Scientific Innovation and Emerging Technologies in the Discovery and Development of Biotherapeutics

(AAPS Emerging Technologies Action Program

Committee – presently Discussion Group)

2014 NBC Dr. Fabio Garofolo

Emerging Technologies Stephanie Fraser (Co-Lead) Fabio Garofolo (Co-Lead)

Assay  Throughput  Team  

Johanna  Mora  Valerie  Theobald,  Allison  Chunyk    Mark  Dysinger    Claude  Ricks  Shobha  Purushothama    Karolina  Österlund  

ET  Leadership  Team  Steering  CommiAee  Stephanie  Fraser  Fabio  Garofolo  Judy  Shih    Johanna  Mora  Valerie  Theobald    Rebecca  Crisino  Alvy  Mikulskis    Sally  Fischer  ScienGfic  Advisors  Binodh  Desilva  Lakshmi  Amaravadi    Philip  Oldfield  

Assay  Sensi6vity  Team  Alvydas  Mikulskis    Sally  Fischer    Alison  Joyce    Mark  Spengler    Yang,  Tong-­‐Yuan  Yao  Zhuang    Marianne  Scheel  Fjording    

Biological Samples & Reagents Management

Aleks Davis(Co-lead)

LBA  Technologies  Discussion  Group  (LBATDG)  

Assay  Interference  Team  

Rebecca  Crisino  Fabio  Garofolo  Brian  Geist    Maura  Kibbey    Linlin  Luo  Yan  Ni  Frank  Spriggs    Jad  Zoghbi      

Real-­‐6me  Measurement  

Team  Stephanie  Fraser  Judy  Shih    Mark  Ware  Mark  Cameron    MarGn  Schwickart    Ed  O’Connor    Michael  Tanen  

Biological  Sample  

Management  Team  

Aleks  Davis  Andrew  Mayer  Medha  Kamat  Jihong  Yang  

   

Reagent  Management  

Team    Presently  non  acGve    

21st cLAB Ago Ahene (Co-lead) Chad Ray (Co-Lead)

Leads  of  Subgroups  AutomaGon  –Ago  Ahene  PlaVorm  –  Frank  Spriggs  Reagents  –  Denise  O’  Hara  Electronic  soluGons-­‐  Sheldon  Leung  

LBABFG  

ET Mission

“The Emerging Technologies Group mission is to on evaluate the potential of emerging

technologies used for biotherapeutics quantification beyond the common current applications and provide these evaluations to the greater scientific community so as to expedite their technology evaluative

processes.”

•  ET Leadership Team: The Emerging Technologies Group mission is to on evaluate the potential of emerging technologies used for biotherapeutics quantification beyond the common current applications and provide these evaluations to the greater scientific community so as to expedite their technology evaluative processes.

•  Assay Throughput Team: To assess newly emerging technologies and their potential practical applications for analyte multiplexing and/or maximizing throughput for ligand binding assays.

•  Assay Sensitivity Team: Provide practical recommendations to the LBA community based on comprehensive evaluation of emerging technologies and new applications of existing technologies in addressing the unmet assay sensitivity needs for quantification of large molecules in PK, immunogenicity, and biomarker assays

•  Assay Interference Team: To evaluate emerging technologies and new applications of existing technologies that will enable us to overcome specific & non-specific interferences from matrix components to allow 1) the quantification of biologics, and 2) the detection of anti-drug antibodies. Provide practical recommendations to the LBA community

•  Real-time Measurement Team: This team will investigate and evaluate new and emerging technologies that will enable the quantification of biologics at the time-point they are detected. A continuous or single detection event and therefore real-time measurement of the biologic must occur to be within our scope of focus

Emerging Technologies Teams

ET definitions

EMERGING TECHNOLOGY •  A novel application of knowledge to achieve

the desired effect (improved drug tolerance, eliminate matrix interference, etc.)

•  A brand new practical application that is not

well characterized or widely utilized in the current LBA community.

ET definitions PROTOTYPE vs. EMERGING

A “prototype” is not considered “emerging” •  Prototype: A first or preliminary model of an

experimental machine •  Emerging: something becoming apparent,

important, or prominent

2014 Accomplishments/Progress

Emerging Technologies Presentations:

1)  8th WRIB (March 2014 Universal City - Los Angeles); 2)  2014 NBC (May 2014 San Diego);

Publications:

1)  Editorial on Special issue in Bioanalysis Journal on Matrix Effect for LBA

2)  Multiple team members’ research articles for Special issue in Bioanalysis Journal on Matrix Effect for LBA

3)  AAPS Journal special issue on Emerging Technologies: DG effort

Preparation of an Assay Interference Evaluation Protocol: MSD vs. ET •  An in-depth evaluation of four emerging technologies for pharmacokinetic

and immunogenic assays in the presence and absence of interfering agents (intended to mimic matrix interference and drug intolerance). All the data collected during this experimental part will be shared with the LBA scientific community and will help implantation of new technologies.

ET Group Participation/Interaction

CONTACT: •  Dr. Stephanie Fraser (Pfizer)

– Email: Stephanie.Fraser@pfizer.com – Office: +1-860-715.4987

•  Dr. Fabio Garofolo (Algorithme Pharma) – Email: fgarofolo@algopharm.com – Office: +1-450-973.3155 Ext. 2301

2014 NBC ET Symposium

“Acoustic Membrane Micro Particle: An Emerging Technology in the Ligand Binding Assay Space”

Dr. Johanna Mora (Bristol-Myers Squibb)

“Importance of Emerging Technologies: Their Impact in Drug Discovery and Development”

Dr. Stephanie Fraser (Pfizer)

“Emerging Technologies for PK Assays” Dr. Sally Fischer (Genentech)

“Emerging Technologies for Immunogenicity”

Ms. Valerie Theobald (Sanofi)

Panel Discussion

Dr. Johanna Mora •  Johanna is currently a Senior Research Investigator

responsible for regulated bioanalysis of biotherapeutics at BMS.

•  She received a Ph.D. in Bioanalytical Chemistry from the University of Kansas in 2004.

•  She worked at Genisphere (Hatfield, PA) until she joined BMS in 2007.

•  At BMS she leads a team of scientists in the bioanalysis of macromolecular therapeutics for PK, immunogenicity and discovery support. She is also responsible for development and execution of novel technologies and scientific strategie for bioanalysis of protein therapeutics.

Dr. Stephanie Fraser

•  After obtaining her PhD in Cellular and Molecular biology from the University of Nevada, Reno, Stephanie has spent the last 15 years in the field of bioanalysis.

•  She has held positions in academia, biotech, contract research and large pharma where she has managed LBA (discovery to Phase IIb clinical) and flow cytometry (preclinical) laboratories.

•  She has also taken the lead on implementing new/emergent technologies.

•  Currently Stephanie leads Pfizer’s Regulated Bioanalysis LBA group, focusing on early clinical biomarker support.

Dr. Sally Fischer •  Sally obtained her Ph.D. in Biochemistry. After postdoctoral

fellowships at the Oregon State University and the Lawrence Livermore National Laboratory, she joined Genentech as a Research Scientist in 2000.

•  She moved to Development Sciences in 2003 and is currently a Senior Scientist/group leader in the Assay Development and Technology (ADT) group within the Bioanalytical Sciences (BAS) department.

•  Her group is responsible for development of assay strategies and validation of methods to evaluate the pharmacokinetics (PK), anti-therapeutic antibodies (ATA) as well as biomarkers in both non-clinical and clinical studies for non-oncology indications. .

Ms. Valerie Theobald •  Valerie is Scientific Associate Director in the Clinical

Laboratory Sciences at Sanofi where she leads the Analytical Assay Development group.

•  Methods developed and validated in her group are used to support Genzyme clinical trials and post marketing studies and include safety, immunogenicity, neutralizing antibody, PK, efficacy and biomarker analysis.

•  Methods to quantify antibody responses specific to therapeutic proteins, impurities, and gene therapy vectors are also developed and validated.

•  In addition, Valerie’s group provides life-cycle management for critical reagents.

•  . .