Silence Therapeutics PLC · NASDAQ:SLN
Silence Therapeutics — JP Morgan Healthcare Conference 2018
35 slides from Silence Therapeutics's conference presentation, January 2018
Slide 1: Corporate Presentation JP Morgan Conference
Corporate Presentation JP Morgan Conference January 2018
Slide 2: Forward looking statements
Forward looking statements 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 dist
Slide 3: Silence Therapeutics - Overview
Silence Therapeutics - Overview > Only quoted European RNA interference (RNAi) drug development Company > Proprietary platform technology builds on years of scientific research and in-house know-how > Silence currently focuses on the liver hepatocyte, which expresses > 7,000 genes, many of these are
Slide 4: RNAi - on the cusp of becoming a new class of therapeutics for patients
RNAi - on the cusp of becoming a new class of therapeutics for patients RNA interference is a natural pathway that can be harnessed to inhibit the expression of disease-causing genes without altering DNA AT SILENCE > Established a competitive GalNAc-siRNA platform technology and advanced our pipelin
Slide 5: R&D with focus on portfolio and innovation
R&D with focus 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 programs in a > Expand
Slide 6: Pipeline
Pipeline Building a proprietary portfolio, two projects advanced into preclinical development Our Programs SLN124 4Q2018 SLN124 Mid 2019 SLN226 Mid 2019 Out-Licensed Programs SLN226 © Silence Therapeutics 2018 6
Slide 7: Experienced Leadership Team: Strong background in discovery and development of RNA therapies
Experienced Leadership Team: Strong background in discovery and development of RNA therapies Ali Mortazavi, Torsten Hoffmann, Ph.D. David Ellam, Chief Executive Officer Chief Operating Officer Chief Financial Officer Dmitry Samarsky, Ph.D. Laura Roca-Alonso, Michael Mulqueen, Chief Scientific Office
Slide 8: GalNAc-siRNA Platform Technology
GalNAc-siRNA Platform Technology © Silence Therapeutics 2018 8
Slide 9: siRNA Mechanism Of Action
siRNA Mechanism Of Action 1 RNA interference is mRNA sequence for target gene X > A Nobel prize-winning mRNA discovery > A natural pathway that 2 can be harnessed to siRNA designed siRNA inhibit the expression specifically against target gene X of disease-causing genes without altering mRNA DNA 3 An
Slide 10: GalNAc-siRNA molecules
GalNAc-siRNA molecules Linker siRNA GalNAc gene silencing hepatocyte targeting Advantages of GalNAc-siRNA technology > GalNAc targets therapeutic siRNA molecules specifically to hepatocytes > Highly specific by targeting a single gene > Patient-friendly via infrequent subcutaneous administration > E
Slide 11: 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 12: 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 13: Advantageous properties of our medicines
Advantageous properties of our 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 leve
Slide 14: Intellectual Property – Pioneers in siRNA chemical modification technology since 2003
Intellectual Property – Pioneers in siRNA chemical modification technology since 2003 We have 13 granted patents and 5 patent applications encompassing our foundational chemical modification technology in US and Europe Modified siRNA (example) > Chemical modifications of siRNA are required to: 1) pr
Slide 15: Milestones for the next 12 months
Milestones for the next 12 months > File Iron Overload CTA Q4 2018 > Secure validating Pharma deal in 2018 utilizing our GalNAc platform technology > Progress existing pipeline, including potential out-license inflexion points > Add new targets to pipeline, and utilize next generation molecules > Co
Slide 16: Summary
Summary LEADING RNA INTERFERENCE PLATFORM > Platform being leveraged to build and progress a therapeutic pipeline > Accelerating pre-clinical discovery, targeting genes in the liver with high specificity > Modular process is readily reproducible > Big Pharma is displaying renewed interest in accessi
Slide 17: APPENDIX
APPENDIX © Silence Therapeutics 2018 17
Slide 18: Board of Directors
Board of Directors Ali Mortazavi Dr. Annalisa Jenkins Chief Executive Officer Non-Executive Chairman • Extensive expertise in UK small companies, particularly • Over 25 years of global industry experience in biotechnology & technology investments & ventures • Expertise in advancing programs from sci
Slide 19: SLN124 Iron Overload Disorders
SLN124 for the treatment of Iron Overload Disorders © Silence Therapeutics 2018 19
Slide 20: Treatment of iron overload disorders
Treatment of iron overload disorders 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 option t
Slide 21: 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 22: 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 23: 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 24: DISEASE MODEL: Therapeutic activity of SLN124 in an iron overload model (HFE -/- mice) - 1/2
DISEASE MODEL: Therapeutic activity of SLN124 in an iron overload model (HFE -/- mice) - 1/2 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
Slide 25: DISEASE MODEL: Therapeutic activity of SLN124 in an iron overload model (HFE -/- mice) - 2/2
DISEASE MODEL: Therapeutic activity of SLN124 in an iron overload model (HFE -/- mice) - 2/2 Collaboration with Prof. Dr. Martina Muckenthaler University of Heidelberg, Germany Transferrin Saturation Haemoglobin Mean corpuscular volume M e a n c o r p u s c u la r v o lu m e [ µ m ] 3 19 60 % T r a
Slide 26: 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 27: Iron Overload Disorders
Iron Overload Disorders Affected organs by iron overload Diseases with iron overload > β-Thalassemia > Hereditary Haemochromatosis > Myelodysplastic Syndrome > Aplastic Anaemia > Sideroblastic Anaemia If untreated, iron accumulation in organs leads to severe damage, e.g. heart, liver & endocrine org
Slide 28: Market opportunity for iron overload disorders
Market opportunity for iron overload disorders 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 > Monothe
Slide 29: SLN124 - Summary
SLN124 - Summary > Highly potent, selective and long acting GalNAc-siRNA > Efficacious in lowering blood iron and well tolerated in healthy mice and non-human primates after single subcutaneous administration > Demonstrated therapeutic efficacy in clinically relevant animal disease models > Currentl
Slide 30: SLN226 Alcohol Use Disorder
SLN226 for the treatment of Alcohol Use Disorder © Silence Therapeutics 2018 30
Slide 31: SLN226 for the treatment of alcohol use disorder
SLN226 for the treatment of alcohol use disorder GOAL > Provide an effective & safe novel treatment option for patients with alcohol use disorder (AUD) RATIONALE > Target ALDH2, a validated target for alcohol aversion therapy, with a GalNAc-siRNA molecule providing a highly specific, effective & saf
Slide 32: SLN226 mechanism of action
SLN226 mechanism of action > Aldehyde dehydrogenase 2 (ALDH2) is the key alcohol metabolizing enzyme > Liver is the key organ for ethanol detoxification by ALDH2 > ALDH2 is rate limiting enzyme in the ethanol metabolic pathway Ethanol Validated target ADH > Clinically: ALDH inhibitors Acetaldehyde e
Slide 33: Alcohol use disorder facts
Alcohol use disorder facts High medical need for effective and safe treatment options to improve compliance and alcohol abstinence Long term effects of alcohol abuse Consequences of alcohol abuse > Liver damage > Cardiovascular complications > Gastrointestinal damage > Central & peripheral neurologi
Slide 34: Market opportunity of SLN226 (US & Europe)
Market opportunity of SLN226 (US & Europe) Patients urgently requiring abstinence > 20-33% liver transplants due to alcohol abuse alone or in 40,000 combination with viral infection Requiring abstinence > Potentially a similar number of patients on the waiting list needing abstinence support > Expan
Slide 35: SLN226 - Summary
SLN226 - Summary > Highly potent, selective and long acting GalNAc-siRNA > Induces acetaldehyde accumulation in mice after single subcutaneous administration > Currently in preclinical development with plans to enter clinical development in Q2 2019* > Studies initiated to show therapeutic efficacy i
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