Synthego’s first phase of development, CEO and co-founder Paul Dabrowski recently explained, focused on developing tools and technologies that made CRISPR gene editing accessible to researchers. In the second phase, Synthego brought those tools and tech into the clinic, helping with validation, target ID, discovery and general workflow.
Now Synthego has launched its third phase, with a focus on cell and gene therapy development that the company plans to carry out through the $200-million Series E financing it has just completed and announced today.
“The third part of our mission is to make biologically engineered cell and gene therapies accessible to all patients,” Dabrowski told GEN Edge. “We’ve built out the tools and the platform. We’ve demonstrated the value in the clinical context, and now we’re starting to move into that last phase. It all builds on each other.”
The Series E accounts for nearly half of the $450 million or more in total financing that the provider of genome engineering products and services has raised since it was founded in 2012 by Dabrowski and his brother Michael. Both were SpaceX executives, where Paul served as lead digital designer and Michael, head of software development.
In the decade since, Synthego has seen its products cited in about 1,000 peer-reviewed publications and grown its customer base to about 17,000 CRISPR researchers across 45 countries. Last October, Synthego said, it attracted more than 12,000 CRISPR researchers who participated online in its second virtual World CRISPR Day, which featured nearly 30 CRISPR experts discussing their latest research on the medical applications of CRISPR editing.
Synthego says proceeds from the latest financing will accelerate its creation of a cell and gene therapy discovery and development “ecosystem” intended to help researchers accelerate and simplify the translation of research discoveries into new therapeutics for serious diseases.
“We’re oriented towards supporting clinical trials and we provide all the components necessary to feed into that,” Dabrowski said. “We are currently not doing the manufacturing of the cell therapy itself, though you might be able to envision that that could be a direction that we could go in.”
Synthego achieved an important step toward that potential future direction last year when it achieved ISO 9001:2015 certification of its entire manufacturing process for GMP-grade single-guide RNA (sgRNA), used by biopharma customers for R&D of gene therapeutics and CRISPR-based gene editing. The company previously adopted Good Manufacturing Practice standards for producing customized GMP-grade sgRNA at its facilities.
In a paper published last year in Cell Chemical Biology, researchers from Synthego and New England BioLabs showed that their modified RNA guides increased the efficiencies of CRISPR activity (from two- to five-fold) over unmodified guides. They also demonstrated that the optimized chemical modifications extend CRISPR-targeting activity from 48 hours to four days.
Scaling and building
“We’re in a portion of the maturity of the business where we’re scaling and building that operational leverage and capacity. This furthers access to our technologies, because the more capacity we develop, the better we get, and the more customers can make use of the products,” Dabrowski said.
A key focus of Synthego will be shortening cell and gene therapy development timeframes for customers. Dabrowski noted that the scramble to develop COVID-19 vacines and drugs, among other factors, have shortened what was once a 10-year development timeframe for new therapies to seven years for recent genetic medicine, down to four to five years for the newest such treatments: “We think ultimately that gets compressed down to possibly even one year from an idea for a therapeutic all the way through clinical trial, though not necessarily validation.”
“Until now, we’ve been dipping our toes into the market and understanding what the customer needs are,” he added. “Now there’s a whole different level of investment into the processes and the capabilities.” That investment, he said, will include new facilities that Synthego plans to announce at a later date: “This is Synthego building additional capacity. It’s a multiple of the current capacity so it’s a big expansion.”
The cell and gene therapy ecosystem envisioned by Synthego begins with basics such as ensuring that its products meet quality standards of the National Institute of Standards and Technology (NIST) and other organizations, as well as interfacing with the FDA and other regulators.
Another element is process development. “Being able to help customers speed up that clinical translation when they’re trying to discover which CRISPR molecule, or if they know which CRISPR molecule, to try and get into the clinic,” Dabrowski said. “We can hand hold them through that process.”
Synthego’s cell and gene therapy ecosystem also envisions expanding upon the company’s two genome engineering platforms—Halo™ and Eclipse™.
Halo, launched in 2020, is designed to deliver tools for precision genome engineering—from CRISPR guide design through GMP-grade sgRNA reagents—by applying Synthego’s expertise in designing, selecting, and formatting optimized CRISPR reagents.
Eclipse, launched last year, is Synthego’s CRISPR-editing platform designed to accelerate drug discovery and validation by providing highly predictable CRISPR-engineered cells at scale. Eclipse leverages the company’s high-quality synthetic guide RNAs, standardized methods, and machine learning closed-loop feedback. Over the past two years, Synthego has applied Eclipse toward accelerate research programs focused on COVID-19 and neurodegenerative diseases.
“We’ve built these platforms and we’re looking to plug them all together, to have a seamless discovery-to-clinic workflow for customers,” Dabrowski said.
Turning CRISPR Off
The latest financing will also be invested in next-generation technologies such as CRISPROff™, a foundational technology for standardized precision and control of CRISPR-based gene editing inside cells using light.
“Effectively, we’ve added certain types of linkers into the guide molecules that we’re producing. That creates a photosensitive sort of region, and that actually allows us to turn a CRISPR reaction off,” Dabrowski said. “That’s a very important sort of capability because on-target effects for CRISPR tend to happen very quickly, within minutes, and off-target effects can actually take hours or days. So, you can modulate which one you’re getting.”
CRISPROff also allows for turning off CRISPR in various areas or being able to control dosing of CRISPR. The technology was successfully shown to control gene expression with high specificity last year in Cell. CRISPROff was first disclosed in Nature in 2020: “We anticipate that the CRISPRoff system will be a valuable tool for both in vitro and in vivo control of CRISPR technologies,” Jared Carlson-Stevermer, PhD, then of Synthego and now with Serotiny, and seven co-authors predicted.
Dabrowski said the technology will retain its usefulness as CRISPR continues to expand beyond simple use of the Cas9 enzyme, to a broader variety of enzymes such as Cas2, Cas12a, and Cas13.
“We’ve tried to create a foundational technology that can apply to any of these enzymes, and we believe that’s actually the case: You can control the dosing, the tuning with most if not all, enzymes,” Dabrowski said. “This is actually one of those foundational technologies which, over time, this or something like it, I believe, will become a standard for therapeutic use.”
The Series E financing isn’t the only time Synthego has been able to raise a nine-figure sum of capital. The company racked up $100 million in Series D funding in August 2020, on top of $110 million in Series C money garnered in 2018. Earlier Synthego raised $41 million in Series B (2017) and $8.3 million in Series A (2013).
“There’s been a lot of financing in the small and medium biotechs. There’s a big war on talent, and it’s very difficult to find qualified people who can set up a lab to actually do CRISPR at a high level. So there’s a lot of build-vs.-buy decisions happening,” Dabrowski acknowledged.
“When they see the products that we offer, it’s a very quick decision to make the buy decision, especially knowing that it’s a productized format. You know it’s going to work. You can basically come to our website, swipe a credit card, and you’ll get a gene-edited cell line,” he added. “It gets away from the mentality of scientists in a lab banging their head against the wall trying to trying to get something to work, which happens so often.”
Perceptive Advisors led Synthego’s Series E financing, with participation from new investors SoftBank Vision Fund 2, Declaration Partners, Laurion Capital Management, Logos Capital, GigaFund, and Chimera Investments—as well as existing investors Wellington Management, RA Capital Management, and Moore Strategic Ventures.
Based in Menlo Park, CA, Synthego plans to grow its workforce beyond its current headcount of “around 400,” Dabrowski said. New hires will fill positions ranging from entry level roles to senior management. One newly announced senior executive is Avi Raval as chief financial officer. Raval joins Synthego from Perella Weinberg Partners, where he was a Managing Director founding member of the firm’s health care group, and served as chief operating officer for the firm’s advisory business.
Raval’s experience has included advising healthcare companies on a wide variety of public and private financings, strategic matters—as well as mergers and acquisitions.
Asked if that augurs more interest by Synthego in growth through M&A as well as organically, Dabrowski said: “The way we view deals is on a spectrum from a transactional, one-time deal, all the way through partnerships and closer collaboration around IP. We could contemplate closer deals and potentially even acquisitions.”