Promising lead molecules identified in the Hit-to-Lead step, that had already have acceptable PK properties and demonstrated hint of efficacy in-vivo, are further optimized to a preclinical candidate suitable for clinical assessment in human patients.
In order that a successful lead optimization is achieved, the following parameters are measured/tested in an effort that adds on to the already existing Lead criteria.
- Ex-vivo and/or in-vivo studies that include understanding of the PK-PD relationship displayed by the lead compounds
- Identification of a potential clinical PD biomarker
- Demonstration of efficacy in a disease-relevant animal model including a time-course study
- Initiation and filing of patent applications relevant to the composition of matter
- In-vitro toxicity studies
- Physicochemical chatacterization and formulation development
Some highlights of Aragen-IDD’s lead optimization infrastructure –
- Digital workplace options (Torx platform): Solutions offered via the DMTA process in a lively, transparent, interactive and collaborative work model. This enables efficient SAR of the optimized lead series, scientific strategy and priotized solutions during the process of Lead Optimization.
- Data generation: Rapid and robust in-vitro data generation of top-tier data and mechanistic assays in two weeks’ time to drive selection of compounds into in-vivo PK and beyond.
- Innovation & Expertise: Integrating wealth of scientific expertise from experienced scientists with the use of ML- & AI-generated models based on Aragen’s proprietary internal fingerprints database generated from literature and vendor databases to deliver innovative solutions.
- Track record: Aragen has delivered over 20 high-quality clinical candidates for our collaborators and partners over the last decade.
- Route development, Formulation expertise & Scale-up: Aragen’s Chemical development expertise together with the Formulation team provides large-scale APIs for studies in GLP or non-GLP safety assessment batches. Both chemical development and formulation team are integrated in the lead optimisation stage to identify early and robust process chemistry solutions before nomination of development candidate. Chemical development team formulation expertise not only accelerates entry into key in-vivo efficacy studies but also expedites the selection and delivery of drug products for initial clinical trial supply in GMP synthesis.
