Biotechnology and Translational Medicine

• Published in: Clinical and translational science Vol. 9; no. 3; pp. 125 - 127
• Main Author: Morrison, BW
• Format: Journal Article
• Language: English
• Published: United States John Wiley & Sons, Inc 01-06-2016; John Wiley and Sons Inc
• Subjects: 1-Phosphatidylinositol 3-kinase; Bioavailability; Biomarkers; Biotechnology; Biotechnology industry; CD19 antigen; CD3 antigen; Chronic lymphocytic leukemia; Clinical Trials as Topic; Drug Industry; FDA approval; Gene therapy; Genotoxicity; Gout; Humans; Leukemia; Liability; Lymphatic leukemia; Lymphoma; Metabolites; Oncolysis; Patients; Pharmaceutical industry; Pharmacodynamics; Ribonucleic acid; RNA; RNA viruses; Safety margins; Science; Subsidiaries; Success; Translational Medical Research; Viruses
• ISSN: 1752-8054; 1752-8062
• DOI: 10.1111/cts.12392

[...]the POC science for lesinurad, a URAT1 inhibitor for the treatment of gout (whose approval was granted to AstraZeneca) was conducted by Ardea Bioscience prior to the AstraZeneca acquisition ; the POC science for blinatumomab, a bispecific anti‐CD3/anti‐CD19 for the treatment of acute lymphoblastic lymphoma (ALL) (whose approval was granted to Amgen) was done by Micromet prior to the Amgen acquisition ; and idelalisib, a PI3K inhibitor for treatment of chronic lymphocytic leukemia (CLL) and other related malignancies (whose approval was granted to Gilead) was already in phase II studies conducted by Calistoga at the time of the Gilead acquisition. [...]a number of large pharmaceutical companies create separate subsidiaries from the small biotech companies that they acquire and the POC science is conducted by scientists from the acquired company (e.g., the Imclone subsidiary of Lilly and the Millennium subsidiary of Takeda). [...]it would appear that upwards of 40% of the POC science done for recently approved products is done by small companies. The 5 R framework RIGHT TARGET Strong link between target and disease Differentiated efficacy Available and predictive biomarkers RIGHT TISSUE Adequate bioavailability and tissue exposure Definition of pharmacodynamic (PD) biomarkers Clear understanding of preclinical and clinical pharmacokinetic and pharmacodynamics Understanding of drug–drug interactions RIGHT SAFETY Differentiated and clear safety margins Understanding of secondary pharmacologic risk Understanding of reactive metabolites, genotoxicity, drug–drug interactions Understanding of target liability RIGHT PATIENTS Identification of the most responsive patient population Definition of risk–benefit for a given population RIGHT COMMERCIAL POTENTIAL Differentiated value proposition against future standard of care Focus on market access, payer, and provider Personalized healthcare strategy, including diagnostic and biomarkers What are the implications of the analyses of Morgan et al. and Cook et al. for biotech companies? [...]as we move into novel modes of therapeutics—such as cell therapies, nanotechnologies, oncolytic viruses, RNA therapies, gene therapies, and regenerative therapies—we do not have a large portfolio of programs to analyze.