio. Um follow us on LinkedIn as well and um yeah like um I think that's that's most of our socials like you can follow me on Twitter personally.

Um that's >> there you go dude. So that was David and Charles for another YC wisdom.