A Molecular Biologist’s Advice For Life

Posted July 1st, 2024 in Bioentrepreneurship, Leadership, Personal, The Human Element | Leave a comment

Having just turned 50, I’ve been reflecting on my first half-century of late… many fun and impactful moments, a few regrets, and a life I’ve tried to live to the fullest. One thread that has run throughout it has been my passion for science as a lens for looking at the world.

In particular, I love connecting science to daily life. I’m reminded of the DuPont advertising slogan of “Better Living Through Chemistry” – which was representative of the role of science in improving everyday lives in the last century. Pfizer’s recent campaign around “Science Will Win” similarly appealed to the ethos of the power of science to help humanity.

So when I was asked recently to share advice to a group of undergraduate students doing research at Penn State, I was drawn to the idea of connecting scientific principles to some life lessons.

Here are the twelve pieces of advice for college and early career STEM folks, using scientific metaphors to frame some life lessons I’ve picked up along the way.

  1. Remember life’s Central Dogma.

The central dogma of molecular biology is that information generally (with few exceptions) flows from DNA to RNA to Protein. Same is true for what I’ll call life’s central dogma: your happiness, health, and self-worth flow outwards from you to your friends & family and on to everyone else. Prioritize investing in yourself – First things first. If you don’t, it’s unlikely you’ll achieve the happiness and life goals you set for yourself.

  1. Express yourself as a heterodimer.

Many of the most important effector functions and signaling pathways in the cell leverage heterodimers: bringing two different proteins together to drive a particular and unique cellular response. There’s a similar benefit to bringing heterodimeric interests together in your life. For me, Science is wonderful, exciting, and powerful – but in a vacuum, it is incapable of achieving its full potential as a driver of meaningful change and impact. Integrating Science and Society to frame the bigger picture around the human condition, this Science-Society heterodimer creates a compelling opportunity for impactful leadership – one I’ve leveraged throughout my career. Try to create your own version of this heterodimer that synergistically brings your scientific interests together with a sense of societal responsibility. It’s critical to go beyond a unidimensional monomeric perspective of science-for-science’s-sake. This heterodimer will bring more meaning to your work, enhance your productivity, and open doors over time.

  1. Don’t differentiate too quickly.

Differentiation is a powerful force in multicellular eukaryotic organisms; thousands of specific cell types derive from a single cell. The pathways of cellular fate are also largely unidirectional (ignoring targeted iPSC efforts).  In the human body, once you’re a dendritic cell, it’s generally not possible to de-differentiate back to a pluripotent HSC. Life is the same way: with time, life terminally differentiates you. It’s often easy or encouraged to specialize quickly in one’s career. But I’d advocate against this: try to resist locking into your “fate” by staying broad and remaining intellectually curious. There is a huge panoply of careers for those interested in science – ranging from the lab, to the hospital, to the office; staying open-minded across a wide range of pursuits will give you a better foundation than a narrow focus. While specialist knowledge is key (eventually), learning how to apply it in an interdisciplinary way and with broader context is a unique enabler. Try to maintain your “STEMness” to do many things in the future, as life will certainly make you specialize over time. Eventually, specialization is fine – just don’t do it too soon.

  1. Embrace Darwinian evolution.

In biology, adaptation to environmental changes is critical for survival. New greenfield opportunities that appear, like in the Cambrian explosion, often require rapid adaption and life-form experimentation. These are truisms for life as much as for evolutionary biology. Embrace change in your career, even if painful. Pain in the short term around a career pivot can open up longer term growth, as it did for me transitioning into my career in venture capital. In addition, the concept of personal inertia – the property of not changing one’s current course or state – is a powerful driver of complacency in life. Fight against this inertia, as Darwinian forces typically don’t treat inertia-based careers very well. If you aren’t adapting, you aren’t growing. Develop new skills, enter new fields, improve yourself – and even reboot yourself if you have to:  such experiments in adaptation will help you strive to be the “fittest” in rapidly changing career environments.

  1. Become a human Pattern Recognition Receptor.

The innate immune system is constantly surveilling for patterns in the cellular environment, so that it may invoke the right responses to pathogens/other foreign entities. Pattern recognition receptors (PRRs) evolved to fill this need  and discern what kind of innate responses need to be kicked in to protect the organism. These PRRs are like historians that watch for things that cells have seen before and anticipate the future. Life is similar: it’s full of patterns and learning to see them is key. History, like a specific pathogen exposure, doesn’t necessarily repeat itself, but it does rhyme. Once you recognize the patterns (e.g., cause/effect, behavior/outcome), you can be better at responding efficiently and effectively. This also rings true for entrepreneurship and venture capital as there are hallmarks of success (and failure) in different types of deals: for instance, “Red flags” raising cautionary diligence questions are in essence PRRs informed by history. Most successful people have a well-refined pattern recognition capability, especially those who have to make bets on the future.

  1. Build your social immunity.

The adaptive immune response identifies and responds to highly specific antigens associated with infections and cancer. This response often involves the development of immunity thru the generation and maturation of antibodies which help eliminate threats. In life, you need to develop immunity against those human “threats” – those people who demean and degrade others, and bring toxicity to those in their vicinity. Sadly, the world has more folks like that than one would like to believe, and you need antibodies against them – to both avoid their engagement with you, and to sequester and clear them out of your life when they do appear. These antibodies provide the effector function for that critical rule in life: the NAR (the No-Asshole-Rule). Having a social immunity from these types, and not compromising or tolerating bad behavior, will help you in the long run. The caveat, though, is to not let this effective immune response over-react and turn into autoimmunity: getting too cynical, too negative, and too pessimistic about people over time isn’t a healthy way to live.

  1. Focus on phenotypes, not genotypes.

Genotypes (AGTC’s) play important roles in biology, but ultimately phenotype is what matters. In biology, how genotypes are translated is complicated; there are significant modifier networks, both genetically and epigenetically, that alter the translation of genotype into phenotype. But for the organism and its ecosystem, it’s the observable physical traits (the phenotype) that are critical for success and survival. In life, it’s not the letters on your resume, what school you went to, or what your GPA is (collectively your “genotype” of AGTCs), it’s what you do when you show up (your phenotype!).  How do you express your traits – your drive, your commitment, your competency – that’s what really matters. Focus on that and ignore the AGTC pedigrees that others may get worked up over.

  1. Seek work-life symbiosis.

Mutualistic symbiosis occurs when two “species” benefit from each other and interact in a bidirectional way. Your “professional” and “personal” lives should be in mutualistic symbiosis. Work-life balance is a fine concept but keeping the two “species” separate from each other doesn’t capture the symbiotic potential. Find ways of integrating your passions into the workplace, and use them to create community, connectivity, and followership. We spend far too much time at work during our lives to not bring our personal passions into it in a beneficial way.  As an example, I love to run – so helped create a running group at work, and help catalyze multiple teams for various races. These have created new professional connections, and deeper relationships, that have undoubtedly helped my (and others) career over time. But running isn’t for everyone: others have brought their passions about particular charities or activities into work.  There are many ways to create this symbiosis between our work and home lives. Of course, boundaries are important: parasitism is a close cousin of mutualism in biology… so don’t let work take advantage of your personal life in a negative way.

  1. Do Friday afternoon experiments.

Every lab rat and scientist knows that no one should do critical and important experiments on a Friday afternoon; too much at stake, including your weekend, and too many distractions make a good result a low probability outcome. Instead, this is the time for crazy experiments – ones that test wacky ideas and novel hypotheses, make new observations, and/or go outside of your lab’s focus. Several elements of my undergraduate and graduate theses came from these explorations. As in the lab, it’s important to do Friday afternoon experiments in your career. Be explicit about carving out time for doing non-linear, non-deliverable-oriented thinking. Take time to wander outside the box, explore new areas, revisit workplace beliefs, write down your random thoughts, or do new analyses of datasets, as examples.  In my own career, starting to write a blog was one of my most impactful “Friday afternoon experiments” – I even called it an experiment in my very first blogpost back in March 2011. Writing a blog during time I’d set aside before work, or in the evening, was as Friday-like as I could find in my schedule at the time. Beyond the lab, Friday afternoon experiments in a career come in many flavors, so find time to explore this intellectual exploration.

  1. Be bold and take calculated risks.

In behavioral ecology, the willingness of animals to take risks is often described along an axis of “boldness and shyness”.  If fish are too shy and don’t move enough, they get eaten by predators. If they are too bold and venture too permissively, they also get eaten. Further, animals only take “bold” risks if they perceive the benefits to be meaningful: food, mates, habitat, etc… In life, taking risks is similar. Be bold but know what you are risking (the downside) in order to achieve the benefits your perceive. As I’ve told my kids, not putting the bar down on a chairlift is taking risk with zero benefit. While going backcountry skiing is more risky, the calculated benefits are wonderfully tangible (the experience!). Being appropriately bold around risk-taking, rather than overly shy, is often key for a successful career. Failure is very much “ok” and is often worth celebrating. But although accepting the risk of failure is valuable, don’t try to make failure a habit or become complacent about failing. Failure stinks, but it happens to all risk-takers at some point. I’ve taken many risks with our capital as a venture investor and have lost more money than I care to think about. Earlier in my career, I failed to get a job in venture at three different firms before joining Atlas. Failure and making mistakes is part of life. But critically, I aspire to only make “original mistakes” (in the words of one of my early mentors in venture, Kyle Lefkoff). Original mistakes are ones that are new to you; learn from them so you never make the same mistake again.      

  1. Celebrate the “social animal”

Aristotle said, ‘Man is by nature a social animal; he must satisfy certain natural basic needs in order to survive’. Others have said that homo sapiens may be the ultra-social animal. As we evolved, collaboration led to culture, tradition, and learning. The transmission of knowledge via social connections became paramount – not only in evolutionary biology, but in life in general. Building deep professional and personal relationships with mentors and colleagues is critical, as most of our learnings come from interacting with others. Develop your networks.  Learn to communicate to others with clarity and enthusiasm. In life, it’s often not what you know, but who you know that opens the most doors. Find the people in life and your career that matter most and keep them close. And, as social creatures, pay it forward by helping build bridges and connections for others.

  1. Acknowledge life’s randomness with humility

Evolution is the result of non-random selective pressure acting across random genetic variation. Our lives are the result of non-random choices we make in the background of random events and fortune. Both skill and luck are important in our lives and careers. Randomness, including timing, is a much bigger driver of life’s outcomes than many people tend to appreciate. Of course one should try to make your own luck, as “chance favors the prepared mind”. But attribution of success in most aspects of life (particularly business!) rarely mentions the phrase “we got lucky” – but it, at least in part, is a contributing factor behind many of the biggest successes I can think of. Further, serial winners are worth following; someone who can put together a string of successes may have figured out how to apply skill to life’s game of chance, while the one-hit wonders may have been particularly lucky (rather than simply smart). The key is to work hard to try to shape your outcomes but acknowledge the randomness in the fortunes of life – and stay humble.

Hope you found these themes fun and thought-provoking: Science for the win!


Mariana Oncology’s Radiopharm Platform Acquired By Novartis

Posted May 6th, 2024 in Exits IPOs M&As, Leadership, Portfolio news, Talent | Leave a comment

Novartis recently announced the acquisition of Mariana Oncology, an emerging biotech focused on advancing a radioligand therapeutics platform, for up to $1.75 billion in upfronts and future milestones.

The capstone of its three short years of operations, this acquisition represents the second largest preclinical M&A deal in history, and the largest ever completed by Novartis.  It also represents a shift in radioligand therapy deal activity: a true platform acquisition, rather than one focused on a late-stage asset.

Mariana’s acquisition and the incredibly exciting radioligand therapy (RLT) space has been covered extensively elsewhere (here, here, here), but we thought sharing a few of the key people-related themes worthwhile.

This deal reinforces the oft-cited axiom in venture investing that finding and backing great teams is critical to success, and a big part of that is leveraging deep relationships across the ecosystem.

Let’s start with CEO-Founder Simon Read, who has now joined that rarefied air of serial entrepreneurs who’ve successfully had more than just a lucky billion dollar singleton; Simon was the CSO at Ra Pharma, which was acquired for $2.5B by UCB Pharma back in October 2019 (here). We had Simon on our “PeopleFlow” list immediately following that acquisition, and by the end of 2019 we were actively recruiting him. Fortunately for Atlas, he started as an Entrepreneur-in-Residence (EIR) in the spring. In fact, Simon was one of our first “virtual EIRs” to start during the early days of the COVID lockdown. For the initial six months or so, Simon worked across multiple Atlas companies, including advising Vigil, Q32, Third Harmonic, and others.

In the fall of 2020, Simon began working closely with my partner Kevin Bitterman and Atlas’ Jernej Godec, who spent the prior year beginning to formulate a thesis around radiopharmaceuticals, an effort termed “Project Curie”.  A critical component of this thesis had become the belief that low molecular weight ligands, such as macrocyclic peptides like those Simon had helped discover and develop at Ra, would be a key enabler of radioligand pharmacology.  Simon was quick to recognize the potential opportunity in this space and began working to strengthen and refine the nascent strategy. To support the effort, we also brought on Sandy Mong from BridgeBio to work as an EIR with Simon on the project.  The final startup pitch to the partnership was in April 2021, and Project Curie was seeded on May 3, 2021 – propitious timing, as it was exactly 3 years to the day that Novartis closed its acquisition of the company.

Initially, we partnered with Dan Becker and Christine Borowski of Access Industries (with whom we’ve done several deals with) on fleshing out the plans for the seed investment, both of whom were exceptional partners in helping pull it all together.  In particular, Christine and Jernej were an invaluable duo for Simon to lean on, in part because they had previously worked together at Appletree. They were both instrumental in the founding of the company and its early plans, especially during the 18+ months that Curie/Mariana incubated in the Atlas offices from mid-2021 until February 2022.

In Atlas’ April 2021 seed investment memo, crafted with Simon and Access, the team spelled out much of the vision for what made Mariana a success: the critical platform enablement that would establish Mariana as a leader in this emerging field, as well as the compelling target opportunity with the initial lead program (now called MC-339) in small cell lung cancer. Great initial target selection is not only important for advancing a pipeline, but also for early platform development.

Shortly after our seed investment, we further strengthened the broader syndicate by combining forces with our friends at RA Capital, Josh Resnick and Laura Tadvalkar, who were working on a NewCo with a similar focus. Notably, CSO Alonso Ricardo, who was an EIR at RA Capital, had previously worked alongside Simon Read at Ra Pharma. And Josh was also previously a Venture Partner at Atlas, and is a good personal friend with many of us at Atlas as well. It was very much like bringing the band back together!

Bernard Lambert, CTO of Mariana, was also a key early hire, joining about a year into the journey from Telix Pharma, a targeted radiopharmaceutical player. Bernard literally has more years of radiopharm experience than probably anyone on the planet, having worked extensively in the field for 24 years, and was a key enabler for the technology. Like most new tech platforms, integrating deep domain experience – including scars and grey hair from prior learning cycles – is critical to success.

Mariana’s COO/CFO Linda Bain was the final member of the senior leadership team to join, and helped scale the company into its $175M Series B raise last fall, in preparation for a potential path to an IPO. Linda came to Mariana from Codiak Biosciences, where she was the CFO for seven years, and helped lead their 2020 IPO. Widely regarded as an exceptionally talented leader, we tried hard for several years to recruit Linda. Thanks to the concerted effort of the entire Atlas team, and in particular Andrea DiMella (our head of talent), we were able to help her land at Mariana.

One of the many recruitment activities that helped: Linda ran the Reach The Beach relay with us in Sept 2022 and was stuck in a van with me for 30+ hours. She may have said yes to joining an Atlas startup just to escape future time in the vans! Funnily enough, Simon also ran RTB with us, back in 2021. Running is the new golf, as we like to say. This highlights another axiom in the venture business: finding unique ways to build deeper community pays dividends over the long run.

As for all emerging biotechs, BD is an ever-present activity – talking to partners and keeping them up to date.  That said, the BD process that culminated with this acquisition really kicked off in earnest last fall as the story came together for the Series B, and we had line of sight for MC-339 entering the clinic. At our “Atlas Venture Retreat” in November 2023, interactions between Linda Bain and Shiva Malek, head of oncology research for Novartis, were key in setting up the BD dynamic in early 2024. The RLT space couldn’t have been hotter, with an incredible wave of M&A happening in parallel with Mariana’s discussions: RayzeBio acquired by BMS, Point by Lilly, and more recently Fusion by AstraZeneca.

While many parties were interested, Novartis stood out for its conviction around RLT (including its existing marketed portfolio of Lutathera and Pluvicto) and our confidence in their ability to carry forward the team and platform into the clinic. In late January, following a call we had with Novartis’ Ronny Gal and Susanne Kreutz about several ongoing dialogues in the portfolio, Novartis expressed their interest in moving forward with an acquisition to both Simon and Atlas. Our partners at Centerview helped finalize the deal – further strengthening their incredible market share in the >$1B deal category: they’ve done at least 55 M&A deals greater than $1B since 2019, more than the next nine advisors combined.

As we close this chapter of what we hope is a much longer Mariana Oncology story, we’d like to thank the entire CurieTx/Mariana team that helped guide this over the past 3-4 years – and all those in the broader ecosystem that helped with its success.

It’s always all about relationships and people – and, of course, the energy those interactions emit!