Slide 1: Sequencing by Expansion (SBX)/AGBT 2025 Virtual IR Event
Sequencing by Expansion (SBX)/AGBT 2025 Virtual IR Event Feb 20th 2025
Slide 2: Welcome
Welcome Bruno Eschli Head of Investor Relations
Slide 3: Agenda
Agenda Welcome Bruno Eschli, Head of Investor Relations Sequencing by Expansion (SBX) Matt Sause, CEO Roche Diagnostics Josh Lauer, Global Head of Customer Area Molecular Labs Q&A Birgit Masjost, Investor Relations Officer Matt Sause, CEO Roche Diagnostics Josh Lauer, Global Head of Customer Area Mo
Slide 4: IR events currently planned for 2025
IR events currently planned for 2025 Additional events driven by readouts Immunology/WCN Update on NGS Neurology Update Diagnostics Day Pharma Day 7 Feb 20 Feb 4 Apr 27 May 22 Sep 16:30 – 17:30 CET 20:30 - 21:30 CET 16:00 – 17:30 CEST 14:00 - 16:30 CEST tbd Virtual event Virtual event Virtual event
Slide 5: Sequencing by Expansion (SBX)
Sequencing by Expansion (SBX) Matt Sause CEO Roche Diagnostics Josh Lauer Global Head of Customer Area Molecular Labs
Slide 6: Introducing Roche SBX technology
Introducing Roche SBX technology The NGS market was valued at USD 6.4b (2024) and projected to grow at 9% per year from 2024 to 2027 driven by clinical and biopharma segments1 Growth in clinical segment is driven by applications such as therapy selection and monitoring in oncology where Roche has a
Slide 7: Roche sequencing portfolio today
Roche sequencing portfolio today From leading tools and technologies to solutions in oncology Biological Obtaining meaningful & Actionable Sample preparation Sequencing sample actionable insights report KAPA KAPA library target prep1 enrichment1 navify® Mutation Profiler AVENIO Edge System2 3rd part
Slide 8: Building towards a differentiated sequencing ecosystem
Building towards a differentiated sequencing ecosystem Iterative development through NGS value chain for tools and solutions Biological Obtaining meaningful & Actionable Sample preparation Sequencing sample actionable insights report KAPA KAPA Consumables & Informatics library target reagents3 solut
Slide 9: Introducing SBX technology
Introducing SBX technology Combination of two powerful innovations creates a leap forward in sequencing SBX chemistry High-throughput sensor module Unique speed and flexibility + = • Novel chemistry from Stratos* turns DNA • 8 million microwell array CMOS chip from • Clear, discrete signal combines
Slide 10: Benefits of SBX technology
Benefits of SBX technology Designed to deliver flexibility and throughput with potential for future improvement Flexible operation Read length Batch flexibility Simplex: 50 - 1000+ bp Duplex: 150 - 350 bp (insert) Accuracy Urgent samples Q39 average for HG001 (Duplex) Sample to VCF in < 7 hours F1 9
Slide 11: Roche's high-throughput sequencing solution (in development)
Roche’s high-throughput sequencing solution (in development) Separate Xpandomer synthesis from single molecule measurement for maximum flexibility Library Preparation Synthesis Instrument Sequencing Instrument Multiplexed & indexed libraries Synthesis of Xpandomer Single molecule sequencing on molec
Slide 12: Roche's high-throughput sequencing solution (in development)
Roche’s high-throughput sequencing solution (in development) Library Preparation Synthesis Instrument Sequencing Instrument Multiplexed & indexed libraries Synthesis of Xpandomer Single molecule sequencing on molecules a CMOS-based Sensor module Illustrations not to scale; CMOS=complementary metal-o
Slide 13: Xpandomer synthesis
Xpandomer synthesis Automated instrument has flexibility to synthesize up to 4 separate library pools in < 4 hours Flexible operation Resulting Xpandomer molecule • Automated instrument creates Xpandomers from • Highly engineered polymerase translates original DNA sequence into an entirely new multi
Slide 14: Roche's high-throughput sequencing solution (in development)
Roche’s high-throughput sequencing solution (in development) Library Preparation Synthesis Instrument Sequencing Instrument Multiplexed & indexed libraries Synthesis of Xpandomer Single molecule sequencing on molecules a CMOS-based Sensor module Illustrations not to scale; CMOS=complementary metal-o
Slide 15: Xpandomer sequencing
Xpandomer sequencing High-throughput sequencing carried out on a reusable sensor module Sensor module Pore formation & reuse Controllable signal Setup Initialize run Sequencing System clean Amplitude Signal Translated Xp basecalls • 8 million microwell CMOS array • Xpandomers are threaded through po
Slide 16: Roche's high-throughput sequencing solution (in development)
Roche’s high-throughput sequencing solution (in development) Library Preparation Synthesis Instrument Sequencing Instrument Multiplexed & indexed libraries Synthesis of Xpandomer Single molecule sequencing on molecules a CMOS-based Sensor module Illustrations not to scale; CMOS=complementary metal-o
Slide 17: SBX library structures and workflows
SBX library structures and workflows Different approaches for different applications SBX-Duplex SBX-Duplex SBX-Simplex SBX Simplex Library Xpandomer High Accuracy Ultra-High Throughput 200-300 bp < 200 bp 200 - 500 bp 500 -1500 bp Potential WGS/WES WTS WTS DNA Structural Variants Future Somatic Onco
Slide 18: SBX-Duplex variant calling performance
SBX-Duplex variant calling performance Potential for clinical accuracy using Roche’s modified GATK and Google’s DeepVariant GATK + Roche Machine Learning DeepVariant F1 Score F1 Score Mean Insert Sample SNV Indels SNV Indels Read Length HG001 235 99.77% 99.54% 99.80% 99.56% • 1 hour of sequencing yi
Slide 19: SBX-Fast workflow can sequence a genome in under 7 hours
SBX-Fast workflow can sequence a genome in under 7 hours Optimized protocol skips amplification and leverages short run capability Sample SBX-Duplex Xpandomer SBX Variant Prep Library Prep Synthesis Sequencing Calls 2 μg DNA Blood 20 min 120 min 140 min 20 min 60 min Enzymatic fragmentation / Reduce
Slide 20: SBX-Simplex applications
SBX-Simplex applications Combination of high-throughput and read length enable more efficient translational research Short read counting applications Longer reads for novel isoform detection Read count (M) Read length (100 bp bins) • 1M cell PerturbSeq experiment performed • 5’ Gene Expression (GEX)
Slide 21: Roche analysis pipelines and open source tools development
Roche analysis pipelines and open source tools development Solution will include on-premise acceleration to enable concurrent data processing Roche On-Premise Local Accelerated Partner / Primary / Post-Primary Analysis Pipeline Variant Calling Customer Cloud SBX-D BAM / VCF Base Intramolecular Reads
Slide 22: Potential uses for SBX technology
Potential uses for SBX technology Ability to advance research, translational and clinical applications over time Whole Genome Spatial Sequencing Overall advance in sequencing • Ultra-high throughput, especially for single Whole Exome cell, spatial, proteomics applications Sequencing Proteomics • Imp
Slide 23: Roche uniquely positioned to use SBX to improve human health
Roche uniquely positioned to use SBX to improve human health Roche has access to a unique ecosystem to drive sequencer content development Roche & Genentech Roche Diagnostics Drug development product development Open platform Roche tools Third-party tools (automation, library (library prep, prep, so
Slide 24: Key takeaways
Key takeaways NGS will grow at 9% Roche SBX has the Roche SBX Roche is building an per year driven by potential to deliver technology has the open platform which clinical and high accuracy with potential to will be the core of our biopharma segments unprecedented accelerate research end-to-end solut
Slide 25: Invitations to upcoming events
Invitations to upcoming events AGBT Roche Diagnostics Day 25 Feb 2025 27 May 2025 Sponsored workshop* London / hybrid event 18:05 – 19:05 CEST / 17:05 – 18:05 BST 14:00 – 16:30 CEST / 13:00 – 15:30 BST 12:05 – 01:05pm EDT / 09:05 – 10:05am PDT 08:00 – 10:30am EDT / 05:00 – 07:30am PDT Highlights: Hi
Slide 26: Doing now what patients need next
Doing now what patients need next
Slide 27: Glossary
Glossary • Q39 – Phred quality score (q-score), a logarithmic measurement of error likelihood • F1 score – measure of variant calling accuracy, which is the harmonic mean of precision and recall • GATK – Genome Analysis Toolkit, a commonly used software package for variant calling • Demux – short fo