"One of my aspirations has always been to bring the complementary disciplines of chemistry and biotech together in an integrated fashion to discover new products that benefit society."

I am writing to tell my story of the founding of Lassogen, a biotech start-up company that is dedicated to advancing novel therapeutics based on lasso peptides.  I was originally trained as an organic chemist but have spent the past 25 years immersed in the biotechnology world.  One of my aspirations has always been to bring the complementary disciplines of chemistry and biotech together in an integrated fashion to discover new products that benefit society. Several years ago, I had a team explore a new technology called cell-free protein synthesis, which involves adding a gene as linear DNA to a cell-free extract that has all the biological machinery necessary to convert the gene into a desired protein.  Our idea was to extend cell-free methods from single proteins to more complex pathways that could serve as a means to rapidly produce diverse natural products. To test the concept, we initially chose to examine several short biosynthetic pathways that were known to involve only a small number of genes.  One of those pathways was associated with a relatively obscure (at the time) class of natural products called lasso peptides.  Little did I know that this exploratory search for a technology proof-of-concept would ultimately change my life so dramatically.

Our first successful production of a lasso peptide using cell-free methods came in late 2016, when no more than 25 lasso peptides had been discovered and they were considered curious and rare structures with largely unknown function.  That notion changed shortly thereafter when Doug Mitchell at the University of Illinois, Urbana-Champaign published a seminal paper (Nature Chem Bio, 2017, 13, 470-478. doi: 10.1038/nchembio.2319) that revealed how prevalent and diverse lasso peptides actually were in nature. The chemist in me was struck by the unusual 3-dimensional architecture of these remarkable molecules and the biotechnologist in me was intrigued by the fact that these structures, with their distinctive lariat-like fold, could only be produced biologically, not chemically. Doug’s results unexpectedly unveiled the expansive scope of natural lasso peptides, which represented a potential treasure trove of novel medicines.  However, there was still a major barrier to unlocking this vast lasso peptide diversity – producing lasso peptides, like many natural products, was a slow, tedious, and challenging endeavor.  Realizing that a cell-free process could allow rapid screening of the thousands of newly discovered sequences, I immediately reached out to Doug and, as it transpired, that initial call unwittingly represented the birth of a new company called Lassogen.

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The idea for a company is easy, but translating that into reality is more challenging and requires at least two major ingredients. Firstly, to realize the dream, you need a great team – it’s all about the people.  In addition to Doug, who was fully engaged as a co-founder, we were fortunate to attract two other outstanding co-founding team members, both of whom I have known for over 30 years. Hiroko Masamune and I did postdoctoral studies together at MIT and she has extensive drug development experience. Hiroko and I had lunch one day and I described my vision for developing a new class of therapeutics based on lasso peptides.  Once she saw their unique structure and learned that they are an untapped source of natural molecules that combine the advantages of small molecules and antibodies, she was instantly hooked and has been our Chief Development Officer ever since. Tracy Handel is a Professor in the Skaggs School of Pharmacy and Pharmaceutical Sciences at UCSD, where she works on chemokines and chemokine receptors. Tracy has been searching her entire career for new ways to modulate these unruly receptors, and she quickly discerned the potential of lasso peptides based on how closely they structurally resemble natural chemokines, especially relative to small molecules and antibodies. Tracy became another inspired Lassogen co-founder.

"Within 3 months of graduating from the Illumina Accelerator program, we were able to raise $4.8 M from venture groups in a Seed round led by Playground Global. We were directly introduced to 4 of the original 5 Seed investors through our involvement in the Illumina Accelerator program, so I would say this engagement was well worth the effort!"

An enthusiastic founding team is important, but research will not go far without a second critical element – financial capital.  We now needed to take the next step and convince others that lasso peptides were destined for greatness. Importantly, we had just received news of our first break - we had applied to and were accepted into the Illumina Accelerator, which is a prestigious incubator in the Bay Area. Before we could accept this amazing opportunity, we needed funds. As with many start-ups, I initially turned to family and friends.  Despite many entrepreneurial avenues taken throughout my career, this was the first time that I attempted to sell an idea to the people I know and love.  This is the last group that you would want to disappoint, or worse, lose their money!  Fortunately, our passion for the lasso story won the day, and with this early support we were able to embark on a fruitful six-month Accelerator program. Despite being cut short by the incipient COVID-19 pandemic in March 2020, the experience at Illumina was game changing for us. Within 3 months of graduating from the Illumina Accelerator program, we were able to raise $4.8 M from venture groups in a Seed round led by Playground Global.  We were directly introduced to 4 of the original 5 Seed investors through our involvement in the Illumina Accelerator program, so I would say this engagement was well worth the effort!

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With initial capital in hand, the fun and hard work begins.  We are now about 18 months into our quest and all I can say is that therapeutics based on lasso peptides are even more compelling than imagined.  Our vision for this new therapeutic modality is grand and we are convinced that real medical breakthroughs are inevitable.  We have developed a platform for discovering and optimizing new lasso therapeutics and we have two programs focused on treating cancer.  There is much more to say, so stay tuned for our future blogs!

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For me, this has been a fantastic voyage that started with an idea, a result, and a call.  The next leg of the journey will be exciting and challenging as we chart a course aimed at improving health and well-being through our lasso therapeutics. We are looking forward to sharing our promising results along the way.

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Thanks for reading!

Mark J. Burk

President and CEO

Lassogen Founder

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