Webinar:

The strategy behind your journey to GMP with emphasis on linker payload development

Sponsored by: Abzena

Focused on:

  • Payload Development

Date: 5 May

51

Time: 3PM London / 4pm CET

For a novel antibody drug conjugate (ADC) to progress to the clinic many challenges need to be addressed before reaching the final ADC drug product meant for patients. While much focus is given to complex conjugation chemistry and purification processes for ADC production, the linker-payload presents its own unique challenges that need to be overcome for the successful assembly of ADCs and their use as valuable therapeutics.

The linker-payload, which generally consists of a highly potent chemotherapy attached to linker has the multipurpose of attaching the payload to the antibody, providing stability to the structure and enabling release of its payload at the target site of disease. The current landscape of linkers and payloads used in ADCs continues to expand meaning there is no single solution to the development and manufacture of these highly complex chemical compounds. Linker-payloads typically fall into two categories; those produced by semi-synthesis from payloads derived from natural sources such as fermentation, and those resulting from total synthesis beginning with less complex commercially available building blocks. Both paths have unique challenges which should be carefully considered to ensure the right molecular approach and design is applied to meet the target product profile of the ADC. Both strategies for creating a linker-payload deal with common problems, and both have proven successful. These approaches will be covered in this seminar exploring how they were used and why.

Once a novel linker-payload is designed, a rational development plan should be put in place to ensure effective linking to the small molecule (cargo) in a scalable process. Many factors contribute to the chosen strategy to balance issues such as exposure of the drug to degradation pathways and high drug loading leading to insolubility and clearance. Different tools, reagents, processes and resources can be applied to optimal linker-payload and design and manufacture.

Once the linker payload has been designed, developed and a synthetic route for an efficacious conjugate is established, the research-based process needs be transferred and scaled-up for IND enabling tox studies and first in human clinical trials. Consideration of the planned manufacturing scale and critical quality attributes needed for the ADC at the start of development will help define the necessary unit operations. Expertise and experience play a crucial role in the journey to the clinic which we hope to convey our learnings as part of this seminar.

In this webinar, we will review the pros and cons of semi-synthetic and synthetic linker payloads as well as discuss the considerations that should be taken when conjugating your linker payload to its antibody, with the ultimate goal of generating successful clinical material. Examples that illustrate how to overcome the challenges of linker payloads will be presented.

Presented by

Thomas Nittoli, PhD,

Senior Director, R&D Chemistry Therapeutic Proteins, Regeneron

Tom Nittoli has over 20 years of experience in the pharmaceutical industry and is currently Senior Director of R&D Chemistry. Tom joined Regeneron in 2010 to advance conjugated antibodies and proteins from discovery to development. Since joining Regeneron, he has developed a variety of small molecules for protein conjugation, led diverse teams of discovery ADC scientists, and led cGMP synthesis and conjugation campaigns.
Prior to Regeneron, Tom held positions at Pfizer, Wyeth, and CIBA-Giegy. He holds a PhD from the department of chemistry SUNY Stony Brook and was a post-doctoral fellow at the University of Pennsylvania.

Ian Glassford, PhD,

Director Project Management, Abzena

Ian is part of Abzena’s Scientific Leader group, bringing key technical expertise in chemistry and experience with clinical development to provide strategic support for synthetic chemistry and bioconjugation. Ian has significant experience in the design and synthesis of structurally complex small molecules, the synthesis and handling of high potent compounds including R&D and early process development, and project management of small molecule and bioconjugate manufacturing projects, including planning and execution. Ian started his career with GlaxoSmithKline where he worked as a medicinal chemist focused on synthesis of novel therapeutics utilizing structure and fragment-based design. Ian has a Ph.D. in organic chemistry from Temple University.

Session Chair:
Campbell Bunce, PhD,

Chief Scientific Officer, Abzena

Campbell is the Chief Scientific Officer at Abzena, a global Partner Research organisation supporting development of drugs and vaccines from discovery to GMP manufacture. His focus is in delivering high quality and tailored services to ensure a quick and de-risked route from drug concept and design to clinical testing. Campbell has been with Abzena for 5 years and beforehand spent 20 years working in the biotech sector for companies such as Cantab Pharmaceuticals, Piramed Pharma and Immune Targeting Systems. He has led the development of many novel vaccine and therapeutic technologies targeting infectious disease, cancer, inflammatory and autoimmune disease, taking them through discovery and design stages to clinical evaluation. Campbell has a PhD in Immunology from the University of Manchester and has published numerous papers on immune mechanisms and novel drug development.

Key Learning Objectives

  • Discover the pros and cons of semi-synthetic linker payloads
  • Discover the pros and cons of synthetic linker payloads
  • What to consider in conjugating your linker payload to your antibody
  • Considerations in combining small and large molecules in the GMP environment leading to successful clinical material.

Audience

  • Biopharmaceutical Consultants
  • Conjugation chemists
  • Scientists & Project Leaders
  • CMC Management & Operations
  • Directors - Preclinical Development
  • Directors - Biotherapeutics
  • C-levels: CSO - COO - CEO
  • Head of
  • Scientific leaders
  • Synthetic chemists