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When Big Pharma Abandoned the Heart | $750m Carduion CSO Dr. Howard Surks
21 Plays19 days ago
Cardiovascular disease remains the world's leading killer, yet cardiovascular drug development has declined dramatically when compared to other therapeutic areas.
Today, we sit down with Dr. Howard Surks, a cardiologist turned bench scientist turned big pharma leader who left Merck and Sanofi to help build Cardurion Pharmaceuticals from the ground up around a first-in-class heart failure drug.
In the episode, Howard's discusses journey from studying blood vessel biology at Tufts to running translational medicine programs at two of the world's largest pharma companies: the real tradeoffs between big pharma and biotech, why cardiovascular trials have become so expensive that most companies walked away. We dig into what it actually takes to move a molecule from the lab into patients, and how decades of basic science research became the foundation for Cardurion's PDE9 inhibitor program.
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Transcript
Introduction of Dr. Howard Sirks
00:00:00
Speaker
Welcome to the Healthcare Theory Podcast. I'm your host, Nikhil Reddy, and every week we interview the entrepreneurs and thought leaders behind the future of healthcare care to see what's gone wrong with our system and how we can fix it.
00:00:15
Speaker
Today we're joined by Dr. Howard Sirks, a physician scientist who's basically done it all in cardiovascular medicine. He started as a researcher at Tufts, then he led trans translational medicine groups at Merck, Sanofi, the largest biopharma firms in the world, and now he's helping build Cardurian Pharmaceuticals, a company that's raised over $100 to a heart failure.
Dr. Sirks' Medical Career Journey
00:00:35
Speaker
And what they basically do is they block an enzyme that breaks in the heart's protective signaling And it's really an interesting story where starting with basic science curiosity has now led to clinical trials that could change outcomes for millions of patients. And we get into all of that, what drew Howard to the heart, why Big Pharma stepped back a little bit from cardiology, and what it's like to bet your career on a single molecule in biotech.
00:01:01
Speaker
Hi, Howard. Thank you so much for coming on to Healthcare Theory. I'm super excited to have you. Thank you. It's really a pleasure to be here. Thank you for inviting me. Of course. And before we get into your background or before we get into what you did today at Cardurion, I want to start off at the beginning of your path.
00:01:16
Speaker
It's cool. You've seen almost every path and worn every hat in cardiovascular medicine. You were a clinician, from my understanding, a bench scientist. Now you're working in drug development at a biotech. So different levels of risk, different levels of science.
00:01:29
Speaker
and how translatable what they are. And I think you also worked in cardiology at Tufts too. So you've seen every lens and I guess that'll sparks the question as to what really drew you here in the first place? Like what drew you to the heart specifically um or opposed to any other organ or even healthcare, why healthcare? But like, yeah, what drew you to cardiology in the first place?
Transition to Cardiology
00:01:47
Speaker
Well, it's it's been a little bit of a a a circumlocuitous path. I would say one thing about the field of medicine is that there are so many different ways to work and so many options that if one is open to ah new ideas and following one's interests, there's just so many interesting things that somebody can do.
00:02:14
Speaker
um And in a sense, my my career has has been kind of emblematic of that. I started off really wanting to take care of patients, and I wanted to go into pediatrics when I first got to medical school.
00:02:31
Speaker
And it wasn't until I had some experience as a third and fourth year student on various clinical rotations that I discovered I really liked adult internal medicine.
00:02:45
Speaker
quite a bit more than pediatrics. um And the one thing that really fascinated me in medical school more than most of the other things, I thought all of it was fascinating, but one area stuck out to me, and that was the elegance of kidney physiology.
00:03:04
Speaker
And um it may not be obvious to to everyone listening, but the way the kidney works is incredibly elegant and complicated. And as a student, I was just transfixed by sort of the beauty of the physiology.
00:03:22
Speaker
And so when I went into my internal medicine training, which was also at Tufts, my initial idea was to be a kidney doctor, a nephrologist.
00:03:33
Speaker
um And then later, when I had some experience um in different disciplines in medicine as an intern and resident, I started to consider other options like cardiology and oncology.
00:03:48
Speaker
um As a student, I wasn't initially very interested in cardiology. It wasn't until I started taking care of patients that um I really started thinking about it as a field to focus on for my career.
00:04:04
Speaker
And the reason for that hit me one day when I was taking care of patient in the CCU, um where I was sitting there looking at all of the patient's ECGs and trying to puzzle them out and and um and um apply them to what I was seeing in terms of what was happening to the patient.
00:04:28
Speaker
And someone next to me said, you're going to be a cardiologist, aren't you? And I said, why do you say that? And they said, well, you really seem to like it. And it just hit me. You know, I really do like this.
00:04:41
Speaker
um And part of the reason is is cardiology
From Research to Pharma
00:04:46
Speaker
was an area where um there was lots of interesting ah medicines that help patients, but they were also really transformative interventions where you could treat someone who is actively having a heart attack and change the course of that problem.
00:05:07
Speaker
You know, if you got to them quickly enough and were able to do what's called a cardiac catheterization and identify a blockage and relieve the blockage, you could stop a heart attack.
00:05:20
Speaker
um And that that didn't exist a number of decades ago. it used to be heart attacks were considered like a bolt of lightning and it just happened or it didn't.
00:05:32
Speaker
Now we know um ah that it is something that occurs over a period of time and we can intervene and and ameliorate it And so, and there were a lot of examples like that in cardiology.
00:05:46
Speaker
And I think that is ultimately what drew me um into cardiology. and i I was very deliberate about choosing a subspecialty like cardiology um because a lot of things interested me in in medicine.
00:06:04
Speaker
um And I took some extra time to really think about it and then applied for fellowships and included some research in my cardiology fellowship. So I could also learn a little bit more of what that was like.
00:06:19
Speaker
And that was also an interesting decision because it ultimately led me to become um more research focused. Yeah, and I think that would be a great time to bridge into that. I mean, first of all, it's cool to see how your career has transitioned so much. A good thing about healthcare, and especially life sciences broadly, is that no matter what your interest is, there's some way to tackle it. And healthcare, there's something for everybody, um to some extent, which is great.
00:06:45
Speaker
But um I would be curious, mean, cardiology, I think as an industry, or or maybe a discipline, it was very reactive for decades, I would say. And then like now it's getting more proactive. You catheterization, other interventions that you maybe can track beforehand. But when you were at Tufts, I mean, you're working as a doctor and and then you're also doing research too. um What was that like? And what were the kind of the research questions that were driving your time as researcher? What were you trying to understand and explore while you're still in academia?
00:07:15
Speaker
um So it was a wonderful opportunity. um I was very lucky during my cardiology training. um I started working with an investigator at Tufts named Michael Mendelson, who was already established cardiovascular basic scientist and cardiologist.
00:07:39
Speaker
And he had a lab that was working on really projects to better understand blood vessel function. And blood vessel blood vessel function is very important because the blood vessels dilate and constrict um and that regulates ah blood pressure.
00:08:00
Speaker
It regulates you know how much blood different tissues receive. um And it when things go awry in how blood vessels are regulated, um that can lead to to diseases like hypertension and atherosclerosis and lead to heart attacks.
00:08:20
Speaker
um And Dr. Mendelson's laboratory was really focused on understanding the basic molecular mechanisms within the blood vessel wall that controlled how the blood vessel constricted or dilated.
00:08:36
Speaker
And I became very involved in that over time, initially as a fellow. And then um Dr. Mendelson helped me to write my first grant application to the National Institutes of Health.
00:08:51
Speaker
ah to get a little bit of funding to help me to come back to the lab after my training as a junior investigator. And so that's the way i I started my career is working on with taking care of cardiology patients in the hospital part time and working in the laboratory part time.
Role in Merck and Sanofi
00:09:15
Speaker
And that is really a increasingly difficult but wonderful, ah wonderful thing to be able to do.
00:09:26
Speaker
And I really feel privileged to have been able to do it. You know, the government and thus the taxpayers, you know, helped fund my work, ah paid part of my salary and my supplies in the laboratory to do basic experiments to try to understand these basic functions of the cardiovascular system.
00:09:52
Speaker
um So I would go see patients who had high blood pressure or heart attacks and things like that. And then I would go to the lab and try to understand some of the basic mechanisms that were underlying those problems.
00:10:06
Speaker
Uh-huh. And I think that it's it's interesting to me because a lot of people, when they think of biotechnology as an industry, they think of, you know, your big pharma companies like Merck and Sanofi, J&J. And I think they're it's easy to get the conceptualization that the science just comes out of some molecule they discover. But a lot that's built off of basic science that might have been going on for 50 years leading up to it. There needs to be some like intrinsic biological just biological discovery to set the way for biotechnology. some molecule or mechanism to be used.
00:10:34
Speaker
And I find that really interesting. So, I mean, at Tufts, I'm sure with Dr. Mendelsohn doing really incredible research and also can practice too. But at around that time, um i mean, you had an NIH-funded lab, which is already a good accomplishment in itself. But um eventually you left to join Merck. And I would love to hear about that now. I mean,
00:10:53
Speaker
The timing is interesting to me because there was already a pretty big um toolkit for heart failure. There beta blockers, um ACE inhibitors, ARBs. There was a lot of good drugs, but i mean at the time, it was it was difficult, especially compared to the discoveries that there were in oncology.
00:11:09
Speaker
I would say cardiovascular R&D was a little bit... um earlier in its kind of discovery. So you walked into that environment. What drove that interest into working for a pharma company? What was your kind of your role there? And how did that maybe change the way you think about cardiology at the time?
00:11:25
Speaker
Yeah, it's great questions. And I'd like to say that I had a really well thought out plan for how and why i would move to industry, but I really did.
00:11:36
Speaker
It only connects looking backwards. Yeah. ah I do think that in the academic setting, there was a pretty large disconnect between what I was doing in the laboratory and how to deliver some of that knowledge and discovery into something that would help patients.
00:11:58
Speaker
um I was really focused on very basic mechanisms, and I didn't understand as a physician scientists in academia, how that could be translated into a therapeutic.
00:12:15
Speaker
and I really needed to go to ah big pharma and drug development to begin to understand that. And um my work in the academic setting was a really ideal training ground of basic principles that helped me when I moved to big pharma and then now to biotech um to have the appropriate perspectives of both what it takes to do the science and what it takes to deliver something meaningful to patients.
00:12:49
Speaker
um So at at the time, um my move was um was really serendipitous in that I had occasionally gotten calls from people who were searching for physician scientists to work in big pharma and decided almost ah on a whim to answer one of them and go to a big pharma company and see what it was like. And I was pretty astonished, to be honest. I mean, I was used to relatively modest resources and being sort of understaffed and um and also having a relatively small enterprise. You know, it was me and the graduate students and postdocs who were and technicians who I was able to hire to help me. But I was always sort of the person who tied it all together.
00:13:48
Speaker
And I was really surprised when I got to Big Pharma that it worked in a such a different manner. um In Big Pharma, the resources were just staggering.
00:14:00
Speaker
I couldn't believe all of the research that was going on and the breadth was just stunning. And I also understood that people and in pharmaceutical drug development really work as teams, almost like teams of, really teams of equals, where everybody on the team brings a particular expertise to the project.
00:14:23
Speaker
And you really, you know, ah if not literally, figuratively sit around the table and do the work together. Uh-huh. And I love that idea. And um when I came back from that visit to a big pharma company, it stuck with me that that would be something really interesting to do. And then um when I learned that from a neighbor who worked at Merck that they were looking for physician scientists to work in their cardiovascular therapeutic area, I applied for the role and and moved there.
00:15:00
Speaker
And, um you know, it's, you know, what I would say for anyone in that position who is considering um moving to into drug development in either a big pharmaceutical company or a biotech. um It's a fascinating experience, and it's so different from working in the academic setting because it is literally um learning multiple new things at the same time.
00:15:31
Speaker
One of them is the setting of working in a huge company. or in in biotech a company and working in a corporate setting as opposed to a university setting is a big change and there's a lot to learn.
00:15:45
Speaker
And second is just the the science and regulation around drug development um and how different questions are tackled um how clinical trials are set up, um how everything is regulated. It's really an extremely highly regulated industry and learning about that is crucial to functioning in that role.
00:16:15
Speaker
And so I found it both a little disorienting and also invigorating at the same time, invigorating in that it was all new and it was very exciting to be exposed to something new. But also, um you know, there was there's the expression drinking from a
Challenges in Drug Development
00:16:34
Speaker
fire hose. And that really is apt for that transition, that it's going to be a period of, you know, three to six months where things don't make a lot of sense. And then all of a sudden, OK, I think I get the hang of this.
00:16:48
Speaker
Yeah. I definitely, it makes a lot of sense. It's, there's a trade-off in every job, which is my opinion. I think that early stage, it's nice because you get to answer your own questions. I mean, no one's exactly telling mean, there's always some, you always have to answer to somebody to some extent, but you get to answer your own questions. You get to lead a team.
00:17:06
Speaker
um You have more command, of course, of how your equipment's used, but in pharma, you get to see more things and you have access to so much. um But the issue is there's maybe some elemental process and regular things matter more. It's later stage. You can't exactly just set out and change your mind and do something new week after week. And I think that there is some really interesting trade-offs there. on And people should try to do both. But at Sanofi, I mean, you moved into an even broader role there. i mean you're head of transitional medicine, working more in clinical pharmacology. And I'd love to hear... i mean, your mandate expanded beyond the heart, from my understanding. So I'd love to hear from that area specifically.
00:17:42
Speaker
um It's a much wider aperture. I mean, the cardiovascular area is already huge and um so many different like frameworks and things came out of that time. But what did that look like working across like multiple therapeutic areas? And what was your actual role like day to day? Like, what were you kind of doing in and out? Like, were you more leading? Were you still doing the basic science? And how did that look like? If you could put me through the shoes of your time at Snuffy, it'd be really interesting to hear um what that was like. You know, it it's it started with my really focusing on the period that is oftentimes in the industry called translational medicine.
00:18:18
Speaker
which is a really crucial um juncture between a new therapy being strictly in the laboratory space, so not yet being tested in people,
00:18:34
Speaker
and then getting all the data and information together, both about safety, both in vitro and in vivo, and efficacy, and how the molecule or the therapeutic performs and all its parameters.
00:18:53
Speaker
Putting together a data package, to submit to health authorities to get permission to and begin to study that therapy in the very first time in human beings and running those exquisitely highly monitored clinical trials in humans ah to get that first bit of safety information that it's OK to treat humans with this ah this new approach and to get any initial signs of
00:19:29
Speaker
um how the molecule or the therapeutic is behaving in humans. That juncture is is what I refer to as translational medicine. And although I started at Merck in late clinical development, designing a big phase three trial,
00:19:47
Speaker
when I had the opportunity to move into translational medicine at Merck and then further at Sanofi, I realized that for me it was really a sweet spot because all the the years I spent in the lab at the bench gave me a very um crystal clear understanding of the science that was needed to develop that data package that would allow us to move a therapy into human clinical development.
00:20:20
Speaker
um And so Once I learned what ah experiments were necessary, i just had a clear understanding of what those experiments were, how they were conducted. All of that made sense to me based on my prior experience.
00:20:37
Speaker
And then my clinical experience helped me to understand um how to approach the initial studies in humans. And to me, that was more of it was just more aligned with the way I was used to thinking and like to think from the research lab.
00:20:57
Speaker
And it pulled together the really basic science and the clinical science into one one discipline, which I just found ah tremendous amount of fun, because really ah in that discipline, what one needs to do with a new therapy is think okay, once I administer this to humans, how am I going to be able to detect how much of it gets i gets to the tissue that we are treating?
00:21:28
Speaker
um How are we gonna determine the and whether there's any evidence that it's having an effect? Do we have ways of doing that or do we need to invent them? Because if we do need to invent them, then we got we have to get started years before that therapy gets into into humans.
00:21:48
Speaker
So we need to develop that toolbox ah to be able to understand how a new therapy is working in people. And that's part of the translational medicine approach.
00:22:00
Speaker
Thinking about what's going to be done in the clinic and how we're going to learn things and prepare for that and then do it. um So I really love that. And i found that, you know, when I joined industry in cardiovascular medicine, it was a time when many companies were doing less cardiovascular drug development.
00:22:24
Speaker
And the reason for that was some of the things that you mentioned earlier, that there were some pretty good drugs available. You mentioned for heart failure ACE inhibitors and ARBs and beta blockers.
00:22:38
Speaker
We also had treatments for heart attacks. And so that meant that, you know, great things had huge leaps of huge advances had occurred in therapy.
00:22:49
Speaker
And that meant the risk to any given person was lower. But because these diseases are so common, it is still a huge burden on a population level.
00:23:04
Speaker
But to show evidence of efficacy in a population that has lower event rates because there are already good therapies requires larger and larger clinical trials. so when the whereas the heart first heart failure trials or lipid lowering trials may have only needed 1,000 2,000 patients, now they need patients to show a benefit.
00:23:33
Speaker
And that made it too expensive for pharma to continue, for a lot of pharma companies to continue. So a lot of companies, including Merck and Sanofi, when I was there, were downsizing their cardiovascular drug development. And I decided I liked that translational space so much that I was happy to become more of a translational medicine generalist.
Industry Trends and Innovations
00:24:02
Speaker
and So not just to work on cardiology ah therapies, but also maybe some immunology, maybe some neurology, maybe some things in rare diseases, because even though I wasn't expert in the those diseases, I could learn about them pretty quickly.
00:24:23
Speaker
um And I could get a sense of what scientifically we needed to do to move again that same question. How do we move this potential therapeutic from the laboratory into the human?
00:24:38
Speaker
And I could apply that to across various disciplines. And that was a lot of fun. you It kind of stretches one's one's brain a little bit to be learning about, and it's all interesting, you know to be learning about you know latest issues in treating multiple sclerosis or in treating you know systemic systemic lupus or other rheumatological diseases.
00:25:06
Speaker
um And then, you know, think about, you know, if there's a potentially interesting new approach to treat it, again, how to study that in patients and what tools do we need?
00:25:19
Speaker
What do we need to develop? There's it's I've never really met someone who likes science and does this type of role and and finds it boring. um There's always so much to be learning, I feel like. And I think if someone isn't liking it, they maybe just don't like science as much as they would expect. But um there's always new mechanisms and new indications and new ideas.
00:25:42
Speaker
molecules. I think it's interesting because it's yet learning never stops in some ways. um You're always a student in this industry. lifelong process. I mean, it's a great career, honestly, because if you like the science and you like helping people,
00:25:57
Speaker
There's few things I can think of that could possibly be better to do. And you're right. You spend your whole life learning new things. When I, you know, I always get email alerts with latest journals and their table of contents and I skim through them and I don't skip things because they're not interesting. I just, I skip things because I have to prioritize. Yeah. you know, it's all interesting. Yeah. Yeah.
00:26:25
Speaker
Yeah, if we had infinite time, I'm sure you could read like every Nature article they sent you. But I mean, like there's there's so much going on. um so I mean, as a generalist, that's both a good thing, but also a burden, I can imagine that you're you're learning a lot. But also that means that it's hard to be an expert in rare diseases and then also oncology and cardiology at the same time. It's like functionally impossible, but I do think cardiology, i find what you say really interesting. i didn't I didn't know that. And I think that I knew there's a huge systemic burden. I mean, six six and a half million people every year, and a half million people have a heart disease. Many are hospitalized every year, which is, yes, like hard to solve, but it's a huge burden on our health system, um hospitals, and and also just deaths. It's one of the light leading causes of death. So we have this macro issue and kind of this other area where it's
00:27:15
Speaker
It's not really that pharma companies don't want to help or it's not that cardiology is not a big issue. It's that the incentives and the financial incentives aren't really there given like how the clinical trial system works.
00:27:26
Speaker
And before we get into Cardirion with Dr. Mendelson, I would love to get like what really changed about the industry or what maybe, maybe nothing changed, but um how was the industry at the time in cardiology in 2017 before you joined? Can you set the stage for what that looked like?
00:27:42
Speaker
What were you looking at? like What was kind of the FDA looking for? What was needed in the industry in terms of new molecules? If you could set the ground layer before we get into what you did today, that would be really interesting.
00:27:55
Speaker
um So I would say that um the things are are always shifting in the industry. I think we the industry is always looking for ways to work more efficiently um and to discover new therapeutic targets that have high probability or higher probability to become therapies.
00:28:24
Speaker
um You mentioned earlier that, you know, a lot of the basic science that's done in academia, you know, eventually leads to drugs. It's just an indirect and circumlocuitous path to get there.
00:28:39
Speaker
But a lot of what happens in industry is um is really sort of standing on the shoulders of basic science. And there's been a lot of basic science that has been transformational two industry So, for example, being able to sequence the human genome easily ah to get, you know, to do whole exome sequencing from cells from patients with different diseases and get a sense going
00:29:11
Speaker
what transcripts are upregulated and what proteins are more important in certain disease states that, you know, that all could be subject to potential new therapeutics.
00:29:24
Speaker
um It's revolutionized the way really basic drug discovery target identification and validation um has um has been done in the last 10 or 15 years.
00:29:41
Speaker
It was unthinkable when I joined industry that you know we could easily take you know cells or tissues from 50 patients and sequence their whole exome.
00:29:55
Speaker
I mean, that that's that would that was crazy. yeah And now it's typical. um and And so it's a tremendous amount of power.
00:30:06
Speaker
um And I think industry has been also looking for ways to do more targeted indications for drug development. So we've seen a lot of this in cardiology.
00:30:19
Speaker
instead of having to do what we're trying to do, which is develop medicines that treat millions of patients and they're going to require very large trials to show benefit, a lot of companies look at more targeted therapies that are addressing smaller subgroups of, you know, very specific types of heart failure, for example, that are caused by genetic mutations, where a therapy might target just ah a small subset of heart failure, but a company can get it
00:30:54
Speaker
to market faster. um And we're also starting to see, um you know, gene gene therapy it also has had a a bit of a um a um tortured path to getting to the clinic.
00:31:15
Speaker
um We saw it start in the 1990s and there were some um there there were some unfortunate um toxicities that emerged and people felt for a long time it wasn't safe.
00:31:31
Speaker
um And then we've seen better and better ways of targeting a gene therapy more specifically to the tissue that needs to be treated and less toxicity. And now it is there are gene therapies on the market for diseases in the past that were untreatable.
Cardurion’s Cardiovascular Approach
00:31:52
Speaker
Um, and now we are beginning to see that happen with gene editing, uh, as well, which is to either take, you know, a patient's cells outside their body and edit the genes and those cells to work a different way and then put them back in the patient or to deliver the machinery to edit the gene to, into the patient where the, that machinery would go to the right cell, edit the genome and,
00:32:21
Speaker
um change a malfunctioning protein to a properly functioning protein or affect a change that will affect that will have a better outcome in and the future.
00:32:32
Speaker
So I think how prevalent gene editing will become, ah we'll see. um There is, you know, I think still some residual concern about the precision of gene editing and potential for long-term toxicities, but that that information will accrue over the next decade and we'll get a better understanding of whether this becomes a common approach.
00:33:01
Speaker
um And even, you know, pay tailoring gene editing and gene therapies to very patient-specific problems where a therapeutic could be developed very quickly and delivered to a specific patient. So personalized medicine reg gene editing could be something considered in the future.
00:33:23
Speaker
um We're seeing changes at the FDA where they are you know now considering you know more rapid approval processes for you know diseases that have very, very high um unmet medical need where, you know, they're they're life threatening or severely debilitating diseases and there's no real way to treat them. And if someone has a promising if a company has a promising product um that if there's evidence of good safety and some preliminary evidence of efficacy, that it it could start to be marketed in a limited way until more evidence is generated.
00:34:11
Speaker
um I think that's a ah positive if it's done really well and carefully. um And we'll see how that plays out um as things go forward. But I know I think regulatory policy is also affecting how things ah how how the field of drug development is is moving forward.
00:34:34
Speaker
Yeah, I think so there's all those different trends going on. I think that precision medicine is really interesting. It ties back to something you said earlier where you said that um where there's one way that you can tackle the whole of disease you can tackle the subset of the disease. And I think that what you're realizing in so many different areas, and I'm assuming cardology cardiology too, is that there might be a thing called heart disease, but the biological basis of it is different. And really, ideally, we'd get more specific subtypes. And I'm sure we already have that. But um to get a personalized level or a very small population level because they really all take on these like niche forums that kind of maybe at a phenotype level look similar, but um they're all quite different. So i want to get into Cardurion now.
00:35:16
Speaker
um I understand that I didn't know Dr. Mendelsohn was your advisor or worked you worked with him at Tufts, but that's um really cool to see. You joined him there. And we'd love to hear a bit more about that from, I guess, my understanding of the science the heart makes protective hormones and um there's an enzyme that breaks that down and this idea of upregulation where the body produces more of an enzyme that destroys a protective signal so the body's kind of doing a weird thing that it does where it kind of hurts itself we see that a lot but what's most interesting to me here is what
00:35:47
Speaker
it's It's a new way of tackling this issue, which is good because you're the first to get there. um You will have lot. It'll be probably better for approval, get patents and everything. But there's also no one ahead of you, no one to really validate the target, no research there. So kind of two questions.
00:36:05
Speaker
First, at the basic level, like what does the science look like? How would you describe it to someone? at a an easy to understand level? And then what gave you conviction that you're taking a lot more of a career risk here?
00:36:17
Speaker
Obviously, you can go back any time, but like the molecule is integral to how the success of the company does. Well, it's Sanofi and Merck. There's many other things going on. So one, like, how does the drug work and what gave you conviction and that as a target? What made you so confident that this is something that you want to embark on?
00:36:35
Speaker
Yeah, great lots of great questions in there. um So um first, I think maybe the big pharma versus the small pharma, which I think was your implicit in your sort of question about taking some risk about going into a really small company that is where you have a couple of ideas and programs. And if they don't work, you know, the company could fold.
00:37:00
Speaker
um that's That's a real risk. Whereas if you're in a big pharmaceutical company like a Merck or a Sanofi, there's a lot of staying power and there's many, many, many shots on goal at the company. So it's a more, you know, not completely stable, but it's a much more stable um job, to to be honest.
00:37:23
Speaker
um And I think, honestly, i like them both. there's There's pros and cons. I loved working and in big pharma because um I love the breadth of the science, so many different interesting programs.
00:37:40
Speaker
And I also loved the people. i mean, really, to be around so many dedicated, motivated, and nice people who genuinely wanted to help patients by making new medicines and all brought you know they're their expertise to the table.
00:38:01
Speaker
um and There's so much expertise around the table. so I love that. I could walk walk down the hall and talk to someone who's an expert on something and learn what I needed to know.
00:38:13
Speaker
Um, is small companies, you know, it's, it's a much is, is there biotech companies are a lot of fun in their own, in their own way. Things are scrappier. You're building it.
00:38:26
Speaker
Um, you're building it up from, from the bottom, you know, from very little. Um, I have to credit, you know, my research mentor and the Carderian founder, Mike Mendelson for having the vision ah to create this company that's really focused on ideas that he had back in his laboratory days that these that, you know, ah understanding what we did from the bench research and how the heart and blood vessels worked.
00:39:01
Speaker
He and now since in and i you know and I fall into this category as well under his leadership, of course, had it sort of an understanding that these were targets that really made sense ah based on the basic cardiovascular biology to to drug, to treat disease.
00:39:24
Speaker
And the evidence was accruing. you know In the time since we left Tufts, until the founding of Cardurian, there was evidence that one of the one of the signal transduction pathways we studied in the lab, if you intervened with a medicine in animal models, ah you could ameliorate heart failure.
00:39:48
Speaker
and And that was the cyclic GMP signaling pathway in the heart and um the enzyme in the heart that we are inhibiting with our lead molecule.
00:40:01
Speaker
P.D.E. nine um is a molecule that dampens down a beneficial signaling pathway in the heart. So if we it's like a break on a beneficial effect in the myocardium. So if we could relieve that break, we could potentially accelerate ah heart benefit.
00:40:28
Speaker
and And that's what we sought to do. I mean, that this was evidence that came from basic science. A colleague from our academic days published this in a very high profile ah paper. was a very careful experiment. And we said, this is something we should try.
00:40:48
Speaker
So when Mike started Cardurian, he tested various inhibitors of PD-9 in the animal models, recapitulated the beneficial data, said, yeah, this this works in this model.
00:41:05
Speaker
extended it to show that it works even with other medicines, that it still works well, said, you know, we've got to get one of these. We've we've got to either acquire one or make one that we can start to test in people because this could help patients with heart failure.
00:41:24
Speaker
And that's what we're doing. you know It's been five and a half years since I joined, but Mike had had kicked this off before I joined. But we've moved this from studying um healthy volunteers to understand how the molecule works to initial small experiments in patients with heart failure to make sure it's safe.
00:41:50
Speaker
And then once we were assured more larger patients, groups of patients to see if that pathway was actually moved in the right direction And now larger experiment larger studies, clinical trials in phase two drug development to see if some of the biomarkers in the body that um indicate if the heart is functioning better ah are affected but in a positive way by this drug. And we're just...
00:42:27
Speaker
getting that information now, which will be really pivotal for whether the program goes to the final step, which is testing it in thousands of patients with heart failure to see if it if if if it ameliorates the problems you mentioned at the beginning of our talk, like the frequent hospitalizations, the the continued mortality risk.
00:42:55
Speaker
even on multiple medicines that have been transformational in heart failure that reduce risk. As you said, there's still a much higher than normal risk of dying um that patients with heart failure have to bear.
00:43:12
Speaker
And we hope to continue to move that needle down and reduce the risk of mortality and worsening heart failure leading to hospitalizations as far as we can possibly go.
00:43:28
Speaker
Because this is a disease where risk has been reduced, but because it is so common, even with a reduced per patient risk, it's still over so many millions of patients, it adds up to a huge burden on the population.
Future of Cardiology and Closing Remarks
00:43:47
Speaker
Yeah, I love to hear how like it's so cool how the translational science and simple discovery or many discoveries accumulated into what you guys are doing today. And it's hard to describe it as a startup anymore.
00:43:58
Speaker
um Now you guys have a PD, nine, like CRD, 4730, like a lot of and a couple of other assets, too, um and hundreds of millions are raised. And so it's really exciting to see where that goes.
00:44:09
Speaker
And a quick last question, a 30 second question. um I mean, what keeps you up at night in this industry, whether it's for better for worse? about cardiology is something that excites you or worries you in the future?
00:44:20
Speaker
What keeps you up and out in terms of where the things might change for better for us in the future? Well, a lot of things keep me up at night, whether I'm excited about because I'm excited or I'm worried. um Yeah. and And I think ah that that is you know, in a way, you know, sort of part of the fun um is to not know how things are going to work. But, you know, you have to do the experiment to find out.
00:44:52
Speaker
um And um but I think more existentially for the field, it's really um How are we going to continue um to make improvements um and try to continue to develop, try to bring to people more medicines that favorably impact their lives when the cost of doing these things is so high?
00:45:25
Speaker
And we haven't talked a lot about that in in the past half hour. But all of the things I've talked about that we're doing in Carderian, you mentioned the money we've had to raise and we're so grateful to our investors for um supporting us.
00:45:41
Speaker
But the money that's required to do the human clinical trials is enormous. um And, you know, we don't make any money because we don't have any approved drugs. So from business perspective, that's not much of a business. You know, we yeah we have to get to the place where we deliver medicines that help people and then make some money for the company that the company can put back into making more medicines. And that's ultimately how it works. But it's very expensive.
00:46:11
Speaker
And I worry that. the The economy and the cost of medical care and the budgets in you know him in the organizations like the and NIH that fund the basic science can't sustain this forever.
00:46:31
Speaker
And how are we going to learn to do these things and innovate to do them less expensively? Will artificial intelligence help? Obviously, that's being incorporated everywhere in drug development to try to make things more efficient.
00:46:46
Speaker
um Maybe the accelerated regulatory pathways, how to do clinical trials more efficiently and less expensively. There's so so many areas, but but that is sort of an existential question that does keep me up at night. Yeah. about The path of drug development in general.
00:47:05
Speaker
Yeah, there's so many different ways to answer that question, but just so hard to fix it in a lot of ways. But I really appreciate you coming on. There's so much going on in this one space. And to see how working as a bench scientist, translational scientist now in biotech, all those band together kind of fit into one viewpoint. It is really interesting. But yeah, thank you for coming on. It's just really great to talk to you and hear more about your experience at Cardurion. But yeah, thanks again.
00:47:31
Speaker
Well, it was really a pleasure. I appreciate you inviting me.
00:47:36
Speaker
Thanks for listening to The Healthcare Theory. Every Tuesday, expect a new episode on the platform of your choice. You can find us on Spotify, Apple Music, YouTube, any streaming platform you can imagine.
00:47:48
Speaker
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00:48:01
Speaker
Repeat, thehealthcaretheory.org. Again, i appreciate you tuning in and I hope to see you again soon.