Naji Gehchan: Hello, leaders of the world. Welcome to “Spread Love in Organizations”, a podcast for purpose-driven healthcare leaders, striving to make life better around the world by leading their teams with genuine care, servant leadership, and love.

I am Naji, your host for this special episode in partnership with Boston Biotechnology Summit, a bridge to collaboration and innovative synergies between healthcare stakeholders. I have the pleasure to be joined today by Mark Namchuk. Mark joined Harvard Medical School in January 2020 as the Executive Director of Therapeutics Translation. In this role, he works with HMS scientists to identify and harness basic insights into clinical therapies, creating an infrastructure that advances the School’s scientific discoveries along a translational trajectory while training the next generation of therapeutics investigators. Mark joined HMS after a 24-year research and development career in the biotech industry, working in a number of areas that included drug discovery, translational science and pharmaceutical development. In 2015, he joined Alkermes as Senior Vice President of Research and Nonclinical and Pharmaceutical Development. Mark had previously held a number of senior research positions at Vertex Pharmaceuticals over 17 years, including Senior Vice President of North American Research and interim Global Head of Research.

Mark, it is great to an honor to have you with me today!

Naji Gehchan: Before we dig in your masterclass during the summit about Optimal Roadmap from a New Idea To a Helpful Medicine, I would love first to learn more about your story and how you became this influential leader and pioneer in biotech?

Mark Namchuk: Sure. Uh, I always, from a scientific standpoint, what I first fell in love with Was how chemistry and biology interacted and and more specifically how biology seems to use energy in the most creative ways to do biological processes or get things thing one to stick the thing to.

And after finishing my PhD in enzymology and doing a postdoc in immunology, uh, I got my first industry job, uh, and about two years into it, this was when I was at Cubist, uh, I was made a project lead for my first antibacterial discovery project and really fell in love with the process of drug discovery, um, really from a scientific perspective, in order to do it well, you need to understand Chemistry, biochemistry, biology, pharmacology, properties of molecules, medicine, all of the pieces and how they fit together.

And every job I took since then has always had a little bit of that piece still in it. Uh, so as I, uh, left Cubist and went to Vertex, uh, started out at the bench and then was there quite a while, uh, and ended up in a more senior position and really had the opportunity to see Vertex go from a company that had its first drug, uh, all the way through to where it ended up today.

And that journey, uh, all the way along really kept to those same principles of. A love of what applied science and drug discovery can do, how can we do that better, how the pieces fit together. Uh, and then similarly, when I went to Alkermes, uh, different therapeutic areas, first time I’d worked in CNS drug discovery, uh, really passionate about trying to improve, uh, healthcare in the area of serious mental illness and addiction, and still very passionate about that area.

But a different, um, stage in my career. I came in as a senior person, wasn’t sort of building my career all the way through. So an opportunity to take a lot of the lessons I’d learned earlier in my career and, uh, decide how I wanted to build the research culture there and a chance to, rather than grow along with a company, but maybe put a stamp on something in the way I’d like to build it.

Naji Gehchan: So I want to go there because in the first chat we had together, we talked a lot about leadership, the culture we build and how this impacts science and ultimately the patients we serve. So you you’ve done it, uh, growing in a company, starting a company, you’re seeing company kind of being built and then going to the next stage.

What is your main leadership learning as you’ve done it and how you think about leadership, building a biotech science company?

Mark Namchuk: Yeah, I think I would touch on something you said in your intro. I, I’m a big fan of this term servant leadership. I think the first thing I’ve always felt is very important is to remember that drug discovery in particularly in the earlier phases through phase two is a deeply creative enterprise.

And everything you should be doing should be fostering your ability to support that creativity. So what are important components of that? A, uh, the people who you have on the team. Do you bring in people that A, have, uh, it, especially in Boston, we have this wellspring of extraordinary scientific talent, but there are these other pieces that are very important too.

How well do they think across disciplines? How much do The people on the team love working with that individual. Um, B, I think we all are familiar, particularly those of us that have worked in industry, there’s timelines and there’s milestones and all these pieces that can be important. You can’t let them, you can’t let the process completely hijack the creative enterprise.

And as a leader, sometimes your job is to fight that a little bit. And then, uh, I would say, lastly, uh, one of the things I always tried to do, and, uh, hopefully did well at times, but held my leadership teams to, is a couple of basic principles. The first is, Your job as a leader in of an enterprise like this is to be the coolest person in the room.

When bad news comes, your job is to also be the person that takes all the stresses that the company might put around that bad news on yourself so that your team feels free to still work creatively and do the jobs that they were hired to do. And B, how approachable are you, uh, from a scientific perspective?

I think too often you have, uh, you have scientific leaders that, uh, feel like their job is to be the smartest person in the room. And I always felt that, uh, That my job was to, to, uh, with conscious intent, not be the smartest person in the room, surround yourself with people who are brilliant and know that your job is to conduct the symphony, not necessarily, you know, ultimately, as leaders, sometimes you make the final decision, but you’re really trying to give everyone in the room a chance to play their instrument well, contribute to the beautiful music and feel like their part is being valued and seen.

Naji Gehchan: I love this example and image, right, about being the conductor and making sure that everything at the end, the creation of all those individuals and people, we’re doing it as, uh, as a larger team. Uh, and as you build this one key component in drug discovery development, I’d argue in any company, uh, is how you build this so that people can stay creative.

And deliver, because as you said, you touched on the timelines, certainly we need to deliver on timelines. You’ve lived also companies. You said from the very first idea to them becoming commercial, how do you combine all this? I know that you talked about servant leadership, the notion of trust to be able to make it happen.

Any, any big learning you would say to us as leaders and operation operational leaders. to keep this happening?

Mark Namchuk: Yeah, uh, maybe two things. Uh, maybe starting at the team level first, uh, one of the, I was really influenced by the book Quiet. Which is a book on introversion and, uh, many scientists are quite introverted.

And I think we’ve all been on teams where you’ve got the classic, uh, type A personality that dominates the room, et cetera. I’m a relatively type A person. So I find myself having to censor myself at times, but what are you doing in that team environment when you’re running the team to ensure that that brilliant quiet voice is heard, right?

At the right time, and there’s simple things you can do that, for example, is, uh, for folks that are, uh, That need a bit more time to think deeply about a problem, get in contact with them two days before the meeting, cue up what the topic is going to be and not necessarily have this as a debate exercise where in 30 seconds, you have to articulate your point of view, building a culture around all those ideas being heard and valued structuring meetings.

So there’s places where you genuinely intervene and those quiet voices are heard. I’ve found to be the most productive way. To make sure that all the ideas that are on the table to foster creativity. Uh, I would say the second piece, maybe a level up from that is to understand that when you are the leader of a project and a goal has been set.

When you’re going to take the responsibility for that goal, but sort of let the team off the hook. They’re 1 of the things that I really believe in is, uh. That ultimately for a scientific enterprise, you have control over the quality of the experiment. If you’re doing really creative science, you have no control over the outcome.

So as, as you get into a more senior role in a company, your salary, your bonus. And your responsibility is to the corporation. You now have, if you run a larger group, many ways that you can be successful. I can have project one work. I can have project two work. I can have project three work. That’s not the same as if you’re only running one project or if you’re running a component of that project and giving the people in the team the opportunity to continue to do good work and understand that if, even if the project doesn’t turn out the way you hope, but they did a work that they’re going to get an A is one of the most important ways that you can ensure that people continue to take risks in the work that they do, as opposed to try the easiest things.

And then I would say lastly, and this is something I talked to the students at Harvard Medical School a lot is, um, I think of biotech in particular as an argument between science, medicine, and business. And it is at times an argument. I, I think any of us that have been in senior management have been in times where everyone is working in accord and in times where it’s a relatively vigorous debate.

Um, I think if you get into a senior role like that, Part of the art is knowing whose turn it is to win. So if you’re the head of research, do you know enough about clinical development to know that for this project, it is now the time for the clinical development group to win in the argument. And that means you maybe don’t do some things you’d like to do or for the company as a whole, it’s time for the financial argument to win.

And so I think from a leadership perspective, training yourself to be bilingual enough that you can have a good conversation with the head of clinical development or the CFO to come to a good conclusion is really important, but also knowing when it’s your turn to push. That it’s researchers turn, for example, more of my career to win for lack of a better way of putting it, finding that balance is very important.

And I think that getting those right is how you can balance the necessities of the company at times, but not necessarily have the corporate goals washed down to your entire team where they feel like suddenly they’re responsible for the stock price. I think that can be a very dangerous way to make people take on a pressure, which honestly, as a leader, that should be your.

Not necessarily theirs. They should be creatively going on to do great science on the next experiment.

Naji Gehchan: Those are incredible insights. Thanks for this, uh, Mark. There’s a lot, a lot to learn from, uh, from what you said. And if I take them now from the leadership aspect that you brought, uh, into what you will be sharing and what you shared, uh, during the summit, really the roadmap and the optimal, uh, roadmap from new idea to a helpful medicine.

So there is. A lot. And as you said, so this is why I love starting with the leadership aspect of things because we hear about all those innovation, but drug development, discovery, development, and bringing it to market is hard. We’re constantly humbled by all those discoveries that never gets there and few of them getting there.

So, I’m eager to hear a little bit about your thoughts on what is the optimal roadmap and how can we bring those ideas from ideas to patients, actually.

Mark Namchuk: Yeah. And I think, uh, uh, I’ll start by saying, uh, I, I have a phrase that I use a lot to build on what you just said is, is, uh, biology will treat you, teach you great humility.

And so understand the world that we’re in, no matter how well planned we’ll have. Uh, I think that in my current role at the medical school, uh, a mission I, I, I want to take on. And I think is a value is to understand the impediments. Between an initial insight at the bench. To getting into phase two, where we can really ask that question in a human being, is this a medicine that has benefit and is well tolerated enough to be used?

I think you can divide many of those impediments into a few buckets. One thing that we’ve tried to do, Uh, within the therapeutics initiative is to bring expertise that would more typically be seen in the pharmaceutical industry in drug discovery science and have that scientific expertise available at the highest level to our P.

I. S. within the H. M. S. community right from the beginning of their idea. So if you are thinking about translational work, Can we partner with you as translational scientists? You’re a brilliant P. I working at the cutting edge of biology in this particular area. You’re interested to see what might happen in terms of drug discovery with that idea.

Let’s make that easy to do. Let’s bring in scientists that you’re going to respect because that are scientific imprimatur. Let’s have a science first conversation. As opposed to this is what you’ll need to do to get an investment opportunity. Let’s really focus on the science first and see if those initial steps can be done more efficiently.

I think the adjacent component to that that I’m very interested in doing is rethinking academic industry collaboration to make the transition from that initial idea into more hardcore drug discovery more efficient. One way to do that Is to work on collaborative structures where scientists from a company, for example, and the academic scientists are working hand in hand very early in the process.

And when benefiting from both sets of expertise to try and get to the best world that one can to, um, be able to, um, move that idea more efficiently. So, and then at the philosophical and business level, I think that we need to put more emphasis on the, how well a partnership facilitates high quality work, moving from the initial idea to phase two as a primary goal.

Maybe even when that might make the financial terms a little different. As opposed to the financial terms as being the primary goal, which sometimes can happen in these negotiations, particularly depending on what the stages of an asset and I think there is a lot of work that can be done to really harness the benefit of scientific minds on both the corporate side.

And on the academic side where everyone is doing what they’re really good at. So I’ll give you, let me give you like one concrete example that really bugged me during the COVID pandemic, but I think is, is a great example where there are things that, uh, we’ve done in industry for decades that are not as well inculcated into academia yet.

So, uh, if you’ve ever worked in infectious disease and you’ve worked on an antiviral or an antibiotic. You know that in order to have a clinically effective agent, you need to essentially shut down all replication of the pathogen. So for antivirals, and this has been shown for SARS CoV 2, for hep C, for HIV, if you take the, uh, adjusted for free fraction, IC90 plus potency of that molecule, it’s a reasonable predictor of clinical outcome.

And yet, for numerous, I’ll go as far as saying thousands of publications that came out from the academic world during COVID, they would use the IC 50 as the main driver of both efficacy and therapeutic index. And because of that mismatch, a lot of the work we did in drug repurposing was never going to work.

There’s an example where if what we knew on the act on the industry side in terms of drug discovery was more broadly disseminated in the academic community, I think we could have done more productive academic research during COVID. And those, that’s just a simple example of the secrets we don’t share with each other very well, but that the science in the middle could be so productive.

Uh, and so I think that’s really what I’m, part of what I’m going to talk about at the conference, but also I think a bit more of a call to action to rethink the process. I think there’s a lot of benefit to everyone involved, but to build it around scholarship and scientific advancement.

Naji Gehchan: Great. Uh, you’re talking and focusing really on the collaboration that we can do between academic partnership with, uh, with industry. You’re mentioning also about a different way of thinking on investments, right? Like where to take the risk. You’re pushing towards, if I understand well, and this is what I would love to dig a little bit deeper, um, early on starting to think about the phase two trials and how you’re getting to clinic and probably take a higher risk.

If I understood well, in the beginning to be able to keep being creative and building the drug that will get to clinic faster? Am I, am I getting it the right way?

Mark Namchuk: I’ll

Naji Gehchan: clarify

Mark Namchuk: it a little bit. I think that, that what I’m really advocating is, uh, if you’ve got a biology idea, even at the very beginning of an academic, in an academic setting, there are certain Experiments one can do that are more translational, that if you have a capability within the university and people that live that world, ask those questions earlier.

So in a way it’s getting to some of those hard questions very early in the process. Academia will never do a translational work on the scale that industry does. It’s just cost prohibitive and skills prohibitive, but are those first framed in a way that if the answer is yes. All parties, including a partner, subsequently, would see value in that answer.

And I think it comes back to being informed by what questions will eventually be asked as you go to the clinic. So I, I, I know your background, Nadja, you and I are fellow travelers in some of this. I always like to think about a project in the early phases in my industry days from designing the proof of concept trial.

To economize on the experiments you were doing to decide when the drug was ready to go. It’s set your pharmacology strategy. It’s set your non clinical development strategy. It’s set whether you had to invest heavily in a biomarker and find a responder population versus you didn’t need to and I think that same sort of thinking going to be applied in maybe in a less comprehensive way in academia.

So, uh, I, I, I think it’s less about, uh, the economic de risking. It’s more about the value of trying to find scientific synergy earlier in answering those questions in a different order than we have traditionally.

Naji Gehchan: Marc, as you were, as we were talking also about those, um, efficiencies as you frame them in those partnerships. I couldn’t, but you know, like these days everyone talks about AI and some use cases, right? And you gave this example about COVID, IC50 versus IC90. How do you think about AI in these things? You know, and I was, as you were describing the COVID example, I’m like, yeah, well actually if data is proprietary and we’re not putting it out, probably we wouldn’t have even know, like AI wouldn’t have picked it, but I’d love to.

Got to get your thoughts about use case of AI in drug discovery and improving efficiencies in the system.

Mark Namchuk: Yeah, um, I think a lot of the best use cases for AI are probably taking place in companies right now because they’re a gonna have a much deeper bench of data. That they can go back to an AI, like any computational approach is going to be best informed by best information.

So I, I, I can say that, um, a lot of work is being done in small molecule generative AI. That’s quite impressive where you can do more from an initial crystal graphic structure. Do a good job of a comprehensive early chemistry campaign. And I think that work is just getting more and more productive. But I would go back to, uh, it’s best informed by having a real bonafide hit on a real bonafide structure.

A question I’m asked a lot of times is, uh, now that we have alpha fold. Do we need all of these other iterative methods to do structure biology and things and the feedback I hear from my corporate colleagues are doing this every day is alpha folds. Okay, but it is a relatively low resolution. Apo structure so a little at this in its current incarnation.

Not that informative from a design standpoint. Now, will it get better with time? Sure. But I think we still have to go back to having a better partnership between the advances in AI in the experiments we run. And I think that partnership, but in the academic setting, one of the things that I, um, I would like to see more of is, uh, Really advanced computational people working hand in glove with people that have deep expertise on the drug discovery side.

So the experiments are designed and then fed into the most advanced models. Let me give you another concrete example is there was a lot of work used done during covert around, uh, repurposing to identify Targets that could be useful targets for covert infection based on large screens of of either the existing pharmacopeia or pharmacologically active molecules.

And, uh, often the mechanistic conclusions that would say, oh, this particular receptor is important for covert replication. We’re flawed because the screens were run at very high concentrations of molecules that are highly molecularly promiscuous. So that there’s nothing wrong with the AI and the computational people are brilliant.

And, and so, but what was fed in, uh, one specific example I, that I was, uh, uh, was some work I was involved in was, uh, seeing that, that, uh, receptors that were more traditionally involved in. Uh, psychiatric medicine like serotonin receptor, et cetera, we’re coming up in rescreening with molecules that hit those receptors, but at very high concentrations of the molecule, if you look at the pharmacologic profile of those molecules at that concentration, there are 100 targets that could be interacting at that concentration.

So it’s a simple example, but I think it’s where we have to think about. Goes back to the symphony example, how do we work together in experimental design to marry the advances that we have in machine learning pertinent data to the question being asked. So, I, I would like to see that done better. I think that’s held back having this, like, aha moment and true drug discovery for AI.

The advances are extraordinary. Our ability to create data is extraordinary. Um, but I, I would like to see it better married, I guess, would be my point of view at this point.

Naji Gehchan: So, Mark, I’m gonna now, uh, give you a word. In this section, and I would love your first reaction to it, whatever it comes to mind. All right.

First one is leadership.

Mark Namchuk: Uh, my reaction to it is I don’t know that there is such a thing as leadership as a proper noun. I think for it to be real, it has to be a blend of, of you and your authenticity and how that melds to the work that you’re trying to lead.

Second one is innovation. I don’t use the word anymore.

Naji Gehchan: Tell us more.

Mark Namchuk: Yeah, I, I, I, uh, it gets used so often in so many different contexts. I don’t know what to do with it. And so, uh, I, I will admit this is more of a personal thing. I have a bit of an adverse reaction to the word now, because so many things get categorized as innovative, and the beauty is in the eye of the beholder.

So, uh, I, I think I would, I guess if I was giving a one word answer, I would say overused. In the sense that, uh, I don’t know what it means.

Naji Gehchan: I love this reaction. If I take the word war that is also already used, innovation, breakthroughs, like all those words, the buzzwords that we have and really apply it to medicine and what we talked about, drug discovery and development and really outcome is bringing them to patients at the end and changing their lives.

Is there one that you’re most excited about for the next decade? Is there one technology? I want to say one innovation, but I’m afraid not to say the word innovation.

Mark Namchuk: Yeah, I would say no. I think as a, maybe a broader principle is, uh, if I look back to when I started 30 years ago, we largely had small molecules and the dawn of protein therapies as our only two, uh, methods.

for manipulating disease biology to get a good clinical outcome. That, those days are done. And so now there is a plethora of tools. They’re at varying levels of maturity. And I think for the first time we can now look at a disease and say, let’s pick the tool based on the nature of the disease, as opposed to say, we have to make a small molecule to treat this disease.

And I think the potential for that Is enormous. Uh, I think all new technologies have their impediments. So, for mRNA or RNA based therapeutics generally, uh, nucleotide based therapies generally, delivery is a big issue. But I think over time, that will get better and better and better. I don’t know where the speed of light for that will be, but I don’t bet against the progress.

And it just opens up an entirely different way of looking at a medicine. Like it, I’m not so sure we have to be concerned about drugability anymore. Because we have this whole argumentarium of ways that we can go after something at the expression level, where the only thing it has to stick to is the messenger RNA.

And that, that I’m very excited about that. That opens up enormous areas that we could get into that just were not available two decades ago.

Naji Gehchan: The third word is health equity.

Mark Namchuk: Yeah, I think that, uh, a responsibility all of us have to live into as best that we can, uh, probably as a discovery scientist, one of the places where I often feel like I can do the least good in the sense that, uh, the biology leads you to different areas that, uh, something looks like a good target.

What you’re going to take to the market is dictated by developability and commercial viability. So I think that an area where, uh, in my current work, I think a lot about it, and it comes back to the health equity principle, is there are areas of enormous Unmet need where, um, they’re just not great areas, uh, economically, but perhaps we can have more of an impact at the academic level.

A specific example of an area that is in enormous need of I’ll use the word innovation. Uh, but, uh, advancement, uh, is addiction therapy. Very difficult business. Generally speaking, uh, the, uh, the neurobiology is very complex. Yet, uh, if you take a look of places where addiction is most prevalent, it’s hard to not come to the conclusion that economic disparity in some ways is overlaying with our ability to get good care for these sorts of things.

And so I think there are, uh, disease areas that. Um, we should really put concerted efforts behind. I think they can disproportionately affect our most vulnerable and we can have, for example, have a cancer moonshot. And I think that’s a very worthy thing to do. But we have a pretty good system for bringing cancer therapies to patients.

It works quite well. I think the shame of it is our system for advancing medicines. Often fails worst in places where the economics, uh, and the people who would be best served just don’t have access to that medicine. I mean, uh, infectious disease is another great example where, uh, a lot of, uh, a viral infectious diseases are, are going to be most prevalent and most devastating in less prosperous countries.

And so how do we square that up again with my background being more as a discovery scientist? How do we get better discovery science aimed in those areas in a credible way that it actually eventually becomes a medicine? This is definitely something I’m thinking about in my academic career.

Naji Gehchan: Um, certainly in my work, as, as you know, I’m also constantly thinking about this and also my, where I come from, my upbringing is certainly something that I’m very attached to.

The last word is spread love and organizations.

Mark Namchuk: What was, I’m sorry, what was the first word? Spread

Naji Gehchan: love and organizations. And organizations.

Mark Namchuk: Uh, so, uh, boy, could we use a little more spreading of love these days. So I would just say bullion, let’s do more of it. I think that there, there’s a, um, there’s a, uh, a debate going on in our society now that I think would be well served To maybe embrace that philosophy that you brought up.

So I spent 24 years in the pharmaceutical industry, and I can think of no industry that is more roundly criticized yet. Uh, if 1 takes the economics out of it and takes a step back. I think a lot of the work that’s done in the medicines that are produced are unto themselves pretty virtuous and can help a lot of people.

So I think from an org, when we think about organizations, and we think about our critiques of organizations, and that can be government, that can be different companies, that can be different corporate entities. I think the organizations themselves need to think a little bit more about their sustainability.

Through the lens of how they benefit society and not just the pure money of it. And there’s, I, I’m actually kind of a, uh, a fan of the whole principle of conscious capitalism, where capitalism is very efficient, but it can have a heart. And when it does, it’s often a better business. I don’t think you have to separate those things.

And, um, I, I think that. One thing I’ve always believed and have been saying a lot lately, unfortunately, uh, just given how loud our arguments are these days is try and find the 10 percent of truth in any criticism. And then maybe take the moment to go back to the critic and thank them for that truth. And that’s just not our reaction these days.

And so I think that, um, we could all present company included do a lot better at trying to see the, the virtue in what someone’s bringing up as an idea or an advancement rather than only the critique. Maybe that’s a better way to find some mutual express on our way to trying to be a little bit more loving.

Naji Gehchan: Try to find the 10 percent of truth. I love it. And the criticism. Well, any final word of wisdom mark for healthcare leaders around the world?

Mark Namchuk: Sure. Uh, well, first of all, thank you for having me. This is fun. And I appreciate the opportunity. I think the, um, one thing I would say is, uh, what ultimately we do when we do it well, is a valuable and virtuous thing.

And I think when we’re focused on that. Uh, you know, if you go back to the old George Merck quote about being patient focused 1st, uh, I think we ultimately are both better, uh, more productive people. We give more back to society, but we create followership of principled people that are in things for the right reasons.

So, I think part of being a servant leader is making sure that your mission is appealing to the kinds of people that you want to have in your organization. So, I think, uh, all healthcare leaders. Have an obligation to explain to the folks that work for them the, uh, ethos of what they do and why what they do, uh, is, has, uh, value in its principles.

And I think that often is, uh, is going to get you a lot more buy in than the dollars and cents arguments, which we have to manage, but I think are often not as compelling.

Naji Gehchan: What a great way to finish our conversation. I could spend hours chatting with you. It was a real pleasure. Thank you again for joining me and being with me today, Mark.

Mark Namchuk: Thank you again for the invitation. It was a pleasure.

Naji Gehchan: Thank you all for listening to SpreadLove in Organizations podcast. Drop us a review on your preferred podcast platform. More episode summarizing Boston Biotech Summit can be found on our website or your preferred podcast app.

Follow us on LinkedIn and connect with us on spreadloveio.com. We’re eager to hear your thoughts and feedback. Most importantly, spread love in your organizations and spread the word around you to inspire others and amplify this movement, our world so desperately needs

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