Summary

On the latest episode of The Bioverge Podcast, David Fajgenbaum, MD, MBA, MSc, Co-founder of the non-profit Every Cure, sits down with Neil Littman to discuss his incredible journey battling Castleman Disease and Every Cure's mission to identify new uses for existing drugs.

Every Cure is pursuing a world where every drug is used to its fullest potential to save lives.

This is one episode you won't want to miss!

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Transcript

00:29
Danny Levine (producer)
Neil We've BV BV david Fajgenbaum show today. For listeners not familiar with David, who is he?

00:37
Neil Littman (host)
So, Danny, I am incredibly excited to welcome David to the show today. David is a physician scientist at the University of Pennsylvania. He is a co founder and president of the Castleman's Disease Collaborative Network and national bestselling author of Chasing My Doctor's Race to Turn Hope into Action. He is also a patient battling a deadly disease called Idiopathic multicentric Castleman's disease, which he discovered a treatment for that is saving his own life as well as other lives. He also co leads Every Cure, a nonprofit drug development organization focused on advancing repurposed treatments. David earned a BS from Georgetown University, a Master of Science from the University of Oxford, and a medical degree from the University of Pennsylvania, as well as an MBA from the Wharton School at the University of Pennsylvania. Just to give a little background here, david was on the brink of death five times and had his last rites read to him.

01:38
Neil Littman (host)
The medical system did everything they could, which was limited given how much was known about his disease at the time, and so the system failed him time and time again. David realized that in order to save his own life, he needed to take his medical care into his own hands.

01:53
Danny Levine (producer)
As I spent a lot of time focusing on the rare disease space where David has been a force and a source of inspiration for so many people. His personal story, which he tells in his book Chasing My Cure, is compelling. What was your response reading the book?

02:12
Neil Littman (host)
It was just such an incredible journey that David was on and my response was just david was in a unique position where he was a medical student at the time and had the medical training to give him the ability to take treatment into his own hands. Throughout the book, he talks about how the system had failed him and he went through four relapses and it was finally after the last one where he, I guess, almost gave up hope in the existing medical establishment and realized that he had to figure this out for himself. Unfortunately, he had the training to be able to do so. From a 30,000 foot view, it really reminds me that we really have to take our treatment into our own hands in many respects, and not all of us have the ability to do what David did. Obviously, we don't have that type of training, but we need to be proactive about our own medical care just at a very high level.

03:06
Neil Littman (host)
So that was incredibly powerful to me. The book was really just so inspiring and just a little additional context. I was actually working at a company by the name of Notable Labs at the time and the founder of that company was inspired by this book because were looking for drug repurposing efforts for glioblastoma at that time. So, as you mentioned, David is just such a a force of nature and a powerful force. I think the story that he shared has inspired so many of us throughout the industry, and his story is just so incredible. To do what he's done, overcome what he's overcame, and now what he's doing at Every Cure, I think is just really amazing. I'm really excited to dive into what he's doing at Every Cure as well.

03:51
Danny Levine (producer)
Beyond his own story, he's really been an innovator who's reshaping the way rare disease patient organizations approach research and drug development. He's also been an outspoken advocate for drug repursing. Now, with his newly created nonprofit Every Cure, what are you hoping to hear from David?

04:11
Neil Littman (host)
Yeah, I'm really interested to hear what Every Cure is doing around drug repurposing. I mean, drug repurposing is nothing new, right? That idea concept has been around for a long time now. There are some systemic barriers that I think have prevented it from really taking off. I'm excited to learn from David what they're doing differently at Every Cure. If you think about rare diseases in general, rare diseases as individual diseases are very rare. But, I think there's seven to 9000 rare diseases that exist in the world, right. I think the latest that I saw is that one out of ten people in the US. Have a rare disease, which is about 30 million people. Taken together, rare diseases aren't rare at all. What David is doing is, I think, can have a huge impact for so many people out there. I'm really excited to learn about how they're doing some of this repurposing and what's different than efforts that have been done in the past.

05:11
Neil Littman (host)
Well, if you're all set, I'm all set. Let's do it. Danny david, I am incredibly excited to welcome you to the show today. Thank you so much for joining us.

05:22
David Fajgenbaum (guest)
Thanks so much for having me, Neil.

05:24
Neil Littman (host)
I first read your book Chasing My Cure when it came out in 2019. I remember it well because I was working at a precision oncology company in the Bay Area called Notable Labs, which was started by a founder who was trying to find a cure for his father who had been diagnosed with glioblastoma. None of these existing therapies were effective, and he and many of us who worked at the company took your story as inspiration. We'll get into your story momentarily, but first, I really just want to say a big thank you for having the courage to share your deeply personal journey with the world.

05:58
David Fajgenbaum (guest)
Thanks so much, Neil. It's been such a journey to use your words and so many ups and downs, and I just feel like if you're going to go through all these challenges and learn things along the way. It's important to share these lessons with the world.

06:14
Neil Littman (host)
I couldn't agree more, and I think you've inspired so many of us along the way. So, David, today we're going to talk about your new nonprofit organization, Every Cure. Your focus around drug repurposing and how your efforts to save your own life from a rare disease led you down this path. For those who aren't familiar with your personal journey, I'd like to start with your story, which you tell in your book Chasing Mike Cure. So, David, take us back to when you were a sophomore in college, because there was a pivotal moment you talk about in the book when your mother was battling and ultimately died from cancer. How did that shape your focus as a medical student and your subsequent journey?

06:52
David Fajgenbaum (guest)
Well, it really changed everything. My mom and I were so close, and to have her be diagnosed first with cancer and then pass away during my sophomore year really just changed everything. It made me decide that I wanted to go into medicine. I wanted to chase cures in her memory. I wanted to treat cancer patients like her. I was just laser focused on this mission, finished up undergrad, went to grad school at Oxford, focused on cancer prevention, and then came to Penn for medical school. I was three years into my medical degree, and I was achieving that goal that I had set out when my mom passed, and I promised her that I would do this in her memory when out of nowhere, as I became critically ill myself. I went from being this healthy medical student who wanted to treat patients in my mom's memory to being the critically ill patient in the ICU myself.

07:45
Neil Littman (host)
And, David, could you talk about that journey? You were diagnosed with recognition Castleman's Disease at that time. What did it take for you to get a diagnosis? How challenging was it at that time to diagnose someone with Castleman's?

07:59
David Fajgenbaum (guest)
It was really tough. There was no diagnostic criteria existed back then, and very little was known about the disease. Basically, I was a third year med student. I was on OBGYN rotation, and I felt more tired than I'd ever felt before. I mean, I was exhausted and hard to even describe just how tired I felt. I noticed lumps and bumps in my neck, and I noticed some pretty bad abdominal pain. Eventually, I took a medical school exam and then went down the hall of the emergency department, and they ran some blood tests, and they told me, david, your liver, your kidneys, your bone marrow, your heart, and your lungs are all shutting down for an unknown cause. We have to hospitalize you right away. It was just so frightening to find out that I was literally all my organs were shutting down. Unfortunately, over the next eleven weeks it would only get worse and I would be transferred to the intensive care unit where a retinal hemorrhage may be temporarily blind in my left eye.

08:55
David Fajgenbaum (guest)
I gained £70 of fluid because my organs weren't working and I drifted in and out of consciousness. I was so sick that I actually eventually had a priest came into my room and read me my last rites when I was 25 years old and really could not have been more sick. Fortunately, at really the last possible moment right around the time I was having my last writes read to me due to this awful disease called Castleman disease, the diagnosis finally came back and my doctors didn't really know anything about the disease. I certainly didn't know anything about the disease. That's when I realized just how important it was to do two things. One is to find the expert who is the expert for your disease. Two is to realize that the expert may know everything that the world knows about a disease, but for diseases like hasslemans, I would need to get involved in the journey, in the fight to try to find more and more information about this horrible, rare condition.

09:52
Neil Littman (host)
David, I want to jump into Castleman's here in a minute, but you mentioned something in the book that really stuck with me where you initially ignored your intuition about being sick in favor of evidence and I think many of us can probably relate to that. What have you learned from that experience?

10:10
David Fajgenbaum (guest)
Well, everyone in medical school thinks that they have horrible diseases like Castlemans and they're going to die very soon because you learn about all these horrible diseases in medical school that you otherwise would never hear about unless you had someone that you love that had them. So, like all of my classmates, I was starting to get sick and I thought, oh my gosh, I have this horrible disease. I even told my medical school roommates, I said, guys, I don't know what this is, but I think I'm going to die. That's just like totally uncharacteristic for me to be so dramatic. I really mean, actually there was some truth to that. I had this horrible disease that was brewing, but no one knew what it was.

10:50
Neil Littman (host)
So let's talk about what it is. So what is Castleman's Disease?

10:54
David Fajgenbaum (guest)
Sure, it's an inflammatory disorder that really sits at the intersection of cancer and autoimmunity. By that I mean that we can't categorize it yet as to whether it is actually a cancer or whether it is actually an autoimmune disease. In medicine, you learn that many diseases sit in the grayness of medicine where they're one thing and another. In humans, we like to lump things into categories. Unfortunately, Castlemans sits at the intersection, so it's got features that are like lymphoma and features that are like an autoimmune disease and I like to say it's kind of the worst features of both in one disease and basically your immune system becomes hyperactivated and then attacks your vital organs for an unknown cause. It's like this fullblown attack on all of your organs and we don't know why it's happening in your immune system. Our immune systems are very powerful and if they want to destroy your heart, your lungs and your kidneys, they can do it pretty quickly.

11:48
David Fajgenbaum (guest)
Unfortunately, the way you treat it is to either target one part of the immune system to figure out how do you basically defuse the bomb, how do you stop this immune system from attacking you or you just wipe out the whole thing with chemotherapy. Back then this was back in 2010, very little was known about the disease. I needed the carpet bomb approach, which is just wipe out the whole thing with chemo.

12:13
Neil Littman (host)
Let's talk about why there was so little known about the disease at that time. David, I think I've heard you reference that Castleman's disease is about as common as ALS, which I think most people have probably heard of and affects about 180 people in the US. Why don't you think more people have heard about Castleman's Disease or why haven't there been more research dollars being funneled into the disease?

12:35
David Fajgenbaum (guest)
It's a great question. I think it's important to get a sense for the scope of rare disease. They're actually about 90 rare diseases and so each one of them on their own is rare by definition but collectively they're really common. When you have 9000 diseases there's a lot for the public to become aware of, right? So, the public can't be aware of all 9000 rare diseases but certainly the public is aware of some horrible ones like ALS. Like you said, Castleman's is similarly common to ALS and unfortunately, much less public awareness, much less funding. I think there's probably a few reasons behind that. One is that ALS is kind of an outlier in terms of rare diseases in the fact that it does have such great public awareness in part because of some celebrities that have sadly had this horrible disease and also in part because it is uniformly fatal.

13:30
David Fajgenbaum (guest)
Everyone who gets ALS as of right now will die from their ALS within anywhere from one to five years after diagnosis. Given that it's uniformly fatal, it deserves lots of attention. A disease like Castle Disease that is similarly common and also uniformly fatal for a subgroup of us does not always get the same attention just because there are so many rare diseases that we get lost in the mix. I've tried really hard through writing, chasing my cure and through trying to raise awareness about the disease or the Castleman Disease Collaborative Network to try to get people aware of this really horrible disease.

14:08
Neil Littman (host)
David, I want to talk about the Castleman Disease Collaborative network here. In a minute. There was a line from your book that really stuck with me where you mentioned that before you got sick, you had this Santa Claus view of medicine. What do you mean by that? What do you think of medicine today?

14:29
David Fajgenbaum (guest)
Yeah, Neil, you may think that I was just very naive, but really when I went into medicine, I really believed that there were teams of researchers working together in a coordinated fashion, collaborating to try to figure out what drugs could treat what diseases. There was this engine at work, and I talked about Santa Claus as the analogy, because I can picture this workshop of elves working together, creating the toys, delivering the present right in time for you on Christmas Day. That's kind of what I envisioned medical research looked like. All of a sudden, I became critically old with this disease and started to dig into what does medical research actually look like? It doesn't look anything like Santa Claus's workshop. I mean, what it really looks like is a bunch of individual researchers spread out all across the globe, not working together at all. In most cases, they've never even met one another.

15:27
David Fajgenbaum (guest)
In many cases, they're working on the exact same things and maybe failing on the exact same approaches. It's frightening how uncoordinated it is, how fragmented it is and how random research is. I think for me, the randomness was maybe the hardest part, is like, wait a minute, we have to kind of hope that the right researcher comes up with the right idea for the right project at the right time, with the right skill set. That's how you get a drug that works for a disease. It's just a bunch of random things, and stars have to align. For me, my mission early on became, how do we take this randomness of, like, all these things, aligning, and create a system here so that we're not just relying on hoping and waiting, but that we can really create a system to encourage and facilitate breakthroughs and cures?

16:15
Neil Littman (host)
You really began researching the disease from your bedside. The system that you just mentioned is the Castleman's Disease Collaborative Networks. It's probably a good segue to talk about that. Can you talk about what that is? I mean, you mentioned some of the problems you're trying to address, but give our listeners an idea of the scope of what that network is and what you're trying to accomplish.

16:42
David Fajgenbaum (guest)
Sure, I alluded to it a bit, but it's helpful to think through the traditional model for rare disease research. The traditional model is that groups like the CDCN, we raise money from families and friends, and then we invite researchers to apply for the funding through what are called Requests for Proposals. We, through the CDCN, may put out a Request for Proposals to do $100,000 or $200,000 worth of research. As a rare disease, we might get a handful of applicants, and then we'll pick the best applicant out of those five researchers who apply for the money, and then they'll do research. Next year, we'll do the same thing over again. There are a number of problems with this approach. One is that what is the likelihood that one of those five people who applies for your grant happens to have the best idea in the world about what should be done?

17:31
David Fajgenbaum (guest)
I mean, it's very unlikely. Secondly, what's the likelihood that the person who applies for it that has the best idea is also the best person in the world to actually do the work? Just because you think genetic sequencing should be done doesn't mean that you're probably the best person in the world at analyzing genetic sequencing data, for example. Another problem with it is that it's not part of a strategy or a plan. It's every year, you look at a new set of applications and you pick. The next year, you look at another set of applications and you pick. There's this randomness to it that was really concerning. We said, okay, let's not do that, because that's been happening for the last 50 years for Castleman's, and we are where we are, which is not very far, and so let's go for the new model. We built the CDCN to bring together physicians, researchers, and patients, first virtually, but then also through in person meetings with the goal that we would connect the community so the community could actually tell us and prioritize what research needs to be done.

18:27
David Fajgenbaum (guest)
Not a handful of researchers applying for what they think should be done, but can the whole community tell us what research should be done? What questions need to be answered? Can we prioritize those questions into the most important research questions? Go out and say, well, who is the best person in the world at answering this question and doing this kind of research? We would go out and we would recruit them and say, hey, we'll give you all the samples and the data and the funding you need to do the study. You're the best person in the world for the most important study for Castleman Disease. The first question I usually got from researchers was, what's Castleman Disease? I'd always think to myself, that's not a good start to this. The important thing is that they didn't really need to know what Castleman Disease was. They used to be the best people in the world at doing the study.

19:10
David Fajgenbaum (guest)
We get them the samples, get them the data. We can share insights about the disease. We want the best people to do it, and so that's the approach we've taken, leverage the community to do the best science, and then from the best science, we would learn things about the disease. Something that's also part of our formula is to then say, okay, if we learn that one part of the immune system is really important from this research study we did with the world's expert what drugs are already FDA approved, they can actually fix that problem. If we find out that the mTOR communication line is turned into overdrive, we can say, well, is there an mTOR inhibitor? We can try to knock this thing down, maybe that'll treat the disease. We always ask whether there are already FDAapproved drugs they can do that because we recognize that if the drug is already FDA approved, it's already your neighborhood CVS.

19:56
David Fajgenbaum (guest)
We can get that drug into a patient within a matter of days or weeks, as opposed to if we find something that's novel, it's not yet approved. It's going to take us decades, maybe years, but certainly could be decades before that drug gets into humans.

20:10
Neil Littman (host)
David, let's pick up on that last point, because that's in fact, what happened in your case specifically. You ultimately identified an approved drug that saved your life and was available at the local drugstore. Could you talk about how you uncovered this generic drug that ultimately helped save your life?

20:30
David Fajgenbaum (guest)
Yeah. We talked through my starting the CDCN. I nearly died five times over a three year period. It was the fourth time that I nearly died that I decided I would dedicate my life to trying to find a treatment. That was when I started the CDCN. In parallel to starting the CDCN, I also realized that we would need to look specifically in my particular blood samples and my immune system to see if we could figure out what was going wrong in me so we could find a repurposed drug that could maybe help me. I'm reasoning that if we could figure out a drug that could help me, it could also help a lot of other patients, too. Over the course of the next year, between my fourth and my fifth deadly flare of this disease, I was running experiments on my own blood samples in the lab.

21:17
David Fajgenbaum (guest)
I was storing blood samples on myself. In the event that I were to relapse, I would be able to go back and do research on them. And sure enough, I relapsed. I nearly died for the fifth time. It was frightening, and it was horrible, and it was terrifying. I had this amazing fiancee by my side, Caitlin. Throughout all of it, she never left my side. The whole time I was fighting to try to stay alive, all I could imagine was being able to get married to Caitlin. If I could just survive, and if this chemotherapy could kick in to save my life, maybe I can get back in the lab and I could find something that could put my disease into remission. I could get married to Caitlyn. Through that research, I did find out, and I discovered that a part of the immune system called mTOR that I referenced earlier was turned into overdrive.

22:03
David Fajgenbaum (guest)
That was really exciting because this communication line is really important for your immune cells to communicate with one another. It's important for them to turn on and turn off. What was most exciting about it is that there's a really great m tour inhibitor, something that blocks this thing. It's been around for decades. I figured, if this is important to my disease, then maybe I could try this blocker of it. Maybe if I block this thing that's important to my disease, maybe I'll stay in remission and maybe this will save my life. But there were certainly no guarantees. I mean, when were looking at this drug and my data, the opposite could have happened. Maybe by turning off this communication line completely, maybe it was the only thing that was keeping me alive. Maybe it was the last bit of hope. And so we had no idea.

22:50
David Fajgenbaum (guest)
But there were no other options. I knew I was going to relapse again shortly. I knew there was no way I could survive to Caitlin and my wedding day. We decided that I would try this drug. It had never been used before for Castlemans, ever. As you said, it was at my neighborhood CVS, because it was already approved for kidney transplantation. To prevent people from rejecting kidney transplants again, but never been used for my disease. I shared the data with my doctors. At this stage, I had finished medical school, but I certainly didn't feel comfortable writing the prescription myself. I shared the data with my doctors, started myself on this drug, and yeah, it's been over eight and a half years that I've been in remission on this drug and just feels like such a dream. I mean, I was able to make it to Caitlin and my wedding day.

23:39
David Fajgenbaum (guest)
We got married. We've had two just beautiful children. During this remission, I've been on a mission to do this for more patients. Once I started benefiting from this drug, we started to figure out what other patients could benefit from it. We started giving it to other casino patients. We found out that it doesn't work for everyone, so we started looking for more and more drugs like it. We've now found ten more drugs like serolimus that can be used in a disease that they were not initially developed for. Now we're on this mission through the organization, every cure that we launched this fall to really do this at scale across all drugs and all diseases.

24:17
Neil Littman (host)
David, it's such an incredible story, and there's so much to dive into there and unpack. Two really questions come to mind based on a couple of things that you said. Number one, obviously you had to take your own medical care into your hands to save your own life, right? You are in a unique position to be able to do that, being in medical school yourself. What about folks without your medical training? I find it hard to believe that someone without your training could have ever come up with a solution. Are there things that the rest of us could or maybe should be doing to be more proactive about our own medical care?

25:00
David Fajgenbaum (guest)
Well, that's exactly why we started and we launched Every Cure because we believe that every drug that's at your neighborhood pharmacy should be able to be utilized for every disease that it can treat and that you shouldn't have to do research on your own samples to figure that out. We basically are creating that Santa's workshop that we talked about earlier in the call to basically have a team and the data engine necessary to constantly be looking for new uses for existing drugs and then take the most promising ideas and opportunities and do clinical trials and prove they work. That way, when you're diagnosed with that disease, we can tell you this is the drug for you. We can deliver that drug to you by your Christmas tree when you need it, so that way you don't have to go on the search for it. So that's why we created Every Year.

25:47
David Fajgenbaum (guest)
It's a nonprofit organization we launched this past fall. We are just on a mission to make sure that every drug is utilized for every disease and can help save every patient possible.

25:59
Neil Littman (host)
David, I want to jump into The Cure here in 1 minute, but I have one follow up question. So, as you mentioned serialimus, the drug that you discovered that works in your subtype of Castlemans isn't effective across all subtypes of Castleman. As I zoom out from maybe a 30,000 foot vantage point as I think about this idea of precision or personalized medicine versus how drugs are currently approved in a randomized controlled trial, which is a gold standard, but there are a lot of drugs that have demonstrated some clinical effectiveness in a subset of patients. The overall trial fails significance because as a broad patient population, how do you think about these drugs that work in the case of N equals one but are never approved or available because they were in an allcommerce clinical trial, for example?

26:51
David Fajgenbaum (guest)
Such a great question. Well, we're really diving into that through this organization because we recognize that it is really expensive and time consuming to get a drug to have a new disease listed on the label. That a label changes is basically where you do a large clinical trial like you mentioned, And you prove the drug works in this disease, and then the FDA adds that disease to the label of the drug, and it can cost tens or hundreds of millions of dollars to do that. What we recognize is that, to your point, if the drug only works in a subpopulation of patients and or if the drug is generic or the disease is rare, then no one is ever going to spend tens of millions or hundreds of millions of dollars to get the label to be changed, to actually prove that the drug works in that disease.

27:38
David Fajgenbaum (guest)
What we're leaning into is this recognition that if a drug works in a portion of those patients, let's generate the data to prove that it works in a portion of patients, or even just to unlock or unearth data that already exists. That point to that it can be used in a portion of patients and make that freely and publicly available so that it's clear that yes, sir. Alignment is not currently approved for Castleman disease, but it's clearly effective for a portion of patients with Idiopathic multicenter taskel disease. We work with the organizations that set guidelines for particular rare diseases to make sure that drug is on the guidelines. Even if the disease is not on the drugs label, if that drug can be on the guidelines for Castleman Disease, then doctors will look at that and say, oh, maybe I should try Sir Lima for this patient who's not responding to some other therapy.

28:26
Neil Littman (host)
Yeah, that's incredible. I've got to ask, there have been some obstacles for drug repurposing in the past. I mean, it seems like it would be an obvious thing to try these days, but there are systemic barriers that I think have prevented drug companies from doing this on a more systemic level. You mentioned a few of those, but I'm curious why this isn't done more routinely today.

28:52
David Fajgenbaum (guest)
You and me both are curious as to why it's not done more frequently today. All jokes aside, I think I do understand it. I think the three biggest reasons that drugs are not fully utilized for all the diseases they can treat. I think number one is that no one is responsible for making sure that drugs are utilized across diseases. So drug companies are responsible. That might be the right term to figure out the first use or the first few uses for a drug. Because they own the drug, they want to get it approved, and they want to demonstrate it can work in at least a few diseases, but they certainly have no obligation or responsibility to figure out all the uses for that drug. They have the right to choose whatever disease they want to take their drug in. I mean, it's their intellectual property.

29:36
David Fajgenbaum (guest)
They can do with it as they please. Drug companies are not responsible for it. You say, okay, what about the FDA? Well, no, the FDA is not responsible for it. FDA is just responsible for saying yes or no to the diseases that drug company presents to the FDA. If the drug company says, I want to get this drug approved for castleman disease, the FDA says yes or no for Castlemans. The FDA is not responsible for saying, well, have you thought about HLH? It's really similar to Casilla disease. It could probably also benefit from this drug. FDA is not responsible for that. That's outside of their jurisdiction. The NIH is also not responsible for this. NIH is responsible for generating the early insights around what's happening within diseases, how drugs work, but not figuring out all uses for all drugs. No one in the entire medical ecosystem is responsible for making sure the drugs are utilized for all the diseases that they can treat, which I think is a real tragedy, because I can't think about anything that's more important than making sure that drugs in your pharmacy are utilized for every disease and every patient that can benefit from that drug.

30:37
David Fajgenbaum (guest)
Billions of dollars go into every drug getting an approval. Much work and effort goes into making sure that it's available at your pharmacy. I really think we have to make sure that it's utilized for all diseases possible. So one, is no one's responsible. Two, there's no central database that can help to link drugs and diseases. Individual companies, individual organizations like the CDCN and others, we build these data infrastructures to find repurposing opportunities, and we build and basically reinvent the wheel over and over again for our own purposes. There's no central repository that says, what tosulism that might be useful for COVID or seralimus, might be useful for calcium or whatever it may be. There is no central database linking these altogether. Finally, probably the most important one of these is that there's no business case for drug companies to repurpose their drugs for every use possible, particularly when the drug is generic or the diseases are rare.

31:33
David Fajgenbaum (guest)
If the drug is generic, no one is really making any money off selling additional doses of that drug. No one is incentivised to spend tens or hundreds of millions of dollars to prove that it works in another disease if they're going to make sense on a dollar for each additional drug sold. On top of that, it's really expensive to do these trials. So as a result, this doesn't happen. Through every Cure, we've really addressed and trying to target each of these systemic hurdles with coming up with what I think is a really exciting solution.

32:09
Neil Littman (host)
And I couldn't agree more, David. In fact, every cure has won financial backing from the Clinton Global Initiative. Can you talk about how that came about?

32:18
David Fajgenbaum (guest)
Sure. And we're right around election day. I know that people will listen to this post recording. Given that we're around our November midterm elections, I'm sure no one wants to hear anything political right now. We've all had enough politics in our life recently. I will tell you that I got the most incredible call about a year and a half ago, and it was totally unexpected, but it was from President Clinton. He had read Chasing My Cure, and he called, and it was March 31. The reason I mentioned that is because it was the day before April Fool's Day. If you ever get a call from someone with a really strong Arkansas accent and they claim to be President Clinton, if you're like me, you would assume that they're actually not President Clinton if it's the day before April Fool's Day. It was President Clinton, and he had read Chasing My Cure, and it really resonated with him.

33:13
David Fajgenbaum (guest)
More so than anything, what really got his attention was this idea that there were cure sitting on the pharmacy shelf that were not being fully utilized. He thought about all the money that he had directed the NIH to spend on research and the Human Genome Project and all the medical research he supported, whether it's HIV research and all sorts of research over the years. He was really blown away by the idea that even with all this work being done, no one is focused on figuring out all uses for all approved drugs. We chatted for about an hour, and he shared his interest and shared a bunch of stories. We both went to Oxford and both went to Georgetown, and so had some fun memories to reminisce on. Since then, President Clinton has really made it one of his primary focus areas. He calls and checks in with me every couple of months, and members of his team check in with me every couple of weeks.

34:05
David Fajgenbaum (guest)
They have really made it part of their mission to make sure that every cure is supported and that we're connected with the right organizations and the right people to make sure that we can really address this huge systemic problem.

34:19
Neil Littman (host)
I want to jump into some examples around some drugs that your team has identified already. Before I do, I want to circle back to something you mentioned before. Obviously there's a big disincentive from pharmaceutical companies to repurpose generic drugs, just from a financial perspective. I'm curious, as you set up Every Cure, why did you feel like a nonprofit organization was the right structure versus doing this as a for profit entity?

34:51
David Fajgenbaum (guest)
It's a great question. Our reasoning for nonprofit versus for profit? A few reasons. One is that we knew as a nonprofit, we could get a lot of data donated to us by companies, and we found that totally be the case. Many companies, literally dozens of healthcare companies have come to us and said, if you can utilize our data to find new uses for existing drugs, please do so. Medical record data, insurance claims, data pathway databases, the medical literature. It's really amazing. One is that we thought that we would be able to access data for free that would be donated to us, whereas, of course, if you're a company, you have to pay for these data sets and we would have to pay tens of millions of dollars for the kind of data that organizations are donating to us. Second, we realized that the biggest opportunity in medicine, in my opinion, it's the low hanging fruit that no one can make any money off of.

35:43
David Fajgenbaum (guest)
It's got the potential for massive human impact saving patients'lives, but no one can make money off it because it's a rare disease or the drug is generic. We didn't want to be in a position where were going to have to put those opportunities aside, like the literally hundreds of other companies have put those opportunities aside because we wouldn't be able to make a profit off of those opportunities. That's a second reason. The third is that when you are a forprofit company and you own these drugs and you're doing trials to prove they could be utilized in new ways, you have to have those results and these indications approved by the FDA. You can't be a company that does trials and then tells people, hey, you should use my drug. It hasn't been approved by the FDA, but you should use it for this other disease that's illegal, and it costs tens or hundreds of millions of dollars to actually do the work that gets the FDA to give you the thumbs up.

36:39
David Fajgenbaum (guest)
As a nonprofit organization, we can do robust but efficient clinical trials that are much smaller, that can demonstrate the drug works, but are not large enough or so big that the FDA is going to give an approval. We can do that because we don't own the drug and we're not going to make any money off the drug being sold. We can do a trial, we can prove it works, and we can tell people to take it because we're not making any money off of it. This is all combined to say this is the right thing to do now. I think in the future, as we build this data engine, I think there probably will be opportunities to think about spinning out companies that could really accelerate the pace of this. For now, we're really excited about the nonprofit route.

37:20
Neil Littman (host)
David, well, let's jump into a few use cases then. I know your team at Every Cure has already identified drugs for repurposing. Are there a few examples of the work that you and your team have done that you can share?

37:33
David Fajgenbaum (guest)
Sure, absolutely. So a few that stand out. One is with a drug called Pembroizumab. We discovered well, actually, we didn't discover it. We uncovered research from 2013 indicating that this one part of the immune system called PD One and PDL One checkpoint may be important in angio. Sarcoma but it was three years later. It wasn't until 2016 that our center actually did the studies to prove in one particular patient that this was involved and was important. We started treating this patient with Pembrolizumab based on this result. Again, we didn't even have to discover that PD One was important. We just had to uncover it from the medical literature. That's one of my favorite examples, in part because this patient, the first patient ever on it that we treated, has been doing well for over six years when he was given a three month prognosis and told by his doctor that there was no way that anything could work for him.

38:29
David Fajgenbaum (guest)
So I shared that example. It's one of my favorites, but also examples of other rare diseases of disease called HLH, where, again, it's a obvious opportunity where this one part of the immune system called Jack is really activated in HLH, yet that Jack inhibitor drug is not approved for HLH and it's not even used routinely. We've done work, and we plan to focus on doing more work to prove that Jack inhibition is effective in HLH and save lives. Kids with HLH die at a really young age because their immune system basically destroys their whole body. This is an obvious opportunity that we're really excited about. We also recently came across an example of a drug called Amantadine that is a flu drug. Amazingly, patients with Parkinson's disease who got the flu and got Amantadine notice that their Parkinson's symptoms improved while they were on a mandatory well, it turns out when you do the clinical trial, amantadine is actually effective in improving symptoms of Parkinson's disease.

39:32
David Fajgenbaum (guest)
No one would have ever known that if it hadn't been for some patients making that observation and sharing that with their doctors. These are the kinds of examples of both discoveries we've made, but also the kinds of discoveries that are out there to be made that we are really excited to build this data engine and to go after it full speed. I should mention, you mentioned that the Clinton Global Initiative has been supporting this launch, and we are very much in launch mode right now. We announced it at the Clinton Global Initiative event in September. We're currently engaging with potential philanthropic organizations and also individuals who want to donate to build this engine. It's the kind of thing where everyone wants it built, but no one wants to pay to build it. We are eager for the right partners to help us to build out this data engine so that way we can really start saving lives right away.

40:22
Neil Littman (host)
It's just incredible. David and actually, I was going to ask about the funding. Obviously the Clinton Global Initiative has provided some initial funding. Sounds like you're still actively fundraising to pursue everything that you're doing at every cure. If people want to get involved, if people want to donate, if they want to learn more, how can they learn more and get involved?

40:44
David Fajgenbaum (guest)
Sure. You can go to Everycure.org to learn more about what we're doing and everycur.org slash donate if you want to donate to what we're doing. Obviously, I got into this world of rare disease and drug development and repurposing because of my own personal experience with this disease and as you shared, wrote a book about chasing my cure. Really, now this is about chasing our cures and recognizing that I'm not supposed to be here. The drug that's keeping me alive was never supposed to be given to me. It was not in the plans. The question is, how many more drugs can we uncover that are sitting in our neighborhood? Pharmacies. I don't know what drugs or what diseases we're going to uncover. In our first pilot of 147 diseases, we found 106 promising opportunities. There's going to be no shortage of drug disease combinations and opportunities to pursue.

41:38
David Fajgenbaum (guest)
Boy, do we need to create this Santa's workshop. Like I said, I don't know what diseases we're going to uncover drugs for. I don't know what drugs are going to be. They may be a drug for someone that's listening to the podcast right now, or they may be a drug for someone listening to the podcast that you'll never meet but could benefit from it. I just feel this incredible obligation to dedicate however much longer I have on this Earth to trying to unearth as many drugs that are hiding in plain sight as we can.

42:07
Neil Littman (host)
David, let's say fast forward three or five years. How do you measure the success of Every cure?

42:15
David Fajgenbaum (guest)
Number one is the number of patients impacted. It's the number, and it's also the depth of impact. It's figuring out, how many of these drugs did we advance forward and change clinical practice? We may not get that Jack inhibitor approved for HLH, but if we can prove that it works through a well done clinical trial and we can work with the HLH Society to make sure it's recommended, we can get patients on this Jack inhibitor and start saving lives tomorrow as opposed to a decade from now. We're going to be measuring success by the number of drugs that we advanced for that were not being advanced, the number of patients whose lives were saved by our work, and frankly, also by the kind of movement we built here. I mentioned the mission that I'm on, but we're not going to do this alone. We know that we can.

43:04
David Fajgenbaum (guest)
If this was easy, someone else would have done it a long time ago. Somehow medical research for centuries has completely avoided this important opportunity. So we can't do it alone. The number of people that are part of this mission, that are donating to our work, that are donating data to our work, that's going to be an incredible metric that I'm really excited to measure as well.

43:24
Neil Littman (host)
Yeah, David, I think, as I mentioned before, you've inspired so many people, and what you're doing with every cure, I think, is going to have such a huge impact. I'm really excited that you're building this and to see where it goes. So, David, we could probably talk for another couple of days about these topics, but I do want to wrap and be cognizant of your time. As you mentioned in your book, they used to call you the beast. Your physical strength and how much you could bench press with, which, if I remember, it was about £375.

43:56
David Fajgenbaum (guest)
That's right. But he's counting.

43:58
Neil Littman (host)
Yeah. Pretty incredible. Honestly, after everything that you've been through and fought through and the countless people you've inspired along the way and the lives you saved, I've got to say, you're much more of a beast now than you ever were at the height of your physical strength.

44:13
David Fajgenbaum (guest)
Neil, thank you so much. If we had video on and you could see me doing this, you would maybe not say that because I don't look like a beast by any means these days, but I do have to say that I have the most incredible team of people that work with me and have worked with me throughout this. As my book is called Chasing My Cure, but I often say that we made a mistake with what we named it. We should have called it Chasing Our Cures because it's been this incredible collective effort of people in medicine, outside of medicine, people who are in business and have no experience whatsoever in this realm, who have just driven after and chased after treatments for councilmans and now some of the other diseases. Really appreciate you sharing those kind of words, but boy, do I have the most incredible team in the world.

45:01
David Fajgenbaum (guest)
Anyone listening, if you're in healthcare and you want to get involved in some way by sharing data from your company, or if you're outside of health care and want to get involved by donating, please do. We need an army for this. Together as an army, we can just make such an incredible difference.

45:19
Neil Littman (host)
Couldn't agree more. So, David, a huge thank you for joining me on the show today and for everything you're doing. You've had such an incredible journey and you've inspired so many of us. So thank you so much.

45:28
David Fajgenbaum (guest)
Well, thanks so much for helping to raise awareness. This means so much. Neil?

45:34
Speaker 1
Well, Neil, what did you think?

45:35
Neil Littman (host)
I thought that was a really amazing discussion with David. I mean, we covered so much ground and his personal journey and stories are so incredibly inspiring. I think you heard us talk about this initial, maybe naive view that he had about the Santa Claus view of medicine, which I think is a view that many of us probably have, where there's a bunch of people working on specific diseases and trying to come up with new treatments and new therapies. That's just not the reality that we live in. Right? I mean, a lot of this research is very disconnected. People are very siloed, researchers aren't necessarily sharing information. You really heard David talk about why he created the Castleman's Disease Network in the first place was to bring everyone together to collaborate. You hear, you take that one step further. What he's doing at every cure is actually really trying to create this Santa Claus idea of medicine, where you are getting a lot of these collaborations, where people are working to repurpose existing drugs that could have an effect on other diseases that they weren't approved for.

46:44
Neil Littman (host)
I think that was really incredible for me to hear firsthand from David.

46:49
Danny Levine (producer)
How about the case he makes for repurposing?

46:52
Neil Littman (host)
Yeah, I mean, there's a powerful case for repurposing. I don't think anyone would say that repurposing is a bad idea. You heard David outline some of the systemic barriers that repurposing faces, right? There are economic barriers, right? It's hard to make money off of generic drugs. It's very expensive to run randomized controlled clinical trials to get new indications approved for drugs. Just from a purely financial and economic standpoint, there are disincentives. David mentioned a number of other disincentives. I think the approach that Every Cure is taking and you heard me ask the question about why a nonprofit versus for profit entity, and David gave some very good responses. I think the way that they're approaching it makes a ton of sense. I think they are set up to do this in a systematic way with the proper incentives that they could really have a huge impact and really take this idea of repurposing to a whole new level.

47:53
Danny Levine (producer)
What about every cures approach? What do you think of that?

47:58
Neil Littman (host)
I think it's a great approach. You heard how they're working with pharmaceutical companies and others to collect data, and they couldn't have done that as a for profit entity. So these large databases are being donated. That's critical just to have that data to mine to come up with drugs that could potentially be repurposed for new indications. You heard David talk about some very specific examples and that they have already identified over 100 drugs that could be repurposed for new indications. So I think that's hugely important. Taking a step back though, you heard David talk about serial limits, which was sitting on the pharmacy shelf at his neighborhood of pharmacy, which was the drug that saved his own life. Well, it's amazing to think, well, how many other drugs are out there that are sitting on the pharmacy shelves for patients and people just haven't connected the dots, right?

48:55
Neil Littman (host)
I think that is largely what they are trying to do and so I think it could be a really powerful force. I think they're going about it in the right way. Obviously they have financial support from the Clinton Global Initiative, right? I think just from a purely social proof perspective, I think that carries a lot of weight, but that's only one piece of funding out of a very larger pie that needs to be developed. I heard David talk about approaching others for philanthropic investments, individuals. I think this initiative is just getting started and it's going to be costly to get a lot of this done, but I think they're getting started and they're making a big bang so far. Well, until next time, thank you Danny.

49:46
Speaker 1
Thanks for listening. The Biobge podcast is a product of Bioburg Eight, an investment platform that funds visionary entrepreneurs with the aim of transforming healthcare. Bioberg provides access and enables everyone to invest in highly vetted healthcare startups on the cutting edge of innovation from family offices and registered investment advisors to accredited and nonaccredited individuals. To learn more, go Neil bioverge.com this podcast is produced for Biofourge by the Levine Media. Music for this podcast is provided courtesy.

50:25
Neil Littman (host)
The Jonah Levine Collect.

50:27
Speaker 1
All opinions expressed in this podcast by participants are sold in. Their opinions do not reflect the opinion of Biobridging or its affiliate. The participants'opinions are based upon information they consider reliable. Neither BioBridge or its affiliates warranted completeness or accuracy and it should not be relied on. Its nothing contained in accompanying this podcast shall be construed as an offer to sell, a solicitation of an offer to buy, or a recommendation to purchase any six journey by BioBrick, its portfolio companies or any third party past performance is not indicative of future results.