Novel technologies aren’t interesting to Rahul Kakkar, M.D. unless they help patients. Sounds rational, but it’s actually a unique perspective in a platform-crazed biotech industry. Dr. Kakkar’s worldview is shaped by his work as a physician—work he continues at Brigham and Women’s Hospital even as he builds Tome Biosciences, where he serves as President & CEO. Tome, which is developing programmable genomic integration technology, is the latest of Dr. Kakkar’s entrepreneurial efforts—he previously led Pandion Therapeutics to a $1.85B acquisition by Merck and Cordivia to a $2.1B acquisition by Novo Nordisk. On this episode of the Business of Biotech, Dr. Kakkar shares why he took on the brainchild of two MIT scientists under his wing, the nascent inflection point for gene editing therapy, how his work as a physician informs his biotech leadership, biopharma’s bad rap, and a whole lot more.
You've listened along for years -- now you can watch along, too! Go to bioprocessonline.com/solution/the-business-of-biotech-podcast, where you can put faces to voices as you watch hundreds of interviews with the world's best biotech builders. While you're there, subscribe to the #BusinessofBiotech newsletter at bioprocessonline.com/bob for more real, honest, transparent interactions with the leaders of emerging biotech. It's a once-per-month dose of insight and intel that you'll actually look forward to receiving! Check it out at bioprocessonline.com/bob!
Novel technologies aren’t interesting to Rahul Kakkar, M.D. unless they help patients. Sounds rational, but it’s actually a unique perspective in a platform-crazed biotech industry. Dr. Kakkar’s worldview is shaped by his work as a physician—work he continues at Brigham and Women’s Hospital even as he builds Tome Biosciences, where he serves as President & CEO. Tome, which is developing programmable genomic integration technology, is the latest of Dr. Kakkar’s entrepreneurial efforts—he previously led Pandion Therapeutics to a $1.85B acquisition by Merck and Cordivia to a $2.1B acquisition by Novo Nordisk. On this episode of the Business of Biotech, Dr. Kakkar shares why he took on the brainchild of two MIT scientists under his wing, the nascent inflection point for gene editing therapy, how his work as a physician informs his biotech leadership, biopharma’s bad rap, and a whole lot more.
You've listened along for years -- now you can watch along, too! Go to bioprocessonline.com/solution/the-business-of-biotech-podcast, where you can put faces to voices as you watch hundreds of interviews with the world's best biotech builders. While you're there, subscribe to the #BusinessofBiotech newsletter at bioprocessonline.com/bob for more real, honest, transparent interactions with the leaders of emerging biotech. It's a once-per-month dose of insight and intel that you'll actually look forward to receiving! Check it out at bioprocessonline.com/bob!
I'm Matt Pillar, host of the Business of Biotech podcast, and if you're listening to my voice right now but not seeing my face, maybe you haven't heard that we've launched a new Business of Biotech video cast page under the Listen and Watch tab at bioprocessonlinecom. There you'll find hundreds of videos of my interviews with biotech builders, categorized by topic, like finance and capital markets, regulatory discovery and manufacturing. Don't try it if you listen while driving, but be sure to check it out when you get where you're going. Go to bioprocessonlinecom, hit the listen and watch tab and choose business of biotech in the dropdown.
Matt Pillar:Some of the best conversations to be had are with biotech execs who, in a life previous to developing therapeutics, were practicing physicians, having exercised patient care from the bedside. Their worldview is often a little more empathetic and they often draw brighter lines between the drug development work done in industry and the patient needs their companies seek to address work done in industry and the patient needs their companies seek to address. I'm Matt Pillar.
Matt Pillar:This is the Business of Biotech, and my guest on today's show is unique in that he never fully turned the corner when he entered the biotech leadership ranks. He's founded and led a couple of biotechs now including the exciting new company he's found in Tome Biosciences. He even held a leadership post at AstraZeneca for a while, but he's also still a practicing physician at Brigham and Women's Hospital. On today's episode of the Business of Biotech, Dr Rahul Kakkar, president and CEO at Tome Biosciences, joins us to talk about his worldview as a physician slash biotech exec, how that perspective informs his affinities and his approaches to different modalities, the gene therapy tipping point and a whole lot more. Dr Kakkar, I'm thrilled to have you on the show and welcome.
Rahul Kakkar, M.D.:Pleasure is mine. It's Rahul, please.
Matt Pillar:All right, there you go. We'll go with that from here on out, and here's where I want to start. I want to start with story time, rahul. That's where I want to start, because there's a story, I'm sure, in the transition from your undergrad to life sciences, because you earned your BA at Tufts in art and architectural history and then at some point and this is the story I want to hear you decided you're going to stick around for an MD. You know, I don't see that every day, so tell us tell us what was going on there?
Rahul Kakkar, M.D.:Yeah, I was, I was. I was laughing as I saw the the, the question you were going to ask. I was like you really had to dig deep in the internet to find that one. Given how long I've been around I have been, I guess there's two answers to that One. I've been a bit of a black sheep. Everywhere I've gone in my professional career, um, and my pivots, uh, in my career, whether it was coming out of undergrad, um, or even moving from academia and industry, has been a series of um. I guess, to be kind, you could call it epiphanies more like panic attacks were probably a more accurate way of saying it.
Rahul Kakkar, M.D.:But I fell in love with art and architectural history over the course of my undergrad. I actually fell in love with it in high school, to be honest. I remember I was the only one sitting in the basement of the converted church taking the architectural history AP class exam in my in high school. That was an. That was an option for you in high school. It was, it was. I was the only one sitting in that basement taking the exam. Cool, I I loved looking at the human experience from the perspective of the things we've built and the things we've made. I think they tell a much more vibrant and interesting story of who we are, rather than the way history is usually taught, and so that's probably because I couldn't stay awake in history class. That's kind of how I chose to really understand, you know, questions that all of us think about at some point in our lives, which is you know, where have we been and where are we going?
Rahul Kakkar, M.D.:Fundamentally, though, moving away from the study of art and art, architectural history or even consideration for a career as an architect, which was a serious consideration for a while, um rested on, um, like many things, the guidance of my parents, um where, you know, moving into the sciences and medicine, um was seen as a more stable career, um, a more reliable career, and my parents were immigrants to this country, um and worked their tails off um to go from effectively nothing Um.
Rahul Kakkar, M.D.:You know, my father's family, uh was one of those families that had to move from what is now Pakistan into India when the British cut the cut the country Um, and so, literally, when he came here, he had nothing to his name, um, and worked very, very hard to put me through school, and so his advice was. You know you can love and study whatever you'd like, but at the end of the day you've got to support your family. So that was sort of the push into the sciences. But I never was satisfied with just I don't want to say just, but with becoming a practicing physician and practicing my entire career, and so that kind of led to the second panic attack becoming a practicing physician and practicing my entire career and so that kind of led to the second panic attack, which was at the end of my cardiology fellowship at MGH, when again I really wanted to be part of the story of how we move in this case human health, but our society forward, rather than being someone who simply practiced.
Matt Pillar:Yeah, yeah, that's, wow, that's a's. That's pretty cool story. I still I. There's still conflict though happening for me, like between the sort of the, the liberal arts bend, you know the right and left side of the brain. Right, like, how, how do you, how do you reconcile that, like I don't know, making the leap, I mean I could see, from art and architectural history to perhaps architecture, but then you know there's a leap to perhaps architectural engineering, and then it's a whole different ballgame to leap into medicine. Right, like, do you? Was there any conflict or struggle internally with you in terms of, like you know the right and left side of the brain, kind of arguing with one another about where your true skills and passions lie?
Rahul Kakkar, M.D.:Oh, intensely, intensely. So I actually got into medical school early in my second year of college and so that really opened up the last couple of years of college to really study whatever I wanted, which is where I focused on art and architectural history and I actually took a year off because I seriously considered moving away from the sciences, because I was already in, yeah, accepted to Tufts Medical School. I was now, you know, graduating with a major in art and architectural history or art history with a focus in architecture, and that struggle that you allude to astutely was front and center when I decided I'm not really sure I want to go to med school at the end of the day. So my father's company, which was in Lynn Massachusetts, a steel manufacturing company, needed a draftsman, and so I went and worked in the family business for a year. Really, yeah, the Logan Airport Terminal, a light fixtures, what I worked on, kind of drafting those out for, lifting the plans from the architect's plans and then detailing them out so our shop could actually make the curved steel to go into the soffits.
Rahul Kakkar, M.D.:And after that year of essentially working in boots on the ground in a steel manufacturing company, going out to the site, to Logan Airport, seeing these things fabricated in the plant and then installed it. I don't know what it is, but it's almost like it got out of my system. At the end of that year came along and I said you know what? I've got this, I've got this acceptance at, at, at medical school, and I think I'll regret it if I don't give it a shot. And um, I I went, uh, you know, matriculated and was happier than I've ever been. And I I don't think I would have really put heart and soul into medical school had not had, I not had that experience. And today gap years are common for people going into medicine. It wasn't at the time, back in the 1800s, when I went to med school.
Matt Pillar:Oh no, don't say that. I think you and I are roughly the same age, so let's not go there.
Rahul Kakkar, M.D.:But I think they're incredibly important because I think it's very hard to relate to patients who are in many cases, decades older than you are when you're a med student or an early resident, unless you've gone out there and actually experienced some part of the world um, some of my um, some of my classmates who I respected the most had traveled the world for a year, um in their gap years um, and, like I said at the time, that was not the norm. So I think, particularly if there is in medicine, it's in many ways a humanity in and of itself and I think to really do patients justice, you have to have some real world experience yourself. And I think getting that early on is incredibly important and I actually applaud the move to more people taking gap years before they head into the rigors of medical school and residency.
Matt Pillar:Yeah, yeah, you mentioned the patient exposure early on and you know, more often than not, when I talk with a physician turned founder or physician turned biotech builder, the physician part is planted firmly in the past. The physician part is is planted firmly in the in the past. You continue to practice and you just mentioned that you couldn't see yourself practicing, you know, being a practicing physician for the duration of your career. Yeah, you continue to do that, even as you build biotech businesses. Why, why do you? Why do you choose to continue to practice right now?
Rahul Kakkar, M.D.:You know I have such incredible respect for physicians who practice full time. It's become an incredibly difficult industry. The course of my career of practicing from 2011, when I graduated from my fellowship, to now even it's only become more fractured. The number of individuals going into medicine and practicing has decreased over time, and the pressures that physicians face day in and day out, battling not just human disease but battling a system that doesn't serve them or their patients, takes an incredible amount of patience and dedication, and so my hat's off to them.
Rahul Kakkar, M.D.:Um, I'm not good enough to to weather those kinds of daily slings and arrows that that my PCP does, for instance, um, when I um when I left mass general, I finished my fellowship and went to AstraZeneca. Um, the dirty little secret is I actually left MGH without a plan. Um been um doing some consulting slash intern work for brian roberts at venrock. Um really open to my eyes to the um ecosystem of venture investment and biotech. This was about the last six months or so of my cardiology fellowship, so would have been end of 2010, early 20 into 2011, first half of 2011, and fell in love with the translation of science to useful tools, diagnostics and medicines, and Brian offered me to come join him in California, which was, for me, a dream come true. But my wife at the time said we're both in medicine, we're planning to to have children, all our parents are out here and you want to go where? California? I don't think so, which was wise because it would have been very hard to raise a family being so far away from the infrastructure, as it was of grandparents and I grew up without grandparents since they were all in India, so I definitely wanted my kids to have their grandparents around, but I left, you know, saying no to MGH and and and hats off to Brian Roberts for continuing to be a mentor and a friend after I told him no all those years ago, which was a hard, one of the hardest professional decisions I've ever had to make in my life.
Rahul Kakkar, M.D.:My life, um and um, and I, at that point, I continued to practice because I had, I think, 2011, um, yeah, 2011,. You know, we were starting a family and and I didn't have a stable job, and even when Don Frail at AstraZeneca rescued me from kind of wandering, wandering a wall fam, looking for a job and Cambridge, I still didn't know what was going to happen in biotech and needed to provide for my family. So at first it was really necessity and I and I will say I did get a bit. I was working at the Winchester hospital, which is a small community hospital town I grew up in, actually Winchester mass, um, pulling intensive care unit shifts overnight, um, and then heading into astrazeneca during the day to do drug development, and it's the kind of thing you can do when you're in your early 30s because you don't need a lot of sleep. It is definitely not something I can do now, um, but at first it was a necessity.
Rahul Kakkar, M.D.:But over those first several years I just found that there was a thrill, thrill of being up all night a patient in septic shock, throwing in a line, doing the right things to pull them through the night and give them a chance at the light of day to overcome their infection or their cardiogenic shock or whatever they were going through. And you know, I said to myself at the time when I hit 40, my biotech career is doing OK, I'll stop practicing. And I hit 40 and I realized I couldn't give it up. And now I'm coming up near 50. I'm not sure I'll ever stop.
Rahul Kakkar, M.D.:There is, even though I haven't been in strict cardiovascular drug development since my first company, since Corvidia, although there are some cardiovascular programs that we're thinking about here at Tome. In fact, I just came out of a meeting where we're discussing one of our first potential cardiovascular targets, which makes me incredibly excited. There is a cross-fertilization of going into the hospital one week a quarter, which is about what I do helping patients and their families understand the risk benefit of whatever procedure, surgery, um, even just medicine that is medically indicated, and then coming back to tone and really thinking about the programs we're pursuing, not from will they work in a mouse, in a monkey, in a what have you? But ultimately, if I were to try to prescribe this drug to a patient of mine, what's the conversation I would have? What's the risk benefit? Could I hand on heart and ethically make that argument to my patient? Whether they are my patient, my family member, what have you? So it's, it's grounding, it's incredibly grounding and it's exhausting, but I can't imagine stopping.
Matt Pillar:Yeah, yeah, I mean that. That. You know that. I guess that's the assumed sort of physician. You know biotech leader connection, right. The assumed sort of physician. You know, biotech leader connection, right. Where is there perhaps still conflict? Or have you seen conflict between the two roles that you play? Now I keep focusing on conflict. I don't mean to do that, I don't mean because I'm negative conversation, but I mean you know, even in your personal life, like that's gotta be, it's gotta be tolling on your family or taxing on your family, I'm sure, to some, some degree, during those weeks where you're, you know, still practicing or For sure.
Rahul Kakkar, M.D.:I think the conflict comes when I routinely particularly given that Tom is in cell and gene therapy right, which are some of the most expensive areas of medicine, and I go into the hospital and I want to put a patient on a fib, on apixaban, which is a branded blood thinner, and there's two to three other drugs in the same drug class that I could choose from.
Rahul Kakkar, M.D.:That's my preferred because it doesn't have as much danger when somebody has kidney disease as well and a lot of cardiovascular patients have kidney disease and myself and the team, whether it's a nurse, practitioner or residents, have to cycle through drug after drug in the drug class, potentially to a drug that's less ideal because their, their insurance company won't cover it.
Rahul Kakkar, M.D.:Um, and we, daily we are dealing with patients being discharged and having to switch medicines because they can't get coverage for because, because whatever the drug that is ideal for them at least in my judgment, is ideal for them, isn't covered. Um, these cost considerations come in routinely in decisions around which drug to choose. Um, and going from that, and these are, these are drugs that are a few thousand dollars a year, never mind cell and gene therapy, which are, you know, are priced in the millions, um. And so there is a conflict which is over time and you know, tom is still very early, we're still pre-clinical but over time, how do we craft a, a commercial strategy around cell and gene therapy that is still grounded in the fundamentals of value to the patient, more so than how do we maximize our return?
Matt Pillar:Do you struggle to put, like keep that in perspective in these early days at home, or like is it your sort of natural inclination to want to fast forward to tackling that problem, given that you've got that patient exposure and the payer experience on a regular basis?
Rahul Kakkar, M.D.:Not, not as much. I mean, I think you know we are many, many years away from approvals, not as many years away from the clinic per se and and honestly, you know if, if these drugs work, we'll be doing good for patients, even on a limited basis in early clinical trials. I don't necessarily want to fast forward it, because I think you know these are very, very novel technologies which are irreversibly manipulating the genome. I think the caution that we and others in this CRISPR DNA space are taking is prudent.
Matt Pillar:You mentioned a little bit earlier. You mentioned that you know, when you got bit sort of by the venture capital bug and started learning a bit about translational science and I mean that's you know that's exciting stuff, right, no-transcript. Had you had prior to that exposure, had you had any translational experience, perhaps in academia?
Rahul Kakkar, M.D.:Like, had you worked in any labs? Did you kind of have a sense of what that was all about when you were, when you were exposed to it in industry? Um, zero and uh but, but, but the differences. I thought I did, but looking back I had no idea what I was doing.
Rahul Kakkar, M.D.:Um, in fact, when I was working in the, one of the reasons I chose the lab that I worked in as part of my cardiology fellowship, which is a lab of Richard Lee at the Brigham, it was because Richard was very entrepreneurial, had started several companies, had always had this translational bent, but you know, he and I have tremendous respect for him.
Rahul Kakkar, M.D.:We had a great time in his lab but we butted heads in a collegial way. But we butted heads because all I wanted to do was take the molecule I was working on that that the science at the time was suggesting was cardioprotective, and move it into pig studies. So we could move it into human studies. And, and Richard's advice, which was absolutely correct, was, if you're going to have an academic career, you need to keep chasing that molecule in a dish, because that's where you're going to write your next grant on. Keep chasing that molecule in a dish, because that's what you're going to write your next grant on, um. So I knew I had an instinct to see this, you know, to see molecules move into into human medicine, um and see what good they can do Um. But I was incredibly naive at how complex and how difficult um that process actually is.
Matt Pillar:Yeah, how did you, uh, reconcile that? Like what, what was the process to getting to the point where you're like, okay, you know, I need to, I need to take a beat. This is how this industry works. Like, what was, what was sort of your modus operandi during those that transition, I guess, in your career?
Rahul Kakkar, M.D.:Yeah, so it was very much.
Rahul Kakkar, M.D.:I need to learn from the best person that will have me, and that's why I think Brian was was, for me, an inspirational figure as an investor, um and um, someone who I continue to value as a friend and mentor, and someone who, um, having never actually been able to directly work for him, has always been sort of regret in my career.
Rahul Kakkar, M.D.:Um is is that I was very for him has always been sort of regret in my career is that I was very, very fortunate. Lightning struck twice in this case, where Don Frail was building a group at AstraZeneca that was focused on drug repurposing and took a flyer on me. He was coming over from Pfizer building a group that was a reorganization of an existing structure within AstraZeneca very experienced drug developers, phd drug developers and a few MDs as well and he took a flyer on hiring me who had absolutely zero industry experience and the only one in the group that had zero industry experience. But what I thought to myself at the time was okay, this isn't, this isn't venture, which is where I thought I would end up, but I am going to learn how to develop a drug from these individuals, from Don and from the team, um at AstraZeneca, and so my solution to that problem, um and that conflict, was uh, try to align myself with um, with the best in the business.
Matt Pillar:Yeah, it's an interesting. Uh, it's a beautiful segue. Rahul, you just gave me the most beautiful segue because in my digging right Like my PI work before I got on the phone with you I found your title at AstraZeneca, and you know I love the way you put it. You know, don sort of like scooped you up and said hey, here's a place for you to get some footing while you get your family started and decide whether you want to practice for the rest of your life. Um, you were director for emerging innovations, scientific partnering and alliances. It's that's probably a one of a kind title, right Like you're talking about the position that you were, you were, you were, uh, working your way into there as being sort of a first of its kind position, and that sounds like a title that's given to someone who's like hey, this is a first of its kind position. What did that all mean? What were you doing?
Rahul Kakkar, M.D.:Yeah, astrazeneca was building a drug repurposing group, which basically means a group that was tasked with looking at all the molecules across the portfolio of the organization and we really had a broad remit uh, molecules that were parked, molecules that were still active, um, and looking orthogonal, which is to say, if a drug like the drug we spun out, the anti-il-6, many, five on one, seven, it was in the metamine portfolio, um, which obviously metamine was acquired by AstraZeneca several years ahead of this was active in development for rheumatoid arthritis. And you know, partly based on my interest in inflammatory mechanisms of cardiovascular disease, myself and another scientist thought, wow, this molecule might be really interesting for cardiovascular disease. And we did some preclinical work. We had some budget to do mouse studies and to retrospectively analyze some of the large cardiovascular trials that AstraZeneca had run and to form this hypothesis around could IL-6 be an interesting cardiovascular drug? But that's really what this group was designed to do. It was designed to look at molecules that were in the portfolio and find indications and diseases which were rational but never originally envisioned by the scientists that developed the drug in the first place. And we had several successes of drugs that showed positive phase two data.
Rahul Kakkar, M.D.:I think the flaw in the ointment or the fly in the ointment. The flaw in the model was, if we hit a positive endpoint, positive trial, whether it was preclinical study or clinical study what do we do with it? Astrazeneca wasn't committed to then advancing that drug forward just because it was positive, and so I think it was a group that continues in a different form today. But I think I was there during some of the most creative and exuberant time for that group when we had fresh budget, fresh ideas. But I think the flaw in the model was when our positives hit the organization didn't know what to do with it, and that was sort of why Corvidia started, because the IL-6 program had a lot of good scientific evidence for it, but the cardiovascular group at AstraZeneca it was completely off the strategy for them, so we had to spin it out to move it forward. There's plenty of ideas that just unfortunately didn't go anywhere because they couldn't be spun out and they couldn't be spun in.
Matt Pillar:Yeah, go anywhere because they couldn't be spun out and they couldn't be spun in. Yeah, and that's a. That's a, it's. It's a greater problem than just the problem. It was that AstraZeneca. Are you familiar with David Fagenbaum? At every cure, I mean you know it's a, it's a fascinating concept. I mean, here's a guy who had a rare disease that he functionally cured himself in a in an end of one trial by trying different things out, and now it's his life's mission to repurpose drugs, you know, to get a headstart. But I imagine that in more organizations than AstraZeneca, that sort of functional hurdle would be the big hurdle of chase, like who wants to take this? Like we think we've got something we're not equipped or you know we can't facilitate us development. Who wants it Right?
Rahul Kakkar, M.D.:Yeah, now you're absolutely right. It is an industry wide problem and it has been an industry wide problem for over a decade, and there are success stories, to be clear. But those are the exception, not the rule.
Matt Pillar:Yeah, yeah, this is another nice segue to the next set of questions I wanted to ask you about because you mentioned that sort of got Corvidia off off the ground of questions I wanted to ask you about because you mentioned that sort of got Corvidia off the ground.
Rahul Kakkar, M.D.:You went on to found Corvidia. Yeah, I was founder and chief medical officer.
Matt Pillar:Yep, and we can talk about that for a little bit. But from Corvidia you went on to, let's see, you went on to that was acquired by Novo Nordisk, correct? So we were at Pandion before that, before Corvidia.
Rahul Kakkar, M.D.:Or was it the other way around? We were at Pandion before that, before Corvidia, no, or was it the other way around? It was the other way around. So Corvidia was acquired by Novo in 2021. Sorry, 2020. I'm holding my breath because that compound is now in phase three in a large cardiovascular outcome trial, and so we'll know in a couple of years whether that first foray, that first hypothesis you know, generated between myself and another scientist at AstraZeneca who founded Corvidia with me, actually will do patients any good. Hypothesis was hatched in 2012. And by 2026, maybe 2027, we should know if it actually bears fruit. But but, my hat's off to Novo for really seeing and believing seeing our seeing and believing our data and the promise of the drug. But in 2019, at the end of the summer 2019, I was asked by Alan Crane and Polaris to become CEO of Pandion Therapeutics.
Matt Pillar:Yeah, Okay. So, and this is where I'm going with the questions. So Corvidia was working in antibodies and you went to Pandion, which was acquired by Merck for a couple of billion dollars. They were an immune modulator company and you know I'm interested in that story as well. But then the big question is, you went from there to Tome, which is selling gene therapy. So now, like you're checking off, you know you're checking off boxes in terms of modality, right. What is your, I guess, rationale between modalities and indications in terms of what Rahul Kakar decides he's going to do with his life next, Because you're kind of chucking them all off right now.
Rahul Kakkar, M.D.:You're absolutely right. So Corvidia was a biologics company. Pandion was a biologic immunomodulatory biologics company working in autoimmune disease, whereas obviously Corvidia was a biologics company working in cardiovascular disease disease, whereas obviously Corvidia was a biologics company working in cardiovascular disease. So a big shift in therapeutic area. But I think the theme here has been Corvidia was really a single asset company. Yes, there were a couple of other things we were working on, but functionally the lion's share of the capital and why the company was acquired was the lead asset. I did try to make Corvidia a platform company.
Rahul Kakkar, M.D.:We had done some interesting work using human genetics to validate IL-6 as a target in cardiovascular disease and we recognized that the way we did that validation was by triangulating the function of different genes. It wasn't a simple like nature has mutated this gene and that tells us it's really important in this disease. It was actually the triangulation of a pathway involving multiple different genes that led us to believe that IL-6 was going to be important in cardiovascular disease and we had this idea that this is very, very complex, multidimensional biology that is very different than the linear, reductionist biology that we usually prosecute. And would a computer program looking at transcriptional data allow us to find more evidence of nonlinear multidimensional genetic mutations to validate other targets. It's effectively AI before we were calling it AI right. This is back in like 2013, 2014.
Matt Pillar:We actually made some, but the idea was there, there's, there's a, there's a platform potential there.
Rahul Kakkar, M.D.:Yeah, yeah, and we actually did some early work with a CRO that worked in early ML models, very, very early ML models, to try to mine publicly available transcriptional data to find more evidence of these multi-dimensional um genetic mutations that nature's created. Uh, that would validate certainly certain targets, and the board wasn't supportive. We never actually resourced it beyond you know a couple hundred thousand dollars to do some pilot work, um, and and so when I got to pandion, um, what, what attracted me about pandion other than the fact that, yes, it was still in the world of immunity, right, my first company was immune mechanisms and cardiovascular disease. This was immune mechanisms across autoimmune disease. Um, I think a couple, a couple of things were attractive. One, fascinated by inflammation and immune mechanisms. Two, I got to work with one of the world's best drug developers, joe viney uh, a far better scientist than I am, which allowed me to really focus on the business side of the business, because I was never going to be a credible scientist in her shadow by any means. But that was a multi-asset company it was. We called it a platform company, but in the strictest sense it wasn't a platform, it was more a design, a protein design, philosophy that had the potential to create multiple targets across numerous autoimmune disease. So, single asset now to multi asset.
Rahul Kakkar, M.D.:And so when Pandian was acquired, I actually wasn't sure I was going to jump into another company. To be perfectly honest, I was like maybe now is my time to go back to venture, which is where my heart was back in 2011, when I was doing that consulting slash intern work for Brian yeah, when I was doing that consulting slash intern work for Brian. And then I saw the paper that underwrites what Tome has become coming out of MIT, from our founders, and I realized, one, this is a true platform. But two, this technology solves the outside of delivery restrictions, solves the key technical limitations that we have today. Um, in the gene editing world and I've never been a rare disease drug developer, I've never done cell and gene therapy before um, but I saw that this was a in order of magnitude more in scale. So, single asset, multi-asset, and now tome is really a step forward into cell and gene therapy right, very, very broad pipeline.
Rahul Kakkar, M.D.:But it also allowed me to do something that I wasn't really able to do with my first two companies, which was craft a truly productive and innovative culture within a company. My first company I was not the CEO. It was run by a commercial head. It was a small company. Clinical stage there wasn't a culture, to be sure, and in my second company I was the second CEO of that company there was a culture in place that was largely led by Joe, a phenomenally productive culture, but not one that I had much of a hand in crafting. So, coming to Tome, it was a chance to work with a technology that could truly revolutionize and move past the limitations of current cell and gene therapy tools, but also a chance to build a culture drawing from all of the lessons I had learned both in biotech but also in the clinic.
Matt Pillar:Yeah, yeah. I'd like you to hover there for a minute and maybe extrapolate some of those experiences that made you an effective culture builder. Because you know you mentioned a minute ago you talked about like having a having an opportunity in one of your positions to take a break from the science and go build the business Right, and that's, that's a learned skill. You know that's a learned skill, especially for someone who's coming out of the science world or the or the practicing world. So was so was culture building right. Like, I mean, I've had enough experience with physicians to know that culture and bedside manner are maybe secondary on the list, which is fine, you know, hey, as long as you keep me alive and healthy, I don't care if you're a nice guy or not, I don't care if you give me a warm, fuzzy feeling or not. But what were some of the I guess, more specific sort of points along this journey? Where, come to Tome, you feel equipped to not just build a business you learn that along the way but also to build a unique and thriving culture.
Rahul Kakkar, M.D.:So let's be clear, matt I don't feel equipped to be a physician, a CEO or a culture builder at this point.
Matt Pillar:You're a Renaissance man, you know clearly.
Rahul Kakkar, M.D.:I think there are a couple of things. One, um I've I've had some true challenges in my life along the way, um things in my family, things, uh, my extended family and my in my immediate family, um hell, just raising three kids, it's a challenge, um, and I think that um I always think about a tagline that is underneath the email, the personal email of um one of my mentors I mentioned a few of them so far brian roberts, alan crane but under the tagline of michael dav Davidson, who was my first CEO at Corvidia and remains again remains a, a, a a friend and a true mentor to this day. Um is things work out the best for those who make the best of the way things turn out. Um, and and I think Michael also has um seen some slings and arrows in his day Um, and I think and I actually was sitting down with Brian a few weeks ago when I was in California over a cup of tea and we were sort of aligning on this idea that one of the most dangerous things for the human um sycophancy and one of the best things for the human mind um is struggle.
Rahul Kakkar, M.D.:Um, you'll learn the most about others and yourself when you're tested in some way, whether it's a difficult relationship, whether it's the unknowns of raising a child, um, whether it's a different, difficult patient, their family, who are really struggling with the disease.
Rahul Kakkar, M.D.:I've had a lot of struggles in my life, I think, both personally and just being a physician in a, you know, in the realm of cardiology where nearly every time I practice medicine someone is passing away.
Rahul Kakkar, M.D.:I mean, cardiovascular is serious disease and just having to learn more about yourself and how people react to adversity, what brings out the best in them and what makes the worst even worse. I think at some point, unless you stick your head in the sand, you can't come out of those experiences as an adult human being without recognizing that there are certain themes that bring the best out of people, and a lot of the words that we use to describe those themes are somewhat trite compassion, genuineness, vulnerability. I mean, some of these are buzzwords today, but they're buzzwords for a reason. I have found that and this is not me, this is really me in partnership with our chief of people here, who, tome, would not be what it is without her hand on the cultural tiller, as it were, without sharing that philosophy of if you truly show up as genuine to individuals. Unless they really have a personality issue, they'll generally be genuine back with you.
Matt Pillar:Yeah. Yeah, I was going to say some of those, what you're referring to, buzzwords. You know, totally get that. But I think they're no longer buzzwords when they're demonstrable, right Like when they're demonstrated.
Rahul Kakkar, M.D.:Well put, well said Well said and, and people come to Tome for that reason. Every every month, I sit down with all of our new hires, um, from the previous month or so, um, and just ask them why they're here. You know where are they coming from. What did they hear about Tome before they got here? And then, for the weeks that they've been here, have we lived up to that expectation.
Rahul Kakkar, M.D.:And really, since our second year in existence and we're now in our third, so for the last year and a half, almost two years, people come here not just for the breakthrough technology, but they come here because somebody they know works here or somebody they know knows somebody they know who works here, and they talk about how wonderful it is to work here. People are helpful, genuine, collaborative, and that these are things that many, many companies talk about. But even just through interviewing, they really felt it and the most gratifying is that when they're several weeks in, they're like, yeah, it absolutely lived up to the hype. I was skeptical, but it absolutely has lived up to that reputation, and so that's why I know, even though we're 150 people now, we're still doing something right and I think it really just us, as leadership, showing up as transparent and genuine.
Matt Pillar:Yeah, I like your reflections on the value of struggle and I want to shift gears here a little bit and talk about some of this groundbreaking technology because, like, the value of the struggle is on full display and selling gene therapy right now, right, like, everyone knows that the struggle is a, it's a, it's a valiant struggle. Um, the last time you and I talked a few weeks ago, you you talked a little bit about inflection points and I think you mentioned that, like we're we're approaching one, maybe not, you know, maybe not on the precipice, but approaching an inflection point right now. So I guess, frame up for us, like, what is the struggle, the technical or scientific struggle that your company is, you know, in lockstep addressing right now, and perhaps you know what are some of the holdups around declaring victory in the struggle.
Rahul Kakkar, M.D.:Yeah, I was actually just having this conversation with John Finar, cso, this morning. There are a series of struggles that we will face over the coming years. The first one to answer your question is proving that this DNA editing technology is worth anything, and what I mean by that is it's not novel. Technology, with all due respect to academic, academic, scientists, is not important. It really isn't, unless it underlies and underwrites a drug that will help a patient in a way that they cannot be helped with any existing technology. I don't, frankly care and this is, this is again the physician and and the physician and non-scientist in me I don't care what, what the mechanism of editing a piece of DNA is. I really don't. What I care about is whether that mechanism can lead to a drug that's going to help someone in a way that no other editing technology, no biologic, no small molecule, no RNAi ever could, and that's why I get somewhat frustrated when I see so many companies going after so many of the same drug targets. To me, that means that your editing technology, no matter what you say, isn't actually all that interesting, because it's only interesting if a patient will benefit. Um, and so for us. I think you know our first struggle that we've overcome is actually identifying a list of targets. A drug drug, sorry, a list of diseases, um, that really we're addressing in a way that nobody else can. That was struggle, one that's behind us and we'd love to talk way that nobody else can. That was struggle, one that's behind us and we'd love to talk about that more.
Rahul Kakkar, M.D.:As we get to the second half this year, we start talking about our pipeline more openly. The second is really proving that the technology can work as a drug development platform. Right, because when it comes out of MIT it's a paper and it's some plasmids and it works in a in a dish and maybe it seems to work a little bit in early mouse studies. That's all been published, it's all public domain. What we need to do is industrialize and industrialize it in a way that, with a speed and a cost, it can actually start creating these drugs in a bona fide manner.
Rahul Kakkar, M.D.:We don't ask those questions of protein engineering techniques. We know they've been working for decades, but you don't always know that about a new DNA editing technique, and so that is where we are now and as a preview of data that we will be showing at the end of this year, towards the second half of this year, excuse me, and into 2025, me and into 2025,. We are at the point where the data that I'm seeing, I have no doubt that programmable genomic integration is a bona fide drug development platform and, frankly, as I see what we're achieving in the preclinical world, it's hard for me not to look at other DNA and technologies as somewhat obsolete at this point, and I'm incredibly excited for where we're going. Our next struggle, quite frankly, there's a struggle I'll talk about in a minute. The ultimate struggle, then, is going to be going into the clinic and showing that what we're doing in animal models we can actually do in patients for their benefit.
Rahul Kakkar, M.D.:I mean, that's sort of an obvious one, but there was an intermediate struggle, and that is an intermediate struggle between where we are now and where will we be then in the clinic. That is unique to our time and that is the risk of capital. Expensive DNA editing platforms are out of favor in our industry right now for pharma, for investors, and so as we talk to investors and bankers and people ask me a somewhat variant of the question you're asking, which is what's the biggest risk in front of you, they're usually asking for a scientific answer and I'll say if you actually understand our data, you'll realize that we've discharged most of the technical risk not all, but most. Our biggest risk is being able to raise enough money to keep doing what we're doing.
Matt Pillar:Is that softening at all? I mean, you know, coming out of JPM there was a lot of pomp and circumstance about biotech coming back and capital markets loosening up again. Or is there specific to this niche gene editing is it still a pretty hard market to operate in?
Rahul Kakkar, M.D.:market to operate in. No, I think it definitely is softening. Um, these things run in cycles and when I talk to um, when I, when I talk to individuals who've seen more cycles than I have, um, so again I go back to Brian quite a bit Um, some bankers that have formed a very close relationship in in, uh, one particular banker who worked very closely with me on the pandion um, sale, um, and, and they, they, they helped me think through what this. The phase of the cycle that we're in. It generally goes like this the, during these periods of downturn, valuations become depressed and large pharma comes in and starts buying things on the cheap, and when that starts happening now, the IPO window starts to open and then that trickles back down to the private markets.
Rahul Kakkar, M.D.:We saw robust M&A right through the most difficult periods of private investing in our industry of the last couple of years. We're now starting to see IPOs move forward. Some do well, some do not. So thawing I think you use the word thawing is an excellent word for it. We're not liquid yet, but we are thawing.
Matt Pillar:I think I said softening, but that's akin to thawing.
Rahul Kakkar, M.D.:I'll give you a thought, absolutely. But I think it's thawing in two ways. It's thawing for clinical stage assets, which is where most of the M&A has been, frankly, and it's taking the really more visionary investors, the really forward-looking investors, to say, okay, I'm going to pull a Wayne Gretzky, I know where the puck is going. If everyone's focused on clinical stage, the next exuberance is going to be in preclinical, so I'm going to start investing there now. And so when we talk to investors, the interest we're getting are really for the more visionary investors and not the momentum investors who are still focused on clinical stage. So it's thawing, it's softening. It's going to take another several quarters for us to get to a place where there's true, true liquidity in the not the capital sense, but liquidity in the investing markets, particularly the private investing markets.
Matt Pillar:Yeah, yeah, that's yeah, opportunities and entertaining investor interest in your company. How important is it for you to be discerning, right? I've had several conversations with biotech execs and finance folks, people who are in the investment community, who talked about how the fact that we were as an industry biotech was overcapitalized leading up to this crash. Right, there was just too much money going into the wrong hands, going into the wrong programs and, unfortunately, a byproduct of that is some good programs getting, you know, put on the back burner, shelved, going by the wayside, but, as you sort of course, correct, away from that you know in your corner of the world, as leader of Tome, how important is it for you to be discerning about?
Matt Pillar:like you mentioned? Like you know, do I see differences in the momentum investors and are they going to be a better bet for us long-term than you know? Perhaps the retail investors, for lack of a better term, that got us into a bunch of trouble a few years back.
Rahul Kakkar, M.D.:I completely agree with the sentiment that we were over-capitalized when interest rates were effectively zero and there was, there was a lot of sort of there was investment that wasn't based on fundamental principles, that was being done in our jammies over Zoom. Completely agree, and we're working through the ramifications of that overinvestment, to be sure, through the ramifications of that overinvestment, to be sure, when I think about a company like Tome. However, we have very high capital requirements. We've actually recently done an analysis looking at our timeline to various inflection points that we were talking about before, the number of people it's taken us to get to each of those points and the amount of capital burnt to get there. We are the most efficient crisper based company in history in terms of amount of capital it's taken us to get to certain inflection points in the pre-clinical world and the number of people taking us to get there. So we are doing our diligence of building a, a dna editing company, for this age and not the over-exuberant age of a few years ago. That being said, it's still an expensive business to run and we will need investors of different backgrounds. We will need a.
Rahul Kakkar, M.D.:I was just having this conversation with an investor yesterday. We are going to need a diversified shareholder base to drive this forward Traditional blue chip venture capitalists, crossover investors, sovereign wealth and even retail at the right time. And so this idea of you're constructing your capitalization table with the right mix and the right diversified mix of investors who can invest over time is is an art, but there's definitely an art to your your capitalization table moving from certain phenotype investor to certain type of investor over time until eventually you're publicly traded. Um, and so this is just something that we think about as a. You know, we released our, we came out of stealth earlier this year, we released how much money we raised off of our A and our B round, and as we think about our next round as a startup, biotech, you're always thinking about your next round. We do think, and I think a lot, about what's the right makeup for this stage of the cap table on our path towards eventually, one day, becoming public.
Matt Pillar:Yeah, you talked about quite a bit earlier in the conversation you talked about, you know, a point in your career where you thought perhaps you wanted to go back to the venture capital. Do you feel like the role that you're in now, like operating with such intentionality around your capitalization structure, moving forward, does it scratch a bit of that itch for you? Just personally, like, do you feel like you're, from some perspective, still in the game?
Rahul Kakkar, M.D.:What scratches that itch actually is my work with Polaris.
Rahul Kakkar, M.D.:So as an entrepreneur partner at Polaris, where I've been able to work actually with some of my existing investors on new companies as well, not just helping the other partners at Polaris when they feel I can help them with evaluating a potential investment, but even working on one new company myself, a stealth company, where I'm now on the board, and I am on the board of another company, atralis, which is a company I've been on the board on for some period of time now as an independent, well before my Polaris days, and so I scratched that itch through my through my board work and particularly through my work through Polaris.
Rahul Kakkar, M.D.:I've found that the individuals of Polaris are exceptional human beings, really have their heart in the right place, share the same values that I do when it comes to, um, you know, building companies uh, for the right reasons, with the right philosophies, um, but it but it does. It is a different viewpoint, it's a viewpoint of an investor, and so I do feel like that's incredibly valuable. I actually really appreciate that they uh that they let me uh work alongside them.
Matt Pillar:Yeah, very cool. Um, we are running short on time. Can you believe how fast time is flying right now? I'm enjoying this conversation so much I could keep you on the phone for another half an hour or so, but I don't want to do that. I want to be respectful of your time. But I do want to shift gears a little bit and get your perspective on this. I I I just cause I've been thinking about it lately.
Matt Pillar:I wrote a reflection recently on on on pharma's pharma in general's PR problem, right, and I'm curious about your take on. You know, I mean, it was Nielsen data that basically said the pharmaceutical industry is held in a lower regard than lawyers, airlines, the federal government. You know we're keeping some pretty rough company in terms of public perception, and public perception is patient perception right, like we're working ultimately to serve the public, and I know that a lot of that reflection is rooted in, you know, payer experiences, big pharma, but we can't pin it all on them. I'm curious about whether you have any opinions on the role that biotech could and should play, given the fact that, like that's where the most exciting, most innovative, most patient centric work is happening. You know, like I said, your opinions on the role that the biotech could or should play in sort of changing the PR paradigm of this industry.
Rahul Kakkar, M.D.:You know it's absolutely correct. It's been correct for a very long time that we are not well regarded. It's really interesting. Patients don't generally hate their doctors and they don't generally hate the medicines they take, but they hold in very low esteem the companies that invent, design, develop and launch those medicines. There's a bit of cognitive dissonance there and I think you're right, there's a reason for it. I think, unfortunately, the pharma industry gets politicized. There are many, many more players in the pharmaceutical industry insurance companies, pbms, etc. Each has its own entrenched interest.
Rahul Kakkar, M.D.:It's incredibly convoluted um, and what the public discourse has done with I don't fault anyone for this is, uh, simplify that for the, the, the, the reading, the reading populace, um, you need a scapegoat, you need, you need an enemy, um, and pharma has done itself no favors in the way it prices drugs and some of the scandals that have happened over the years. So so I understand where it comes from. Yeah, your question about can biotech do something? In my mind, biotech in general is on the earliest stages, right startup, early r and d, um&d early to late R and then into early D, right Into clinical and in my experience so far, by and large the folks that work in biotech do it for all the right reasons and are equally flummoxed by you know why we get such a bad rap. But can biotech really help the perception of the industry that is driven largely by the public's understandable anger over commercialization of drugs? The honest answer, matt, is I'm not sure. Not sure. That's not the realm in which we play.
Matt Pillar:Yeah, I just feel like you know, and this is a raw thought, like it's a raw thought, right. Like Sure, not sure. That's not the realm in which we play. Yeah, I just feel like you know, and this is a raw thought, like it's a raw thought, right. Like I just feel like so much of the positive news, so much of the excitement happens in biotech and maybe you know, maybe it's a matter of you know, you share the good news that's happening in early R&D and biotech and there's such a dichotomy between that and the current standards of care that it just creates more ill will. I don't know. You know what I mean. Like it's just. I feel, like to your point, like I live in that bubble too. Like I live in this bubble where I talk to guys like you and women like you all day, every day, day, and I'm like what is, you know, where's the good news and the hard work and the altruism getting lost in the, in the translation. You know, but you know, perhaps your point, it's it's just too soon.
Rahul Kakkar, M.D.:No, I think you're, I think you're right, cause even when we go out there and talk about the promise, I do wonder if people look at that and say, oh, that's just spin, that's just a way for us to buy for us, because my experiences with my loved ones and my own health have been, you know, the same for the past 30 years.
Rahul Kakkar, M.D.:My loved one can't afford like I was talking about with you know putting a patient on a blood thinner. My loved one can't afford X medicine because the pharma companies price it too high, and the reality is so much more complicated than that. But I do to me when a patient's day-to-day experience is difficulty affording their medicines. Until we fix that, we're not going to be able to punch through that. What's really happening in biotech, which is truly groundbreaking and revolutionary science that will extend life.
Matt Pillar:Yeah, yeah, all right. One last question for you and then I will let you get on with your day. As I said, the physician turned founder, turned biotech builder is always super interesting to me. You're continuing your practice in the clinic and also leading a biotech, but that's, more often than not, a difficult transition for physicians and scientists to make. So if you were, if you were speaking specifically to you know, mds and scientists turn biotech builders or aspiring to. What would be your pithiest advice for those folks? To to, I guess, encourage them and inspire them along that transition?
Rahul Kakkar, M.D.:There's not enough of us.
Rahul Kakkar, M.D.:I look, I think back to my away medical rotation in Tanzania, where I would spend the day seeing children die of cerebral TB something that doesn't even happen in our country and spend my evenings reading Ayn Rand of all things, and what came together during that sort of dichotomous period of experiences during the day versus reading at night was the people that really changed the world. Are the Howard Rourkes, who know how to rivet and then go on to design buildings, or the Hank Reardons, who know how to smelt and then go on to design buildings, or the Hank Reardons, who know how to smelt and then build a successful business on breakthrough technology? We need more people who have their boots on the ground in medicine, who know how to rivet and smelt but then move in to actually build the businesses that change the world. There's not enough of us, and I think that the industry would be better served by more of us making that. I wouldn't even say transition, but straddling the boundary between both practicing medicine but also working in the wonderful business of making new drugs for patients.
Matt Pillar:Yeah, all right, I lied. One last question to follow up on that. Please, where would you point those people? To, uh, to, to surround themselves with the right people, to be equipped to not just rivet and smell but develop businesses, build businesses that that then create medicine.
Rahul Kakkar, M.D.:Yeah, um, I did it the hard way, um, I I found people that believed in me. That doesn't always happen. There are ways to do it. The most tried and true way are going through consulting agencies like the McKinsey's of the world and the Boston Consulting Groups, which are fine, because you really do learn valuable, valuable lessons there. My only advice would be don't give up practicing along the way, because you lose something. If you do, yeah, very good.
Matt Pillar:Well, it's been a pleasure, a real pleasure, to talk with you, rahul. I appreciate you taking the time with us. I think I really enjoyed our time. I hope we get to do it again. You actually mentioned maybe toward the back half of this year, so I'm going to hold you to that. Maybe towards the back half of the year we'll have you back on for an update on what's going on at Tome.
Rahul Kakkar, M.D.:I've enjoyed our conversations to date. I would love to do it again later this year.
Matt Pillar:Fantastic, thank you. Take care, sir. Thank you. That's Tome Biosciences President and CEO and Brigham Women's Hospital Physician, dr Rahul Kakar. I'm Matt Pillar and you just listened to the Business of Biotech. We are produced by Life Science Connect and its community of websites and publications designed to help life science decision makers learn, solve and source their way through the rigors of this dynamic industry. If you like listening in on conversations with biotech leaders like Dr Kakar, subscribe to the podcast anywhere you listen, leave us a review, get in touch and, as always, thanks for listening.