Day Two

Thursday August 31 2023

9:20 am Chair’s Opening Remarks

Optimizing Manufacturing & Process Efficiency for Oligonucleotides

9:30 am From Development to Manufacturing Oligos: Opportunities and Stumbling Blocks

  • Tim Turner Senior Manager, Synthetic Process Development, Alexion Pharmaceuticals Inc.

Synopsis

• Elimination or modifications to existing unit operations

• Reducing the burden of IPC and release testing

• Optimizing process parameters that impact COGs

10:00 am Navigating Oligonucleotide Early CMC Development Challenges With Late-Stage Readiness in Mind

Synopsis

• As a new therapeutic modality with emerging novel approaches, oligonucleotide CMC development comes with its own challenges

• Understanding that a good early-stage CMC development strategy is essential for future late-stage and commercial success

• Establishing phase-appropriate and forward-looking CMC development strategies for novel oligonucleotide therapeutics

10:30 am Morning Break

11:30 am Panel Discussion: Scaling Up & Meeting Oligonucleotide Demand

Synopsis

• Moving into non-rare disease areas and producing oligonucleotides at scale for larger populations

• Evaluating technologies and the advantages and limitations of scale

• Analytical readiness for process change and late phase: strategic, regulatory, and technical perspectives

12:15 pm Challenges for Development, Scale Up & Production of Novel Oligonucleotide Products

  • Richard Welch Vice President - Chemistry, Manufacturing & Controls, Sirnaomics

Synopsis

• Discussing the unique supply chain requirement challenges

• Sourcing of CDMO support

• Evaluating multiple regulatory challenges faced in a global production environment

12:45 pm So You Wanna Make an Oligo: Oligonucleotide Outsourcing for Novices

Synopsis

• Addressing the outsourcing challenges faced by emerging companies and by established companies new to the field of oligonucleotides

• Transitioning between research-grade and clinical-grade oligonucleotide production

• Covering key similarities and differences between oligonucleotides and other products in terms of scale-up and outsourcing

1:15 pm Networking Lunch

2:15 pm Looking at Oligonucleotide DS CMC Capabilities

  • Peter Smith Director - New Modalities Chemistry, Astra Zeneca

Synopsis

  • Early-phase oligonucleotide CMC challenges: achieving phase-appropriate controls, quality & regulatory oversight whilst maintaining agility against project delivery requirements
  • Evolution of AstraZeneca's approach to oligonucleotide portfolio expansion drives new ways of working
  • The expansion and uplift of internal capabilities enables the future growth of oligonucleotide DS CMC development within AstraZeneca

Process Purification & Synthesis Techniques

2:45 pm Development of Kilogram-Scale Convergent Liquid-Phase Synthesis of Oligonucleotides

Synopsis

• Development of the novel convergent liquid-phase synthesis for an 18-mer oligonucleotide drug candidate to manufacture large quantities

• Synthesising and assembling fragments containing tetra- and pentamers into the 18-mer at a 2.5kg scale

• Controlling all critical impurities at low levels ensuring that after standard full-length oligonucleotide chromatographic purification the products have higher purities than those manufactured by SPOS

3:15 pm Orthogonal Purification Methods for Oligonucleotides

Synopsis

• General introduction of various purification methods applicable to oligonucleotide isolation

• Identifying the purification methods and selecting appropriate media based on the structure of the oligonucleotides

• Identifying suitable orthogonal purification processes applicable for large-scale manufacturing

3:45 pm Chair’s Closing Remarks

4:00 pm End of Conference