OLIGONUCLEOTIDE THERAPEUTICS
XCHANGE EUROPE
Brussels, Belgium
June 27, 2023
Welcome to hubXchange’s Oligonucleotide Therapeutics Europe 2023, 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: DoubleTree by Hilton Brussels City, Ginestestraat 3 Rue Gineste, 1210 Brussels, Belgium
SNAPSHOTS OF DISCUSSION TOPICS
- A perspective on oligonucleotide therapy: approaches to biomarker-driven patient selection for early clinical trials
- Recent advances in oligonucleotide therapeutics development
- Best practice for the oligonucleotide therapeutics hit-to-lead process
- Targeted delivery of RNA using viral biology
- Regulatory challenge in developing/commercialising Oligonucleotide drug products
- Challenges in drug substance and drug product manufacturing
- Extra-hepatic delivery of oligonucleotides therapeutics
- Advances in oligonucleotide drug delivery
Full Xchange Agenda
Click on each track for detailed agenda
New Modalities
Opening Address & Keynote Presentation
Industrializing the treatment of nano-rare patients for free for life
n-Lorem is a non-profit foundation I established in January of 2020 with the mission of discovering, developing and providing experimental ASOs to nano-rare patients (patients with mutations expressed in <30 patients worldwide, for free for life. The combination of the efficiency of the technology and the special guidance issued by the FDA for ASOs to be provided for free to nano-rare patients makes the mission possible. To date, we have received more than 180 applications for treatment and accepted more than 80 patients for treatment. We established processes that assure that patients are exposed only to prudent risks and that each step in the process is the highest quality possible and that we learn maximally from each patient and the aggregate experience. I will describe the progress registered to date and our plans.
A perspective on oligonucleotide therapy: approaches to biomarker-driven patient selection for early clinical trials
- Challenges and prospects of integrating biomarker development into the early testing of novel agents.
- Biomarker-driven early clinical trial enrollment Vs. an unselected populationbased approach.
- Main concerns over the use of biomarkers in early clinical trials:
- the use of assays that are not validated or certified, incorrect patient selection, increased cost, logistical issues related to the prescreening strategies, and ethical issues regarding sampling strategies.
- Can current development of companion diagnostics for targeted therapies (one assay–one drug) can be replaced by multiassay platforms?
- Building an ecosystem of cooperative environment to avoid duplication of effort:
- collaboration between academic institutions, regulatory authorities, pharmaceutical and diagnostic companies (data sharing, standardized procedures, technology exchange, interpret large-scale genomic data in actionable format).
Programme Leader, HAYA Therapuetics SA
Amela Jusic is a patient oriented biomedical scientist with over 15 years’ experience in genomic biomarkers. She is leading a ViewHAYATM, a top-notch platform for biomarker discovery and validation, and CDx development for HAYA’s therapeutic assets. Prior HAYA Therapuetics, as a Marie Skłodowska-Curie Actions fellow, she has been leading the Horizon 2020 funded project on the biomarker potential of microRNA in hypertension at the Luxembourg Institute of Health in Luxembourg. In addition, she has been an associate professor at the Faculty of Medicine and Faculty of Natural Sciences and Mathematic, University of Tuzla, Bosnia and Herzegovina. Dr Jusic is dedicated to being an impact player in translational research thorough gathering complementary expertise from clinicians, basic researchers, systems biologists, and industrials, towards the satisfaction of unmet medical needs.
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n-of-1 batches from the perspective of a CMO
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Working with the n-of-1 sponsors
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Lessons learned based on n-of-1 projects to date
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What does the future landscape look like in this area
Director of Custom Oligonucleotides, ChemGenes
Jeremy Little is currently the director of custom oligonucleotides at ChemGenes Corporation in Wilmington, MA, and is responsible for the company’s custom oligonucleotide manufacturing group. He joined the team at ChemGenes in early 2019, having more than 10 years of experience in the field of nucleic acid drug discovery and oligonucleotide manufacturing. Prior to joining ChemGenes, Jeremy held positions at AnaSpec, BioSpring GmbH, and Pfizer. While at Pfizer, he established and managed on-site oligomer production laboratories to support Pfizer’s internal efforts in the field of oligonucleotide drug discovery. Before his transition into the world of oligonucleotides, Jeremy spent the first 7 years of his career as a medicinal chemist at Pfizer and Millenium Pharmaceuticals. He received his Ph.D. from the University of Wisconsin-Madison in 2001 where he developed a novel route into the ring system of a class of compounds termed aziridinomitosenes and related to Mitomycin-C.
Networking Lunch
Spotlight Presentation
What are your expectations of a drug substance oligonucleotide contract manufacturer?
- What are the timeline and scale expectations?
- What is most important factors in selecting your CMO – relationship, cost, timelines, project management
- How important is innovation and the move towards greener processes
Director, Business Development (US), PolyPeptide
Trishul is involved in industry peer groups such as the TIDES Advisory committee, Boulder Peptide Symposium Scientific Board, a member of the PolyPeptide Group’s Executive Strategic Team in the US and member of the Global Management Group at PolyPeptide.
13:20 – 13:50
Poster Session
Thiophosphoramidate Morpholino Oligonucleotides (TMOs): A novel class of PMOs compatible with conventional automated oligonucleotide synthesis
Phosphorodiamidite Morpholino Oligonucleotides (PMOs) are short oligonucleotides (ON) where the sugar moiety and phosphate bond of the nucleotidic backbone are substituted by a morpholino ring and a phosphorodiamidite linkage respectively. These rigid structures, with low off-target effects act as steric blockers by specifically targeting mRNAs exons responsible for the production of defective proteins. PMOs emerged as valuable antisense therapeutics given the FDA approved two PMOs (Exondys 51® and Viltepso®) for the treatment of Duchenne Muscular Dystrophy.
Director of Custom Oligonucleotides, ChemGenes
Jeremy Little is currently the director of custom oligonucleotides at ChemGenes Corporation in Wilmington, MA, and is responsible for the company’s custom oligonucleotide manufacturing group. He joined the team at ChemGenes in early 2019, having more than 10 years of experience in the field of nucleic acid drug discovery and oligonucleotide manufacturing. Prior to joining ChemGenes, Jeremy held positions at AnaSpec, BioSpring GmbH, and Pfizer. While at Pfizer, he established and managed on-site oligomer production laboratories to support Pfizer’s internal efforts in the field of oligonucleotide drug discovery. Before his transition into the world of oligonucleotides, Jeremy spent the first 7 years of his career as a medicinal chemist at Pfizer and Millenium Pharmaceuticals. He received his Ph.D. from the University of Wisconsin-Madison in 2001 where he developed a novel route into the ring system of a class of compounds termed aziridinomitosenes and related to Mitomycin-C.
Recent advances in oligonucleotide therapeutics development
- Recent advances in oligonucleotide drug development in the cardiovascular and metabolic field
- How far are we from a broad use of oligonucleotides in common illnesses, such as cardiovascular or metabolic diseases?
- How to optimize delivery to extra-hepatic tissues?
- Novel targets specific to cardiac, vascular, and metabolic diseases
- How to evaluate on-target activity of non-coding RNA-targeting oligonucleotides in clinical setting – without biopsies
- What are the advantages of oligonucleotides over small molecules or antibodies?
Head of Medical Research & Intelligence, Cardior
Dr. Batkai, co-founder of Cardior Pharmaceuticals GmbH in Hannover, is currently Head of Medical Research & Intelligence and part of the clinical team at the company. He is an internationally recognized translational researcher in the cardiovascular field, specializing in oligonucleotide and RNA therapeutics pharmacology. Dr. Batkai is a leading medical scientist with over 150 publications in high-ranking scientific journals, as well as a certified expert in preclinical drug development. Prior to joining biotech industry, Dr. Batkai spent several years at US National Institutes of Health (NIH) in Bethesda, MD where he led Cardiovascular Phenotyping Core Facility, and then moved to Hanover Germany to become the head of Cardiovascular Phenotyping and Translational Strategies Group at IMTTS of Hannover Medical School (MHH).
Oligonucleotide Discovery
Opening Address & Keynote Presentation
Industrializing the treatment of nano-rare patients for free for life
n-Lorem is a non-profit foundation I established in January of 2020 with the mission of discovering, developing and providing experimental ASOs to nano-rare patients (patients with mutations expressed in <30 patients worldwide, for free for life. The combination of the efficiency of the technology and the special guidance issued by the FDA for ASOs to be provided for free to nano-rare patients makes the mission possible. To date, we have received more than 180 applications for treatment and accepted more than 80 patients for treatment. We established processes that assure that patients are exposed only to prudent risks and that each step in the process is the highest quality possible and that we learn maximally from each patient and the aggregate experience. I will describe the progress registered to date and our plans.
Best practice for the oligonucleotide therapeutics hit-to-lead process
- Identification of lead oligonucleotide therapeutics requires a different approach to those used for small molecules and monoclonal antibodies.
- Even within the oligo field distinct approaches are needed for siRNAs, ASOs, splice skipping, gene upregulation, editing etc.
- With a focus on siRNAs and ASOs, we will discuss best practices for initial lead id screens.
- We will also focus on how active sequences can then be further assessed and optimized prior to commencement of GLP toxicology studies.
Vice President, Discovery and Translational Research, Alnylam Pharmaceuticals
Paul joined Alnylam in March 2018 and is responsible for leading the Discovery and Translational
Research function. He has overall responsibility for new target identification/validation, biomarkers and all preclinical drug discovery programs. Building on his depth of prior experience, he also leads the Alnylam Human Genetics Center which focuses on the identification of new drug targets from large genotype-phenotype datasets. Paul has over 18 years of biotech and pharma experience. He joined Alnylam following a tenure at Amgen and deCODE genetics where he held roles of increasing responsibility. Recently he was appointed as the Director of the Translational Systems Biology group and led a large team that was focused on making discoveries from human genetics to influence target selection. Paul obtained his academic training at the University of Edinburgh (BSc, Pharmacology) and the
University of Dundee (PhD, Molecular Biology).
Networking Lunch
Spotlight Presentation
What are your expectations of a drug substance oligonucleotide contract manufacturer?
- What are the timeline and scale expectations?
- What is most important factors in selecting your CMO – relationship, cost, timelines, project management
- How important is innovation and the move towards greener processes
Director, Business Development (US), PolyPeptide
Trishul is involved in industry peer groups such as the TIDES Advisory committee, Boulder Peptide Symposium Scientific Board, a member of the PolyPeptide Group’s Executive Strategic Team in the US and member of the Global Management Group at PolyPeptide.
Manufacturing
Opening Address & Keynote Presentation
Industrializing the treatment of nano-rare patients for free for life
n-Lorem is a non-profit foundation I established in January of 2020 with the mission of discovering, developing and providing experimental ASOs to nano-rare patients (patients with mutations expressed in <30 patients worldwide, for free for life. The combination of the efficiency of the technology and the special guidance issued by the FDA for ASOs to be provided for free to nano-rare patients makes the mission possible. To date, we have received more than 180 applications for treatment and accepted more than 80 patients for treatment. We established processes that assure that patients are exposed only to prudent risks and that each step in the process is the highest quality possible and that we learn maximally from each patient and the aggregate experience. I will describe the progress registered to date and our plans.
Regulatory challenge in developing / commercialising Oligonucleotide drug products
- Oligonucleotides are excluded from small molecules and biologics ICH guidelines
- Currently there is no regulatory consensus on the CMC best practices for oligonucleotides
- Oligonucleotide complexity is increasing significantly with conjugation to different delivery vectors posing additional regulatory challenges for the industry
Senior Principal Scientist New Modalities, AstraZeneca
Nadim Akhtar, Ph.D., is a Senior Principal Scientist in the New Modalities and Parenteral Development Department in Pharmaceutical Technology and Development function at AstraZeneca. Nadim has been working for AstraZeneca since 2007. During this time Nadim has worked on both early and late-stage portfolio supporting development and commercialisation of small molecules and new modalities i.e. oligonucleotides, peptides, polymeric nanoparticles, dendrimers, and mRNA products. Nadim is currently responsible for developing characterisation and control strategies for New Modalities.
11:20 – 12:20
Discussion on how to manage unusual building blocks from sourcing, patents, quality
- How to manage requests for use of GalNac
- Where can unusual patented building blocks like GalNac be sourced from
- How do you ensure qualification of building block vendors
Director, Business Development (US), PolyPeptide
Trishul is involved in industry peer groups such as the TIDES Advisory committee, Boulder Peptide Symposium Scientific Board, a member of the PolyPeptide Group’s Executive Strategic Team in the US and member of the Global Management Group at PolyPeptide.
Spotlight Presentation
What are your expectations of a drug substance oligonucleotide contract manufacturer?
- What are the timeline and scale expectations?
- What is most important factors in selecting your CMO – relationship, cost, timelines, project management
- How important is innovation and the move towards greener processes
Director, Business Development (US), PolyPeptide
Trishul is involved in industry peer groups such as the TIDES Advisory committee, Boulder Peptide Symposium Scientific Board, a member of the PolyPeptide Group’s Executive Strategic Team in the US and member of the Global Management Group at PolyPeptide.
13:20 – 13:50
Poster Session
German reliability for scalable cGMP therapeutic oligonucleotide manufacturing
- Designing a state-of-the-art solvent mixing facility
- Small to large-scale scalable manufacturing
Product Manager, empBIOTECH
Christian Frauendorf is Product Manager within the Nucleic Acid Synthesis Reagents department (NSR) at empBIOTECH. He joined the company in 2020. As Product Manager he is responsible for gathering customer requirements, defining the products long-term vision as well as overseeing the marketing strategy. He also coordinates production activities and strengthens the collaboration with clients on a day-to-day interaction. Christian has more than 20 years of experience in the field of nucleic acid synthesis and modification. He has been working on targeted delivery of oligonucleotides and CMC of therapeutic oligonucleotides (Antisense, siRNA).
Challenges in drug substance and drug product manufacturing
- Stereochemical Purity:
- How should we address diastereomer control in phosphorothioated oligonucleotides?
- To what extend control is at all needed and what is an acceptable level of variability?
- Large scale manufacturing:
- How can we tackle the challenge of large-scale manufacturing and improve manufacturing and formulation processes in order to cover the increasing demand for oligonucleotides?
- How can enzymatic methods (ligase, polymerase) contribute to synthetic strategies of oligonucleotide assembly?
- Oligo Conjugates:
- What kind of oligo conjugates beyond GalNAc do we see on the rise?
- What kind of associated CMC challenges do we anticipate with the surge of non-GalNAc conjugates?
- Solution API:
- E.g., is avoiding lyophilization and providing drug substance in solution a better approach?
- How can we accelerate and improve DS dissolution during DP manufacturing (i.e. low wettability)?
- What advances are you excited about bringing into your DS / DP process in the next 3 years?
Scientific Lead and Project Leader, Novartis
Ulrike Rieder is Scientific Lead and Project Leader for Oligonucleotides and other New Modalities within the Technical R&D unit at Novartis. She joined Novartis in 2017 and since then she has been actively shaping and supporting the development of oligonucleotide therapeutics. As Scientific Lead she oversees the activities and strengthens the interface and collaboration with different departments. Ulrike has more than 15 years’ experience in the field of nucleic acids. She has been working on the synthesis of modified nucleobases, phosphoramidites and oligonucleotides and has been implementing chemical tools to analyze functional RNA/DNA in-vitro/in-vivo. She also has been exploring DNA-encoded chemical libraries elaborating conjugation chemistries for oligonucleotides.
Drug Delivery
Opening Address & Keynote Presentation
Industrializing the treatment of nano-rare patients for free for life
n-Lorem is a non-profit foundation I established in January of 2020 with the mission of discovering, developing and providing experimental ASOs to nano-rare patients (patients with mutations expressed in <30 patients worldwide, for free for life. The combination of the efficiency of the technology and the special guidance issued by the FDA for ASOs to be provided for free to nano-rare patients makes the mission possible. To date, we have received more than 180 applications for treatment and accepted more than 80 patients for treatment. We established processes that assure that patients are exposed only to prudent risks and that each step in the process is the highest quality possible and that we learn maximally from each patient and the aggregate experience. I will describe the progress registered to date and our plans.
09:05 – 10:05
Extra-hepatic delivery of oligonucleotides therapeutics
- Conjugates (e.g. lipids, peptides) are among the most promising strategies for delivery: What are the current main limitations in oligonucleotide-conjugates? How can we overcome them?
- Targeting cell surface receptors (e.g. ASGPR) has been a successful delivery approach. Is it plausible to find similar receptors? How do these approaches compare with passive targeting approaches like ApoE-binding LNPs? What are the challenges and opportunities of both approaches?
- Can we use in vitro studies to predict in vivo fate? What questions are answerable in vitro?
Senior Scientist II, Sixfold
Aurélie is senior scientist II at Sixfold Bioscience, a London-based company developing RNA delivery systems for oligonucleotide therapeutics. She focuses mainly on characterizing RNA vehicles in biological and non-biological matrices as well as elucidating their mechanism of action. Aurélie completed her Ph.D. in Chemistry at McGill University (Canada) with Prof. Sleiman, where she worked on DNA nanostructures. She is an active member of the Oligonucleotide Therapeutics Society (OTS), a leading non-profit organization that fosters academic and industrial R&D of nucleic acid therapeutics internationally.
Networking Lunch
Spotlight Presentation
What are your expectations of a drug substance oligonucleotide contract manufacturer?
- What are the timeline and scale expectations?
- What is most important factors in selecting your CMO – relationship, cost, timelines, project management
- How important is innovation and the move towards greener processes
Director, Business Development (US), PolyPeptide
Trishul is involved in industry peer groups such as the TIDES Advisory committee, Boulder Peptide Symposium Scientific Board, a member of the PolyPeptide Group’s Executive Strategic Team in the US and member of the Global Management Group at PolyPeptide.
15:35 – 16:35
Advances in oligonucleotide drug delivery
- What makes an effective drug delivery system for oligonucleotides?
- What are the current challenges and opportunities with bioconjugates and nanotechnologies?
- What are the strategies to enhance delivery of oligonucleotides?
- How can we better translate drug delivery systems from bench to the clinic?
Principal Scientist, Ochre Bio
Duygu completed her PhD in Biochemistry in the University of Groningen, the Netherlands. Her research involved re-engineering and reconstituting ion channel proteins into liposomes to create stimuli-responsive drug delivery systems. Afterwards, she held positions at small biotech companies where she specialized in RNA therapeutics. Duygu’s work involved utilizing various RNA modalities, including antisense oligonucleotides, siRNAs, and mRNA, with the goal of effectively delivering the therapeutic cargo to target cells. Through collaborating with many academic groups, Duygu has worked with different drug delivery platforms. Currently she is a Principal Scientist at Ochre Bio, developing RNA therapies for chronic liver diseases.