MedTech, Medical

Twist Bioscience Launches Portfolio of RNA Sequencing Tools

Businesswire | May 23, 2023 | Read time : 04:00 min

Twist Bioscience Launches

Twist Bioscience Corporation a company enabling customers to succeed through its offering of high-quality synthetic DNA using its silicon platform, today announced the launch of a portfolio of RNA sequencing tools, which includes the Twist RNA Exome, Twist RNA Library Prep Kit and the Twist Ribosomal RNA (rRNA) & Hemoglobin (Globin) Depletion Kit, as well as custom target enrichment capabilities for RNA and whole transcriptome sequencing. This comprehensive suite of RNA tools can enable targeted or whole transcriptome research across fields including precision medicine, biomarker discovery and immuno-oncology research.

“Twist’s RNA sequencing portfolio builds on our established NGS capabilities in genomic sequencing and methylation detection and expands into gene expression analysis, opening a new and significant market for Twist,” said Emily M. Leproust, Ph.D., CEO and co-founder of Twist Bioscience. “This offering allows our customers to leverage Twist’s leading target enrichment platform to discover and resolve low abundance RNA transcripts in the human transcriptome. Our RNA sequencing workflows are designed specifically for challenging samples. By enriching relevant transcripts, we can enable researchers to get high-quality data from a range of sample types, including damaged RNA.”

Unlike the genome, which is relatively static, the transcriptome changes over time in response to varying disease states and drug therapies. Gene expression levels also differ across tissues and cell types. To fully understand this dynamic quality of RNA, researchers often sequence RNA samples from the same source at multiple time points, incurring additional costs and resource burdens. Each component of the Twist RNA sequencing portfolio is purpose-built to maximize data quality, minimize workflow inefficiency, decrease wasted sequencing reads, and support comprehensive transcriptomic profiling across even low-quality and low-input samples common in oncology.

The Twist RNA sequencing portfolio provides end-to-end workflows that can be used to study total RNA and measure the whole transcriptome, protein coding sequences of messenger RNA (mRNA) or custom targets. These products can also be integrated into customers’ existing workflows. Twist RNA sequencing tools enable minimal hands-on time and increase the scale of samples sequenced through utilizing automation. They are compatible with a wide range of sample inputs, including difficult or low-quality samples. RNA panel designs can also now incorporate Twist’s new exon-aware design algorithm, which reduces bias in detection and can provide an important tool for researchers studying rare gene transcripts that drive tumor biology.

Twist Targeted RNA Sequencing Workflow

Twist target enrichment for RNA leverages the performance, efficiency and sensitivity of Twist target enrichment for sequencing of RNA transcripts of interest across samples and species. It can be used to enrich relevant transcripts with the RNA Exome or in custom RNA panels.

Twist RNA Exome

The Twist RNA Exome with Twist’s exon-aware design algorithm enables targeted sequencing of the protein coding regions of the human transcriptome without bias toward specific combinations of exons. The Twist RNA Exome covers up to 99.9% of protein coding sequencing in Gencode and RefSeq databases. This coverage, along with the exon-aware design approach, could enable researchers to capture important transcripts including those in low input and degraded samples from formalin fixed paraffin embedded (FFPE) sections.

Twist Whole Transcriptome Sequencing Workflow

Twist Whole Transcriptome Sequencing can be used to discover novel transcripts, including low expressing genes and novel isoforms. It can be used with a variety of samples including whole blood, fresh and frozen tissue samples and low quality samples, such as FFPE samples. The Twist rRNA & Globin Depletion Kit can be used with this workflow to deplete rRNA and hemoglobin targets so that researchers can study the rest of the transcriptome. The full workflow can be completed in less than five hours with minimal hands-on time.

About Twist Bioscience Corporation

Twist Bioscience is a leading and rapidly growing synthetic biology and genomics company that has developed a disruptive DNA synthesis platform to industrialize the engineering of biology. The core of the platform is a proprietary technology that pioneers a new method of manufacturing synthetic DNA by “writing” DNA on a silicon chip. Twist is leveraging its unique technology to manufacture a broad range of synthetic DNA-based products, including synthetic genes, tools for next-generation sequencing (NGS) preparation, and antibody libraries for drug discovery and development. Twist is also pursuing longer-term opportunities in digital data storage in DNA and biologics drug discovery. Twist makes products for use across many industries including healthcare, industrial chemicals, agriculture and academic research.

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Tango Therapeutics Announces First Patient Dosed in TNG260 Phase 1/2 Trial in Patients With STK11-Mutant Cancers

Globenewswire | July 25, 2023

Tango Therapeutics, Inc. a clinical-stage biotechnology company committed to discovering and delivering the next generation of precision cancer medicines, today announced that the first patient has been dosed in the phase 1/2 trial evaluating TNG260 in combination with pembrolizumab in patients with STK11-mutant cancers. TNG260 is a first-in-class inhibitor of the CoREST complex . “The TNG260 phase 1/2 clinical trial is the first trial to use genetic patient selection in combination with checkpoint inhibitor therapy to reverse the cancer-specific immune evasion caused by STK11 loss of function mutations. Resistance to immunotherapy is a major challenge faced by patients with STK11-mutant cancers, which TNG260 is specifically designed to overcome,” said Adam Crystal, M.D., Ph.D., President of Research and Development of Tango Therapeutics. “Our pipeline of precision oncology treatments based on synthetic lethality has advanced significantly this year, as we now have initiated three clinical trials.” The phase 1/2 trial will evaluate the safety, pharmacokinetics (PK), pharmacodynamics and efficacy of TNG260, with a one cycle single agent run-in phase to evaluate the safety and PK of TNG260, in combination with pembrolizumab, in patients with locally advanced or metastatic solid tumors with an STK11 loss-of-function mutation. STK11 loss-of-function mutations occur in approximately 15% of non-small cell lung cancer, 15% of cervical, 10% of carcinoma of unknown primary, 5% of breast and 3% of pancreatic cancers. Based on preclinical xenograft studies and retrospective clinical analyses, the majority of STK11-mutant cancers are thought to have primary resistance to checkpoint inhibition. The CoREST complex plays a central role in regulating immunomodulatory signaling in STK11-mutant cancers. In preclinical studies, TNG260 reverses the immune evasion effect of STK11 loss-of-function mutations, restoring sensitivity to an anti-PD-1 antibody, inducing complete remissions in the majority of animals and creating immune memory that prevents re-implantation and regrowth of the tumor. In April 2023, the U.S. Food and Drug Administration granted Fast Track designation for TNG260 in combination with an anti-PD-1 antibody for the treatment of patients with previously treated advanced non-small cell lung cancer with STK11-mutations. About Tango Therapeutics Tango Therapeutics is a clinical-stage biotechnology company dedicated to discovering novel drug targets and delivering the next generation of precision medicine for the treatment of cancer. Using an approach that starts and ends with patients, Tango leverages the genetic principle of synthetic lethality to discover and develop therapies that take aim at critical targets in cancer. This includes expanding the universe of precision oncology targets into novel areas such as tumor suppressor gene loss and their contribution to the ability of cancer cells to evade immune cell killing.

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MedTech, Medical

NanoString Platforms Advance Groundbreaking Studies of Immune Response in Pig-to-Human Organ Transplants

Businesswire | August 22, 2023

NanoString Technologies, Inc. a leading provider of life science tools for discovery and translational research, The seminal research led by Alexander Loupy, MD, Ph.D., in cooperation with a global medical team, unravels the complex molecular characteristics of antibody-mediated rejection following the first and second-ever pig-to-human kidney transplants that occurred in 2021 at NYU Langone Transplant Institute. In an accompanying Lancet commentary, scientists praised the team “for laying the foundation for deeper assessment of xenoimmunology and establishing immunological research pathways to advance xenotransplantation.” They also commented on the importance of “state-of-the-art spatial techniques” to decipher transcriptional immune activation. “We gained vital data and, for the first time ever, we were able to see what is happening immunologically in defined regions of the tissue,” said Dr. Loupy. “This data, enabled by NanoString’s platforms and an Allo - Xeno gene expression repository, allowed us to understand both the similarities and the novel aspects underpinning organ rejection in xenograft transplantation compared to human organ transplantation. NanoString’s nCounter and GeoMx instruments harmonized to create a holistic view of the immune response.” Researchers from the Paris Institute for Transplantation and Organ Regeneration, University of Paris, France’s National Institute of Health and Medical Research contributed to the study. Xenotransplantation, the process of transplanting organs from animals to humans, is a crucial area of research dedicated to addressing the profound shortage of healthy human organs available for transplant patients. The groundbreaking experimental transplant surgeries performed by Dr. Robert Montgomery at NYU since 2021 involve patients in a state of brain death. Their families and ethical committees have consented to artificially maintain blood circulation during the transplants to advance scientific knowledge on xenotransplantation with the hope of offering more healthy organs for future patients. The research team, including co-first authors of The Lancet study, Dr. Valentin Goutaudier and Dr. Alessia Giarraputto characterized the human immune response to the porcine kidney using bulk tissue transcriptome profiling on the nCounter Analysis System. Scientists used the nCounter Human Organ Transplant Panel, a process NanoString developed with the Banff International Classification Consortium. It is used by nearly one hundred global research institutions. The panel was adapted to xenotransplants by using bioinformatics-based pig and human gene sequences with homologies alignment. This analysis revealed a molecular architecture of antibody-mediated rejection, including interferon-gamma response, endothelial activation, macrophage activation, and injury repair response in the xenografts. The GeoMx Digital Spatial Profiler was used next to isolate the immune response to specific regions of the kidney. The GeoMx Whole Transcriptome Assay revealed that antibody-mediated injury was mainly located in the glomeruli of xenografts, with significant enrichment of transcripts associated with monocytes, macrophages, neutrophils, and NK cells. Drs. Loupy and Montgomery say their findings represent a treasure trove of new information for optimizing genetically modified pig models that may be useful in developing more advanced immunosuppressive treatments for future recipients of xenografts. “An estimated 100,000 people are waiting for organ transplants in the United States. Thousands die on the wait list. Numbers like these drive us at NanoString to provide researchers with the tools they need to find innovative solutions to solve extraordinary medical challenges,” commented Brad Gray, President and CEO of NanoString. “We congratulate Dr. Loupy and his extended team on their findings and celebrate the on-going successful studies in humans.” About NanoString Technologies, Inc. NanoString Technologies, is a leader in spatial biology, offers an ecosystem of innovative discovery and translational research solutions, empowering our customers to map the universe of biology. The GeoMx® Digital Spatial Profiler is a flexible and consistent solution combining the power of whole tissue imaging with gene expression and protein data for spatial whole transcriptomics and proteomics. The CosMx™ Spatial Molecular Imager is a single-cell imaging platform powered by spatial multiomics enabling researchers to map single cells in their native environments to extract deep biological insights and novel discoveries from one experiment. The AtoMx™ Spatial Informatics Platform is a cloud-based informatics solution with advanced analytics and global collaboration capabilities, enabling powerful spatial biology insights anytime, anywhere. At the foundation of our research tools is our nCounter® Analysis System, which offers a secure way to easily profile the expression of hundreds of genes, proteins, miRNAs, or copy number variations, simultaneously with high sensitivity and precision.

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Medical, Industry Outlook

NANOBIOTIX Announces License Agreement for Worldwide Co-development and Commercialization of Potential First-In-Class Radioenhancer NBTXR3

Globenewswire | July 13, 2023

NANOBIOTIX a late-clinical stage biotechnology company pioneering physics-based approaches to expand treatment possibilities for patients with cancer, today announced a global licensing, co-development, and commercialization agreement with Janssen Pharmaceutica NV one of the Janssen Pharmaceutical Companies of Johnson & Johnson, for the investigational, potential first-in-class radioenhancer NBTXR3. NBTXR3 is currently being evaluated in several studies across solid tumor indications including NANORAY-312, a global Phase 3 pivotal study evaluating NBTXR3 for the treatment of patients with locally advanced head and neck cancer. NBTXR3 is also being evaluated for its potential as a systemic agent in combination with anti-PD-1 immune checkpoint inhibitors for patients with metastatic cancers. Under the terms of the license agreement, in collaboration with the Interventional Oncology R&D Unit at Johnson & Johnson, Nanobiotix will grant Janssen a worldwide license for the development and commercialization of NBTXR3. The license is exclusive, excepting territories previously licensed to Nanobiotix partner LianBio. Dial-in information for a conference call Nanobiotix will host to discuss the agreement can be found below. “As pioneers in the field of nanotherapeutics for the past 20 years, we knew that the true impact of our innovation in oncology would be in its potential to reach millions of patients around the world. For that, we needed to find the right partner, at the right time, with proven global development and commercialization capabilities,” said Laurent Levy, Nanobiotix chairman of the executive board. “We are delighted to collaborate with Janssen as we aim to improve the lives of patients with cancer around the world.” Nanobiotix will receive near term cash and operational support valued up to $60 million. This includes an upfront cash licensing fee of $30 million, and in-kind regulatory and development support for study NANORAY-312 valued at up to $30 million that Janssen may provide at its sole discretion. Nanobiotix will maintain operational control of NANORAY-312 and all other currently ongoing studies, along with NBTXR3 manufacture, clinical supply, and initial commercial supply. Janssen will be fully responsible for an initial Phase 2 study evaluating NBTXR3 for patients with stage three lung cancer and will have the right to assume control of studies currently led by Nanobiotix. Nanobiotix is eligible for success-based payments of up to $1.8 billion, in the aggregate, relating to potential development, regulatory, and sales milestones. Moreover, the agreement includes a framework for additional success-based potential development and regulatory milestone payments of up to $650 million, in the aggregate, for five new indications that may be developed by Janssen at its sole discretion; and of up to $220 million, in the aggregate, per indication that may be developed by Nanobiotix in alignment with Janssen. Following commercialization, Nanobiotix will also receive tiered double-digit royalties on net sales of NBTXR3. “We expect this agreement, and the collaboration it enables, to further drive the expansion of NBTXR3 development and accelerate the realization of its promise for patients in need,” said Bart van Rhijn, Nanobiotix chief financial officer. “We look forward to maximizing the value of NBTXR3 for our global stakeholders.” Separately, Nanobiotix is eligible to receive up to $30 million in equity investments from Johnson & Johnson Innovation – JJDC, Inc. (“JJDC”) including, as part of capital increases without preferential subscription rights: (1) an initial tranche equal to the lower of 5% of the Company and $5 million; and (2) a second tranche of $25 million subject to certain maximum ownership caps in connection with a future financing. The price of the initial tranche will be equal to $5.21 per American Depositary Share (“ADS”) if that price (1) is approved by Nanobiotix shareholders or (2) exceeds 85% of the volume-weighted average price (“VWAP”) of Nanobiotix ordinary shares on Euronext: Paris for three consecutive trading days, starting with the fourth trading day after the date of agreement, in each case if occurring within the ninety trading days following the date f the agreement. Also, JJDC may elect any time during that ninety-trading day period to instead consummate the initial tranche at a price per ADS equal to 85% of the VWAP of Nanobiotix ordinary shares on Euronext for three consecutive trading days starting with the fourth trading day after the date of the agreement. The second, $25 million tranche is conditioned upon, and at the same price as, a concurrent Nanobiotix financing with gross proceeds of at least $25 million (excluding the potential investment by JJDC) occurring prior to certain long-term development milestones or December 31, 2027, at the latest. For illustrative purposes only1, in the event that the initial tranche is implemented at $5.21 per ADS, the dilutive impact for shareholders resulting from this capital increase would be 0.97% and JJDC group would own 2.65% of the Company’s share capital. The transaction is subject to customary closing conditions and regulatory clearances including clearance by US antitrust authorities under the Hart-Scott-Rodino Act, and will become effective as soon as these conditions have been met. As of the date the license agreement becomes effective, prior to utilizing the second tranche of equity investment outlined above and excluding near term development milestones, Nanobiotix expects to extend its cash runway into the first quarter of 2024. About NANOBIOTIX Nanobiotix is a late-stage clinical biotechnology company pioneering disruptive, physics-based therapeutic approaches to revolutionize treatment outcomes for millions of patients; supported by people committed to making a difference for humanity. The Company’s philosophy is rooted in the concept of pushing past the boundaries of what is known to expand possibilities for human life. Incorporated in 2003, Nanobiotix is headquartered in Paris, France. The Company also has subsidiaries in Cambridge, Massachusetts (United States), France, Spain, and Germany. Nanobiotix has been listed on Euronext Paris since 2012 and on the Nasdaq Global Select Market in New York City since December 2020.

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