Category: Therapeutics & Vaccines

Developing Circular RNA-based Therapeutics with Esperovax

Posted on by Narendra Maheshri

Initial focus of partnership will aim to develop cancer therapeutics

Today, we announced a partnership with Esperovax, an innovative developer of oral mRNA biologics, to develop circular RNAs (circRNAs) for a variety of therapeutic applications. Initially, Ginkgo and Esperovax will work to develop circRNAs harboring payloads to specifically target colorectal cancer by inducing cell death only in cancerous cells.

CircRNAs represent an emerging, powerful mechanism for delivering therapeutics and vaccines due to their protein-coding potential and improved stability in comparison to their linear mRNA counterparts.

This partnership aims to further exploit circRNAs by developing a novel mechanism to facilitate RNA circularization specifically in colorectal cancer cells. This would result in extended expression of the toxic payload solely in cancer cells, reducing toxicity and resulting side effects from the death of normal cells. By combining omics datasets, computational approaches, and high-throughput screening capabilities, Ginkgo will design, build and screen large numbers of RNA designs that leverage and optimize Esperovax’s novel mechanism of cell-type specific circularization.

Through our growing portfolio of programs in cell and gene therapy and RNA therapeutics, and recent acquisition of Circularis, Ginkgo is uniquely positioned to enable new solutions in these areas with circRNA.

“Given therapeutic developments in recent years, the idea of inducing a suicide gene therapy system in a tissue-specific manner has gained traction,” said Randy Wayne Schekman, a Nobel Prize recipient in Physiology or Medicine and Advisor at Esperovax. “As we aim to build off that traction with the ultimate goal of improving cancer patient outcomes, Ginkgo’s momentum and achievements in the therapeutics space made the company an essential and trusted team to partner with, giving us the confidence that we can eventually make this goal a reality.”

We’re thrilled to use our platform to further develop and optimize Esperovax’s novel mechanism for circularization and enable advancements in the therapeutics space – a core area of our work together.

Find the full press release here along with all of the latest news from the Ginkgo team.

What will you grow with Ginkgo?

High Throughput Screening for Designing Novel CAR-T Cell Therapies

Posted on by Shawdee Eshghi

Pooled screening platform for discovering the next generation of CARs

Image of a poster containing CAR-T data

Ginkgo is proud to present a poster this Friday, November 11 at the 37th Annual Meeting of the Society for Immunotherapy of Cancer (SITC). The poster highlights our Foundry-enabled methods for large-scale, combinatorial library design and screening of chimeric antigen receptor (CAR) domains for improved persistence. The ability to screen hundreds of thousands of CAR designs in primary human T cells can enable discovery of variants with desired characteristics. This capability has the potential to discover CAR-T therapies that are effective against solid tumors.

CAR-T cell therapies show tremendous promise for the treatment of cancer. But so far, their use has been limited to targeting blood cancers, as CAR-T has failed to show consistent efficacy in treating solid tumors, which represent approximately 90% of adult human cancers. Part of the challenge when applying CAR-T therapies to solid tumors lies in T cell exhaustion, a state of dysfunction arising from excessive antigen stimulation in the immunosuppressive environment of a solid tumor.

Therapeutic outcomes of CAR-T cell therapies—including CAR-T persistence—correspond to T cell behaviors driven by signaling cascades that are triggered by the intracellular domains (ICD) of CARs. Until now, technical constraints in high throughput screening have made the systematic design and testing of novel ICD combinations that drive more favorable T cell phenotypes onerous. New data we are presenting at SITC will demonstrate that our high throughput screening method enables massively parallel testing of CAR designs and has led to the discovery of new ICD combinations that outperform the canonical CD28-CD3z and 4-1BB-CD3z combinations.

Discovering next generation CAR-T cell therapies

Our platform for cell programming enables synthesis and screening of diverse libraries of genetic constructs to explore biological space. Applying these capabilities to the design of CARs enables screening of hundreds of thousands of possible combinatorial variants of different CAR ICDs. The data we will present at SITC will show how this method could be used to screen for variants with increased persistence in a serial tumor rechallenge assay. As an enabling platform company, we can leverage our full stack of mammalian cell engineering expertise and capabilities to enable the high throughput screening of CAR-T cells to discover and optimize next generation therapeutic candidates for our partners.

While innovation in CAR-T cell therapies continues to grow at a dramatic pace, CAR-T is still a relatively new modality whose potential is just beginning to be fully explored. With large scale screening and automation, we have created a tool we believe can dramatically expand the variety and functionality of CAR domains so that our partners can build therapies targeted for particular tumor environments.

“We’ve only seen a small sliver of what revolutionary modalities like CAR-T can achieve in terms of patient outcomes. Being able to explore broader design space for this powerful technology can help unlock new potential in solid tumor treatment, inflammatory and autoimmune diseases, and beyond.” said Arie Belldegrun, Executive Chairman and Co-Founder of Allogene Therapeutics and Kite Therapeutics and member of the Board of Directors for Ginkgo Bioworks. “The scale of Ginkgo’s platform helps to enable discovery and innovation in this important arena.”

You can view our poster at SITC. To register, visit www.sitcancer.org/2022.

Presentation details:

Date & Time: Friday, November 11, 2022 at 9 am – 8:30 pm, EST
Title: Pooled screening platform for discovering the next generation Chimeric Antigen Receptors
Presenting Author: Taeyoon Kyung, PhD, Senior Mammalian Engineer, Ginkgo Bioworks
Poster Number: 242

Click here to speak with our team and learn more about leveraging our platform.

Find the full press release here along with all of the latest news from the Ginkgo team.

What will you grow with Ginkgo?

Optimizing Crucial Drug Manufacturing of APIs with Merck

Posted on by Cindy Chang

Ginkgo to engineer key biocatalytic enzymes for potential use in Merck’s drug manufacturing processes

Today, Ginkgo is proud to announce a collaboration with Merck to optimize the manufacture of active pharmaceutical ingredients. The aim is to engineer up to four enzymes for use as biocatalysts in Merck’s active pharmaceutical ingredient (API) manufacturing efforts. Through this collaboration, we will leverage our extensive experience in cell engineering and enzyme design, along with our capabilities in automated high throughput screening, manufacturing process development/optimization, bioinformatics and analytics to deliver optimal strains for expression of targeted biocatalysts.

Biocatalysis is a sustainable and effective alternative to some steps in industrial chemical synthesis

Enzyme biocatalysts can reduce costly synthesis and purification steps, thereby decreasing production costs. Through this collaboration, we aim to optimize several biocatalysts by leveraging our world-class proprietary fungal strains, cell line development, enzyme engineering and optimization, and multiomics expertise.

“Ginkgo’s fungal strains present a major opportunity for improving biocatalysis. E. coli is currently the mainstay host for expressing enzymes, but a large number of enzymes will not express properly in E. coli, and those that do express in E. coli may have better homologs that only express in fungal strains,” said Behzad Mahdavi, our Senior Vice President of Biopharma Manufacturing and Life Sciences Tools. “This enzyme optimization project with Merck has the potential to help reduce the cost of goods and enable a more robust supply chain for APIs.”

Merck is a pioneer in biocatalysis, improving manufacturing of crucial medicines. We’re thrilled to be partnering with Merck and to be leveraging our platform capabilities for improved enzyme activity and production. Ginkgo’s platform model enables us to identify improved enzymes and develop powerful fungal strains and fermentation processes for enzyme manufacturing, empowering downstream API production for our customers.

Under the terms of the collaboration, Ginkgo will earn an upfront research and development fee and is eligible for success-based research and development milestone payments. In addition, Ginkgo is eligible to earn commercial milestone payments for each of a specified number of biocatalysis targets, which have the potential to total, in the aggregate, up to $144 million. To learn more about Ginkgo’s work in enzyme discovery, visit this webpage and talk to our team today.

Find the full press release here along with all of the latest news from the Ginkgo team.

What will you grow with Ginkgo?

Developing Synthetic Biotics for Gout with Synlogic

Posted on by Patrick Boyle

Ginkgo and Synlogic announce the second drug candidate—a treatment for gout—in their partnership to develop synthetic biotics

Last November, we announced that SYNB1353, an engineered strain of the probiotic bacteria E. coli Nissle (EcN) designed and developed through a collaboration between Ginkgo and Synlogic, was to be nominated for investigational new drug (IND) status with the U.S. Food and Drug Administration (FDA). This would mark the first medicine developed on Ginkgo’s platform to enter IND-enabling studies but just the beginning of our work with Synlogic to create living medicines.

Today, we’re pleased to share Synlogic’s announcement of SYNB2081, a new drug candidate developed in partnership between our two companies for the treatment of gout.

Addressing unmet needs for patient care

Gout is a complex form of inflammatory arthritis that occurs when excess uric acid in the body forms crystals in the joints. Patients experience a range of symptoms, including intense joint pain, inflammation and redness, and limited range of motion in the affected joints. Unfortunately, current treatment options present limitations in both safety and efficacy, highlighting a need for new approaches.Gout is also a recognized risk factor in chronic kidney disease (CKD).

SYNB2081 is a synthetic biotic designed to lower uric acid for the treatment of gout. We’re honored to work with the Synlogic team in this pioneering next step to potentially help patients living with gout. As we’ve seen the Synlogic pipeline develop the past year, we’re eager to continue supporting Synlogic in generating additional therapeutic candidates.

SYNB2081 is named after one of the largest and best-preserved Tyrannosaurus rex specimens in the world. Nicknamed “Sue,” the specimen is housed at the Field Museum in Chicago and is officially named FMNH PR 2081. Data from “Sue” suggests that dinosaurs like the Tyrannosaurus rex suffered from gout much in the same way as other reptiles and birds do.

What if we could program microbes to act as medicine?

“With our second drug candidate into clinical development, this not only demonstrates the value of combining Ginkgo’s Codebase with our Synthetic Biotic platform, but also highlights the potential to develop Synthetic Biotics across a range of diseases, giving us the potential to provide meaningful new treatment options to patients in need,” said Dr. David Hava, Chief Scientific Officer, Synlogic.

The advancement of SYNB2081 and SYNB1353 are clear indicators of the transformative platform Synlogic has created to power new medicines through synthetic biology.

Find the full press release here along with all of the latest news from the Ginkgo team.

What will you grow with Ginkgo?

Unlocking the Potential of Expression Systems for Medicines with Novo Nordisk

Posted on by Jason Kelly

 

Novo Nordisk will leverage Ginkgo’s Foundry and Codebase to create novel expression hosts for its pharmaceutical products.

Hundreds of millions of people currently live with diabetes, obesity, and other serious chronic diseases, putting a strain on individuals, families, and healthcare systems. More effective medicines could improve treatment options for these people. — Today, we announced that Novo Nordisk, a leading global healthcare company, will leverage Ginkgo’s cell programming platform to unlock the potential of expression systems, which may accelerate and enhance the discovery and development of their biological medicines for chronic diseases.

What if you could grow medicines?

It’s an honor to work with partners like Novo Nordisk that not only have an incredible range of critically important products, but that also provide us with the opportunity to do meaningful work that could help so many patients. At Ginkgo, we are always on the lookout for projects that will have an outsized impact on people’s lives and well-being. We’re excited to be working with Novo Nordisk in our efforts to use biology to create better medicines for patients with chronic diseases.

The work aims to expand and improve the treatment options available for the millions of people with chronic diseases.

“Novo Nordisk is constantly pushing the boundaries for innovative tools to bring new treatments to people living with diabetes and other serious chronic diseases,” said Brian Vandahl, Senior Vice President, Global Research Technologies, Novo Nordisk. “Using synthetic biology and the reprogramming of expression system genomes, we have the potential to engineer biological systems that will expand the chemical space of biological medicines.”

Under the terms of the partnership, Ginkgo and Novo Nordisk will launch a multi-year collaboration. Ginkgo will receive an upfront R&D fee and is eligible to receive milestone payments as the parties advance in the collaboration.

Find the full press release here along with all of the latest news from the Ginkgo team.

What will you grow with Ginkgo?

Discovering Novel Live Biotherapeutics with Microba

Posted on by Jen Wipf

What if you could use bacteria as therapeutics?

Microba Life Sciences, a precision microbiome science company, and Ginkgo announced a partnership to identify single-strain, live bacteria product (LBP) candidates against autoimmune diseases. The collaboration aims to build on Microba’s precision approach to LBP development with an in-depth evaluation of the company’s strains using Ginkgo’s high throughput, automated screening capabilities.

Microba will leverage Ginkgo’s high throughput screening capabilities to identify potential therapeutic candidates for autoimmune diseases.

The human gut microbiome is composed of trillions of bacteria that have an outsized influence on human health and disease. In recent years, scientists have developed a deeper understanding of the relationship between specific bacteria residing in the gut and various health outcomes, leading to a growing interest in using bacteria for therapeutic applications. Clinical trials using live biotherapeutics – biological products that contain live microorganisms applicable to the prevention, treatment, or cure of a disease – have delivered promising results.

There is growing consensus that live biotherapeutics may represent a major class of therapeutics in the coming years.

“We believe the human microbiome currently represents a missing piece in the treatment of major chronic diseases, and as a result a number of microbiome-based therapeutics are progressing through clinical development globally” said Luke Reid, CEO at Microba. “Ginkgo’s high throughput screening automation combined with our novel data-driven approach to therapeutic discovery from the microbiome can potentially accelerate development of breakthrough new drugs for autoimmune diseases.”

Leveraging Ginkgo’s platform to discover, develop, and optimize live biotherapeutics

Through this partnership, Ginkgo will provide high-throughput screening for Microba’s proprietary library of human microbiome-isolated strains, with the goal of improving treatment for autoimmune diseases such as lupus, psoriatic arthritis, and certain autoimmune liver diseases. Microba plans to leverage Ginkgo’s high-throughput anaerobic culturing, multi-omics data collection and analysis, functional bioassay screening, and media and fermentation optimization capabilities to generate data sets that may help characterize potential therapeutic and non-therapeutic uses of the strains. The initial partnership combining Microba’s biobank and Ginkgo’s anaerobic development capabilities is expected to run approximately two years.

Microba is doing truly innovative work during an exciting time for the field of microbiome science. We’re happy to welcome new partners like Microba as we apply our platform to more applications in the living therapeutics and microbiome space.

Microba plans to launch its initial Public Offering (IPO) on the Australian Securities Exchange on April 5. In connection with the partnership, Ginkgo is investing $3.5 million USD in Microba. The IPO was fully underwritten by Canaccord Genuity and Bell Potter.

Find the full press release here along with all of the latest news from the Ginkgo team.

Developing Next-Generation Gene Therapy Capsids with Selecta Biosciences

Posted on by Ankit Saxena

Selecta Biosciences intends to use Ginkgo’s cell programming platform to develop next-gen gene therapies using AAV capsids.

Gene therapy is one of the newest wave of treatments for many rare or orphaned diseases. However, current methods often result in unwanted immune responses.

What if you could grow the newest generation of therapies for human disease?

Together with Selecta Biosciences, Ginkgo is launching a collaboration to develop safer and more effective next-generation gene therapy adeno-associated viral capsids. Adeno-associated viruses (AAVs) are a type of gene delivery vector system. But several obstacles, including how these viruses interact with the immune system (immunogenicity), how well they can get into the cells (tropism), and how well they get DNA into the cells’ genomes (transduction efficiency), must still be overcome before fully realizing the AAV vector systems for many patient treatments. There are many types of AAVs, and they each work differently in different tissues, partially because of variations in the capsid–the protein coat of the virus.

The partnership with Selecta leverages the unique platforms of both companies as we seek to develop next-generation viral capsids with improved transduction, enhanced tissue tropism, and reduced immunogenicity. Ginkgo plans to design and engineer the capsids, and Selecta will conduct all pre-clinical and clinical studies thereafter.

“We are excited to continue our partnership with Ginkgo in a second collaboration that leverages Ginkgo’s leading cell engineering platform to design viral vector capsids with the goal of improved transduction, enhanced tissue tropism and reduced immunogenicity” said Carsten Brunn, CEO of Selecta Biosciences. “By combining ImmTOR with next-generation, fit-for-purpose AAV vectors, we hope to further improve the safety and efficacy of AAV-mediated gene therapies.”

Under the terms of the collaboration, Ginkgo is eligible to earn upfront research and development fees and milestone payments, including certain milestone payments in the form of Selecta common stock. In addition, Ginkgo is eligible to earn clinical, regulatory and commercial milestone payments of up to $200 million in cash for each of a specified number of products, which have the potential to total, in the aggregate, up to $1.1 billion. Ginkgo is also entitled to potential further downstream value in the form of royalties on sales.

Jason Kelly, CEO of Ginkgo, added, “Gene therapies utilize naturally occurring viral capsids that elicit immune responses and often exhibit safety and toxicity issues. We believe our collaboration with Selecta has the potential to confront major challenges within the gene therapy space and represents an important application of our cell programming platform. We look forward to executing on our shared vision and offering a potential solution for challenges in gene therapies that prevent treatment for millions of patients.”

Read the full press release here.

Improving the Manufacture of Biosynthetic Heparin with Optimvia

Posted on by James Waters

Optimvia will leverage Ginkgo’s cell and enzyme engineering platform as well as its fermentation process development expertise to improve the manufacture of biosynthetic heparin.

Heparin is a life-saving drug that prevents blood clots and is classified as an essential medicine by the World Health Organization. In addition to acting as an anticoagulant, it is important in treating a great number of medical issues, including adult respiratory distress syndrome, allergic rhinitis, asthma, and inflammatory bowel disease. Currently, however, it is isolated from animal sources, mostly pig or cattle, which are limited by livestock availability.

What if you could grow life-saving medicines on demand?

Optimvia is a biotechnology company specializing in engineering enzymes and their cofactors to synthesize complex therapeutic molecules. Ginkgo’s platform serves customers across industries seeking to develop new and better products using biotechnology, including partnerships to improve manufacturing processes and strengthen supply chains of key medicines. Producing non-animal derived heparin on Ginkgo’s platform is intended to be the proof of principle for Optimvia’s technology for the synthesis of sulfated glycans.

Enabling enzymatic manufacturing could create supply chain diversity and reduce or eliminate the need for high volume extraction of heparin from porcine intestines.

“The goal of producing biosynthetic heparin is similar to Genentech’s famous breakthrough of creating insulin through recombinant cell-based methods as opposed to relying on extraction from pig pancreas,” said Keith Kleeman, CEO, Optimvia. “We believe that combining Optimvia’s novel technology and Ginkgo’s capabilities will enable commercially viable, cost effective and safe biosynthetic heparin that could eliminate the world’s dependence on livestock sourced heparin entirely.”

Under this partnership, Optimvia seeks to leverage Ginkgo’s cell and enzyme engineering platform, as well as its fermentation process development expertise, to rapidly improve the performance of Optimvia’s biosynthetic heparin manufacturing technology.

“Ginkgo’s platform helps emerging startups develop and optimize their products and reach commercial scale,” said Ginkgo CEO Jason Kelly. “We’re pleased to welcome Optimvia as the newest member in our ecosystem. We believe scalable synthetic heparin could introduce much needed resiliency to the drug supply chain, improve access to this essential medicine, and reduce our dependence on industrial animal agriculture.”

Read the full press release here.

Investigational Synthetic Biotic Medicine for Homocystinuria with Synlogic

Posted on by Patrick Boyle

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

Posted on by Ankit Saxena

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.