Ginkgo Bioworks, Backed by Bill Gates and Y Combinator, Files IPO Prospectus to Revolutionize DNA Programming Like Software

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In March 2015, the company raised $9 million in Series A financing; in July of the same year, it raised $45 million in Series B financing.

In June 2016, the Series C financing round raised $100 million;

In December 2017, the company raised $275 million in its Series D financing round. Following this round, its valuation exceeded $1 billion, placing it among the “unicorns.”

In September 2019, the company raised $290 million in its Series E financing, setting a current record for fundraising in the biotechnology sector. To date, the company has raised a total of $719 million.

Ginkgo Bioworks, a U.S.-based genetic programming company founded in 2009, completed five major funding rounds within four years, rapidly becoming an industry unicorn. As a technology enterprise focused on synthetic biology, what are its standout features that have consistently attracted investor interest? We may gain some insights by examining its development history.

In 2008, the U.S. financial crisis erupted. Tom Knight, a senior research scientist at the Massachusetts Institute of Technology’s Computer Science and Artificial Intelligence Laboratory (CSAIL), was grappling with a shortage of experimental funding. Meanwhile, four other co-founders—Jason Kelly, Reshma Shetty, Barry Canton, and Austin Che—were approaching their Ph.D. graduations and planning their future directions.

At this time, the American Society for Engineering Education established a benefit program for recent Ph.D. graduates: providing an annual salary of $70,000 and health insurance to students employed at engineering-related companies.

The five founders coincidentally secured this funding by establishing their company. Amid the economic crisis, which led to the closure of numerous businesses, Tom Knight and others acquired second-hand laboratory equipment at bargain prices, enabling them to set up a lab at minimal cost. Thus, Ginkgo Bioworks was founded.

It is worth noting that Tom Knight is one of the founders of synthetic biology and the iGEM (International Genetically Engineered Machine competition). Synthetic biology is an interdisciplinary field that builds upon the knowledge and materials acquired from traditional biology, employing engineering principles and computer science technologies to reengineer existing biological systems, enabling them to perform various tasks envisioned by researchers.

iGEM was born out of a small course on synthetic biology offered by Tom Knight in 2004.

Ginkgo Bioworks shares a deep-rooted connection with iGEM. All five founders not only participated in the iGEM competition but also served as advisors to the 2006 MIT iGEM team, providing guidance on the renowned “Eau d’e coli” project, which engineered E. coli to emit banana or wintergreen scents. This project laid the foundation for Ginkgo’s subsequent research in fragrance ingredients. Since its inception, Ginkgo has maintained its ties with iGEM, with approximately 10% of its employees having participated in the iGEM competition in various capacities.

Ginkgo Bioworks, headquartered in Boston, USA, employs engineering techniques to reprogram cells as an alternative to traditional manufacturing processes. By engineering yeast and bacteria, the company provides customized microorganisms for enterprises. Its business encompasses software and hardware tools that enable rapid prototyping and high-throughput screening, serving sectors such as food, industry, agriculture, and healthcare. Publicly disclosed products include chemical intermediates, flavorings and fragrances, as well as microorganisms that offer health benefits to the human gut microbiome and the root microbiota of agricultural crops.

In its early days, Ginkgo Bioworks was not viewed favorably by the capital markets. The company primarily secured funding through federal research grants and collaborated with various government agencies, including the National Science Foundation and the Defense Advanced Research Projects Agency (DARPA), on a range of projects.

2014 was a watershed year for Ginkgo Bioworks. After completing a $1.2 million seed funding round that year, the company closely followed up with five additional rounds of financing within the next five years. The Bill & Melinda Gates Foundation participated in its Series D round, and Y Combinator remained an investor throughout all stages.

2016 was a bumper year for Ginkgo Bioworks, with a significant increase in the number of partners.

On June 29, Ginkgo Bioworks and Amyris entered into a collaboration agreement to jointly advance the commercialization of up to 70 cultured ingredients.

In September, Ginkgo Bioworks announced a series of successes. On the 22nd, it partnered with Cargill to improve industrial fermentation processes; on the 23rd, it finalized a collaboration with Archer Daniels Midland Company (ADM) to design and produce microbes for cultured ingredients used in agricultural processing and the food ingredient industry; on the 29th, Genomatica also became a partner of Ginkgo Bioworks, focusing on scaling up and commercializing microbes and specialty chemical products produced by Ginkgo Bioworks.

On October 19, Ginkgo Bioworks announced a partnership with Prospect Bio to develop a novel biosensor aimed at accelerating the development of new strains (defined as pure cultures of the same microbial species from different sources) and reducing the cost of biological prototype development.

This biosensor will accelerate the process of organism screening (testing for desired traits). Organism screening is one of the slowest steps in Ginkgo Bioworks’ design-build-test system for biological development. Each microbe produced by Ginkgo Bioworks typically requires individual screening, whereas a single biosensor can screen many microbes simultaneously. Ginkgo Bioworks aims to reduce screening costs by 40-fold and increase the speed at which commercializable microbes are developed.

On January 20, 2017, Ginkgo Bioworks announced the acquisition of Gen9, a pioneer in DNA synthesis and assembly. Gen9’s proprietary DNA synthesis and assembly platforms further strengthened Ginkgo Bioworks’ capabilities in microbial engineering. These DNA sequence synthesis technologies are critical to Ginkgo Bioworks’ design of multi-gene enzymatic pathways.

On December 8, 2017, Ginkgo Bioworks and Synlogic, a company specializing in microbiome therapeutics, announced a collaboration. Synlogic will leverage Ginkgo Bioworks’ cell programming platform to construct and test thousands of microbial strains, accelerating the progression of early preclinical leads to develop and optimize clinical candidates.

Six days later, Ginkgo Bioworks completed a $275 million Series D financing round. Prior to this round, the company’s valuation had reached $725 million. Ginkgo Bioworks used these funds to establish Bioworks 3.

On March 20, 2018, Ginkgo Bioworks announced the establishment of a joint venture with Bayer’s Crop Science division, named Joyn Bio. Joyn Bio will focus on designing soil microbes to improve the root microbiomes of crops, particularly by providing nitrogen fixation to reduce reliance on synthetic fertilizers.

In May 2019, Ginkgo Bioworks announced the acquisition of Warp Drive Bio’s genome mining platform and entered into an antibiotic collaboration agreement with Roche, leveraging synthetic biology to discover novel small-molecule drugs produced by bacteria.

On October 1, 2019, a $150 million partnership was established with Berkeley Lights, integrating its optofluidic platform into an automated gene engineering foundry.

Ginkgo Bioworks has previously leveraged biotechnology primarily to produce fragrances and other ingredients for the perfume, pharmaceutical, and food industries. By employing rigorous engineering principles in the design of genetic modifications and conducting highly systematic, large-scale design-build-test-learn cycles, the company develops microbes capable of producing target products that meet customer demands. It has now expanded into the fields of nutritional products and consumer health goods.

The research scope includes treating antibiotic-resistant bacteria, utilizing microbes to convert carbon dioxide into fuel, endowing yeast with a rose-like fragrance, and synthesizing scents through genetically engineered or even customized microorganisms.

To better learn and design microbes, Ginkgo Bioworks has established a genetic engineering foundry.

The foundry boasts integrated software and automation tools that significantly enhance production efficiency, with software serving as the driving force behind its operations. Ginkgo Bioworks is making microbes easier to engineer, paving the way for DNA to be programmed like software in the future. Software engineers build systems for microbial engineers that can generate, process, and store vast amounts of data, thereby enabling the automated encoding of DNA structures.

Ginkgo Bioworks’ capabilities in enzyme discovery, pathway assembly, and high-throughput analysis enable engineers to construct complex metabolic pathways in microorganisms. These pathways are designed to produce culture components, degrade materials, and enhance strain performance.

Let’s illustrate this with a specific case. A leading company in the field of industrial fermentation sought to significantly reduce its reliance on expensive raw materials. Ginkgo Bioworks was tasked with engineering complex metabolic pathways and fine-tuning them into microbial strains capable of utilizing lower-cost substrates. The project required the synthesis, screening, and optimization of an enzyme library comprising 1,000 members, as well as the assembly of flux-balanced pathways to redirect carbon equivalents toward specific products.

Overall, Ginkgo Bioworks leveraged its capabilities in DNA synthesis and high-throughput screening to synthesize 109 million DNA base pairs, screen 7,117 enzymes across 12 enzyme classes, evaluate 2,719 pathways, and conduct a total of 30,445 strain tests. It then identified the genes encoding the most active enzymes, combined them with a validated library of regulatory elements, and assembled the metabolic pathway using Ginkgo Bioworks’ platform. As a result of this comprehensive workflow, the resulting strain exhibited nearly 25-fold greater uptake capacity compared to the original strain.

BioWorks 1 is the world’s first fully automated foundry for microbial strain engineering. This foundry can execute up to 15,000 automated laboratory tasks per month, enabling Ginkgo Bioworks’ microbial engineers to test thousands of new organisms monthly without performing most repetitive laboratory work. BioWorks 2 is an upgraded version of BioWorks 1, featuring 25,000 square meters of automated space—twice the size of the original. Through more efficient equipment integration and miniaturization, it increases the productivity of the original BioWorks 1 foundry by sixfold.

From the bacterial production of insulin in 1980 to today’s CAR-T cells, engineered living cells have fundamentally transformed the pharmaceutical industry. Ginkgo Bioworks seeks to harness the power of DNA programming to revolutionize all industries, enhancing operational efficiency and technological adaptability.

On December 8, 2017, Synlogic entered into a partnership with Ginkgo Bioworks, leveraging the latter’s cell programming platform to construct and test thousands of microbial strains. This collaboration aimed to accelerate the progression of early preclinical leads, thereby facilitating the development and optimization of clinical candidates.

Synlogic leverages its proprietary drug development platform to create novel live biotherapeutic products, employing the tools and principles of synthetic biology to genetically engineer beneficial microbes to perform or deliver key functions that are lost or impaired due to disease. These synthetic biologic drugs are designed to exert local effects while providing systemic efficacy to address patients’ diseases.

Synlogic has developed an early-stage prototype strain for the treatment of rare metabolic disorders. While this strain holds considerable market potential, there is still room for improvement. At the Ginkgo Bioworks Foundry, engineers prototyped and individually screened more than 1,000 variants of three enzymes within the designed pathway. Leveraging its large-scale foundry capabilities, Ginkgo Bioworks helped Synlogic’s scientists select the optimal strain with significantly enhanced functionality both in vitro and in vivo.

Ginkgo Bioworks Announces $80 Million Equity Investment to Leverage Combined Strengths in Drug Design and Development with Synlogic, Expanding Collaboration and Enriching Synlogic’s Pipeline to Drive New Innovations in Live Biotherapeutics

Ginkgo Bioworks has successfully deployed its platform to serve a variety of internal and external projects, including pharmaceuticals, therapeutics, agriculture, Motif, and Cronos.

Ginkgo Bioworks primarily provides companies with customized microorganisms, achieving this by engineering yeast and bacteria. In recent years, the plummeting cost of DNA synthesis, efficiency gains from automated high-throughput equipment, and the integration of biotechnology with computer technology have ushered in unprecedented development opportunities for downstream applications of synthetic biology. The emergence of industry unicorns such as Ginkgo Bioworks has also encouraged greater participation.

Cathay Biotech is a well-established enterprise founded in 1997, specializing in the technological development and practical application of industrial-scale biomanufacturing. Its projects that have achieved large-scale industrialization include long-chain dicarboxylic acids, bio-based pentamethylenediamine, and bio-based polyamides. Cathay Biotech’s long-chain dicarboxylic acid production base in Shandong Province commenced industrial production in 2003 and currently has an annual capacity of 40,000 metric tons. As the world’s largest supplier of this product, it holds over 80% of the global market share. The success of this project represents a notable commercial case worldwide where bio-based processes have replaced petrochemical methods.

In recent years, Cathay Biotech has developed bio-based pentamethylenediamine and utilized it to produce a series of high-performance bio-based polyamides, successfully completing industrial-scale pilot operations in 2014. Cathay’s bio-based polyamides are derived from renewable biomass feedstocks. This represents a new class of “bio-manufactured” materials introduced many years after the invention of traditionally chemically synthesized nylon 66 and nylon 6. Having been trialed and endorsed by users both domestically and internationally, these materials are widely applicable in the textile and engineering plastics sectors.

Bluepha is a startup focused on applying synthetic biology technologies to molecular and material innovation. On November 15, 2019, Bluepha, founded in 2016, completed a RMB 40 million Series A financing round. The funds will be used to industrialize its existing product pipeline, advance collaborative R&D pipelines with multiple Fortune 500 corporate clients, and further develop its genetic component technology platform.

On October 28, 2019, Bluepha signed a strategic cooperation agreement with Sinochem International, a chemical giant under China’s central state-owned enterprises, at Tsinghua University. The two parties will join hands to promote the industrialization of Bluepha’s existing product pipeline—bio-based biodegradable material PHA (polyhydroxyalkanoates).

PHA is a novel, fully biodegradable thermoplastic material that can be applied in packaging materials, medical implants, and the food and chemical industries. Its production principle involves utilizing microorganisms to convert biomass feedstocks into biopolymers. PHA exhibits properties similar to those of conventional petroleum-based plastics but can completely degrade after use.

Notably, Dr. Li Teng and Dr. Zhang Haoqian, the two co-founders of Bluepha, were among the earliest young scholars in China to engage in synthetic biology research and have won numerous awards at the International Genetically Engineered Machine Competition (iGEM), the premier international competition in the field of synthetic biology.

Yikolai Biotech was established in 2015, dedicated to achieving the industrialization of chemicals through enzyme technology. Yikolai Biotech performs directed evolution of enzymes to catalyze reactions and mass-produce final products.

In the pharmaceutical sector, Yikelai Biotech successfully screened a transaminase mutant and developed a novel synthetic route for sitagliptin—the first globally to successfully circumvent Merck’s patent. Additionally, based on the successful screening of a dehydrogenase mutant, the company devised an entirely new process for producing R-3-aminobutanol (an intermediate for dolutegravir). Dolutegravir is currently one of the most prominent antiretroviral drugs for HIV/AIDS and has been included in the procurement lists of charitable organizations such as the World Health Organization (WHO) and the Bill & Melinda Gates Foundation.

According to Crunchbase data, total financing in the synthetic biology sector reached $3.8 billion in 2018. In the first half of 2019, 65 synthetic biology companies raised a combined $1.9 billion. Synthetic biology has clearly become a hotbed for investment capital. Will latecomers make strong moves to claim a share? How will the synthetic biology market be divided in 2020? All eyes are watching.