This document provides an agenda and background information for an immunobiology day event hosted by Charles River Laboratories. The event will cover regulatory frameworks for developing biological therapeutics, suitable animal species for testing, bioanalysis techniques, immunophenotyping assays, and challenges of pharmacokinetics for large molecules. Speakers will discuss regulatory guidelines, validating cell-based assays, analyzing macromolecules, using nonhuman primates in safety testing, and strategies for drug metabolism and pharmacokinetics research on large molecules. Attendees will learn about typical development programs and challenges in preclinical testing of biotherapeutics.

1. © 2015, Charles River Laboratories International, Inc.
askcharlesriver@crl.com
www.criver.com
IMMUNOBIOLOGY AND
NEW CHALLENGES
IN DRUG DEVELOPMENT
June 25, 2015
This immunobiology day will provide the opportunity for those involved in developing biotherapeutics, but have yet to
undertake any preclinical testing, to learn about typical programs and the challenges associated with them. Starting with
an outline of the regulatory framework, we will discuss the choice of suitable species. Large molecule bioanalysis and
testing for antibody response, as well as monitoring of the immune system by immunophenotyping and functional
assays, will also be covered. Finally there will be a talk on large molecule DMPK, its relevance and practice.
a Charles River event
Agenda
11:00 Opening/overview
11:15 Regulatory steps in the development of biological
therapeutics – Pete Gaskin, PhD
11:45 Development and validation of cell-based assays to
support immunology and discovery – Kurt Sales, PhD
12:15 Bioanalysis of macromolecules – Alison Catalano, PhD
12:45 Networking lunch
13:15 Use of the nonhuman primate in the safety evaluation of
biologicals – Warren Harvey
13:45 Strategies and challenges of large molecule DMPK –
Marco Bottacini
14:15 Questions & Answers
14:45 Closing remarks
Regulatory steps in the development of biological therapeutics
Speaker: Pete Gaskin, PhD
Bio: Peter Gaskin graduated with a BSc (Hons) in Biochemistry from the University of Surrey and later completed a PhD in Mechanistic
Toxicology at the University of Nottingham. He is an expert in program management with over 20 years of life sciences experience, having
successfully lead the non-clinical development of many products from discovery to market. Prior to joining Charles River he was a principal
and an associate director, providing consultancy services on strategic early development issues and acting as a non-clinical expert and
Scientific Advisory Board member. Prior to working in consulting roles he held various senior positions in program management at a large,
non-clinical and clinical CRO, latterly as head of the group. During his career Pete has been the toxicology representative on multiple project
teams for small molecules, novel biologics, advanced therapies and biosimilars in a range of indications.
Abstract: The presentation will focus on the regulatory environment in Europe and the US in regard to the development of biological
therapeutics. Key aspects of the relevant guidelines will be discussed in relation to their impact on the design of the non-clinical program.

2. © 2015, Charles River Laboratories International, Inc.
askcharlesriver@crl.com
www.criver.com
Development and validation of cell-based assays to support immunology and discovery
Speaker: Kurt Sales, PhD
Bio: Kurt Sales is the immunology manager at Charles River Edinburgh, UK. Kurt has more than 14 years’ experience in academia, where he
worked as an academic at the MRC Human Reproductive Sciences Unit in Edinburgh and the Division of Medical Biochemistry, Institute of
Infectious Disease and Molecular Medicine at the University of Cape Town. Before joining Charles River, he worked for the Western Australia
AIDS Council where he ran a community-based clinic (M Clinic) for HIV and sexually transmissible infection testing, treatment and prevention,
and initiated and coordinated the first rapid HIV test trial in Western Australia. Kurt has a BSc degree in Biochemistry and Physiology, a BSc
(Med) (Hons) degree in Pharmacology, a MSc degree in Biochemistry and a PhD in Medical Biochemistry from the University of Cape Town,
South Africa as well as a Postgraduate Certificate in Management from the University of Northampton, UK.
Abstract: New biologic applications (including biosimilars and neutralising antibodies) are required to demonstrate efficacy as well as safety.
As biologics are normally produced by living production systems small changes in production can drastically alter the biosimilar in comparison
to the innovator substance, leading to clinically relevant changes and toxic side effects. For biosimilars, comparison of both biological activity
and physiochemical characterisation is required and new guidelines for biologic and biosimilar applications are being/have been prepared by
regulatory agencies detailing requirements for functional cell-based assays. Here we will discuss some of these requirements and describe
the development and validation of cell-based assays to support discovery and development of new biologic applications.
Bioanalysis of macromolecules
Speaker: Alison Catalano, PhD
Bio: Alison Catalano is a scientific manager for the Immunochemistry group in the Bioanalysis and Immunology Department. Alison has a
BSc degree in Biological Sciences and a PhD in Molecular Immunology from University College London. She held post-doctoral positions at
Washington University Medical School, USA and at University of Warwick and was then employed at two biotech companies in Cambridge,
working on ribosome display techniques for creating and improving affinity of novel antibodies. Before joining Charles River, she worked for a
GMP manufacturing company, AbBiotech, which specializes in producing antibodies, and started the assay development team there.
Abstract: This presentation will cover PK/TK analysis, immunogenicity analysis and oligonucleotide hybridisation assays. The different types
of PK/TK assays will be explained together with their clinical relevance and assay design considerations. The importance of the matrix effect
will be discussed, as well as the types of platforms available at Charles River. Immunogenicity analysis will be discussed with the different
types of assays necessary: screening assays, confirmatory assays and neutralizing assays. There will be a discussion on oligonucleotide
hybridisation assays and the different types of assays, along with advantages and disadvantages of each.
Use of the nonhuman primate in the safety evaluation of biologicals
Speaker: Warren Harvey
Bio: Warren Harvey joined Charles River in 2001 as a study director in the Department of Acute and General Toxicology where he is
responsible for the conduct of toxicology studies primarily in rodents, dogs, swine (mini-pigs and domestic pigs) and primates (cynomolgus,
rhesus and marmosets). Promoted to scientific manager in 2005, Warren also has the responsibility of co-ordinating projects within the
department, with a particular focus on general toxicology studies, for the development and training of personnel and for developing the
scientific expertise of the department.
Abstract: Nonhuman primates (NHP) are increasingly being used as a non-rodent animal model during preclinical safety evaluation on the
basis of proven suitability and comparability between NHP and humans. The introduction of humanised and fully human antibodies imposes
further demands on NHP models since many biopharmaceuticals do not interact with rodent or other non-rodent receptors but frequently only
cross-react with primate tissue. This talk will provide a brief overview on the use of the NHP as the pharmacologically relevant animal model
and the practical considerations when conducting a preclinical toxicology study with an immunomodulatory monoclonal antibody.
Strategies and challenges of large molecule DMPK
Speaker: Marco Bottacini
Bio: Marco Bottacini joined the Metabolism and Pharmacokinetics Department at Charles River Edinburgh (formerly Inveresk Research) in
2002 as a study director to conduct absorption, distribution, metabolism and excretion studies. He was promoted to functional manager in
2003. Marco currently leads the regulatory pharmaceutical team within the department of Metabolism and Pharmacokinetics at Charles River
Edinburgh. His main areas of interest are radioisotopic techniques, QWBA, in vivo regulatory ADME and project risk analysis.
Abstract: For small chemical entities, the correct management of the PK/PD relationship and the ADME properties has been demonstrated
to help effectively to refine and streamline the quest for successful therapies. An understanding of the concentration-effect relationship and
the ADME characteristics is crucial for large molecules as well. The regulatory framework has also been changing over the last few years in
response to the increased number of large molecules at different stage of development. In order to continue to assist in the drug development
process and fulfil regulatory requirements, DMPK has been challenged to develop new strategies and to implement new approaches to
address the complexities associated with determining the disposition of these large molecules. In this presentation we will show examples of
the typical challenges that DMPK scientists face when dealing with these agents and provide insight into potential solutions.