Silence Therapeutics PLC · NASDAQ:SLN
Silence Therapeutics — Cowen 38th Annual Health Care Conference 2018
22 slides from Silence Therapeutics's conference presentation, Mar 13, 2018
Slide 1: Cowen Healthcare presentation March 13th 2018
Cowen Healthcare presentation March 13th 2018
Slide 2: Disclaimer
Disclaimer The information contained in this presentation is being supplied and communicated to you on a Securities in the Company have not been, and will not be, registered under the United States confidential basis solely for your information and may not be reproduced, further distributed to Secur
Slide 3: Silence Therapeutics - Overview
Silence Therapeutics - Overview > Developing RNA interference (RNAi) therapeutics, a highly innovative, specific, new class of medicines with life-saving potential for patients with serious and rare diseases > Only quoted European RNAi drug development Company > Proprietary platform technology build
Slide 4: Experienced Leadership Team: Strong Background in Discovery & Development of RNA Therapies
Experienced Leadership Team: Strong Background in Discovery & Development of RNA Therapies Ali Mortazavi, Torsten Hoffmann, Ph.D. David Ellam, Chief Executive Officer Chief Operating Officer Chief Financial Officer Since 2012 Since 2017 Since 2016 Dmitry Samarsky, Ph.D. Laura Roca-Alonso, Ph.D. Mich
Slide 5: GalNAc-siRNA Platform Technology
GalNAc-siRNA Platform Technology © Silence Therapeutics 2018 5
Slide 6: GalNAc-siRNA Medicines
GalNAc-siRNA Medicines Schematic structure of our therapeutic molecules: Linker Binds siRNA to delivery moiety Chemical A C G U U C G A C C G A A G U C A modifications U G C A A G C U G G C U U C A G U siRNA GalNAc (N-Acetylgalactosamine) Mediates gene silencing Mediates targeted delivery to hepatoc
Slide 7: Platform Performance
Platform Performance Platform technology: GalNAc-siRNA, able to mediate highly specific gene silencing in hepatocytes (liver) – “Specificity upon specificity” ~7,000 genes operate in the liver. We can target any of them by adapting the siRNA sequence, using the same technology Target 1 Target 2 Targ
Slide 8: Advantageous Properties of Medicines
Advantageous Properties of Medicines > Subcutaneous administration, patient friendly > Long duration of action (variable depending on target gene) > Well tolerated > Our GalNAc-siRNA medicines are suitable for a wide range of indications Target KD induction Trend toward recovery to baseline levels N
Slide 9: SLN124 for the treatment of Iron Overload Disorders
SLN124 for the treatment of Iron Overload Disorders A case study of our platform © Silence Therapeutics 2018 9
Slide 10: Treatment of Iron Overload Disorders (IOD)
Treatment of Ion Overload Disorders (IOD) GOAL > Provide an effective and safe novel treatment option for patients with iron overload conditions, such as β-Thalassemia RATIONALE > Target a key modulator in iron regulation with a GalNAc-siRNA molecule providing a highly specific, effective & safe opt
Slide 11: TMPRSS6 is a Negative Regulator of Hepcidin and Plays a Key Role in Iron Homeostasis
TMPRSS6 is a Negative Regulator of Hepcidin and Plays a Key Role in Iron Homeostasis Normal hepcidin levels control iron release hepcidinlevels, Low hepcidin levels, asβ-Thalassemia as in in β-Thalassemia from cellular stores & intestinal uptake result in high iron levels & overload in organs Liver
Slide 12: siRNA Screen and GalNAc Conjugate Testing in Primary Hepatocytes
siRNA Screen and GalNAc Conjugate Testing in Primary Hepatocytes TMPRSS6 mRNA TMPRSS6 mRNA N o r m a lis e d T M P R S S 6 m R N A 1° Hep (mouse) (in vitro screen – Selected siRNAs) 1 .0 (receptor-mediated uptake) 0 .5 1.5 h Hep3B cells Normalised TMPRSS6 mRNA 0 .0 0 .0 1 0 .1 1 10 100 1000 G a lN A
Slide 13: Silencing TMPRSS6 Lowers Serum Iron Levels in Mice
Silencing TMPRSS6 Lowers Serum Iron Levels in Mice Study design d1 d4 SC, n=4-6 mice TMPRSS6 mRNA (liver) Hepcidin mRNA (liver) Iron (serum) 4 40 N o r m a lis e d T M P R S S 6 m R N A N o r m a lis e d H e p c id in m R N A 1 .0 S e r u m ir o n [µ m o l/L ] 3 30 2 20 0 .5 1 10 0 .0 0 0 10 1 3 1 0
Slide 14: SLN124 Lowers Iron Levels for at Least 6 Weeks After Single Administration in Mice
SLN124 Lowers Iron Levels for at Least 6 Weeks After Single Administration in Mice Study design d1 wk 1 wk 3 wk 6 SC, n=4 mice, 3 mg/kg TMPRSS6 mRNA (liver) Iron (serum) 40 N o r m a lis e d T M P R S S 6 m R N A 1 .0 S e ru m iro n [µ m o l/L ] 30 20 0 .5 10 0 .0 0 1 1 3 6 w eeks 1 1 3 6 weeks PBS
Slide 15: Therapeutic Activity of SLN124 in Iron Overload Model (HFE -/- mice)
Therapeutic Activity of SLN124 in Iron Overload Model (HFE -/- mice) Collaboration with Study design d1 wk 3 Prof. Dr. Martina Muckenthaler University of Heidelberg, Germany SC, n=6-7 mice TMPRSS6 mRNA (liver) Hepcidin (serum) Iron (serum) 2 .0 800 N o r m a lis e d T M P R S S 6 m R N A S e r u m H
Slide 16: SLN124 Normalises ROS Species & Improves RBC Parameters in β-Thalassemia Disease Model
SLN124 Normalises ROS Species & Improves RBC Parameters in β-Thalassemia Disease Model Study design Collaboration with d1 wk 2 wk 5 Prof. J. Vadolas & Dr. Grigoriadis Monash Medical Centre/Melbourne, Australia SC, n=6-8 Hbbth3/+ mice Reactive oxygen species (ROS) Reticulocyte proportion Haematocrit
Slide 17: Feedback by Key Opinion Leaders on SLN124
Feedback by Key Opinion Leaders on SLN124 International KOL workshop with clinical and regulatory experts in the field of iron overload disorders > High medical need to reduce iron overload and number of transfusions in patients > Not met by currently available therapies > SLN124 has the potential t
Slide 18: Market Opportunity of SLN124 (US & Europe)
Market Opportunity of SLN124 (US & Europe) β-Thalassemia intermedia & T. major (TDT) > Combination with transfusions & chelators to reduce frequency & dose 40,000 20,000 > Improve erythropoiesis and TDT NTDT reduce secondary iron overload burden β-Thalassemia intermedia (NTDT) >150,000 > Monotherapy
Slide 19: Why we are Excited about SLN124?
Why we are Excited about SLN124? Science Indication Patient Market What does the Mode of How does the science What is the patient When and where do we action bring? connect to the diseases? benefit? want to market it? 2018: Gene silencing via siRNA is a beta-Thalassemia SLN124 has the potential to b
Slide 20: Pipeline - Building a Proprietary Portfolio
Pipeline - Building a Proprietary Portfolio Internal programmes advanced into preclinical development Our Programmes SLN124 4Q2018 SLN124 Mid 2019 Mid 2019 SLN226 Out-Licensed Programmes SLN226 © Silence Therapeutics 2018 20
Slide 21: Platform Strategy
Platform Strategy ~7,000 accessible gene targets…We have the technology and the team to discover and develop a wide range of therapeutics Target & Indication In silico In vitro KD POM* Disease pPOC** NCD, CMC, CTA*** Phase I ... Selection selection screen in vivo models Regulatory Cost: $ $ $ $ $ We
Slide 22: Outlook: Significant Milestones for the Next 12 months
Outlook: Significant Milestones for the Next 12 months 2018 will be a year of continuity and building upon success to capture value by executing on pipeline development and leveraging its platform > File clinical trial approval for iron overload by end of 2018 > Add further development expertise to
Silence Therapeutics — Cowen 38th Annual Health Care Conference 2018 on 6ix