Silence Therapeutics PLC · NASDAQ:SLN
Silence Therapeutics — 2018 BIO International Convention
19 slides from Silence Therapeutics's conference presentation, June 2018
Slide 1: BIO partnering
Non-confidential presentation BIO partnering June 2018
Slide 2: Disclaimer (US)
Disclaimer (US) The information contained in this presentation is being supplied and communicated Safe Harbour statement: this presentation may contain forward-looking statements to you on a confidential basis solely for your information and may not be reproduced, that reflect the Company’s current
Slide 3: Silence Therapeutics' summary
Silence Therapeutics’ summary Valuable > Reproducible, proprietary RNAi therapeutics platform, rapidly HQ in London Platform generating internal pipeline and diversifying out-licensing options > SLN124 (Beta-Thalassemia & MDS) planning to enter the clinic in early Haematology 2019 after promising ef
Slide 4: Our pipeline
Our pipeline Out-Licensed Technology to Quark Pharmaceuticals © Silence Therapeutics 2018 4
Slide 5: GalNAc-siRNA Platform Technology
GalNAc-siRNA Platform Technology © Silence Therapeutics 2018 5
Slide 6: R&D focused on portfolio and innovation
R&D focused on portfolio and innovation Technology Drug Discovery & Innovation Development > Improve performance of > Build proprietary our GalNAc-siRNA therapeutic portfolio by molecules applying validated siRNA > Strengthen and broaden technologies IP portfolio > Partner programmes in a > Expand R
Slide 7: Fine-tuning molecular design to enhance performance
Fine-tuning molecular design to enhance performance siRNA modification pattern Linker composition End GalNAc composition stabilization > Modification pattern: reduced number of non-natural modifications > End stabilization: increased circulation half-life, activity and duration of action > Linker: s
Slide 8: Platform performance
Platform performance Platform technology with FTO: Target 1 Target 2 GalNAc-siRNA, able to mediate highly specific gene silencing in hepatocytes N o r m a lis e d ta r g e t m R N A N o r m a lis e d ta r g e t m R N A (liver) – “Specificity upon specificity” 1 .0 1 .0 0 .5 0 .5 Patient friendly: Su
Slide 9: Populating our pipeline: Target selection strategy
Populating our pipeline: Target selection strategy Selection criteria Identification of high conviction target • High unmet need genes and indications • Validated target gene • Good clinical feasibility Commercial IP • Established and attractive regulatory path R&D KOLs and • Competitive environment
Slide 10: Risk-diversified portfolio
Risk-diversified portfolio Haematology franchise Rare diseases • SLN124: Lead candidate for two indications • Expanding our existing rare portfolio (beta-Thalassemia and MDS): additional expansion potential in larger populations • Aiming to progress through clinical (Hemochromatosis) development int
Slide 11: Unlocking value through our BD strategy
Unlocking value through our BD strategy We intend to strategically partner our programmes at different stages to fully unlock the value of our platform – Rapid path to value creation Collaborations, Our pipeline JV’s and other programmes structures Technology platform deals Remaining flexible – able
Slide 12: 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 12
Slide 13: Treatment of Iron Overload Disorders (IOD)
Treatment of Iron Overload Disorders (IOD) Iron overload disorders: GOAL > Myelodysplastic > Provide an effective and safe novel treatment option for Syndrome (MDS) patients with iron overload conditions with infrequent > β-Thalassemia > Hereditary s.c. dosing Haemochromatosis > Aplastic Anaemia > S
Slide 14: Market opportunity of SLN124
Market opportunity of SLN124 US and EU patients Standard of Care β-Thalassemia ~40,000 TDT ~20,000 NTDT MDS >100,000 Benefits of SLN124 Advantages v Competition Advantages Competition SoC: Quality of Life Transfusions + SLN124 aims to: Chelators Safety 1. Reduce organ iron levels & Antisense RNA 2.
Slide 15: SLN124 mechanism of action
SLN124 mechanism of action HJV BMPR Macrophages > TMPRSS6 (Transmembrane BMP Protease, Serine 6) is a negative regulator of the Ferroportin BMP/SMAD signaling TMPRSS6 P Fe pathway Iron recycling > Inhibition of TMPRSS6 in P SMAD hepatocytes induces Hepcidin Hepcidin expression > Hepcidin reduces Iro
Slide 16: 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 POM 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
Slide 17: Therapeutic activity of SLN124 in a disease model of hereditary haemochromatosis
Therapeutic activity of SLN124 in a disease model of hereditary haemochromatosis (HFE-/- mice) Collaboration with Study design d1 wk 3 Prof. Dr. Martina Muckenthaler SC, n=6-7 HFE-/- mice Heidelberg University, Germany TMPRSS6 mRNA (liver) Hepcidin (serum) Iron (serum) 2 .0 800 p<0.0001 N o r m a li
Slide 18: SLN124 reduces ROS and improves RBC parameters in a b-Thalassemia disease model
SLN124 reduces ROS and improves RBC parameters in a b-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 p = 0 .
Slide 19: Upcoming corporate milestones (2018)
Upcoming corporate milestones (2018) > SLN124: file CTA in Q4 2018 > Add new targets to pipeline utilising next generation technology > Add further clinical development expertise to the senior team as pipeline progresses > Secure further validating collaborations utilising our GalNAc platform techno
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