Non-Invasive Blood Sampling with Leuko
- Digital Health, Startups, Tech, TWIDH

Non-Invasive Blood Sampling with Leuko

Leuko is a company that spun out from the Massachusetts Institute of Technology and the Madrid–MIT M+Visión Consortium. The founders were research fellows in a biomedical technology innovation initiative who felt compelled to solve a significant unmet medical need for cancer patients undergoing chemotherapy.

You can read more about their story at the MIT Innovation Initiative.

We’re here today with Carlos Castro-Gonzalez. Can you give us a background of Leuko?

It was spun out of MIT. That’s where the team of co-founders initially met. It’s a team of four co-founders – myself, Ian Butterworth – Chief Technical Officer, Aurelien Bourquard – Chief Data Scientist, and Alvaro Sanchez-Ferro – Chief Medical Officer. We met while we were doing our postdoc as part of the Madrid-MIT M+Vision program. This program focused on finding new solutions to existing unmet medical needs or critical clinical problems. Unfortunately, these problems don’t have an answer today, so we were tasked with designing new technical solutions that would be uniquely positioned to solve them.

The problem that we initially identified was related to cancer patients undergoing chemotherapy. One of the significant side effects for these patients is that their white blood cells routinely drop to very low and dangerous levels. That exposes them to frequent and life-threatening infections.

At the time, I had a personal experience with the issue. One of my best friends from Madrid was undergoing chemotherapy, so I was susceptible to that problem. I could experience firsthand how worried he was about his white blood cell levels. So that was a personal motivation for me to start working on this particular problem.

I’m glad to report that my friend’s treatment was successful, by the way. It worked. He is now cancer-free, so that was great news.

That is good to hear.

Can you elaborate on how they monitor the white blood cells and how difficult that is? And then that will lead us into your ultimately into your product.

One of the limitations to monitoring the white blood cells of these patients is that they all require a blood draw. Patients must go into the clinic to get a blood sample, limiting how frequently this test can be performed. You cannot be bringing the patients back to the clinic every day. This is especially relevant in today’s context because of COVID.

Between doing chemotherapy cycles, these patients are actually at home, while their white blood cells may or may not drop. There is no way to track what is going on currently. As a result, the physicians are in the dark. They don’t know which patients are actually at risk of these life-threatening infections.

What we set out to develop was a method that wouldn’t require blood sampling whatsoever. An utterly non-invasive way that would allow, for the first time, patients to do this test from home and much more frequently. Those in trouble can be detected earlier, and preventive treatment can be deployed to those who need it.

If white blood cell count has dropped, they’re compromised, so we don’t want them to be in the clinic environment any more than they have to be, correct?

Absolutely. That’s another reason we want to keep patients away from the hospital environment, particularly in those situations when they are compromised.

This is even more obvious today because of COVID. So we think that our solution fits very well in reducing the exposure risk.

You identified this problem from a use case where you knew a person who had this pain point. How did you go about building a solution for that?

We were looking for ways to solve this in a non-invasive way. So we thought of a product that would involve microscopy. Our product is a portable microscope that looks through the finger’s skin, particularly in an area that is well known to have very superficial capillaries. These capillaries are very narrow blood vessels, and by taking videos through the skin, we can see the blood flowing through these very narrow vessels. They are so thin that the white cells must pass through one by one.

We are using one particular wavelength absorbed by the red cells, but white blood cells are transparent to it. So we can see them as bright spots passing through these capillaries in our videos. We can then analyze with AI algorithms to get a measurement.

How accurate is the diagnostic?

We performed a clinical study with our prototype. Where we tested our prototype with forty chemotherapy patients in two hospitals in Boston and Madrid. We compared the results of our tests with blood samples taken by traditional means at the hospital.

We demonstrated that we could identify with high specificity and sensitivity those patients with low values. So our first product, the Minimum Viable Product, is not replacing the blood draws; it’s just providing a warning. It can give a binary reading, if you will, about whether patients are critically immunocompromised or not.

We showed that we were very accurate in making that binary classification.

Will this device have the ability to give them a warning? Will it provide them with reading, and will they have to understand what the result is? Or will it send a notification to the primary care provider? How does that work? How do they get their results, and what do they do with them?

They can conduct the test by merely having the tip of their finger in the device for one minute to perform the measurement. Then, the test results are sent back with this device to the care team that follows up with the patient if there are any problems.

We interviewed more than 50 opinion leaders in oncology to determine what actions care teams would do if they had this information. These specialists told us that if they knew which patient was immunocompromised, they could follow up with prophylactic antibiotics or growth stimulating factors. These are drugs that boost the creation of white cells. This could reduce the number of hospital readmissions for these patients by fifty percent.

So the patient, a result of the test, doesn’t directly know the outcome? They’ll know based on whether, and they get a response from the office saying, “Hey, come on in.”

That’s a great question. We have been discussing it with the FDA. We recently met with them to discuss the protocol for approval of our product, which was the same question they were asking. The FDA raised this concern.

We initially planned that the patient would know the test results, but the FDA was worried a bit about the information’s consequences. The results will likely be sent to the care team to evaluate. They would have the ability to follow up with the patient in case there is anything wrong.

The patient would get a notification notifying them that they have performed a test successfully. There are currently other home monitoring solutions in the market today that work this way. There is a product for people with diabetes to monitor diabetic patients from home that follows the same procedure. Patients are only notified that they completed the measurements successfully. The care team is notified of the results of the tests.

So, we are following the same standard here.

That’s interesting because there’s such a push on transparency, and yet there isn’t. The idea is patients can’t have access to direct medical information without the specialist there, you know, guiding them as to what they should do next. Then it depends on the team’s turnaround time as to how long the person is wondering how they’re doing.

See also  TWIDH - Empowering Connected Care with Gilles Lunzenfichter, CEO & Chairman

Our device provides the extra benefit because it reminds the patient to follow what is called neutropenia precautions. When the patients are critically immunocompromised, they are typically warned or advised to stay at home and avoid contact with others. Some of the reminders that our patients are shown on the device would be reinforcing the standard of care, even without the intervention of the care team.

The care team would follow up if there were any problems. And that’s where

you get the benefit in terms of reduced in-hospital admissions. Keeping in mind that our product is quite innovative. This is the first time that something like this is being done.

So, the FDA’s first concern is the patient’s safety, and they don’t want to create extra.

Concerns or complications for them. They want to make sure that the results are always channeled through healthcare professionals. So, we are following the FDA’s guidance on this point.

Is this a daily test or every couple of hours? How often would they perform this?

The goal is for patients to do this daily. Previous data from studies show that doing daily measurements is the sweet spot or the optimal frequency for testing to catch when the patient’s white blood counts drop. So, that’s what we intend to do.

And I’m assuming the intent here is that complement this with AI. So you will have you know earlier you indicators that something is changing or the blood cells are dropping, and therefore you have the opportunity for the care team to intervene, correct?

That’s precisely correct. As I was saying, to give an example, 650,000 patients start chemotherapy treatments every year in the US. And 110,000, which is 1 in 5 or 1 in 6, end up hospitalized because of an infection while their white blood counts are critically low. So each of these hospital admissions has adverse clinical outcomes for those patients. And also, it comes at the cost of $25,000 for hospital readmission.

So, if you do the math, the US healthcare system is spending $3 billion on this problem alone. If we catch those cases early and follow up with antibiotics or growth factors, they could be reduced by 50%. So this is a huge problem.

I’m assuming that there are other means other than the blood draw to sort of determine something’s going on. So how much earlier does this device combined with AI sort of, you know, give the patient a heads up versus other traditional means?

Traditionally, we currently detect if something’s going wrong with the patient by a thermometer. These patients are instructed to take their temperature daily or frequently. If they have a temperature, then it’s a sign of fever or infection, But by then, they already have an infection. So, it’s already too late. They need to report to the emergency room, and that’s where the cost and the clinical outcomes come into play.

We are developing a better thermometer or a predictive thermometer tool that can tell when patients are very likely to develop an infection before they acquire it. And based on the previous data published, we could detect that in three or four days before infection. So that gives caregivers a window to deploy those preventive treatments.

When you were developing this product, you were supported by the NIH, correct?

That’s correct.

Can you tell us a bit of how that support and the SBIR program helped you and how it changed outcomes for you?

The NIH is the national program of health in the US. They have this program called SBIR, which stands for Small Business Innovation Research. The NIH wants to support innovative startups that are making products that can contribute to Americans’ healthcare.

We were fortunate to have the support of one of these awards, which are very competitive. So, that was very exciting for the whole team. In addition, we recently got notified that we got a Phase II SBIR award. That means that we will be securing $2 million in non-dilutive funding for our company, Supporting our product development and clinical trials for the FDA regulation. So, we can take this product to the market.

Having the NIH support and the SBIR award was vital for this company, and we are very fortunate. I’m excited to go ahead with the next steps on this project.

I mean, the money is great. No one denies that. But what other things do you get? Do you have a mentor? Do you have access to advisors? What else does the program bring? So, as I said, I’m not complaining about the money. But there’s more to it. So, tell me a bit of that as well.

These grants and these awards are very competitive. Many companies are applying for them. I believe a benefit was the review process. You have scientific experts and clinical doctors reviewing your application for the significance of your problem and your solution’s feasibility.

So, the fact that we were granted the award validates what we are doing. This came after an in-depth review. That’s extra credibility for our company. That’s one side benefit. There are many other ways that they support apart from the dollar amount.

We were recently brought in a program offered to SBIR companies called Innovation Corps (I-Corps), where NIH connects you to industry mentors. It guides you through a customer discovery process over two months. The goal is to conduct at least 100 customer interviews. They want to ensure that once you get their support, that will be a good product-market fit.

They encourage you to get out there and interview at least 100 of your customers. I guess that in every startup, you have a business plan and some hypotheses or assumptions about whom you will be selling to at every stage. In our case, we had our business plan based on making sales to private cancer clinics and insurance companies, for instance. So we set out to interview 100 of those customers.

That was a great exercise to get a good feel of customer needs, navigate that whole process, how a sale is conducted with each of these customers. What is the lead time? We were able to develop a few relationships with a few key customers. And this process was supported and guided by NIH. So that was, just to give an example, another side benefit.

You are pursuing this both in the United States, as well as in Europe, correct? Product certification, market entry – compare and contrast. What’s it like trying to do this in the US versus Europe? What are the benefits of the US, and what are the benefits here (Europe)?

I’m glad you bring up this question because our companies are half in America and half in Europe. We have an office in Madrid and an office in Boston.

Tell me a bit if you know your experience in the US compared to your experiences in Europe.

In the US, there are many advantages. A huge market. Probably one of the biggest markets in the world for health care. It has access to 300 million consumers, and it’s easier to scale. Once you start selling to one hospital system or one state is relatively easy to expand geographically.

See also  How Should Healthcare Providers Choose CRM Systems

The European Union, even though it’s a common market, every country has its regulations making it more challenging to scale.

And language?

Language is one of the barriers to the process. You have to do it on almost country by country basis. That being said, the US healthcare system has its peculiarities. It’s based on private insurers, and most of the market is based on fee-for-service.

You do a procedure and get a specific reimbursement for it. Specific reimbursement codes exist. It’s a challenge for innovative products if you don’t fit precisely into one of those reimbursement codes. So it’s kind of tricky to find a way to get paid for what you do. Notably, in our case, it is sometimes challenging to align all the stakeholders.

We have a value proposition that is more based on what is called value-based care. Using our device, you will have fewer hospital admissions to a certain degree that works against the private hospitals because they get paid by admissions. So if they have fewer admissions, they are billing less.

Most of the US market works in that way.

But the US is changing and adopting Value-based care more than they were before. Payers know if you can intervene early, you will change the cost structure of the overall care. So there are benefits to that.

It’s not fully implemented. But, hopefully, it’s a direction that the US is heading in.

Absolutely, but it’s going too slow. For example, 90% of the US market is on a fee-for-service scheme today, and only 10% of the market is value-based. So, until you have a fee-for-service value proposition, the size of the medical market you can access is much smaller.

As a startup, you have to have both your value-based pitch, which I agree with you is the future, and obviously what the patients care about. But, you also have to have your fee-for-service pitch. That’s very important to convince investors. To demonstrate that you can access revenue earlier. That’s very challenging in the US to navigate this process.

In Europe, since the healthcare systems are more public, the interests of the health care system are to spend less money. That’s good for us.

On the other side, however, since these are large healthcare systems, the contracting process is challenging. The lead time to sign a contract with one of the national healthcare systems is very long. So, that results in an extended sales cycle.

Each area has its pros and cons.

You are having a dialogue with investors. What are the US investors like relative to? I don’t even know if you are speaking to investors here, European investors?

We have spoken to both, and actually, we have both kinds of investors on our cap table. An investor group led our seed round in the US called Good Growth Capital. They invest in every stage startup that has a substantial scientific component. We have the participation of a seed group in Barcelona called Nina Capital. They invest particularly in digital health startups with European entrepreneurs.

Generally speaking, in the US, investors are willing to take more risks than those in Europe. They are eager to go with early-stage startups. Often, they invest when there is no revenue yet.

I think that Europe is more conservative. Typically, investors in Europe want to see commercial traction already and only want to invest when making sales. This is my impression. They want to get in the game once you are much further along the road. So I think it is a little bit more challenging to raise capital.

Healthcare and digital health, I mean, there’s a pretty good buzz these days. These are all hot spots if you could add in remote monitoring and throw in a little bit of telehealth. How does that help you?

To a certain degree, the COVID pandemic has impeded our efforts because we haven’t been able to start our clinical studies and get a testable device for patients. But, it has accelerated the trend of moving all the health care to remote monitoring and the home setting. The regulatory and reimbursement bodies are putting much more emphasis on all of those trends. This works to our advantage.

There has been an increasing awareness of the importance of keeping patients away from the hospital. Especially if they may be compromised, That’s exactly kind of the value proposition that we were offering. So, for instance, there has been a push to allow reimbursement codes to apply to procedures performed at home in the US. Before COVID, reimbursement was only possible if the treatment was delivered in the hospital setting.

There is an increased chance of using those reimbursement codes to provide our service in a remote setting. So those trends have been accelerated now.

Where are you as far as product development, and what are the next steps?

We have a working prototype. We have tested it with 40 patients. So we have proof of principle in humans. That was a huge milestone for the company. That was the milestone that allowed us to raise our seed financing and spin-out from MIT.

Moving forward, our next steps are now focused on building an industrialized version of that prototype. A product that we can put into the hands of users. That’s our next milestone, and then once we have the industrialized product completed, we will conduct clinical trials for the FDA.

What timelines are we looking at?

We are looking at completing the product by the end of this year and starting clinical trials. So, that by the end of 2021, we have the data to perform our FDA submission and start selling.

Will you raise money in the midst of that? Or do you have enough on hand to get to that period?

We raised our round before setting out to perform this much. We’ve received additional support from the NIH SBIR program and the Mass Tech Collaborative. With that, currently, we have enough resources to focus on these milestones. We are planning to raise a Series A once we complete these milestones. From there, it will focus on how actually to start selling and getting the product to market.

How long have you been working on this?

We’ve been working on this for a fair amount of time. We started back at MIT in 2014. So it’s been like five or six years. This was a research project before it was a startup, and we started from scratch to figure out the science behind the technology. This is something that is being done for the first time. To date, nobody has ever taken white blood cell measurements through the skin.

Our research was from four years at MIT, and we spun out a couple of years ago, 2018.

In hindsight, what would you have done differently? What did you learn along the way?

I guess many things. For instance, I think that today I would do it differently because we

Raised money simultaneously, we finished our clinical studies, completed our prototype, and worked on our regulatory reviews. So we were doing a lot of different activities at the same time. I think that it is crucial to focus your effort. I would have had a more focused attempt to complete your regulatory strategy, prototype, and clinical studies first. Then, when you believe you got to the best possible shape, you can go on to fundraise and focus 100% of your efforts on it.

See also  How Medical Devices Benefit Healthcare

I think when you fundraise, it should be a focused effort of three to six months. After that, it becomes a full-time job. We were juggling that job with five other responsibilities, so that was very challenging. I think it would be essential to be more focused if I were to do it again.

We might have approached another area differently because we were working with consultants for our FDA study. They had a lot of experience with big prior submissions, but they have experience.

With products that were a little bit different than our product. And then, at some point in our FDA discussions, we got to a very detailed level of reviews, and they could not prepare us for that.

We would do differently from the beginning. We would hire consultants with specific expertise, particularly in the same area and products that we have, That they have done a similar process many times before. As they say, “The Devil is in the details.” It’s important; they know your product.

You’re innovating. Hopefully, there are not many similar products or people out there who have already done this. That’s through the catch-22, right?

Sometimes they did an excellent job, but it would have been helpful if their guidance was more specific at the end of the day. Despite being innovative, the FDA has a process. It is pretty standard. If that’s the case, you want to look for somebody who has a lot of experience submitting the FDA submissions. That is one example.

I know that your initial intent is to use this product for people undergoing chemotherapy, but then you could expand beyond that. For example, this technology can be used for other types of diagnostics, correct?

Initially, we focused on patients undergoing chemotherapy because this is a massive problem for this population. There are probably others who are immunocompromised and could benefit from increased access to white blood cell monitoring. Some other conditions and drugs also produce low white blood cell levels as a side effect, medications for psoriasis, schizophrenia, Parkinson’s, and other conditions like organ transplants where the patient is immunocompromised. These populations are at risk of having low white blood cells.

In other instances, some patients have a chronic neutropenic disease, where they lack neutrophils, which is the most common type of white blood cells. That’s a very rare disease, so there are not many patients with that condition. But that’s another population that could benefit from this. That population needs to get weekly, or bi-weekly blood draws to ensure that they are not compromised.

They should not travel or interact with the general population for the risk of infections. That’s a population that could benefit from our product. These are just a few examples.

Beyond these patient groups, there are applications for drug development and pharma companies. While developing drugs, many of them go through what is called dose escalation trials when they need to determine a safe dosage for humans. They need to perform white blood cell measurements for that. So this could be good for drug discovery.

What does the competitive landscape look like? Who is addressing this currently, and then how do you differentiate from some of the other solutions that already exist in the marketplace?

A few startups provide developing products to measure your white blood cells by pricking your finger, similar to the tools of people with diabetes. You prick your finger, and each measurement requires a small blood draw. However, some papers and studies have demonstrated that when patients do that unsupervised, they may introduce interstitial fluid into the sample. That may impact the reliability of the test.

If this all goes the way that you want this to go, do you keep adding more products? Do you add more technology and innovate? Where would you like this to go?

We see this as our first Minimum Viable Product. After that, we have a technology development roadmap to expand our capabilities. This MVP only gives a binary determination of whether patients are immunocompromised or not. We plan to expand beyond that and be able to provide more quantitative measurements. To be able to differentiate different levels. Move towards giving a number. The same way that current blood draws do.

As we increase our technical capabilities, that opens up new use cases and applications for other conditions. But, we also want to go beyond that, and we have a few ideas on how to measure other blood parameters to measure red blood cells, platelets, and hemoglobin levels.

We see this as a platform technology with several products in the pipeline for our portfolio. But, we are starting with this one.

Who do you want to talk to in the next six months based on where you’re hoping to go? I know you’re busy, but who are the people that you want to be talking to? What introductions do you want?

We want to be talking to healthcare insurance companies; they are prospective customers for us. We want to understand what they are looking for and what their needs are. We did our push with those hundred interviews in the past, but we want to continue developing those relationships with insurance companies and private cancer clinics.

Also, companies are developing drugs that can produce immunosuppression. So we have this hypothesis that this would be an excellent tool to help in their drug discovery process or even once the drug is out in the market as a companion diagnostic.

We would like to interact with these stakeholders and learn more about their needs.

It’s exciting because those players or those groups that you’ve talked to talk about have different objectives. For example, the payers are focused on value-based care because they aim to look at when providers intervene to reduce the overall cost. So this is potentially an other objective than what the providers are looking at, which is different from what the pharmas are looking at.

How are you selling the same project to three different prospects from three different value propositions?

The company is starting with the proposition that is more focused on value-based care. We have identified different customer profiles with the support of NIH. We are honing our value propositions for various stakeholders. We think that our technology can provide value for different customers. There is a different value proposition for each of them.

We’re talking about our next steps, and I spoke about the scientific and the technology and the product and the clinical milestones. But, I forgot to mention that it is essential that, in parallel to that, we have a track of market discovery and pre-marketing activities.

We cannot sell our product until FDA approval, but we want to interact with our customers early. In addition, we want to understand the sales process, so we are ready to hit the road running once we get FDA approval.

I very much appreciate your taking the time to speak with us and sharing what’s going on at Leuko. So, again, thank you very much, and please send updates. We love to keep in touch and share with our readers and listeners what you are up to.

Non-Invasive Blood Sampling with Leuko

European Digital Health Open Calls