High Throughput Screening for Designing Novel CAR-T Cell Therapies

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

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

What will you grow with Ginkgo?

Developing Water Quality Biosensors with FREDSense

Ginkgo’s strain development capabilities to help develop advanced biosensors

Today, we’re excited to announce our partnership with FREDsense Technologies Corp, a next generation water quality platform company leveraging synthetic biology to build field kits for faster, cheaper, and more efficient analysis. Through this partnership, we seek to build four distinct microbial strain biosensors, compatible with FREDsense’s field-ready hardware for remote water quality monitoring applications.

Demand for scalable monitoring and testing systems has increased, as water quality becomes an ever-growing environmental and public health concern. Conventional water quality test results are often delayed, since samples must be transported to labs for chemical analysis. FREDsense builds portable solutions to efficiently assess the chemicals in the water at the source. This allows for rapid modification of water treatment processes in real-time without the need for external lab equipment.

Supporting real-time field detection of harmful molecules and toxins in any water source

The biosensors in development by Ginkgo aim to support real-time field detection of harmful molecules, and may be used to generate solutions for groundwater and industrial water management systems.

Partnering with FREDsense is an exciting opportunity to apply our strain development capabilities to powerful biosensor technology for an important application. Protecting our water sources is a mission critical initiative: life on this planet as we know it depends on it. We’re eager to work toward enhancing the capabilities of FREDsense’s platform to monitor for harmful contaminants in water.

“Water is our most critical resource, and we now have the technology to detect in real-time many of the threats or contaminants that can impact the water that our environments and communities depend on,” says David Lloyd, CEO of FREDsense. “Through this partnership with Ginkgo, we aim to introduce rapid, simple and accurate testing to deliver water quality monitoring systems to those that most need it. We believe that synthetic biology is the key to solving some of the biggest challenges facing the water industry globally and are very excited to partner with Ginkgo on this vision.”

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

What will you grow with Ginkgo?

Developing Next-Generation Gene Therapy Capsids with Selecta Biosciences

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

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.

New Platform Venture: Arcaea

The products we traditionally use for personal hygiene and beauty can have large ecological impacts. Many of them use chemicals that are byproducts of fossil fuels or harvest ingredients from threatened or endangered ecosystems. What if we could grow the things that make us feel clean and beautiful, sustainably? Beyond environmental concerns, synthetic biology promises the possibility of products with new functions and a vision of nurturing our personal hygiene and redefining our sense of beauty.

Arcaea, LLC (Ar-kay-uh), incubated on the Ginkgo platform and formed under the name Kalo Ingredients LLC, was launched with the mission to build a new foundation for the beauty industry through expressive biology. The company sees biology as a valuable creative tool for self expression and aims to grow new ingredients and product experiences for beauty through the tools of the synthetic biology ecosystem fostered on the Ginkgo platform. By culturing industry-leading, safe, and sustainable ingredients, Arcaea intends to create a new supply chain for the industry that does not rely on petrochemicals or on harvesting and dwindling natural resources.

By harnessing the power of biology, Arcaea is poised to produce highly sustainable products that can deliver new functionality and performance across skincare, bodycare, haircare, and aesthetics.

The company will be led by Jasmina Aganovic, a chemical and biological engineering graduate from MIT. She brings more than a decade of industry experience translating innovation in beauty through brands and products at various beauty companies, including Fresh and Living Proof and the innovative microbiome beauty company Mother Dirt, which changed the way we think about clean and healthy skin. Jasmina saw the powerful role that biology can play in the cosmetics industry, which prompted her interest in creating tools to better realize its potential. She joined Ginkgo as an Entrepreneur-in-Residence, where she spent the last two years building the foundation for Arcaea.

“Through Arcaea, we see biology as a creative tool that will drive the next generation of products and innovation. We can now access many more molecules on earth ethically and sustainably, and therefore can unlock unlimited and previously unimagined possibilities for beauty,” said Aganovic. “By bringing together new advances in technology with designers, brand builders, and leaders from every point of the supply chain, we can spark a change across the entire ecosystem to create an industry that is reflective of the future we want to see for the industry.”

Arcaea has raised $78 million in Series A funding from a consortium of strategic and financial investors including Cascade Investment L.L.C., Viking Global, CHANEL, Givaudan and Wittington Ventures. This Series A financing round brings together a mix of expertise across the value chain of the industry. It will enable Arcaea to initiate multiple technical programs across key categories in beauty to develop a pipeline of ingredients and brand launches and create a world of previously unimaginable possibilities in beauty, such as: a fragrance that no one on earth has ever smelled before; proteins that can memorize hair styles; contouring through skincare and not just makeup; and biological filters that protect skin from the elements.

“One of the most impactful things we can do at Ginkgo is support entrepreneurs and help them accelerate their timelines to make incredible things happen with biology,” said Jason Kelly, co-founder and CEO of Ginkgo. “We are thrilled to see Arcaea launch and begin its journey to deliver creative solutions to the beauty industry through biology.”

Read the press release here.

Engineering Living Biotherapeutics for Gastrointestinal Health with Tantu

Digestive disorders affect tens of millions of people in the U.S. each year, and current treatments don’t sufficiently promote gastrointestinal healing, resulting in many patients undergoing invasive surgeries to improve their quality of life.

But what if you could specifically design a living medicine—a microbe—that aids intestinal healing, transforming the way these patients are cared for?

That’s exactly what Tantu Therapeutics is trying to do. They’re working to create an orally administered, living biotherapeutic that will produce and apply anti-inflammatory therapeutic proteins directly into diseased sites in the gut. The living medicine aims to improve gut barrier function and faster mucosal healing in patients where systemic anti-inflammatory therapies are not enough.

And they’ve come to Ginkgo to help accelerate the research and development of this new therapeutic. We plan to apply our automated foundry to speed up the traditionally slow process of candidate strain construction and genomic integration and validation. Our goal is to accelerate Tantu’s first program and potentially help them reach clinical proof of concept in patients faster.

Tantu’s lead therapeutic candidate is an engineered microbe that produces anti-inflammatory and healing agents from inside the gut lumen—something that no clinically approved therapeutic currently does. Tantu’s local delivery strategy is designed to improve patient outcomes by reducing reliance solely on systemic anti-inflammatory drugs, which can suppress a patient’s immune system. Their living biotherapeutic products are being designed to complement proven approaches to further improve patients’ health and quality of life.

Through our platform, we’re able to support startups in the biotech industry as they bring new innovations to the field and society.

We’re excited to partner with a pre-seed company like Tantu; our goal is to reduce their time-to-market. Our program with Tantu gives us the opportunity to leverage our expertise in pharmaceuticals and support the development of a potentially transformative therapeutic for the millions struggling with digestive disorders.

Companies across numerous industries use Ginkgo’s cell programming platform to find more effective, environmentally friendly ways to create products including food ingredients, fragrances, cosmetics, medicines, and more. By enabling the design of organisms that can produce valuable biological products, we’re helping accelerate the development of innovative, bio-based solutions to the world’s most pressing challenges.

Optimizing Silk Protein Production with Bolt Threads

We built our cell programming platform to make it easier for people to develop apps with biology. And while we love working on brand new ideas with partners, we also really love helping them improve their existing products and processes to make them more efficient and accessible. This week, we’re thrilled to announce Bolt Threads as our latest partner enhancing an existing product by running a cell program on the Ginkgo platform.

Bolt’s cell program seeks to improve the sustainability, efficiency, and cost effectiveness of their b-silk™ protein manufacturing process by leveraging our expertise in strain engineering.

Bolt is a biotechnology company creating the next generation of advanced materials. Their team of engineers and designers have spent nearly a decade at the forefront of the synthetic biology industry, securing partnerships with consumer brands including Kering, Stella McCartney, Adidas, and Lululemon to bring advanced biological materials to consumers around the globe.

In recent years, Bolt has developed b-silk protein, an innovative ingredient inspired by the strength and elasticity of spider silk. They’ve shown that the protein is able to deliver silk-like softness, provide powerful skin defense, and has the potential to sustainably replace synthetic ingredients—like silicones—in skin and hair care products.

While the protein is currently used in premium product lines like Vegamour, the new cell program will leverage Ginkgo’s strain engineering capabilities to improve their production efficiency of b-silk protein, scaling b-silk protein to more mass availability, and potentially unlocking further applications for the ingredient throughout the clean beauty and personal care industries.

We believe in the power of biology to transform every industry that produces physical goods and have built our platform to enable innovators like Bolt to bring their vision to life.

New Platform Venture: Introducing Motif

When people talk about the future of food, they often start by talking about how the human population is projected to reach 10 billion people by the year 2050. To feed a rapidly growing population with an expanding middle class on a warming planet, we’ll have to use new technologies and build new systems to grow and distribute food. But whether it’s about choosing our next meal or feeding a growing population, the stories we tell about the future of food are full of impossible tradeoffs between taste, cost, health, and the environment (think Soylent vs. Whole Foods). And when it comes to GMOs specifically, the tradeoff is even more stark. Will it ever be possible for food be sustainable, healthy, delicious, and affordable?

At Ginkgo, we believe that biotechnology is an essential part of the future of food, and we hope that it can give us more options, not fewer. We’re working towards a future where genetic engineering and cultured ingredients can help make foods that are more sustainable, healthier, delicious, and more accessible for everyone. It’s what drives our work with customers in the flavor & fragrance and food industries to make cultured ingredients and the work of Joyn Bio, our joint venture with Bayer engineering microbes for more sustainable agriculture.

Today we’re thrilled to be launching Motif Ingredients, a new company built on Ginkgo’s platform to address one of the biggest challenges and changes emerging for the future of food—protein. Recognizing the benefits to health and sustainability that come from a plant-based diet, consumer demand for complements to animal proteins has exploded in the past few years, for products ranging from oat milk to “bleeding” veggie burgers. Companies ranging from brand new startups to industry giants have rapidly innovated new foods based on alternative proteins, but there’s so much more to do to make these options as healthy, delicious, sustainable, and accessible as they should be. Motif Ingredients will use Ginkgo’s Foundry to discover and develop these necessary new alternative protein ingredients that can be made via fermentation, not animal agriculture.

Motif Ingredients is launching today with $90M in Series A funding from Breakthrough Energy Ventures, Fonterra, Louis Dreyfus Company, and Viking Global Investors. Our investors come from both high tech venture capital and traditional food producers that have been feeding the world for more than a century, all believing in our platform’s ability to deliver more alternatives for everyone’s “food future”. Motif will operate from Ginkgo’s offices in the Boston Seaport and leverage our foundries to discover the next generation of alternative proteins. We’re also excited to welcome industry veteran Jon McIntyre to the team as Motif’s CEO. Formerly the head of R&D at Indigo Ag and prior to that, a Senior VP of R&D at PepsiCo, Jon brings a wealth of experience in global food systems and alternative proteins to Motif.

A platform for discovering the next generation of food proteins

Proteins in animal products like meat, dairy, and eggs are essential for the taste, texture, nutrition, health impact, and overall experience of many foods that we eat. Food proteins have unique structural and functional properties, whether they are egg proteins giving a dessert its fluffy texture, or milk proteins protecting a baby’s digestive system from dangerous bacteria. Motif will make different proteins like these via fermentation of engineered microbes, without animal agriculture, to create a rich palette of alternative protein ingredient options for people developing new foods.

An introduction to Motif’s technology by Karen Ingram

Ginkgo’s platform enables biological engineers to deeply study thousands of different protein options across a vast space of biological diversity, discover the proteins that provide the greatest functional benefit, and increase their accessibility at large scale. There is so much that we don’t yet know about even the most common foods, so the ability to search this breadth of biological diversity is essential. Even in the last 5 years, hundreds of new proteins have been discovered in milk and eggs that confer benefits to people who eat them. With Motif, we’re on a mission to explore all that animal proteins have to offer, to enable the next generation of alternative proteins.

Beyond cow’s milk and hen’s eggs, there are also foods with vital benefits that are impossible to access in large amount sustainably, such as sturgeon eggs, camel milk, and everything in between. Just one year ago, scientists discovered a new protein in platypus milk that has surprising antibiotic properties. Using DNA sequence analysis and synthesis, Motif’s scientists will be able to discover and produce hundreds of proteins from many different animals, to understand how their milk and eggs nourish and sustain life in its earliest stages and identify important new ingredients.

At Ginkgo, we are always learning from the creativity of biology and the full breadth of biodiversity to grow better, more sustainable products. We’re so excited to work with Motif as they look to biodiversity to find the proteins that will enable new creativity in food. We’re thrilled to welcome Motif to our platform and to support the next generation of chefs, food designers, and food visionaries who need new ingredients and tools for the future of food.

For more about Motif, visit their website at motifingredients.com. You can also follow them on Twitter and Instagram, and sign up for their newsletter.