Kevin Hof, Maven Health: 0:00

You can almost describe it as an epidemic. Over 1 billion individuals worldwide have these dysregulation of their metabolic system.

Alex Jani, X-Health.show: 0:13

Hi, I'm Alex and welcome to the X-Health.show where I talk to visionaries behind the latest innovations in healthcare. For the eXtra health of the future. We're in a pretty fancy wood-walled conference room at Büro Züri in Zürich, Switzerland, free but "too fancy for a startup" my guest laughs. His name is Kevin Hof, and he's a co-founder and CTO of Maven Health. A data scientist, medical biotechnology engineer, and researcher who wants to help healthcare providers prevent metabolic diseases. Maven Health is an early-stage startup that develops saliva-based metabolic health test. 47 metabolites are analyzed through custom methods on NMR, Nuclear Magnetic Resonance, and presented in a report that says which of them don't work for you. You'll hear about AI-powered analysis, the difference between NMR and MRI, how you can be overweight and still malnourished. But first, are you sure you're healthy?[INTRO ENDS] Kevin, how many of 120 healthy 25 to 40-year-olds did you have to send to a doctor after performing a metabolic tests?

Kevin Hof, Maven Health: 1:24

In Lausanne, at EPFL, we've completed our human research project, where we had these 120 participants come in and do these tests. We had to inform three people to see their GP right away after these test results. They are quite severe cases.

Alex Jani, X-Health.show: 1:41

What does it mean? Because you didn't choose people who were sick or who felt ill?

Kevin Hof, Maven Health: 1:48

Exactly. We test healthy people, meaning that we have a pre-screener asking if they're already taking medication for cardiovascular disease or things like this. So in principle, these people are healthy. But of course, there's an undiagnosed part in it. And for these three individuals particularly, it means that their ranges or their values are so out of range that the clinical intervention is required. This is because our project, that's why it has such a long name – a human research project, is approved by the ethical committee from the Canton Vaud. And we have to follow the ethical guidelines, meaning that above a certain range for certain values, we have to inform them that I have to see a doctor.

Alex Jani, X-Health.show: 2:32

And you're not doctors.

Kevin Hof, Maven Health: 2:35

Exactly. We're not allowed to make this medical diagnosis but of course, when we see these values, we are ethically obliged to tell them to see a doctor right away.

Alex Jani, X-Health.show: 2:45

What kind of tests did you perform?

Kevin Hof, Maven Health: 2:47

We've done many different tests in one goal, so actually to look at our saliva test, because that's what we're focused on with Maven Health, of course, but we've tested participants in a very broad setting. So it's a roughly a 45 minute consult that people came in and we've collected the standard parameters such as age, gender, height, weight, blood pressure. We've also collected a standard survey for health and quality of life. Of course, we've done our saliva tests where we measure 47 metabolites. Lastly, we also tested for blood markers. So we've tested for HbA1c, HDL, LDL, cholesterol, triglyceride, and fasting blood glucose. These are roughly all the blood markers that are very interesting for a particular aspect of metabolic health. And that's focused on cardiovascular health and diabetes type 2 risks. So when we're just talking about these three people that had to go right away, basically, these people would have clinically poor values, meaning that actually, for one of these individuals, they had a HPA one C level, that would correspond with somebody having diabetes, this person actually didn't know that they have diabetes didn't know. Oh, okay. No, that's, that's very, very interesting. And I mean, this is like full blown diabetes. Talking about this value, particularly, we also had 10 other individuals that would be classified as prediabetics.

Alex Jani, X-Health.show: 4:14

And also they had no idea about that.

Kevin Hof, Maven Health: 4:16

No.

Alex Jani, X-Health.show: 4:17

Okay, that's kind of amazing. We'll come back to what you measure but first, I'm just curious because your solution is saliva tests, right? Why did you measure blood?

Kevin Hof, Maven Health: 4:33

That's a very good point. Also, to put upfront, our goal is not to replace the blood test actually. The blood test is a great method currently for diagnosis and doctors and healthcare professionals can use this to a very good degree. Where we see a gap is in the preventative part, before leading up to disease. Our current system is more like the curative healthcare system, we basically wait until we get sick, they we will go to a doctor.

Alex Jani, X-Health.show: 5:01

I'm laughing but it's not funny anymore, right. You basically start getting treated when you are sick. Preventative health just slowly starts but we're not there yet.

Kevin Hof, Maven Health: 5:16

I would say by far not, no. A lot of work needs to be done. We, of course, are only a small part in this journey. But if we look at the current system, it's much

more binary. We basically say: 5:26

you're healthy until the doctor says there's something wrong with you. And then sometimes you're too late, depending on the disease. We just talked about diabetes type 2. Once you have it, it's not easy to get rid of, or even possible to get rid of.

Alex Jani, X-Health.show: 5:44

And with your test, you want to catch people before they are diagnosed with diabetes.

Kevin Hof, Maven Health: 5:49

We really go into like the vision, future, etc. Our first goal is to benchmark our test versus all these blood values, versus the standard health parameters.

Alex Jani, X-Health.show: 6:01

Hence the two tests.

Kevin Hof, Maven Health: 6:03

Yes, exactly. We want to launch our first product by the end of this year, in 2024, in Switzerland. We're looking at a non-IVD, it's non- in vitro diagnostic regulated products, we will not make any diagnosis with our product. First, we want to build a good measurement system where we can measure all these metabolites in saliva, that already in literature have proven correlations with all these types of metabolic health. But of course, we don't want to just rely on academic literature, we actually want to prove it ourselves and also publish this data and show that with our newly developed method, we can measure this in a very robust and good way.

Alex Jani, X-Health.show: 6:49

A general question, why is metabolic health important? What can you measure there?

Kevin Hof, Maven Health: 6:55

Yes, of course, we focus on metabolic health, so I will tell you that it's very important. But overall unbiasedly, I would also really argue metabolic health is extremely important. It's the cornerstone of overall health and vitality. It influences almost all the aspects of your body's function, from energy production to disease prevention. It impacts the quality of our life enormously. Think of aging healthily, staying fit, energetic. It has even strong links with mental fitness. In literature, there are strong links between your metabolic health and the risk of developing Alzheimer's and other neurodegenerative diseases.

Alex Jani, X-Health.show: 7:33

It's like gut health, basically.

Kevin Hof, Maven Health: 7:38

Gut health – we are looking more at microbiota in your intestines. Actually, that is a very interesting field as well and it has many links. Metabolic health is more your body and your cellular processes. What is going on in your gut, of course, plays a role in the entire story but that's not what we're focused on. So we're more

Alex Jani, X-Health.show: 8:01

All right, so we've got the focused on the overall metabolic health in the body. difference here. And yeah, these 10 people that you tested, and were like, not yet to be sent to the doctor,

Kevin Hof, Maven Health: 8:12

Are you talking about the pre-diabetics?

Alex Jani, X-Health.show: 8:15

Yes, the ones that you mentioned. When we were speaking before you said something about the metabolic syndrome? What is it? Like this pre-diabetes phase, it can be called metabolic syndrome?

Kevin Hof, Maven Health: 8:32

It's very much related, yes. In this particular case, we classify them as pre-diabetics based on their HbA1c, this is more the blood marker for diabetes, metabolic syndrome is defined a bit differently. But it's very much correlated. I have to be honest, metabolic syndrome is not fully agreed on what it is exactly. You could see it as a complex disorder defined by interconnected factors that increase the risks of cardiovascular disease and diabetes type 2.

Alex Jani, X-Health.show: 9:03

What is discussable? What scientists don't agree on?

Kevin Hof, Maven Health: 9:08

It's more the what defines these risks. There are multiple aspects and there is a bit of debate on what plays a role or not, and what should be included in the selection criteria or not. Some are very clear. For example, your elevated triglyceride levels, especially elevated fasting blood glucose, elevated LDL, some others like the waist circumference, so how large your waist is, it is included in some, it isn't included in all definitions. But if you go by perhaps like a definition from the CDC or WHO you get a very good impression but in literature, it's not completely yet defined.

Alex Jani, X-Health.show: 9:52

Let's speak a bit about your solution. How does it work? It is a saliva test. Like me, I guess people would prefer a saliva test to a blood draw. What does it look like? You brought here your sample kit. I let you describe it.

Kevin Hof, Maven Health: 10:18

Happy to. Maybe to come back to your Roughly 1/7th of the world's population. last topic a bit because I know people love numbers, or at least I'm one of those people that really loves numbers. If you Yeah, so quite a lot. In the Western world, this is even look at metabolic syndrome, you can almost describe it as an higher, also due to our lifestyle, around 20 to 25% of epidemic. Over 1 billion individuals worldwide have this dysregulation of the metabolic system. everybody, also here in Switzerland, has metabolic syndrome. Just thinking about the scope. Then to come to our test. We test saliva and our kit works rather simply. We have a box that holds a collection tube. It is a tube that is connected with a small funnel. You can maybe best compare it with one in your kitchen. You maybe have a container where you want to put sesame seeds in, for example, and you want to pour them but you don't want them everywhere in your kitchen, so you use the funnel to pour them right into your container. This is what you click into the tube and this funnel you then place between your lips and your teeth, and you lean forward and you salivate. You produce new saliva and this goes into the container.

Alex Jani, X-Health.show: 11:48

How much of it do you need?

Kevin Hof, Maven Health: 11:50

Roughly one milliliter. So we're not asking much here.

Alex Jani, X-Health.show: 11:53

Yeah, it's not much really. What happens after that? You have the sample and I guess, you need to send it to a lab.

Kevin Hof, Maven Health: 12:04

Yes. Well, there's actually one step before. There's nothing invasive, that's really where we also went for saliva, but people are expected to fast for two hours beforehand. This means that you don't eat, drink, chew gum, eat bubblegum or smoke, for example. Because of course, this will be otherwise measured in your saliva. And you rinse your mouth with water multiple times. So you basically create, it sounds very tasty, but you create fresh saliva. That is what we collect and analyze. Your sample will then go first to our lab in Switzerland, where we will do pre-processing. This means that we will add a compound that stops all the bacteria from being active. Even though you rinse well, there will be bacteria in your mouth and they will have their own metabolic activity. And of course, we want to measure your metabolic activity, not the one of your bacteria. So we add something that is very toxic for bacteria, we block them from influencing your test results. And we do this as soon as possible.

Alex Jani, X-Health.show: 13:11

Oh, this is fascinating. I'm speaking also with startups who actually focus on these bacteria that you want to block. Amazing.

Kevin Hof, Maven Health: 13:26

They might want to see, which ones they are. We want them to not bother us. Different aspect. We pre-process these samples and we batch them together. Then we send the samples to our commercial lab partners. These are partners that use Nuclear Magnetic Resonance machines and they run these samples with the method that we have developed at EPFL ourselves. We receive the results from these machines and we convert this into an identification and quantification of these 47 metabolites.

Alex Jani, X-Health.show: 14:00

How did you choose these categories of metabolites and then metabolites themselves? Why 47? Why these groups of metabolites?

Kevin Hof, Maven Health: 14:10

That's an interesting aspect. That technology we use, it's not like an assay. Most people in the medical field are used to measure one thing and then you measure another. The machine that we use, NMR, measures everything in one go. In one run. We optimize the method, the instructions of this run, to be specific for smaller metabolites because we're really interested in glucose metabolism, amino acids, and short chain fatty acids. It's shown in literature that these have the strongest links with the things that we discussed before, diabetes and cardiovascular health. So instead you can see it as we wanted to measure the core. That's what we delivered and developed the method. Then we have a bit of bycatch because we are measuring it anyways. If we can identify and quantify it up to a certain level, we're using the ICH standards of analytical measurements on basically being able to have the right analytical precision and accuracy, if it reaches those standards, then we include it into our results. Also, if we improve our method in the future, we might have 50, or 60 metabolites that we can measure. We really see it as a complex system. As we mentioned before, metabolic health is a complex system. We don't want to just measure one or two and say this is the biomarker for cardiovascular. We want to measure all of them and understand how all of them fit together in that picture and give you a really good score, a good interpretation of your metabolic health. Because we think it's a complex measurement.

Alex Jani, X-Health.show: 15:51

And here comes your report that I saw. You actually give a total metabolomic score after this test. Could you say, what people or health healthcare providers receive back after this test?

Kevin Hof, Maven Health: 16:10

We also see the report really as something that we would like to provide to the healthcare professional but also to the end client. We think this is a challenge in the current day testing as well. I don't know if you have done a blood test recently or a while back but they kind of all look the same. They're very tough to understand for the end customer, even if your doctor shares it in the first place.

Alex Jani, X-Health.show: 16:32

That's a very good point! Because you've got to ask for it and here in Switzerland, you basically get a bill for the test and then the doctor may just say, everything's all right. And that's it. You don't even see it. I actually really like to see my tests and then compare them. But obviously, you always have to go to a doctor to have it analyzed properly with the knowledge that a doctor or medical doctor has.

Kevin Hof, Maven Health: 17:03

Absolutely. So our goal here is to share that with both. And what you see in normal blood tests now is that you most often only see an interpretation on the individual level. Of course, doctors are very well trained to understand this but they have very little time and if they are measuring 20 different blood values at the same time, and they have two minutes to prepare for your consult, do we really realistically expect them to understand the complex interactions between all those 20 measurements you might see? Or are they going to look at which ones fall off the boat or out of range and going to make their diagnosis based on that? Of course, they're doing the second thing, no one can blame them. But we think that the interpretation and the levels of interpretation on top that you can provide are very useful, both for the healthcare professional and for the end customer. That's why we broke it down in three levels in our report. We have the individual interpretation of those 47 metabolites – if they are optimal, sub-optimal or out of range. Then we have a second level on top of that, where we do it based on the classifications – we're talking about the class of amino acids, the class of short chain fatty acids, the class of glucose metabolism, intermediaries. How many of those fall out of range? So you can quickly see that with one simple graph.

Alex Jani, X-Health.show: 18:28

So what are your strengths? And where you need to work on?

Kevin Hof, Maven Health: 18:31

Exactly. You don't have to go through all the 47 to then do a mini analysis on which ones fall out of range. You can easily see that right from the start. And then – the overall metabolic health score. Here, we really want to give you a personal interpretation as well on how do you score versus your peers. This will be a score between zero and 100 and it will be compared with your peers, meaning within your age and your gender group. How do you compare versus them? I can talk a bit more about how we make that score.

Alex Jani, X-Health.show: 19:06

I'm very interested because it takes a doctor years of experience and knowledge also to see what with what can be dangerous to a patient's life or just unwanted, and what is just something that doesn't mean anything. It may be out of range but you just don't have to do anything about that. So I'm very curious, how did you train your algorithms to come up with this score, conclusion.

Kevin Hof, Maven Health: 19:44

This is also why it's one of the main reasons why we've done this human research project at EPFL. [This conversation continues on the podcast]