Singular Genomics Systems, Inc. operates as a life science technology company that develops next-generation sequencing and spatial multiomics technologies.
The commercially available G4 Sequencing Platform is a highly versatile benchtop genomic sequencer designed to produce fast and accurate results. In addition, the company is developing the G4X Spatial Sequencer, which will leverage the company’s proprietary sequencing technology, applying it as an in situ readout for transcriptomics, proteom...
Singular Genomics Systems, Inc. operates as a life science technology company that develops next-generation sequencing and spatial multiomics technologies.
The commercially available G4 Sequencing Platform is a highly versatile benchtop genomic sequencer designed to produce fast and accurate results. In addition, the company is developing the G4X Spatial Sequencer, which will leverage the company’s proprietary sequencing technology, applying it as an in situ readout for transcriptomics, proteomics and fluorescent H&E in tissue, with spatial context and on the same platform as the G4.
The company developed a unique and proprietary NGS technology, which the company refers to as its Sequencing Engine. The core of the company’s Sequencing Engine is consisted of unique and proprietary chemistry, including novel chemical compounds, polymers and enzymes. This chemistry is designed to produce high-accuracy sequencing and rapid cycle times that can drive improvements in NGS. To take full advantage of the company’s proprietary chemistry, the company has developed and continue to develop purpose-built instrumentation consisting of high-speed, high-resolution imaging and innovative fluidic design. The company’s Sequencing Engine, together with its proprietary innovations in molecular biology techniques, will enable differentiated applications in fast-growing markets, supported by the company’s intellectual property portfolio.
The G4 is a benchtop next-generation sequencer designed to produce fast and accurate sequencing results. The G4 is designed to target the NGS market in particular applications that require power, speed, flexibility and accuracy. The company commercially launched the G4 in December of 2021, and the company began recognizing revenue on sales of the G4 in the fourth quarter of 2022.
The company is also developing the G4X Spatial Sequencer for in situ multiomic analysis. The G4X is designed to offer high-throughput in situ direct sequencing of RNA (‘Direct-Seq’), targeted transcriptomics, proteomics and fluorescent H&E profiling from formalin-fixed, paraffin-embedded (‘FFPE’) tissues. The G4X is designed to share the same platform as the existing G4 sequencer and is expected to be the first dual-purpose instrument offering both traditional NGS and tissue-based spatial sequencing capabilities. The G4X is designed with 40 cm2 of flexible imaging area and single-day run times, which is expected to provide significant advantages in throughput over existing technologies. The company has applied the learnings from its PX development program and the previously announced PX technology access program to the development, methods and features of the G4X, and plan to offer spatial sequencing technology access services on the G4X in the middle of 2024. The company plans to deliver the G4X to initial customers through an early access program by the end of 2024 with an initial immuno-oncology panel of transcripts and proteins, and the ability to customize content. The company expects to release Direct-Seq and additional panels at a later date.
The PX is a development-stage multiomics platform that the company designed to target the markets for single-cell, spatial analysis and proteomics and leverage the company’s Sequencing Engine as a readout mechanism to provide a high-resolution view of biology at the single-cell and tissue level. As a result of focusing the company’s development efforts toward the G4X, the company has paused the development of the PX. The company is pursuing partnership opportunities to provide funding and further the development of the PX.
Sequencing Engine
The company’s Sequencing Engine is the platform technology of the company’s products. The core of the Sequencing Engine is a novel and proprietary sequencing-by-synthesis (‘SBS’) chemistry that enables high-accuracy sequencing and rapid cycle times that will drive improvements in NGS and spatial multiomics. The Sequencing Engine enables performance of highly accurate and massively parallel sequencing at speed. The company built the Sequencing Engine from the ground up, and it incorporates the following innovations:
Cluster amplification: The company has developed an optimized cluster amplification method that is designed to ensure generation of high-quality and high-density clusters with minimal sequence bias and high signal-to-background ratios. This enables high-accuracy sequencing regardless of the type of genetic input material.
Paired-read sequencing: The company has developed a novel method to read DNA from both ends of the fragment, called paired-read sequencing. The company’s method is fast and efficient with reagent usage, while providing efficient mapping and detection of gene rearrangements, higher-quality data and single-cell genomics.
Sequencing chemistry: The company has developed a new and proprietary sequencing chemistry. This chemistry includes novel enzymes and nucleotides. The company has also designed and synthesized its own dyes to optimize performance. This new and proprietary chemistry enables fast sequencing cycle times.
Detection technology: The company has developed a proprietary high-speed and high-resolution imaging system. The imaging system has been designed to optimize throughput, cycle time, accuracy and efficiency.
Products
The company’s active product development pipeline is consisted of two products, each of which is designed to leverage the Sequencing Engine and purpose-built to address different applications. The company’s first product, the G4, targets the NGS market. The company’s second product in development, the G4X Spatial Sequencer, will leverage the company’s proprietary sequencing technology applying it as an in situ readout for transcriptomics, proteomics and fluorescent H&E in tissue, with spatial context and targets the spatial biology market. The G4X will share the same platform as the G4. Each of the company’s instruments are designed to use flow cell consumable kits sold separately by the company.
G4
The company surveyed numerous labs and key opinion leaders while developing the G4 to listen to their needs and to identify the limitations of current solutions. In parallel, the company engineered an instrument around the Sequencing Engine to address those real-world needs. The G4 consists of the company’s G4 instrument and associated consumables and is designed to seamlessly fit into existing workflows, including library preparation up front and bioinformatics on the back end. It is also designed to provide flexibility in terms of scalable sample volumes with the use of one to four flow cells in a sequencing run. This design will enable customers to better manage a wide range of daily sample volume demands without sacrificing turnaround times or incurring extra expenses from inefficient reagent kit use. The company is targeting applications for which power, speed, flexibility and accuracy matter, and where the company’s novel molecular biology methods offer unique advantages.
Capabilities of the G4
The G4 is designed with the following capabilities:
Speed: Innovative high-resolution imaging, rapid fluidics, and novel high-speed proprietary chemistry enable cycle times of approximately 2.5 minutes and single-day run times for various applications.
Flexibility: The G4 has four flow cells, each intentionally designed with four independent lanes, which reduces sample pooling and simplifies experiment project management. The G4 provides scalable run capacity to empower labs that have variable volume and time-sensitive samples with cost efficient sequencing.
Power: The company designed the G4 with four flow cells, which is designed to provide over 120 gigabase throughput on each flow cell per run depending on consumable kit and application.
Accuracy: Q30 quality is considered to be the ‘gold standard’ for a sequencer. The G4 provides Q30 or higher quality on more than 85% of base reads.
Paired-read sequencing: The company’s novel method allows for flexible read length paired-read sequencing of up to 2x150 cycles.
Read lengths: The G4 can sequence in common read configurations for the most common applications and support up to 2x150 read lengths.
Workflow: The company has designed the G4 for customers to efficiently switch to the company’s products. The upstream workflow and downstream analysis are compatible with many current NGS applications, and to enable this efficiency the company has partnered with industry-leading library preparation and data-analysis organizations.
Max Read Kits for Single Cell Sequencing
Next generation sequencing of short reads has enabled advances in a wide variety of applications, including detection and quantification of RNA in biological samples, cell-free DNA fragment detection and counting, high-throughput NGS barcode sequencing, CRISPR-screens, single-cell analysis, proteomics and others. Short-read NGS is typically performed with one set of single-end or paired-end reads on a single flow cell. The company’s Max Read kit enables multiple sets of independent single-end or paired-end reads on the same flow cell. Compared to conventional NGS formats, this workflow enables higher output of short reads for the same flow cell, without a significant impact on read quality.
The Max Read kits boost the potential output of the G4 to a market-leading 3.2 billion reads per run (800 million reads per flow cell) on a benchtop system for single cell sequencing. The Max Read kits, specifically designed to match the format of popular 10x Genomics assays, enable users the flexibility to sequence 4, 8, 12 or 16 samples per run, each in its own lane.
Specialized Applications for the G4
The G4 has broad potential application across various markets. Additional potential targeted applications for the G4 include rare variant detection with high-definition sequencing (‘HD-Seq’), detection of gene fusions with unknown partners or breakpoints with Ring-Seq, and longer gene sequencing through extended range sequencing (‘XR-Seq’). Development for these additional potential targeted applications has been paused as the company focuses development on other products. The company is considering partnership opportunities to provide funding and further the development of the G4 for these applications.
Rare variant detection with HD-Seq: The company designed the G4 to support HD-Seq, a unique library prep kit and sequencing method for double-stranded DNA in order to provide higher accuracy than standard single-strand NGS methods. HD-Seq is designed to enable rare variant detection with higher efficiency and lower costs and is intended to achieve accuracy levels of Q50, which can help differentiate a real mutation from random errors. Accuracy is especially important in oncology for the detection of somatic mutations, including rare single-nucleotide polymorphisms. It is also critical in liquid biopsy where the frequency of mutations in a sample is extremely low.
Gene fusion detection with Ring-Seq: Gene fusions are an important and actionable type of genetic aberration in cancer. The company designed a novel method, called Ring-Seq, for the targeted detection of gene fusions, including those with unknown partners or breakpoints. The method aims to deliver the sensitivity and speed of traditional multiplex polymerase chain reaction (‘PCR’)–based assays, but with the ability to detect gene fusions with unknown partners or breakpoints. The method includes an innovative wild-type suppression mechanism to increase sequencing efficiency, which would result in reduced sequencing costs per sample.
Extended range sequencing with XR-Seq: Other possible applications include extended range sequencing, which would facilitate longer gene sequence reads of up to 3,000 base pairs and support comprehensive analysis of the immune system, particularly the adaptive immune response consisting of B- and T-cells. A high throughput, high accuracy, cost-effective solution for reading these longer gene sequences can advance the understanding of the immune system, improve the diagnosis and monitoring of blood cancers, provide new insights into immunotherapy for cancer, facilitate therapeutic antibody and T-cell discovery and accelerate the development of vaccines for infectious disease.
G4X Spatial Sequencer
Building on the company’s foundation in NGS and its advancements in spatial multiomics with the development of the PX, the company began designing a product that could bring sequencing directly into cells and tissues, and to create a universal readout for spatial biology. The company is designing the G4X to offer high-throughput in situ direct sequencing of RNA (‘Direct-Seq’), targeted transcriptomics, proteomics and fluorescent H&E profiling from formalin-fixed, paraffin-embedded (‘FFPE’) tissues. The company designed the G4X to share the same platform as the existing G4 sequencer, and it is expected to be the first dual-purpose instrument offering both traditional NGS and tissue-based spatial sequencing capabilities. The company plans for the G4X to be offered with specialized consumable kits. With its expected industry-leading throughput and direct spatial sequencing, the G4X will empower more researchers to incorporate spatial tissue profiling into their work and to perform increasingly larger studies. The company plans to offer spatial sequencing technology access services on the G4X in the middle of 2024. The company plans to deliver the G4X to initial customers through an early access program by the end of 2024 with an initial immuno-oncology panel of transcripts and proteins, and the ability to customize content. The company expects to release Direct-Seq and additional panels at a later date.
Expected Key Features of the G4X
The company is designing the G4X to have the following key features:
Industry-leading Throughput: An imaging area of 40 cm2 per run across four spatial flow cells is expected to significantly increase sample throughput while retaining flexibility for smaller runs compared to other products.
Direct-Seq: In situ sequencing of RNA, designed to sequence variable gene regions directly within cells and tissues, with potential applications in immunology, immuno-oncology, cancer research, and gene editing.
Transcripts: Hundreds of gene transcripts, which will be available in curated panels and custom gene target selection.
Proteins: Dozens of proteins, which will be available in curated panels and custom protein target selection.
Fluorescent H&E: Fluorescent H&E stain overlayed with transcripts and proteins on the same tissue sample.
Rapid Turn-around-time: With a specialized tissue transfer process, streamlined sample preparation workflow, and high-speed single-day sequencing, the company expects users will have the ability to go from sample-to-discovery in as little as three days.
Cost-Effective: With its high throughput, the G4X will significantly reduce the cost per sample to less than half that of alternative approaches, making spatial multiomics more accessible.
PX
The company commenced the development of the PX, which is focused on the single cell and spatial analysis markets and consists of the PX instrument and associated consumables. The company was designing the PX to leverage its Sequencing Engine as both a universal detection method and in situ sequencing to enable multiomics analysis of single cells and tissues. The company was designing the PX to provide high-throughput analysis of nucleic acids and proteins, while also generating high-resolution images of cellular morphology to enable analysis of cellular phenotypes together with spatial context. Additionally, the company was designing the PX to use a well-plate approach to process 10,000 to 100,000 cells per well at a throughput of 1 million to 10 million cells in a single run on its 96-well plate. The PX could have broad applicability across multiple large disease areas, including oncology and immunology; and could enable researchers to perform large-scale experiments that may fundamentally advance the company’s understanding of biology, and in turn, advance human health.
The company has applied the learnings from its PX development program and the previously announced PX technology access program to the development, methods and features of the G4X, and as a result of focusing the company’s development efforts toward the G4X, the company has paused the development of the PX. The company is pursuing partnership opportunities to provide funding and further development of the PX.
Markets
The company’s product pipeline targets multiple market opportunities across life sciences. Due to the comprehensive capability to analyze biology that the company is designing into its products, the company anticipates that much of this opportunity will be available to the company. The company estimates that the G4 and the G4X target substantial market opportunities in NGS, spatial multiomics and potential new markets, such as clinical applications.
The company plans to initially sell and market its products for research use only (‘RUO’) to academic institutions, life sciences and research laboratories, and biopharmaceutical and biotechnology companies for non-diagnostic and non-clinical purposes. Additionally, CLIA-certified laboratories are able to develop laboratory developed tests (‘LDTs’) using RUO products. Today, a significant majority of NGS-based diagnostic tests are performed as LDTs on DNA sequencers that are labeled for RUO. While the company’s initial products are intended for RUO, the company’s longer-term plans include seeking the U.S. Food and Drug Administration (‘FDA’) clearance for in vitro diagnostic (‘IVD’) products and corresponding clearances in other countries.
Commercialization
The company’s business model focuses on first driving customer adoption of the G4, followed by the G4X. Customer adoption will then form a base of users who in turn drive an ongoing revenue stream by purchasing the company’s consumables. The company plans to focus the company’s commercial efforts on: (i) expanding the installed base of the G4 and planned G4X across a wide array of key customer segments; and (ii) driving applications, scale of experimentation and discoveries that lead to increasing utilization of the company’s products by its customers. Similar to the company’s strategy of developing purpose-built products based on feedback from potential customers, the company is developing a service and support organization that focuses on creating an unparalleled customer experience.
The company commercially launched the G4 in December of 2021, and the company began recognizing revenue on sales of the G4 in the fourth quarter of 2022. For the G4X, which shares the same platform as the G4, the company has applied the learnings from its PX development program and the previously announced PX technology access program to its development, methods and features, and plan to offer spatial sequencing technology access services on the G4X in the middle of 2024. The company plans to deliver the G4X to initial customers through an early access program by the end of 2024 with an initial immuno-oncology panel of transcripts and proteins, and the ability to customize content. The company expects to release Direct-Seq and additional panels at a later date.
The company has built its commercial organization to have direct commercial staff in sales, customer support, applications support, field service and marketing and communications. As the company continues its commercial activities, the company may need to scale each function within the company’s commercial organization in response to demand and with the intent to deliver exceptional customer experiences. Coupling customer experience with a transformative integrated solution will allow the company to deliver substantial value to the company’s customers, build long-term customer loyalty and enhance the company’s competitive differentiation. Additionally, as part of the company’s commercialization strategy, the company plans to provide flexible purchase offerings to customers such as in the form of leases, reagent rentals and subscriptions, and the company plans to provide discounts to certain customers or other sales incentives including discounted upgrades to the G4X.
The company has initially targeted customers in North America through direct sales and customer support organizations. The company also plans to expand outside North America to sell and support the company’s products in the European Union, the United Kingdom, the Asia Pacific and Japan; and expects to expand access to the company’s products in other geographies through well established distribution networks. In 2023, the company expanded its commercial infrastructure on a limited basis in Europe to support the company’s international growth.
Intellectual Property
As of December 31, 2023, the company owned or exclusively licensed 43 issued U.S. Utility patents, 11 issued U.S. Design patents, 93 pending U.S. Utility patent applications, nine pending U.S. Design patent applications, 21 issued European Registered Community Design Certificates, 28 pending European patent applications, two issued Other International (i.e., Australia, Canada, China, Israel, and/or Japan) Design patent, 55 pending Other International patent applications, 15 pending Patent Cooperation Treaty (‘PCT’) patent applications, and 25 pending U.S. Provisional patent applications. The pending European patent applications were filed in the European Patent Organization (‘EPO’), designating all 38 member countries. The company’s U.S. owned patents and patent applications, if issued, are expected to expire between 2036 and 2043, in each case without taking into account any possible patent term adjustments or extensions and assuming payment of all appropriate maintenance, renewal, annuity or other governmental fees.
Of these, the company exclusively licenses from The Trustees of Columbia University in the City of New York (‘Columbia’) two issued U.S. patents, four pending U.S. Utility patent applications, one pending European patent application, and certain materials and technical information provided by Columbia. The pending European patent application was filed in the EPO, designating all 38 member countries. These patent applications are directed to compositions and methods for sequencing utilizing nucleotides containing disulfide linkers. The company’s in-licensed patent applications, if issued, are expected to expire in 2036 and 2037, in each case without considering any possible patent term adjustments or extensions and assuming payment of all appropriate maintenance, renewal, annuity or other governmental fees.
In addition to the company’s reliance on patent protection for its inventions, products and technological advancements, the company’s strategy relies on trade secrets, specialized know-how, robust confidentiality agreements, and continuing technological innovation and licensing opportunities, to develop and maintain its competitive position. For example, several core aspects of the company’s manufacturing processes such as its nucleotide synthesis and flow cell assembly, analytic techniques and assays, imaging and optics implementations, as well as computational algorithms and related processes and software, are based on unpatented trade secrets and know-how that are not publicly disclosed.
The company uses Singular Genomics, G4, XR-Seq, XR/T-SEQ, HD-Seq, Max Read, Ring-Seq, PX, Direct-Seq, G4 SeqOS, and G4X as trademarks in the United States and internationally. For one or more of the aforementioned trademarks, the company applied for trademark registration in the United States, Australia, Brazil, Canada, China, Europe, Israel, Japan, Mexico, South Korea, Switzerland, and the United Kingdom.
Columbia License Agreement
In August 2016, the company entered into an Exclusive License Agreement (the ‘License Agreement’) with Columbia. The License Agreement includes a number of diligence obligations that require the company to use commercially reasonable efforts to research, discover, develop and market Patent Products and/or Other Products (as defined in the License Agreement) by certain dates.
Competition
The company’s primary competitors and potential competitors are large publicly traded companies or are divisions of large publicly traded companies, including 10x Genomics Inc., Becton, Dickinson and Company, Bio-Rad Laboratories, Inc., Illumina Inc., MissionBio Inc., Nanostring Technologies, Inc., Oxford Nanopore Technologies Inc., Pacific Biosciences Inc. and Thermo Fisher Scientific Inc. There are other companies, both established and early stage, such as Element Biosciences, Inc. and Ultima Genomics, Inc., who have begun commercializing NGS and/or spatial technologies and offering products to the company’s target customers.
Customers
The company is initially targeting customers who are already familiar with genomic analysis, including academic institutions, genomic research centers/core labs and government laboratories, as well as pharmaceutical, clinical research organizations (‘CROs’), biotechnology, consumer genomics, commercial molecular diagnostic laboratories and agrigenomics companies.
History
Singular Genomics Systems, Inc. was founded in 2016. The company was incorporated in the state of Delaware in 2016.
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