New Approach Methodologies (NAMs)
New Approach Methods, or NAMs, are in vitro and in silico screening methods developed and validated to help assess toxicity risk associated with chemicals. The goal of developing NAMs is to support the reduction, replacement and refinement of animal use (3Rs) in chemical toxicity risk assessment.
Do the screening services provided by AsedaSciences fall under the definition of NAMs?
Yes, the screening services provided by AsedaSciences and our partners are designed to help predict potential toxicity risk of chemicals earlier in R&D without the use of animals, and thus fall under the definition of NAMs. We use a range of cell-based screens and analytical measurements designed to help predict toxicity risk and improve the selection, prioritization and progression of safer compounds to support 3Rs initiatives.
What types of NAM screening services do you offer?
AsedaSciences, and our partners, offer a suite of validated NAM screening services. The SYSTEMETRIC® Cell Health Screen is a standardized, highly validated, multiparametric flow cytometry-based screen that uses integrated biological fingerprinting and machine learning (ML) to predict acute toxicity risk for new compounds. The ZBEscreen is a zebrafish embryo screen that measures the effect of chemicals across multiple acute and developmental neurotoxicity endpoints at the organ and behavioral level. Biomimetics uses highly validated HPLC based methods to assess properties of a chemical, such as lipophilicity, human protein binding and phospholipid binding which can be indicators of in vivo distribution and a variety of properties that could lead to toxicity. AsedaSciences will continue to expand the range of screens available.
What is biological fingerprinting?
The biological fingerprint of a chemical can be defined as a set of biological signals or features, measured using a standardized method, that when combined, represent its biological effect or fingerprint. When these signals or features are measured using a standardized approach for large numbers of chemicals, the resulting biological fingerprints can be used as a means to compare differences and similarities of their biological effect – both desired (e.g. therapeutic effect) or undesired (e.g. toxic effect). In the case of the AsedaSciences SYSTEMETRIC Cell Health Screen, the biological fingerprints represent the acute cellular stress, or acute toxic effect, of a compound based on measuring 12 parameters of acute cellular stress, across 10 concentrations (100 uM down to 5 nM) of a compound, measuring ten thousand cells individually per concentration. These biological fingerprints for a new compound are then used by our ML algorithms for comparison to a training set of fingerprints from withdrawn and discontinued drugs, known toxins and on-market therapeutics. Based on similarity to fingerprints for known human toxins in our training set, a risk probability of a new compound being acutely toxic in humans can be generated.
Are you open to partnering for increasing your menu of products and services?
Absolutely. We encourage commercial and academic developers of synergistic NAMs, software applications and screening services to reach out to us if they would like to take advantage of the 3RnD platform. We will work with NAM developers to support validation efforts and generate new software applications where needed to provide additional revenue streams. We would like to encourage anyone who feels they have synergy with the tools and services we are providing through 3RnD to reach out to us – we are eager to discuss ways to work together
What types of compounds are included in your chemical and fingerprint library?
The chemical library screened by AsedaSciences consists of 3,000 chemicals across diverse chemical space, classes, targets, mechanisms, status, industries and market segments. For pharmaceuticals, we have compounds across hundreds of targets, mechanisms and diseases as well as on-market, discontinued and withdrawn drugs. We also have screened a diverse set of agricultural and industrial chemicals across various chemical classes and market segments. Our goal is to continue to expand the broad fingerprint library available for comparison by screening diverse compound sets from across all industry segments.
What additional information is available for the compounds you have screened?
All of the compounds screened by AsedaSciences have a “Details” page where annotations are provided based on manual curation of publicly available information (e.g. drug labels) and scientific literature. These annotations are summarized succinctly to provide information that is valuable when conducting nearest neighbor comparisons to support compound selection decisions. Information such as physical chemical properties, target, disease, ADME properties, toxicity information, status and market segments are examples of some of the categories provided. Our approach is focused on providing the key information required for rapid decision making.
Where can we find more information about the various screening methods you provide?
When you register and log in to 3RnD, you will arrive at the “Welcome” page. This contains a series of tiles representing the various features, tools and services that are available. There is a feature titled “Our Biology” which provides a menu containing all of the various screening services provided and a technical description of the method, the biological parameters measured, explanations of normal and abnormal results, analytical approaches and interpretation guides. Descriptions are again designed to be succinct, coupled with illustrations that provide a visual guide of normal versus abnormal for the various biological features measured.
How can we compare our compounds to the compounds in your fingerprint library?
AsedaSciences has implemented cutting edge visualization into 3RnD and there are various ways to compare your own compounds to those screened by AsedaSciences and our Partners. In the Compound Universe, you can visualize and compare your own compounds to those we have screened based on chemical structure or based off the biological fingerprint if your compounds have been run through the same screens. You can also group your compounds or SAR series with compounds from our library by creating “Favorites”, allowing you to create a range of Favorites that can represent chemical series, classes or properties of your choice. Nearest neighbor analysis based on fingerprint or chemical structure similarity is simple and intuitive and provides tremendous potential for accelerating decisions on compound selection, prioritization and progression
Will you be adding more screens to your menu in the future?
Yes, we plan to expand the range of screens available, including new multi-parameter adverse outcome pathway screens based on the same platform developed by AsedaSciences. This will focus on different classes of toxicity. We will also be validating and integrating additional screens from current and new Partners, both commercial and academic