Computational predictive toxicology and mechanism of action investigation
Harmonic Pharma has developed computational solutions that combine computational predictive toxicology and mechanism of action investigation.
Many compounds currently in development will never make it to market because of toxicity issues related to regulatory tightening. Using computational tools to drive decision-making process can help increase probability to move compound to the next phase of development. Thanks to its technology – Compound Toxicity Profile (CTP) and Rediscovery Platform®, Harmonic Pharma supports its customers by generating important insights during the R&D stage and focusing on the most promising compounds to be further investigated. Implementing the predictive tools in product development process is a profitable solution to optimize time, cost and reduce risk to reach the market.
1. Compound toxicity profiling
Compound Toxicity Profile (CTP) is part of the toxicological investigation service and consists of Quantitative Structure Activity Relationship (QSAR) based statistical models of toxicity that generate profiles for chemicals and subsequent toxicity alerts in diverse areas:
- Endocrine disruption
- Persistent-Bioaccumulative Toxicity (PBT)
- Skin sensitization
Harmonic Pharma addresses the needs of clients, by providing a rationale to support decision-making processes:
- Generate toxicity alerts: QSAR based statistical models are trained to recognize compounds with a toxicity issue linked to structural descriptors
- Prioritize the most promising compounds at an early stage by discarding chemicals with toxicity bottlenecks
- Substitute compounds for more compliant ones: models can also be used to select a safer compound in a more advanced development stage
2. Compound polypharmacology profiling
Over the years, the Rediscovery Platform® has evolved continuously to address the needs of clients in a variety of applications including:
- Drug repurposing: the platform is suitable for providing a biological rationale for new therapeutic applications of drugs and/or drug candidates
- Target(s) identification: the platform enables the profiling of a chemical with the ensemble of associated targets (polypharmacology profile) allowing to identify potential novel targets to be further assessed.
- Target deconvolution following phenotypic screening: the platform helps identify targets and clues for deciphering the mechanism of action of hits
- Adding scientific objective criteria about natural extracts: following the characterization of the molecular content of a natural extract, the technology is offering solutions to decipher associated biological targets and subsequent applications
- Off-targets responsible for toxicity: the platform is used to generate an alert regarding newly identified biological targets linked to toxic events
- Substitution of potential toxic compounds: the in silico screening and profiling platform provides clues to choose a safer compound with regard to an unwanted toxicity profile
Harmonic Pharma is part of the Seqens’Lab ecosystem located near Paris (center of excellence for Research and Development) and Seqens has supported the development of Harmonic Pharma through a capital increase in 2017. The access to Harmonic Pharma’s technology broadens Seqens’ services offering to its customers
3. Complete compound representation
The compound investigation is proposed through :
- 3D representation of chemicals by visualization through an interactive user-friendly interface
- Hierarchical clustering to select promising subgroups inside a chemical dataset
- Natural Language Processing (NLP) to retrieve information (experimental assessment, doses, toxicity threshold, associated targets, …) from scientific literature.
By characterizing chemicals more comprehensively, Harmonic Pharma provides additional pieces of a rationale for making decisions:
- Visualization tools to help understand complexity
- Classification of chemicals to detect beneficial features
- Gathering data to expand knowledge and regulatory requirement regarding chemicals
Harmonic Pharma is part the Seqens’Lab ecosystem located near Paris (center of excellence for Research and Development) and Seqens has supported the development of Harmonic Pharma through a capital increase in 2017. The access to Harmonic Pharma’s technology broadens Seqens’ services offering to its customers.
Safety by design ® : a new approach to toxicological risk management
In October 2019, in partnership with the laboratory LORIA*, Harmonic Pharma, located in the startup area of Mines Nancy, started the Chemical Range ® program dedicated to toxicological risks. This dual innovation program for civil and military purposes embodies the Safety by design ® approach.