#287 - 🚀 End-Tidal Carbon Monoxide Monitoring for the Management of Neonatal Jaundice

Hello Friends 👋

In this special Tech Tuesday episode of The Incubator Podcast, Ben and Daphna sit down with Anthony Wu, CEO of Capnia, Inc., to explore how end-tidal carbon monoxide (ETCO) monitoring is impacting neonatal jaundice management. Anthony explains how this technology, based on decades of research, provides a real-time, non-invasive biomarker for hemolysis and thus indirectly, bilirubin production, allowing clinicians to better assess and predict neonatal jaundice severity. Unlike traditional serum bilirubin tests, which only measure bilirubin levels at a given time, ETCO screening gives insight into hemolysis rates, helping identify newborns at risk for severe jaundice before complications arise.

Anthony shares his personal motivation behind this innovation, discussing how his own children experienced neonatal jaundice and how many families suffer the emotional and financial burden of this pathology. He envisions a future where universal ETCO screening becomes standard practice, allowing for earlier interventions and reducing the risk of preventable neurological damage.

Tune in for an eye-opening discussion on how this innovation could change the way we approach neonatal jaundice forever!

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Short Bio: Anthony is a seasoned senior business executive and operator with decades of experience in leading business operations, strategic development, and investments. Since 2017, he has been at the helm of Capnia, Inc., where he spearheads the company's mission to revolutionize jaundice management for newborns and advocates for ETCOc universal screening. Before his tenure at Capnia, Anthony was a partner at Affinity Equity Partners, one of Asia's largest private equity firms, and played a crucial role as a founding member and investment manager for the USB China Asia Direct Investment Fund. Anthony's extensive expertise as an investor and entrepreneur continues to drive significant advancements in the healthcare industry.

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The transcript of today's episode can be found below 👇

Ben (00:00.444)

Hello, everybody. Welcome back to the Incubator podcast. We are back this week with a new episode of Tech Tuesday. Daphna, good morning. How are you?

Daphna Yasova Barbeau (00:10.013)

Good morning. So glad to be back at Tech Tuesday.

Ben (00:15.076)

I agree. We are joined today by Anthony Wu. Anthony, good morning and welcome to the podcast.

Anthony Wu (00:21.325)

Good morning. Good morning, Ben. Good morning, Daphna. I'm honored and very happy to be on the first podcast of the year in 2025.

Ben (00:28.658)

Yeah, that's right. That's right. We are recording this on January 2nd. So it is for us the brand new start of a recording season. Anthony, you are the CEO of Capnia, Incorporated. It is a company that focuses on innovative solutions for John, this management and newborn and advocating for end title carbon monoxide screening universally.

I wanted to start this morning by asking you if you could describe a little bit what is entitled carbon monoxide monitoring and why is this a tool that you think could be useful in newborn care.

Anthony Wu (01:10.521)

Okay, thank you. Well, entitled, carbon monoxide, the science was discovered in 1970s by Dr. Jeffrey Maisels, and where he discovered that there's a one-to-one ratio at the breakdown of a red blood cell where a bilirubin is produced at the same time one carbon monoxide is produced. So they're produced at equal molar. And the importance of that discovery is that finally we have a biomarker that are able to measure the production of bilirubin, which underlines neonatal jaundice. And without production, will not be jaundice. And so the importance is to how to measure production. But the technology, I the science to the product was a 35-year journey. And until 2014, Capnia obtained its first clearance from FDA for our non-invasive and title carbon monoxide monitor. So the science and the technology, it takes a very long time to evolve and then to the product level that's even longer past. The importance we think is now, neonatal jaundice is now measured by this particular biomarker called total serum bilirubin, which is the gold standard for measuring jaundice in that regard. unfortunately, we do not know production or elimination. But jaundice is really the result of an imbalance between production and elimination. So it's almost like solving the equation of X, Y, and Z, where we only know one of the components and we don't know two of the components. And that makes managing this disease challenging over many, many years. And therefore introducing another component into this equation would elevate the level of management of neonatal jaundice and especially in regards to production, which is really the key that I talked about.

Ben (03:34.437)

Mm-hmm.

Anthony Wu (03:37.75)

and n-tidal carbon monoxide is the perfect biomarker for measuring that.

Ben (03:45.202)

And I think what's interesting about that is that you're referring to an issue that we're seeing in the newborn nursery in the NICU where we measure serum bilirubin to make management decisions about whether to initiate treatment such as phototherapy and so on and so forth. However, we're sometimes surprised by certain babies that the bilirubin really doesn't budge, it stays very low, and some other babies where the bilirubin really spikes and we don't sometimes understand why. And it's hard for us to have a good assessment of

how much hemolysis is actually happening. And what you're describing is that by peeking behind the curtain a little bit with carbon monoxide, we might be able to find and identify infants that are hemolyzing more than others and then tailor our management and anticipate maybe a little bit more who might need a little bit of a closer attention than another. think that's pretty neat.

Anthony Wu (04:35.981)

Yes, you summarized it very, well. Good at Smith Cattle Research Institute in San Francisco, he has been doing research on visual cortical bind for decades. And what he has discovered was, as you've just said, at Bilirubin,

that bilirubin levels that were considered safe in the old days, that visual cortical bind occurs in these babies. And it's purely because of hemolysis. So you're already seeing a direct connection between hemolysis and bind. And that makes being able to diagnose unambiguously and accurately.

Ben (05:16.124)

Yeah.

Anthony Wu (05:29.593)

determining which baby has our hemolytic becomes paramount important.

Ben (05:38.48)

Yeah, and when you talk about BIND for the people who are not familiar with that acronym, we were talking about bilirubin-induced neurotoxic injury, neurodysfunction, sorry. I was blanking on the D. And I just want to make, I mean, I'm going to let Daphna ask some questions as well, but I just want to mention as well that end-tidal carbon monoxide is not something that is coming out of the woodwork, like you said just now. There's a lot of data that's been published.

Anthony Wu (05:47.107)

dysfunctions. Yeah. Yeah. Yeah.

Ben (06:05.84)

And to be honest with you, if I could refer people to a couple of publications, the one that comes to mind is an article published in the Journal of Perinatology not too long ago. It's a perspective called A Gold Standard Test for Diagnosing and Quantifying Hemolysis in Neonates and Infants with first author Robert Christensen, where really there's an interesting section on carbon monoxide and mentioning its benefit in the diagnosis of hemolysis. So we'll link to that paper as well in the show notes.

But with that, definitely I'm going to turn it over to you.

Daphna Yasova Barbeau (06:37.825)

Yeah, and you've touched a little bit about the journey that it took to get here. So I want to make sure we talk about that. But before we do, I'm sure people are wondering, what are kind of the logistics of using the monitor? What would this look like in our day-to-day practice, in the hospital, in the nursery? And which babies would it have kind of the most utility for? Or do we anticipate we might use this for every baby that we're screening for Billy Reuben?

Anthony Wu (07:06.125)

Yeah, I definitely, you know, we've done now close to 10,000 babies globally in terms of clinical research. And that involved babies that are prematurely and babies that are near term or full term. We've done studies on phototherapy use and we've done studies on term baby screening before discharge.

What we have found is the most effective use of End tidal carbon monoxide is universal screening before discharge. And the reason is we kind of touched on it earlier. We would be able to accurately determine the production of bilirubin and be able to diagnose hemolysis, which is pathological production of bilirubin.

And again, the importance of bilirubin of doing so is we're often not distinguishing between the two phases of bilirubin. We have the angel face and we also have the devil side of the bilirubin. The unconjugated bilirubin is the devil side of the bilirubin. That comes straight from production. And that is the neurotoxic version of the bilirubin.

And when it's conjugated, then you become the angiocytosis its antioxidant and it does no harm to the body. And therefore, we have to be able to determine how much of this bad version of the bilirubin is being introduced into the bodies of these newborn babies and early enough to determine what the treatment should be.

And the use of our carbon monoxide monitor is exceptionally simple. It's the size of a laptop and it's portable. We usually in hospital settings are just set on a stand, rolling stand where they can go from bed to bed, room to room. So it's a bedside test. The collection time for a breast sample through a cannula that is connected to the monitor.

Anthony Wu (09:30.421)

is usually less than 30 seconds. In most cases, a breast sample is collecting less than 10 seconds. And then the machine will do its work without any other manual assistance. And a result is usually displayed on the screen within five minutes. So it's a very fast bedside non-invasive test. And in terms of the collection,

the babies wouldn't even notice it. And as we use this more and more, oftentimes one of the biggest praise we get from clinicians is that, wow, this is very simple to operate, very simple to learn, and very simple to use. And the result is all, very, it displays on the screen very quickly.

Ben (10:24.432)

Yeah, and it's very easy to interpret as well. It gives you a reading and it gives you a number in parts per million. It's very straightforward. I wanted to turn this discussion a little bit towards you, Anthony. I think this is a project that has consumed you on many levels. You are so invested in this technology, in the impact that this technology can have, both on

personally with your time, can you tell us a little bit what is the mission of your company and why is this such an important topic and such an important issue for you to take on? You have had such a successful career before diving into hyperbilirubinemia. Why does this matter so much to you?

Anthony Wu (11:15.747)

I have kids that, all of my kids have jaundice. And this is very fresh to me. My daughter, my youngest daughter is three years old. So this is not something that is remote to me. It's very personal to me. What has struck me is not being able to know that this jaundice is not going to harm my baby. And the assurance I can get

is either don't worry about it, it's going to go away, or if you worry about it, we can put the baby under phototherapy. That's not the kind of modern medicine that I'm looking for my newborn babies and for my own children. And I just found that we're still living in kind of the...

the antiquated times in terms of hyperbilirubinemia management. If you read the guidelines, the guidelines would say that, you know, the guidelines is developed based on expert opinions. We're in that era of, you know, evidence-based medicine. And, you know, I'm disappointed that we're not taking a completely curable and reversible disease, if you call it, and manage it, you know,

with the capabilities that a lot of other disease are being able, are being managed nowadays. And so the mission for Capnia is really to revolutionize neonatal jaundice management. The concept of hyperbilirubinemia and its biomarker, total serum bilirubin, you know, I found it is, they're not, you know, the concept is a bit awkward in the sense that

In most cases, jaundice are not worrisome, but there are cases that are worrisome. And to this day, that decision is left to clinical opinions rather than clinical evidence. And we know the fact that the guidelines was developed to prevent neurotoxicity risk factors, to prevent neurological damage. It was not developed to prevent jaundice.

Anthony Wu (13:40.197)

And you know, nearly every baby is going to have some level of jaundice. And so jaundice is not harmful. It is the neurotoxic risk that is harmful that we want to prevent and eliminate. And so the concept of managing hyperbilirubinemia perhaps should be the management of bilirubin. You know, as probably Dr. Tim Barr had shared, many of my KOLs agree with me that, hey, you know,

what's underlying hyperbilirubinemia is this two-faced substance bilirubin. And shouldn't we be managing that? And what's more important of managing that is, you we should be managing the bad version of that bilirubin, which comes straight from production. And how come we still don't have a way to measure it and quantify it and diagnose pathological production? And that sets the mission for us.

at Capnia is to be able to provide a technology and a means simple enough, non-invasive enough that everybody can use so that we would be able to measure production of that baby at any time.

Ben (14:52.722)

Especially considering that we don't have a good idea as to how much bilirubin exactly crosses the blood-brain barrier, we don't have too much data on these thresholds and we're really in the dark when it comes to that. And just waiting for the symptoms of brain injury to develop is a frightening thought.

Anthony Wu (15:11.417)

Absolutely, absolutely. So our mission is really to be able to now we do have this tool and we do have this biomarker and so our mission is really to make it available to every baby in the world so that they are able to know how much of you know of Production is happening and using this biomarker to determine a better way of managing the bilirubin issue and as you said

perhaps technology will evolve one day into the fact that we are going to be able to measure how much blue ribbon is crossing over to the brain, crossing through the brain barrier. Then it's a time that we can, using that tool at the time. But knowing production is always the first line of defense where we can use that to prevent

know, hemolytic jaundice, we can prevent, you know, any of this low bilirubin levels where I'm still leading to bilirubin induced neurological dysfunctions and so on and so forth. That is the mission of CAPNIA. So over the seven years, I personally put in the personal resources committed to this mission and my team who has been, you know, working on this for decades.

They're all committed to this mission of revolutionizing neonatal jaundice management or hyperbilirubinemia management so that every baby can enjoy the benefit of echo screening.

Daphna Yasova Barbeau (16:49.775)

Anthony, it's obvious that this is a mission of passion for you. I'm especially struck about your stories of how your own children were affected. I wonder, you sometimes as clinicians, we see Bilirubin every single day, in and out every day. Okay. Lights on, lights off. But what is kind of the, you know, the unnoticed burden on, on patients and families for dealing with Bilirubin, which, you know, especially as neonatologist, we sometimes think is like,

Okay, just something, just something that we're dealing with in addition to the medical stuff that's going on with babies. But I think especially for the quote unquote healthy newborn in the nursery, this is a major stressor for families.

Anthony Wu (17:35.449)

Yeah, yes. One of the other reasons that drove me is my neighbor. When I was living in Beijing, my neighbor had a perfectly healthy son that was born and he developed Kernicterus. And as a result of delayed treatment because among the Chinese, oftentimes they believe the ancient treatment of just exposing their kid to sunlight.

And they think that will cure, you know, they will cure jaundice. And not knowing that the baby had hemolysis and by the time the baby was taken back, kernicterus was there. So I saw him, I saw this little baby growing up into a teenager and I saw how much of the suffering and the financial burden that was brought to the family as a result of that.

particular case and this was my neighbor that had this case. To clinicians and to many of the doctors who see John this every day, they look at the statistics. They look at the statistics and they say, well, we haven't seen one case in decade and why are we worrying about this? But to the family and to a father like me, my kid.

Daphna Yasova Barbeau (18:54.973)

Mm-hmm.

Anthony Wu (19:04.959)

is it's not statistics, it's one. If any one of them is impaired, even in the short term, the burden to me emotionally and financially is not measured by statistics. And it's personal, it's psychological. And then to that kid, where a disease that's completely preventable, why do we let it happen? By just having a simple

Daphna Yasova Barbeau (19:19.901)

Mm-hmm.

Anthony Wu (19:34.105)

universal screening of production, we could have prevented that from happening.

Daphna Yasova Barbeau (19:41.691)

Yeah, absolutely. Absolutely. Thank you for your candor and sharing those stories. think it comes, your technology is coming at it a very opportune time also where we've become a little bit more relaxed with the Bilirubin threshold levels. so, I sometimes wonder, sometimes worry if we will start to see a broader effect of BIND than we've seen in the past because we were using such conservative.

thresholds. You told us a little bit about the mission of CAPNIA and that the future would be universal screening. What are the next steps? Once you've been able to accomplish bedside monitoring of neonates, what is CAPNIA looking to do next?

Anthony Wu (20:30.393)

As a matter of fact, we are now looking at working with some of leading researchers in the world on finding a therapeutic solution. At this junction, I cannot disclose more, but there are researchers who are very, interested in finding a solution that are better than phototherapy and that are able to cure hemolysis and

with minimally harmful versions of therapeutics that are required for babies of that nature. So we could be looking at 10 years from now, we would have a world where echo universal screening complemented by transcutaneous

serine bilirubin measurements plus this innovative therapeutics. And that would be able to allow us to completely eliminate the possibility of kernicterus bind 10 years from now. And Capnia is deeply involved in that and we will be part of that process. And so that is one.

The other part of the Capnia development in the next four to five years is that we're looking at taking perinatal screening and perinatal use of EDGO in the hyperbilirubinemia management, or bilirubin management. We're looking at taking it to prenatal. Some of the advanced work done by Dr. Christiansen.

and Dr. Ken Moise at UT Austin Dell Medical Center have proven the concept of screening fetal hemolysis in the last 10 weeks of pregnancy. And there two papers already being published. A larger multi-center study is now currently being conducted. And so prenatal use of echo screening for

Anthony Wu (22:53.837)

Fetal hemolysis and anemia is something that we plan to commercialize in the next four to five years. And then we think that would also be able to help some of the most difficult issues currently that is not available. That is again being done using inaccurate measurements of ultrasound measurements, which is not being able.

quantify or accurately diagnose fetal hemolysis.

Ben (23:28.082)

Anthony, thank you so much for joining us today and for sharing all this, for sharing your story, for sharing your mission, for sharing the technology with us. People can find out more about Entitle Carbon Monoxide Monitoring and Capnia at capnia.com. We will link that in the show notes at capnia.com and they can inquire there directly to learn more about implementing this.

new innovative and useful technology in their unit. Anthony, thank you so much for your time and we wish you best of luck for the future and a good rest of your day.

Anthony Wu (24:07.309)

Thank you very much.