CONFIDENTIAL TREATMENT REQUESTED
BACE RESEARCH COLLABORATION AND LICENSE AGREEMENT
PRELIMINARY RESEARCH PLAN
Preliminary Research Plan BACE Inhibitor Project
The aim of this project is to identify BACE inhibitors which lower amyloid b-peptide (Ab) production in the CNS. Based on experiences and published data with BACE or gamma-secretase inhibitors, we expect that in an acute study design an Ab reduction in the **** should be of therapeutic benefit. In APP-transgenic animal models, this is measured as a reduction of the amyloid plaque load in chronic prevention studies.
The high-level work plan shown in the schematic below will be continuously updated in the course of the project, continuously integrating the progress made. The project team will be responsible for data review and prioritization of program activities on a weekly basis.
The intent of the defined labor allocation is to tailor current lead optimization strategies to the actual status of the respective compound series. Both parties will continue the optimization of the current two lead series identified at Vitae and will position the back-up classes accordingly. Timing and location of co-crystallisation (and soaking) work will be agreed between the parties. **** The compounds will additionally be profiled in vitro with regard to their potency on the enzyme level, for which a BACE assay is available at BI. Another enzymatic assay that could ideally be used at both sites is currently developed by BI (availability not yet confirmed). Representative compounds will be tested at BI for their potency on primary neurons (BI assay format). All in vivo pharmacology studies will be performed at BI. **** These optimization parameters are reflected in the DDS profiling scheme. DDS profiling is foreseen to be primarily conducted at BI. In general, decision-relevant in vitro PK assays will precede the in vivo PK studies. Due to the time-consuming prevention study in the transgenic mice (7-8 months), we expect that if the acute efficacy of the compound plus the other criteria for SoPD is reached this study will be initiated during the candidate selection phase, i.e. not be done before SoPD, but before SoD.
A more detailed work flow will be discussed by the parties after signing the collaboration agreement.
****CERTAIN INFORMATION HAS BEEN OMITTED AND FILED SEPARATELY WITH THE COMMISSION. CONFIDENTIAL TREATMENT HAS BEEN REQUESTED WITH RESPECT TO THE OMITTED PORTION.