Main Conference Day 3 - CET (Central European Time, GMT+01:00)
Oligonucleotides therapeutics have a great potential in a wide range of conditions – many of them where no therapy is currently available. A huge number of products have been approved over the last years. Synthetic oligonucleotides are at the interface of small molecules and biologicals and, from a quality point of view, specific considerations apply to this class of therapeutics. The European Medicines Agency EMA has recently published a draft ‘Guideline on the Development and Manufacture of Oligonucleotides’ which will be presented.
- René Thürmer, PhD - Deputy Head, BfArM Federal Institute for Drugs & Medical Devices
- John Lopez, PhD - Associate Director Science & Technology, Novartis
The talk will share the cross-industry perspective developed within the Synthetic Peptide Working Group of the International Consortium for Innovation and Quality in Pharmaceutical Development (IQ Consortium) on selection of Regulatory starting materials for synthetic peptides. The established approach when using solid phase peptide synthesis leads to all protected amino acids and dipeptides being designed regulatory starting materials (RSMs). As the industry strives to reduce carbon footprint and costs related to drug substance manufacturing, newer alternative manufacture strategies (such as fragment-based approaches) could lead to opportunities for enhanced RSM positions. This talk will give an outline on alternative options, include theoretical case studies.
- Martin Kenworthy, PhD - Principal Scientist, Chemical Development, AstraZeneca
The global deprotection step is the final stage in the upstream process of peptide synthesis. When peptide elongation is performed via solid-phase peptide synthesis (SPPS), this step coincides with resin cleavage. Traditionally, polyfluoroalkyl substances (PFAS), particularly trifluoroacetic acid (TFA), have been the reagents of choice. However, increasing regulatory scrutiny and anticipated usage restrictions necessitate the development of alternative strategies. Here, we present ongoing efforts in our laboratory to identify and implement viable substitutes for TFA.
- Fernando Albericio, PhD - Research Professor, School of Chemistry, University of Kwazulu-Natal
Ethris, a clinical stage biotechnology company, uses proprietary, spray-dryable, clinically validated, non-immunogenic messenger RNA (SNIM®RNA) and lipidoid nanoparticle (SNaP LNP®) technology platforms to discover, design, and develop innovative therapies and vaccines including mucosal vaccines. ETH47 is a first-in-class mRNA-based treatment for uncontrolled asthma patients that was uniquely designed to be administered through a nasal spray. The mRNA contained in ETH47 encodes interferon lambda (IFNλ), a protein crucial for innate immune defense in the airways. ETH47’s versatile, virus- and mutation-independent mode of action has the potential to broadly address seasonal and emerging viral triggers of asthma exacerbations, one of the most common causes of acute symptoms in patients with asthma. ETH47 demonstrated favorable safety and tolerability at all tested doses in a Phase 1 clinical trial in healthy volunteers. The trial confirmed targeted activity in the respiratory tract, with robust local induction of IFNλ and activation of antiviral genes, with no systemic exposure to mRNA, IFNλ, or the lipidoid nanoparticle, thereby minimizing the risk of off-target effects. Ethris is now embarking on a Phase 2 clinical trial that will assess the ability of intranasal ETH47 to reduce asthma-related symptoms, following a rhinovirus challenge in adults with asthma.
- Thomas Langenickel, MD, PhD - Chief Medical Officer, Ethris GmbH
mRNA vaccines have emerged as transformative tools in both prophylactic and therapeutic medicine. Their rapid design and manufacturing enable swift responses to emerging infectious diseases, while their robust efficacy and favorable safety profiles have set new standards for vaccine development. In prophylactic applications, mRNA vaccines offer adaptability to novel pathogens, high immunogenicity, and the potential for scalable production. In therapeutic contexts, especially in oncology, mRNA technology enables the encoding of multiple tumor antigens in a single construct—empowering the immune system to mount a broad and targeted response. Despite these advantages, current delivery platforms—most notably lipid nanoparticles (LNPs)—face significant challenges. These include the need for stringent cold storage, instability in multidose formats, inconsistent biodistribution, and immune reactions linked to excipients such as polyethylene glycol (PEG). Moreover, high-dose and frequent administration, especially in cancer immunotherapy, exacerbates concerns over reactogenicity, anti-PEG antibodies, and off-target effects like liver accumulation. To address these hurdles, we have developed innovative LNP formulations tailored for both prophylactic and therapeutic (oncological) settings: 1) Prophylactic Innovation: Our next-generation LNP platform employs proprietary ionizable lipids, advanced helper lipid compositions, and PEG alternatives. These advances enhance vaccine stability at refrigerated and even ambient temperatures, simplify logistics, and minimize acute immune reactions. This enables the use of mRNA vaccines in broader, real-world scenarios where cold-chain requirements are a barrier; and 2) Oncological (Therapeutic) Innovation: For cancer immunotherapy, we present a PEG-free, liver-bypassing LNP platform optimized for the delivery of multi-epitope mRNA constructs. This design supports repeated, high-dose administrations typical in oncology by reducing reactogenicity and improving biodistribution. Our approach facilitates the induction of potent, broader T cell responses while minimizing off-target effects—key for the efficacy and safety of personalized or off-the-shelf cancer vaccines. By transforming both the prophylactic and therapeutic delivery of mRNA, CureVac’s tailored LNP platforms are designed to overcome current technological barriers—unlocking the promise of mRNA vaccines in infectious disease prevention and cancer therapy.
- Vusala Ibrahimova, Ph.D. - Research Scientist, CureVac SE
Until recently, interpretation of the Quality Working Party Questions and Answers on API Mix as the only available guidance drove the industry toward energy-intensive lyophilization as the preferred isolation format for highly water-soluble oligonucleotide APIs. The July 2024 EMA draft Guideline on the Development and Manufacture of Oligonucleotides opened the door to registration of oligonucleotide API in solution as an active substance rather than a drug product intermediate. While the solution option affords advantages for sustainability, scale, and supply chain flexibility it also requires a microbial control strategy more typical of biological than synthetic processes. This presentation will propose a robust microbiological control strategy for a generic oligonucleotide purification process, highlighting the appropriate principles of Annex 1 applied to such a non-sterile manufacturing process.
- Victor Goetz, PhD - Executive Director, TS/MS New Modalities, Eli Lilly and Company
Exploring novel technologies in solid-phase peptide synthesis designed to improve CMC outcomes—enhancing crude purity, reducing solvent use, and enabling precise temperature control. These innovations support robust process development and tech transfer, offering practical solutions for cost-efficient and scalable peptide manufacturing.
- Hanson Chang - VP/GM, Engineering & Instrumentation, CSBio
- Bertrand Guélat, PhD - Senior Expert Science & Technology, Novartis
Tag-Assisted Peptide Synthesis (TAPS) is a solution-phase synthetic approach that offers several advantages to the established Solid-Phase Peptide Synthesis (SPPS), for example by reducing the environmental footprint of peptide synthesis through significantly lower solvent use. TAPS has to date mainly been employed for linear synthesis of short peptides and peptide fragments with subsequent convergent assembly, but herein we disclose for the first time the development and application of a TAPS platform to produce full-length, complex peptide active pharmaceutical ingredients in a linear manner, on manufacturing scale.
- Henrik Johansson Castro, PhD - Senior Development Scientist, Novo Nordisk