Integrated Drug Discovery

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STRUCTURE ACTIVITY RELATIONSHIP TO CANDIDATE NOMINATION

 

Once lead compounds have been identified Beacon will initiate lead optimization with the goal of advancing a pre-clinical candidate into development. 

Lead Optimization

 

Beacon will utilize internal and external resources to conduct typical activities during this phase including:

1. Extensive medicinal chemistry to elaborate lead series, with continued in vitro profiling to assess potency      and selectivity as defined by the target product profile 
2. Assessment of physicochemical properties suitable for intended administration route and dosage form
3. Optimization of pharmacokinetic and metabolic properties of the lead series, in an approved formulation        and via the proposed route of administration, avoiding active metabolites if possible
4. Ongoing pharmacological testing via the intended route of administration in relevant animal                              species/models in-vivo with clearly demonstrated PK/PD relationship 
5. Ensuring absence of overt genotoxicity, CYP inhibition, and hERG liability
6. Demonstration of sufficient exposure needed for pharmacological and toxicological studies
7. Initiation of Chemical and Analytical R&D activities at least six months prior to candidate nomination in            order to identify an initial safe scalable route to the lead compound.

 
 

Pre-clinical Candidate Criteria
 

  • Repeated dose pharmacology studies carried out in relevant animal species/models with clear PK/PD relationship

  • Early safety evaluation including in vitro mutagenicity and chromosome damage studies completed with no reported liabilities

  • Completed non-GLP rat single ascending dose and repeat-dose range finder tox studies 
    No liabilities in CNS safety assessment (Modified Irwin)

  • No Cardiovascular liabilities in vitro (hERG) or in vivo (Telemetry)

  • Acute, single oral dose ascending study to establish the Maximum Tolerated Dose (MTD) in a higher species

  • Established the presence of a physically stable form which meets Pharmaceutical Sciences X-testing criteria

  • Drug-drug interactions in terms of CYP inhibition and/or induction

  • Putative metabolites of the candidate should be identified where possible. On and off-target activity (e.g. hERG, Ames etc.) of major metabolites should be measured

  • Protein binding potential should be established in multiple species 

  • PK characteristics should be evaluated in at least one higher species to assist with the selection of species for safety evaluation

  • The predicted dose in man should be estimated. 

 

© 2017 Beacon Discovery

6118 Nancy Ridge Dr, San Diego 92121

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