N. Bermingham:
0:00
Be very fair. You don't know it all and be willing to actually listen to people. And when you're wrong, tell people you're wrong.
John Simboli:
0:06
That's the voice of Nessan Bermingham founder, president and CEO of Triplet Therapeutics. Listen in now to hear my conversation with Nessan at the Triplet headquarters in Cambridge, Massachusetts. I'm John Simboli. You're listening to BioBoss. This afternoon I'm in Cambridge with Nessan Bermingham, President and CEO of Triplet Therapeutics. Nessan, welcome to BioBoss.
N. Bermingham:
0:32
Thank you.
John Simboli:
0:33
How did you find yourself at Triplet Therapeutics?
N. Bermingham:
0:36
I've been working in the venture industry, in and out, for about the last nearly 20 years. I'm originally trained as a scientist, so genetics has been my primary driver when I think about my actual educational background. I've been very fortunate in being a founder of a company called Intellia Therapeutics to focus on CRISPR CAS9 genome editing technology and built that company, took it public. And when I left as CEO there, I took a little bit of time off , and Atlas Venture came back—whom I'd worked with before and co-founded Intellia with—came back and asked if I'd be a venture partner within Atlas. Ultimately, I agreed to come back and do it. I thought I'd retire. I didn't. So I rejoined Atlas. They opened up the door and said take a look at various things and figure out what you'd like to do next. So I very quickly got involved with two of their portfolio companies as chair. F star, an immuno-oncology company with bi-specific antibodies in the UK, Cambridge, UK. And then a newer investment that they'd made , called Akrevia Therapeutics, which also is in the oncology space. As I was working with those companies as chair, a number of publications came across my desk people from a number of people within Atlas. And those publications really talked about a new mechanism and that seemed to be a unifying biology driver, biological driver, in repeat disorders. So as you look at repeat disorders, historically we had thought that they were very much driven by this repeat of a very specific sequence. Different repeats, different for different diseases, but it's a bit like reading a book where you've got the same word like "the" repeated multiple times in a row and this is n ormal in your genome. But if that word or that repeat is too long, it actually destabilizes that DNA and it can lead to toxicity from and RNA and, in some cases such as H untington's disease, a protein standpoint. There's about 40 of these diseases. We had thought that each disease was independent and they had a different driver. So as we thought about therapeutic models for it, we actually would have to make a bespoke therapy on a per indication basis. So here's a series of papers that hit my desk, t hat actually showed that that does not appear to be the case. What actually looks like i s happening is that that repeat from an individual being born to when they show disease to ultimately, unfortunately when they die, that repeat is actually getting bigger and bigger and bigger. And as you look across many of these indications, the biological mechanism by which that repeat gets bigger is actually conserved. So we can very clearly show that this mechanism called the DNA damage response pathway basically is going and driving the instability and expansion of that repeat over time within these patients. And that there's a lot of data now to indicate that if you actually go in and target that pathway, you can stop that expansion from taking place and by stopping that expansion, potentially then be able to prevent the onset of disease in these patients or prevent the progression or delayed progression, onset and progression, within these patients. So I looked at it and I was going, this is great. As we think about therapeutic intervention, great biology, great data from the human patient data, all of this work that we're doing is driven by human patient data, which I think is very unprecedented in the industry. So I couldn't, but not, actually found the company and be CEO.
John Simboli:
4:14
One obvious question is I've read you described sometimes as a serial entrepreneur and I get that suggests thing to thing, to thing, to thing. But at some point does a serial entrepreneur say, that's it, I'm done serializing or does, does one go forever?
N. Bermingham:
4:32
The more recent companies that I'm involved with, there's been really very fundamental biology and data driving it. So, I'd spent, I don't know , 10-15 years looking at this sort of genome editing, gene therapy space for a long time. I was very familiar with it. And when things like CRISPR CAS9 technology came out, it was very clear that that was the tool that ultimately we needed at that point in time. As I look at these things, it really is a confluence of different capabilities and different datasets that guides it. So as we think about the CRISPR CAS9 technology, one of the reasons why people were so interested in it, I know, was we could move so quickly with it was—when we think about synthesis of nucleic acids, so making RNA and DNA oligonucleotides of extended length—the technology was there to allow us to do it. When we thought about, the chemistry around it being able to stabilize it, that data had been around for work that have been done in the antisense oligonucleotide siRNA space. When we think about delivery, both from viral delivery mechanisms like AAV into lipid nanoparticles, again, a lot of the capability was there. W e're not all the way there. We have a lot of work to do, still, in delivery, but there was certainly a foundation that we could actually leverage. And then, very importantly, when we think about deploying the technology, we had a clear sense, for initial indications, to actually start to deploy the technology as we think about w here t o target it in the genome. And it really was decades of data and work by multiple economic institutions, multiple companies that really provided this data to us that then allowed us when this technology was i dentified to actually be able to take it and then very quickly be able to co-opt it in this manner. I think that that's what's so exciting, and Triplet's another great example of that where the genome-wide association studies in large patient populations allows us now to be able to tease the genome apart and try to understand and try to figure out which areas of the genome are really driving your disease and how best to think about therapeutically intervening there. So while we understood the GWAS, genome wide association study, data from these patients, it really was then being able to take things like antisense oligonucleotides and siRNAs, where there's a history now in developing these as therapeutic modalities, and then be able to deploy them against these targets. So when I think about founding companies, it's really a confluence of data points coming in and really taking pieces to build the proverbial jigsaw that then allows you to build a company and be able to move forward. And that's not always the case. Triplet took, before we really got it going, it was six, nine months of just digging into the publications , digging into the strategy for it. We started another company at exactly the same time called Korro Bio and the sort of next phase of nucleic acid editing technology, that was founded around the same time. And , we've now just actually brought in some additional funding into the company. So it's really a very temporal dynamic that's taking place as we think about starting these companies.
John Simboli:
7:49
I would guess that the idea of dealing with disease at the source level must be very important.
N. Bermingham:
7:55
Yes. You look at it and you think about any individual for most diseases that there are today, it's your genome that really is driving it. It's the foundation for it. And that may be a foundation either having a protective sequence in there to prevent the disease or delay onset or severity of disease or being able to go in and actually repair some deficit in the genome in its own right. And I think that we still have a lot to learn about that. So I think there are certainly one aspect of that and that information and those data sets are growing to actually help educate us. I think we believe we understand a tremendous amount of the genome and the reality is we don't. And if you look at the genome, the genes people were working on before the human genome was sequenced and what they're working on today, hasn't changed an awful lot. So there's a lot of the genome that we actually don't know about, and a lot of putative genes there that, frankly, we don't know functionally what they do. So, I think of the opportunities in our industry as we think about treating disease is very much going in and trying to actually understand and segment these regions of the genome to understand how targeting them m ay actually prevent or treat or cure disease. I think that's certainly one aspect. The other aspect also that we s pend a lot of time thinking about is how do you think about from a personalized medicine standpoint? A nd then thirdly, so certainly costs. So we've had our first truly personalized medicine drug be approved for Batten disease. I think it was between 12 to 18 months, this was done here in Massachusetts, 12 to 18 months from starting to develop the drug for the individual to getting approval for the individual, which again, completely unprecedented in the industry a nd the tool set that's available to us today has really allowed us to be able to do it and then the regulatory framework that's still being optimized, but also actually facilitated being able to move so quickly. And again, we're seeing these significant steps forward, in being able to actually target these diseases, these genetically based disorders and actually going in to treat them and potentially cure them. And I think that is so exciting as we think about patients and the potential to be able to address m any o f these diseases.
John Simboli:
10:17
In those early research stages, when you were in your first zeroing in on this, did it occur to you that you could take something that was already out there, some research that was already done, maybe a company that was already working on it and then transform that or develop that? Or was it pretty clear from the beginning, "I have to start this thing fresh."
N. Bermingham:
10:35
It was pretty clear: start off fresh. And I think that's part of the excitement though also.It's a blank sheet of paper. You have some academic publications that have come out that you review and really turn to, so how do you tackle this problem? And how do you think about doing it in a quick cost-effective manner and then really thinking about, obviously, the safety as you think about actually moving into human clinical trials. So in all the companies I've been involved with that's been the driver. It's a new chapter, it's a new book that you're writing versus going in and piggybacking, frankly, on another company that's doing exactly the same thing that you're doing and trying to actually develop that and compete against them, which can be very good, i n some respects, competitive can be actually very healthy, especially as we think about platforms. And again, genome editing is a great example of that, where it is healthy. In other cases, it actually can become a hindrance. , can delay actually progression of these companies. So, yeah, blank sheet of paper.
John Simboli:
11:39
When you meet someone who is dealing with that blank sheet of paper, in the sense of not being an insider, and they say, "What are you doing these days?" And you think, how deep do I go? How do you answer that ?
N. Bermingham:
11:51
I'm a facilitator. I mean , at the end of the day I think that one of the . . . frankly, the thing that I do is facilitate. Working with venture capitalists who have a clear sense as to how they think about deploying their capital and the stage of company that they actually want to get involved with, to facilitating, bringing the right people together into a construct of an organization that they actually can be given the opportunity to excel , to grow their careers. Excel in the research that they're doing and then, frankly, facilitate building out the strategy, asking questions, helping people think through things. But I think, ultimately, my job is to facilitate and actually support where necessary and make decisions. Ultimately sitting there, a CEO sitting there and making a decision, a determination, and standing behind that decision. Some decisions are good and they work out well. Other decisions frankly, don't work out well. And you have to stand behind those decisions too, and basically accept the fact that, actually, you screwed it up.
John Simboli:
12:54
Takes courage.
N. Bermingham:
13:01
It is a very humbling job to be perfectly frank with you. Having to manage multiple different people, personalities , expectations, their expectations obviously for your employees, expectations for your investors , expectation from your boards, your scientific advisory board and from the patients. So really, you very quickly learn that you have to be humble about it and you have to be very pragmatic and realistic about what can and cannot be done. So I think it's a very humbling job at times and at times also very frustrating.
John Simboli:
13:41
Can you remember when you were, let's say eight or nine and what your self image was, what you thought you might want to do and does that have anything to do with what you're doing?
N. Bermingham:
13:48
No, not at all. Certainly not the cool kid in the class at all. I grew up on an army base. My dad was in the army and my mom was a nurse. The army base in Ireland, we don't have a big army, it was very small army base, sheep everywhere. I was about five miles from the local town where I went to school. So eight or nine, no idea. 16, no idea. At 17, I went to university, I left home and went to university. I actually started doing genetics because it was the only degree at the time that I could get out in three years. So the rest of them would take me four years to do it. And I really wanted to be done with university in three. So I ended up doing genetics at Queens University in Belfast. And then my PhD, I did at Imperial St. Mary's Hospital and Imperial College of Medicine in London. And the only reason I did that was I happened to break up with my girlfriend at the time and it was Valentine's Day weekend. And they invited me over to interview and I said, I don't need to be around here for Valentines's. I was cool for an interview for the PhD. And then went from there to Baylor College of Medicine in Houston, Texas. The reason I chose there was the PI was great. Huda Zoghby, but there was somebody in her lab, a guy called Chris Cummings who, he and I got on extremely well and we had a lot of hobbies that were similar. So I could see that I'd resonate well and enjoy working in the lab so I moved there. Then I went to Wall Street, no idea what it was when I went there, and learned very quickly about that, and then into venture capital. So to be honest with you, I didn't even know these jobs existed. The reality was that there were opportunities that presented themselves to me and I was probably . . . I was pretty arrogant to think I could do them a s I jumped in and tried to do them and sometimes fell flat on my face. Other times succeeded. But not at all, no idea.
John Simboli:
15:50
When people ask you, do you have a management style? How do you like to answer?
N. Bermingham:
15:53
You know, it's a really interesting question. And before I took operating roles, I thought about it and I was like, I had no idea. It's great to talk about operations when you've never done it and then you wake up in reality when you've been at a board meeting and the board demands or wants you to do X, Y, and Z and you're like, Oh, and they want it want it done in a day. And you're like going, Oh, how do I do this? Right? So I think that management style . . . there are certain philosophies I have. So one is if you hire somebody to do a job, you should only hire them if you're going to trust that they're going to do the job and you can't micromanage. So you really need to give them the leeway to let them run and do the job that they've been hired to do. Give them the tools to enable them to be able to execute. Be very fair. You don't know it all and be willing to actually listen to people and when you're wrong, tell people you're wrong. I think it's a learned skill or at least it was a learned skill for me. It was something that did not come naturally to me So I think there's an element of that. I think there's an element of also being very clear about direction. Sitting there and saying, this is the decision. I've taken all the data. This is the decision. Let's move forward with this. Do we have consensus? Yes or no? And even if there isn't consensus there, it's what you believe. You have to stand behind that decision one way or another. So I think you've g ot t o be very clear and provide people with that clarity so that they can see what's going on. I think that, how an organization is doing, being very upfront about it. Things like financing, how is the finance going? If it's not going well, you need to tell people and be very upfront with that. As you look at your burn and your runway, be very clear with people around that also. I have a philosophy of paying bonuses in January. And the reason for that is I don't want people staying around until March who are going to resign. They might as well resign in January or leave. So there are other elements whereby making a decision . . . I remember, once, there was a decision around business development , a deal that we were working on for another company. At the time the company had maybe four months of cash on the books. And the deal just wasn't right. Now this deal would bring us in enough capital to run the company for another18 to 24 months but it was the wrong deal for us to do. And sitting down with the senior management team and saying this is the deal that's on the table today. This brings 18 to 24 months into the company, but it's flawed and these are the reasons why it's flawed. If we don't do this deal, we have maybe four months of capital open to us that we would need to find something else to be able to keep the company going. My recommendation is not to do the deal, but I cannot make this decision on my own. Like all of you, we'll live with these consequences as a senior management team. How do you want to do it? So I think that there are elements also of just being very upfront about it and saying, we all have to live with this so let's have a discussion about it and make a decision. So I think my style is very much in that way. There is an element, I move very quickly. For some people that's great. And other people, it's not so great. And I also think it's having very frank discussions with people. Where you're seeing challenges, be upfront about it and try to figure out a way to resolve that. And if you can't resolve that, talk about a strategy for separation to actually deal with it. I think the other aspect is that you're very clear with people about benefits, h ealthcare. You give them the best you possibly can give them so that when they walk in the door, as best you can facilitate it, e nsure that they're not worried about dental, eye, health o r a ny o f the ancillary aspects as you think about benefits for an individual. And then the other aspect I'm very clear with the organization is about taking vacation. I take vacation, I take all of my vacation. I think it's extremely important to do that because I don't think that anybody can be working 24/7. People that tell me they work 24/7 is a head scratcher to me. So it's very much, I work Monday to Friday. Saturday and Sunday is family time. During the summer and winter I take the time off. And taking time off is checking my email once or twice a day, but it really is leaving that behind and it's being very clear within the organization that you need downtime. Spend it with your families, spend i t doing the things that you love because then you come back refreshed and you can take a more measured view of the work that's going on and you're not so caught up in the work. If it means that you need to shift the direction of a project or you need to actually say that something's not working and figure out why it is, it gives you that separation to actually think like that. So, part of the management, I think part of the role I have is to ensure that people actually step back from the organization t o take the time out and then come back refreshed so that they do the job in the best way that they possibly can do. And that's not determined by time. It's determined by the design of the e xperiment. It's by thinking through things, scenario analysis, risk mitigation analysis and open d ialogue and being very comfortable with that open d ialogue. So I think that my style is very much around that. And my presentation—I think also very much reflects my style .
John Simboli:
21:27
Display as discourse, as a teacher of mine once said. . . That has to do with respect and dignity and allowing people to have a life in addition to this life that they live with you. Has that meant that people have come along with you from company to company?
N. Bermingham:
21:48
Yes, in many cases people have come from company to company with me and there are positives and negatives to that, to be perfectly frank with you. There's a way of thinking that a team can fall into and as you think about that and as you think about a way of working, you bring that style with you and for new people coming into an organization where the style is prebuilt can be, actually, very challenging for them. I think you've got to be careful about that. I think the other area, too, is each c ompany i s very different. The mission for the company is different. The direction i n which the company goes is invariably different. The lessons you're going to learn are invariably different. So it's almost, a priori, I don't think you can step in and say, this is how it's going to be. I think it's more of you need to let the culture, in its own right, develop and actually build over time. But I think part of that also for companies, it's very much dependent on the stage of the company and where it is in its evolution. So stage is one thing people think about the development of a drug or financing but also evolution as you actually think about the culture of the organization. They are not necessarily linked. It was very clear to me within Intellia, i t was time for me to go because the company got to a certain point in its evolution that I was not the right CEO for that company anymore and the company was not right for me anymore. So it's really also being attuned to thinking about where in a company's evolution or growth is the best place for you to be. I think one of the things that I've heard from a lot of CEOs, especially the newer ones, is that they really want to make that step into , for example, being a public company and move very quickly to get them into that. And I think that there's not necessarily an awareness or understanding as to what that actually implies. And all of that flows through every aspect, both over an organization but also from a very personal standpoint. So you look at the size of your organization, you look at communication and discussion and material, data or material events that are taking place within the organization. As a public company, you look at the reporting requirements around it. You look at your friends, your neighbors, your relations, understanding how the company is doing from the public releases that are out there. You have to be very careful about what you're talking about, how you present yourself. In addition, many of them will now understand what your compensation package is. Or how the media may present that compensation package versus what reality actually is. I think you see these elements of people rushing to do these things and they may be better served by actually having an apprenticeship or delaying a little bit and not rushing into it quite as quickly as we see a lot of people doing it today.
John Simboli:
25:07
What's new at Triplet Therapeutics?
N. Bermingham:
25:09
Triplet is about a year and a half old. The company was founded late in 2018. And that really was with a piece of paper, working with some people over at Atlas. We brought in two employees towards the end of 2018. One on IP and one computational biology and computational design, and really started building the company from there. So in that period of time, over the last 12 to 18 months, we've built an organization now of about 40 people and we've progressed multiple programs now to nonhuman primate studies. We have just completed, technically, what's been called a series A, but historically you'd have called it a series B. We got 10 million seed financing from Atlas and we brought in another $49 million. So our total raise in the last few months is $59 million into the organization. And we've built out and moved into new facilities here in Cambridge, Mass. So I think we've accomplished a lot in a very short period of time. We're on track to move into human clinical trials next year, which, given how old we are, I think that that's pretty phenomenal. And it's a testament to the team here and the work that they've done and also the academic people that we've had the good fortune to work with today. So, yes, there's been a lot that's gone on with the company and I'm excited about the biology and excited about where we are. And on our website, there's a patient testament in there, not about the company, but about the disease. It can be easy to lose sight of why we're actually doing this. Within the testament, a mother talks about her husband who had Huntington's disease and unfortunately died of it. Had a son who also died of it and has another son who has symptoms. So it's remembering that. And I think that really pushes the company to move quickly and move into the clinic, but also tempering that with ensuring that when we move to the clinic it's safe and is, hopefully, doing what we expect it to do. So we've moved quickly and we will continue to do that.
John Simboli:
27:34
How do you go about focusing so keenly, as I know you must, on the day-to-day, and the moment-to-moment and making things flawless—and also remembering to remember what you just described.
N. Bermingham:
27:48
So the focus , some of it comes back to the the sports I love to do. So I love to mountain bike, downhill mountain biking. I snowboard and box. So I do ultra runs and things like that. But when you think about focus, it's really interesting. You're bombing down a mountain, right. and you're holding on to the bars of the bike. If you lose focus, you'll fall. It's not a good outcome. It's the same with snowboarding and with boxing you get punched. And I think there's an element of, it actually forces your mind to actually stay on one track and actually stay on and keep that track going. That focus, bringing that to a company, I think is very important. And when you talk about science, it's really amazing to sit down and learn new things. And as an experiment is being run, what the data as it comes out, and sometimes it leads to very tantalizing things that you want to go down and that can send you down rabbit holes. And the reality, and we have this conversation all the time, is does this experiment move us closer to where we need to get to or is it a fishing expedition that may take us down a rabbit hole? So scientifically, it's very interesting, but actually, practically, and from a patient standpoint, it does not move the ball forward as we think about getting a drug to a patient. So it's really bringing people back and asking that question on a consistent basis. It can be very difficult, to be very honest with you. There are times you get so caught up with the experimental design and the data that's coming out, you actually can lose sight of the patient and that things are moving quickly. So we try to bring patients in to actually talk to the team and remind us again and again why we're doing this and why it's so important that we actually do move forward quickly. It also, as you start thinking about moving into studies like nonhuman primate studies, being very careful and very clear about the study that you're running and why you're running it and how, again, this moves you forward or closer to actually being able to run human clinical trials and be able to treat patients. So I think you've got to always keep that front and center in your mind. The other aspect of it, that I would say is important, is the dollars that an investor gives us. When people think about investors, in many cases they're thinking about some hedge fund manager or some venture capitalist that's flying around in their jet and X, Y, and Z. But the reality is the dollars that many of these individuals are investing into us are your pensions. So we have to be very careful with the capital that we're spending because at the end of the day, we're spending money that people are putting into 401k for their retirement. So we actually have a responsibility to them also. So when we talk about spending a dollar in an experiment in some operational aspect of the business, we have to be clear that that dollar is coming from somewhere and that we have a responsibility to that individual that ultimately has invested that dollar into the venture capital company through, potentially, some other mechanisms. But it all goes back to an individual , they want to be considered, also, as we think about how we're using it and that we're not wasting that money as best we can. And that's a really very important element,I think, also as we think about the ecosystem in which we live,
John Simboli:
31:40
When you do have that moment of silence around you and you're just thinking about the good that the company can do—I'm not talking about financially or anything having to do with building a business—but the patient part of it. When you allow yourself to think, Oh my God , if this thing turns out, I could do this. What, what does that image, what's that picture?
N. Bermingham:
31:58
Within Triplet there really is this potential to be able to treat 40 diseases. The biology here seems very strong and robust. And again, all of this data is being driven through human genetic analysis. So it's not a cell culture, some cell in a dish in a lab, or it's not a mouse where you've seen this response. It's actually human patients. And that's really guided us. And the potential to be able to have a biological mechanism that is applicable across 40 different diseases is unprecedented in our industry. And it allows us, potentially, to be able to move from thinking about individual indications to really thinking about tissue. So if you have a repeat disorder in the CNS, this is the drug. And it kind of doesn't matter which repeat disorder you have. If you have it in the muscle, it's this drug. So it really changed. it's a paradigm shift as we think about not only treating large numbers of diseases with potentially the same drug, but also as we think very much about a drug development label expansion, regulatory approval, similar to some of the work that we've seen within something like cystic fibrosis where you have drugs now for multiple different mutations within the CFTR gene. So that's really exciting to me. I think that the area that I'm certainly very focused on now is how do we think about pricing? As we start thinking about these gene therapies that are coming through or some of these cellular therapeutics that coming through, the pricing of these are exorbitant and the healthcare system cannot sustain that. And as we think about healthcare democracy, everybody should have equal rights to be able to access these things. And when I say equal rights to access it, these drugs, it's equal rights, not just here in the U.S., but when we think about it from a global standpoint. Somebody with Huntingdon's disease here in the U.S. is no different, has no more right to a drug, than somebody with Huntington's disease in India or in Ireland. So when we start thinking about this, we've got to start addressing or thinking about how do we think about structures that will allow us to be able to treat these diseases and get them to patients in a reasonably fast fashion through the regulatory structure. But also when they're approved, how do you think about the cost effectiveness of them? How do you think about the distribution of them and how do you really think about that healthcare democracy? Which, frankly, I think our industry has not been particularly good at today. And one only needs to look at the gene therapies and one only needs to look at the celluar therapies that are out there to know that, for many individuals, it's cost prohibitive. Many of the patients that we're talking about here have difficulty paying for the bus to get them to the hospital, take time off from their job where they may be on minimum wage, to be able to just go to a hospital, have somebody take care of their kids while they go to the hospital, never mind having infusions for hours or taking days to actually have these treatments. How do we think about that? So we've got to think about a mechanism, we've got to think about, and people think I'm crazy, but we've got to start thinking about systems whereby we can get it directly to your door and you can inject yourself. You could deliver it to yourself. So if you think about, our distribution networks today, if you think about Amazon getting a book to you, there are some cases where Amazon literally will print that, book, bind it and ship it out to you after you've ordered it. When we think about computational design for drug design, there are computational systems that are to start allowing us to design these and synthesize some of these oligonucleotides. They're relatively straightforward, on a relative basis. They're relatively straightforward. When we think about things like Cosentyx, Humira—when Humira came out, originally, we never thought that we would be able to manufacture enough through the manufacturing capabilities that we had to be able to treat the population that needed this drug. And that really, we would not be able to distribute it out to people's homes. Look at it today. If you are on some of these drugs, the drug is shipped directly to your door or to your local pharmacy. You walk in, you pick it up, you go home to your own home and you inject it into yourself. So in the last 20, 25, 30 years, we've come a long way. And as we start to look at some of these drugs now in these therapeutic approaches,, the infrastructures are there to allow us to start to actually realize these things. So we now need to start thinking about, well, how do you actually affect that and how do you actually leverage it? And that allows us then to start moving from not only here in the U.S. and in Europe and the Western world, but actually start to move into other countries. I was in Tanzania a few years ago and when you look at the infrastructure there . . . celluar phones. People had cellular phones, were able to access them and pay to actually be able to get their medicines. So, as we start thinking about the evolution of our technologies, the evolution of our infrastructure and distribution channels, we've got to start thinking about how do we utilize those as we think about medicines and getting them to people that need them and how do we do it in a cost-effective, affordable manner that everybody will be able to get access to them? And that, to me, is the next big thing we need to address.
John Simboli:
37:35
You opened my eyes. I, like many people. I picture Amazon bringing things I don't really need that I probably should never have ordered and the drone arriving at my office or at my door. But this is different. This is potentially that drone carrying . . .
N. Bermingham:
37:49
There is no reason to believe, as you think from a distribution network standpoint, that actually you can't do that. And also as you start thinking about design, I mentioned the drug for Batten disease, the first truly personalized medicine, you could argue that some of the CAR T therapies are truly personalized medicines also, I think that's a fair argument to make. But when we think about a synthetic drug that's actually been designed and developed for that individual versus taking cells out of your body, modifying them, putting them back in. And that's the first instance of that. And as you think about that, that really opens up the door of really starting to think about personalized medicine. So if you think about where we are today, and we talked a little bit about convergence of all of these tools and capabilities, but we're moving from a situation whereby your human genome, in the near future you will be able to sequence for $100- $150 . It can all be captured up in the cloud and the analytics that can be done around it. As you start to actually look at SNP variants in there, as you look at mutations in there, as you look at, given where you live , lifestyle, you start to think about the potential for different diseases, cardiovascular disease as a very good example, and then start thinking about being able to design based on your unique human genome sequence, synthesize an oligonucleotide or a drug, formulate it, package it and ship it to you. So ,many of these tools are there, they haven't been put all together. And there's a big element here which is clearly the genetic understanding, understanding the implicatios, and ensuring that whatever we modify or whatever we impact is safe and well-tolerated. But we are getting to the point now where the integration of these capabilities now is starting to become more of a reality. And really it's up to us now to think about how best to actually utilize that. And I look at things like diseases such as the triplet repeat disorders, where really you can start to think about, potentially, being able to have a far more personalized approach as we think about targeting or treating these diseases. And, that to me is extremely exciting and hopefully will allow us to bring the cost of our drugs way down.
John Simboli:
40:14
When you encounter someone who has one of the diseases that Triplet is looking to address, are you thinking in terms of transformative, life saving? What is the degree of severity and sadness that you're trying to deal with?
N. Bermingham:
40:31
For many of these diseases it very much depends on the stage the patients at. There are some stages, late, that unfortunately with our approach, there's nothing you can do. So really we're aiming to move much earlier in disease onset and progression so that either we're delaying or preventing the onset of symptoms in these patients or we're delaying the progression of the disease in these patients. You make a very good point. I mean, for a lot of these genetic disorders, there is no treatment. So when you talk about being diagnosed, I think for a lot of people, they may not want to be diagnosed because, frankly, there's nothing that they can do. We're starting to see that shift now where people are being diagnosed more and more because there are a number of different therapeutic opportunities in development today that they may benefit , from if they are ultimately approved. I think one of the challenges though, from a patient standpoint, is I've sat on advisory boards where we've had patient representatives there also. And the challenge that sometimes you face on the flip side is that these are such devastating diseases that no matter what idea comes along, there is a drive and desire to invest into it. And the challenge in a number of cases is—that drive and desire one completely understands—but the actual project or the program that that's being looked at to be funded and that the individual wants to fund doesn't make any sense at all. And from a scientific rationale and clinical development standpoint , it's very challenging, if not impossible to actually justify the investment in that. And when you think about these, these are finite dollars. We're back to this idea about this is not a bottomless well. So if you spend a dollar in a treatment for program X , that means you have a dollar less for Y and Z. So, the patient is an absolutely central and critical consideration as you think about these companies, as you think about these programs, as you think about the input, but there's also an element that you need to take a step back and be very clear on allocation of dollars and how you think about that allocation because not everything is going to work and sometimes the data is very clear—this is not going to work and it's not in the patient's best interest to actually try and develop this.
John Simboli:
43:23
That sounds like it could be the toughest part of the job, Nessan.
N. Bermingham:
43:25
The advisory board I sat on, we had patient representatives from multiple different diseases for the various programs that we were evaluating. And it was extremely challenging because I remember one instance where we had a patient, this was an individual we'd worked with for multiple years and it was a neurodegenerative disease. And over the years, so clearly was degenerating and on a very personal level, like this is somebody that you've known, it's heartbreaking. And yet there were times that programs will come in and we could not fund them simply because they made no , from a scientific and clinical standpoint, they made no sense. And it was devastating to the patient at the end of many of these meetings. It was like, but that could be the one that cures me. And it's trying to actually navigate that, is extremely, it's extremely challenging and I can completely empathize. I mean,, it's just terrible. These are terrible diseases.
John Simboli:
44:36
Nessan, you've been doing this for awhile . As you look to the future, what do you anticipate? What do you see for the future of biotechnology?
N. Bermingham:
44:43
I think we're in an extremely exciting time. We have these toolkits now available to us. Antisense, siRNAs, small molecules, viral vehicles for gene therapy, cellular therapeutics. So we've toolkits. We are on our way as we start thinking from a manufacturing standpoint. We're not there yet; for certain aspects of the aspects we really are there and we're very effective and good at what we do. From a genetic base of diseases, there's a lot of data coming through.I think that is really exciting. And it's data that's actionable. You know, Triplet's a great example of that. As long as we don't trip ourselves up. I mean, one of the issues that people ask aboutTriplet, well, this has been known for a while . Like, why now? And it strikes me a little bit of, you probably remember—ulcers, everybody thought it was like stress, right? And like there is stress, stress driving. Then one guy is like, no, no, no. It's a bacterial infection. And finally it's turned round that actually, that is the case. So Prion disease, everybody was going around saying, there's a nucleic acid component to it, there's no such thing as a catalytic protein, blah, blah, blah. A couple of people said, no, no, no, we believe it's catalytic protein. It turns out it's catalytic protein. Or even the human genome, right? Ah, we are so complicated, right? We are these complex organisms. There must be at least a 100,000 to 120,000 genes, right, to actually make us, given how complex we are. It looks like it's about 23,000, maybe 25,000 genes in there. So I think we can drive our own failure in our thinking if we're not open minded and could be very open minded. So very exciting times, a lot of tools, a lot of capabilities. Closed minds will prevent us from really being able to understand, be able to develop and utilize those systems in place. The other aspect I think is a complete lack of understanding of sick people. We talk about developing drugs and bringing drugs to the market. And as we talked a little bit about earlier, the pricing of some of these is just, t's not viable. Some of it is pricing. Some of it is actually administrative paradigm. Where you're talking about, again, people who may be living 200 miles away or 300 miles away from the hospital where they're going to get this treatment, who may be on minimum wage, who may have young kids, who may be actually very old. How do they get to the hospital? How do they afford to pay? How do they afford to be away from home for that period of time? All the actual components around actually treating the patient. How do we think about that? So I think there's a certain lack of thinking clarity as we look at how our industry generally thinks, or some groups within our industry, think about this and think about access to these therapeutics. So I use the word healthcare democracy and I don't use it lightly. We're a democratic society, one person, one vote. Well, it should be the same as we think about medicine. So how do we do that? And it's going to be absolutely critical over the next few years that actually we figure this out and we find a way where actually that there is true democracy here from a healthcare standpoint, that everybody is actually able to access it as they need it. And we've got to figure that out. So that's my biggest concern from a very macro standpoint. From a micro standpoint, certainly the Cambridge ecosystem is becoming challenging. Just as we think about access to capability , people's capabilities or expertise, is space.Space is a at a premium here. , and I think it's very important where we took new facilities here in Cambridge, Massachusetts, we were very fortunate to work with Alexandria in being able to design and outfit the facilities here. But there's a dearth of it and we're seeing companies being forced out of here because either they can't afford it or they just can't find the facilities. How do we think about that? Because how can people in a localized ecosystem, I think, is only helpful to all the companies within it. And then the requisite expertise and capital. So there's a lot of areas that we need to stay focused on within the greater Cambridge area. But also as we think about any cluster of academic institutions, any cluster of scientists, any cluster of companies that actually we think about how to resource them appropriately and ensure that that system is in place to be pragmatic, inquisitive, consider it as you think about strategy and really actually has that inherent capability to be able to move forward—back to being thoughtful about the patient. Because this is only good for the patient and for the investor in the utilization of their dollar. So, I think, these are all very important elements as we think about our industry.
John Simboli:
50:01
Nessan, thanks for taking time to talk with me today.
N. Bermingham:
50:03
Thank you very much for hosting me.
John Simboli:
50:06
It takes just a moment of conversation with Nessan Bermingham to know you're talking with someone with keen insights. That's not unusual when speaking with a CEO or founder of a company, but there's another quality that stands out with Nessan. He's listening carefully to you. During our conversation, Nessan described leadership of a biopharma company as a humbling experience. He says, while some decisions work out well, not everything turns out as planned . "You have to stand behind those decisions and accept the fact you actually screwed it up." In my experience, this kind of integrity at the top goes a long way toward building the trust necessary for a team to thrive, and it's not only an efficient way to lead—fewer misunderstandings, less time wasted, trying to guess what leadership is thinking—but it's also the kind of personal respect that makes people want to do everything they can for the CEO and the company. As Nessan said in the quote that opens his BioBoss podcast, "Be very fair. You don't know it all. And be willing to actually listen to people. And when you're wrong, tell people you're wrong." I'm John Simboli. You're listening to BioBoss..