This manuscript was developed with the support of the International Consortium for Innovation and Quality in Pharmaceutical Development (IQ, http://www.iqconsortium.org). IQ is a not-for-profit organization of pharmaceutical and biotechnology companies with a mission of advancing science and technology to augment the capability of member companies to develop transformational solutions that benefit patients, regulators, and the broader research and development community.

The authors would like to take this opportunity to thank numerous scientists and colleagues across their respective companies for dedicated discussions, thoughts, input, and critique which helped to craft this body of work. The following individuals contributed significant efforts in the experimental work, analysis, and conclusions reported within. The authors would like to specifically thank the key contributors from the following companies: AbbVie (Michael Hoffman, Brian Anderson, Laurie Mlinar, Gregory Doddridge, and Hesham Fahmy), Amgen (Yong Xie, Jiemin Bao), AstraZeneca (Catherine Hallam, Vivien McAlpine, Rob Shaw), Boehringer Ingelheim (Annett Keller, Barbara Kühnle, Sarah Barthold, Peter Sctöckel and Shubhajit Paul) BMS (Gary McGeorge, Sherif Badawy, Dong Xiang and Tracy Gaebele), GSK (Daniel Goodwin and David Greenhalgh), Eli Lilly (James Miesle, Pedro J. Paredes and Jacob Smith), Merck (Nathan Pixley), Pfizer (Tim Graul) and Roche (Laura Rolinger and Dominique Kummli).