Oligonucleotide Drugs: Key ADME & DMPK Insights

Recorded: June 2024

This webinar discussed practical experience of conducting ADME/DMPK studies with this class of molecules and specific considerations.

Agenda

• Intro to Oligo Bioanalysis
  • What are the PK properties of Oligos and how can we influence their distribution?​
  • M & E – How are 2nd and 3rd Gen oligos cleared?​
• Radiosynthesis of Oligos
  • What are the options available and considerations needed?​
• ADME of Radiolabelled Oligos
  • Practical considerations for performing radiolabelled non clinical ADME studies – examples provided​

Moderated by:

Chris Bode, Ph.D. – VP of Scientific Affairs at Pharmaron

Speakers

Steve Hood – Senior Scientific Director in Non-Clinical Sciences at GSK

Steve Hood received a PhD in Molecular Toxicology from the University of Surrey in 1993 and joined Glaxo Group Research as an Industrial Post doc in the Molecular Biology department in Greenford where he cloned and expressed CYPs in recombinant cell lines. Steve transferred to GlaxoWellcome at Ware in 1995 and became a manager in the new GSK DMPK Molecular Mechanism and Extrapolation Technology team in 2001. In 2010 Steve seconded to Scinovo and co-ordinated the GSK Oligo delivery (GOLD) project and was also Industrial co-lead of the IMI COMPACT consortium that ran from 2012-17 and evaluated delivery mechanisms for oligos and peptides. After a brief return to DMPK in 2015, Steve joined Bioimaging as a senior Scientific Director, responsible for the external imaging collaborations that are members of the Bioimaging Expertise Network (BEN). As part of this network, Steve was also Co-Director of the GSK Centre for Molecular Imaging (COMI) at the University of Illinois at Urbana Champaign, where he worked closely with Professor Stephen Boppart and his team.

In addition to his “day job”, Steve has spent most of the last 2 decades working on GSK’s diverse oligo portfolio and has supported projects ranging from inhaled SiRNAs, TLR antagonists, DMD exon skippers (Drisapersen) and ASOs for TTR (Innotersen) and HBV with Ionis (Bepirovirsen). More recently Steve has been involved with the Wave collaboration (Wve-006), the Jade HBV siRNA in licence project and the formation of the Boston Oligo hub. In January 2024 Steve rejoined DMPK with the role of Director of Oligo ADME Strategy.

Thomas Gregson​ – Tritium Team Leader at Pharmaron

Tom Gregson graduated from Sheffield University with a Masters in Chemistry and undertook a PhD at the University of Manchester with Professor Jim Thomas in natural product synthesis.  He has worked in radiolabelled synthesis for 20 years at Sanofi-Aventis and Covance before joining Pharmaron at their Cardiff site.  His background has been in carbon-14 synthesis and lately Tritium.  He is currently the Tritium Team Leader.

Stephen Harris​ – Biologics Team Leader at Pharmaron​

Steve has over 35 years’ experience working within DMPK groups, initially at Roche and Pfizer, working mostly on the pre-clinical development of radiolabelled small molecules.  Since joining Pharmaron  in 2010 he has led the group responsible for radiolabelled ADME studies on Biologics, ranging from peptides and nucleic acids to recombinant proteins, mAb’s, fusion proteins and ADC’s.  The primary end point for these studies has often been tissue distribution of radioactivity utilising radiolabelled imaging techniques such as Quantitative Whole Body Autoradiography (QWBA) and microautoradiography of IHC stained tissues.