The Bioprocessing Summit

Cambridge Healthtech Institute’s Inaugural
CMC Strategies for Antibody-Drug Conjugates
Strategies for Overcoming Developability and Manufacturability of ADCs
Part of CHI's 6th Annual The Bioprocessing Summit

August 18-19, 2014 | Renaissance Waterfront Hotel | Boston, Massachusetts


Antibody-Drug Conjugates are, as experts put it, “conceptually very simple, but in practice, extremely complicated.” The complexity of the ADC, which combines an antibody and a drug via a linker, means that it requires triple the amount of control and characterization to achieve the right formulation, stability and consistency for effective scale up and manufacturing that meets the regulatory requirements.  As more and more ADCs come down the pipeline, it becomes imperative for companies to consider the manufacturability of the ADCs, and to incorporate process design and CMC strategies early on in the development stage.

CHI’s CMC Strategies for Antibody-Drug Conjugates conference offers a platform for scientists and engineers to come together to outline the challenges, share creative strategies, methods and solutions for the safe and efficient manufacture of these highly potent and complex molecules.

Enhance your learning objectives by attending a Short Course on ADC Developability: Critical Quality Attributes Inform Formulation and Process Development. This short course is conducted by Dr. Janet Wolfe of Wolfe Laboratories, and is aimed at providing a molecular understanding of ADC CQAs, and developing an array of analytical and biophysical techniques that you can use to characterize these attributes for formulation and process design.


Day 1 | Day 2 | Short Courses | Download Brochure | Speaker Bios 


Monday, August 18

8:00 am Pre-Conference Registration and Morning Coffee


9:00 – 11:30 Short Course:* ADC “Developability:” Critical Quality Attributes Inform Formulation and Process Development 


*Separate registration required


11:30 Main Conference Registration

1:00 pm Chairperson’s Opening Remarks

Janet L. Wolfe, Ph.D., President, Wolfe Laboratories


KEYNOTE PRESENTATIONs

1:10 Innovations, Challenges and Opportunities in Antibody-Drug Conjugates

Janet WolfeJanet L. Wolfe, Ph.D., President, Wolfe Laboratories

Antibody-drug conjugates (ADCs) are a rapidly growing therapeutic class that leverages the targeting specificity of antibodies with the potency of small molecules. These highly complex molecules require synchronized tuning of multiple components, creating large technical challenges. Excitement within this burgeoning field is causing enormous innovation around various ADC formats, creating even greater technical barriers. An overview of the field will be provided, with a focus on the challenges and opportunities of well defined CMC strategies.

1:45 Druggable Extracellular Targets

James PrudentJames Prudent, Ph.D., President & CEO, Centrose

The rate limiting internalization step for ADCs requires extremely toxic drugs. If there were external drug targets that could be mined, antibody conjugates would not require internalization and less toxic drugs could be employed. This talk discusses potential targets that rest on the outside of the cell and show data on how such extracellular drug conjugates can be used for numerous indications. The talk will also review some of the development and CMC benefits that extracellular drug conjugates bring.


BIOCONJUGATION ENABLING DEVELOPABILITY AND MANUFACTURABILITY OF ADCs

2:15 Generation of ADCs 2.0 Using Novel Toxins and Site-Specific Coupling

Andreas PahlAndreas Pahl, Ph.D., CSO, Heidelberg Pharma

Toxic warheads of today’s ADCs are exclusively based on compounds acting on microtubules or DNA replication and seem to suffer from limitations in certain cancer indications and tumor cells. New generations of payloads enter the field including Heidelberg Pharma’s amanitin, a highly effective inhibitor of the eukaryotic RNA Polymerase II. Site specific conjugation is going to overcome some these limitations. This presentation will summarize the current status of new toxins and appropriate conjugation methods.

2:45 Refreshment Break

3:15 Carbohydrate-Mediated Site-Specific Antibody-Drug Conjugation

Qun Zhou, Ph.D., Principal Scientist, Protein Engineering, Genzyme, a Sanofi Company

Multiple antibody-drug conjugates have been approved recently. However, the classical chemistries to produce these conjugates by targeting primary amines and disulfides have some shortcomings including heterogeneous product profiles. We have developed a novel site-directed conjugation strategy targeting native carbohydrates of proteins to improve the anti-tumor efficacy of antibody-toxin conjugate. Our method provides a viable alternative without re-engineering of protein sequences.

3:45 Optimizing ADC Properties through Site-Specific Conjugation

Olivier LaurentOlivier Laurent, Ph.D., Vice President, CMC, Ambrx, Inc.

Antibody-drug conjugates, or ADC, combine high potency payloads with the targeting specificity of antibodies. They hold tremendous potential in the treatment of cancer but are also emerging as therapeutic agents outside of oncology. Unfortunately, ADC have also been historically complex to manufacture and characterize due to the use of non-specific conjugation chemistry. Here, we present data on using site specific conjugation to improve the attributes of ADC and improve their chance of success during development.

4:15 Breakout Discussions

This session provides the opportunity to discuss a focused topic with peers from around the world in an open, collegial setting. Select from the list of topics available and join the moderated discussion to share ideas, gain insights, establish collaborations or commiserate about persistent challenges. Then continue the discussion as you head into the lively exhibit hall for information about the latest technologies.

Topics include:

Emerging Technologies & Novel Linker Payloads

Michael S. Wolfe, Ph.D., Professor, Neurology, Center for Neurologic Diseases, Harvard Medical School/Brigham and Women’s Hospital

• Overview of new targets, antibody scaffolds, developability assessment, linkers and payloads
• Discussion of emerging technologies to enable developability assessment
• Discussion of novel payloads for ADC discovery
• Prospects for nontoxic payloads and indications other than cancer

Externalization of ADC Manufacturing – Challenges and Complexities

Vincent Turula, Ph.D., MBA, Director, Biotherapeutics Pharmaceutical Sciences, Pfizer, Inc.

• Dependency on contract manufacturing:  With 40+ Clinical ADC projects in various stages of clinical development, and with a majority of the clinical manufacturing for these projects outsourced, how does an organization secure capacity?
• Safety:  How are early stage programs managed when a full toxicology profile has not yet been completed?  What are the CMOs told as far as an OEB and occupational hygiene?
• Logistics:  How are the arrangements, connectivities between various parties involved in the supply chain, testing, etc. managed
• Intellectual Property:  How is IP protected during external development, technical transfer and outsourcing activities?

CMC Development and Manufacturing Challenges of ADCs

Steven Max, Ph.D., Associate Research Fellow, Biotherapeutics Pharmaceutical Sciences, Pfizer

• Manufacturing options/challenges for ADC drug substance and drug product and linker-payload
• Acceptance criteria for cytotoxicity (potency) assay and its relation to clinical dose escalation scheme
• Aggregate in DS/DP – how high is acceptable?
• DAR and its relation to efficacy – challenges associated with maintaining DAR from early Tox through clinical material

Which Conjugation Method is Most Appropriate for ADCs Approved In 5-10 Years

Andreas Pahl, Ph.D., CSO, Heidelberg Pharma

• Will the FDA accept random lysine conjugated ADCs in 5-10 years?
• Enzymatic versus chemical conjugation
• Many enzymatic conjugation techniques become available, what are the respective advantages ?
• Does enzymatic conjugation add another layer of complexity to ADCs?

Stage-Appropriate Method Development Strategies: From R&D to Clinical

Lily Liu, BS, Principal Associate, Formulation and Analytical Development, Agensys, Inc.

This discussion will focus on the strategies for analytical method development at the following product development stages: R&D, process/formulation development, pre-clinical (tox, pilot), early phase clinical (Phase I-II), and late phase clinical (Phase II-III).  
• What are the common CQAs at all stages of product development?  What are the common analytical methods that are used for the different stages of product development?
• How do we determine the method is fit-for-purpose at the R&D stage vs. the clinical stage? What is an acceptable level of precision and accuracy for the methods at each of the stages?
• Should all CQAs be monitored from the early stages? Which CQAs (and therefore analytical methods) can wait to be tracked until the later stages?
• At what stage is it appropriate to pay close attention to analytical method performance? Which analytical methods should be fully characterized early on?  
• What would be some time-saving strategies for analytical method development? What are the advantages and disadvantages of shifting the analytical timelines? 

5:15 Discussion Report-Outs

5:30 Grand Opening Reception in the Exhibit Hall with Poster Viewing

7:00 End of Day


Day 1 | Day 2 | Short Courses | Download Brochure | Speaker Bios