OLIGONUCLEOTIDE THERAPEUTICS
2024
San Diego, February 28, 2024
Welcome to hubXchange’s San Diego Oligonucleotide Therapeutics 2024, bringing together executives from pharma and biotech to address and find solutions to the key issues faced in oligonucleotide therapeutics.
Discussion topics will cover New Modalities, Oligonucleotide Discovery, Manufacturing and Drug Delivery.
Take advantage of this unique highly interactive meeting format designed for maximum engagement, collaboration and networking with your peers.
Venue: Handlery Hotel San Diego, 950 Hotel Circle North, San Diego CA 92108
SNAPSHOTS OF DISCUSSION TOPICS
- Drugging the genome to address base casuality
- Enabling cell type specific expression from RNA vectors
- Challenges in the synthesis and development of long oligos for editing
- Best practice for the oligonucleotide therapeutics hit-to-lead process
- Effective strategy for screening oligonucleotides at early stage
- Digital process and product development for oligonucleotide therapeutics
- Regulatory CMC challenges
- Challenges in drug substance and drug product manufacturing
- New receptors for targeted delivery of oligonucleotides
- Revisiting peptide and lipid conjugation for oligonucleotide delivery
Full Xchange Agenda
Click on each track for detailed agenda
New Modalities
Overcoming challenges in the utilisiation of novel self-amplifying RNA (saRNA) vaccines for emerging and endemic infections
- saRNA in the size range 9-16 kb have been historically very difficult to manufacture
- saRNA has a significantly more challenging stability profile than conventional linear mRNA
- Public perception of saRNA will be challenging for prophylactic vaccines given the current resistance encounter for the COVID-19 mRNA vaccines
Dr. Andy Geall is the Chief Development Officer and cofounder of Replicate Bioscience, a San Diego (California) based Biotech. The company has developed a diverse proprietary repertoire of virally derived self-replicating RNA vectors, which are being used to tackle a range of disease indications in oncology, infectious disease, autoimmune and inflammatory disorders. Dr. Geall has over 20 years of professional experience in the development of drug delivery systems and is a pioneer in the fields of mRNA vaccines and nucleic acid delivery. He is an inventor on 41 patent families, with 505 applications and 203 issued patents in multiple jurisdictions.
Networking Lunch
Spotlight Presentation by PolyPeptide
What Are Your Expectations of a Drug Substance Oligonucleotide Contract Manufacturer?
Enhancing the effectiveness of oligonucleotide therapeutics through medicinal chemistry
- What key properties of oligonucleotide therapeutics do you feel are the most amenable to being impacted by medicinal chemistry?
- Traditionally, performing high-throughput medicinal chemistry on oligonucleotides has proven challenging, what approaches do you take to innovate in this area?
- What classes of modifications do you find most interesting (sugar, phosphate, nucleobase, etc.)?
Kyle Knouse received his B.S in Chemistry from Temple University in Philadelphia working on novel antibiotic compounds to overcome resistance mechanisms, he then moved to San Diego where he received his Ph.D. in Chemistry from the Scripps Research Institute working in the lab of Phil S. Baran on novel organophosphorus chemistry. In 2021 he co-founded Elsie Biotechnologies where he is currently the Director of Chemistry. At Elsie he works to enable performing high-throughput medicinal chemistry on oligonucleotide therapeutics and explores novel delivery strategies. He has published 18 peer reviewed articles and 6 patents.
Oligonucleotide Discovery
Emerging opportunities for liver-targeting and extrahepatic areas with oligonucleotide-based therapeutics
• Current therapeutical landscape of oligo based therapeutics
• Expanded disease and therapeutical areas for liver targeting oligo therapeutics: from rare disease to big indications
• Emerging breakthroughs of extrahepatic therapeutics: delivery and diseases (nervous system, eye, muscle, lung, oncology and beyond)
Enthusiastic and dedicated scientist and industrial leader with experience of leading drug discovery from target identification, nomination and validation to selection and optimization of pre-clinical candidates. More than 16-years of post-graduate experience specializing in investigating molecular mechanisms and exploring innovative therapies, including ASOs, siRNA. With background in RNA-targeting therapies, including efficacy, toxicity, PK/PD, I have worked on neurological, ocular diseases, muscular diseases and liver-targeting indications.
Networking Lunch
Spotlight Presentation by PolyPeptide
What Are Your Expectations of a Drug Substance Oligonucleotide Contract Manufacturer?
Nucleic acid therapeutics optimization through in vitro and in vivo assays
- Correlate in vitro assays with in vivo findings
- Establish key assays with crisp endpoints
- Key differences between different nucleic acid therapeutics
Hans is heading activities for bioanalytical method development at Ionis Pharmaceuticals since 2005 to support various research programs. These include antisense oligonucleotides, siRNAs and microRNAs. His main focus is to establish methods for identification and quantitation of oligonucleotides and their metabolites from cells and tissues.
From 2000 to 2005 he was a member of the ADQC department, where he introduced mass spectrometry-based techniques for quality control of oligonucleotides and their starting materials.
He received his Ph.D. from the University of Tuebingen (Germany) for his work on capillary electrophoresis and hyphenating techniques to mass spectrometry in 1994.
Manufacturing
Future application of novel manufacturing oligonucleotide synthesis approaches and considerations for oligo-based conjugates
- Future of solution phase synthesis of oligos vs. traditional solid-phase synthesis
- Traditional solid–phase synthesis utilizes large volumes of solvents.
- Oligo synthesis suffers reduced yields as number of bases increases. How to synthesize long oligomers with greater yield and purity?
- Field is expanding into complex oligo bioconjugates. What are the current approaches are there benefits form stochastic vs. site-specifc conjugation?
Innovative and successful leader in oligonucleotide (ASO and siRNA) drug discovery and development from early stage screening and lead optimization to clinical GMP drug supply. Led the successful discovery and development of oligonucleotide delivery platforms including GalNAc, lipid, mAb, peptide and LNPs. Passionate about developing novel targeted oligonucleotide delivery approaches to fully realize the human therapeutic potential of oligonucleotides.
Networking Lunch
Spotlight Presentation by PolyPeptide
What Are Your Expectations of a Drug Substance Oligonucleotide Contract Manufacturer?
Downstream manufacturing challenges for synthetic oligonucleotides
- Chromatography, desalting, and isolation
- Conjugation
- Annealing for double stranded products
- Analytical characterization
A synthetic organic chemist by training, he has been working at Ionis Pharmaceuticals for 14 years in the Process Chemistry department. His work at Ionis involves optimizing various manufacturing processes for oligonucleotides and understanding their composition through analytical studies.
Drug Delivery
Using Lipid Nanoparticles (LNPs) as vehicles for intracellular delivery of nucleotide-based therapeutics
- Low drug loading efficiency, particularly for non-charged moieities
- Short blood circulation time
- Toxicity concerns
- Intracellular delivery obstacles due to particle size, tissue microenvironment, etc.
- Endosomal escape limitations
Dr. Grundy received his PhD from the University of Alberta and has more than 27 years of experience working in the pharmaceutical industry, including at Ionis Pharmaceuticals, Regulus Therapeutics, Neurocrine Biosciences, and Arena Pharmaceuticals. He has worked on multiple approved drugs , such as Kynamro® , Spinraza®, and Velsipity®, and has successfully progressed numerous small molecule, biologic, and oligonucleotide assets from early nonclinical testing thru to late-stage clinical development. He also previously co-founded and served on the board of directors of DTx Pharma, a preclinical stage biotechnology company addressing the delivery challenges of oligonucleotide therapeutics using its novel fatty acid ligand conjugate platform and that is now a subsidiary of Novartis.
Analytical assays to assess drug delivery efficacy
- What are the pain points for ADMET pertaining to Oligo drug delivery?
- What are the inherent difficulties when using assays to determine biodistribution? Intracellular localization?
- Advances in cell targeting and cell penetration: vesicle loading, SNAs, nanotechnology
- Emerging trends for oligo modifications and 3-D secondary structures to aid Oligo delivery
Dr. Carl Ascoli is the Chief Scientific Officer at Rockand and has over 30 years of experience in academia and industry. He works closely with team leaders of production, R&D, QC, and QA and has assisted in the development of thousands of primary antibodies and assays during his tenure.
Networking Lunch
Spotlight Presentation by PolyPeptide
What Are Your Expectations of a Drug Substance Oligonucleotide Contract Manufacturer?
Tissue target delivery and translation of novel targeted therapeutics
- Receptors for tissues targeted therapeutics
- Clinical and preclinical data in targeted therapeutics
- Challenges in translation of tissue-targeted therapeutics
- Cross-species translation in tissue-targeted therapeutics
- Regulatory strategy for tissue-targeted therapeutics
Ron is a co-founder and joined Locanabio full-time in March 2018. Ron serves as Senior Vice President, Research and Development and was a significant contributor to the foundational work of RNA-targeting CRISPR therapeutics for microsatellite expansion diseases. Prior to joining Locanabio, Ron worked at Verily. Ron is an expert in RNA splicing and development of therapeutics of RNA-mediated diseases. He was awarded the Myotonic Dystrophy Foundation (MDF) postdoctoral fellowship for his work at the laboratory of Gene Yeo PhD at UC San Diego. During his time at UC San Diego, he also worked with the department of Neurology, studying pathology and disease mechanisms of neuromuscular diseases. Prior to UC San Diego, Ron completed his PhD degree in Genetics at University of Florida where he studied RNA biology and gene therapy of neuromuscular diseases. Ron was awarded the 2019 Biocom Catalyst award for biotech leaders under 40 in California, and was a finalist for Endpoints News’ “20 under 40” biopharma leaders in 2021 and top 25 health care leaders in San Diego by The Healthcare Technology Report in 2022. Ron has published more than 25 papers and patents in RNA biology and RNA therapeutics.