Wolfe Laboratories - ADME and CMC

>	CASE STUDY 1 Parenteral dosage form development of a highly insoluble molecule
>	CASE STUDY 2 Salt form optimization and lyophilized parenteral formulation development
>	CASE STUDY 3 Oral liquid formulation development
>	CASE STUDY 4 Accelerated stability studies to support a screening IND
>	CASE STUDY 5 Lead Optimization: Solubility and formulation screen for efficacy and PK studies

Integrated ADME and CMC Technology Platform

At Wolfe Laboratories, we believe that integration of critical path drug development activities allows us to help our clients rapidly advance de-risked molecules from discovery into the clinic. ADME, CMC, and Drug Product Manufacturing are essential drug development functions that, if done right, can form the foundation of a highly effective program. Many companies treat these critical path activities as items to be checked off a list, rather than using them strategically to de-risk their drug discovery and development programs.

Effective drug development requires not only a molecule that has high biological activity, but one that has the “drug-like” properties and is stable, safe, and able to reach its biological target. Many compounds lack these properties and yet are advanced into the clinic, requiring heroic drug development efforts. Some of these compounds ultimately are approved, but many of them fail during clinical trials, driving up the overall cost of drug development. Since discovery and development research paradigms that include an assessment of the “drug-like” properties are more effective at producing high quality drugs, we consider advancement of molecules that lack these properties to be a waste of precious resources.

Wolfe Laboratories has built an integrated ADME and CMC technology platform over its ten year existence to address these issues. Initially working in the analytical and formulation space, we have expanded our technology offerings to include ADME services and QA programs so that we are able to provide our clients with integrated early-stage drug development, facilitating rapid advancement of high quality molecules into the clinic. Our clients leverage the knowledge gained to de-risk their compounds with respect to metabolic or physicochemical liabilities. Upon candidate nomination, our seamless development programs are augmented by our GLP bioanalysis and cGMP analysis.

During discovery and candidate nomination, our technology allows our clients to understand the pertinent factors that could impact the success of their programs. Depending upon the administration route, these factors may be physicochemical and/or biological. Orally delivered molecules require that the molecule be sufficiently soluble, permeable and metabolically stable in order to achieve sufficient systemic exposure. Elucidation of exposure-limiting mechanisms, many of which intersect at the CMC-ADME interface, allow us to systematically and rationally inform candidate nomination on behalf of our clients who are in discovery. Molecules delivered by routes other than orally typically have similar challenges, although first-pass metabolism is not a factor.

For clients that begin to work with Wolfe Laboratories after they have already nominated their candidate molecule, our technology yields a mechanistic appreciation of the strengths and limitations of the candidate molecule. This allows to rapidly advance the molecule through preclinical and clinical milestones by the development of an optimal form and formulation, determination of metabolic and clearance pathways, and through the provision of the GLP and cGMP support that is essential in early stage development. Specifically, our technology platform evaluates the solid state properties, formulation options, and absorption characteristics to yield enhanced exposure.

Wolfe Laboratories’ ten year track record in the development of parenteral formulations for many administration routes supports preclinical development through commercialization. In recognition of our contributions to the advancement of many early stage programs for biopharmaceutical companies, we recently were awarded Accelerator Funds from the Massachusetts Life Science Center, which is being used to build a cGMP aseptic processing facility that will support early clinical trials. It is anticipated that this facility will be available in 2010-2011.

In the case studies that follow, we have provided a brief description of how we have helped our clients discover and develop experimental therapeutics that have the potential to improve human health as well as return increased value to their investors. View WLI case studies.