John Cumbers, founder of SynBioBeta

Any doubts about synthetic biology’s attractiveness to investors were likely shattered during the first quarter, when investors pumped $4.6 billion into such companies—more than four times the $904.7 million invested in the sector during Q1 2020, according to figures compiled by SynBioBeta, a community of engineers, investors, and other synbio stakeholders.

“It’s Silicon Valley investing in the next big thing, and the next exciting thing, and paying it forward to the next generation of entrepreneurs,” John Cumbers, SynBioBeta’s founder, explained during a recent GEN Live focused on synthetic biology’s growth and challenges (Download the episode here).

While synthetic biology has applications that include flavors, food, fragrances, and numerous things not beginning with the letter “f,” it was life sciences companies that led the synbio financing rush during Q1, according to a SynBioBeta report. ElevateBio scored the quarter’s largest financing with a $525 million Series C round intended to support the acceleration and scaling of ElevateBio’s end-to-end cell and gene therapy technology platform offering.

Next-highest, raising $400 million in Series C capital, was Insitro, which uses machine learning and data generation at scale to carry out drug discovery and development—in the process attracting two biopharma giants among its collaboration partners, Bristol-Myers Squibb and Gilead Sciences.

Looking beyond this year, synbio is expected to more than triple in size as an industry from $9.5 billion this year to $30.7 billion, according to a MarketsandMarkets report released in May—a compound annual growth rate of 26.5%.

Below is GEN’s first-ever A-List for synthetic biology—the five largest public companies and five largest private companies. The public companies are ranked by their 2020 revenues as disclosed in regulatory filings, including sales of products or services, as well as revenue from collaborations and R&D activity. Private companies are ranked by the total capital they have raised, as disclosed by the companies themselves, either in press statements or in responses to GEN queries verifying figures compiled by other sources.

Also included in this list are several “up and comers” that have either raised significant capital in recent months, shown positive data for their technologies, and/or launched significant new collaborations with partners.

Each company is listed with a short explanation of their recent activity.

 

Top Public Companies

#5. Codexis

Revenue: $69.056 million in 2020; $18.032 million in Q1 2021

Codexis on June 17 raised its 2021 investor guidance after receiving a binding purchase order from an undisclosed global pharma for up to $13.9 million of a proprietary “high-performance” enzyme. Total revenues are expected to range between $89 million and $93 million, up from $82 million to $85 million. Codexis has also increased its product revenue guidance to between $45 million and $48 million, up from $36 million to $39 million. Codexis signaled its commitment to synthetic biology in November 2020 by announcing the SynBio Innovation Accelerator collaboration with Casdin Capital. The Accelerator aims to fund early-stage companies with disruptive technology platforms or unique product development capabilities in synthetic and industrial biotechnology. Codexis’ first Accelerator investment was made in Arzeda, a privately-held computational protein design company.

 

#4. Ginkgo Bioworks

Revenue: $77 million in 2020

Ginkgo Bioworks took on additional financial muscle by agreeing to go public in May through a $17.5 billion merger with a special purpose acquisition company (SPAC) that is expected to provide up to $2.5 billion of gross cash proceeds. The SPAC merger with Soaring Eagle Acquisition Corp. implies a pre-money equity valuation of $15 billion for Ginkgo, launched in 2008 by co-founders who have worked together for close to 20 years since meeting at MIT. Their goal was to develop a platform that could program cells as easily as computers across applications that include food, agriculture, pharmaceuticals, and industrial chemicals. In June, Ginkgo agreed to apply its organism engineering expertise to an unidentified Sumitomo Chemical bio-based commercial product and explore bio-based production methods that can replace petroleum-based products.

 

#3. Twist Bioscience

Revenue: $90.1 million in fiscal year ending September 30, 2020; $59.364 million in October 2020–March 2021

Twist Bioscience, whose disruptive platform manufactures synthetic DNA by “writing” DNA on a silicon chip, joined Illumina, Microsoft, and data storage giant Western Digital last year to co-lead the DNA Data Storage Alliance they established with 11 partner tech-based companies and institutions. The alliance aims to advance DNA data storage by agreeing upon a “roadmap” of definitions and standards to help the industry achieve interoperability between solutions. In June, Twist acquired iGenomX, which offers multiplex library preparation tools for next-generation sequencing (NGS) workflows; and partnered with Regeneron Genetics Center to produce a custom NGS population genetics genotyping assay designed to incorporate genetic differences of global populations, thus gaining insights into disease mechanisms, identifying novel drug targets, and accelerating drug discovery and development.

 

#2. Precigen

Revenue: $103.178 million in 2020; $24.511 million in Q1 2021

Precigen’s wholly-owned subsidiary Precigen ActoBio on June 10 reported positive topline results from a Phase Ib/IIa trial (NCT03751007) assessing its microbe-based therapeutic AG019—developed through the company’s ActoBiotics™ platform—in recent-onset type 1 diabetes. Following an eight-week treatment cycle of oral AG019 alone, 5 of 9 adults (56%) showed stabilization or increase of C-peptide levels during the first six months—as did 7 of 10 adults (70%) and all four adolescents treated with AG019 and teplizumab. Earlier this year, Precigen launched a first-in-human Phase I trial (NCT04724980) PRGN-2012, the company’s first off-the-shelf AdenoVerse™ immunotherapy targeting infectious disease. Trials are also in progress for PRGN-2009 in HPV-associated cancers, as well as the UltraCAR-T® trials evaluating PRGN-3005 in ovarian cancer and PRGN-3006 in acute myeloid leukemia.

 

#1. Amyris

Revenue: $173.137 million in 2020; $176.859 million in Q1 2021

Amyris, which produces sustainable ingredients for the Clean Health & Beauty and Flavors & Fragrances (F&F) markets, has also developed a COVID-19 vaccine with the Infectious Disease Research Institute. On July 1, Amyris licensed the vaccine to Nant Africa through an agreement “expected to generate several million dollars in near term upfront and milestone payments” for the company, plus long-term royalties. Amyris Q1 revenue surpassed all of 2020’s; President and CEO John Melo credited continued product-related revenue growth and completion of the company’s second strategic ingredients transaction, a potentially more-than-$500 million supply/manufacturing agreement inked in March with DSM Nutritional Products, a subsidiary of Royal DSM to supply Amyris’s product portfolio of F&F ingredients. That deal alone added $144 million to Amyris’ quarterly revenue total.

 

Top Private Companies

#5. Apeel Sciences

Total Capital Raised: $390.1 million1

Not many companies can brag about having Oprah Winfrey and Katy Perry among their investors, but Apeel Sciences can. Based in Goleta, CA, Apeel manufactures plant-derived coatings used by fresh food growers, suppliers, and retailers use to keep produce fresh—and thus curb global food waste. Apeel’s approach to innovation made it one of 61 companies designated 2018 World Economic Forum Technology Pioneers, and landed it on TIME magazine’s Best Inventions 2019 and Fast Company’s World Changing Ideas 2019 lists. Apeel completed its most recent financing, a $250 million Series D round, in May 2020, which brought the company’s valuation to over $1 billion, after raising $70 million in Series C (2018), and lesser amounts in earlier rounds and seed stage financings.

  • 1Apeel referred GEN to the $390.1 million “total funding amount” figure compiled by the venture capital market data tracker Crunchbase.

 

#4. Insitro

Total Capital Raised: $643 million

More than half of Insitro’s total capital raised came through a single financing, the $400 million Series C round completed in March and led by Canada Pension Plan Investment Board (CPP Investments). The financing capped a busy but productive 12 months during which the company launched an up-to-$2 billion-plus collaboration with Bristol Myers Squibb to discover and develop novel therapies for amyotrophic lateral sclerosis and frontotemporal dementia; built and demonstrated its target discovery platform in a NASH collaboration with Gilead Sciences, for which Insitro received its first operational milestone payment; and acquired Haystack Sciences, aiming to strengthen its machine-learning enabled drug discovery efforts. Earlier, Insitro raised $143 million in Series B capital (May 2020) and $100 million in Series A (2018).

 

#3. ElevateBio

Total Capital Raised: $869.3 million

ElevateBio in March completed a hefty $525 million Series C financing, with plans to use the proceeds toward developing and expanding its technology platforms, growing its process development and GMP manufacturing capacity, advancing industry partnerships, and developing drug candidates. Based in Cambridge, MA, ElevateBio creates and operates a portfolio of companies across platforms that include gene editing, induced pluripotent stem cells, and protein, viral, and cellular engineering. A recent job ad sought an associate scientist who can, among other skills, “apply recent advances in synthetic biology to create and characterize the next generation of CARs/TCRs.” ElevateBio completed a $150 million Series A financing in May 2019 upon its launch, followed by a Series B that closed last year at $193 million.

 

#2. National Resilience (Resilience)

Total Capital Raised: Over $964 million

National Resilience (Resilience) describes itself as “the next generation of life sciences manufacturing.” Resilience defines next-gen to include synbio, as it listed “synthetic biology experimental approaches” among preferred experience sought for a recent job opening, vp/head of platform R&D.  Resilience plans to modernize and expand the production capacity of its Ontario-based subsidiary Resilience Biotechnologies using C$199.2 ($164 million) from the government of Canada’s Strategic Innovation Fund awarded in May. A month earlier, Resilience acquired privately-held Ology Bioservices, an Alachua, FL, biomanufacturer, for an undisclosed price, adding 300 staffers and expertise developing and manufacturing drugs and biologics for commercial customers and the U.S. government. Resilience previously acknowledged having raised “over $800 million” in private capital, most of that being the eye-popping $750 million Series B financing completed in November 2020.

 

#1. Impossible Foods

Total Capital Raised: More than $1.5 billion

Nearly a year after raising $200 million in Series G financing, bringing its total capital raised to “more than $1.5 billion,” plant-based meat company Impossible Foods remains hungry for growth. The company spent the first six months of the COVID-19 pandemic accelerating the rollout of its Impossible™ Burger from 150 to more than 8,000 grocery stores nationwide, including national chains such as Kroger, Trader Joes, and Walmart. Impossible Burgers can also be found at Burger King, Red Robin, and White Castle. Behind the meatless meat-like taste is heme, a plant-based molecule produced by fermentation of genetically engineered yeast to which DNA from soy plants are inserted. Long-term, Impossible Foods plans to create plant-based versions of every major category of animal-derived food products.

 

Up & Comers

Antheia

Privately-held Antheia closed an oversubscribed $73 million Series B financing June 30, bringing its total capital raised to $98 million. Proceeds are intended to support commercialization of Antheia’s first pharmaceutical compound, and production scale-up for several critical active pharmaceutical ingredients and key starting materials. Using bio-based fermentation, Antheia produced several classes of plant-inspired pharmaceuticals it said cannot be manufactured through conventional scalable synthetic chemistry. The company has produced its first molecule, a key starting material for several medicines, at “commercially relevant” titers at pilot scale (300 L), showing chemical equivalence to material extracted from plants. In September 2020, Antheia co-founder and CEO Christina Smolke, PhD, described in Nature the first successful microbial biosynthesis of tropane alkaloids, used for treating neuromuscular disorders.

 

Beam Therapeutics

Beam Therapeutics is combining its base editing technology with Apellis Pharmaceuticals’ complement expertise to co-develop six research programs focused on C3 and other targets in the eye, liver, and brain. The collaboration, announced June 30, brings Beam $75 million in upfront cash and near-term milestones. Beam said in May it was on track to submit its first IND application for BEAM-101 (in development for sickle cell disease and beta thalassemia) and begin IND-enabling studies for BEAM-102 (sickle cell disease) and BEAM-201 (T-cell acute lymphoblastic leukemia), plus nominate its first development candidate from its portfolio of liver disease programs. Earlier this year, Beam acquired Guide Therapeutics for up to $440 million, integrating Guide’s in vivo lipid nanoparticle screening platform and library of lipids and lipid formulations.

 

Berkeley Lights

Berkeley Lights just missed being ranked among GEN’s top 5 public synbio companies after finishing 2020 with $64.303 million in revenue. The developer of a tech platform designed to enable rapid functional characterization of single cells at scale nearly tripled its cash and cash equivalents last year, to $233.408 million, a figure that dipped 1% in Q1, to $230.165 million. Much of that cash windfall reflected the $187.9 million in aggregate net proceeds that Berkeley Lights raised from an IPO launched in July 2020. Synthetic biology is one of Berkeley’s four markets (the others are antibody therapeutics, cell therapy, and gene therapy), accounting for nearly 11% ($1.984 million) of Berkeley Lights’ Q1 revenue and 12% ($8 million) of 2020 revenue.

 

Codex DNA

Codex DNA closed its IPO on June 22, generating approximately $122.7 million in aggregate gross proceeds through the sale of 7,666,664 shares of common stock at $16 per share, including the full exercise of the underwriters’ option to purchase up to 999,999 additional shares at the IPO price. The company’s products aim to enable researchers to rapidly, accurately, and reproducibly build or “write” high-quality synthetic DNA and mRNA that is ready to use in many downstream markets. Codex DNA markets the BioXp™ system, a fully automated benchtop end-to-end automated workstation designed to provide a turnkey, end-to-end solution for generating synthetic DNA and mRNA starting from DNA sequence. The company’s gene synthesis portfolio also includes BioXp™ biofoundry services, Gibson Assembly® reagents, and Vmax™ chemically competent cells.

 

Sana Biotechnology

Sana says it is building capabilities enabling high throughput cell engineering and gene editing and control, through technologies that include synthetic biology.  The preclinical-stage developer of in vivo and ex vivo cell engineering platforms—aimed at revolutionizing treatment across numerous therapeutic areas—has advertised recently for a principal scientist, synthetic biology. Sana’s cash, cash equivalents, and marketable securities more than doubled during Q1, to $981.9 million as of March 31, following an IPO in February that generated net proceeds of $626.4 million. Most recently on June 26, Sana presented data showing survival of transplanted stem cells without immunosuppression in non-human primates. The transplanted cells were induced pluripotent stem cells engineered with Sana’s hypoimmune gene modifications designed to enable immune evasion.

 

Synlogic

Synlogic saw its share price plunge 25%, to $1.81 in June 2020 after announcing the end of a collaboration launched in 2016 to develop Synthetic Biotic medicines with AbbVie to treat inflammatory bowel disease. Since then, Synlogic’s shares have more than doubled, to $4.01 on June 29, following more positive news about other Synthetic Biotic candidates. At the American Association for Cancer Research virtual annual meeting in April, Synlogic presented data on its solid tumors and lymphoma immunotherapy drug SYNB1891 from a Phase I trial (NCT04167137). A month earlier, Synlogic said another Synthetic Biotic, SYNB8802, achieved proof of concept mechanism in a Dietary Hyperoxaluria study where healthy volunteers on a high oxalate and low calcium diet were treated with multiple ascending doses of the drug.

 

Synthego

Synthego, which has raised “over $250 million” in total capital, says its position as a key accelerator of therapeutic development from early research through clinical trials was reinforced in May when it obtained ISO 9001:2015 certification based on an independent audit 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. As GEN reported in May, Synthego has ridden the single-cell analysis trend in CRISPR screening, applying machine learning and automation to handle the massive data output from these types of experiments. In April, Synthego launched Eclipse™, a new high-throughput cell engineering platform designed to accelerate drug discovery and validation by providing highly predictable CRISPR-engineered cells at scale through the integration of engineering, bioinformatics, and proprietary science.

 

Zymergen

Zymergen raised approximately $530 million in net proceeds in April—more than four times its $121.035 million in cash and cash equivalents as of March 31—through an IPO with full exercise by underwriters of their option to purchase additional shares. The IPO followed nearly $1 billion in past private financings by Zymergen, which sums up its innovative manufacturing approach as “biofacturing,” declaring: “We Make Tomorrow.” Zymergen’s approach integrates molecular biology, chemistry, materials science, lab automation systems, software applications, unique databases, and machine learning algorithms in order to launch products in about half the time and a tenth of the cost incurred by traditional chemical and materials companies. In May, Zymergen appointed Aindrea Campbell, formerly of Apple and Ford, to oversee global manufacturing and supply chain activities.