Samuel Murphy
And so I was talking to my Ph.D. advisor and he had a great perspective. He was the Vice Dean for Research at Penn. And he told me, you know, you should go pick a disease and cure it.
John Simboli
That's the voice of Sam Murphy, co-founder of Salubris Biotherapeutics headquartered in Gaithersburg, Maryland. Listen in now to hear my conversation with Sam—his thoughts about leadership and biopharma and advances in therapeutics for the treatment of cancer, cardiovascular, and metabolic diseases.
John Simboli
I'm John Simboli. You're listening to BioBoss.
John Simboli
This afternoon I'm in Cambridge with Sam Murphy, Co-founder of Salubris Biotherapeutics. Welcome to BioBoss, Sam.
Samuel Murphy
Thanks for having me, John.
John Simboli
How did you find yourself at Salburis?
Samuel Murphy
Well, it was a little bit of a circuitous, I would say, around the world journey in a way. I came from a research background doing my Ph.D. and postdoc at Penn and then moved over into commercial strategy consulting and spent over a decade in that world and during that time worked for several large global companies, the last of which was IMS. And many people know IMS for their data, really first in class data set within the industry. There's also a very well regarded consulting arm and I was a part of that team for a number of years. And we were a global operation. So it was actually the head of consulting in China, who first connected me to the CEO of Salubris Pharmaceuticals, which is a China-based pharma company and the parent company of Salubris Biotherapeutics. And that introduction led to some discussions about setting up a venture fund and those sort of evolved into joining Salubris and working in a business development capacity, which I did. I joined as Head of international business development, and at that time was introduced to what was then forming U.S. biotech subsidiary of Salubris, Salubris Biotherapeutics, headquartered in Gaithersburg, Maryland.
John Simboli
So how did you decide you wanted to lead a biopharma company?
Samuel Murphy
I'm really excited about the science that is behind our lead program, and in fact, several of our programs in development, and there was a lot of scientific talent, a lot of manufacturing talent within the team, but nobody who had a business background, clinical regulatory background. And so I just saw an opportunity to really help out the company and drive these programs forward and be a part of something that I think is going to be really special.
John Simboli
When people you know, who are smart people, but aren't in the field, ask you and say, "What do you do?" How do you answer?
Samuel Murphy
I think that the simple answer to that question is always I develop new medicines, or I'm helping to make new medicines to treat people and cure people.
John Simboli
And then when they say, yeah, but what do you do? Do you pick up the phone? Do you write stuff? Do you tell people what to do? Do you read stuff? I mean, how do you spend your day?
Samuel Murphy
I know the common answer in consulting to that question is always it's different every day. And for me, I never gave that answer in consulting because I found it to be really frustratingly uninformative, right. So, I started to give you that answer. But let me give you a little more detail.
Samuel Murphy
I am for our lead program currently heading up clinical and regulatory and thinking through commercial implications of all of our decisions. I deal with the IP. And so on any given day, I'm working with clinical sites that we're setting up, the investigators, working with our CRO to develop protocols for the trial. And then also, you know, thinking about competitive positioning for our molecule and market size and market opportunity and how we project that or present that to potential partners down the road. So it can be a lot of different things. And then also, I do continue to serve in the role as head of international business development for our pharmaceutical parent company in China. So that takes up a fair amount of my time, looking for deals, and negotiating deals, meeting with companies. And then as a result of strategic investments that we've made through the parent company. I'm also on four boards. And so that takes up a fair amount of time as well.
John Simboli
How'd you go about choosing Salubris Biotherapeutics from what probably were many different opportunities you had at the time? What made you think this will allow me to do the thing that I would like to achieve, I'd like to do at this point in my life?
Samuel Murphy
Well, it really comes back to the CEO. I think he's such an outstanding translational scientist and this is coming from somebody who did his postdoc in translational medicine, Children's Hospital in Philadelphia in the lab that became Spark Therapeutics and working for Kathy High was an incredible experience. She's a great translational scientist—will probably win the Nobel prize for the work she's done in gene therapy. But john Li, who's the CEO of Salubris Bio, has this very, I would say unique way of blending physiology and molecular biology and medicine together—understands how molecules work inside the body in a way that nobody else I've ever encountered in this industry does. And that's why I think our programs are so exciting.
Samuel Murphy
I think the other aspects of this role and this opportunity, which is really exciting is China for a long time has not been on anybody's radar in the biopharmaceutical industry. And within the last few years, I think most people are aware that there's been a strong push in China to move their industry from a generics focus to an innovation focus. And they've done that through regulatory changes to push down the price of generic medicines in China and improve reimbursement for innovative medicines. And they're funding all kinds of research initiatives. They're building cities of biotech, whereas we have hubs. It's incredible what they can do in China when they put their mind to it. And they have made the decision, they want to be a global leader in innovative drug development. But it takes time to get there. And so they are attracting talent trained in the US and trained in Europe. But primarily the U.S., I think, back to China. And then also a number of Chinese companies have set up their own entities here in the U.S. to try to do innovative research where, you know, at the core of global innovative research here in the U.S.
Samuel Murphy
I think that we can be one of the leading companies to really push the edge of what innovation means. So a lot of companies from China got into biosimilars, and that was innovative at the time, you know, biologic, and then maybe biobetters and then maybe best in class, but I don't think any company yet that was based in China has really developed a completely novel original and innovative product. And I'm not saying we will be the first but I think we've got a shot with our lead program. JKO 7.
John Simboli
So it sounds like it was almost a love at first sight in the sense of the right person, the right company, as opposed to "This looks like an interesting idea; let me do research for six months about similar entities to see if that's the one." Or, you know, was it clear that this was the one?
Samuel Murphy
Oh, very clear from the beginning, and I will say part of it . . . So I love working with John Li, CEO of Salubris Therapeutics, also Kevin Ye, who is the CEO of Salubris Pharma. He spent over 15 years in the U.S. He went to undergrad at Michigan, he did his MBA at Yale. He worked in Silicon Valley. He understands Western culture very well. He's more or less my age. He's got kids, my kids' ages, and very easy to get along with, very enjoyable to speak with and work with. That's not typical for a CEO of a China-based pharma company. They tend to be older. They've been in generic medicine for a long time. They're pretty risk-averse. They don't understand what's right. And there's nothing wrong with that from where they're coming from. But it makes it more of a difficult culture fit to have a U.S. biotech working under the China-based entity. But Kevin makes it possible because of his unique background and experience.
John Simboli
When you mentioned kids, it took me back to the simplification question one more time, Sam, can I ask how old are your kids?
Samuel Murphy
11 and eight,,
John Simboli
So when an 11-year-old or an eight-year-old gets asked in school, I don't know if I still ask questions like this. Like, what's your mom and dad do? Have you ever heard them give the answer to what Dad does?
Samuel Murphy
Yeah, well, my son says I'm a drug dealer. I think my daughter's a little more politically correct about it and says something like Dad makes medicines.
John Simboli
Do you feel that you have a management style? And can you describe what that would be and why that works for you?
Samuel Murphy
I do, I think my quintessential management style, the way I would characterize it is flexible. You know, I can sit here and talk to you for an hour, I could lecture at you for an hour. And I can sit here and listen to you talk for an hour. And I'm equally comfortable in any of those roles. And I can be firm when I need to be firm, and I can be soft when I need to be soft. And I think that adaptability allows me to be a better fit with different people and teams that I work with.
John Simboli
Can you remember back when you were eight or nine years old? What your self-image was? What you thought you might be in the world at some point and does it have anything to do with what you're doing?
Samuel Murphy
Absolutely. I mean, I knew even back then I wanted to be in science and medicine. And you know, I think for a while that meant going to medical school and becoming a doctor. And as I approached the time when I was almost ready to enroll in medical school, actually, I got into medical school out of high school in one of these accelerated programs. And I turned it down because I wanted to have the full, normal university experience. But in the end, I think I'm in the perfect place for me working on medicine, but not engaging with patients on a day to day basis.
John Simboli
What's new at Salibris Bio?
Samuel Murphy
Well, I think the most exciting recent news for our company is the FDA approved our first IND here in the U.S. And so that enables us to go into our first clinical trial which will actually be a trial in heart failure subjects. Our lead program is called JKO 7, and it's a bispecific, bifunctional antibody-based molecule. We will be, as our team of 20 people here in the U.S., the first company globally to put a bispecific antibody into the clinic in a cardiovascular indication. And you know, we've talked a bit already about why am I so excited about Salubris Bio and why do I enjoy being a part of the team so much? You know, there is such a large focus in Cambridge and in the U.S. and pretty much everywhere outside of China on oncology and rare disease. You see a lot of immunology also. But oncology and rare disease, probably number one and two in terms of who gets funded and where all the resources allocated in drug development. And there's a good reason for that, right? There's big unmet needs, clinically, and there is a lot of inelastic pricing, particularly in the U.S. in those areas.
Samuel Murphy
But the consequence and sort of the casualty of that is more research and more resources allocated into diseases that affect millions of people. I mean, metabolic disease, you see A couple of big players but for the most part, there's not a lot of activity there outside of that core set of large pharma companies,. Cardiovascular, the exact same thing. And because we're coming from China, because all of our products have to be relevant in China, we have a focus on cardiovascular disease, in addition to oncology. We're hedged and I will acknowledge that all of our other preclinical programs are oncology. We focus specifically on complex biologics and we focus on validated targets and there aren't a lot of validated targets for complex biologics in cardiovascular disease. But our lead program is exactly that. And we're very proud to be the first company to achieve that milestone as a small team. Even ahead of all of the big pharma interested in cardiovascular.
John Simboli
What do you say when people ask who is Salubris Bio?
Samuel Murphy
I always say to start we are the U.S. biotech subsidiary of a China-based pharmaceutical company. And then I think as we move into the clinic with this program, the image will change and will start to be defined more by what we're doing here in the U.S. and what we're doing globally because this program is very exciting. We have some very high profile sites and investigators that we're working with, and we think there's a lot of potential. So eventually, I think we'll be known more as a leader in complex biologics,
John Simboli
When you're trying to describe in a terse way, what the gap is that you're trying to fill, how do you attempt to answer that one?
Samuel Murphy
So the gap is very easy. And this comes back to what we were talking about with kind of ignoring of cardiovascular medicine and broader indications. So let me give you a little bit of an epidemiology background in heart failure. Heart failure, there are about 5 million to 6 million Americans with that disease and it's divided into basically 50/50 into two different types of heart failure.
Samuel Murphy
There's heart failure with reduced ejection fraction or HFrEF, where your heart simply isn't pumping enough blood through the circulatory system. And then the other 50% have heart failure with preserved ejection fraction, which is essentially a stiffening of the heart so that there's a normal amount of blood flowing through the system, but the heart is working extra hard to make that happen. And over time, bad consequences result. And so for either of those diseases, there's a very high mortality rate once you hit the first hospitalization. We're talking millions of Americans who die from heart failure. And on the heart failure with reduced ejection fraction side, there are a number of pharmaceutical interventions and there are devices, also MedTech interventions, that can be used to alleviate symptoms and prolong life, you know, essentially modify the course of the disease. In HEfREF there is literally nothing approved. You could open up the guidelines and it says, we have nothing we need new trucks.
Samuel Murphy
Our product is based on a recombinant growth factor that has been tested in the clinic by several companies, one in China, and this goes back to our China heritage. We know that program very well. We know that company very well. Another is here in the U.S. And both of them have seen very promising efficacy results, but they had several challenges with their molecule. So one is that there were some tolerability issues in the GI tract. Two is that they had some safety concerns about promoting cancer because it's a growth factor. And three is a very short half-life for these molecules. So the infusion schedules were particularly burdensome, especially the China-based company, they had 10 consecutive days of 10 hours per day infusions. So that's not really going to be tenable for a large population.
Samuel Murphy
So what we've done is we've taken this growth factor, and we carved out the active domain, and we fused it to the tail of an antibody. And so that gives us an antibody-like half-life in circulation. And that solves the PK problem. But it's more elegant than that because the growth factor binds to two different proteins. One is called HER3 and one is called HER4. HER4 is what appears to be responsible for all the cardio regenerative effects of the molecule. And the binding to HER3 is what appears to be responsible for all the GI side effects and all the cancer risk. And so our antibody specifically blocks HER3 signaling and the tail, therefore, is biased very much in favor of the HER4 so we think we will have solved the safety problems, the tolerability problems, and the PK problem. And in addressing the PK problem, we think we can actually get much better efficacy in addition to a wider therapeutic window.
John Simboli
That sounds like a compelling story. And I'm guessing that when you deliver that, and the people on your team do and you tell that story, a certain number of people at a conference, let's say, come to you afterward and say, I understand it, and I'm really interested, let's talk more. And then a certain number, for whatever reason, may say they're not interested. The part that interests me right now, of the ones who say, yeah, I'm interested, and then kind of repeat it back to you what you just told me, the ones who don't get it, the ones where you have to come back and say, well, it's actually this. What what is that? What is that misunderstanding? How do you help them to understand what it really is?
Samuel Murphy
Well, I think from a clinical standpoint, it's very clear when you have no options when you have a 50% chance of dying within a few years once you have your first hospitalization. You're talking about over a million people in the U.S. who fit that description with HFpEF and look at the cost, the standard cost of biologics today. Look at the cost to our system of heart failure today is somewhere on the order of $40 to $60 billion here in the U.S. You look at the epidemiology and you look at the standard price benchmarks, and you can see that the market for this type of product would be huge. And because we're dealing with a complex biologic that has to be tightly regulated in its activity, we think we're probably four or five years ahead of anybody else who would even consider starting and right now, not a lot of companies even know what we're doing.
Samuel Murphy
So I think that's a pretty compelling case. The challenge for us is that because there hasn't been such a focus on cardiovascular research within the biotech community, here in Cambridge anyway, I think people aren't as educated on the targets and the background. So they might hear that our molecule's active domain is NRG1, and not be very familiar with what that molecule has shown in non-clinical models and how it has been demonstrated as active in the clinic in the past. And so our challenge is really to educate people and to bring them up to speed on cardiovascular research more so than they probably are right now.
Samuel Murphy
I think then, part of that is telling them NRG1 is so fundamental to the human heart that in an animal model if you knock it out, it's lethal in utero. If you knock out its receptors of HER3 or HER4, it's lethal in utero. If you do selective knockout later in development, you get severe heart problems. And I think the other thing that people around here, more focused on oncology, will be familiar with you Is the Herceptin cardiotoxicity. And that's really the intersection of this program and oncology that I think will resonate with a lot of people. So Herceptin is an antibody that blocks HER2 signaling. And I think very well known, regarded as one of the best oncology drugs out there of all time, right. But it's also known that in some patients HER2 blockade does have a deleterious effect on ejection fraction. And eventually, people figured out that it's worse in the presence of an anthracycline. And so you never get simultaneous use of anthracyclines and trastuzumab, or Herceptin, in patients today. HER2 is the dimerization partner for HER3 and HER4, and the induction of signaling is NRG1, our molecule for cardiovascular regeneration. So what happens is when you block HER2, you're actually blocking the NRG1 signaling pathway. And the reason that it's worse in the presence of anthracyclines is anthracyclines themselves damaged the heart. And this is the fundamental repair pathway in the heart. So when you're blocking a damaged heart from repairing itself, you get a worse outcome than if you have sort of a steady-state equilibrium with the heart.
John Simboli
What can you tell me about the pipeline and how it helps to differentiate who Salubris Bio is?
Samuel Murphy
I don't think that we're the only company out there that's focused on complex biologics, but I do think that there's a limited number of them and we don't have a single standard monoclonal antibody in our pipeline. Everything is a fusion protein or bispecific or an ADD, somehow antibody plus, right? And then I think beyond that, there are some companies out there that have a lot of great ideas about complex biologics but they don't know how to build them successfully. They don't know how to build them in a way that's scalable. And when you look at the composition of our team, it's the CEO is a scientist, and me, and an admin; two early-stage research scientists, everybody else is in manufacturing. We have such a heavy emphasis on developability because . . . the last thing I would say that separates us is coming from our China-based parent company, we don't undertake programs in highly risky novel big biology. And we're rather focusing on validated targets and using this complex biology and our skills to develop molecules that are clinically meaningfully improved in some way, but without making the next big discovery. And so that, together, I think, is what really defines us as a team and as a company.
John Simboli
What makes a good partner to Salubris Bio?
Samuel Murphy
Well, obviously we're a small entity right now. And cardiovascular programs tend to be fairly large, expansive. And so I think right now, our partners are the clinical sites that we're working with. But eventually, we would expect to explore partnerships with larger pharmaceutical companies to really fully take advantage of the potential of this molecule if things go the way we expect them to go in the clinic.
John Simboli
I know now that you're focused very much on your preclinical and clinical work. Can you find the time to step back at this point and say, you know, if this thing develops the way I hope it will, I can be a part of something that actually, really significantly helps people?
Samuel Murphy
You know, this question reminds me when I was sort of wrapping up my postdoc and my postdoc, to give you some context, this is before Spark Therapeutics formed. And so I was in the lab. It was not a typical research experience. We were running two trials out of the lab, the Leber Congenital Amaurosis trial and the Haemophilia B trial that eventually rolled into Spark Therapeutics. We had in house GMP manufacturing, we had in house process development.
Samuel Murphy
It was like a midsize biotech. I mean, there were 50 people in the lab, the vast majority focused on supporting these programs in some way or another. And seeing actually subjects from the trials, patients walk up and down the halls, and they were cured of their disease. You know, I guess it's too early to say lifelong cure, but certainly cured for a number of years now. And it was really exciting and very meaningful for me to be a part of that. And so I was talking to my Ph.D. advisor, and he had a great perspective; he was the Vice Dean for Research at Penn. And he told me, you know, you should go pick a disease and cure it. And you know, in the context of being in a lab that was really at the cutting edge of gene therapy. But here I am, 13 years later, and the disease that I've picked is heart failure with preserved ejection fraction. No cure, no treatment, no symptom relief, no functional improvement, no disease modification. There's nothing for these patients, and we have what we think could be a really powerful treatment for that patient population. And so I'm still inspired by that moment when he told me, pick a disease and go cure it, and I hope that our product is is an answer for those patients.
John Simboli
How did Salubris Bio decide to establish a presence here in the U.S. in Gaithersburg, and where we are today in Cambridge?
Samuel Murphy
I think eventually you will see Salubrious Bio getting a bit of separation from the parent company in China and starting to engage with investors here in the U.S. Cardiovascular trials are not cheap. And I think we'll want to have some access to capital in the U.S. over time. So I think that we will have more connections and roots established here in the coming years. But just being a part of this community, there's a coffee shop a couple blocks up the street, A4, Area Four, great coffee, and was in there with my kids after swimming lessons on a Sunday afternoon, sat down with them and see the woman next to me is reading a book on liver disease. And of course, I struck up a conversation because I find this very interesting, and it turned out she was Kathy Bowdish. She was at the time CEO of Permeon Biologics and now running the sunrise startup program at Sanofi. And, you know, kept in touch over the years.
Samuel Murphy
It's that type of interaction more than anything else that I think makes Cambridge a special place versus San Francisco. You know, I've spent a fair amount of time in South San Francisco. And actually, I'm impressed at how built up it is. And I think it's a little closer to getting that critical mass of density that will give it the Cambridge vibe, but they're not there yet. Certainly, San Diego, a driving community, San Francisco, most people are still getting in their cars in the parking lot and driving home. Here, there's so much walking and so much personal interaction on the streets, that I think it gives you more of a connection to the community than it does in those other cities. I'll give you another example. So same setting, swimming lessons, in the locker room, my kids getting changed. And I hear two people talking about moving out of consulting and into a pharma role. And I was looking to hire somebody at the time. So struck up a conversation, turned out, this guy worked for McKinsey. Now he is at Arix Bioscience as an investor. And we're talking about investment opportunities. You don't get that anywhere else in the world.
John Simboli
What have you learned about how to work across cultures? Gaithersburg and Cambridge are different cultures, even though obviously, it's U.S. culture and then going back and forth to China, what have you learned about how to make that work?
Samuel Murphy
There was a bit of an adjustment period, I would say in terms of the mixing of cultures. And this is coming from somebody who worked for a long time for multiple global companies where you know, early morning calls are normal. Late-night calls can happen from time to time. It's different with China because there's so much drive and ambition to be successful and to make things happen. I've spent now years doing four or five nightly calls a week. I also get up In the morning at 5:00 AM and I have an inbox that's completely full. And so getting used to this rolling sort of continuous workflow was an adjustment. And I think it's not for everybody. I love what I do. And so that makes it an acceptable work life balance for me because it's not balanced, but it is what I want to be doing. And I'll take that trade-off anytime. At the beach, they have these t-shirts that say it's 5:00 PM somewhere, and you got cocktails. For me, it's it's 9:00 AM somewhere.
Samuel Murphy
You know, one thing that I find really interesting is where will China originated and China-based companies be in this industry in 10 years? And nobody knows the answer. There's a lot of dynamics at play. So on the one hand, there is such a huge amount of resources being poured into biotech and innovative medicines in China. At the same time, they have 1.5 billion people to provide health care for. And so they're very intolerant of high prices and prices have come down very quickly on the generic side, once they decided that that had to happen. Prices have come down within crowded branded classes, because there is, you know, a need for inexpensive effective medicines. And so I think that that is going to be a bit of a drag on innovative medicine in China. Because there's this tension between investors who don't want to take on too much risk and scientists who are trained to engineer things in a way that's better rather than doing you know, novel discovery, research, and prices that just don't support return on investment once you get to the market.
Samuel Murphy
I think though that over time, you will see some companies emerge, which originated in China, to be global leaders. I think BeiGene is pretty much there. In my mind, there will be more. And, you know, a couple of years ago, I used to go to panels and, everybody in this room can name five Japanese pharma companies. And there probably are only a handful of people that can name five China-based pharma companies. I'm so immersed in my own world, I don't know if that's true or not anymore. I think most people know BeiGene and Zai Lab. I'm not sure how many other China-based companies people could name off the top of their head. But eventually, you're going to have some winners emerge from that pool of companies and I do think that Salubris Bio will be one of them. I think we won't be the only one and I'm excited to be a part of that movement.
John Simboli
Sam, thanks for taking the time to talk with me today.
Samuel Murphy
Thanks for having me again, John. And I really appreciate the opportunity to tell our story.
John Simboli
As Co-founder of a company with offices on two continents, Sam Murphy's multi-tasking, multi-time zone life will sound familiar to many BioBoss listeners. As Sam says, "I've spent years doing four or five nightly calls a week. I get up at five each morning with an inbox that's completely full. It's not for everybody, but I love what I do. You know, at the beach, they have these t-shirts to say it's 5 pm somewhere, with a picture of cocktails. For me, it's 9 am somewhere.
John Simboli
While getting things done in this multi-continent workplaces is a daunting task, the most significant challenge is the leadership required to develop and communicate a vision for what sets the company apart. From my perspective, a guy who was accepted to medical school straight out of high school is probably the right kind of person to meet this leadership challenge.
John Simboli
I'm John Simboli. You're listening to BioBoss.
