Antibody Therapeutics Xchange West Coast 2019
Target Selection
- What is the situation?
- Swiss Army Knife Approach: piling multiple non-dependent targets on a single molecule
- MoA completely depends on BiS
- MoA may be enhanced by BiS
- Early regulatory and CMC advantages may come back to bite you in later stages
- Is there a future regulatory path for recombinant polyclonal therapeutics?
Vice President Antibody Therapeutics
Gritstone Oncology
- Optimal discovery method versus available budget – how do we decide the best path?
- Animal immunizations, natural human antibody repertoire library selection, or synthetic library selection – what are the pros and cons?
- What is the best strategy for choosing the lead candidate selection criteria and at what point should a functional study be integrated – early or later?
- What are the ideal immunization and selection tools? If appropriate cell lines and/or recombinant proteins are not available?
Director of Sales
ImmunoPrecise Antibodies
Barry Duplantis received a double major in Biochemistry and in Chemistry, and his Ph.D. in Microbiology from the University of Victoria in 2011, where he specialized in intracellular pathogenesis, bacterial genetics and synthetic biology. He subsequently founded and was CEO of DuVax Vaccines and Reagents Inc, a biotechnology company that specialized in the development of bacterial vaccines. Under Barry, DuVax successfully entered into collaborative research projects with two major pharmaceutical companies and delivered vaccines candidates for two separate pilot studies. He has also sat on the advisory board of biotechnology companies in the Victoria and Vancouver, B.C. areas.
- What does it mean (to you) to validate a target?
- What alternative criteria are used to justify discovery on a non-validated target?
- Can an imperfect animal model stand in the way of a perfectly good drug?
- When is a cell-based model superior to an animal model?
Principal Scientist
NGM Biopharmaceuticals
Alan is experienced with pre-clinical biologic drug discovery campaigns for a wide range of targets. He has served as project leader and engineering lead for both antibody and non-antibody biologic drug candidates.
Prior to NGM, Alan received his Ph.D. from UC San Diego for investigations of transcriptional regulation, post-doctoral training at UCSF, and then stints with Roche (Palo Alto), and Altravax.
- How do you nominate a potential drug target?
- How do you rate target tractability?
- What do you require before committing any resources to investigate a target?
- How do you deal with competing priorities within you discovery group?
- How early do you engage other groups in target prioritization (translational, Non-Clinical, Clinicaland business development?
Head of Antibody & Assay Development
Prothena
Robin has been involved in the development of monoclonal antibodies for over 25 years. At Elan, she headed the group that developed both the murine version of Natalizumab for Multiple Sclerosis and Bapineuzumab for Alzheimer’s Disease. At Prothena, currently 2 additional antibodies developed by her group are in Clinical Trials, one for the treatment of Parkinson’s Disease in Phase II, and the other for the treatment of TTR amyloidosis in phase I. Additionally, her group develops all pre-clinical and clinical assays for PK, ADA and biomarkers needed for Prothena’s programs.
Lead Identification
- What are the primary factors that influence your selection of a discovery platform?
- How do you weigh scientific, operational, and IP/technology access concerns?
- When seeking an antibody with a particular function (like ligand blocking or receptor agonism) in addition to target specificity, do you change your discovery platform?
- Are there any new discovery platforms or technologies on the horizon that have attracted your interest? Which platforms and why?
Antibody Therapeutics Expert
Shelley Force Aldred recently served as VP for Preclinical Development at TeneoBio where she led the preclinical efforts creating a CD3xBCMA bispecific antibody, from product concept to IND-ready package. Shelley was formerly director of R&D for Active Motif following the acquisition of SwitchGear Genomics in 2013. In 2006, she co-founded SwitchGear Genomics and she served as its COO. Prior to founding SwitchGear Genomics, Shelley was a Scientific Director on Stanford’s ENCODE Project and received her Ph.D. from Stanford University.
- How can you be confident in your data when measuring tight binding interactions?
- When can native expressing cells be used versus over expressing cells?
- What are the current methods available for measuring affinity to cell surface receptors?
- What are the current methods available to measure expression of cell surface receptors?
- How can problems such as receptor internalization and shedding be overcome?
Senior Scientist
Sapidyne Instruments
Thomas Glass is a co-founder of Sapidyne Instruments Inc. where his present position is Senior Scientist. He is a co-inventor of the KinExA technology which underlies their successful line of KinExA instruments used in characterizing the binding constants of reversible interactions including receptor-ligand, antibody-antigen etc. His undergraduate training is in Physics and his interest in measurements and instrumentation lead him through a Masters degree in Optics and a PhD thesis centered on environmental immunoassay. He actively supports development of new and improved binding measurement techniques centered on KinExA’s core interest of accurate binding constant measurement.
- What are the biggest challenges to overcome to enable selection of antibodies specific for multi-pass membrane proteins?
- What are the available technical solutions to these challenges?
- How can recombinant virus display and VLPs be used to overcome these challenges?
Team Leader, Antibody Selection
Vaccinex
Maria is a 20 plus years experienced Scientist leading a Therapeutic Antibody Discovery team with focus on innovation and difficult targets at Vaccinex, a clinical-stage biotechnology company located in Rochester, New York. Maria is a graduate of Cornell University. Prior to joining Vaccinex in 2003 she has gained research experience at the University of Rochester, Wyeth and Johnson & Johnson Ortho Clinical Diagnostics. Currently her work is focused on Therapeutic Antibody Discovery using Vaccinia Virus Display, Antibody Functional Characterization and ActivMab technology development. ActivMab™ Vaccinia Virus particles display complex antigens (GPCRs, Ion Channels, & Multispanners) for Antibody Discovery.
- It is a numbers game. How many is too many?
- How to address affinity and epitope of antibodies during lead optimization?
- What are the preferred lead optimization strategies for various biologics modalities?
- How to address immunogenicity during lead optimization?
- How to derisk the pharmacokinetic issues during lead optimization?
Senior Director, Protein Sciences
CytomX Therapeutics
Vangipuram Rangan is currently leading the Protein Sciences group at CytomX to support all the Probody discovery and development programs. He has more than 30 years of experience in enzymology and protein chemistry and about 18 years of experience in therapeutic biologics drug development. Prior to joining CytomX, he led the antibody process and analytics group at Medarex/BMS for 17 years. He has successfully transitioned more than 15 antibody therapeutics and 3 ADCs from discovery to IND for oncology, IO and immunology assets including approved drug Opdivo. Rangan obtained his PhD in Biochemistry from the University of Mysore, India.
Antibody Optimization
- What factors should be considered when determining the affinity needed for a functional activity?
- When and how should we remove sequence liabilities and T-cell epitopes?
- Is there a platform that could assist in the evaluation of the Ab sequence to improve its affinity, remove liabilities and reduce T-cell epitopes?
Senior Director
Pfizer
Isaac Rondon has over 20 years of experience in the field of antibody engineering. He is a Senior Director in BioMedicine Design at Pfizer Inc. where he has been part of the discovery and development of several biotherapeutic programs. Prior to joining Pfizer in May 2011, Isaac held Director position at Xoma, Catalyst Biosciences, Kalobios and Dyax where he contributed to the development of their technology platforms and the discovery and engineering of biologics. Isaac received his PhD in Pharmacology from Tulane Medical School and did his post-doctoral research at Harvard Medical School.
- Mechanism of action (MOA) drives affinity decisions – how do you determine this? What if MOA is not clear?
- Select appropriate epitope then affinity-mature to gain maximal efficacy? How/when is epitope selected?
- How do you balance affinity v avidity? What assays do you do to inform this decision?
Chief Scientific Officer
Carterra
Prior to joining Carterra as CSO in 2016, Yasmina Abdiche worked for twelve years at Pfizer-Rinat where she was a Research Fellow leading a bioanalytical team discovering therapeutic antibodies and served on Rinat’s leadership team and the governing committee for Pfizer’s Postdoctoral Program. She graduated from Oxford University with a PhD in Biological Chemistry and a Master’s degree in Chemistry, and did postdoctoral research at the University of Utah. Yasmina is co-inventor of fremanezumab, an anti-CGRP antibody set for US market approval in 2018 for chronic migraine and PF-06801591, a PD-1 inhibitor currently in PhI clinical trials for cancer immunotherapy.
- Balancing germlining with introducing poly/non-reactivity- where is the tipping point?
- How does the creation of multi-specific antibodies affect the potential for poly/non-specificity?
- Should screening out polyreactivity be an early and essential step for higher potency antibodies, ADCs and CAR-Ts?
Director, Antibody Discovery
CytomX
Arun Kashyap is Director, Antibody Discovery at Compugen USA, Inc in South San Francisco. His work has focused on the creation and utilization of peptide and antibody phage display libraries for therapeutic discovery in cancer, inflammatory disease, and infectious disease. Arun received an A.B. in Zoology from the University of California, Berkeley and a PhD from the University of California, Santa Cruz.
- What are the biggest challenges in therapeutic development where mathematical modeling could help?
- What types of questions can mathematical modeling help with in antibody optimization?
- Where is the biggest ROI for incorporating mathematical modeling into a program?
Co-Founder, President & Chief Executive Officer
Applied Biomath
John Burke received his PhD in Applied Mathematics from Arizona State University, and his BS and MS in Applied Mathematics from the University of Massachusetts, Lowell. Prior to co-founding Applied BioMath, John was at Boehringer Ingelheim as Associate Director, Head of Systems Biology and promoted to Senior Principal Scientist. John has also held positions at Merrimack Pharmaceuticals, the Systems Biology Department at Harvard Medical School, and in Douglas A. Lauffenburger’s lab at MIT.
Alternative Formats
- Discovery of novel CD3 binding antibodies
- Contribution of epitope and affinity to CD3 agonist antibodies
- T-cell redirecting bispecific antibodies applied to liquid and solid tumors
Chief Technology Officer
TeneoBio
Nathan Trinklein is the Chief Technology Officer at Teneobio. Teneobio employs a sequence-based approach for antibody discovery that leverages next-generation sequencing and high-throughput functionally assays to develop fully-human multi-specific antibodies. Prior to Teneobio, Nathan was co-founder and CEO of SwitchGear Genomics, a venture-backed company that was acquired in 2013. He served as the Technical Director of the Stanford ENCODE project and received his Ph.D from Stanford University. Nathan has published over 20 peer-reviewed papers and is an inventor on over 15 patents.
- How to optimize antibody sequence without introducing unnatural mutations?
- How to thoroughly explore natural antibody sequence space around your lead?
- Humanizing and optimizing your lead at the same time – pitfalls?
- How do you exclude potential developability dipeptide motifs from your library?
Chief Scientific Officer
Twist Biopharma, a division of Twist Bioscience
Aaron is Chief Scientific Officer of the Biopharma Vertical at Twist Bioscience. Prior to Twist, he served as Chief Scientific Officer of LakePharma, leading the California Antibody Center, which discovers novel antibody therapeutics for its clients. He also oversaw all discovery research functions both as Vice President of Protein Sciences at Surrozen, and previously, as Vice President of Research at Sutro Biopharma, Inc. He also held director level positions at both Oncomed and Dyax Corp.
- How much do species differences in FcR affinity, expression pattern or receptor distribution impact target validation and safety predictions?
- Enhanced ADCC: it’s not just for tumors anymore! What are the risks of depleting non-tumor cells with ADCC enhanced antibodies?
- Binding analysis: What assays are critical and how much information is enough for lead selection/optimization?
- Do human polymorphisms in FcR impact antibody screening and selection strategy
- How will Fc optimization impact immunogenicity, half-life or binding to FcRn, or developability?
Vice President, Discovery Research
Apexigen
Frances Rena Bahjat serves as Vice President, Discovery Research for Apexigen. She has nearly 20 years of experience encompassing target discovery and preclinical and clinical development of biologics and small molecules for cancer, as well as autoimmune and inflammatory diseases. She studied Biomedical Sciences and Immunology at the University of Florida College of Medicine where she earned her Doctorate in Immunology. She also served in scientific roles at BMS Biologics Discovery and Rigel Pharmaceuticals and in between was an Assistant Professor at Oregon Health & Sciences University. As Associate Director of Pharmacology at Rigel Pharmaceuticals she contributed to the preclinical and clinical development of kinase inhibitors for cancer, allergy, and autoimmune diseases, including recently approved Tavalisse™ for Chronic Immune Thrombocytopenia.
- Which antibody (protein) properties affect the safety and efficacy of ADCs?
- How might new antibody formats improve ADC safety? – increase specificity to target tissue, reduce non-specific internalization, etc.
- How might new antibody formats address limitations of ADC efficacy? – tissue penetration, internalization, etc.
Senior Director, Protein Engineering
CytomX Therapeutics
Madan Paidhungat is Senior Director and Head of Protein Engineering at CytomX Therapeutics, Inc., where he is engaged in developing activatable antibody-based therapeutics. His career has focused on developing and leveraging novel in-vitro-evolution based technologies for therapeutics R&D. Before CytomX, Madan was Director, Biology at Dice Molecules, LLC where he directed biology and informatics to establish a DNA-programmed combinatorial chemistry platform for small-molecule discovery. Prior to that he spent over 12 years at Maxygen Inc., Perseid LLC, and Astellas Inc. applying DNA shuffling to the development of protein-, antibody-, and bi-specific therapeutics.
Targeted Immunotherapies
- Affinity for CD3: how low can we go?
- Can avidity reduce on-target but off-tumor toxicity without compromising efficacy?
- How can we validate tumor protease-based prodrug approaches?
- Are tri-specific formats ready for prime time?
President & Chief Technology Officer
Amunix
Volker Schellenberger is President and CEO of Amunix Pharmaceuticals, which he co-founded in 2006. He initially served as Amunix’ Chief Scientific Officer and is the lead inventor of the company’s XTEN as well as XPAT platforms of protease-activated T cell engagers. Volker has over 20 years of industry experience in protein engineering and drug discovery. Prior to co-founding Amunix he served as head of Genencor’s protein engineering department.
Volker received his Ph.D. from Leipzig University (Germany) in 1986. He is author of over 40 scientific papers and inventor of more than 70 issued or pending patent applications. He is a recipient of the Karl Lohmann prize of the German Society of Biochemists.
- How can immunogenicity be assessed early on?
- How to interpret the results and address any immunogenicity concerns?
- What is the perspective of the regulatory authorities on the subject?
Founder & Chief Technology Officer
ImmunXperts
Sofie has over 20 years of experience in the field of immunogenicity assessment (vaccines and biotherapeutics). She has extensive hands-on lab experience and has managed and coached several In Vitro teams over the last decade. From 2008 till 2013 she was Head of the In Vitro Immunogenicity group at AlgoNomics (Ghent, Belgium) and Lonza Applied Protein Services (Cambridge, UK). Prior to that, she worked at Innogenetics, Belgium for over 15 years.
- Which antibody formats are most suitable for antibody-cytokine fusions and what are the critical design components
- What have we learnt so far from current antibody-cytokine fusions (eg.FAP-IL-2) with regards to therapeutic index
- Fine tuning’ an optimal orchestration of the immune response against the tumor while reducing the systemic toxicity of potent cytokines using antibody-cytokine fusions – Can we make this a reality?
Executive Director, Biotherapeutics
Exelixis
Seema Kantak is currently Executive Director, Biotherapeutics at Exelixis where she is leading the oncology biotherapeutics external R&D effort, focusing on the identification, evaluation and early development of biologics assets and is responsible for establishing, building and advancing a biotherapeutics portfolio. Prior to Exelixis she was Chief Scientific Officer at a start-up, Symic Bio. Prior to joining Symic, Seema held leadership positions at Nektar Therapeutics, XOMA, Celera Therapeutics and Axys Pharmaceuticals. Seema has contributed to several IND submissions in multiple therapeutic areas. She received her Ph.D. in Cancer Biology from Wayne State University School of Medicine, and completed her postdoctoral work at UCSF. Dr. Kantak also holds a M.S. in Biology from Wayne State University and a M.S. in Biophysics from Bombay University.
- Utility of mouse cross reactive CD3 bispecific antibodies in translating efficacy and toxicity to the clinic
- Pros and cons of using CD34+ humanized mice, PBMC or T cell engrafted efficacy models
- Importance of using cell lines vs PDx with/without autologous T cells to understand efficacy of CD3 bispecific antibodies and translation to clinical trials
Vice President, Immuno-Oncology
IGM Biosciences
Angus Sinclair PhD is the Vice President Immuno-oncology Research at IGM Biosciences Inc with over 16 yrs experience in the biotech industry. Prior to joining IGM Biosciences, Angus was the Senior Director of Oncology at Northern Biologics Inc, Toronto and Scientific Director of Oncology at Amgen. During his tenure in biotech, Angus has progressed multiple antibody-based and small molecule therapeutics through preclinical research and development to the clinic. Before joining Amgen, Angus held academic positions at UT Southwestern Medical Center, Texas; University of Cambridge, UK and UCSD, California.