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Abbas Kazimi: CEO of Nimbus Therapeutics · BioBoss

• 0:00
  John Simboli: Welcome to BioBoss, Abbas,
• 0:01
  Abbas Kazimi: Thanks, John, it's great to be here.
• 0:03
  John Simboli: Abbas, what led you to your role as CEO at Nimbus therapeutics?
• 0:08
  Abbas Kazimi: Honestly, John, it's been a journey, both by circumstance and purpose. You know, I joined Nimbus more than a decade ago after getting a call from our first Chief Business Officer in 2014 and it was a moment where he called and said, I'm looking for BD talent.
• 0:24
  Abbas Kazimi: Do you know anyone good? And at that point, I said, Yeah, me.
• 0:27
  Abbas Kazimi: And so that moment really opened a door, and I've been here ever since. I think it's rare in our industry, especially in biotech, to find people who've stuck around a mission that's gone through so many cycles in our industry, but cycles as a company. And that first time, actually, when, when I got that call, was also the first time I realized the simplicity of just asking, for yourself, and the confidence that can give you of saying, Well, if you're looking for talent, and perhaps it's my turn, to transition from the investor banking side of the industry to a more operational role. So since day one, I've just been drawn to the company's mission, you know, using deep science, cutting-edge computation to make these transformative medicines,John.
• 1:11
  Abbas Kazimi: It started in business development, doing a lot of deals, from our sales of TYK2, our sale to Takeda, to our sale of our NASH product to Gilead, but, honestly, over time, I just became invested in the people, the platform, and I was doing the deals in the background, where it just became more natural. And so for me, it was a transition from doing deals and transacting to eventually building a company. So when our former CEO stepped aside after 11 years—we were together for those 11 years—a deep relationship, and the board asked me to step in. I took on the role with this deep respect for the legacy Nimbus has built, and just a real responsibility to lead Nimbus into the next chapter. So I didn't just land in the role. I look at this as I grew into the role the organization, for me till this day, it's just not defined by a single leader, a single modality, a single platform or a single investor, and it's much more than that. And for me, it's the ability to honor the legacy that we've built, because I believe in our science, our team and the ability to make this lasting impact in the industry.
• 2:23
  John Simboli: A couple of year ago, I interviewed a leader, a CEO at a biopharma company, who had come to the job from Chief Business Officer. And in his case, he had recently joined the company, and he had been Business Officer at some other places. He was accustomed to ,as Chief Business Officer, coming to meetings with the C-suite team with a series of ideas, and saying, What do you think of this, this and this? And then he said, once he became CEO, almost by default, he did the same thing. And at the first meeting, he said there was a long quiet period, and people said, Yeah, but which one are we going to do? You know, your job is not to propose all these options. Your job is to help us choose which one. That's a real simplification. But did you experience anything like that?
• 3:08
  Unknown: I think what was unique about Nimbus has been, you know, I am, I would say, the fourth CEO at Nimbus over 16 years that we have been around. The first one was, you know, Bruce Booth, Atlas venture partner who started Nimbus, and then officially, we hired our first CEO in 2014, when I started as well, by an individual named Don Nicholson. And Don came from an experience from Merck., extraordinary career, really successful, retired. We brought him out of Merck to run Nimbus.
• 3:38
  Unknown: So more of your PhD-science-CEO type. Eventually, when Don, after our phase one exit to Gilead, he left to go back into retirement around 2016-2017. Jeb Keiper, our CBO, at that point, took on the CEO role for the next six, seven years until this recent transition. So why I'm giving that history perspective here is because I think the way we run the organization, it's disseminated where even now, my style is more about this. It's I bring in the team to a very depth perspective. We share BD updates with our executive team.
• 4:18
  Unknown: So head of biology, head of chemistry, head of TOX. They're fairly aware of the conversations that were happening, and that's just because our business model.
• 4:27
  Unknown: Eventually, Nimbus is a BD sort of driven business model. In all of our years, in 16 years, I haven't really forecasted a sales force to hire. I've thought about how far we can take a drug to build value, and I think it's a culture we have to cultivate. And that culture has implications on how leadership shows up. And what I've learned from, you know, mentors within Nimbus, outside of Nimbus, is we disseminate this leadership, and when it comes down to the most complicated part of our industry, John, the question around who makes decisions.
• 5:04
  Unknown: That's an inevitable conundrum every company will have every year. I think for us right now, it's always been the, well, the BD person or the CBO brought deals forward, now you're going to decide. I think the decision factor at the end of the day, we all make a strong recommendation together. Our board is a spectacular board where it's never felt in the past decade or so, where they're telling us what to do. So I'll go to them for advice, as you should with a recommendation, and once I feel confident that I have all the viewpoints from my team, from our investors and our board, a decision feels more natural and more inclusive versus the classic, I'm going to make a hierarchical decision, and you're all going to fall in line. So we're reversing the script here. We're reversing where decisions naturally grow versus decisions are actually written down with the 10 Commandments, and you must follow them.
• 6:00
  John Simboli: It seems to me that, just reading a bit about your blog about potential for advancing through failing fast, I think, is the title of the work, and just how you're talking about Nimbus and what its background was, maybe you're more prepared to deal with that kind of uncertainty than some folks.
• 6:23
  Unknown: I would say I'm pretty self aware of what I am and what I'm not. I think, you know, I'm not a classically trained, you know, MBA from a leadership school of thought here. I'm more of a curiosity-driven leader.
• 6:34
  Unknown: I'm more of a believer in the power of teams. So what I've learned about myself, and especially now in this past transition and even the past couple of years, I had a fortunate position to be as a CBO, part of the board conversations, that leadership, for me, has never really felt about having the answers. It's about having better questions, creating the space for others to lead. And so it is challenging, especially when I had a partner in crime for 11 years, where the CEO and myself, at that time would candidly tell each other we're fairly comfortable with 70-75% information and taking a risk. And I think that is how biotechs move fast, but also we can move fast with confidence.
• 7:28
  Unknown: And you know, we know that we're managing and fortunate to work with incredible scientists who need to see all the data to take that risk on the next step. I think where leadership comes in is the ability to convey confidence that even if we were taking this risk, even if we're going to kill this program, as you mentioned in that blog we wrote, there's net benefit, because ultimately, we're driven by the same collective, and that same collective is our purpose, and our purpose is to serve patients. And so I think when I began my career in the industry, I always found it humorous, I found it's, you know, really rudimentary to, Why do they always keep mentioning the mission? Why is it always everyone opens in the meeting?
• 8:13
  Unknown: And over the years, I realized that it's so powerful because it actually is what kept me grounded. It keeps me grounded even now to the team. And so to answer your question more clearly, it's first, there's comfort in taking risk with knowing very little if you believe in the value of the individuals around you. Two, I think gratitude is the backbone of how I lead. It keeps me grounded, especially when the stakes are high, and so the gratitude comes in that we're very fortunate in this where we've developed a business model that allows us to take risk, and if there's failure, we actually celebrate that failure, because we know there's more opportunities that we can go back to, to continue serving our mission. Our mission isn't to serve a single individual with a single disease. It's to impact, broadly, patients. And so I just try to keep myself grounded in that gratitude perspective and the perspective of, why are we here together, and that allows us to take risks together. And so I think that is a very unique culture that we built. And again, I'll credit that to being around for this many years, but also the company going through a lot of changes in 16 years, allows you to keep redefining yourself, but you decide at what point what kind of holds you together. And I think those two aspects of gratitude and mission really have allowed us to take these risks together.
• 9:35
  John Simboli: Your decision making process sounds like it's collegial. Sounds like it's based on a lot of interaction.
• 9:42
  John Simboli: Now that you're CEO, as opposed to business officer, is that process of communicating it and bringing people on board any different than the way it was before?
• 9:50
  Unknown: The title is a service role, so you define how you're going to be in servitude. So I've learned the best leadership isn't about control at that point, John. I think a lot of people like to convey control, and it's easy. And I've met, myself, a full spectrum of CEOs who are probably really well known in the public sector, and if you kind of talk to their brain trust, they said, he knows all the answers, or she knows how to make all the decisions. I would say, to your question, what has changed? It's the role has changed, and for me, it's still less about control. What I've tried to amplify further is clarity, trust and presence. I think those three, you know, stools are so critical to holding up a foundation that, you know, early in my career, I thought I had to have all the answers. Now I know it's way more powerful, again, to ask the right questions, create that space for others, to bring their best. And if we're doing that, I really believe reciprocity and understanding—okay. Well, actually, I do believe him—and I do have trust in him, and I do understand this clarity. And so we will go back every year.
• 10:58
  Unknown: Nimbus is fortunate, we take the whole company off-site, and inevitably, one of the conversations for all these years has gone back to the fundamental of, how do we make a decision, right? How does this come down? And I think right now, because I have been such a presence at the company for these years, they already know me. They already know a little bit of my style, I think what they're trying to figure out is, how much is that going to change? And I think what they're realizing, the change is now further enhancement of clarity, further enhancement of trust and further enhancement of presence.
• 11:32
  John Simboli: Do you think that those are characteristics that you came to the the world with, or do you think those are things that you learned?
• 11:40
  Unknown: It's probably nurture.
• 11:40
  Unknown: You know, I grew up in a family that worked extremely hard. Son of immigrants, my siblings, you know, both very successful in their own right. You know, one's, you know, a child psychiatrist at the hospital system down in Houston, a brother who's been at McKinsey for over 20 years, advising a number of companies in private equity, oil and gas, and I in the biotech sector. And we always kind of go back and remind ourselves, from a humble beginning of our parents did something that's probably, in our mind, more difficult than starting a company or running a company. To leave a culture, to leave family, essentially, to leave memories with your siblings, to take on a risk, to take on a risk that comes with a lot of sacrifice, to go through periods of humiliation, to go through periods of not understanding what it takes to succeed. Because sometimes it's not just about putting your head down and getting good grades or doing the best job. There's other attributes. So that, for me, is foundational, right? At the end of the day, the sole message my parents had was we had each other. And we had the sense that education and service mattered, and we were a classic family, where every night we had dinner together, no matter what.
• 13:03
  Unknown: When dad came home, we all waited, and even till this day, my wife and I, who's also in the pharma industry, we tend to create that culture of conversation. And those conversations, at the end of the day, they get summarized by doing something bigger than yourself. And so I think about memories a lot, and I think about the immigrants and I asked, you know, even someone who lost a sibling. I said, you know, what memories do you hold on to your sibling who's much older? And they said, listen, when we left our family at 18-19, years old, we left the formation of those memories. The memories started becoming the interactions we had, not the I was there for your graduation, I was there for your wedding, I was there for your first child.
• 13:49
  Unknown: And so that weight, it's actually positive, it's uplifting, and I bring that into what I do at work every day, because it now goes on to two levels of personal attributes.
• 14:01
  Unknown: Number one, illness has been prevalent in my own family, watching members of my family get sick. I've lost my father to AML. He had MDS, originally. My mother has had a long diagnosis, which I talk about very openly with my teams here, because when I get a call about, hey, we have a new patient enrolled in our trial, I know what it feels like to be a family, to say, Okay, we're going to take a risk and join. So to bring that humility and gratitude to the table, it helps you clarify. It helps you manage the pressure. And on the other side, if you work in gratitude of wow, we made it here because of the sacrifice someone took for us, it makes all the other pressures less about you and your ego proving yourself and more about the individuals around you and saying, I want everyone to hear and feel what success looks like. When we signed one of our first transactions, I just couldn't wait to be with a team.
• 15:00
  Unknown: Because for so long, we talked about how we're trying to find the right shepherd for our drug, not the term sheet. And I think that inevitably felt right when we realized that wow, Gilead can take our ACC drug and impact the most patients with NASH. Wow.
• 15:17
  Unknown: Christophe Weber from Takeda has a bigger vision for TYK2 drug than we ever had, right? He's thinking globally. He's thinking about 11 indications. We thought about two. And if you find that balance in life where you are completely in service of the molecules and the patients, and I go back to how I was educated, by watching family, by watching parents, by watching other immigrants grow through it John, it feels more natural to me. It feels more, an ability to make more connections with individuals at the company, because now they get to see someone who's not looking out for his deal sheet or his own resume.
• 16:00
  John Simboli: Along the way, do you recall picturing yourself in any particular role other than, I'll find that out; I'm curious?
• 16:08
  Unknown: You know, I would probably say it's the last piece, curiosity. And it's so fascinating that you're reflecting on a question that I still think about till this day.
• 16:20
  Unknown: You know, I was fortunate, in undergrad, when you're in Texas and you're a certain percent of your graduating class, you're guaranteed admission into the University of Texas System. So I went to UT, Austin, and then I applied, I got into the business school, and McCombs Business School, phenomenal school, highly ranked and a coveted role. After the first year John, I was like, What is this? Right?
• 16:40
  Unknown: There's a lot of soft skills here that they're not teaching, and they're teaching a lot of fundamentals here that I'm not really sure sparked my curiosity. So I began my jumping around within the university that offered so much. And at one point, I think I told myself that you're never going to be here again. This is a once in a lifetime opportunity at such an extraordinarily large school with so many resources. So at one point, I jumped from business to chemistry, from chemistry to biology. At some point, being South Asian, I was pre-med. I was like, I guess I'll be a doctor eventually, because everyone's a doctor, somehow, in our family. But it really didn't tick me enough.
• 17:20
  Unknown: And towards the end of my undergrad, I graduated with a degree in Asian studies, Liberal Arts. I figured I would never read a book about Japanese anthropology or learn about Southeast Asia. And when I got into grad school, molecular and cell biology, interesting. I think I was two and a half years into it, on a microscope, looking at C elegans and counting these eggs that were hatching out of these CMA, SMA, long knockouts. I got bored again. I was like, Wait, is this really it? What are we doing?
• 17:53
  Unknown: And by chance, and most of my career has been one of circumstance and chance, and being confident about telling people I am curious. So I met an individual. Decided at that point I was going to join him.
• 18:08
  Unknown: He was one of the founding partners at MPM capital, but was running Bain and BCGs healthcare practice. At some point, he ran BCG for 26 years, and then Bain for seven years on the life science consulting side. And it was just the individual I gravitated towards, and figured, you know what, I'm going to take a chance here. So again, going back to a family that worked really hard, that had clear career paths, here's their youngest son deciding to jump, out of curiosity. But you know, it was those moments that taught me the most. When I joined the investment banking side in seven and eight, it was learning about how companies were making good decisions and bad ones. A lot of companies were shutting down.
• 18:49
  Unknown: And it went back to the, I was curious about how do these leaders make these decisions?
• 18:56
  Unknown: How are they actually going to navigate through success? How are they actually going to succeed or fail and return money to investors? As an advisor, we had a chance to give them options, but it was my first foray. Inevitably, I did not plan on being in biotech. I did not plan on being in a management role, but that curiosity till this day, has led me to a point where I've learned about what I can do, I learned about my own leadership style, my ability to make decisions with less information, and, most importantly, my decisions to connect with individuals more.
• 19:29
  Unknown: And so, over the years, it's less about doubt on why didn't I have a direct shot from here to the moon? It was more about I'm more confident now about going through curiosity. And again, chance and fortune and luck are definitely a part of it. But you can come back and say, maybe you were inevitably put in this position because you followed your curiosity. And so being in biotech, I like to find mentors, and I do have mentors who have had similar paths where none of us really kind of planned to be here. But what has allowed us to succeed goes back to the foundation of what every company has, it's great talent and a long term vision.
• 20:17
  John Simboli: Let me see if I can make a connection there. I'm going to refer to something that's kind of old, so you can let me know if it's just doesn't apply anymore. When I was doing my research, I came across the YouTube interview from, I think it's 2020, when you're talking about, you're obviously in a different role there, but you're talking about, I guess you could say the origin story for Nimbus and I felt it, in terms of an experiment, a curiosity about Schrodinger and all those things.That may be so old that it's not worth talking about this point. On the other hand, it struck me, I thought, this is an unusual reset. Is that useful in terms of talking about what your vision is?
• 20:59
  Unknown: There's a theme here, John, about, about how we can go about making breakthrough medicines to impact patients.
• 21:07
  Unknown: And I think that is, you know, it's not as direct, not as clear as some companies will say, I have an mRNA vaccine for X indication, or I'm going to validate so and so pathway. And purposefully, and probably not surprising, now, I gravitate towards that ability. And for me, look, Nimbus is a biotech that invents new small molecule medicines for serious diseases.
• 21:31
  Unknown: Across cancer, across inflammation, across metabolic disorders. And we're a team that believes that you can do science at the highest level and still keep your soul intact. And our soul is to eventually help patients. And we don't define it. And that curiosity has, I believe, allowed us to be successful. If I define success as four molecules discovered internally that have gone into the clinic, and they're still there; raising over $600 million in 16 years, which is not a lot, if you think about it, but yet able to return over $4 billion back to investors. And each one of those data points, a company would say is their definition of success. Some would say it's the clinic. Some would say it's the ability to raise money. Some would say it's the ability to return money. I think we don't think about it as myopic as that. I think first we just think about it as, what celebrates at Nimbus is the ability to say we've had four INDs, and all have successfully gone to the clinic. And knock on wood, so far, all of our drugs that we have invented are still active in patients, and everything else is a result of that focus. And so the curiosity part of our brain says, Where can we make a difference? At any level, we could have decided to enter the GLP-1 race and say we're going to make a small molecule, or else GLP-1., Or we decided, well, what's going to happen in four or five years?
• 23:03
  Unknown: There's probably going to be a lot of GLP-1s that are emerging.
• 23:07
  Unknown: You're probably not going to overcome the challenges that if you listen to the leaders in the GLP-1 space of patient experience, they want an oral drug, great, but what else are they dealing with? Well, they're probably dealing with a lot of lean muscle mass loss, and that's the next wave. And so there are a few targets that Nimbus decided that we can go after. Let's go after it. Let's take that risk. And if we fail, we have this platform, quote, unquote, that we have an ability to think about what are other indications to go towards. And those could be completely outside of metabolic diseases.
• 23:47
  Unknown: They could to be in inflammation. It could be back in oncology. And that, again, is challenging on managing a team, because you're oscillating between such vast spaces. But the culture I continue wanting to cultivate is going back to the basics of be curious and be driven by the impact of patients we're going to have. I think at some point someone asked a question around you're talking about psoriasis, or you're talking about IBD, that's not as impactful as an oncology company. I said, have you ever been around a patient who has IBD? Have you been a father or a mother lifting their child off the floor because they're in so much pain from their Crohn's disease or ulcerative colitis?
• 24:31
  Unknown: And so we're not ones to judge an illness. We're ones to decide, how can we help alleviate their suffering? And I think that is really hard to do.
• 24:43
  Unknown: But knowing what we're good at, and knowing that we have a longer term vision, I think really has driven and makes Nimbus totally unique in this sector. We build real medicines.
• 24:55
  Unknown: We've done it again and again.
• 24:55
  Unknown: Our approach is deeply integrated. We bring together computational chemistry, biology and development from day one.
• 25:02
  Unknown: And that speeds us up and sharpens our decisions.
• 25:08
  John Simboli: When people hear the thoughts you've been sharing and they say, Oh, I think I understand now, you're a x company, a platform company, you are a, you're in this space, and then you may think, well, that's part of the answer, but it's not really the answer. So is there a pattern when people kind of don't yet understand what categories they like to pigeon hole? How do you extricate yourself?
• 25:34
  Unknown: One form of intelligence is the ability to put things into categories, and people try to do that with Nimbus all the time. After our NASH exit, we were the metabolism company, and then came TYK2, and we were suddenly, oh, now you're an I&I company.
• 25:50
  Unknown: If it's not a therapeutic area, it's a technology angle. Wait, you're the first AI-enabled company to take a molecule to the clinic. You're a tech-bio company, right? Aren't you very similar to all the new tech-bio phases? The truth is, and what investors do like to hear, is that we're not defined by a single category. Not a single asset, not a single partner or a single investor. What makes Nimbus differenct, and what investors like to hear, is that, A, we've repeatedly evolved.
• 26:21
  Unknown: We've evolved from an ability to say we're going to actually win in the immunology space. We're going to crack the code on how to get a best in class, TYK2 inhibitor. We're also going to be able to go from an idea into the clinic and welcome attrition as part of it. I have learned investors equally celebrate our ability to pause programs and have the confidence to say we're actually not going to work on this investment as a thesis for this drug. We're actually going to take those resources and put it against another asset. So I remind people, the story isn't just about the exits, it's this engine. And I think at the end of the day, John, where investors want to get to with Nimbus, it's the engine. And when I talk about engine, it's the team, it's the process, and the scientific depth. The cultural DNA allows us to keep doing what we're doing. We then get to this large pipeline, and it feels like an a la carte, for the investor to say, Well, where is my liquidation event going to come from? And we can, with high intelligence and high confidence, dig into a single asset and talk about now, let's talk about our Werner helicase program. Why are we the best in class? How are we going to continue beating pharma like Novartis and Roche and GSK? We tend to put our hat in the ring against the biggest. We'll talk about our SIK2 program. And investors now can say, wow. Do I want to take a bet on an oncology play with a very competitive landscape, or do I want to go into an immunology play where Nimbus is advancing a selective SIK2 program? Is there space in the I&I world of this novel mechanism? How will this hold true? And you talk to our team, and they see that conviction, you can start seeing the investor thesis formulate together. And where they end up is, here is a company—and for me, on a personal leadership side, I love the oscillation between balancing conviction and discipline. And every investor we talk to, and again, I'm so fortunate to have an investor base that goes from your venture creation organizations, Atlas, still a very strong supporter, Lghtstone Ventures, you start getting into the SR Ones of the world, who do both public and private, and then we have a lot of crossover investors—Baker Brothers, BVF, Google Ventures, RA Capital, SV Health Investors.
• 28:49
  Unknown: And so that broad spectrum has taught me that, why do we have such a broad investor base? It's because we speak candidly about where we can have conviction on we're going to win, and yet management applies discipline on saying actually we're going to save some capital dollars and decide that we're not going to progress X program, because we don't see us actually winning.
• 29:13
  Unknown: That, I think has worked in our favor for years, and I want to continue cultivating that, knowing that right now I can actually leave this meeting and go to the next one and talk about what's happening at ASCO, how are we positioning our molecule for the next year's presentation? What's going on at AAD? Where will our SIK2 compound fit? And that, I think, is fun. It goes back to my personality of I like being in immunology one day and metabolism the next day and oncology the next day. So for me, I found the perfect match.
• 29:43
  Unknown: Go depth and breadth across the board where we can make an impact,
• 29:47
  John Simboli: This openness to breadth of challenges. How does that relate, if at all, to this idea that mega blockbuster is something that interests you?
• 29:59
  Unknown: I think, ultimately, the business model, and going
• 30:00
  Abbas Kazimi: Let's just talk about one of our emerging back to one of your earlier questions, it's actually still programs, it's a salt-induced kinase 2. So, yes, we're in play today. The question around our formation was around number one, can we work with Schrodinger and discover virtual. So FTEs were still hovering around 75-80, 76 to be molecules in silico? As of today, we work with a lot of broader companies outside of Schrodinger. They're one of our partners, but we have a number of them to continue advancing precise,. 80, because we have a few consultants that we're going our ability. Number two, the second business model principle was, can we still be virtual?
• 30:28
  Abbas Kazimi: That still holds true today. But to bring on board and but we have this, this feeling of to answer your question, the third part of it is our business structure. We're still a LLC holding company. And what that hundreds of FTEs because we've had these relationships with implies is that ultimately, as of today, there is going to be an eventual exit to a partner.
• 30:43
  Abbas Kazimi: Now, our last program that was either consultants that have been working with us for years, in phase 2b, multiple we had two phase 2bs ongoing. We were ready to get our CRO to raise money if we needed to bring on Bain. And but more specifically, the CROs we have been working with. We've Bain came in and supported us multiple times to get that phase three ready launch, knowing that if we launched a phase three study, we would probably start thinking about sale. We've had known them for over 15 years.
• 31:03
  Abbas Kazimi: Any company can come today and business engagements across all of our programs the day we announce them. Even now some of our, even unannounced programs, start a virtual model, I think what you can start Is this, the there's BD partnering interest.
• 31:15
  Abbas Kazimi: So we nominate our new targets, at a fundamental level we think about, is that target human element of the relationship. So when we call genetically validated? Is there biology that we can actually utilize and move quickly? Is there chemistry that we can our colleagues at Wu Xi or Pharmaran or Aurigene in India actually get ligands to prosecute that program? But the fourth leg of that chair is what is a potential commercial or Charles River, we're calling them by name. We're calling, by opportunity? So mega blockbusters, pipeline in a pill, is kind of where people are focusing. We'll think about how to balance our portfolio.
• 31:43
  Abbas Kazimi: There are some programs like our name, these 10 med chemists on this project. And when we talk salt induced kinase 2 program, SIK2, which we think is a mega blockbuster. It's indicated across multiple cytokines. It about a project, we talk about, what are we trying to achieve?
• 31:55
  Abbas Kazimi: can actually give pro-inflammatory resolution to inflammatory diseases. So any partner would think about So salt induced kinase 2, it's a program that Galapagos attempted Nimbus, get your best molecules to the clinic, and we're going to take over and go fairly broad, just as we did with TYK2,. The other spectrum, oncology, our Werner program to go after. They kind of muddied the water. They had a synthetic lethal target, it's very specific to MSI high patients. And until today, people are still thinking pan-SIK inhibitor, meaning there's three isoforms, SIK1, through between endometrial gastric cancers, how big is that patient population? So commercially, the question will SIK2, SIK3, and they're very close to each other. So this was be there. For Nimbus, it's an opportunity to still impact those patients who aren't doing well on a PD-1 or refractory or relapse. And again, it's also an ability to say we can balance an opportunity to say, is there a thesis that we have? And the our portfolio between what you call a mega blockbuster, but yet a drug that Nimbus feels is going to be best in class and hypothesis we wanted to test was, what if we go after SIK2 will still impact patients. So we think about that at an early level. I think it's a portfolio that you can manage those risks.
• 32:51
  Abbas Kazimi: only it's a powerful metabolic, immunometabolic target at the You know my colleagues who I talk to, I would say once or twice a week from different pharma relationships, we're not intersection of inflammation and innate immunity. It regulates always doing BD, but we're always building those relationships. They want to know, hey, that early metabolic program, where is it? Are you talking about partnerships?
• 33:08
  Abbas Kazimi: key immune cells inflammatory pathways, including cytokine Nope, we have confidence we can take it fairly far. And when you say, No, you and I both know people get more interested, and production and the resolution of inflammation. So at Nimbus, we so they want to start digging deeper. And that's not just to say we have a strategy there.
• 33:23
  Abbas Kazimi: It's honestly, I love being very said, how can we do this? Using our computational tools, using open with people. I love being very candid of what I think our team can do and where I think our team can benefit from our ability to work with not just one platform, but a variety partnering. So we like to balance that portfolio. And you know, in a year like this, in 2025 we have not stopped thinking about the next generation of targets. And so of different partners, to, number one, generate this our Gantt chart will go out to 28-29 with our current programs as leads. But yet we have this massive investment about what protein structure, look at that protein and figure out, are are the new targets coming up, knowing that we're still going to probably average between our 70 to 75% attrition rate. And there pockets that we actually can go after? And then two, the team is confident in that.
• 34:00
  Abbas Kazimi: They're confident knowing that one of these will actually do something that's going to return drive with our computational tools such high selectivity that money to investors. One of these, or two of these, hopefully will go to the clinic and continue impacting patients, we're going to get a SIK2 inhibitor that no one's seen and one of these programs may stop because there's an opportunity cost to work on another program. to either, A, before, and biologically start showing robust anti-inflammatory go to broader patients, or, B, a smaller set. So again, my job has always been in my career to create those options, and I think we're very fortunate to be able to have a portfolio that effects without this kind of broad immune suppression you've gives us optionality. Our board meetings are fun. Some may not agree, but for me, they're fun because you have strategic seen in other approaches, and we've achieved that again. And conversations on which path do you want to take forward. And the conversation becomes Let's weigh the pros and cons. And so when you go to the pharma partners, and they have the every board meeting ends with the same conversation of great job, continue creating more options. And I love that. I love exemplars in their mind that you were the first company to have that curiosity side of the picture.
• 34:59
  Unknown: the world, as you see it?
• 35:03
  Unknown: in the immuno oncology space, the most selective HPK1 inhibitor in the clinic, you're seeing responses. You were able to actually get the most selective TYK2 inhibitor going after allosteric pockets, the way Bristol did, but clearly with more selectivity, which translated to more efficacy, which is why Takeda bought it.
• 35:43
  Unknown: You're able to get a Werner program to go after a helicase that's turning over every six hours, but to suppress that helicase in patients with MSI high tumors, to shut down that helicase to drive cell death with the selectivity that Nimbus has with its platform,. You did that, and now with SIK2, we're on the path to nominate our clinical candidate by the end of the year, and first in human next year. It just shows that we have this belief that we can use our computational tools with our partners outside of our four walls to really offer a transformative new mechanism that's applicable across multiple inflammatory diseases where steroid-sparing, cytokine-targeted approaches are falling short in our mind. So that, I think, is a nutshell of how Nimbus is able to do it, select a target, work with the right collaborator, bring on the right tools from either academic institutions or established partners like Cresset or Schrodinger or Proteros to get a structure, and we just have this ability to kind of bring on the best of minds at the right time and uniquely position our lead based on our chemistry strength, our strength, our deep target, conviction and a track record of just building real drugs that, for me, is a formulation that I don't hear too often, that in two minutes, are you able to summarize a virtual platform, a technology platform, and highlight a drug that is going to be transformative? That's why I stuck around for this many years. John, I think it's very I think about that from two lenses, the word you stuck out unique of what Nimbus has been doing and what it's continuing to do in there, what good you can do in the world and what Nimbus can do. So the first part, if Nimbus succeeds the way I hope it will.
• 39:42
  Unknown: Will have brought life changing medicines to people who are sick and out of options, and that's the most important thing. We will have made science matter the most human way possible. But beyond that, what I do hope is that we show what's possible in biotech. That we can build a company that's fast, rigorous, but rooted in purpose. That you can scale without losing your soul. That culture, creativity and compassion are competitive advantages and not just feel-good values. And if we do it right, we'll not only help patients, we'll also help shape the next generation of leaders and companies. The ripple effect that I see that we get calls all the time about, can you talk to this investment that I've made?
• 40:25
  Unknown: They want to emulate Nimbus.
• 40:29
  Unknown: They want to have the same business model. They want to have the same principles. And that is great. I love that. I love being able to talk about how we've done it, why we're doing it. And that kind of good is what I want to leave behind as an organization on what good we could do in the world. Kind of goes back to how we were raised. My wife and I have a very similar upbringing, being fortunate to travel the world, to see the world as its flat, to see the world in terms of anything as accessible, but yet humbling ourselves on how how much disparity there also is in the world. And so knowing that we've worked hard, knowing that we will continue working hard for a greater purpose, we also have been very fortunate in this industry to be able to give back. And so we are giving back on two levels, one on the research side. I think that was important for me, knowing that my mother, who continues to be treated at MD Anderson, my sibling as well, and my father who was treated before he passed away, to MD Anderson, we established an endowment at this integrated data sciences group within MD Anderson. It spoke to both of what we do for a living, a lot of data sciences within oncology, and being able to take some of the computational background I've built and learned about at Nimbus, knowing that MD Anderson is doing that to serve patients. So giving back from an endowment perspective, especially in an environment where academics and human academics and universities are being attacked, we were really excited to be able to support their mission and make a difference. And then more on a local level, just giving back to the community. We've been really active with CASPAR homeless shelter out here in Cambridge, and by chance, we had a chance to meet them a couple of years ago in Cambridge. They were situated right behind MIT, and they're still there. But for me, it's all of it. I know science and medicines are important, but ultimately the humanity of it all matters as well, and so being able to support local causes of where we're from in our community, people with addiction, people who are homeless, I think it's important that we don't lose ourselves in just about the headlines on what's the next big deal going to look like. This idea of being altruistic in your work, but being altruistic in your community. For me, that's just so important. So my ambition is to never lose sight of that.
• 43:01
  Unknown: Never lose sight of being grounded with humility and being grounded by gratitude. And so if Nimbus can allow us to achieve that by the organization, being grounded in gratitude and humility, I think as individuals, inevitably, we'll have that spillover effect.
• 43:19
  John Simboli: Abbas, thank you for speaking with me today.
• 43:22
  Unknown: My pleasure. Our mission is to serve patients and to make medicines and leadership. Will have to navigate through all the inevitable questions of what may or may not happen, but yet manage risk with a deep, deep purpose to serve others.