ADC Development and Manufacturing


Developing and producing highly potent small molecules conjugated with monoclonal antibodies presents a host of challenges ranging from chemistry to analytics, processing to formulation. Advanced analytics and ADC-specific assays are required for batch comparability and toxicity detection; process optimization and scaling-up are critical to ensure a smooth transition from clinical to commercial phase, while dosage and formulation hold the key to patient safety and efficacy. This conference offers a platform for scientists and engineers to share creative strategies to overcome the production challenges of ADCs from early development to commercial phase.

Day 1 | Day 2 | Download Brochure | Speaker Bios 

Recommended Pre-Conference Short Course* 

Novel and Emerging Conjugation Methods for ADCs - View Detailed Agenda 

*Separate registration required. 

 

WEDNESDAY, MAY 7

7:00 am Registration and Morning Coffee

8:00 Chairperson's Opening Remarks

Peter U. Park, Ph.D., Vice President, Biology, Mersana Therapeutics, Inc.

 

Process Development and CMC Challenges 

8:10 FEATURED PRESENTATION: ADC Process Development and Scale-Up Strategy from Early Phase Development to Commercial

RayNityaNitya G. Ray, Ph.D., Senior Vice President, Manufacturing, Process Sciences/Manufacturing, Progenics Pharmaceuticals, Inc.

ADCs require innovative approaches to manufacturing process development and scale-up. This presentation will address process development and manufacturing strategies for ADCs from early phase clinical development to commercial. Critical considerations for process development with emphasis on systems approach, control of conjugated species and scale-up will be presented. Finally, Progenics’ ADC therapeutic program, currently in phase 2 clinical development to treat prostate cancer, will be discussed.

8:40 FEATURED PRESENTATION: Development and Manufacture of ADCs – The Seattle Genetics Perspective

NathanIhleNathan C. Ihle, Ph.D., Executive Director, CMC Strategy & Management, Seattle Genetics, Inc.

Due to the hybrid nature of ADCs, their production is more complex than for typical biological products. CMC strategies for developing manufacturing processes and product quality characterization will be discussed. Key factors in Seattle Genetics’ selection of manufacturers for clinical and commercial production of ADCs, as well as future trends for ADC manufacturing will also be presented.

9:10 Antibody-Drug Conjugates: Challenges and Critical Considerations for Developing Early-Phase Clinical Manufacturing Processes

Marie ZhuMarie M. Zhu, Ph.D., Director, Process Sciences, Technical Operations, Agensys Inc., an affiliate of Astellas, Inc.

Developing a scalable and robust process that generates ADC products with desired drug-to-antibody ratio and consistent product quality attributes is important for clinical manufacturing. We will share the challenges experienced during developing ADC processes. Further, through case studies, we will discuss critical aspects in ADC process development and will elucidate development strategies that resulted in successful process scale-up and tech transfer for ADC production.

9:40 Effective Manufacturing of Antibody Drug Conjugates

AadVanDeLeurAad van de Leur, MSc, COO, Biopharmaceutical Development, Synthon Biopharmaceuticals B.V.

Synthon recently finished the construction and qualification of a new ADC GMP manufacturing plant. The implications on facility design to handle larger batch sizes to meet biopharmaceutical industry standards for safe, effective and reliable manufacturing will be discussed. The challenges and different approaches to develop a robust conjugation process as well as results of this conjugation process including preclinical data will be presented.

10:10 Coffee Break in the Exhibit Hall with Poster Viewing

 

Developability of ADC – Overcoming Heterogeneity and Tumor Resistance 

11:10 Next-Generation Antibody-Drug Conjugates Designed with Fleximer™ Platforms Enable High Drug-Loading (DAR >15) of Payloads with Excellent Biochemical Properties and Pharmacokinetics and Potent Anti-Tumor Activity

PeterParkPeter U. Park, Ph.D., Vice President, Biology, Mersana Therapeutics, Inc.

The application of biodegradable, polyacetal polymer Fleximer™ to ADC design can provide numerous advantages, including significantly higher capacity for drug payload, the improvement of physicochemical properties for ADC, especially with highly hydrophobic payloads and the use of protein recognition scaffolds beyond the commonly used IgGs. Examples of these benefits achieved using Mersana’s polyacetal-based conjugation system to create and characterize next-generation ADCs will be presented.

11:40 Addressing Tumor Heterogeneity and Resistance: Production of Homogeneous Multispecific ADCs with Combination Warheads

Trevor HallamTrevor Hallam, Ph.D., CSO, Sutro Biopharma

Cell–free protein synthesis methods have been developed for production of homogeneous therapeutic proteins, including ADCs. Many variants can be expressed in hours and within days, production of chosen variants can be scaled to generate clinical materials. The power and utility of the platform to design and manufacture single species bispecific and multispecific antigen-targeted antibodies with conjugated combination warheads will be described.

Concortis12:10 pm ADC-2x, the Development of Multifunctional ADCs

David Miao, CTO, Concortis Biosystems, The ADC company of Sorrento Therapeutics, Inc.

Conventional ADCs, targeting one type of cancer antigen and bearing one class of payload, promise to vastly improve cancer treatment. Nevertheless there is an urgent need to further increase the therapeutic window of ADCs by discriminating the tumor cells from normal tissues and preventing the development of multiple drug resistance. To maximize the potentials of ADC therapeutics, we have developed a new category of multifunctional ADCs, i.g., ADC-1.2, ADC-2.1 and ADC-2.2. Designs, technologies and data of enhanced potencies will be presented.

12:40 Luncheon Presentations (Sponsorship Opportunities Available) or Lunch on Your Own

 

1:40 Session Break

 

FORMULATION AND STABILITY OF ADC 

2:00 Chairperson's Remarks

Peter U. Park, Ph.D., Vice President, Biology, Mersana Therapeutics, Inc.

2:05 Pfizer Case Study of ADC Formulation and Process Optimization

ShannonMacMillanShannon MacMilian, MSc, Principal Scientist, Biotherapeutic Pharmaceutical Sciences R&D, Pfizer, Inc.

Pfizer has developed ADCs that incorporate a labile linker technology to enable site specific delivery of payload to targeted cancer.  Custom drug product formulation and process optimization requirements will be presented as an ADC case study.  Additional considerations for isolator based manufacture of an ADC will also be discussed.





2:35 Optimizing ADC Development Using PK/PD Modeling and Simulation

DhavalShahDhaval K. Shah, Ph.D., Assistant Professor, Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, SUNY Buffalo

The talk will introduce different PK/PD/TD models employed for ADC development, and will demonstrate: (1) how to employ the models to gain insight into ADC disposition, and (2) how to use M&S to aid clinical development and discovery of ADCs.

 

3:05 Oral Poster Presentation

New Site-Specific Conjugation Based on Bacterial Transglutaminase

Delphine BregeonDelphine Bregeon, Ph.D., R&D Scientist, Innate Pharma

Here, the work relates to ADCs synthesis through BTG approach based on site-specific modification of mAbs with single point mutations. Stability, pharmacokinetics, as well as in vitro and in vivo efficacy of resulting BTG-ADCs were investigated. ADCETRIS®, brentuximab vedotin, has been used as comparator, hence for consistency BTG-ADCs have been conjugated with the different linkage strategies (one-step and two-step) containing the same protease sensitive moiety as ADCETRIS®, i.e. valine-citrulline-PAB-MMAE. BTG two-step process leads to ADCs with DAR of exactly 2.0 or 4.0 for antibodies with N297S or N297Q single point mutation respectively.

 

3:20 Sponsored Presentation (Opportunity Available)

 

3:35 Refreshment Break in the Exhibit Hall with Poster Viewing

 

4:20 Problem Solving Breakout Discussions

These interactive discussion groups are open to all attendees, speakers, sponsors, & exhibitors. Participants choose a specific breakout discussion group to join. Each group has a moderator to ensure focused discussions around key issues within the topic. This format allows participants to meet potential collaborators, share examples from their work, vet ideas with peers, and be part of a group problem-solving endeavor. The discussions provide an informal exchange of ideas and are not meant to be a corporate or specific product discussion.

CMC Challenges to Produce ADCS

Moderator: Aad van de Leur, MSc., Chief Operating Officer, Biopharmaceutical Development, Synthon Biopharmaceuticals B.V.

• How important is site directed conjugation and which problems does this solve?
• As most ADC processes utilize solvents will we be able to design a process using only single use/disposable materials?
• Is there sufficient manufactory capacity available?

Analytical Challenges for Antibody Drug Conjugates Characterization

Moderator: April Xu, Ph.D., Sr. Principal Scientist, BioBtx-ARD, Pfizer

• What are the critical quality attributes (CQAs) to test for antibody drug conjugates?
• What are the challenges in developing methods for CQAs?
   o Dependent on conjugation chemistry?
   o Dependent on linker/payload characteristics?
   o Dependent  on development stages?
   o Which assays are more critical, which assays are more challenging, which assays are more time consuming?
   o What else?
• How to characterize the heterogeneities in ADCs?  To what level is acceptable?
• How to characterize high-order-structures (HOS)  in ADCs ?

Holistic Approach to Product Design and Manufacturing Processes for Successful ADC Development

Moderator: Nitya G. Ray, Ph.D., Senior Vice President, Manufacturing, Process Sciences/Manufacturing, Progenics Pharmaceuticals, Inc.  

• Opportunities and challenges in ADC development
• Process-driven drug development
• Importance of integrated approach to product design and manufacturing

Learnings from Clinical Failure of ADCs

Moderator: Dhaval K. Shah, Ph.D., Assistant Professor, Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, SUNY Buffalo

• Initial discussion on the failure rate of ADCs, and famous failures in the industry
• Discussion about the impact of target antigen and clinical indication on the failure of ADC.
• Impact of conjugation chemistry and payload selection on the fate of ADCs.
• Role of PK/PD and Translational Research in helping us assess the clinical performance of ADCs.
• Any common trend or mistakes we can identify from the clinical failures of ADCs, so far.

 

5:20 Networking Reception in the Exhibit Hall with Poster Viewing

 

6:30 End of Day

 

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