Publicly traded Invizyne Technologies is renaming itself eXoZymes, a rebranding intended to raise the company’s profile by highlighting the sustainable, cell-free enzyme technology its co-founders and colleagues have spent more than a decade working to develop for uses that include active ingredients for nutraceuticals and biopharmaceuticals.
eXoZymes replaces traditional chemical production methods with an approach that integrates widely available feedstocks like sugar and biomass with advanced enzymes engineered to thrive outside living cells. Those advanced enzymes are what the company now calls “exozymes,” a name that combines “exo-,” the Greek-derived suffix for outside, with “enzymes.”
“We have gone from saying, ‘Let’s just see if we can get the technology to work fundamentally,’ to now where we are focusing on applications. We actually now have a defined strategy,” said eXoZymes CEO Michael Heltzen.
That strategy, Heltzen said, will entail eXoZymes applying its cell-free, enzyme-based biomanufacturing systems toward commercial-scale production of molecules and chemicals for applications ranging from flavors and fragrances, to sustainable aviation fuel, to nutraceuticals—and over time, to biopharma drugs.
In nutraceuticals and pharmaceuticals, eXoZymes sees a market opportunity in expanding the universe of small molecule drugs that have traditionally accounted for most drugs that have reached the market, until the growth of biologics and more recently, cell, gene, and gene-edited therapies.
“There is a reason why people had started to work on the much larger molecules that are much harder to develop, because the [small molecule] space was maxed out,” Heltzen explained.
Expanding small molecule space
“What we find is that for each drug target and for each scaffold, if we sit down and we play around with making new versions of small molecules, we can vastly expand the space of small molecules there because we can get enzymes, especially these exozymes that are highly, highly engineered to do things specifically. We can get them to attach all kinds of things to the scaffold that have never been done before.”
Why focus first on nutraceuticals? “Because that is a fast way to market, and people need to see this platform work for real. We will demonstrate that, and we will also make good business on it,” Heltzen vowed.
Headquartered in Monrovia, CA, eXoZymes has attracted interest from potential partners willing to collaborate on nutraceutical solutions but won’t disclose partners until they sign collaboration agreements with the company. eXoZymes is also not saying yet how much of its business is expected to come from nutraceutical and pharmaceutical development but plans to address that question when it offers guidance to investors later this year.
“We will focus on nutraceuticals that have a pharmaceutical potential. That’s the market segment we are going to lead with and then extraordinary business cases—basically, when a technology fits with either a need or a want that is so strong that it can’t wait for later,” Heltzen said.
One such extraordinary business case entails sustainable aviation fuel. In November, the company was awarded a $2 million cost share grant from the U.S. Department of Defense’s BioMADE initiative, in partnership with the University of Georgia, toward enzyme production for cell-free biomanufacturing of isobutanol. Using the grant, the company will develop an enzyme production and processing pipeline and deploy the technology in 100 L pilot-scale facilities.
SynBio’s “natural extension”
eXoZymes hopes to improve on the performance of numerous synthetic biology companies whose share prices and market capitalizations (share price times number of outstanding shares) have plunged over the past couple of years.
One of the highest profile companies in the segment, Ginkgo Bioworks, saw its shares crater more than 80% in the year before it disclosed plans to chop an estimated 400+ jobs last June. The company carried out a 1-for-40 reverse stock split in August, and shares have since rocketed 75% from $7.71 to $13.50 on Monday. In November, privately held Molecular Assemblies confirmed on LinkedIn that it had laid off “many” employees and was exploring strategic alternatives, with a website listing 42 alumni of the company.
Heltzen says the trouble with synthetic biology has been that its key innovations of designing production pathways inside of living cells turned out to be its biggest hurdles, as the field’s most advanced companies found compounds or small molecules in nature that worked in the clinic but weren’t able to commercially scale their solutions successfully.
SynBio envisioned transforming the cell into mini chemical factories, an approach that didn’t work for several reasons. Inserting DNA into cells to carry out functions triggered mechanisms to turn off those functions. Efforts to produce a given chemical in a cell didn’t work, either because the chemical was toxic to the cell or because it resulted in a cell slurry requiring isolation of the product being produced.
“The isolation cost was higher than the value of the compound. So no matter what you do after that, you’re not going to have a profitable business,” Heltzen said. “Our take on the next generation of biomanufacturing takes the enzymatic pathways outside the cells—exozymes—thereby eliminating the bottleneck for scaling these biosolutions. In other words: Our approach both scales in the lab and for mass production, so it’s the next generation of biomanufacturing—the natural extension to SynBio.”
Keeping it simple
eXoZymes will continue to focus on developing its SimplePath
platform, which applies artificial intelligence (AI), high-quality enzyme data generation, and rational design optimization in the company’s lab to design, test, and commercially scale its biosolutions.
SimplePath consists of a series of enzyme-based biomanufacturing systems that use natural processes to perform complex chemical conversions designed to convert a starting material into a desired end product. Each SimplePath system has one or more “modules” which consist of one or more enzymes that work together to perform a defined biocatalytic conversion. A module can operate independently, or multiple modules can be coupled and designed to work together in a defined sequence, called a “cascade” or “enzyme cascade.”
Each system consists of a “substrate” or substance on which an enzyme acts, enzymes, a “cofactor” or substance other than the substrate, whose presence is essential for the activity of an enzyme, defined operating conditions, selected purification processes, and other system-specific elements.
Rather than needing months to optimize a single enzyme using AI as is customary, eXoZymes says it needs just a couple of days, with tens of suggestions for optimizations rather than one or two.
“While it’s just a single component of our tech platform, this represents a paradigm shift on its own,” Heltzen said. “Similar to how multiple languages with millions of words, can be represented with just 26 common letters, we are already on that same journey with the basic 20 amino acids—that combine to form all of our enzymes—to design and make enhanced enzymes that, in addition to being able to build all-natural chemical compounds, can produce better and new-to-nature chemical compounds.”
Nobel approaches
The company says SimplePath combines approaches at the center of four recent Nobel Prizes in Chemistry:
• Directed evolution, through which the company enhances its enzymes to become exozymes (Frances H. Arnold, PhD, 2018).
• CRISPR, which eXoZymes uses to design DNA strands and insert the right DNA code into E. coli in order to express desired enzymes in the cell (Emmanuelle Charpentier, PhD, and Jennifer Doudna, PhD, 2020).
• Bio-orthogonal click chemistry, the definition of which encompasses eXoZymes’ cell-free approach which incorporates enzymatic reactions, the company says (Carolyn R. Bertozzi, PhD, Morten Meldal, PhD, and K. Barry Sharpless, PhD, 2022; Bertozzi keynoted GEN’s “The State of Biotech 2023” flagship virtual conference).
• Computation protein design, which eXoZymes applies by using Rosetta and Google DeepMind to enhance its exozymes (David Baker, PhD, Sir Demis Hassabis, PhD, and John M. Jumper, PhD, 2024; Baker keynoted GEN’s “The State of AI in Drug Discovery 2024” in October).
The rebranding as eXoZymes comes nearly six years after the company was established to commercialize synthetic biochemistry research developed in 2016 in the lab of James U. (Jim) Bowie, PhD, at the University of California, Los Angeles (UCLA). Working with Bowie at the time were postdoctoral researchers Tyler Korman, PhD, and Paul Opgenorth, PhD.
Korman is now eXoZyme’s vp of research and Opgenorth, is the company’s vp of development. They co-founded the company in 2019 with Bowie, now a board member at eXoZyme and professor emeritus at UCLA. Bowie and colleagues focused on a biomanufacturing system designed to apply environmentally friendly chemical production processes.
Traditionally, biomanufacturing had entailed producing desired chemicals by introducing enzyme pathways into cells. Yet such processes encountered often insurmountable challenges that included low yields, low titers, or expensive product isolation—challenges that have been especially problematic for biofuels and other low-value products where containing production costs are critical.
Bowie developed an alternative approach in which the pathway enzymes are housed in a bioreactor rather than within cells, then developed methods to build robust enzyme systems, much more complex than previously thought possible for industrial chemical production.
“There was an a-ha moment where Dr. Jim Bowie came out of his office at UCLA one day and said, let’s just get rid of the cells, because this doesn’t work all that great. And we were just naive and talented enough to say let’s do it,” Korman recalled last year in a LinkedIn post. “Once Jim had that idea, we were off to the races, trying to figure out what cell-free enzyme systems to put together and how we would do it.”
“Stumbled upon a system”
“We stumbled upon a system that worked very well with our cannabinoid project from start to finish—the design to testing to demonstrating it worked—took less than three months,” Korman added. “Once we showed we could make cannabinoids, then we expanded that system to not just one cannabinoid, but multiple. And the rest is history.”
eXoZymes wrote the latest chapter of its history this week, announcing its rebranding on Monday and capping it two days later by starting to trade shares on Nasdaq using its new ticker symbol of EXOZ. Shares rose nearly 3% in early trading Wednesday, from $16.50 to $16.94 as of 11:12 a.m. ET.
Those shares had been traded on Nasdaq under the symbol IZTC for less than three months since the company carried out an initial public offering (IPO) in November. The company raised $15 million in gross proceeds ($13,277,747 in net proceeds) by selling 1.875 million common stock shares at $8 per share. Invizyne also issued 93,750 warrants at $.125 per warrant, each entitling holders to purchase one share of common stock at $8 for five years from date issued.
Invizyne shares climbed from the $8 IPO price to a high of $23 a share December 30 but have yo-yoed in recent weeks—from $10.46 on January 16, back up to $18.83 on February 3, then sliding again to $15.50 on Monday before climbing to $16.50 Tuesday, the final day of trading under the old name and ticker.
Net losses
Invizyne finished the third quarter with a net loss of $1,656,373, more than triple (218%) its $520,596 net loss of Q3 2023, and no operating income. For the first three quarters of 2024, Invizyne’s net loss more than quadrupled to $4,025,361 from $939,825 during Q1-Q3 2023, with no operating income.
Originally from Denmark, Heltzen, who marks a year as CEO this month, oversaw Invizyne’s launch as an independent public company, having joined as chief strategy officer in October 2023. Before Invizyne, he was executive vice president for strategy at graphene-based electronic device maker Paragraf, and earlier served as CEO of Cardea Bio, as well as CEO and chairman of Nanosens Innovations before it merged with Cardea Bio in 2019.
“[Korman and Opgenorth] came to me right after the exit of my former company. And frankly, I said, ‘There’s no way you can run pathways outside of the cell. That must be something you’re making up.’ They basically opened the doors and said, ‘I understand your reaction, but come kick the tires on it, come see it,’ Heltzen recalled. “It took me a couple of visits to deeply fall in love with the technology and the team here.”
That team has grown to 30 people—a workforce that eXozymes isn’t looking to expand.
“We have very, very good talent here and I’d rather invest into making them more productive, especially as people are starting to realize that what we are doing is not just something that we’re saying,” Heltzen said. “Empowering the right people with the right tools, with the right data is much more potent than just having extra people.”
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