
Trends from the Trenches
Trends from the Trenches
Episode: 37 - A Father’s Mission to Find a Cure: Casey McPherson on Rare Disease Research
Rare diseases do not receive enough attention for the impact they have on patients and their families. This is what AlphaRose’s founder and CEO Casey McPherson learned after his daughter was diagnosed with a rare condition. In a conversation with host Ari Berman, McPherson shares how he switched from music to founding his own pharmaceutical company, what technologies AlphaRose is developing, and how his company is creating environments that allow innovation and iteration. He also shares his thoughts on embracing failure in order to make progress and emphasizes holding compassion and understanding for the patients and families that are impacted by rare diseases—because you never know what it’s like until it happens to you.
Bio-IT World’s Trends from the Trenches podcast delivers your insider’s look at the science, technology, and executive trends driving the life sciences through conversations with industry leaders.
Welcome to the Trends from the Trenches Podcast, co-produced by Bioteam and BioIT World. I'm your host, Ari Berman, CEO of BioTeam. Today we have a truly remarkable guest who has navigated the worlds of music and science with an incredible purpose. He's a guy I'm lucky to call a friend, and his story is one of artistry, fatherhood, and a relentless fight for a cure. You know him as a captivating frontman for two incredible bands, the anthemic indie rock group Alpha Rev and the progressive rock super group Flying Colors. He's brought us songs that have topped the charts and filled stadiums around the world with instantly recognizable hits such as New Morning and Sing Loud. But beyond the stage and studio, our guests' most profound journey began at home with his two daughters, Weston and Rose.
Ari Berman:When his youngest daughter, Rose, was diagnosed with a rare debilitating genetic mutation, HNRNPH2, which encodes a protein that belongs to the heterogeneous nuclearibro protein family and plays a role in RNA processing and transport, his path changed forever. What he discovered was a heartbreaking reality. While there are over 10,000 known rare diseases affecting millions of people, as reported by the National Center for Advancing Transactional Science, most of them, including this disease, have no treatment. Refusing to accept that fate, he channeled the same passion and creativity he poured into his music into a new mission. He founded Alpha Rose Therapeutics, a biotech company dedicated to finding a treatment for Rhodes' rare disease. And in doing so, created a scalable model to help thousands of other families facing similar challenges utilizing approaches like antisence oligonucleotide-based treatments. He is a testament to the fact that a parent's love can move mountains, or in this case, revolutionize our understanding and ability to diagnose and treat rare diseases, bringing hope where there wasn't any before. Please join me in welcoming welcoming the one and only Casey McPherson. Hey, Casey.
Casey McPherson:Hey, Ari. I wish you were around. That was the best intro I think I've ever had.
Ari Berman:Oh, awesome. I'll give it to you then. Oh, welcome. Um, but it's I've really enjoyed getting to know you over the last few years, uh, as randomly as that happened. And story is one that I felt like the Bio-IT community could really grab onto, I think. Um, and given that the mission and purpose of what you're doing is largely about kids, about your kid, um, but also kind of about just pushing the envelope of persistent medicine, which we talk about in our field all the time. I thought it'd be fun to hear your story. So tell us a bit about your journey and how you came to entirely switch fields from record deals to running a startup pharma company.
Casey McPherson:Wow. Well, um, you know, what what do they say that if you knew how hard something was, you probably would never do it, you know? And but that's been, you know, you look at the rare disease metrics or pharma metrics or the success of a drug metrics, and actually they're better than being a successful artist, those metrics. So I'm sort of used to the deck stacked against you, you know. Uh, but I I think that there were things in learning music inherently is about creating something out of nothing. And if you've really been in that environment for long enough, you will find times when you make something that you were just surprised it even came out of you.
Casey McPherson:And then, but that's just the beginning, and that's actually the easy part. The hard part is turning it into a product that, you know, can have uh some sort of global reach. And so this the songwriting, you know, in in some ways I would account that to preclinical drug development for genetic treatments. We have the tools and technology now to to cure and treat hundreds, maybe even thousands of uh of these diseases that have no treatments right now. But but it's that next step of turning it into a product and getting it available. And so, you know, when Rose was diagnosed, my experience was as an entrepreneur, my experience was at a as a creator. And uh when I saw that it wasn't a technology issue, it was a business model problem, it was a systems problem. I thought, wow, maybe this super passionate, naive, like I'll never give up, Scotch Irish kind of guy, like hit me one more time, kind of person, and uh just see, just try to take me down. Um, that we have that in common. Yes, we do. Uh blends for punishment. Maybe we could look at some new models that uh would work for these small population diseases because it's a you know bigger than cancer and AIDS combined when you look at it as a whole. But the way we've been looking at it is these tiny diseases one by one by one by one.
Casey McPherson:And a so, you know, when I saw that ASOs in particular were programmable medicines, um, it was relatively safe to get into the clinic if you did X, Y, and Z around safety and talks. Um that that was it was sort of, you know, kind of calling saying, hey, I might be scalable, you know, I might be able to treat a lot of kids. And so, you know, we made an ASO, I I well, I recruited some scientists, right, that had been doing drug development um to really teach me and train me on the high-level side. And and then ultragenics and some other rare disease biotech companies really took me under their wing um to mentor me. But it was, you know, it was really scary at first to add a record deal from Sony on my desk or go after a treatment for my daughter. I knew I couldn't do both, you know. And it's the first time in my life that I chose that something was more passionate for me than than making music. And and uh I gotta say, man, making these making these treatments is is pretty freaking rock and roll, you know, and it's uh it's it's not there's there is uh it's not for the faint of heart, you know. And so I I feel strangely very at home in in this environment.
Ari Berman:That's uh awesome. And it's funny because I don't think I've ever really thought about like drug demand as rock and roll, I guess because I've been exposed to it for so long, but I think you're right, because it really is. It's like, what have we not done yet? Let's try that, right? Absolutely.
Casey McPherson:You're you have the you have the gall to make an assumption that you have an idea that has never been done before, even within, even within an assay or even within a study, you know, like all these little points in time through the development process, everybody's got to have a little bit of a there is something inside me that's creative enough and smart enough to be able to produce something that has never been produced before. And it's a humbling thing, but it's also, I mean, that's what rock and roll is. Rock and roll is, you know, it's like it's like I am not going to do what other people say is the way this is just how you're supposed to be or how you're supposed to do it. And, you know, I mean, maybe you could argue that that we haven't really seen that movement since the 70s. It's an ideal, it's a it's a type of person. And and now, now the lead singers are the for me, are those are the uh uh scientists in the lab. I'm just continually amazed at uh what people come up with.
Ari Berman:Yeah, it's interesting. I think I've told you this before, but uh people often ask me why scientists are nuts, and I sell them because science is 99% abject failure. Um, and I guess rock and roll is too.
Casey McPherson:Absolutely it is. Yeah, it's like it's it I remember at the height of my career when I had a top 10 hit and a video on VH1, and I was everybody's best friend. You know, people were like, you're famous, you're like it was as if you had never been anything else. But for me, all I could think of was the decades of failure and bart, you know, empty rooms I played, um, broken down vehicles, living under the poverty line, you know, all the labels that told me no or said you're not good enough, you know, and and seeing how science works, it's like you have to like re-engineer how you think about failure because failure is is acting as if like you've lost. And that's just not the case with with music or with science. Failure is like one step further to the solution.
Ari Berman:The truth is failure is never actually failure unless you decide it is, right? Because we don't learn without failure. No, we don't we don't we don't better ourselves, we don't look inward, we don't you have to fail to move forward. You just there's no way to do it otherwise. Otherwise, you think, oh, I'm great, everything's great.
Casey McPherson:So yeah, I completely agree. And it's almost as if, and and I'll tell you this this thing with Rose, you know, the amount of suffering that these rare diseases cause family, the amount of pain that she goes through, you know, we often look at things like failure and pain as these things we try to avoid.
Ari Berman:Yeah.
Casey McPherson:And yet you cannot make anything great or learn to be anything great or learn to do anything great without an immense amount of failure through that process. And that I don't know for me, I look back at what we've accomplished. And without the pain that Rosie goes through, without the pain that I feel, I don't think I would have had the self-discipline to learn the science and the business and do the amount of work and failures to get, you know, even just to the point that we're at now. And so I, you know, I think it sort of turns everything on its head of of sometimes it's best to jump into all that because it's it motivates you in a way that nothing wrong with living life on the beach, but living life on the beach doesn't really encourage you to change a whole lot.
Ari Berman:Not necessarily, no. And there's nothing like you're, you know, being connected to a problem like your kid being the the you know, having the problem, right? So well, I mean, that's a great segue. Why don't you tell me a little bit about how Rose's mutation has affected her and you know, what does she what does she deal with?
Casey McPherson:Yeah, so I'll start on the kind of micro and then where the light bulb went off for me for alpha rose on the macro level. You know, so Rose lost her ability to talk. This gene starts expressing, you know, postnatally, and um, and then she, you know, she really struggles with walking. She doesn't have any friends, she can't go to school. You know, she's she is not potty trained, and she's nine now, nine years old. And um and she's cute as can be, by the way. She is she's so cute. I gotta say, um uh she and she's even her even through all these things, her personality still shines through where she purposefully does something she knows is gonna piss me off. And it like makes her really happy because she feels like she was defiant, you know. And that's a long line of uh females in my strong-willed females in my family that that say, I'm gonna break the rules and you're gonna watch me, you know.
Casey McPherson:Um and so I love even though it's a pain in the butt sometimes, I love seeing it. Um, and she recently started having seizures, you know. This is it's been a year since she had a seizure where her heart stopped and she lost her breathing. And uh mom had to bring her back. And so she's on seizure meds, but we don't know how long that's gonna last. And you know, what I learned, and so that's we don't go out to eat. We don't going on vacation is a nightmare. All these things that you typically do as a family just scratch them off, or know that you have an immense amount of logistical planning ahead of you just to do something very simple. And that's so where are all these hundreds of millions of families? They're all at home surviving day to day. And that's where like this macro piece hit me, where these families usually don't have the resources or the amount of energy to do anything about this. And so consequently, they're they're sort of uh we call them underserved. Well, they're underheard, they're ignored, you know.
Ari Berman:Absolutely.
Casey McPherson:And and if if more children are dying, or they say 30% of children with a rare disease die before their fifth birthday, and they and there's about 200 million kiddos out there with a rare disease, you can imagine like we talk about 9-11, or we talk about the stuff happening in the Middle East, or like genocide. This is the largest silent genocide that I think we've seen in you know our day and age that is is solvable to some degree, you know, not like completely curable, but we have science. And and and so that that really drove me to say I it can't just be about rows. Um, because I watched families develop these genetic treatments, especially those with a little bit of means.
Ari Berman:Yeah.
Casey McPherson:You can go make an ASO or gene therapy for a few million bucks and treat treat rows and in a clinical trial and move on with money, which you may not know this, or a lot of people may not know this, but there are families doing that now. Yeah. And it's a thing. And and they're saving their kids' lives. And but it's not scalable. And no parent should ever have to become a CEO of a biotech company, you know. So that's kind of what I want, I hope to prevent and I hope to stop is the burden, the financial burden and the educational burden, you know, on these families so that those we can get these treatments out and accessible.
Ari Berman:Well, I think that last term is the most important part there, accessible, because if it costs a couple million bucks, there's not a lot of families that can do that. Yeah, we're both CEOs, and if neither of us can do it, right? So that's that's why I had to learn fundraising.
Casey McPherson:And yeah, and it and and you know, there's this huge misconception that ultra, you know, most rare diseases genetic, most genetic disease ultra-rare. So that's that is true. But there's this huge misconception that ultra-rare drugs do not make money. And so it's been yeah largely in the nonprofit world, which is completely unscalable. And you're just dump, you're just pouring money into a big black hole, you know, without some sort of sustainable plan. And so that's why I started a company eventually, you know, for alpha rose, was that the the finances work. Maybe it's not a billion-dollar drug, but it certainly doesn't cost me a billion dollars to get it to commercialize it. You know, so it's it's like the difference between like building a residential house or building a skyscraper. We've been building skyscraper medicines with these small molecule programs, and those have like what a 90 to 95% failure rate. And genetic treatments, now no one's published on this, and I hope I hope I can publish on this at some point. Genetic treatments have a exponentially higher chance of success. I'm watching dozens and dozens of these being developed by people for the first time, and they're working in the clinic, you know. Um so to me, it feels like this is where medicine needs to go if we're gonna start, you know, bringing down drug prices and action making medicines to fix, you know, disease.
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Ari Berman:Well, as we've discussed before, and you brought it up, uh, the only way to change anything in this world is to figure out how to make money from it. It's not because it's the right thing to do. If you can align those things, then uh something good could happen, right? Uh, but you gotta figure out how to make money from it. And the traditional pharma model of, you know, 12 years and billions of dollars of investment into this one small molecule that has nine billion side effects, but it might actually treat your symptoms. Um, uh, and also it's gonna cost you $120,000 a pop, um, you know, that's you know, that's the model. Um and, you know, precision medicine, personalized medicine has been something we've been throwing around for a long time. And you're right, it is partially there, but it's not accessible. And most people don't know that it's there. And yes, and since all things on some level start with the genetics, especially diseases that arise from genetic mutations, uh, you know, is this something that can be knocked down through some sort of anti-sense, you know, thing uh, you know, attaching to it? It's uh really cool.
Casey McPherson:That's I think, you know, it's it it's interesting how accessible this was to me. Like a lot of the companies and family foundations and families that have sort of paved this road in some ways, you know, Eli Lilly started a group called Chorus and they created this drug development model. Um, and if you if you look at what they published, um, this is a huge, you know, pharma corporation trying to figure out how to create like lower risk and create efficiencies. And I'm reading through it and sort of laughing because I'm like, this is exactly what families are doing. But they developed it, they developed this model on their own of what is enough, you know, when time equals life and and you don't have a money tree sitting next to you, then how do you do efficient product development for a patient that's gonna save their life, you know? And and to your point, you know, I've never been motivated by money solely, like that's never been enough for me. And but I think the it's it's it's actually a fun part of this job for me because I know that proving to the investors when they make their great returns with lower risk off these genetic medicines, it means that the investment community is gonna start shifting to what they used to call orphan, meaning like no home, to being like, oh man, I'd rather invest in these because you know, I don't invest in 20 of those instead of one big drug because that they're gonna, you know, most of them are gonna work. And I I want to be a part of that shift.
Ari Berman:Yes. Uh well, and so all you need is some high profile thing out there, and then people are gonna jump on it and you're out there making lots of good noise in the investor communities, which tell us about Alpha Rose a little bit.
Casey McPherson:Yeah, well, so you know, the first thing that a lot of venture capital don't like is we're a public benefit corporation. And so what blew my mind is that healthcare companies as a corporation are only required to be fiduciarily responsible to their shareholders. That's correct. So you can screw over as many patients as you like, um, with with sort of zero uh, you know, uh blowback into well, maybe in the press, you know, but but so what I love about public benefit corporations is more of a balance between your investors and your patients. And so you can't really screw either over, you know? And and and I think in healthcare, there's this unique relationship between capital and patients. And it's it's like capitalism's great when you get great medicines out there that patients have access to. Capitalism's not great when you have shell drugs that are working, but they, you know, aren't gonna make as much money. And or when you have when you're choosing assets based on revenue, not based on the impact it's gonna make on a patient. So there's a ba— I think there's a really nice balance. And so Alpha Rose is sort of fundamentally started with that approach and co-founded by Belinda Tremir and Alan Waltz, who, you know, if you're familiar with the Gen zyme story, Henry Kermere was one of the most innovative CEOs for rare disease, and Gen zyme sold for 20 billion. And and these two help build that company. My presence Masoko Nakamura, she was also at Gen zyme, commercialized over 20 rare products in her career. So I have these really incredible folks on the executive level that believe that if you put patients first, you can build a very lucrative company um by focusing on getting a treatment into patients as quickly and safely as possible and providing as much access as humanly possible. And and they used to have a bell they would ring every time they treated a patient, you know. Oh, I love that globe. And so that culture is something I want to continue, Henry's legacy in that a company doesn't have to be a big, bad company to make money and to treat patients. And it's simply just where's your focus? Is your focus solely to make money? And then, yeah, patients are a part of that, you know. Well, then you become the big, bad, you know, healthcare company. But if you actually put patients, you can do good and make money. It's possible, you know.
Ari Berman:You can, yes. It's harder.
Casey McPherson:The goal, yeah. It requires drawing some lines in the sand for sure. Um, and it requires a different kind of culture. But you know, we've so for AlphaRose, we've we've had we're we're sort of this integration between ASO technology and software, AI, eventually some robotics, and and the idea that these are programmable medicines. So the more we can layer on automations through the preclinical, clinical, and commercialization process, the more ability we will have to scale these treatments. And what I realized in the lab, which was like the first company I started, was this preclinical lab, uh, is that so many of these pieces are repeatable. And we're screening many, many compounds to try to figure out which one's toxic and which one's not. And I'm a musician, so you know, is it crazy to think that there might be some patterns in our biology to start to start helping us make the argument for predictive toxicity and predictive interaction with the gene, you know, some predictive, at least genetic efficacy. Um, and and and so far nobody's told me that's crazy. And so we've been building some some uh pilot systems to design our ASOs around uh around this, and and I'm very excited about it.
Ari Berman:That's awesome. Clearly, we're well aligned on these things. So yeah, uh, I I love the story. Um, so talk a little bit about some of the technology to guys are uh using that this audience is both tech and science. So yeah, what would that you've told me about this thing and I I can't wait to go see it.
Casey McPherson:So it's yeah, well, I mean, you know, there's so many things that need to be built. Um, but but the way I've been looking at this is we have this car, it kind of runs, and in the current regulatory environment, we can do this. These little diseases will still make some money, they'll still be expensive drugs. Yeah, but all of it works as an efficient if you create an efficient pipeline with the current technologies we have, which are ASO therapeutics, you know, using that chemistry set, and then particular assays and uh animal studies that are required to like make sure it's safe. But then you start adding in um uh software, and ASOs are a sequence of nucleotides. And so so are genes, right? Yeah, it's we quickly saw like, what if we have a database of genetic mutations and we design some uh automation, some machine learning, and maybe some magnetic AI to look at the amenability of each mutation for our technology. So building that database right now with neurodevelopmental and just pulling from Omen, Plimbar, and I think, oh, this sounds like a great idea. Then the first problem we have is that you know, Omen doesn't communicate with Nomad and they use different. And so I'm like, oh shit, it's like Chinese and uh English and Spanish all trying to to to collaborate together. So so that that became something we started building was this was that a stone to get the the the gene databases talking to each other. And and then we built, which I we showed you, you know, and and and you know, we've got a long way to go on this, but kind of the first iteration of an ASO design tool that could look at all of the factors that would create toxicity. So usually you design these in a spreadsheet and you've got thousands of designs just walking down the gene. But now there are certain things like aspects around what's the most active area of the gene where if we wanted to uh uh downregulate or upregulate a gene, what are those most, you know, best areas to do that in? So that's shortlists. What are the type nucleotide sequences that could be potentially more toxic? We can shortlist around that. And then there's there's some calcium stuff that also, this is where it gets a little bit like, well, a lot over my head. There's these these sort of chemical and bioalgorithmic uh assessments that we're able to make now to even shortlist. And so I think you know, we have really great potential by with this design tool, by the more data, the more quality data we can feed it and order that. The last thing that I'm excited about is we're taking, you know, Rose's drug, Ros iphersen, is ready for the clinic. And so we've been partnering with some wearable companies because the way they do clinical trials, like I don't know, I didn't go to school for this, but when they told me this is how you do a clinical trial, I was like, I'm sorry, but this seems really dumb to me. If you told me you're gonna see efficacy based on the studies that you're currently doing, you're not. Like you're gonna the measurements that they've come up with were like made in the 70s. Like, think about how much we've developed here, and yet our yet are yet the how we're collecting data in our clinical trials has not. So we're using these wearables like to track Rose and these kids to establish a baseline and like a three-dimensional digital footprint unbiased that we can we can collect from video, uh EEG and and motor and cognition at their home, doing what they always do instead of being at a clinician's office. So I think where there's gonna be a lot of really cool innovation in that area to shorten a six-year trial down to a year or two, you know. Yeah. Uh so that these are all you know, technology pieces that now are super, super important that interface really, really well with this, with antisensal organopotides.
Ari Berman:I'm excited to see where that goes. The uh wearable, the Internet of Things groups that have been trying to figure out how to pull this stuff in for a long time. There's there's uh like pediatric moonshot is another thing that's really interesting. They they've been doing this, but wanting to take all that data and process it on the edge and then take the processed data and pull it into the middle to do something cool with it, right? Um, but uh yeah.
Casey McPherson:I mean, I think that's that's I'm excited about um, you know, kind of the tools we have now. And it reminds me again, like being in a music studio where you've got your analog synthesizers, you got your great compressors, you've got all these great tools to work with. The trick is, is if the focus is that time does equal life and that patients are waiting for these treatments, and we're in a war that that kids and patients are dying every minute right now, that we have to be able to create an environment where we can quickly innovate and iterate on these technologies because it's like you're you're in a world war and you're trying to make a new gun or a new defense mech, you know, you don't have unlimited time to to to do this, you know. So I do feel this sense of urgency and and like bringing people in, like, let's work on this, let's fix this. You know, we can do it, it's possible. So, you know, that's exciting but also frustrating. Well, it's a short fuse, right?
Ari Berman:Some people are like, uh, what are you talking about? You got the rest of your life, could be that long, right? That's what people don't realize. And also people are like, eh, you know, it's a rare disease. And well, you'll say that until it happens to you, right?
Casey McPherson:Yeah, you got a one in twenty chance of it happening to you or family under. And, you know, we love to, I mean, I'll tell you, when I saw families with special needs kids, I had zero desire to meet them. I sure am glad that isn't me. Yeah. And when it happens to you, you're, you know, it's like then all of a sudden you see all the other families out there that are struggling with this. And, you know, it's uh it's a very different, different thing. But it's, you know, there's the people that it hasn't happened to that actually have the capacity to do this stuff. Those are the people I consider true rock stars that are like, all right, we got to change this. Let's fix it. Where do we start?
Ari Berman:Absolutely. Absolutely. Well, um, I guess the last bit I'll ask you is to wrap up is how can people get involved and help?
Casey McPherson:I mean, you know, we're uh always looking for great minds that um have gifting that can help, you know, participate and solve this problem. We're also looking for more mission-driven investors. I mean, you could easily turn our company into a large pharma company.
Ari Berman:Yep.
Casey McPherson:So it's very important that our investors align with the fact that we're only going to be commercializing these ultra-rare products and we're gonna be focused on building the scale as opposed to just being a traditional company. Um, and so, you know, we're we're running an equity crowdfunding uh campaign where anyone can invest. Uh, you know, that's started in dot com slash AlphaRose. And then, you know, you can always find us on our website and on social media that that if if someone's interested in being a part of this in some way, um, you know, we're we're looking for you. You know, it's like the the uh the US uh who was the old Uncle Sam Uncle Sam Uncle Sam is like, you know, we want you because at the end of the day, there's hundreds of millions of patients waiting, and none of us can do this alone. So the more that we can partner, band together, put our resources together, Alpha Rose is merely a vessel to break open this space. I hope that many, many other companies do this like we're doing it and and benefit from it too.
Ari Berman:Awesome. Well, I'm super excited to see where this goes, and I hope that uh that I get to jump in and help too, because it's an awesome, awesome effort. So um too, Ari.
Casey McPherson:Um we we needed many we we don't need many excuses to work together because I have so much respect for you and your team and what you guys do.
Ari Berman:Uh appreciate that. Well, we're looking forward to it and thanks for being on the podcast today. Really appreciate it. And uh uh I hope uh people reach out and get involved and Uh realize, hey, precision medicine is closer than we think. And it's not just for the ultra-rich.
Casey McPherson:Yeah, absolutely. Thanks for having me, Ari.
Ari Berman:Thanks, Casey. Take care.
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