Technical advancements in genetics and supercomputing are driving an astonishing amount of scientific progress, colloquially known as the biology revolution. The advances come at a fortuitous time. Environmental threats are chipping away at the quality of life for millions, while new viral illnesses continue to emerge and thousands of known diseases lack effective treatments.
Evozyne, founded by Paragon Biosciences, was created on the premise that the new-found ability to create high-performance proteins can deliver solutions to the most intractable modern problems. The company believes that by learning from evolution, it is possible to engineer future-proofed interventions for patients and address environmental challenges in carbon capture and energy storage.
To learn more about its biology-based advancements, we at Insights Success crossed paths with Evozyne’s team, and in the following interview, the company outlines its pathbreaking vision to benefit humanity.
Below are the highlights of the interview.
What was the initial idea behind the inception of Evozyne?
Evozyne was founded by Paragon Biosciences to advance boundary-breaking biology from the laboratory and into the real world, where it can solve complex problems.
Believing that the engineered proteins will dramatically accelerate scientific breakthroughs, in two years we recruited a world-class team of nearly 100 computational scientists, researchers, and commercial leaders to conduct a series of validation projects from Evozyne’s new 30,000-square-foot lab in Chicago.
Evozyne’s evolution-based design is about encapsulating vital information from the evolutionary history of a protein into a computationally defined latent space that enables rational design of natural-like proteins. When combined with an iterative design-build-test approach, the models generate protein designs that far exceed performance of natural proteins and can be deployed in in real-world applications.
In an early project, Evozyne partnered with Takeda, the Japanese pharmaceutical company, to improve the therapeutic potential of a specific target to treat a severe genetic disease. This inherited disorder causes a dangerous build-up of phenylalanine when a person eats protein or foods containing aspartame, which severely alters their quality of life.
Evozyne delivered an engineered enzyme that greatly exceeded Takeda’s design specifications, which led to an initial multi-asset licensing agreement worth up to $400 million plus potential royalties from any commercial product resulting from the collaboration. Our technology outperformed expectations in this critical test and resulted in an important collaboration for both companies. We are hopeful this partnership with Takeda will lead to new treatments that significantly improve the quality of life for patients.
What are the primary objectives and philosophy of Evozyne?
We believe boundary-breaking biology is the key to transformational applications in therapeutics and sustainability. Understanding that nature is the original and best engineer, we use deep evolutionary learning in the lab to understand millions of years of evolution.
By using evolution-based design, we’re able to tackle some of society’s biggest challenges, like finding treatments for patients with untreated diseases and developing solutions for sustainability concerns.
Philosophically, we are highly pragmatic and our design-build-test approach is applied to every aspect of our work. We partner with like-minded entities, working together to find world-changing solutions.
To realize the impact and potential of our engineered proteins, we need partners who share our vision for a better world and a commitment to the breakthrough approaches required to get there. Our next-generation proteins can be tailored across functions, and our efficient design-build-test cycles enable commercial-scale solutions that unlock new products and IP for our partners.
What are your key offerings that have a foothold in the industry?
Evozyne began by combining artificial intelligence, specifically machine learning, with applied biology to accelerate scientific discovery. The process speeds up lead identification for new medicines, which can result in findings that support investigational new drug applications and biologic license applications for experimental therapeutics. From a timeline point of view, Evozyne works from the earliest points, identifying and optimizing lead targets, and continues its work through developing experimental therapeutics and supporting them to Phase 3 clinical trials.
Currently, we are creating high-performance enzymes for our partners at Takeda and developing antibody, gene optimization, and CRISPR technology platforms that we believe will lead to the development of breakthrough therapeutics for patients.
On the sustainability side, protein engineering moves the science beyond traditional chemical catalysts by developing enzymes that can withstand industrial conditions, functioning in high-temperature conditions, and overcoming pH resistance.
Our lead sustainability candidate is engineered to perform at temperatures above 260 degrees Fahrenheit in an industrial setting. Until now, no enzyme has been able to function in the high-heat conditions associated with power generation.
Our tests indicate that we have a product that meets the challenge of enzymatic on-site carbon capture, which means the CO2 from power generation is never released into the atmosphere. We look forward to proving its performance, first at the University of Kentucky this year and later at the National Carbon Capture Center in Alabama.
What are the roadblocks that Evozyne faces in the ever-changing landscape of the business world?
Science is unpredictable, and it’s hard. Those two facts, plus the competitive nature of biotech businesses, make it tempting to rush products to market. There are notable examples of synthetic biology companies that gave in to that temptation, sold products that didn’t perform as billed and subsequently failed.
Evozyne followed those stories closely, and our team is committed to doing things differently. Our highly pragmatic, design/built/test model requires us to repeatedly prove to ourselves, with objective data, that the technology performs as expected in real-world conditions. Evozyne will bring products to market when and if they are proven to a high level of certainty.
Being first can be a disadvantage if you fail to meet market expectations. Protecting our reputation is a top priority for Evozyne, and that means making sure we’ve done the hard work to prove the performance of our technology platforms.
Beyond reputation management, recruiting top scientific talent is a hurdle for many biotech companies. Fortunately, Evozyne has proven its ability to hire top talent, which we attribute to our pragmatic approach, the impact of the problems we’re working to solve, and the financial health of our company. It helps that Chicago is a world-class city, with globally renowned universities and a thriving ecosystem that supports emerging biotech and pharma companies. The scientific talent we need to succeed wants to work here and, more important, are happy living here.
How is your company adapting to market orientation?
Nearly half of the world’s disease burden will be addressed by biology in the next 20 years. With that in mind, we’re pursuing life-changing treatments for patients and finding ways to improve life for patients with diseases that aren’t currently treatable. There are more than 10,000 diseases for which no medicine exists, and we hope to be part of the solution for patients who lack options.
On the sustainability side, we’re working to address climate change with an on-site solution for carbon capture. We’re uncovering new paths to replace harmful plastics and addressing global warming by making carbon capture a reality. Our goal is to build high-performance proteins, with exceptionally advanced functionality that makes what’s possible a reality. They are designed to be consistent with the laws of nature and match the complex character of natural environments, enabling biology-based solutions that open our imagination to what’s possible in solving some of society’s most intractable problems.
What is your approach to implementing innovative technologies?
It’s important to understand that the protein sequence space is impossibly large—much larger than the number of atoms in the known universe—and no existing approach can comprehensively search it. Yet that’s where we believe we’ll find answers to the world’s most pressing scientific questions.
Our machine learning models help us find evolvable proteins from that vast space that can be engineered to meet real world challenges. More importantly, we learn from every sequence generated in the design process, not just from the ones that work.
Evozyne generates genotype-phenotype mapping for every sequence generated, adding to our libraries and ability to find desired solutions faster. The design rules uncovered from these sequences help us simultaneously optimize several protein functions. That’s a whole lot more efficient than optimizing one property at a time.
This functional innovation forms our design philosophy, unlocking the natural potential of evolved proteins.
How does your company provide a societal benefit?
We’re using science to solve some of the most complex problems our society faces.
Think about it like this. Our platform is capable of creating molecules that surpass the current limits of performance. We can achieve targeted improvements in function that mirrors the capabilities of natural evolution. If nature is the world’s best engineer, imagine what it can do if it’s fast-forwarded by a few million years.
What is the next chapter for Evozyne?
Our focus is on developing technology platforms for therapeutics and sustainability. On the therapeutics side, the focus is on gene optimization, gene editing, and future-proofed antibodies.
Gene replacement therapy requires better-than-wildtype performing genes to minimize dosing, maximize efficacy, and reduce immunogenicity. Existing gene therapies are not simultaneously optimized across all these dimensions. Furthermore, certain diseases require replacement of genes that are too large to fit into existing delivery technologies, rendering them inaccessible.
Using our computational biology approach, we engineer transgenes with superior performance in activity, affinity, stability, and immunogenicity. In addition, Evozyne’s technology enables miniaturization of the gene cassette, unlocking cures for previously inaccessible diseases.
Gene editing with CRISPR-Cas nucleases has introduced new therapeutic modalities to treat a wide range of diseases. Yet the existing nucleases are not specific enough and can cause off-target editing, which means they edit the genome in areas that are not intended.
By augmenting and redesigning the nucleases created by nature, Evozyne is developing a comprehensive library of highly specific Cas nucleases that can access most of the genome. This combination of accessibility and specificity will allow previously untreatable diseases to be cured safely and effectively with our enzymes.
The Pandemic provided another complex problem that we hope to solve. We all know that as viruses mutate, they develop resistance to antibodies, rendering therapeutics ineffective. The problem treating viral infection is one of understanding the evolvability of the virus. Despite widespread research, current discovery tools have limited success in countering viral resistance.
Using our ability to understand the constraints on viral evolution, Evozyne is developing an approach to generate future-proofed, broadly neutralizing antibodies. Our first application of this platform is a variant-resistant COVID-19 antibody.
Evozyne’s sustainability practice is focused on carbon capture and battery technology.
Capturing carbon at the point of production has been inefficient and energy-intensive. Right now, it’s too expensive to reduce emissions. While naturally occurring solutions can improve efficiency, they cannot withstand harsh industrial conditions and can’t perform at high temperatures.
Leveraging design rules encoded by nature, Evozyne is developing a highly efficient organic catalyst that remains stable in the required industrial conditions, making carbon capture at the point of production cost-effective.