Founder Spotlight #34: Swamy Vijayan @ Zafrens
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Zafrens works at the cutting edge of biology, chemistry and engineering to build single-cell multi-omics tools. When combined with high throughput genetic or chemical perturbations, the Zafrens platform allows studying how the functional states of cells track with their transcriptional states, unlocking insights into the complex regulatory layer of the cell. The ability to track and manipulate the conversion of genetic code into functional output has a number of applications across diagnostics, therapeutics and synthetic biology. The combination of proprietary tools for cell analysis and insights into cellular architecture allows Zafrens to build innovative products in different verticals, with an initial focus on understanding and manipulating the RNA regulatory layer in the cell.
Swamy Vijayan is a serial entrepreneur, having run 3 companies as Founder & CEO, with deep experience bringing interdisciplinary technologies to market.
After his PhD in Physics from the University of Pennsylvania he started his professional career working across optics, molecular biology, nanofabrication and computational analysis at various genomics companies, eventually managing research on novel sequencing technologies @ Illumina as Nanobiology Group Leader.
He started his first company, Omniome, to simplify instrumentation around DNA sequencing — allowing inexpensive, single sample-to-answer workflows rather than have to batch samples. Omniome pioneered advancements in multiple disciplines — from plasmonic label-free sensing and ultra-widefield fluorescent optical detection, to novel nucleotide synthesis methods, to enzyme engineering for novel polymerase properties — all designed to integrate on a tiny sample-to-answer cartridge. Omniome exited to Pacacific Bioscience for up to $800M.
He next started Plexium to replace the traditional 96-well plate experimentation platform with a 150,000 well plate format and led the development of cell-based drug screening using DNA-encoded libraries in this format. He set the research and drug discovery strategy at Plexium pioneering screening and validation approaches for true small-molecule molecular-glue protein degraders. He also led business development efforts towards multiple large partnerships with pharmaceutical companies. Plexium is currently series B stage, having raised nearly $170M in venture funding since inception.
His current venture, Zafrens, builds on Swamy’s learnings pushing boundaries and perspectives at the interface of various disciplines. Zafrens unlocks comprehensive cellular analysis through ultra-highthroughput single cell screening. The novel techniques required to map functional states of cells to their transcriptional state provides deep insights that unlock unprecedented diagnostic and therapeutic value.
Personal Spark
What prompted you to pursue a career in Life Sciences?
It was initially the dissatisfaction with theoretical physics as the focus of my graduate studies than any pull from the life sciences. Though I was quite poor with experimental work initially I managed to graduate with some experience in polymer science, which I utilized as a framework to model DNA at my first job at Bionano Genomics. I realized the power of biophysical manipulation of biochemical systems in this role and was lucky to be given the space to teach myself molecular biology, bioinformatics and nanofabrication principles on the job. The rest of my career has built on this foundation, picking up additional hands-on skills in different areas of science over time. What is most exciting from my vantage are the tremendous opportunities to unlock value and insights once you build intuition in multiple disciplines. I have noticed without this intuition we are likely to end up building tools searching for applications or applications built on underpowered tools. Having jumped in head-first on some big ideas, I’ve learned how to integrate the personalities, perspectives and technical abilities across disciplines in the service of transformational commercial opportunities. My wish at Zafrens is to create a large cadre of leaders at this tech-bio interface who can continue to push boundaries and open more doors to value and insights.
How did you get your training, if any to be able to build your company? Life Sciences increasingly has interdisciplinary academic backgrounds, while other founders take the plunge and jump straight off the deep end. Which one are you & why?
I have a very strong interdisciplinary background across both technology and operations accumulated from years of jumping in and trying things. Zafrens is my third company. I have tried to do essentially the same thing at every one of my companies — build a foundation for (lots of) smart people to do (lots of) important things for at least the next 100 years. My skills have been in anchoring such a grand ambition in just a handful of tasks in the near term. At Omniome it was reinventing sequencing to enable a century of new genomics applications and at Plexium it was reinventing drug discovery to enable a century of new therapeutic explorations. While it was an absolute joy carving out this path with our teams, I failed at external messaging and creating investor synergy to appreciate this vision. The lessons are too many to list, but they have been hard-earned. (This is a longwinded answer to the question of whether Zafrens is built from experience or jumping off the deep end — it is very much built from experience jumping off the deep-end a few times trying to do atypical things in atypical ways). I haven’t tired of wanting to build a great place for smart people to do important things. The past experiences have clarified my purpose and highlighted challenges to implementing my vision, so I feel more confident I can help guide Zafrens to be the transformational company we’d like it to be.
Can you tell us a little bit about your background & career thus far? What were you doing before you started running a high potential venture backed startup?
I have built my career around convincing myself of the ‘trueness’ of something and helping execute whatever is needed to implement the most broadly useful manifestation of my conviction. (Other people get it, as well, if we are going after something fundamentally true and useful, and it becomes a shared pursuit. This has been the true privilege of my career). I come from a background of asking questions and trying things without limitation to training or experience. The breadth of fields I have worked on have provided me intuition (and empathy for interdisciplinary complexity and its cadence) that is somewhat rare. At this point, I have an overarching background in instrumentation, genomics and drug discovery — not from any formal training, but from trying to do impossible things in these areas and succeeding, or coming close to succeeding, a few times.
Anything else you’d like to share about your life, academic trajectory, etc.?
I have found the most useful skill I’ve picked up is being able to imagine things from first principles. So I like reading beginner textbooks and articles in different areas to learn foundational concepts. I suspect other tech-bio entrepreneurs might find it interesting also.
Company Overview
What problem is your company solving? How did you become motivated to tackle this particular problem?
Currently, cell biology and specifically functional cell assays are an incredibly inefficient step in the drug discovery process. Over the last several years we’ve been able to make moderate improvements in this space, however it is still lagging far behind what we’ve been able to accomplish in other areas. For example, with the invention of DNA encoded libraries we can now screen millions of compounds against a single target simultaneously. Zafrens aims to achieve this same scale for cell biology through development of a single cell analysis and manipulation platform. This technology has many potential applications across many modalities. We are currently converging our technology stack towards alternative perspectives on cell and gene therapies. The conventional notion with C&G Tx has been to interject directly at the DNA and RNA level to modulate proteins that are undruggable. We take the view that how those DNA and RNA become proteins is a richer vein to mine — firstly because we think they can be modulated with oral drugs, and secondly because they allow a new layer of control over biology we currently do not possess. Unlocking this profound regulatory layer requires us to be able to 1.) understand and 2.) modulate disordered protein interactions, both of which are incredibly hard problems. However, our unique screening platform will allow us to systematically study and manipulate how RNA become proteins at high throughput. The motivation was to identify the biggest opportunity in all of biology (in term of commercial value and insights unlocked) that can be solved by engineering and then working out the tools needed to solve it.
What does your company do?
We are a life science products company built on engineering tools that allow us to study and understand the compiler of the cell so that we may manipulate them to cause (selected) genetic code to be processed differently.
Now in technical language, what are the specifics of what your company does?
As most people in biotech know, there is very little correlation between RNA levels and protein levels in eucaryotic cells. How can this be if all proteins come from RNA? RNA-binding proteins (RBPs) are a small set of disordered proteins that assemble on various regions of RNA and determine when, how, where, how much, how often (etc.) the RNA is converted to its encoded protein, including which isoform of the protein is created. There are only a handful of RBPs in the cell, different RBPs specializing in different steps of RNA processing. How can a handful of RBPs regulate the fate of the entire transcriptome and proteome, oftentimes with exquisite selectivity? They can only do this if they somehow are able to generate higher diversity and complexity from few building blocks. It tuns out RBPs interact with each other combinatorially, and with RNA, to generate the complexity of regulation. These combinatorial interaction of RBPs are what we are interested in. We believe this to be the compiler layer of the cell. We are interested in understanding as much as we can about the interactions of RBPs, as well as manipulating these interactions systematically, with small molecules, so we can alter how RNA become proteins. We believe this to be an incredibly exciting frontier in therapeutic and synthetic biology. This has been an impossible area to study, however, due to the large number of potential interactions and the completely unexplored frontier of drugging disordered proteins. We are developing proprietary tools that allow us to dissect these layers of biology and chemistry. As it turns out, the same tools could transform the research, diagnostics and cellular analysis market. We are hoping to carefully stage the company growth and our business and commercial activities to exploit the full capabilities of our tools, insights, and drugs. We will likely highlight and monetize the capabilities of our proprietary tools first, since the therapeutic insights we are going after may need a little time to mature.
Why does your solution matter for the world when you get it right?
We can transform multiple industries through the depth and scale of insights we can generate, because how RNA become proteins is vital to all of biology. More immediately, it requires us to build tools that can relate the functional state of the cells with its transcriptional state, at scale. This is an unprecedented capability that can transform our understanding of biology.
Genesis
What is your company’s founding story?
Zafrens was born out of a desire to build a company that can thrive for 100+ years. Defining and dominating a new area while commercializing blockbuster products is how other companies have done it historically (the most successful companies also create a culture that can define and dominate new areas over time). In trying to replicate this strategy, the regulatory layer of the cell and the novel tools required to unlock it felt like the biggest areas to take on to build a large company.
Timing is everything — how did you know the timing was right?
There is enormous interest from pharma and the scientific community in accessing undruggable targets via their RNA. A number of companies have formed in recent years addressing this space with small molecules and a number of significant partnerships with big pharma have also been signed. The tools we are developing are independently valuable and represent the biggest growth segment in the genomics research market.
Accomplishments
What are some of the notable milestones your company has achieved thus far?
We’ve put together an exciting team and are proud to be backed by a dynamic team of ambitious and technically sophisticated investors.
What are some of the biggest hurdles ahead? How do these create points of value inflection?
Driving to substantial value as soon as possible and maintaining a consistent growth trajectory are vital to enabling the long time-horizon we aim to work within. Rather than specific hurdles and accomplishments, we aim to think in terms of constant progress (constant hurdles) and continual value accretion in order to build a lasting, multigenerational company. Our progress and value is spread across our collection of tools, insights, chemical assets and products — we expect this diversification to allow consistent, stable growth over long periods.
Pay It Forward
Throughout the journey, what have been some of your biggest takeaways thus far? What advice/words of wisdom would you share from your story for other founders?
The entrepreneurial journey is more enjoyable with the right investors and close partners. Working only with partners who fully buy in to the vision and plans for the company is highly advantageous. That said, entrepreneurs also need to fully embrace the expectations of investors — to generate significant returns in a short period of time during the private stage, and to continually build value throughout the life of the company as a public enterprise. Understanding this may be crucial for technical founders — the science is an important part, but it has to be positioned to generate a lot of tangible value (10X your largest venture investors fund size is my rule of thumb).
What are some of the must haves for an early stage Life Sciences startup in your eyes?
Agility to correct course when needed and always remain focused on building value. I feel the first part comes naturally to technical entrepreneurs, the second part could come through investors you trust to be able to guide your thinking or team members with business and operations expertise.
What are some of the traits that make a great founder? What type of risk profile/archetype does someone need to have to be a founder in your opinion?
Being clear about values and purpose helps greatly. Why do you want to start a company? Need to have an unshakeable purpose to weather the constant storms and need to have firm values to help the company step through the difficulties together. Founders can be as diverse as the purpose and values they hold, don’t think there is one archetype.
For folks coming out of academia, what advice would you share?
Don’t know that coming out of academia is any different from coming out of another place. Spending some time in industry can provide perspective on working with people, project management skills, commercial insights etc. Coming straight from academia allows freshness in thinking about operational matters and sheer drive to solve problems. If they have a keen interest and ability to learn non-technical skills, folks coming straight from academia have the edge in breaching new frontiers. I wish them the very best!
Not everyone knows everything. Often founders have to learn either the science or the business side better. What advice would you give for someone picking up a new skill set such as this?
The holy grail is finding someone you enjoy talking with who understands your technology as thoroughly as you, but has deeper industry and business experience (ideally some executive experience). It is magical when you can find this person (as a cofounder or advisor or team member) because you can learn rapidly from them. Having a clear sense of purpose and values around why you are running a company can help clarify how you should run the company and whom you should bring on board to help you. Then it is a matter of reaching out to as many people as you can who might meet the criteria and see if you can build the right team around yourself.
What advice for managing and hiring a great team can you share?
Hiring and leading teams is a very personal style and will have to reflect your true values and vision. I would warn against hiring opposing views at the early stages of the company — coherence and shared views are enormously valuable in getting things off the ground.
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