Karelle Menochet

Since 2012, my career at UCB has evolved from a DMPK representative on NCE projects whilst also head of the in vivo ADME group, to a biomarker lead developing translational strategy for an asset in early development. Thanks to my strong modelling background, I was able to transition to a non-clinical PKPD lead role on NCE and NBE projects. With UCB’s entry into the world of Gene Therapy, I led the development of the integrated Development Science strategy with my counterparts from the toxicology and bioanalysis. I took the head of the Non-Clinical PKPD group in January 2021, leading the implementation of the “Quantitative Pharmacology plan” initiative across UCB portfolio to harness the benefit of MID3 from target identification to FIH and deliver candidates with added benefits over the competition at their time of launch. Head of Non-Clinical PKPD • Provide non-clinical PK-PD strategy for all UCB assets (NCE, NBE, Gene Therapy, TPD, Novel modalities), from a target pre-portfolio perspective through to FIH. • Assess and drive the non-clinical package to progress assets to FIH, working closely with toxicology and bioanalysis. • Act as scientific reviewer of functional contributions to reports and regulatory documents. • Ensure growth and personal development of team members from Associate Scientists to Directors. • Manage resources to ensure appropriate support to the discovery portfolio through key collaborations with external vendors. PKPD lead • Leading the PKPD strategy of NBE and gene therapy projects from target identification to FIH • Development of the concept of Quantitative Pharmacology Plan to be applied to all non-clinical projects

Developing the quantitative pharmacology strategy to drive New Therapeutic Modalities projects through drug discovery and development.

PKPD lead • Leading the PKPD strategy of NBE and gene therapy projects from target identification to FIH • Development of the concept of Quantitative Pharmacology Plan to be applied to all non-clinical projects Biomarker sub-team leader • Leading a cross-functional team of scientists to deliver an appropriate biomarker strategy to expedite the clinical development of a UCB asset • Initiation of collaborations with various KOLs to ensure access to relevant human samples to characterise potential biomarkers, managing a budget of ~£2,000,000 • Ensuring appropriate resourcing of the sub-team activities for a timely delivery of relevant biomarker assays • Contribution to FIH protocol development and acceptance by internal governance bodies

DMPK rep on NCE discovery projects • Leading the DMPK strategy leading to the delivery of 3 candidates to full development • Management of DMPK strategy and resources for a large multi-company discovery project. • Sole representative of the DMPK function at the Chemistry Joint Steering Committee for this project Head of in vivo ADME • Leading a group of two scientists to deliver tailored in vivo solutions to answer ADME questions Subject matter expert • Definition of UCB transporter strategy in collaboration with Hugues Chanteux • Contributor to various working groups that delivered UCB wide strategies (human PK prediction, DDI)

Role of uptake transporters in the prediction of hepatic clearance

Discovery DMPK • Strategic and hands-on in vitro, in vivo and bioanalytical support to lead optimisation projects resulting in the nomination of 6 candidates to full development • Development of an in silico model to predict renal clearance of acids in dogs

In vitro Drug Metabolism • Design of in vitro metabolism studies in collaboration with European and Japanese sponsors to support regulatory submissions to health authorities • Assessment of the phase 1 and phase 2 metabolism of NCEs using animal and human microsomes and hepatocytes.

Discovery DMPK • Elucidation of the transporter involvement in the disposition of candidate drugs • Investigation of pharmacokinetics and brain delivery of gabapentin in rat using a brain microdialysis technique

Discovery DMPK

Mechanistic modelling of active uptake in in vitro systems: Impact on the prediction of hepatic clearance Supervisors: Dr A. Galetin, Prof. JB Houston, Dr K. Kenworthy