Slide 1: FY2023 Annual Result Presentation
Sirnaomics Ltd. (2257.HK) FY2023 Annual Result Presentation 0
Slide 2: Disclaimer
Disclaimer By attending the meeting where this presentation is made, or by reading the presentation materials, you agree to be bound by the following limitations: The information in this presentation has been prepared by representatives of Sirnaomics Ltd. (the “Company”) for use in presentations by
Slide 3: Sirnaomics – International Vision in RNA Therapy
Sirnaomics – International Vision in RNA Therapy Next Generation of Leadership in RNA for Dual Proprietary Pharmaceutical Drugs Cancer on the Global Stage Delivery Platforms 1st to achieve positive Ph II clinical result Target specific disease-causing genes PNP Platform & GalNAc Platform, both in on
Slide 4: Experienced Management Team
Experienced Management Team Patrick Lu Francois PhD, Lebel MD, Chairman， Senior VP President & CMO CEO 30+years of 20+ years of experience experience Edward Xiaochang Wang PhD, Dai PhD, CPO Chief Strategy Officer 30+ years of experience 25+ years of experience Rick Welch Nigel Yip， PhD, MBA, VP, CMC
Slide 5: Two Clinically Validated Delivery Technology Platforms
Two Clinically Validated Delivery Technology Platforms 1 Polypeptide Nanoparticle (PNP) Platform 2 GalNAc Platform CPP Activity siRNA GalAheadTM HKP and HKP(+H) Carriers for siRNA and mRNA Drug and Vaccine Delivery Skin Cancers Medical Aesthetics Solid Tumors Anticoagulant Hypertriglyceridemia STP70
Slide 6: GalAhead – Sirnaomics Proprietary GalNAc 2.0 Delivery
GalAhead – Sirnaomics Proprietary GalNAc 2.0 Delivery mxRNA : miniaturized single-targeting RNAi triggers ▪ 30-34 Nucleotides ▪ Single stranded ▪ Smallest RNAi Trigger ▪ Easier CMC Process ▪ Good Safety Profile ▪ Long-Lasting Efficacy Linker ▪ Strong IP Position muRNA : multi-unit multi-targeting RN
Slide 7: Prioritized Product Pipeline for RNA Therapeutics & Vaccine Delivery
Prioritized Product Pipeline for RNA Therapeutics & Vaccine Delivery Candidate Gene Targets Indications R&D IND Phase I Phase II Phase III Rights Platform isSCC Global STP705 TGF-β1/COX-2 PNP-IT BCC Global Multiple Oncology STP707 TGF-β1/COX-2 PNP-IV Global Solid Tumors Multiple STP355 TGF-β1/VEGFR2
Slide 8: Guangzhou Fill & Finish Pilot Base
Guangzhou Fill & Finish Pilot Base ◼ Expand the production capability of our Guangzhou plant in 2023 to support our growing GalAhead product line ◼ Achieve GMP certification for the production of freeze-dried and hydro-needled products in various dosage forms in 2023 ◼ Completion of several batches
Slide 9: Product Progress
° ° Advancing RNAi Therapeutics PEAS Product Progress ele
Slide 10: NMSC Clinical Imperatives in Multiple Global Markets
NMSC Clinical Imperatives in Multiple Global Markets Differences in morbidity and mortality between China and the U.S. (1990-2019) SCC BCC STP705 Ph IIa & IIb isSCC STP705 Ph II BCC Optimal dose 90% complete Optimal dose 100% complete Efficacy clearance Efficacy clearance Safety No Skin reaction, no
Slide 11: STP705 isSCC – Late-Stage Guidance from Type B Meeting
STP705 isSCC – Late-Stage Guidance from Type B Meeting Type B Meeting: May 2023, type B meeting confirmed STP705 as the clinical endpoint for the treatment of isSCC. The late-stage clinical trial will need to be divided into two major phases and will require a significant clinical sample size. 10 ce
Slide 12: STP705 isSCC – Recognize Pivotal Clinical Trial Designs
STP705 isSCC – Recognize Pivotal Clinical Trial Designs The type C meeting will validate STP705 as a Pivotal Clinical Trial Endpoint Assessment Indicator for the treatment of isSCC. The Pivotal Clinical Trial will be divided into two major phases. The innovative design by Dr. Lebel, Chief Medical Of
Slide 13: STP705 Focal Fat Reduction – Dual-targeted with clear MOA
STP705 Focal Fat Reduction – Dual-targeted with clear MOA 資料來源：Int. J. Mol. Sci. 2019, 20, 3115; TGFβ1 and Obesity Recent findings on the role of TGFβ1/Smad3 signaling in the pathogenesis of obesity and type 2 diabetes have underscored its importance in metabolism and adiposity. Indeed, elevated TGF
Slide 14: STP705 Focal Fat Reduction – Mechanism in Adipose Tissue
STP705 Focal Fat Reduction – Mechanism in Adipose Tissue Labeled Nucleic Acid Drugs Retained in Target Target knockdown gene in adipose KD effect of HKP/Cy3-siTF1 tissuetissue in adipose Mean±SEM, n=4, intra-fat injection, 9μg, single dose Adipose Tissue siRNA residue quantity of HKP/Cy3-siTF1 in ad
Slide 15: STP705 Focal Fat Reduction Vs Commercial Product X
STP705 Focal Fat Reduction Vs Commercial Product X STP705/Commercial Product X Comparison Study Preclinical Animal Model Study Results Product X Thickness of Adipose Tissue Control (µm) STP705 Treatment Study Design ◼ Animal Model：minipig, N = 3 ◼ Administration: Subcutaneous， Comparison ◼ Commercia
Slide 16: STP705 Focal Fat Reduction – Phase I Clinical Design
STP705 Focal Fat Reduction – Phase I Clinical Design Ph I Clinical Study Design ▪ Evaluated safety and tolerability in 18–65-year-old subjects ▪ 8 subjects were enrolled at 2 U.S. sites. ▪ The abdominal area for abdominoplasty was divided into 3 zones with 1-3 injection sites each, totaling 7 sites
Slide 17: STP705 Focal Fat Reduction – Histological Sample Analysis
STP705 Focal Fat Reduction – Histological Sample Analysis Clinical Study Summary Clinical Study Key Results 240µg/1ml Cohort Showed Best Result 16
Slide 18: STP707 Multiple Solid Tumor – Phase I Study Design
STP707 Multiple Solid Tumor – Phase I Study Design Phase I study design Clinical Centers Principal Investigator SCRI Denver Dr Henry Jason In November 2021, we initiated a NEXT Oncology, Austin Dr Andrae Vandross Phase I clinical trial for solid tumors Atlantic Health Dr. Angela Alistar in the U.S.
Slide 19: STP707 Multiple Solid Tumor – Exhibit Clinical Benefits
STP707 Multiple Solid Tumor – Exhibit Clinical Benefits Stabilization and tumor shrinkage can still be observed in endline patients with different tumor types. Treatment >28 days: 74% Stable Disease > 100 days: 22% Exhibited reduction in tumor burden per Response Evaluation Criteria in Solid Tumors
Slide 20: Preliminary Observations for Pancreatic Cancer
Preliminary Observations for Pancreatic Cancer Experience with third-line drug therapy for advanced STP707 Clinical Phase I： pancreatic cancer (USA): • Average value of stabilization for all 11 patients is 3.5 months • Chemotherapeutic agent: 4.4 months (105 days) • Chemotherapeutic drug + combinati
Slide 21: Further Enrichment of GalAhead Pipeline in 2023
Further Enrichment of GalAhead Pipeline in 2023 mxRNA Candidate IND Drug Target Indicator R&D Phase I Nomination enabling STP125G APOC3 Hypertriglyceridemia STP144G Complement Factor B Complement - diseases STP145G Complement C5 Complement - diseases STP146G Complement C3 Complement - diseases STP15
Slide 22: mxRNA and muRNA - Mechanism of Action (MOA)
mxRNA and muRNA - Mechanism of Action (MOA) mxRNA muRNA SBS GN GN GN 5’ 5’ GN GN SBS GN GN GN RNAi Trigger 2 GN 5’ 3’ RNAi Trigger 1 5’ 5’ 3’ 5’ GN GN GN cleavage RISC mRNA target X mRNA target Y RISC cleavage Key points: Key points: ▪ One single strand,1 Hairpin structure ▪ Two single strands,1 Dup
Slide 23: STP122G FXI Anticoagulant – Better Anticoagulant Therapy
STP122G FXI Anticoagulant – Better Anticoagulant Therapy Control 1mg/Kg 3mg/Kg 125 10mg/Kg 3mg/Kg x2 3mg/kg x3 100 Plasma FXI activity (% of baseline) 75 75% suppression at 15 weeks 50 50% suppression at 24 weeks 25 0 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30
Slide 24: STP122G FXI Anticoagulant – Signaling Pathway
STP122G FXI Anticoagulant – Signaling Pathway Prothrombin time (PT) factor B Activation of partial thromboplastin time （aPTT） 1.7 Control 10mg/Kg Ellagic acid 1.6 1mg/Kg 3mg/Kg x2 Normalized aPTT 1.5 3mg/Kg 3mg/kg x3 1.4 1.3 1.2 1.1 1.0 0.9 0.8 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 2
Slide 25: STP122G FXI Anticoagulant Vs similar siRNA drugs (NHP)
STP122G FXI Anticoagulant Vs similar siRNA drugs (NHP) Control 10mg/Kg 125 100 Plasma FXI activity (% of baseline) 75 50 21周 25 0 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 0 1 2 3 4 5 6 7 8 9 Weeks Ribocure Sirnaomics Maximum dosage 9mg/kg 10mg/kg Maximum 76% 82% suppre
Slide 26: STP122G FXI Anticoagulant – Phase I Clinical Study Design
STP122G FXI Anticoagulant – Phase I Clinical Study Design First Clinical Drug Developed Using GalAheadTM Delivery Platform Phase I Clinical Study Design ◼ Applications across a broad range of disease indications such as the potential prevention and treatment of stroke after atrial fibrillation, canc
Slide 27: STP144G Complement Diseases – Bb Levels with Lead Compounds in NHP
STP144G Complement Diseases – Bb Levels with Lead Compounds in NHP Single Treatment Comparison Multiple Treatment Comparison BLQ BLQ Range Range Days Days Max reduction of Factor Bb and duration of response Max reduction of Factor Bb and duration of response ➢ 106-13(4) ➢ 106-13(4) • Max suppression
Slide 28: STP125G Hypertriglyceridemia – Duration Response
STP125G Hypertriglyceridemia – Duration Response Test compounds: • STP125G - A28(14-4)mF mxRNA Dosing: • 10 mg/kg mRNA levels in liver tissues protein levels in plasma (ELISA) p < 0.0001 p < 0.0001 p < 0.0001 p < 0.0001 p = 0.0005 p < 0.0001 ➢ Duration Response: ➢ Duration Response: • 83-85% KD betw
Slide 29: STP136G Hypertension – Duration Response
STP136G Hypertension – Duration Response Test compounds: • AGT27A Dosing: • 30 mg/kg Protein levels in plasma (ELISA) mRNA levels in liver tissues ➢ Duration Response: ➢ Duration Response: • 75% NADIR at Week 2 • 85% max reduction at Week 2 • 70% mRNA KD at Week 4 • 79% reduction at Week 4 and 58% r
Slide 30: STP237G Hypertension & Hypertriglyceridemia – Duration Response
STP237G Hypertension & Hypertriglyceridemia – Duration Response • AGT27A-A28 30mg/kg mRNA levels in liver tissues Protein levels in plasma (ELISA) % KD of mRNA % Protein reduction in plasma AGT APOC3 AGT APOC3 Week 2 75% NADIR 89% NADIR Week 2 78% NADIR 72% Week 4 54% 79% Week 4 61% 75% NADIR Week 8
Slide 31: Financial Overview
° ° Advancing RNAi Therapeutics PEAS Financial Overview ele
Slide 32: Measures to Increase Cash Inflow and Reduce Cash Outflow
Measures to Increase Cash Inflow and Reduce Cash Outflow • In order to extend the Company’s cash runway and have sufficient financial resources for business operations, the Company is actively working on improving liquidity and cash flow by implementing different programs and measures. In terms of c
Slide 33: Profit and Loss
Profit and Loss 1. Changes in fair value at FVTPL 2023 2022 For 2023, the balance decreased to $1.5 million (75%) primarily Note due to a lower rate of increase in the valuation of preferred $ million $ million shares of RNAimmune (non-cash) Revenue Nil Nil . Other income and Other gains 2. Impairme
Slide 34: Cash Flow Statement
Cash Flow Statement Note Cash Flow Statement 2023 $ million 1. Net cash used in operating activities Opening balance 105.2 Due to change of Group’s overall cost cutting strategy, the net cash used in operating activities has reduced from $88.7m to Net cash used in operating $70.3m 1 (70.3) activitie
Slide 35: Advancing RNAi Therapeutics – Q&A
° ° Advancing RNAi Therapeutics Las) Q&A