Investigational Synthetic Biotic Medicine for Homocystinuria with Synlogic

Homocystinuria (HCU) is an inherited disorder that affects tens of thousands of people every day. HCU occurs when a person is unable to metabolize the amino acid methionine, a precursor to homocysteine; the result is an excessive accumulation of homocysteine and its metabolites in a person’s blood and urine. Patients develop multiple symptoms, including bone defects, intellectual disabilities, and life-threatening blood vessel obstructions. Many patients are required to comply with rigid, restrictive diets and have few treatment options available.

What if we could tell bacteria inside these patients to metabolize methionine, lowering homocysteine levels and reducing the effects of diseases like HCU?

SYNB1353, an engineered strain of the probiotic bacteria E. coli Nissle (EcN), was designed and is being developed through a collaboration between Synlogic and Ginkgo to do exactly that. This novel strain has the ability to consume methionine in the human gut, helping to avoid excessive accumulation and conversion to homocysteine in plasma. High-throughput testing of codebase libraries by Ginkgo enabled SYNB1353 to advance from preclinical proof-of-concept to candidate strain in the space of a year.

“SYNB1353 is an exciting addition to the Synlogic pipeline aimed at helping patients living with diseases of methionine metabolism. Starting with HCU, we see these diseases as the natural next step in our metabolic portfolio after the successful proof of concept of synthetic biotics in phenylketonuria announced earlier this year. This program builds on what we have learned from our metabolic program work to date, with the potential to provide a new therapeutic option to reduce the devastating consequences of these diseases.” said Dr. David Hava, chief scientific officer at Synlogic. “The advancement of SYNB1353 illustrates both the potential of our Synthetic Biotic platform to generate new therapeutic candidates and the value of our collaboration with Ginkgo.”

SYNB1353 is the first product developed through a research collaboration between Synlogic and Ginkgo and the first investigational medicine developed on Ginkgo’s platform to enter IND-enabling studies.

Synlogic expects to file an investigational new drug (IND) application with the U.S. Food and Drug Administration (FDA) for SYNB1353 and begin clinical development in 2022. Researchers from Synlogic and Ginkgo will present preclinical data supporting advancement of SYNB1353 into IND-enabling studies at the International Congress of Inborn Errors of Metabolism 2021. The poster, Development of an Investigational Methionine-consuming Synthetic Biotic Medicine (SYNB1353) for the Treatment of Homocystinuria, will be available at the International Congress of Inborn Errors of Metabolism 2021 on November 21-23, 2021 in Sydney, Australia.

We’re so honored to be able to support Synlogic in building their incredible platform to provide potential new treatment options for people living with difficult to treat diseases. This is just the beginning for a new generation of medicines unlocked by the power of synthetic biology, and we’re excited to be working with Synlogic on multiple additional preclinical programs in their portfolio.

Read the full press release here.

Advancing Treatments for Orphan and Rare Diseases with Selecta Biosciences

Rare and orphan diseases affect hundreds of thousands of Americans, and many treatments cause unwanted immune responses.

What if you could mitigate unwanted immune responses and amplify the efficacy of therapies?

This is exactly what Selecta Biosciences aims to do in collaboration with Ginkgo. Together, we plan to design novel and improved enzymes with transformative and therapeutic potential to advance treatments for select orphan and rare diseases. This partnership leverages the unique platforms of both companies: Selecta’s clinically-validated ImmTOR™ platform, which is developing tolerogenic therapies, and Ginkgo’s horizontal platform for cell programming.

Under the terms of the collaboration, Ginkgo is eligible to earn upfront research and development fees and milestones, including certain milestone payments in the form of Selecta common stock, clinical and commercial milestone payments of up to $85M in cash, as well as further downstream value in the form of royalties on sales.

“We are excited to partner with Ginkgo and expect that our ImmTOR technology, in combination with Ginkgo’s high throughput enzyme discovery, design, and screening capabilities will bring us one step closer to improving the sustained efficacy of novel biologic therapeutics,” said Carsten Brunn, PhD, CEO at Selecta Biosciences. “Further, this collaboration builds on extensive preclinical as well as strong clinical data from Selecta’s Phase 2 COMPARE trial for the treatment of chronic refractory gout that further supports ImmTOR’s potential for sustained therapeutic benefit when combined with immunogenic enzymatic therapies. We look forward to expanding our pipeline and ultimately delivering on our shared mission to improve the lives of patients in need.”

Ginkgo works with a growing list of industry leaders that are addressing outstanding medical challenges with diverse therapeutic modalities, and we are thrilled to partner with Selecta in an effort to discover, engineer, and develop next generation therapeutic enzymes. We’re excited to support Selecta in its mission to improve the quality of life for patients with unmet medical needs by expediting and maximizing Selecta’s capabilities.

Read the full press release here.

Developing High-Efficacy Adjuvants for Vaccines with SaponiQx

Adjuvants—substances known to enhance our immune response—are a key component of many existing vaccines. And while vaccines are one of the most powerful tools we have to fight pandemics, ensuring widespread access to efficacious vaccines continues to be a major challenge around the world.

SaponiQx, a new subsidiary announced today by Agenus, plans to use Ginkgo’s platform to drive innovation in novel adjuvant discovery and vaccine design.

Their efforts will focus on building an innovative adjuvant platform to deliver both sustainable manufacturing approaches and a secure supply of known adjuvants, as well as discover novel adjuvants and develop new, more effective vaccines utilizing optimized antigen-adjuvant pairings.

Ginkgo’s experience in metabolic engineering, enzymatic diversification, and process optimization can be applied to discover novel adjuvants and improve current manufacturing processes that can then be applied toward developing better-integrated vaccines. We’re proud that our platform is being used by companies across the vaccine supply chain to develop and manufacture the materials necessary for life-saving vaccines.

Garo Armen, CEO and Chairman of Agenus and Executive Chairman of SaponiQx, had this to say: “Agenus is pleased for SaponiQx to collaborate with Ginkgo Bioworks to develop its novel saponin products from sustainably sourced raw materials, with a goal to meet the current demands placed on the vaccine industry for pandemic vaccines. The QS21 Stimulon™ adjuvant has shown long term efficacy and long-term protection in both commercially launched and experimental vaccines.”

New Platform Ventures: Launching Verb Biotics, Ayana Bio

Today we’re announcing the launch of two new companies via the Ferment Consortium: Verb Biotics and Ayana Bio.

Verb—a probiotics innovation company—will focus on identifying and designing new strains of probiotic bacteria with advanced properties for human nutrition, health, and wellness. Ayana plans to support human health and wellness by harnessing bioactive compounds for use as complementary medicine.

Verb Biotics
The probiotics category is a $50B global industry that’s growing rapidly. As awareness and understanding of the human microbiome—the trillions of bacteria that live in and on your body—has grown over the past decade, there’s been tremendous interest in probiotic-enhanced foods, beverages, and supplements. Many existing probiotic products use strains of bacteria common to yogurt and other fermented products, but these strains have a number of challenges including limited shelf life, poor stability, and restrictive metabolic profiles.

Since Ginkgo has significant expertise in the discovery and design of microbes with a wide array of functions, Verb plans to leverage our high-throughput platform to perform sequencing, proteomics and metabolomics analysis, pathway design, cell culturing, and fermentation work in order to improve the design and development of probiotics.

Verb is launching with $30 million in Series A funding provided by Viking Global Investors and Cascade Investment.

Ayana Bio
To address issues ranging from supporting a healthy immune system, to aiding metabolism, to promoting healthy aging, consumers are looking for health products that are complementary to conventional medicine. Two categories of products that offer complementary health products—nutraceuticals and traditional medicines—represent over $400 billion.

The bioactive ingredients that go into products in these categories come from a range of natural sources such as medicinal plants and fungi. However, unsustainable harvesting, variability in the source organisms, and the methods of preparation all contribute to uncertainty around these important molecules and limit the potential for widespread use.

Ayana plans to collaborate with global industry leaders in consumer packaged goods, supplements, specialized nutrition, over-the-counter medicines, and traditional medicines to bring to market standardized bioactives that provide consumers with confidence in quality and reliability. Our cell programming platform will support Ayana’s mission to bring to market high purity, clean and reliable medicinal bioactives in convenient forms.

Ayana is launching with $30 million in Series A funding provided by Viking Global Investors and Cascade Investment.

Ferment Consortium
The Ferment Consortium is a company creation studio that works with Viking Global Investors and Cascade Investment to help incubate, fund, and launch new companies that use cell programming to support human and environmental health and wellbeing. (Psst! If you have a great idea of how to grow the future, Ferment Co would love to hear from you.)

Verb and Ayana join our other Platform Ventures: Joyn Bio, Allonnia, and Motif FoodWorks, which recently raised a $226 million Series B round led by Ontario Teachers Pension Plan and BlackRock.

Accelerating Production of Essential Medicines with Antheia

Partnership enables Antheia to broaden its pipeline of critical active pharmaceutical ingredients and key starting materials

Nearly half of all medicines today are sourced from nature, and many of the most widely used essential medicines are sourced directly from medicinal plants. The World Health Organization classifies “essential medicines” as medicines “that satisfy the priority healthcare needs of the population.”

But the supply chains for some of our most critical plant-based medicines are quite fragile. The specialty plants that are currently used to produce these medicines can require years to grow and harvest, and uncontrollable factors — such as weather — affect availability and reliability of supply. Transporting and processing adds more cost, complexity, and risk. In short, our reliance on specialty plants comes with many supply chain risks. When there’s extreme demand or a constrained supply, many plant-based medicines, including widely used analgesics and sedatives, can quickly become in short supply. We recently saw this occur during the COVID-19 pandemic. Furthermore, extracting medicines from specialty plants can be very expensive; the high cost of production means many developing countries cannot afford some of these essential medicines.

Synthetic biology platforms, such as those created by Antheia and Ginkgo, make it possible for critical medicines to be produced on-demand in a much more efficient and environmentally friendly process. Additionally, when it comes to plant-based pharmaceuticals, biomanufacturing has significant advantages in supply chain resiliency and agility, cost, quality control, sustainability, and efficiency compared to conventional crop farming and processing. Synthetic biology gives us an additional way to grow these essential medicines.

Antheia, who is enabling next-generation plant-inspired medicines, and Ginkgo, with our leading horizontal platform for cell programming, are announcing today a new cell programming partnership to accelerate the development and production of essential medicines using synthetic biology. Antheia plans to leverage our industry-agnostic platform — specifically, our high-throughput enzyme design and high-throughput screening capabilities — to broaden their pipeline of critical active pharmaceutical ingredients (APIs) and key starting materials (KSMs).

Antheia will leverage Ginkgo’s industry-agnostic platform — specifically, our high-throughput enzyme design and high-throughput screening capabilities.

Kristy Hawkins, CSO and co-founder at Antheia had this to share about the news: “We’re committed to using synthetic biology to enable more equitable access to essential medicines. By partnering with Ginkgo, a global leader in organism engineering, we are greatly increasing our ability to develop essential medicines at the speed and scale necessary to drive change in global pharma supply chains.”

Antheia’s focus is on plant-inspired pharmaceuticals that are too complex to be produced through scaled synthetic chemistry processes. They’ve managed to efficiently produce highly-complex pharmaceuticals by pioneering whole-cell engineering, a technique that reconstructs multiple steps of a biosynthetic pathway of unprecedented complexity in yeast cells. This partnership with Ginkgo enables Antheia to tap into a set of complementary capabilities and resources at Ginkgo to create synergies that allows Antheia to achieve more with its own technology platform. Through our partnership, Antheia plans to leverage Ginkgo’s extensive and rapid cell programming platform and biological codebase to greatly expand and accelerate its strain and enzyme engineering work.

Both organizations are committed to using biology to build a better future, and we look forward to a long lasting partnership and positive impact in the world. We believe Antheia is at the cutting edge of using synthetic biology to produce entire classes of medicines that were previously inaccessible; we’re thrilled that Ginkgo’s platform can support innovators like Antheia and create next generation manufacturing technologies for essential medicines.

Improving Living Medicines with Synlogic

At Ginkgo, we believe that the power to program DNA will transform all industries, making technology more adaptive, efficient, and renewable. Engineering living cells has of course already revolutionized the pharma industry, from insulin-producing bacteria in the 1980s all the way to CAR-T cells today.

A few weeks ago we announced our acquisition of the Warp Drive genome mining platform and a partnership with Roche, using synthetic biology to discover novel small molecule medicines made by bacteria. Today I’m thrilled to announce an expansion of our partnership with Synlogic, who is ushering in a new paradigm for therapeutics, where the bacteria aren’t just making the medicine, they are the medicine.

Synlogic is developing an incredible platform that enables them to program probiotic bacteria to treat many different complex diseases using the power of biology. Living cells have the ability to do what chemicals can’t: they can sense and respond, they can deliver enzymes and small molecules directly where they’re needed, and they can consume and break down potentially toxic molecules before they cause any harmful effects. Today, Synlogic’s pipeline includes strains of E. coli that live in the gut and consume molecules like phenylalanine or ammonia in diseases where patients’ bodies are unable to do this on their own, leading to toxicity and neurological damage if left untreated. They also are working on engineered bacteria that can be injected directly into tumors, sending up signal flares that alert the immune system to attack the cancer cells.

As organism designers, we’re so excited by Synlogic’s vision and we’ve been so inspired by the talent and passion of the team and their ability to program cells to fight so many different diseases. Their expertise is a perfect complement to the work we do programming cells in our foundries and we’ve been collaborating successfully with Synlogic since late 2017. We’ve been thrilled by the promising early results for our first collaborative project that shows how our two companies can work together to accelerate the development of a new living medicine.

Synlogic had developed an early prototype strain for the treatment of a rare metabolic disease that was promising but had room for improvement. In our foundry, we prototyped and screened over 1000 versions of each of the three enzymes in the designed pathway, zeroing in on the sequences with the highest activity in combination. Because of the scale of our foundries to build and test so many strains, we could help Synlogic’s scientists choose the best strains with significantly improved function both in vitro and in vivo. We’ll be sharing all those details and the results from nonhuman primate studies at the SEED conference in a couple weeks.

Based off of the success of our proof of concept partnership and the enormous potential that Synlogic has in therapeutics, today we are excited to announce an expansion of our collaboration to drive new innovation in living medicines through the combined strength of Synlogic’s expertise in drug design and development and Ginkgo’s foundries for biological engineering. We are making a premium equity investment of $80M and beginning a range of new projects, expanding Synlogic’s pipeline and helping accelerate more promising candidates to the clinic.

We see living medicines as the source of many future drugs. Recombinant DNA technology first made it possible to manufacture protein-based drugs nearly forty years ago, and today a large percentage of promising new drugs are biologics. We can only imagine what might be possible in the age of living programmable medicines.

As with many of our partnerships, we’ve also worked with artist Karen Ingram to illustrate the technology and highlight the beauty of living medicines. As you take a closer look, you’ll notice several of important elements that describe the work of Synlogic and Ginkgo’s collaboration: bacteria sensing and targeting various compounds, biofilm formation, and the gut lining in the background.