Cambridge Healthtech Instituteの第15回年次
Immunogenicity Assessment and Management
- 5:00 pm Main Conference Registration1:00 pm
Recommended Pre-Conference Short Course2:00 pm
SC3: In silico and Machine Learning Tools for Antibody Design and Developability Predictions
*Separate registration required. See short courses page for details.
Dessert Break in the Exhibit Hall with Poster Viewing1:40 pm
RISK ASSESSMENT, MITIGATION, AND TRANSLATION
Computational and in vitro Immunogenicity Strategies for Biotherapeutics and Novel Therapeutic Modalities
Increased complexity and protein engineering of biotherapeutics have increased the potential for human immunogenicity in patients. Comprehensive immunogenicity risk assessment strategies in combination with protein engineering can mitigate these risks resulting in safer and more efficacious therapeutics for patients. Machine learning tools can be used to mine in vitro data sets to develop high throughput computational tools to push comprehensive immunogenicity risk assessment earlier into the discovery process.
De-Risking Strategies and Tools: Simultaneous Humanization, De-Immunization, and Elimination of Chemical Liabilities for Antibody-Based Biologics
Lead sequence optimization consists of sequential steps addressing efficacy, safety, and developability. However, sequence optimization of one parameter leads to unwanted consequences on the other two resulting in suboptimal drug substances. We present a framework to simultaneously de-risk immunogenic and physico-chemical sequence liabilities while maintaining parental efficacy parameters. This framework employs open source in silico tools and is achieved by simultaneous humanization, de-immunization, and sequence optimization of antibody-based biotherapeutics.
Yurogen's SMab antibody discovery process is a superior platform for generating monoclonal antibodies for drug development, particularly for developing antidrug (ADA) and pharmokinetic (PK) antibodies. SMab offers a streamlined process that reduces turnaround time while increasing specificity and yield. Yurogen's SMab antibody discovery process can deliver monoclonal antibodies in just 15 weeks, providing critical PK and ADA antibodies for drug development and IND-enabling studies in a timely and cost-effective manner.
Refreshment Break in the Exhibit Hall with Poster Viewing3:50 pm
Innate Immune Response Modulating Impurities Testing for Generics and Biosimilars: Where We Are and What We Are Missing
Comparative in vitro analytical methods to characterize innate immune response modulating impurities could potentially provide a more robust understanding of immunogenicity risk for generic peptides and biosimilars and help streamline their development. This talk will discuss the risks posed by innate immune response modulating impurities, available assays, and data interpretation, as well as common pitfalls and remaining knowledge gaps.
THE IMMUNOPEPTIDOME LANDSCAPE
The Landscape of the MHC II Ligandome
I will discuss all the variables which contribute qualitatively and quantitatively, to the composition of the MHC II ligandome. Altogether, ensuring that the immunopeptidome landscape is highly sensitive to any changes in the composition of the intra- and extracellular proteome for a comprehensive survey of the microenvironment for MHC II presentation to CD4 T cells.
Close of Day6:00 pm
Dinner Short Course Registration6:00 pm
Recommended Dinner Short Course6:30 pm
SC8: CAR T Cells: Improving Safety While Retaining Therapeutic Activity
*Separate registration required. See short courses page for details.
Registration and Morning Coffee7:30 am
CLINICAL RELEVANCE OF ADA
Developing an Integrated Summary of Immunogenicity to Assess Clinical Relevance of ADA/NAb
An Integrated Summary of Immunogenicity (ISI) is a component of regulatory dossiers for biopharmaceutical product submissions, facilitating product review, approval, and labeling. A multifactorial approach is required, incorporating immunogenicity risk assessment, bioanalytical strategy, and evaluation of clinical impact of anti-drug antibodies and neutralizing antibodies on pharmacokinetics, clinically relevant biomarkers, efficacy and safety parameters. This presentation will discuss our experience developing ISIs, including overall strategy and case examples.
Immune Tolerance and the Dynamics of ADA Responses of Therapeutic Proteins
ADA responses vary widely not only between different drugs, but also between recipients. Interestingly, it is frequently observed that an ADA response may be transient. Here we discuss examples of such variable responses, the factors contributing to dampening the ADA response, and the clinical significance thereof.
ADA Results Reporting - A Harmonized Approach
The presence of anti-drug antibodies (ADA) is an important factor in contextualizing clinical study PK, PD, safety, and efficacy. Recent efforts in harmonizing ADA validation and incorporating immunogenicity information into drug product labeling underscore the need for consistency and scientific rigor to facilitate proper communication and understanding of ADA impact. To support this effort, a cross-industry group established harmonized recommendations and a report template for clearly summarizing the essential aspects of ADA clinical study testing and reporting. This talk will present the recommendations for ADA bioanalytical report elements such as the method, critical reagents, equipment, data analysis, and study results.
Integrated platforms can be used to mitigate immunogenicity risk and characterize immune responses during the drug design and development stages. ProImmune offers mutational activity mapping for optimal protein design, DC-T/T cell proliferation assays for biologic lead selection/optimization, a Mass Spectrometry assay for characterization of antigen presentation; HLA-peptide binding assays to characterize individual epitopes & undiluted whole blood cytokine storm assays.
Coffee Break in the Exhibit Hall with Poster Viewing10:30 am
Transition to Plenary Keynote Session11:10 am
PLENARY KEYNOTE SESSION
Advancing Innovative Biologics Modalities from Research to Clinical Application - Novel Platforms, Automation, and Computation
Addressing disease biology in the clinic with protein therapeutics has become increasingly complex. Turning to innovative and novel scaffolds offers opportunities to tailor therapeutics not previously possible due to advances in host cell engineering and protein design approaches. Designing and developing these modalities requires a next-generation approach as we exploit increased potential design space and also growing data sources to leverage as we invent the next wave of therapeutics.
YOUNG SCIENTIST KEYNOTE
Engineering Prime Editor Proteins for Therapeutic Applications
Precision gene editing technologies have the potential to address a wide range of genetic diseases. Prime Editing is a recently developed “search-and-replace” gene editing approach that can precisely perform a wide variety of DNA sequence edits at programmed target sites in human genomes without requiring double-strand DNA breaks or donor DNA templates. I will describe advances to prime editing technology that improve its efficiency, specificity, and capabilities for therapeutic applications.
Session Break1:00 pm
Assays that correlate with human pharmacokinetics, immunogenicity, and manufacturability are invaluable for Biologics Drug Discovery. We use a high throughput analytical suite to assess critical developability parameters using orthogonal tests including in silico tool and in vitro assays such as AC-SINS, Baculoviru/DNA/insulin ELISA, FcRn binding, Serum stability, PBMC based immunogenicity tests. The panel includes 96WP with sample consumption of ~100ug/assay, which is especially suitable for early lead ID/lead op stage.
Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own1:40 pm
Interactive Discussions are informal, moderated discussions, allowing participants to exchange ideas and experiences and develop future collaborations around a focused topic. Each discussion will be led by a facilitator who keeps the discussion on track and the group engaged. To get the most out of this format, please come prepared to share examples from your work, be a part of a collective, problem-solving session, and participate in active idea sharing. Please visit the Interactive Discussions page on the conference website for a complete listing of topics and descriptions.
TABLE 9: Clinical Relevance of Anti-Drug Antibodies - IN-PERSON ONLY
- Identify assay design parameters to ensure detection of relevant antibodies
- Planning assay implementation timelines using immunogenicity risk assessment
- Designing schedule of assessments within clinical trials
- Integrate multiple findings to assess clinical relevance
- Conducting analysis using immunogenicity status as an outcome, not a baseline characteristic
TABLE 10: Predictive Assays, Studies, and Tools: How Can These be Improved? - IN-PERSON ONLY
- In-silico and in-vitro tools: State-of-the-art
- In-vitro/in-vivo correlation of immunogenicity: What do we know?
- Immunogenicity strategy: How do we select the right assay?
- Interpretation of results and decisions: De-immunization vs immunogenicity risk and impact on project timelines
- Examining the regulatory requirements
NEUTRALIZING ANTIBODY CHARACTERIZATION
NAB Assay Strategies and Mitigation of Matrix Interference
Determining the neutralizing activity of an anti-drug antibody response is critical to understanding the safety and efficacy profile of a therapeutic. In order to achieve a sensitive assay, the concentrations of reagents in the assay system need to be carefully balanced; excess amounts of target or therapeutic can lead to inaccurate results. We will discuss considerations for mitigating the influence of these interferents during assay development.
Novel Approach to Overcome Drug Interference in Neutralizing Antibody Assays
Interference from free drug in patient serum is a key challenge in assessment of neutralizing antibodies (NAb). PABAD (Precipitation, acid Dissociation and Biotin-drug as Assay Drug), our new approach for assaying NAbs improve the drug tolerance of NAb assay while being compatible with both acid-sensitive and stable NAbs. Minimal requirement of Biotin-drug, unnecessity for magnetic beads, are additional advantages of PABAD that reduce cost and time of NAb assessment.
Solutions of monoclonal antibodies (mAbs) can show increased viscosity at high concentration, which can be a disadvantage during protein purification, filling, and administration. We present a modeling approach employing artificial neural networks (ANNs) using experimental factors combined with simulation-derived parameters plus viscosity data from 27 highly concentrated (180 mg/mL) mAbs. These ANNs can be used to predict if mAbs exhibit problematic viscosity at distinct concentrations or to model viscosity-concentration-curves.
High-throughput in silico and in vitro workflows allow for early comprehensive triage and lead candidate optimization. By leveraging data from over 1,800 clinical benchmarks, the in silico workflow from IPA provides 3D structural models depicting an immunogenicity composite ranking from HLA binding predictions based on customizable phenotype distribution and humanness scoring. Combining over 12 in vitro assays with the in silico outputs, a comprehensive data package is provided.
Ice Cream Break in the Exhibit Hall with Poster Viewing4:35 pm
PEGS BOSTON COMMON: SPEED NETWORKING
How Many New Contacts Can you Make? - IN-PERSON ONLY
Bring yourself, your business cards or e-cards, and be prepared to share and summarize the key elements of your research in a minute. PEGS-Boston will provide a location, timer, and fellow attendees to facilitate the introductions.
RECENT ADVANCES WITH NOVEL MODALITIES
Assessment of Transgene Immunogenicity in Gene Therapies
Discussion of gene therapy immunogenicity has focused mainly on anti-AAV antibodies, particularly pre-existing responses. However, the transgene protein may also induce a humoral or cellular immune response. This presentation will discuss the approaches to assessing immunogenicity against the expressed transgene product.
Immunogenicity Characterization for a Bispecific and ADA
Bispecific antibodies are a novel class of complex molecules. Despite great interest in these new modalities to increase efficacy for treatment of complex diseases, recent clinical data indicate unique development challenges with high immunogenic potential which could potentially cause the failure of clinical program. Here, we present the evaluation of preexisting reactivity, anti-drug antibodies, and domain specificity to understand the immunogenicity response to multiple domain biotherapeutics.
Networking Reception in the Exhibit Hall with Poster Viewing6:40 pm
PEGS BOSTON COMMON: WOMEN IN SCIENCE MEET UP
Women In Science Meet Up - IN-PERSON ONLY
The Women in Science Meet Up celebrates women trailblazers who are setting their own course in science. We invite women and men to come celebrate the successes of these women in breaking down barriers and inspiring future generations of female leaders. Come join fellow scientists and share your personal and professional journey.
- Who or What inspires you to explore a career in science?
- What fuels your imagination and spirit when you’re faced with challenges?
- What is your proudest moment?
- What can each of us do to improve things further?
Close of Immunogenicity Assessment and Management Conference7:40 pm