The Pediatric Moonshot
Welcome to the Pediatric Moonshot Podcast. The mission of the Pediatric Moonshot initiative is to reduce healthcare inequity, lower costs, and improve outcomes for children both locally and worldwide. This is to be achieved by developing real-time, privacy-preserving applications that access and leverage data from every one of the one million healthcare machines across all five hundred children’s hospitals globally.
Join us for engaging 1:1 interviews hosted by Dr. Timothy Chou, the driving force behind the Pediatric Moonshot initiative, as he talks to visionaries from diverse fields, ranging from esteemed clinicians to influential business leaders – all united by their dedication to enhancing the well-being of children.
Each episode provides an in-depth exploration of the current pediatric healthcare landscape, shedding light on the challenges we face, and the innovative solutions driven by passionate professionals from all walks of life.
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The Pediatric Moonshot
E44: From Fragmentation to Cure: Funding the Future of Congenital Heart Disease with Kirstie Keller
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In this episode, Dr. Kirstie Keller, CEO of Additional Ventures, shares how a bold, mission-driven approach is transforming research and innovation in single ventricle heart disease. She discusses the shift from fragmented efforts to a coordinated ecosystem—leveraging AI, data integration, and targeted investment to accelerate progress toward a cure. The conversation highlights the need for collective funding, cross-sector collaboration, and a redefinition of pediatrics as a true frontier for medical innovation.
This episode is brought to you by BevelCloud—powering distributed AI in healthcare and driving the Pediatric Moonshot forward. Learn more at BevelCloud.ai."
Good morning, good afternoon, good evening, everyone, to another edition of the Pediatric Moonshot Podcast. Today I am very pleased to have a guest from the Additional Ventures, Dr. Kirsty Keller, who earned her PhD in biology from John Hopkins in 2014. She did a little consulting for people like the Milken Institute. And about six years ago went to Additional Ventures. Two years ago was named the CEO. Additional Ventures, for those of you do not know, really focuses on single ventricle heart disease, which includes five of the 24 structural congenital heart diseases. For those of you don't know, one in 100 children in the U.S. are born with a congenital heart disease. Outside the U.S., it is a large reason for mortality. So really pleased to have you today, Dr. Keller.
SPEAKER_01Nice to be here.
SPEAKER_00Why don't you start us off with what's the origin story of additional ventures? How'd this come to be?
SPEAKER_01Absolutely. So as you mentioned, I'm a scientist by training, did my PhD and my postdoc at Hopkins, consulted, and then eventually went to the Milken Institute where I was doing philanthropic advising for ultra-high net worths. One family approached the Milken Institute and said, we're really interested in investing our philanthropic capital in single ventricle heart disease. And that ultimately ended up being our founders, Aaron Hoffman and Mike Shepherd. They said, you know, we really want to take a deep dive in this disease and see where we can put our capital to work. So I approached it like any scientist would. I started reading papers, going to scientific conferences, trying to understand what are the biggest questions that need to be answered, what are the infrastructure needs and data needs, clinical care needs, where are their discoveries and other fields that might fit into the single ventricle scape, and really kind of came up with a consolidated state of the science, if you will, in single ventricle heart disease. And at the same time, there was a publication that was released, I believe it was 2019 in circulation. And it was essentially, you know, where are we at with fontan care? And fontans are the last, is the last surgery for a single ventricle patient. They have a unique circulation and ultimately their blood flow has to be rerouted so that uh their systemic flow goes through the remaining ventricle, but the rest of the flow goes passively to the lungs. Um, this is a very altered system. But clinicians had published this statement saying here are all these challenges with Fontan health and Fontane health surveillance and long-term physiology for these patients. And we honestly don't know what to do. We don't have a lot of data, we don't have a lot of understanding, we don't have a lot of tools. And for me as a scientist and also somebody who had been an advisor in biomedical research, it was very unique that a field was very aware of its limitations. And so the scientific statement coupled with this kind of clinical realization kind of came together and said, like, this might actually be a really interesting moment to do something big in this space. And we were kind of looking around at other organizations saying, like, could we, you know, fund or expand someone else? But we realized very quickly that there was no other organization that was going to spend the time on single ventricle heart disease as we would like them to. So came to the kind of joint decision, well, there should be an organization. Mike and Aaron can found it, and that would be wonderful. Um, and I ended up becoming their first employee in January of 2020. Um, tough time to start a foundation. Um, but you know, it was it ended up being okay. Um, and and from there, really, you know, we worked with the community, talked to hundreds of experts, and then developed a research roadmap that was intended to guide the next five to ten years of work and to say, what are the scientific questions and infrastructure questions by which we should invest, um, and then kind of move on from there. Um, but really it it kind of started as a a scientific project to some degree and then really evolved quite uh quite rapidly over time to saying, you know, there's a moment right now and we need to, we need to step into that moment and do something.
SPEAKER_00Do you just talk a little about where you guys are now? How big is additional ventures? What are you funding today, right?
SPEAKER_01Absolutely. Um, so we uh have funded about, I think so far, around 120 million into this space um over the past five and a half years. Um we do everything from foundational science grants through equity-based investing, and really we design programs and use financial vehicles that fit the problem at hand. So we're not making equity-based investments because we want to make a ton of money or have a return. It's just sometimes there are interesting and important companies that are popping up, uh, entrepreneurs that are popping up, that we say that technology is very important, and the financial vehicle for that is this. And similarly, there are still so many outstanding foundational science questions that need to be addressed and answered that we do things over in Netscape too. And kind of everything in between. Um, we have a whole genome sequencing study for patients and families called single ventricle source, and the data is available for free. And we created a platform with some partners uh for data analysis. Um that's called resource. Um, and you know, we do all sorts of things in the middle. We have partnerships with other organizations. Um, but really primarily our goal in the beginning was different than our goal is now. When I've said this broadly to some folks in my community, um, so apologies for the analogy, but when I first entered the space, I felt like the single ventricle landscape was kind of akin to the show Fallout, where it's a post-apocalyptic world. Um, a bit of a strange analogy, I know. Um, but I think like it really speaks to the how the field was structured, is you had all of these siloed individuals, all brilliant, all talented, but they really didn't have um, they didn't have the resources or the roadmap to explore um and or take risks. So we had kind of this small science going on, small clinical medicine with very well-meaning people, but they just didn't have the ability to have resources. So when Additional Ventures started, we said basically, how do we create an ecosystem for discovery and innovation? And that means going deep in with the researchers, clinicians, engineers, getting themselves to see themselves in our problem because single ventricles sounds so niche, but in reality, it is a systemic problem that affects nearly every organ system. You can tackle it through tissue engineering, devices, therapeutics, basic science approaches. So the early days were trying to get others to see themselves in our problems so we can create this in this place for innovation, this place for discovery, and to say, you know, single ventrible is not a quiet corner of pediatric cardiology. It's where people should go and it's where you can stay. And then now we've kind of developed that ecosystem, that culture, that community, and now we can ask bigger and deeper questions. How can we actually turn scientific progress into patient progress and make sure that we are building the tools, the resources, the infrastructure along the way while also providing really smart capital at the same time?
SPEAKER_00Wow. So you you talked a little about a roadmap. Just kind of sketch it. I know it's probably a big presentation, but sketch it out what what does that roadmap look like? What are the things that you're looking at in the future?
SPEAKER_01Sure. So we're actually about to launch a new one. Um so this is a sneak peek into that. And you said it's a big presentation, but in reality, it kind of simplifies into two concepts. So our goal at Additional Ventures is to cure single ventricle heart disease, which that mission statement is not something we actually originally adopted because we didn't want to seem too audacious in our goal, too crazy, maybe out of touch with what was real. But now, after five, six years of investment, we believe that's possible. So that's the first thing is like our mission is clearly now cure single ventricle heart disease. And we think that's a tractable problem. But when I think about, you know, the ways that you can cure single ventricle heart disease, that might look different to different people. You can prevent it from happening, you can fix it when it does, or you can replace the heart, right? Like just very simplistically, those are kind of your three options. Well, in the fixing it, we we kind of decided as a as an organization that we're gonna focus on fixing the problem when it happens. Prevention is important and replacing the heart is also important, but this middle structure can really get to the patients that haven't been born yet and the patients that are existing with it right now. And there are a lot of challenges to overcome just within that narrower fix it phase or repair. Um, and you can think very simplistically too, how can you repair it? And I think of that in two ways. You can add back the pump. So that's one part of our roadmap, add back a pump. You can do that mechanically or biologically. So, can we create um mechanical circulatory support that is a single ventricle assist? Can we create a tissue-engineered product that would replace the subpulmonary pump? And then on the other side, you can address the many complications and comorbidities, the clinical sequela of the palliative procedures, uh, so of the fontan, for example, and address all of those and say that is also fixing the problem and curing the disease. Because if we're able to restructure the blood flow and have no complications and comorbidities, I think we'd call that a win. Um, so our roadmap is literally divided into two halves. Add back a pump and address the clinical sequela. And there is a beauty in the simplicity of that. Um, certainly there's complexity within both of those domains, of course. Yeah. But, you know, being able to frame it as such and then break down, for example, the sequela into, you know, neurodevelopment, lymphatics and immune, um, uh cardiac integrity, liver health, et cetera. And so to be able to kind of take both a wide and also narrow approach in each of those sectors to say, where are we right now in our understanding? And that's a big thing our roadmap does is say, you know, one part of our field might be just on the cusp of creating an intervention, just needs, you know, some push and translational accelerator. Other parts, people are like, what are we even doing here? We don't even know how to monitor this. Or in lymphatics, for example, people use like super glue in the lymph system to help plug holes. I mean, innovative, but yet is that sustainable? We don't, it's not really guided by a lot of of science or or or knowledge. So there are different start points to all of these spaces. So part of our roadmap is identifying what spaces are we interested in investing in and really moving forward. And then where are they at on that continuum of maturity, if you will? And then saying, okay, now I'm going to create a bespoke program that hits at that organ system and also hits at that maturity, looking at it through the lens of is there clinical data available? Um, how large is the research field? Like what are the past publications, where, you know, all of those pieces that come together to help us understand where are we starting? Um, so that is our new roadmap, which is an it's a departure from our original, which focused, which had a lot broader themes, less um specificity, if you will, because we are now at a stage where we can have more specificity and we can ask more nuanced questions. So I think that is also the you know, the reflection of five, six years is hopefully we can ask better questions.
SPEAKER_00Yeah, amen. Amen. So since we're we're talking about advancing the state of the art, I mean, AI is in the ether or whatever. So talk about what what do you see the role of AI in what you guys are doing?
SPEAKER_01I think that so there are so many inroads for AI in the future of congenital heart disease and single ventricle. And we're already seeing those inroads being developed, and I'm very excited about many of them. I talked a little bit about how you know we need infrastructure and resources and tools in this space. And amongst those tools, we need to have AI tools. So I can think of it as simple as simple as we have so many disparate registries. They need to come together in order for us to have smart insights. And in order to do that, things that improve data abstraction, data entry, how do we automate some of those processes? But we know that we can't do that always in a structured way. There's not all structured data in the EMR, EHR, wish there was, and there's, but there's not. So so much is in the clinician notes, um, so much is in imaging. So, how do we start to apply those tools to make the parts of you know registries less about data, data abstraction and even data analysis and more about implementation and and really real world application? Um, so I think that's a big bucket. And pediatrics is generally behind in many spaces because it is so under-resourced. So finding places where we can increase efficiency and reduce cost in pediatrics, and including congenital heart single ventricle, I think is really key to making this field be able to move forward faster. Other places, you know, even today, which I think should be surprising to people, we still have folks that say they did not receive a prenatal diagnosis. And that is still happening in this country today, notwithstanding other countries that don't have the level of medical access that we do. So improving the ability to even flag the situation to say we have AI tools that can read an echocardiogram or read a 20-week anatomy scan and say, oh, something's a little off here. At least here, let's go to a referral. Or at best, say this is your this is your subset of diagnoses that we think you have. I think that would very much improve care because there is such a big bucket of planning that happens before a child is born, particularly when they have a complex congenital heart disease. And I think broadly, risk prediction, um, modeling, computational modeling, understanding, for example, what if we were to put a pump back into the system? What does the remodeling look like of a heart, a vascular system, lymphatic system? How can we model that over time? How can we use digital twins and other tools to say what would this intervention look like? We're already seeing, of course, the advancement, and I think FDA is moving in this direction too, of using new tools to validate, you know, early stage devices and drugs. And I think that in our population, when you think about kids, being able to do more rigorous testing, more validation and verification on that front end would I think benefit us because now we're more certain of the drugs and things that and devices we're we're putting in in young children. So I those are only three things. I mean, I'm there's probably hundreds more that I'm missing.
SPEAKER_00Hundreds more. Uh I'm curious about something you you had already mentioned. I mean, there's the um we'll call it medical device approaches. Are there therapeutic approaches to single ventricle?
SPEAKER_01So there are no approved therapeutics for single ventricle heart disease right now. Um I think that that is going to change. Um, but I it's easy, and I have actually been guilty of this in the past myself, saying, well, single ventricle is a structural problem, so they're probably going to require a structural solution. Right. Obvious, right? Sounds smart when you say it. But in reality, that may not necessarily be the case. Certainly adding back a pump could be incredibly mechanical or even a tissue engineering approach, whatever we're classifying that as. But on the other side, for managing some of the complications and comorbidities, you know, fontan-associated liver disease, a huge challenge in this population. They have basically because there's a high central venous pressure and the liver is not really able to clear this. So you see fibrosis and then potentially cirrhosis or hepatocellular carcinoma. We could think about, you know, drugs that help with liver clearing. Um, there are new therapies that are coming out for MASH, for example. Could those be applied? Um, there's a clinical trial fuel too about eudenophil, um, so vasodilators, um, SGLT2 inhibitors, GLP1s, um, which seem to be the wonder drug. But I think that there are real solutions on a therapeutic side that can help manage or prevent complications and comverbidities that we haven't even really thought about. The challenges, you know, in these smaller, rare populations, we often run into the place where sometimes drugs are repurposed and repositioned because clinicians are trying to reach into their toolkit and find anything that can work. So we oftentimes lose equipoise. We don't even know if a therapeutic is effective or not because we're beg bar we're borrowing and stealing from every other condition, which makes sense. But we're in the process of launching a therapeutics accelerator because we believe that there are purpose-built or there should be purpose-built drugs for our patient population, and that people will and do already have great ideas and have known therapeutic targets that might benefit. Um, so the short answer is yes.
SPEAKER_00Very cool. Uh, I'm learning so much from this conversation, but uh let me kind of wrap it up by talking about uh the future of funding. So, as we all know, right, I mean, uh funding in pediatrics is limited, funding federal government is being impacted. Yeah. How do you see the future of funding, you know, single-ventrical pediatrics, etc.
SPEAKER_01I think the future of funding for our space, and it it's not unique to our space, but it definitely I think is amplified in our space, is collective. Um, no one organization is going to be able to solve all of the challenges in our field. What notwithstanding solving things like a pediatric commercial market failure that happens in devices, or um, you know, how do we get rare drugs or rare devices out to market? Or how do we even fund the basic science approaches that, you know, at a time where federal funding is eroding? And I think really what we have to do is look around and find like-minded partners, but also, again, get people to see themselves in our problem, similarly to what we did in the very beginning, but we're from a different lens. Tissue engineering is not unique to single ventricle. It is a there are a lot of people that are interested in this problem. But if you can bring things back to first principles, you find that there's much more alignment than there is separation. And so I think that is more where we need to go in the future is creating funding syndicates for early stage startups where we can reduce due diligence due diligence efforts, but share the ability to fund things that are interesting and really come at these problems together, to have you know collective grants and places for early stage scientists to ask those basic questions that are really fundamental to everything else that we're doing. And also have things in the middle that say, because we're not industry or venture or or what have you, as philanthropy, we can take on more risk because it's fine for us if the answer is no, actually, that can be exciting too. But in places where there's a lot of risk of being able to do that in a collective way, um, where missions are aligned, priorities are aligned, and risk tolerance is aligned. Like those are the places where I think that collective philanthropy can work together. But also, too, is the collective in terms of working with industry, working with government, working with venture, working with private equity, working with tech. I think we have all worked in our own environments for so long. But again, I do think those silos are starting to come down to some degree. We see people going into those spaces. Like I would love to have conversations with the bigs in device companies and say, what would make you want to take a pediatric device? What would change it for you? What devices are you interested in? And again, to tackle this as like a miniature device is not a bad thing for adults either. So I think that there are ways to position ourselves to be less in the, oh no, we're in pediatrics and we have nothing in a scarcity mindset, and to say, actually, we have a really great story here. We can bring things to first principles. We can talk about really cool tech. Like pediatrics is the place to be, like growth technologies, long-term, low, you know, side effects, uh, all sorts of like technology innovation, battery improvement. I think it's here in pediatrics, but no one views us as like the innovation center. So we need to recreate that narrative and come together. And I think that's the only way that this field is gonna make progress. Um, because alone we can't do that.
SPEAKER_00Yeah. Well, I'm just gonna say amen to that. And uh I clearly see why they made you CEO of this.
SPEAKER_01Thank you.
SPEAKER_00They chose one.
SPEAKER_01Very kind.
SPEAKER_00Uh let's wrap it up by saying if people want to know more, what what should they do? Where should we point them, etc.?
SPEAKER_01If you want to know more, you can go to additionalventures.org um and check out our website. If you're interested in our genomics study, then you can go to sbsource.org and look at it there.
SPEAKER_00Well, uh again, thank you for taking the time, Christy, and uh you have a good rest of your day.
SPEAKER_01Thank you. This was great.