Silence Therapeutics PLC · NASDAQ:SLN
Silence Therapeutics — Technical Presentation (June 2024)
22 slides from Silence Therapeutics's technical presentation, Jun 27, 2024
Slide 1: Results from Ongoing SANRECO Phase 1 Study of Divesiran in Polycythemia Vera
Results from Ongoing SANRECO Phase 1 Study of Divesiran in Polycythemia Vera June 27, 2024
Slide 2: Forward-Looking Statements
Forward-Looking Statements Statements contained in this presentation regarding matters that are not historical facts are “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995, as amended. Words such as "anticipates," "believes," "expects," "intends,"
Slide 3: Divesiran Has the Potential to Be First siRNA for PV
Divesiran Has the Potential to Be First siRNA for PV • To-date, divesiran has eliminated the need for phlebotomy in all well- controlled patients after infrequent dosing • To-date, divesiran has been well tolerated with no serious safety issues • Divesiran represents second wholly owned program demo
Slide 4: SANRECO Phase 1 Study of Divesiran in Patients with Polycythemia Vera
SANRECO Phase 1 Study of Divesiran in Patients with Polycythemia Vera 4
Slide 5: Polycythemia Vera (PV): A Rare Blood Cancer with Significant Unmet Needs
5 Polycythemia Vera (PV): A Rare Blood Cancer with Significant Unmet Needs • Myeloproliferative neoplasm characterized by the excessive production of red blood cells (RBCs) o Elevated hematocrit (Hct) is a hallmark of the disease, indicating Treatment goal is overproduction of RBCs to control HCT <4
Slide 6: Our mRNAi GOLD Platform Considers All Elements of siRNA and Ligand Design
Our mRNAi GOLD Platform Considers All Elements of siRNA and Ligand Design siRNA molecule Linker GalNAc Ligand (delivery tool) • siRNA matched to target gene • Silence has developed • GalNAc ligand delivers proprietary linkers, enabling molecule to specific liver • Silence has developed chemical the
Slide 7: Divesiran Rationale for targeting TMPRSS6
7 Divesiran Rationale for targeting TMPRSS6 > TMPRSS6 is a negative regulator of the BMP/SMAD HJV BMPR Macrophages signaling pathway; activation of the pathway induces BMP hepcidin expression > Hepcidin reduces uptake of dietary iron and the Ferroportin release of iron from storage cells TMPRSS6 P F
Slide 8: SANRECO: Phase 1 Trial Design
SANRECO: Phase 1 Trial Design Key inclusion criteria: • PV diagnosis • At least 3 phlebotomies in the last 6 months or 5 in the last year prior to screening • Stable dose of cytoreductive agents allowed Dosing schedule and follow-up: • Subcutaneous injections on days 1, 43, 85 and 127 • Follow up fo
Slide 9: SANRECO: Phase 1 Current Status (21 enrolled)
SANRECO: Phase 1 Current Status (21 enrolled) as of 27 June 2024 Enrollment Status Cohort 1 - 3mg/kg • 6 patients enrolled; 4 completed study Cohort 2 - 6mg/kg • 8 patients enrolled; 5 completed study Cohort 3 - 9 mg/kg • 7 patients enrolled; 4 completed Day 127 SANRECO will stop enrolling new patie
Slide 10: SANRECO: Patient Baseline Characteristics
SANRECO: Patient Baseline Characteristics Data cutoff 29 March 2024 (16 patients) Patient Cohort Age Sex Race Aspirin (mg) HydroxyUrea Hct baseline (%) 14011001 1 52 Female Caucasian 100 None 39 1000QD M-F 14071001 1 62 Male Caucasian 100 43 1500QD Sat-Sun 500QD 14071002 1 51 Female Caucasian 100 44
Slide 11: Treatment with Divesiran Substantially Reduced Phlebotomy Requirements in PV Patients
Treatment with Divesiran Substantially Reduced Phlebotomy Requirements in PV Patients Phlebotomy History 6 mos prior Screening EoS 239
Slide 12: Divesiran Elevated Hepcidin in PV Patients, Demonstrating Robust Target Engagement
Divesiran Elevated Hepcidin in PV Patients, Demonstrating Robust Target Engagement 16 Cohort 1 (n = 4) 14 12 Cohort 2 (n = 8) Hepcidin (nM) 10 Dosing 8 6 4 2 0 -2 10 20 30 40 50 60 70 80 90 100 110 120 130 Days Note: error bars represent +/- 1 SD 12
Slide 13: Divesiran Treated PV Patients Achieved Target Hematocrit Levels of 45% or Below
Divesiran Treated PV Patients in Both Cohorts Achieved Target Hematocrit Levels of 45% or Below 55 Cohort 1 (n = 4) Cohort 2 (n = 8) Haematocrit (%) 50 Dosing 45 40 35 0 10 20 30 40 50 60 70 80 90 100 110 120 130 Days Note: error bars represent +/- 1 SD 13
Slide 14: Hematocrit Change from Baseline Suggests a Potential Dose Response
Hematocrit Change from Baseline Suggests a Potential Dose Response 6 Cohort 1 (n = 4) Change from baseline 4 Cohort 2 (n = 8) 2 Dosing 0 -2 -4 -6 -8 0 10 20 30 40 50 60 70 80 90 100 110 120 130 Days Note: error bars represent +/- 1 SD 14
Slide 15: Divesiran Controls Hematocrit Regardless of Baseline Level
Divesiran Controls Hematocrit Regardless of Baseline Level 55 Hct > 45% at baseline (n = 8) Hct ≤ 45% at baseline (n = 8) Haematocrit (%) 50 Dosing 45 40 35 0 10 20 30 40 50 60 70 80 90 100 110 120 130 Days Note: error bars represent +/- 1 SD 15
Slide 16: Divesiran Increases Ferritin Levels Representing Improvement in Iron Deficient Status
Divesiran Increases Ferritin Levels Representing Improvement in Iron Deficient Status 140 Cohort 1 (n = 4) 120 Cohort 2 (n = 8) 100 Ferritin (μg/L) Dosing 80 60 40 20 0 -20 0 10 20 30 40 50 60 70 80 90 100 110 120 130 Days Note: error bars represent +/- 1 SD 16
Slide 17: Divesiran is Associated with Limited Increases in Platelets
Divesiran is Associated with Limited Increases in Platelets 1200 Cohort 1 (n = 4) 1000 Cohort 2 (n = 8) Platelets (g/L) 800 Dosing 600 400 200 0 0 10 20 30 40 50 60 70 80 90 100 110 120 130 Days Note: error bars represent +/- 1 SD 17
Slide 18: Divesiran Effect on Platelets Does Not Appear to be Dose Dependent
Divesiran Effect on Platelets Does Not Appear to be Dose Dependent 600 Cohort 1 Change from baseline 500 400 Cohort 2 300 Dosing 200 100 0 -100 -200 0 10 20 30 40 50 60 70 80 90 100 110 120 130 Days Note: error bars represent +/- 1 SD 18
Slide 19: SANRECO: Summary of Efficacy and Safety
SANRECO: Summary of Efficacy and Safety Efficacy • All divesiran treated patients who were well controlled at baseline remained so without the need for phlebotomy • All patient groups, regardless of baseline hematocrit, demonstrated reduction and control of hematocrit • Divesiran was associated with
Slide 20: Silencing diseases through precision engineered medicines created with proprietary siRNA technology
Silencing diseases through precision engineered medicines created with proprietary siRNA technology
Slide 21: Q&A Session
Q&A Session SANRECO Phase 1 Results 21
Slide 22: Thank you!
Silencing diseases through Thank you! precision engineered medicines created with proprietary siRNA technology 22
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