Codexis, Inc. · NASDAQ:CDXS
Codexis — TIDES USA 2024
12 slides from Codexis's conference presentation, 2024
Slide 1: Two Enzymatic Approaches for Large-scale siRNA Synthesis
Two Enzymatic Approaches for Large-scale siRNA Synthesis TIDES USA, 2024 Mathew Miller, PhD
Slide 2: Enzymatic Solutions for siRNA Synthesis are Increasing
Enzymatic Solutions for siRNA Synthesis are Increasing Chemical Hybrid Enzymatic Traditional siRNA Synthesis using ECO Synthesis (Enzyme-Catalyzed PAC fragments + Ligation Oligonucleotide Synthesis) Phosphoramidite Chemistry (PAC) Manufacturing Platform 1
Slide 3: Oligonucleotide Synthesis Experiences Purity Declines with Length
Oligonucleotide Synthesis Experiences Purity Declines with Length Cumulative effects of <100% coupling efficiency on oligonucleotide purity 100 99% Coupling 11-mer → 73 – 91% purity 90 Efficiency 9 – 27% impurities 80 Theoretical Purity (%) 23-mer → 51 – 80% purity 70 20 – 49% impurities 60 50 97% C
Slide 4: Fragment Ligation Strategies are Increasing for siRNA Manufacturing
ssRNA Fragments Fragment Ligation Annealing Strategies are Increasing for siRNA Ligation Manufacturing Full-length dsRNA 3
Slide 5: Engineered Ligases Enable Lower Manufacturing Costs
Engineered Ligases Enable Lower Manufacturing Costs Wild Type dsRNA Ligase Codexis Engineered dsRNA Ligase Low Activity High Activity • Poor ligation efficiency on clinically-relevant ✓ Higher ligation efficiency results in higher molecules yield of siRNA • Low activity requires high enzyme loading
Slide 6: Codexis Center of Excellence for Enzymatic RNA Synthesis
Codexis Center of Excellence for Enzymatic RNA Synthesis Services Offered • Design of RNA fragments for optimal ligation Screening & • Identification of lead ligase by high-throughput screening of large Optimization libraries of engineered RNA ligases • Optimization of ligation protocols • Tailored
Slide 7: dsRNA Ligase Services: Screening & Optimization
dsRNA Ligase Services: Screening & Optimization Evaluating customer’s fully modified dsRNA substrates against our ligase variant libraries, consisting of hundreds of differentiated, engineered enzymes at high substrate loadings 6 5 Relative Activity dsRNA Ligases engineered for: 4 3 • Substrate spec
Slide 8: dsRNA Ligase Services: Screening & Optimization
dsRNA Ligase Services: Screening & Optimization Optimizing customer’s fully modified dsRNA substrates with selected Codexis engineered ligases for maximum product yield and ligation efficiency at high substrate loadings 1.4 ~6x 100 Ligation Efficiency (%) 1.2 Product Yield (mM) [Product] (mM) 1.0 75
Slide 9: Codexis Center of Excellence for Enzymatic RNA Synthesis
Codexis Center of Excellence for Enzymatic RNA Synthesis Services Offered • Design of RNA fragments for optimal ligation Screening & • Identification of lead ligase by high-throughput screening of large Optimization libraries of engineered RNA ligases • Optimization of ligation protocols • Tailored
Slide 10: dsRNA Ligase Services: Enzyme Customization for Your Process
dsRNA Ligase Services: Enzyme Customization for Your Process Tailoring enzyme performance to Specific Substrates or Substrate Classes (Platform) under desired process conditions via Codexis CodeEvolver® technology Purified Enzyme Yield (g/L) ~5x ~7x Ligation Efficiency(%) 60 50 40 40 30 20 20 10 0 0
Slide 11: Codexis Center of Excellence for Enzymatic RNA Synthesis
Codexis Center of Excellence for Enzymatic RNA Synthesis Services Offered • Design of RNA fragments for optimal ligation Screening & • Identification of lead ligase by high-throughput screening of large Optimization libraries of engineered RNA ligases • Optimization of ligation protocols • Tailored
Slide 12: Your Pathway to Lower Cost and More Scalable RNA Manufacturing
Codexis Center of Excellence for Enzymatic RNA Synthesis Your Pathway to Lower Cost and More Scalable RNA Manufacturing Hybrid Enzymatic RNA Ligase Services ECO Synthesis Booth #628 Manufacturing Platform 11