John Simboli
Today I'm speaking with Joan Perelló, CEO and co-founder of Sanafit, headquartered in Palma, Spain with offices in San Diego. Welcome to BioBoss, Joan.
Joan Perelló
Hey, John, thanks for inviting me.
John Simboli
What led you to your role as co-founder and CEO at Sanafit?
Joan Perelló
Well, first, I was doing some research as part of an academic group at the university. And during those years, during my Ph.D. work, you do research, we made some discoveries, hopefully. I was part of a group that had already filed some patents in the past and I was part of some of these filings. And then, one day, one of my colleagues just saw, this is quite a funny story, that there was an innovation contest here in our country, in Spain. And we decided to present a business plan to that contest. It was not specific for life sciences or biotech, it was any sector. And as you can imagine, in Spain, and even more in the Balearic Islands, there was a lot related to the touristic industry. But we just did our thing. And we won the first prize in that contest. There was some funding associated with that prize, but you couldn't claim the money unless you were registering your company. So, you know, Bernat, who is the other co-founder at Sanifit, and myself, had to create a company just to get our prize. And, you know, then we started all these adventures.
John Simboli
So that sounds like it was not, necessarily, something that you were planning from college on, forward, but this was something that evolved.
Joan Perelló
When I started at university, I was thinking more like a traditional academic career, doing my Ph.D. and going abroad, have some experience, and then go back to the university and have my position in there, which is okay, it's something that I have done, I'm teaching at the University, have been teaching for the last 15 years there. But, you know, starting Sanifit just gave me the opportunity to see another part of the research. We had been doing research for a while in kidney stones. For a number of reasons, kidney stones was not the ideal area to start doing work preclinical, and then clinical development, and started diversifying the research and looking at other therapeutic areas. And that was the origin of Sanifit. I cannot imagine having done all this type of research that we have done here as a company from the university.
John Simboli
Was there a point at which you said, this is interesting research, these are interesting data, I think I'll find a large or large-ish, biopharma company and take it to them and become part of that, as opposed to starting something yourself?
Joan Perelló
No, because our story started in the way I described. We were really young by then, because I was like, 25, when we started the company, so we were not even thinking of, you know, let's bring this technology and license out to a pharma. No, we just did our own thing. But where we needed to spend quite some time was in finding the right opportunity. Because at the beginning, you have a technology, you have an idea, you have a mechanism of action, but you need to find the right place to prove that this works. In our case, it was about calcification, and as I said, we were looking at kidney stones at the beginning, but that was complex for multiple reasons. But then we discovered that there is this group of patients on dialysis who's offered this massive problem of calcification in the arteries, and we started digging into that population. And so that actually, there is a huge unmet medical need, there was a lot of benefit that could be given to those patients. And we started our development.
John Simboli
A moment ago, you were saying one of the most challenging things was to find the right starting point, the right gateway, I don't know exactly the word that you used, but can you tell me a little bit more about that.
Joan Perelló
The way I'd like to describe this is there are two types of calcium in the body. You have soluble calcium, for example, the one that's circulating in your blood and you have solid calcium. And then you have two types of solid calcium, the physiological and healthy one, the one that's building your bones and your teeth, and the pathological one, which is any other form of solid calcium. Wherever you can find solid calcium in the body, other than in bones and teeth, it's always because there is a disease. And people have not studied a lot, the problem of calcification disorders, because this is not the natural thing. You would expect that when companies look at target receptors, you think of a protein, an enzyme, a membrane receptor, but it's always if you think of the structure, an organic thing. So our target, our receptor is an inorganic thing. It's an inorganic stone, a three-dimensional structure that grows in your body, in your joints, in your arteries in your, in your heart, in other organs. And how do you really target that?
So this is what our technology was about, about targeting this type of inorganic target, something that had not been studied before in the field of medicine. I am a chemist, by the way, I'm a chemist by background. So the chemists had been studying how to address the problem of crystallization, since the 60s, in the last century. So you know, from the chemistry point of view, this is old science, we knew how to manage crystals since 60 years ago. So what we have done at Sanafit is just bring that knowledge from the field of chemistry, apply it to the field of medicine, and find the right target patient population. We have identified and of course, that was not at the beginning, because we have learned more and more over time, but there are 30 to 55 diseases that are connected to or linked to pathological calcification. When the problem affects the cardiovascular system, it leads to increased morbidity and mortality because of cardiovascular complications. And when you have renal insufficiency associated with that, the problem is just more severe and more prevalent. And that was our first, I would say, important decision, targeting these patients with renal insufficiency. But although many people see Sanifit as a renal company, we're not; we're a cardiovascular company, because we're treating cardiovascular conditions. So call it cardio-renal, whatever you want. But strictly speaking, we're not a renal company.
John Simboli
When you're talking with investors, which I presume, is frequently either one on one or investor conferences. I know that it's largely, if not completely virtual at this point. When you tell that story you just told to me and make that distinction between the renal and the cardiovascular, do people get it? And do they want to pigeonhole you? And if they do, how do you help them get out of that?
Joan Perelló
I think there has been not been confusion, but it's something that puts you in a certain bucket. And for us, it has been important, because it's not exactly to your to your question, but innovation in the field of renal diseases, and more specifically in dialysis, has been suffering a lot over the past 10 years, because there is this system of reimbursement of drugs in the renal space through a bundled payment system that, has been affecting, dramatically, innovation. So, people tend to say, oh, you're a renal dialysis company bundle. No, we're not; we're talking about cardiovascular indications. Imagine, this is like, if you're giving a statin to a patient on dialysis because that patient has hypercholesterolemia. Is that the statin for a renal disease? No, of course, it's not, it's for a cardiovascular disease, it just happened to be in a renal patient. So in our case, it's the same. But maybe it helps to create this perception. The fact that as SNF-472, which is our lead product, is not highly bioavailable when given orally, it has to be injected. And for convenience, we have started with patients on dialysis. Because if you think of that patient population, probably because they are, unfortunately, a captive population, they have to go to the dialysis unit three times per week, sit there for four hours while the blood is purified, and so on. This is the perfect population to give them chronic intravenous administration. So if you wanted to do that in other patient populations, maybe that would be challenging. So you were asking about this perception with investors, some of that it's, it's related to this to these aspects
John Simboli
Do investors ask you the question about how widespread the target populations are? Do they talk about whether it's rare, whether it's ultra-rare or whether it's not rare? How do you answer that question?
Joan Perelló
We have orphan drug designation for the two indications we're pursuing. So at this point, it's patients on dialysis. One disease, it's called calciphylaxis. Calciphylaxis is the most severe and devastating form of vascular calcification. It happens in patients on dialysis and without dialysis, with or without renal insufficiency. It's more prevalent in dialysis. But we have the orphan drug designation, specifically for dialysis patients. And the second indication it's in peripheral arterial disease, which is also something that happens in the general population with or without renal disease. But again, the problem is more severe and more prevalent in patients on dialysis, because of these components that we have, in the case of renal insufficiency of calcification in the arteries, that's more severe in these patients on dialysis. So we just got also the orphan status from the FDA in patients on dialysis. So, how widespread are these diseases? They affect the number of patients but in these sub-segments, where we have the orphan status actually, it's like, you know, 10,000 patients calciphylaxis, 5000 in the US., another 5000 in Europe, and for peripheral arterial disease, which affects one-third of the patients on dialysis, which is like 150,000-170 5000 on both sides of the of the Atlantic. So on the very high end of the orphan range.
John Simboli
What what's new at Sanafit?
Joan Perelló
Well, we have one living asset, SNF472, for two indications one, phase three ongoing, another program phase three ready; the two of them with the orphan drug designation, and that's following its own development pathway. But there are another 30 diseases, most of them are unmet medical needs, where there are needs to develop new drugs. So we started a couple of years ago working on drug discovery in our platform of inhibitors of calcification, looking at how we could address other diseases with follow-on compounds. And this is probably what's going to be next. We'll have another preclinical-stage program during this year with the idea to be with another asset in the clinic soon. So, in time, and you know, looking at not that we have disclosed the areas we will be focusing on but certainly will be related to pathological calcification, but not on patients on dialysis. We're covering the unmet medical needs there with SNF-472 what we have SNF-473s and SNF-474s coming.
John Simboli
When someone who's outside the industry asks you what do you do for a living, let's say not someone from the biopharma industry, and they say Joan, what do you do for a living? What do you say?
Joan Perelló
I think that over the last year, more and more people have become aware of what developing drugs is about with all these vaccines, due to COVID. So now you say phase one, phase two, phase three. And a lot of people know what you're talking about. That was not the case, literally one year ago. So it's easier. But as I was telling you, just a few minutes ago, when we tell this story about the two forms of calcium, the soluble and the solid calcium, the healthy one and the pathological one, this is very easy to convey message. And then when you add, and this problem is especially important in patients with renal disease because that leads to decreased quality of life and increased mortality, then that rounds out the story.
John Simboli
Several of the founders and CEOs I've talked to over this last year, this COVID year, when I've asked that question, what do you do for a living, they sort of smile and they said something along these lines, "Well, now that my partner, my wife, my partner, whoever it is, sees me at work because we're in the same house, they say things to me like Is that all you do? You talk on the phone all day? So I'll ask that question in a different way, as a CEO, what do you do each day?
Joan Perelló
In my case, it was not about my wife but it was about my kids because I have to give—because they are eight and 10 and when they were asking me, what do you do, Dad, for a living, so i explain although we develop these very important drugs because we want to improve the lives of patients. And now because I've been traveling literally every week for 15 years so my kids have seen me always traveling you know and maybe more present over the weekend than during the week and now they see me so this is the way you develop drugs you're sitting in your room in front of your laptop and talking all day with people. But in a positive way, they think it's quite fun being talking all day to people. Because they have to do their homework and so on and for them, it's a different perception now.
But what you're asking what does a CEO do? In my case I am the founder and CEO, so I have a technical background and i can understand the deep aspects of the science of what we are doing but in reality, I would not need to be an expert in any of the areas. Just being able to understand the big picture, ask the right questions to each of the areas of each of the functions that we have here. Actually orchestrating the different aspects of clinical development is what you do with your team internally and then similar but you know with different purpose at the corporate level you know talking to your shareholders, your investors, potential new investors talking to pharma all the time and maintaining this open communication because you never know how things will develop in the future and how potential partnerships my might happen down the road. So it depends; it might look like you're doing the same sitting in front of your laptop but actually, you know every hour is completely different. Just the conversation we're having now, the one I was having before talking to you, or the one I will have when we finish this conversation
In your years of being the founder and CEO what have you learned about your management style? what works for you what your approaches and what makes it you?
Well, first I had to learn a lot because we started the company when i was very young and you know all the learnings have been learning by doing and sometimes it's not easy because you have to learn very fast if you want to keep the pace that the company is taking. But I'm a pretty straightforward person so I just like to talk to people in the way I like people to talk to me and that's as simple as it is. I'm transparent with people, be approachable and just be natural but at the same time, you have to be firm with what needs to be done with the work and the activities that need to be done and you know, I have one of my investors who's actually a very good friend who always says you have to be all the time with the whip and the flower, combining these two elements appropriately.
John Simboli
if you can remember back to when you were eight or nine or 10 and most of us wanted to be what we thought our parents wanted us to be at that point then, of course, but do you remember what you wanted to be at that point? How did you want to grow up? What kind of profession did you want to be in? Does it have anything to do with what you're doing now?
Joan Perelló
I was taking piano classes. I'm still playing the piano right now. Eight, nine years ago we signed a small license for a small product that we had by then and I used part of what I got from that to invest in a grand piano that I have here. And now because of COVID, we're at home and if I have more stress than I can handle, I just need to go out of the room, play the piano and continue with the work. But that was a serious thing. One thing people don't know about me is that I was really thinking of undertaking a professional career as a musician and ultimately I just decided to go to the university and it was the other way around. I just studied maybe one more year of piano, was close to completing the professional level, and never did that so became a chemist, and that's the story we're talking about now.
John Simboli
Do you see any links between the kind of thinking that one becomes trained to do as a musician and a performer and the kind of thinking that you do as a chemist and as a CEO?
Joan Perelló
That's an interesting question, John. I think in general innovation and being creative has a part of your brain that's somehow connected. And as a musician, you need creativity for sure, as an entrepreneur you need much more than that. Another way to describe what we do is solving problems all the time because you have a problem with an animal model you have a problem with a clinical trial you have a problem with recruitment here you have a problem in manufacturing you have a problem in fundraising and you just need to be creative and adjust things all the time and create multiple options to make sure that you can continue one way or another. You keep focused on your values and your mission; why you are doing these things.
John Simboli
And how about the performance part of it. I'm not a musician, I admire musicians greatly and performers; the performance part has to do a lot with poise, right? And being a presenter of ideas about biopharma must have something to do with that as well.
Joan Perelló
One thing that I think is important, and I like to think that I have some of that, is putting a lot of passion in everything you do. And you know continuing with this comparison between music and the work in leading a biopharma company, I think that's very important. The same thing that you need to do to convey when you talk to people because at the end of the day you're talking to pharmas, you're talking to investors but you're working to bring drugs to patients you know to improve their lives and in our case, it's a very specific thing. People have not paid historically a lot of attention to the problem of calcification maybe because they were not aware of the unmet medical need because of this type of inorganic target that i was describing before but you know I think it's important to be able to convey this passion.
John Simboli
Can you tell me about the unmet need in terms of severity?
Joan Perelló
I think it's dramatic. You have approximately 3.0-3.5 million patients on dialysis globally. The main cause of death is cardiovascular. There was some research that was published and amongst the top unmet medical needs, as perceived by the nephrologists, vascular calcification in general and calciphylaxis, the most severe form of vascular calcification in particular were on the top of the list. Calciphylaxis, affects 1-2 percent of the patients on dialysis. This number, 10,000 patients that I was was mentioning before, well there's nothing approved for calciphylaxis. There's nothing other than SNF-472 in clinical development. So you know the closest option to treat this disease is our ongoing phase three program. Our phase two study in this patient population is the only completed, ever, interventional study in patients on calciphylaxis. There have been some other attempts; I think there have been three other companies that tried to do development in this space and the studies were terminated early. Maybe because of operational complications, maybe for other issues. But it's an unmet medical need because there is nothing for them but the mortality rates are above 50% the first year. From the moment of diagnosis, it progresses very fast. You can start with this calcification in the skin arterioles that affect the circulation of blood across the vessel and leads to ischemic pain ulceration. The formation of these necrotic skin ulcers that get infected evolve to sepsis, and sepsis is normally the final cause of death. But it's up to 55% after one year, so this is what we are talking about in calciphylaxis. It may be a small setting, 10,000 patients, but not much attention is paid to these patients.
If we talk about the opportunity in peripheral arterial disease, because this is much larger now it affects one-third of the patients on dialysis. It's 350,000 patients between Europe and the United States. It's a significantly larger opportunity. And then if it's such an opportunity, why don't we have anything for these patients? Well, because the traditional cardiovascular approach using vasodilators, and anti-clotting agents do not really work in patients on dialysis. Because the traditional cardiovascular risk factors do not fully explain what's happening in this patient population. And here, it's about this progressive arterial calcification. So now, when it happens, not in the skin arterioles, in the larger arteries in the legs, it has an impact on blood circulation as well. But when it happens in the legs, it's affecting the walking capacity. So patients because of the ischemic features start having pain on walking, and that impacts the walking capacity. So there's nothing indicated for peripheral arterial disease patients on dialysis. Actually, these patients have always been excluded from clinical trials in PAD, literally. So to the point that now we're about to start a phase III program in PAD, and we are conducting, as we talk, an observational study, in a non-interventional setting, with PAD patients on dialysis, just to have a bit of a better understanding on this patient population, understand better their baseline characteristics, because this is the population we're going to work with. And also to understand operational and logistical aspects that could influence the clinical conduct, and want to have some learnings before we actually start a phase three study.
So, a huge population, in this case, with mortality rates in dialysis in general are high. So we're talking about a 20% loss in mortality rates. But, their quality of life is severely affected. And the FDA, the EMA have these rules, you know, a drug can be approved based on how a patient feels, functions or survives. If you can impact, if you can improve, if you can restore the physical function that's meaningful for these patients that lose a lot of mobility when this progresses. So these are the two unmet medical needs that we're working on.
John Simboli
In peripheral artery disease, you mentioned that one of the outcomes is the patients who are not being treated, there is no treatment right now. They, in the way that you've described, they have trouble walking, how does that progress, what kinds of outcomes occur after that?
Joan Perelló
The problem in peripheral arterial disease in patients on dialysis starts with the problem of vascular calcification. But it doesn't stop at the point of impacting the physical function, it can continue evolving because if you continue calcifying you have less flexible arteries, less compliant, they are not able to maintain the blood flow across the legs, the situation can evolve, ischemia can become more severe and devolves to critical limb ischemia. That puts the limbs at risk. So many of these patients get amputations because of the disease progression. The ischemia also ends up provoking necrosis because the surrounding tissue dies, it can lead to the formation of ulcers in the skin, which also can evolve you know, get gangrene and this is also another way that can end up with computations. What do we know about the disease is that almost 50% of the patients die after a surgical intervention because of an activation.
John Simboli
When people ask you who is Sanifit, I know you said in the negative we talked about it, well people think that we may be a renal company; we're actually a cardiovascular company. Is there a way that you try to bring those two thoughts together? I believe you gave me a hyphenated version of that at one point. So when people say who is Sanifit, how do you like to answer that?
Joan Perelló
We're a leading company in the space of vascular calcification disorders because actually, we're the only company that has now a clinical program in this space, a space that didn't get much attention in the past, hopefully, we have now some others. Companies, are still early stage; drug discovery, preclinical stage but starting to look also with interest at this space. We're proud of being one of the leading biotechs in Spain. When we started the company almost 16 years ago there was no ecosystem in the country; we didn't have life sciences investors; we didn't have other peer companies to look around so i could do I could pick up the phone and talk to another CEO and ask for some advice. No, because there was no ecosystem. So now the situation has changed but actually in a modest way we can be proud of having contributed to creating this ecosystem and we have grown up with the sector in Spain. It's not that there are many life sciences investors now in the country; we have very few but five of them are shareholders at Sanifit so almost every single one has trusted in Sanifit at some point. Six years ago we raised our first international financing round. Those investors across Europe and some U.S. investors, invested in a Spanish company for the first time, and now several of them have done their second and third investments in Spain so somehow we're very happy to have paved the way for others and helping in creating a better environment in life sciences, So now, not that this is a place where you have multiple clinical-stage companies, but there are a number of companies doing important things. You have other CEOs with whom you can talk and exchange experiences and this is always enriching.
John Simboli
Can you talk to me a little bit about what it's like to be not only one of the forerunners for Spanish biopharma companies but probably one of the very few that's located on the Island of Palma? How does that work out?
Joan Perelló
I think it works exactly as in any other place. Many people tend to laugh; so where are you based? In Spain; we're in Spain. In Madrid or Barcelona? No, no, in Palma. And so you think okay we're on the beach; we check and understand but in reality to do science you can do it from any place in the world and you know I am from the islands so it was a natural place for me to start the company because I'm here; I studied here and we can advance the technology from the University of the Balearic Islands and we're very proud of that.
John Simboli
Thanks for speaking with me today, Joan.
Joan Perelló
John, it's been an enjoyable conversation.
