S T R A T E G Y
EDI has adopted a “market-back science-forward” strategy to the selection and progression of its drug candidates. Successful programs will ideally have demonstrated through novelty and innovation, the potential to address a clear un-met medical need with the prospect to discover and develop highly differentiated and commercially attractive products.
P R O C E S S
Programs successful in the EDI selection process will be provided access to capital and specific scientific/technical expertise from EDI’s SAB to advance a program to defined decision (go/no-go) milestones. This process will involve the development of a specific work-plan with clear objectives, together with an associated budget to support the agreed development activities.
Programs successful in the EDI selection process will be provided access to capital together with and specific scientific & /technical expertise from EDI’s SAB and consultants to advance programs to defined decision (go/no-go) milestones. Following successful project selection, EDI will develop a detailed project specific work-plan and budget with the investigator and the SAB. Funding will be provided to support the project specific objectives and milestones defined in the work-plan. EDI funding will be applied to the direct support of the program. It is envisioned that certain aspects of the work will be required to be conducted within an investigator’s laboratory. However, many aspects of the development program will require collaboration and engagement with Contract Research Organizations (CRO’s). These activities will be planned, outsourced and managed by EDI.
S T A G E S O F S U P P O R T
Stage 1: Discovery Biology
• Programs at the discovery biology stage will typically be too early for EDI support
• EDI staff will be happy to meet with investigators at this stage to discuss future applications
Stage 2: Target to Hit
• Minimum entry level; requirements include:
• Demonstration of a novel (ideally validated) target or pathway relevant to human disease
• Identification of a probe molecule (or initial proof of concept in e.g. knock-in/knock-out model)
• Hit ID through e.g. High Throughput-Screening (HTS), fragment screen, focused screen, virtual screen, NMR screen, structure aided drug design
• A “Hit” is defined as a compound with the desired activity in a screen that is confirmed on re-testing
• Patent application made or granted or unpublished composition of matter ready for patent application
Stage 3: Hit to Lead
• Refinement of Hit series; establish “Structure-Activity Relationships” (SAR)
• Introduction of “drug-like properties” (solubility, lipophilicity / permeability)
• Improved potency/selectivity in vitro
• Initial Pharmacokinetic (PK) profile
• Initial demonstration of efficacy in vivo
Stage 4: Lead Optimization
• Conduct Lead Optimization by maintaining/increasing efficacy of analogues while improving deficiencies
• Minimize/eliminate e.g. hERG, CYP, transporter liabilities
• Minimize/eliminate “off-target” binding e.g. screen against panel of pharmacologically important receptors & enzymes
• Improve stability & ability to formulate
• Establish Pharmacokinetic/Pharmacodynamic (PK/PD) relationships
• Improve PK and metabolic profile (ADME studies)
Stage 5: Pre-Clinical (IND Enabling) Regulatory Studies for Human Clinical Trials
• Develop analytical methods for drug substance/drug product, stability testing and impurities (establish release criteria)
• Scale up chemistry for Toxicology batch and cGMP synthesis
• Develop and validate bioanalytical methods for PK studies
• Develop biomarker assays for assessing efficacy outcomes and for PK/PD studies
• Conduct GLP toxicology (rodent & non-rodent); Single & multiple dose Toxicology and Toxicokinetic analysis
• Conduct in vitro clinical pharmacology/drug-drug interaction studies (test CYPs & transporters)
• Develop suitable formulation for Phase 1 trials
• Select & test container/closures & develop drug packaging/labeling
• Prepare Phase 1 trial plan & clinical protocol
• Prepare regulatory strategy and write IND sections FDA submission
• Prepare pre-IND meeting package & questions (conduct Pre-IND meeting)
• Submit IND to FDA for regulatory review
It is anticipated to take approximately 5 years to advance a molecule from Stage 2 (Target to Hit) to Stage 5 (Pre-Clinical Development) with the completion of IND-enabling regulatory studies to facilitate clinical testing.
E X A M P L E S O F S U P P O R T
Small Molecule Drug Discovery & Development
Typically, small molecule drug development programs will require comprehensive medicinal chemistry support through the process from “hit to lead” to “development candidate”. This will be accomplished through the engagement of consultants and contract research organizations (CROs) with e.g. high-throughput screening capabilities, advanced computational drug design capabilities and access to diverse compound libraries to serve as the starting point for the development and optimization of a new compound series.
EDI will also provide support for activities such as, assay development, in vitro and in vivo testing, formulation development, drug metabolism and PK, toxicology, drug substance and drug product scale-up/manufacture and regulatory affairs support as needed. EDI has identified and will contract with a number of strategic partners for these specialized pharmaceutical development services.
EDI’s SAB will also provide expert support to assist the discovery and development of biologic-based therapeutics, as well as gene-therapy, oligonucleotide and cell-based approaches as these opportunities are identified.