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7:00am - 8:00am 60 mins
Workshop Registration
8:00am - 8:15am 15 mins
Workshop #1: The State of the Art in mRNA Delivery
Workshop Moderator’s Opening Remarks
  • Örn Almarsson, PhD - Head of Formulations, Moderna Therapeutics
8:00am - 8:20am 20 mins
Workshop #2: Oligonucleotide Drug Development at Warp Speed: Managing CMC Operations to Support Accelerated Clinical Development
Workshop Co-Moderators’ Opening Remarks
  • G. Susan Srivatsa, PhD - President, ElixinPharma
  • Fran Wincott, PhD - President, Wincott & Associates, LLC
8:00am - 8:15am 15 mins
Workshop #3: Potential Green Chemistry Solutions for Peptide Manufacturing
Workshop Moderator’s Opening Remarks
  • Trishul Shah, MS - Director Business Development, PolyPeptide Laboratories Inc.
8:00am - 8:15am 15 mins
Workshop #4: Accelerating Peptides to IND: Moving to the Clinic, CMC and Beyond
Accelerating Peptides to IND: Moving to the Clinic, CMC and Beyond
  • Bruce Morimoto, PhD - Vice President, Drug Development Operations, Alkahest
8:15am - 8:45am 30 mins
Info
Workshop #1: The State of the Art in mRNA Delivery
LUNAR®: Enabling mRNA Therapeutics and Vaccines
  • Pad Chivukula, Ph.D. - Chief Scientific Officer and COO, Arcturus Therapeutics

Arcturus has developed a novel platform called LUNAR®, a proprietary lipid-enabled delivery system for RNA medicines. The challenge for mRNA therapeutics, however, is delivering the mRNA to the target cell type. Arcturus’ LUNAR platform technology provides effective delivery of mRNA to appropriate cell types in liver, lung and other tissues.

8:15am - 9:00am 45 mins
Info
Workshop #3: Potential Green Chemistry Solutions for Peptide Manufacturing
Solid-Phase Peptide Synthesis: Being Greener, Being Better
  • Fernando Albericio, PhD - Department of Organic Chemistry, University of Barcelona

Although, the concept of the “solid-phase” by itself is totally green since the point that all reactions are carried in only one reactor with a clear minimization of mechanical losses and of mass transfer, SPPS is using highly reprotoxic solvents, being classified as a Substance of Very High Concern.  Our work is a first and important step toward a greener SPPS in terms of replacement of toxic solvents, waste generated, and energy efficiency.

8:15am - 9:00am 45 mins
Info
Workshop #4: Accelerating Peptides to IND: Moving to the Clinic, CMC and Beyond
Analytical Methods, Pre-formulation, and Formulation for Early Phase Development
  • Christopher Rhodes, PhD - President and CEO, Drug Delivery Experts

The discussion will focus on all aspects of drug product development. We will start with analytical methods required for drug product, including in process controls, QC release methods, and stability, and how they differ from those for drug substance. In addition, we will discuss preformulation and formulation development of peptides to support non-clinical research studies, toxicity studies, and clinical programs. A third topic area to cover will be the selection, design, and development of delivery systems for peptides.

8:20am - 8:50am 30 mins
Workshop #2: Oligonucleotide Drug Development at Warp Speed: Managing CMC Operations to Support Accelerated Clinical Development
Points to Consider with US and EU Expedited Regulatory Pathways
  • Paul Manley - President and Principal Consultant, Orvieto Consulting
8:45am - 9:15am 30 mins
Info
Workshop #1: The State of the Art in mRNA Delivery
Safe Delivery of Nucleic Acid Cargoes Using Anionic Carriers
  • Steffen Panzner - CEO, Lipocalyx GmbH

Anionic carriers represent a safe way for delivering of nucleic acids due to much reduced immunostimulation. Anionic carriers therefore open new routes for repeated dosing or targets residing within antigen presenting cells.

8:50am - 9:20am 30 mins
Workshop #2: Oligonucleotide Drug Development at Warp Speed: Managing CMC Operations to Support Accelerated Clinical Development
From Target to Patient; Options for Oligonucleotides as Personalized Medicines
  • Chantal Reed, PhD - Vice President, Brain Hz Consulting, Inc.
9:00am - 9:45am 45 mins
Info
Workshop #3: Potential Green Chemistry Solutions for Peptide Manufacturing
Evolved Enzymes for Commercial Chemical Synthesis Pathways
  • Christina Boville, PhD - Resnick Prize Postdoctoral Scholar, CalTech

Enzymes have been widely applied in manufacturing, where they are valued for their high efficiency. When compared to traditional synthetic chemistry, processes using enzymes offer reductions in energy costs and hazardous waste. However, the applications of existing enzymes are severely limited by the scope of the natural chemical reactions they can catalyze. Using directed evolution—the subject of the 2018 Nobel Prize in Chemistry—it is possible to merge the environmental benefits of enzymes with the versatility of chemical manufacturing to provide a sustainable route to useful products. We have used directed evolution to create an evolved variant of tryptophan synthase that is able to produce nearly 100 noncanonical amino acids in a single step from cheap materials, with water as the only byproduct. This method can be broadly used to manufacture noncanonical amino acids on gram to kilogram scales, and the enzyme can be easily separated, allowing it to be reused or biodegraded. Unlike existing methods for producing ncAAs, our approach does not require hazardous chemicals such as cyanide or rare metals such as palladium. As enzyme engineering continues to expand scope of available products, this may lead to a new, more efficient path to manufacturing noncanonical amino acids.

9:00am - 9:45am 45 mins
Info
Workshop #4: Accelerating Peptides to IND: Moving to the Clinic, CMC and Beyond
IND-enabling, Nonclinical Safety Studies for Peptides: Pharmacokinetics, Bioanalysis and Toxicology
  • Bruce Morimoto, PhD - Vice President, Drug Development Operations, Alkahest

Peptides bridge small molecules and biologics, not only in their size, but also in specificity and selectivity. These unique properties of peptides require specialized consideration when designing and executing the safety studies to support first-in-human clinical trials. This talk will outline and discuss the pharmacokinetics and bioanalysis of peptides and the design of toxicology studies for peptides.

9:15am - 9:45am 30 mins
Info
Workshop #1: The State of the Art in mRNA Delivery
Chemical Design of Synthetic Carriers for CRISPR/Cas Gene Editing and mRNA-mediated Protein Replacement Therapy
  • Daniel Siegwart, PhD - Associate Professor, UT Southwestern Medical Center

We will describe structure‐guided, rational optimization of nanoparticle carriers for delivery of long RNAs to achieve mRNA-mediated protein replacement and CRISPR/Cas gene editing. For example, we will show how mDLNPs effectively delivered fumarylacetoacetate hydrolase (FAH) mRNA that normalized liver function and significantly extended survival in difficult‐to‐treat Hepatorenal Tyrosinemia Type I (HT‐1) mouse model.

9:20am - 9:50am 30 mins
Info
Workshop #2: Oligonucleotide Drug Development at Warp Speed: Managing CMC Operations to Support Accelerated Clinical Development
Use of Prior Knowledge to Establish Enhanced Flexible Platform-based Control Strategies
  • Zhijie Sui, PhD - Senior Scientist, Biogen

The talk will discuss development of an enhanced and flexible control strategy to support antisense oligonucleotides programs at Biogen. By leveraging knowledge accumulated from prior experience, the control strategy uses risk-based scientific approach to determine control points and testing scheme to reduce redundancies, increase quality and responsiveness, show process control, and enable rapid release of material.

9:45am - 10:15am 30 mins
Workshop #1: The State of the Art in mRNA Delivery
Networking Refreshment Break
9:45am - 10:15am 30 mins
Workshop #3: Potential Green Chemistry Solutions for Peptide Manufacturing
Networking Refreshment Break
9:45am - 10:15am 30 mins
Workshop #4: Accelerating Peptides to IND: Moving to the Clinic, CMC and Beyond
Networking Refreshment Break
9:50am - 10:20am 30 mins
Workshop #2: Oligonucleotide Drug Development at Warp Speed: Managing CMC Operations to Support Accelerated Clinical Development
Networking Refreshment Break
10:15am - 10:45am 30 mins
Info
Workshop #1: The State of the Art in mRNA Delivery
Advancing the Delivery of LNP-encapsulated mRNA Therapeutics
  • Frank DeRosa, PhD - SVP, Research and Process Development, Translate Bio

Translate Bio has demonstrated the potential of messenger RNA (mRNA) therapeutics as a new approach for the treatment of diseases caused by protein or gene dysfunction. We have observed successful production of desired proteins through delivery of lipid nanoparticle-encapsulated mRNA to various target tissues. Our proprietary lung delivery system has supported the advancement of our lead program in cystic fibrosis into the clinic. We have applied this delivery technology via other routes of administration in multiple target tissues to assess the potential across a broad array of diseases. We present here various routes of administration of mRNA in lipid nanoparticles which result in successful protein production and distribution in multiple target tissues.

10:15am - 11:00am 45 mins
Info
Workshop #3: Potential Green Chemistry Solutions for Peptide Manufacturing
Convergent Peptide Synthesis in Flow: Preferred Regulatory Strategies for Commercial Peptide Manufacture
  • Michael Kopach, Ph.D. - Senior Research Advisor, Eli Lilly and Company

Hybrid SPPS/LPPS is a well known method of peptide synthesis. A key benefit is that coupling peptide  fragments insolution (LPPS) can significantly reduce solvent use, resulting in greener synthetic approaches.  For synthesis of small fragments (< 10 mer) SPPS provides certain advantages over full solution phase chemistry approaches peptides  can be synthesized more rapidly and isolated with a higher purity.  These small peptide fragments can be well characterized with high purity which make them ideal candidates as regulatory starting materials.  As a peptide chain grows longer in SPPS challenges with increased levels of deletion  impurities can lead to marked increases in costs associated with purification, largely due to decreasing coupling efficiency related to mass transfer resistances and steric hindrance.   Additionally, convergent approaches to peptide synthesis are far more amenable to alternative reactor designs such as flow infrastructure given the low concentration, high potency and high value of the peptide assets.  Control strategies for convergent approaches can also be significantly simplified given that peptides are routinely terminally purified through chromatographic means.  Synthesis impurities that are markedly different in molecular weight which are expected by hybrid SPPSLPPS /are often more effectively separated in preparative chromatographic systems due to large differences in retention time.  Despite the potential large upsides of hybrid SPPS/LPPS strategies, most companies manufacturing peptides presently do not utilize this strategy. The focus of the presentation will be on efforts at Eli Lilly to develop novel flow methodology to produce commercial peptides in internal or external facilities. This methodology has been applied extensively in small molecule manufacturing and is known to improve yield, purity and can reduce solvent usage by up to 50%. Our initial results indicate that this approach could be transformative to the peptide industry.    In addition, the presentation will deliver a scientific and business  case for establishing short to medium size peptide fragments (<10 mer ) as regulatory starting materials.

10:15am - 11:00am 45 mins
Info
Workshop #4: Accelerating Peptides to IND: Moving to the Clinic, CMC and Beyond
Peptide CMC Approaches for a Fast and Successful IND Filing
  • Mimoun Ayoub, PhD - Director and Head of North American and Emerging Markets, CordenPharma International

This presentation will focus on the FDA requirements but also highlight the roles of the sponsor and the manufacturer. Understanding the manufacturing process, developing appropriate analytical methods allowing for reliable monitoring on the impurities and setting the product specifications are key elements to address any potential safety concerns. The IND dossier should address all of the sections related to the process, analytical methods and justification of the specifications. An overview of the various sections will be presented.

10:20am - 10:50am 30 mins
Workshop #2: Oligonucleotide Drug Development at Warp Speed: Managing CMC Operations to Support Accelerated Clinical Development
Process Validation Approaches for Accelerated Programs
  • Lisa DeCardenas - Regulatory Program Manager, Genentech
10:45am - 11:15am 30 mins
Info
Workshop #1: The State of the Art in mRNA Delivery
Development of Nucleic Acid Delivery Platforms; a pan-RNA approach
  • James Heyes, PhD - SVP, Technology Development, Genevant Sciences

At Genevant, we are pursuing a modality agnostic “pan-RNA” approach to develop a diverse pipeline of RNA therapeutics. Genevant’s lipid nanoparticle (LNP) platform has enabled several clinical trials for nucleic acid therapeutics and is used in the first approved RNAi product. It has been used to deliver RNAi payloads targeting both viral and endogenous gene targets, and mRNA in vaccine applications. In this presentation, we will describe further application to mRNA payloads, showing how structural changes to component lipids can influence biological performance in rodents and NHP. We have also developed a potent ligand conjugate platform for delivery of oligonucleotides to the liver, similarly deploying it against both viral and endogenous gene targets. We describe its further refinement, resulting in a substantial increase in activity paired with a more rapid onset. The potential of these platforms for extrahepatic delivery will also be discussed.

10:50am - 11:20am 30 mins
Workshop #2: Oligonucleotide Drug Development at Warp Speed: Managing CMC Operations to Support Accelerated Clinical Development
Late Breaking Presentation
11:00am - 11:45am 45 mins
Workshop #3: Potential Green Chemistry Solutions for Peptide Manufacturing
Perspectives on Green Chemistry
  • Jon Holbech Rasmussen, Ph.D. - Director Global Development, PolyPeptide Group
11:00am - 11:45am 45 mins
Info
Workshop #4: Accelerating Peptides to IND: Moving to the Clinic, CMC and Beyond
Regulatory Issues during Early Development of Peptide Product from R&D to IND
  • Duu-Gong Wu, PhD - Senior Director, Regulatory Consulting, PPD, PPD

As a part of successful development program for a peptide product, a careful planning on the regulatory strategy is necessary. It is critical to have a good understanding on the phase-dependent regulatory requirements based on the unique characteristics of the peptides to avoid pitfalls and delay. The regulatory issues may be related to the design of pre-clinical studies, impurities determination and qualification, bioassay, immunogenicity, and comparability following the manufacturing changes. Any of these issues can present significant regulatory challenges for the development program. The presentation will discuss how to navigate these regulatory issues during R&D and different phases of clinical investigation.

11:15am - 11:45am 30 mins
Info
Workshop #1: The State of the Art in mRNA Delivery
Delivering mRNA Products from Discovery through Development - Opportunities and Challenges
  • Hari Pujar, PhD - Head, Technical Development, Moderna Therapeutics

The talk will cover issues related to delivery of mRNA products from discovery through development for different therapeutic areas and routes of administration – from local delivery of prophylactic and therapeutic vaccines to systemically delivered therapeutics.

11:20am - 12:00pm 40 mins
Workshop #2: Oligonucleotide Drug Development at Warp Speed: Managing CMC Operations to Support Accelerated Clinical Development
Panel Discussion with Workshop Speakers
11:45am - 12:00pm 15 mins
Workshop #1: The State of the Art in mRNA Delivery
Concluding Remarks and Discussion
11:45am - 12:00pm 15 mins
Workshop #3: Potential Green Chemistry Solutions for Peptide Manufacturing
Concluding Remarks and Discussion
11:45am - 12:00pm 15 mins
Workshop #4: Accelerating Peptides to IND: Moving to the Clinic, CMC and Beyond
Concluding Remarks and Discussion
12:00pm - 1:00pm 60 mins
Spotlight Presentations 1
spotlight luncheon
12:00pm - 1:00pm 60 mins
Spotlight Presentations 2
Spotlight Luncheons
12:00pm - 1:00pm 60 mins
Spotlight Presentations 3
Spotlight Luncheons
1:00pm - 1:05pm 5 mins
Workshop #5: Peptide Aggregation – Challenges, Effects, and Solutions
Workshop Moderator’s Opening Remarks
  • Christopher Rhodes, PhD - President and CEO, Drug Delivery Experts
  • Ved Srivastava, PhD - Vice President of Peptide Chemistry, Intarcia Therapeutics, Inc.
1:00pm - 1:15pm 15 mins
Workshop #6: The Path to A Successful Oligonucleotide IND/IMPD Submission: Regulatory, Nonclinical and CMC Perspectives
Workshop Moderator’s Opening Remarks
  • Jennifer Lockridge, PhD - Senior Vice President, Program Development, Dicerna Pharmaceuticals, Inc.
1:00pm - 1:15pm 15 mins
Workshop #7: Evolving Regulatory CMC Requirements for Peptides
Workshop Moderator’s Opening Remarks
  • Gary Musso, PhD - President, Musso and Associates LLC
1:00pm - 1:15pm 15 mins
Info
Workshop #8: Analytical and Bioanalytical Strategies and Techniques for the Discovery and Development of Oligonucleotide Therapeutics
Workshop Moderator's Welcome and Opening Remarks
  • Klaus Charisse, PhD - Director, Analytical R&D, Alnylam Pharmaceuticals

As more and more oligonucleotides are entering preclinical and clinical evaluation, both analytical and bioanalytical techniques play an ever more important role. This workshop will explore the most commonly used analytical and bioanalytical techniques and their applications throughout the oligonucleotide development process. You will learn about the challenges, considerations, perspectives and expectations for both analytical studies and bioanalysis in oligonucleotide drug development and manufacturing. You will also hear a variety of case studies from industry experts to illustrate lessons learned.

1:05pm - 1:35pm 30 mins
Info
Workshop #5: Peptide Aggregation – Challenges, Effects, and Solutions
Introduction to Peptide Aggregation, Gelation, and Injection Site Precipitation, and the Consequences
  • Christopher Rhodes, PhD - President and CEO, Drug Delivery Experts

The presentation will provide an overview of gelation and aggregation in formulations and methods to prevent or delay formulation instability. It will also provide an overview of injection site precipitation and the consequences, as well as methods to prevent or delay precipitation.

1:15pm - 2:00pm 45 mins
Workshop #6: The Path to A Successful Oligonucleotide IND/IMPD Submission: Regulatory, Nonclinical and CMC Perspectives
Regulatory Perspectives and Points to Consider in Making Successful Oligonucleotide IND/CTA Submissions
  • Paul Manley - President and Principal Consultant, Orvieto Consulting
1:15pm - 2:00pm 45 mins
Info
Workshop #7: Evolving Regulatory CMC Requirements for Peptides
Regulatory Recommendations in Development – EU vs USA differences
  • Gary Musso, PhD - President, Musso and Associates LLC

This workshop will provide an overview of CMC requirements for peptides including discussions on a wide variety of topics including 1) Risk assessments 2) Genotoxic impurities and justification 3) Related substance impurities and qualification justification 4) Report results vs a defined specification 5) Compendial Tests – Ph Eur vs USP vs Harmonized or not harmonized 6) Regulatory starting materials 7) Method Validation requirements at Phase 2- US vs EU and more.

1:15pm - 1:45pm 30 mins
Workshop #8: Analytical and Bioanalytical Strategies and Techniques for the Discovery and Development of Oligonucleotide Therapeutics
Analytical Presentation Title TBA
  • Matthias Kretschmer, PhD - Senior Director Analytical Sciences, Alnylam Pharmaceuticals
1:35pm - 2:05pm 30 mins
Info
Workshop #5: Peptide Aggregation – Challenges, Effects, and Solutions
Non-aqueous Approaches to Peptide Aggregation
  • Steven Prestrelski, Ph.D., MBA - Chief Scientific Officer, Xeris Pharmaceuticals, Inc.

Peptides are typically formulated in aqueous-based formulations and aggregation and fibrillation can pose significant challenges. Formulation in biocompatible non-aqueous systems can often provide greater control over aggregation/fibrillation whilst providing a means for safe and effective injections. This presentation will focus on mechanisms of solvent influence on aggregation and review several case studies.

1:45pm - 2:15pm 30 mins
Workshop #8: Analytical and Bioanalytical Strategies and Techniques for the Discovery and Development of Oligonucleotide Therapeutics
Analytical Presentation Title TBA
  • Hans Gaus, Ph.D. - Director of Structural Biology, Ionis Pharmaceuticals, Inc.
2:00pm - 2:45pm 45 mins
Workshop #6: The Path to A Successful Oligonucleotide IND/IMPD Submission: Regulatory, Nonclinical and CMC Perspectives
CMC Perspectives on Oligonucleotides
2:00pm - 2:30pm 30 mins
Info
Workshop #7: Evolving Regulatory CMC Requirements for Peptides
European Regulatory Update on CMC Requirements for Synthetic Peptides
  • René Thürmer, PhD - Deputy Head, Unit Pharmaceutical Biotechnology, BfArM Federal Institute for Drugs and Medical Devices

Many synthetic peptides are currently worldwide approved as drugs. Nevertheless, identification of critical quality attributes (CQAs), analytical challenges and characterization issues are still discussed in the community. This presentation will also focus on regulatory starting materials and related substance impurities qualification.

2:05pm - 2:35pm 30 mins
Info
Workshop #5: Peptide Aggregation – Challenges, Effects, and Solutions
In Vitro and in Vivo Models for Injection Site Precipitation and Formulation Solutions
  • Laxma Reddy, PhD - Fellow, Formulation and Product Development, Drug Delivery Eexperts

Injectable drugs that are insoluble at physiological pH are formulated at a different pH or containing non-physiological concentrations of salts and excipients to enhance the solubility of the drug substance.   Such formulations upon injection have a tendency to precipitate at the injection site causing injection site reaction. Here we present in vitro and in vivo screening methods to develop formulations to prevent injection site precipitation.

2:15pm - 2:45pm 30 mins
Workshop #8: Analytical and Bioanalytical Strategies and Techniques for the Discovery and Development of Oligonucleotide Therapeutics
Strategies for Chiral Thioates
  • Pallavi Lonkar, PhD - Principal Scientist, WAVE Life Sciences
2:30pm - 3:00pm 30 mins
Workshop #7: Evolving Regulatory CMC Requirements for Peptides
Networking Refreshment Break
2:35pm - 3:05pm 30 mins
Info
Workshop #5: Peptide Aggregation – Challenges, Effects, and Solutions
Peptide Gelation: Characterization and Importance of Reversibility of Aggregation
  • Ved Srivastava, PhD - Vice President of Peptide Chemistry, Intarcia Therapeutics, Inc.

This presentation will discuss higher-order structure and hydrogel assembly of oligopeptides, characterization of the rheological behaviour, factors effecting gel properties and biomedical applications of peptide with gelation characteristic.

2:45pm - 3:15pm 30 mins
Workshop #6: The Path to A Successful Oligonucleotide IND/IMPD Submission: Regulatory, Nonclinical and CMC Perspectives
Networking Refreshment Break
2:45pm - 3:15pm 30 mins
Workshop #8: Analytical and Bioanalytical Strategies and Techniques for the Discovery and Development of Oligonucleotide Therapeutics
Networking Refreshment Break
3:00pm - 3:45pm 45 mins
Info
Workshop #7: Evolving Regulatory CMC Requirements for Peptides
Of Peptides and PANDAS: Innovative Preclinical Assessment Tools for Safety and Efficacy of Protein and Peptide Therapeutics
  • Annie De Groot, MD - Founder, CEO and CSO, Epivax, Inc.

The FDA recently released a new draft guidance defining the equivalence of a rDNA peptide product and a synthetic peptide product. The draft guidance enables generic manufacturers of peptide drugs to file an Abbreviated New Drug Application (ANDA) for synthetic peptide drug products that refer to listed drugs of rDNA origin. Since the processes for manufacturing the generic and reference drug (RLD) are not equivalent, peptide drugs can be associated with impurities. Impurities can result from changes in the sequences due to deletions, insertions, integration of incorrect amino-acids and modifications and also impurities related to the synthetic production. The FDA draft guidance requires manufacturers to prove that the synthetic peptide product does not contain impurities that have an increased affinity for major histocompatibility complexes and potential for engaging immune response, which may drive undesired anti-drug antibody development. We have used both immunoinformatics-driven analysis and in vitro validation assays to perform immunogenicity risk assessment of peptide generics. This combination of in silico and in vitro tools is referred to the PANDA assay which can be used to support generic peptide drug equivalency in an ANDA application. This presentation will provide insight as to the process of performing the PANDA assay, illustrating the process with two case studies (such as Calcitonin and Teriparatide).

3:05pm - 3:30pm 25 mins
Workshop #5: Peptide Aggregation – Challenges, Effects, and Solutions
Networking Refreshment Break
3:15pm - 4:00pm 45 mins
Info
Workshop #6: The Path to A Successful Oligonucleotide IND/IMPD Submission: Regulatory, Nonclinical and CMC Perspectives
Getting Your ASO in Top Shape for IND/IMPD Submission: How to Successfully and Efficiently Identify A Solid Development Candidate
  • Sebastien Burel, PhD - Executive Director, Nonclinical Development, Ionis Pharmaceuticals

Sebastien Burel, Ph.D., Executive Director, Nonclinical Development, Ionis Pharmaceuticals (Invited)

3:15pm - 3:45pm 30 mins
Workshop #8: Analytical and Bioanalytical Strategies and Techniques for the Discovery and Development of Oligonucleotide Therapeutics
Analytical Presentation Title TBA (Invited)
  • Ingo Roehl, PhD - Director, Analytical Chemistry, LGC Axolabs
3:30pm - 4:00pm 30 mins
Info
Workshop #5: Peptide Aggregation – Challenges, Effects, and Solutions
Protein Aggregation in Consequence of Siliconization and Preservation: Challenges during Formulation Development
  • Kathrin Spielberger, PhD - Head of Laboratory Product & Process Development, Sanofi

The stability of therapeutic proteins can be influenced by multiple factors leading to chemical and physical instabilities. This case study of a synthetic peptide addresses the key development challenges during formulation development. A narrow pH-window, gel formation at higher concentration and incompatibility with silicone oil and preservatives made it challenging to develop a multi-use formulation for parenteral use. The different siliconization processes of glass barrels and packaging material (baked versus spray-on) had a great impact on protein aggregation. In this study, the siliconization of plunger stoppers could be identified as one trigger factor for aggregation. The implementation of silicone-free packaging material and optimization of the formulation led to a stable parenteral formulation. Performing compatibility testing of different packaging materials and investigating the interaction of preservatives with peptides early during formulation development could be beneficial with respect to shortened clinical timelines.

3:45pm - 4:30pm 45 mins
Info
Workshop #7: Evolving Regulatory CMC Requirements for Peptides
Quantification of Impurities in Synthetic Peptides Using Proteolytic Sample Preparation and RP Chromatography
  • Michael Berger - Director, Quality Control, Bachem AG

The establishment of the UHPLC technology opened the door to efficient and robust separation of many impurities in synthetic peptides. Nevertheless, the separation of some impurities remains challenging even using most recent UHPLC RP techniques and development approaches. Among these “separation resistant” impurities are the D-His1 analogues of many GLP peptides. Up to now special methods such as IEX-HPLC or chiral GC amino acid analysis must be applied in these cases.

An alternative method for the quantitative determination of D-His1-Glucagon in Glucagon will be presented as case study. The method comprises a proteolytic digest of Glucagon followed by RP UHPLC quantitation of the histidine-containing peptide fragment. The method can be validated for routine analysis and represents an example for a general application of the approach for peptides with different kinds of impurities that were difficult to separate otherwise.


3:45pm - 4:15pm 30 mins
Workshop #8: Analytical and Bioanalytical Strategies and Techniques for the Discovery and Development of Oligonucleotide Therapeutics
Analytical Presentation Title TBA (Invited)
  • Marjie Hard, PhD - Executive Director of Clinical Pharmacology & DMPK, Moderna Therapeutics
4:00pm - 4:30pm 30 mins
Info
Workshop #5: Peptide Aggregation – Challenges, Effects, and Solutions
Charge Variant Analysis of Therapeutic Peptides
  • Anuja Rane, PhD - Associate Scientist, Teva Pharmaceuticals


Charge heterogeneity can occur in synthetic peptides due to chemical degradation (e.g. oxidation, deamination, etc.) during synthesis, purification and storage which can impact safety and efficacy. In this study, we explored the feasibility of using capillary isoelectric focusing to characterize the charge heterogeneity of >30 amino acids peptides.

4:00pm - 4:45pm 45 mins
Info
Workshop #6: The Path to A Successful Oligonucleotide IND/IMPD Submission: Regulatory, Nonclinical and CMC Perspectives
Case Study: DCR-PHXC, An siRNA Therapeutic Being Developed for the Treatment of Primary Hyperoxaluria
  • Jeffrey Foy, PhD - Senior Director, Toxicology, Dicerna Pharmaceuticals

DCR-PHXC, an siRNA targeting LDHA, is being developed for the treatment of primary hyperoxaluria and has demonstrated proof of concept in a Phase I study.  This case study will be used to examine CMC and nonclinical strategies that may be helpful for early stage oligonucleotide development programs.

4:15pm - 5:00pm 45 mins
Workshop #8: Analytical and Bioanalytical Strategies and Techniques for the Discovery and Development of Oligonucleotide Therapeutics
Panel Discussion with Workshop Speakers
4:30pm - 5:00pm 30 mins
Info
Workshop #5: Peptide Aggregation – Challenges, Effects, and Solutions
Shining Light on Therapeutic Peptide Aggregation Kinetics in the Presence of Excipients
  • Katelyn Smith, PhD - Sr. Scientist, Merck & Co., Inc.

Physical and chemical instability of peptides pose a significant risk to the successful development of a solution formulation product. While methods for predicting chemical stability have been developed, the prediction of physical stability remains a key gap in industry. Accelerated approaches to screen formulations are developed for rank-ordering; however, the extent to which the rank-order remains at relevant storage conditions has yet to be established. Therefore, current formulation selection requires robust long-term data at relevant storage conditions, which is lengthy and demands significant resources. The peptide discussed herein has a narrow pH window for optimal physical and chemical stability. Indeed, fibril formation has been observed when pH < 8 however above this pH significant chemical degradation occurs. As the impact of excipients required for formulation stability and sterility are difficult to determine a priori, it becomes necessary to monitor large screens of unique candidate formulations for analysis of physical and chemical stability. In an ideal situation, prediction studies would be performed on freshly prepared peptide or utilize short incubation times for formulations of interest. In this work, the fluorescence-based assay implemented to study physical stability involves the simultaneous heating and agitation of peptide formulations to accelerate peptide fibril formation. Solutions of peptide in the absence of excipients display Arrhenius behavior, where increased temperatures lead to faster fibril formation. Surprisingly, the addition of stabilizing excipients essentially reverses this trend: fibril formation is observed at lower temperatures but is inhibited at higher temperatures. Of greater importance, the data collected at lower temperatures better reflects the behavior of peptide formulations under the relevant real-time storage conditions. These results are supported by isothermal titration calorimetry studies which report the enhanced binding of stabilizing excipients to the peptide at elevated temperatures. Further NMR experiments provide molecular-level insight into this phenomenon. These finding can have great impact on product development strategy as we gain further insight on peptide-excipient interactions. The growing understanding and increased ability to predict peptide physical stability will enable a more robust and efficient development of peptide therapeutics.


4:30pm - 5:00pm 30 mins
Info
Workshop #7: Evolving Regulatory CMC Requirements for Peptides
Genotoxicity Assessment of Impurities in Peptide/Protein-containing Biotherapeutics
  • Zhanna Sobol, PhD - Genetic Toxicology Head, Pfizer, Inc.

Peptide/protein biotherapeutics fall in a grey area between biologics and small molecules when it comes to assessment of genotoxic impurities. Although, the ICH M7 guideline considers biologics out of scope, some of the concepts and strategies described there can be applied to all process-related impurities. Nonetheless, there are unique properties of biologics that must be taken into consideration when performing a genotoxicity assessment. This talk will describe the output of a Health and Environmental Sciences Institute’s Genetic Toxicology Technical Committee Workgroup that formed to address these topics.

4:45pm - 5:00pm 15 mins
Workshop #6: The Path to A Successful Oligonucleotide IND/IMPD Submission: Regulatory, Nonclinical and CMC Perspectives
Concluding Remarks and Discussion