contract Manufacturing Organization BIOTECH Development London 23 rd September 15

3P OBJECTIVES TECH TRANSFER OF A TANDEM CORE PROTEIN PRODUCTION PROCESS NON- GMP PRODUCTION FOR PRECLINICAL STUDIES GMP PRODUCTION FOR PHASE I CLINICAL STUDIES

3 Documentary tech transfer to 3P Final RCB, characterized (P. pastoris) Final developped Bioprocess: USP and DSP Analytical methods fully developed for IPCs and API analysis (final SOPs). MTA Tech transfer run at sending facility  30L Tech transfer run at 3P  10L Comparability studies TECH TRANSFER TO 3P

4 TIMELINES: Analytical Methods Transference: 16/06/2015 – 13/11/2015 X RCB transference: 24/08/ /09/2015 Tech Transfer at 3P: 30/11/ /02/2015 STATUS: RCB is already at 3P facility. Documentation provided is OK USP: finalized protocol that is being tested at UCL DPS: will be test next week with IQUR. Analytical Methods: pending information (Final Analytics techniques and SOPs)

PHASES: Scale-UP to 100L Non GMP 100L Batch (1 X Engineering Run) NON- GMP PRODUCTION FOR PRECLINICAL STUDIES TIMELINES: Scale Up: 15/02/2016 – 25/03/2016 Engineering Batch: 04/04/ /05/2016

PHASES: Generation and characterization of MCB and WCB Validation of analytical Methods for phase I (ICH Q2) GMP production of API DP release GMP PRODUCTION FOR CLINICAL STUDIES TIMELINES: Analytical Validation: Depends on Analytical Transference 01/09/ /02/2016 MCB/WCB: 14/11/2015– 25/03/2016 (including the final characterization) GMP Batch: 30/05/ /07/2016 Final release: 15/07/2016

Polígono Mocholí, c/ Mocholí nº Noáin (NAVARRA) SPAIN T F AV_V4