Businesswire | June 26, 2023
Enveda Biosciences, a biotechnology company discovering new medicines from natural sources, released the details of one of its foundational AI models, MS2Mol, in a pre-print posted on ChemRxiv. MS2Mol is designed to predict the structure of metabolites, which are the building blocks and breakdown products of the cell. Despite their essential role in all cell processes, it is estimated that less than 1% of all naturally-occurring metabolites are known to science. The ability of MS2Mol to rapidly predict the structure of previously uncharacterized metabolites without lengthy laboratory experimentation enables their prioritization as potential drug candidates and expands our knowledge of the natural world.
“Metabolites have a long and successful history as the basis for impactful drugs including aspirin, taxol, metformin, artemisinin, and statins. This is particularly impressive given that we, as scientists, have barely scratched the surface of natural metabolite diversity. With MS2Mol integrated into our platform, we can tap evolutionary chemical intelligence for the next generation of powerful medicines at scale,” said Viswa Colluru, Ph.D., founder and CEO of Enveda.
Enveda’s proprietary platform solves the long-standing obstacles in natural product drug development including active molecule identification, property and structure prioritization, amenability to medicinal chemistry, and large-scale material access. The company recently closed its Series B1 round and will progress multiple platform-derived molecules to the clinic in 2023 and 2024 across inflammation, fibrosis, and neurosensory indications.
“Metabolite identification used to be a process that was time-consuming, prone to failure, and required highly specialized expertise. MS2Mol takes the most easily accessible – but extremely cryptic – form of data on metabolites, the mass spectrum, and translates it into a language that scientists can use: the chemical structure. Solving this translation problem with AI puts the most useful information in the hands of drug hunters at massive scale,” said David Healey, Ph.D., VP of Data Science at Enveda and senior author of the pre-print.
“While other companies use AI to predict what you want to buy, we use AI to discover what humanity needs to know,” said Tom Butler, Ph.D., VP of Machine Learning at Enveda and first author of pre-print.
“Unlocking bioactive chemistry honed by billions of years of evolution for modern drug discovery has led us to discover a slate of exciting candidate medicines at a remarkable pace,” said Sotirios Karathanasis, Ph.D., CSO at Enveda. “We look forward to modification of disease pathophysiology by our medicines in the clinic and redefinition of the concept of target undruggability with the Enveda platform.”
With the creation of MS2Mol, Enveda continues to deliver field-changing technology for the discovery and utilization of natural metabolites to drive novel therapeutic development.
About Enveda Biosciences
Enveda Biosciences is a biotechnology company building the first high-resolution chemical map of the natural world to tackle the toughest problems in drug discovery. Enveda’s platform is the world’s most advanced drug discovery search engine from the expanse of nature’s unknown chemistry, building on years of cutting-edge advancements at the intersection of metabolomics and machine learning. Complementing its breakthrough technology, Enveda’s team includes seasoned drug hunters with decades of experience in the pharmaceutical industry working with preeminent data scientists.
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.
Businesswire | August 03, 2023
A new study demonstrates how the combination of DNA-encoded libraries (DELs) and NanoBRET Target Engagement technology can accelerate early-stage drug discovery. Reported in Cell Chemical Biology, researchers from Promega Corporation and WuXi AppTec generated new chemical probes from molecules identified through a DEL screen. This research opens new opportunities to develop novel NanoBRET Target Engagement Assays aimed at many understudied classes of proteins, rapidly accelerating “hit to lead” efforts in identifying new potential therapeutics.
Generating Novel Chemical Probes from DELs
DELs are increasingly popular tools used to rapidly screen billions of molecules for early-stage drug discovery. Each molecule is tagged with a short DNA “barcode” that can be used to identify those that successfully bind to a given target. In the Cell Chemical Biology paper, scientists from Promega and WuXi AppTec aimed to develop new chemical probes using molecules selected from these massive pools. These probes would be used in a NanoBRET Target Engagement Assay, a tool for studying the interaction between a chemical compound and its target protein in live cells.
The authors screened 16.8 billion compounds from WuXi AppTec’s 41 established DELs against aurora kinase A, a protein implicated in the invasive growth of certain cancers. They identified two representative “hits” that bound to the target and developed a method to replace the DNA barcode of each “hit” with a fluorophore. The fluorophore is responsible for the light signal generated in a NanoBRET assay in live human cells. The team found that this new probe could be used effectively to characterize novel inhibitors targeting aurora kinase A, providing critical engagement characteristics such as affinity, selectivity and cellular permeability.
“It was very clever of the authors to appreciate that the DEL read-out not only identified a chemical binder for a protein, but also a place to attach a tracer,” says Aled Edwards, Chief Executive of the Structural Genomics Consortium, a public-private partnership that develops open-access chemical probes to support drug discovery and development. “One can only imagine what could be if there were DEL hits for all human proteins.”
Accelerating Drug Discovery
The authors demonstrate that DELs can benefit chemical biologists who require verification of live cell target engagement for their protein of interest. This is particularly beneficial for understudied protein classes that may not have existing chemical probes. Additionally, they note that the NanoBRET assays help drug discovery researchers accelerate their workflow by providing data used to identify the most promising leads.
They conclude, “Our findings support that DEL-derived BRET probes facilitate prioritization of not only the chemical matter identified from the DEL but may also serve as general live-cell screening tools for surveying broader chemotypic diversity at the target of interest.”
Read the open access paper, “DELs enable the development of BRET probes for target engagement studies in cells”.
About Promega Corporation
Promega Corporation is a leader in providing innovative solutions and technical support to the life sciences industry. The company’s portfolio of over 4,000 products supports a range of life science work across areas such as cell biology; DNA, RNA and protein analysis; drug development; human identification and molecular diagnostics. These tools and technologies have grown in their application over the last 45 years and are used today by scientists and technicians in labs for academic and government research, forensics, pharmaceuticals, clinical diagnostics and agricultural and environmental testing. Promega is headquartered in Madison, WI, USA with branches in 16 countries and over 50 global distributors.