The AAPS Scientific Programming Committee presents this PharmSci 360 overview.
The Six Tracks
View the full program and add sessions to your schedule today!
BUGS, DRUGS, AND THE MICROBIOME: WHAT'S THE HYPE, WHAT"S THE PROMISE?
Prologue: Engineering and Formulating Microbes to Advance Microbiome-Based Therapy
Attendees will have a contemporary background of human microbiome basic research and development activities including transplant, engineering, immune system interactions, and, finally, an introduction to the clinical research underway in the field. This prologue will give a brief review of the field, leaders in the field, as well as framing out regulatory considerations for the progression of therapies in the clinic .
Tuesday, Oct. 27 9:30 am – 10:00 am
Symposium: Designing Living Diagnostics and Therapeutics
The engineering of biology presents infinite opportunities for therapeutic design, diagnosis, and prevention of disease. We use what we know from Nature to engineer systems with predictable behaviors. We also seek to discover new natural strategies to then re-engineer. This presentation covers concepts and experiments that address how we approach these problems in a systematic way.
Tuesday, Oct. 27 10:30 am – 11:00 am
Symposium: Delivery Strategies for Microbe Therapeutics
My lab has modified the surface of living biological therapeutics (LBTs) for enhanced adhesion to intestinal epithelial cells and developed a film-based polymer encapsulation technology that is compatible with standard oral capsules to facilitate adhesion and sustained release of LBTs. This presentation will highlight these results and broadly discuss the potential of applying pharmaceutical, bioengineering, and drug delivery approaches for improving the delivery of LBTs to the gastrointestinal tract.
Tuesday, Oct. 27 11:00 am – 11:30 am
Symposium: Product Development for Microbiome Therapeutics—Concepts for a New Paradigm
This presentation will discuss upstream and downstream challenges and solutions in developing microbial therapeutics. I will describe challenges in current good manufacturing practice testing of microbial therapeutics, list several strategies for using microbial therapeutics, and discuss regulatory concerns and solutions surrounding microbial therapeutics.
Tuesday, Oct. 27 11:30 am – 12:00 pm
Symposium: Regulatory Considerations for Microbiome Based Therapeutics
This presentation will cover the basics of submitting an Investigational New Drug application as well as specific requirements for chemistry, manufacturing, and control information to be provided for microbiome-based therapeutics including both live biotherapeutic products and fecal microbiota for transplantation.
Tuesday, Oct. 27 12:00 pm – 12:30 pm
Keynote: Blocking Bacterial Lipopolysaccharide to Relieve Immune Suppression in Colorectal Cancer
When colorectal cancer (CRC) grows in the wall of the colon intestine, LPS can penetrate across the epithelium and enter the tumor. We will discuss a therapeutic strategy for targeting LPS or its receptor TLR4 as an effective means to control tumor growth.
Leaf Huang, Ph.D., University of North Carolina at Chapel Hill
Tuesday, Oct. 27 2:00 pm – 3:00 pm
Rapid Fires
Tuesday, Oct. 27 3:30 pm – 4:30 pm
NOVEL ONCOTARGETS
Rapid Fires
Wednesday, Oct. 28 9:00 am – 10:00 am
Prologue: Targeted Protein Degradation: PROTACs and Molecular Glues for Pediatric Cancers
Targeted protein degradation (TPD) is an emerging therapeutic modality that has attracted much attention in drug discovery recently, owing to potential advantages over conventional inhibitors with respect to dosing, selectivity, drug resistance, and modulating “undruggable” targets. In this presentation, we will describe the TPD platform at St. Jude through case studies from our ongoing efforts in the design and biological evaluation of novel proteolysis targeting chimeras and molecular glues.
Wednesday, Oct. 28 9:30 am – 10:00 am
Symposium: Discovery of Potent, Selective, and Orally Bioavailable Inhibitors of USP7 with in Vivo Antitumor Activity
The deubiquitinase USP7 is a key regulator of oncogenic driver proteins. We discovered a series of structurally novel USP7 inhibitors that exhibited good selectivity compared to other deubiquitinating enzymes. These studies suggested changes could be made to the structure that both maintain potency and improve oral exposure. This has led to compounds that show promising activity in anti-tumor models.
Wednesday, Oct. 28 10:30 am – 11:00 am
Symposium: Brain Penetrant Pi3ka Inhibitors
In addition to each of the factors that affect the identification of a successful oncology drug candidate, drug discovery aimed at treating neurological cancers must also consider the presence of the blood-brain-barrier (BBB). High expression of transporters at the BBB limits most kinase inhibitors from freely reaching CNS malignancies within the brain. This talk will discuss the unmet need for neuro-oncology treatments and the discovery of paxalisib, a blood-brain barrier penetrating inhibitor of PI3 kinase.
Wednesday, Oct. 28 12:00 pm – 12:30 pm
Keynote: Novel Treatment Strategies for Treatment of Hematopoietic Malignancies in the Context of the Bone Marrow Microenvironment
Lori A. Hazlehurst, Ph.D., West Virginia University
Wednesday, Oct. 28 2:00 pm – 3:00 pm
PRECLINICAL BIOMARKER STUDIES: CONNECTING DISCOVERY AND CLINICAL DEVELOPMENT
Prologue: Novel Non-Invasive Methods for Early Disease Detection
In this session, you will hear from experts in emerging technologies who are at the forefront of disease detection and diagnosis using noninvasive and highly sensitive methodologies. Topics will include an introduction to the detection of circulating cancer cells, a novel methodology for urinary detection of cancer-derived exosomes, and diagnosing adverse cardiac events and their correlation to low serum ApoA-IgG levels.
Thursday, Oct. 29 9:30 am – 10:00 am
Symposium: Nanoengineered Surfaces for Effective Capture and Analysis of Tumor-Derived Exosomes and Circulating Tumor Cells
Tumor-derived blood-circulating exosomes have potential as a biomarker to greatly improve cancer treatment. However, effective isolation of exosomes remains a tremendous technical challenge. This study presents a novel nanostructured polymer surface for highly effective capture of exosomes through strong avidity. Our results support that the dendrimer surface detects tumor exosomes at high sensitivity and specificity, demonstrating its potential as a new cancer liquid biopsy platform.
Thursday, Oct. 29 10:30 am – 11:00 am
Symposium: A Non-Invasive Liquid Biopsy Approach Using Urine-Derived Exosomes As a Biomarker Source for Predicting Treatment Outcomes in Cancer
Thursday, Oct. 29 11:00 am – 11:30 am
Symposium: Don’t Lose Heart: Advancing Biomarker Discovery
The identification of the immune system as a major driver of cardiovascular disease has shifted our understanding of the disease’s mechanisms. Referencing 359 subjects with cardiovascular disease, we identified a unique antibody profile that is associated with a decreased incidence of adverse cardiovascular outcomes. Identification and characterization of this antibody profile will be presented along with evaluation of subjects from retrospective and prospective cohorts. Molecular characterization of the antibodies and their target epitopes will also be discussed.
Thursday, Oct. 29 11:30 am – 12:00 pm
Keynote: Single Cell Profiling of Coding & Noncoding RNA As Predictive Inflammatory Biomarkers
Musa Mhlanga, Ph.D., University of Cape Town
Thursday, Oct. 29 2:00 pm – 3:00 pm
Rapid Fires
Thursday, Oct. 29 3:30 pm – 4:30 pm
MAKING THE IMMUNE SYSTEM BEHAVE: VACCINES, IMMUNOTHERAPIES AND OTHER TREATMENTS
Prologue: Opportunities and Challenges of Intranasal Vaccine Delivery
This presentation will cover nasal vaccination advantages and problems associated with the very few nasal vaccines that are brought to clinics; challenges developing nasal vaccines, potential solutions to the challenges, and additional innovations needed to overcome the challenges; and experience we have with nasal immunization.
Monday, Nov. 2 9:30 am – 10:00 am
Symposium: Shedding Light On Chitosan-Based Nanoparticles As Intranasal Vaccine Adjuvant
This presentation will cover anatomical and physiological factors affecting intranasal systemic and local drug delivery and implications on the design of antigen delivery systems to be administered by nasal route. It will also provide a case-study showing chitosan-based nanoparticles for recombinant protein and DNA vaccines, including the influence of the composition of the nanoparticles on the immune response generated.
Monday, Nov. 2 10:30 am – 11:00 am
Symposium: Intranasal Immunization: Promises and Challenges
This presentation will review the nasal cavity anatomy and physiology that makes nasal vaccination both an opportunity and a challenge. Device developments as well as formulation strategies for both aqueous and powder-based platforms will be discussed. The presentation will also highlight challenges with drug absorption and bioavailability, mucociliary clearance, and the enzymatic environment within the nasal cavity.
Monday, Nov. 2 11:00 am – 11:30 am
Symposium: Acetalated Dextran Enhances Vaccine Delivery
Polyesters often have degradation rates measured in months, in addition to acidic degradation byproducts. This contrasts with Ac-DEX that has tunable degradation rates that can range from hours to months and degrades into benign levels of dextran, acetone, and ethanol. This presentation will illustrate the utility of Ac-DEX’s degradation tunability for vaccine delivery applications, in that fine tuning of rate has dramatic effect on formulation efficacy.
Monday, Nov. 2 11:30 am – 12:00 pm
Symposium: Coordination Polymers for Controlled Vaccine Delivery and Enhanced Antigen Presentation
This talk will provide background on vaccine technology and highlight its principle deficiencies—the poor stability of antigens and difficulty in producing strong humoral responses from single injections. I will cover the coordination polymers and immunology at a level suitable for a general audience.
Monday, Nov. 2 12:00 pm – 12:30 pm
Keynote: Biodegradable Polymeric Particles As Adjuvant and Vaccine Delivery Systems
Antigen and adjuvant loaded biodegradable particles are capable of being actively taken up by antigen-presenting cells, thereby stimulating potent antigen-specific immune responses against the target antigen. Various formulation parameters can be used to modulate the overall immune response generated. Adjuvant loaded particles can be synergistically used in combination with other therapeutic strategies such as viral based vaccines, chemotherapeutics, and checkpoint blockade agents.
Aliasger K. Salem, Professor, University of Iowa
Monday, Nov. 2 2:00 pm – 3:00 pm
Rapid Fires
Monday, Nov. 2 3:30 pm – 4:30 pm
TAMING THE BLOOD-BRAIN-BARRIER IN CNS DRUG DELIVERY
Rapid Fires
Tuesday, Nov. 3 9:00 am – 10:00 am
Prologue: Targeting The Blood-Brain Barrier: Exploiting Biology to Optimize Neuropharmacology
In this session, established experts from academia and industry will discuss state-of-the-art approaches to target the blood-brain barrier (BBB) for delivery of therapeutics via 1) endogenous transport systems; 2) receptor-mediated endocytosis; 3) nanotechnology strategies; and 4) intranasal drug delivery. Each speaker will also provide perspective on how these delivery strategies can be employed in the discovery and/or development of safe and effective treatments for neurological diseases.
Tuesday, Nov. 3 9:30 am – 10:00 am
Symposium
Tuesday, Nov. 3 10:30 am – 11:00 am
Symposium
The presentation will introduce key concepts for antibody transport across the blood-brain barrier (BBB), including receptor-mediated transcytosis (RMT). BBB receptors engaged in RMT, their targeting antibodies, as well as mechanisms of their trans-cellular trafficking will be reviewed. The talk will then focus on examples of brain-targeting bi-specific antibodies, methods for quantifying their exposure in different brain compartments, and determining their pharmacokinetics-pharmacodynamics relationship. Finally, translation of findings from rodents to primates will be discussed.
Tuesday, Nov. 3 11:00 am – 11:30 am
Symposium: Intranasal Delivery
This presentation will cover an overview of relevant anatomical and physiological factors governing intranasal delivery from the nasal passages to the CNS. In addition, evidence of extracellular pathways associated with the olfactory and trigeminal nerves in delivery of drugs to the CNS after intranasal administration will be discussed. I will also show the potential involvement of cerebral perivascular spaces in widespread brain distribution after intranasal administration.
Tuesday, Nov. 3 11:30 am – 12:00 pm
Symposium: Transporter-Mediated Delivery of Small Molecules Across The Blood-Brain Barrier
Endogenous transporters expressed at the blood-brain barrier (BBB) provide an excellent opportunity to advance stroke therapy via optimization of small molecule drug delivery to the brain. In this presentation, we review current knowledge on targeting of organic anion transporting polypeptides (OATPs in humans; Oatps in rodents) for improvement of ischemic stroke treatment and provide state-of-the-art perspective on the rationale for considering BBB transport properties during discovery/development of novel stroke therapeutics.
Tuesday, Nov. 3 12:00 pm – 12:30 pm
Keynote: The Permeability of The Blood-Brain Barrier to Peptides, Regulatory Proteins, and Antisense: Physiological Foundations and Pharmacological Implications
William A. Banks, University of Washington
Tuesday, Nov. 3 2:00 pm – 3:00 pm
INNOVATIONS IN PHARMACEUTICAL BIOENGINEERING
Prologue: Novel Drug Delivery Techniques for Biologics
Wednesday, Nov. 4 9:30 am – 10:00 am
Symposium
This presentation will discuss our ongoing efforts in developing physiological signal-triggered bioinspired drug delivery systems. I will first present the glucose-responsive synthetic systems for biomimetic delivery of insulin for diabetes treatment. Development of smart insulin patches will be emphasized. I will further discuss the local and targeted delivery of immunomodulatory therapeutics for enhanced cancer therapy. Our latest studies using platelets, cell conjugates, and sprayed gels for delivery of immune checkpoint inhibitors will be specifically introduced.
Wednesday, Nov. 4 10:30 am – 11:00 am
Symposium
Wednesday, Nov. 4 11:00 am – 11:30 pm
Symposium: Extracellular Vesicles and Exosomes As The Emerging Nano-Delivery Platform
This presentation will focus on the cutting-edge exosome-based nano-delivery platform, including sourcing the natural exosomes for delivery, engineering the exosomes for targeted therapy, and clinical utility.
Wednesday, Nov. 4 11:30 am – 12:00 pm
Symposium: RNAi Therapy Delivery Systems
This presentation will delve into advances in RNAi therapy, review of delivery systems for RNAi drugs, discussions on new developments in EV-based delivery systems, and examples of clinical development of RNAi drugs.
Wednesday, Nov. 4 12:00 pm – 12:30 pm
Keynote: Development of Microneedle Technology for Simplified Vaccination, Long-Acting Contraception and Wearable Diagnostics
To improve vaccination, we formulated microneedles measuring hundreds of microns in length with water-soluble excipients and vaccines. We will report findings from preclinical and clinical studies of microneedle patch vaccination. We have also designed microneedles made of biodegradable polymer that encapsulates contraceptive hormone. Finally, microneedles can be used to create transdermal micropores through which interstitial fluid can be collected as a novel source of skin and systemic biomarkers using a cell-free fluid that does not clot.
Mark R. Prausnitz, Ph.D., Georgia Institute of Technology
Wednesday, Nov. 4 2:00 pm – 3:00 pm
Rapid Fires
Wednesday, Nov. 4 3:30 pm – 4:30 pm
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BIOMOLECULAR
PRECLINICAL DEVELOPMENT OF NOVEL THERAPEUTIC MODALITIES AND APPROACHES
Rapid Fires
Tuesday, Oct. 27 3:30 pm – 4:30 pm
Rapid Fires
Wednesday, Oct. 28 9:00 am – 10:00 am
Prologue: Introduction to Cell and Gene Therapies
This symposium will cover translational pharmacokinetics and pharmacodynamics (PK/PD) approaches and strategies in early stage development of cell and gene therapies. Topics will include an overview of cell and gene therapies, highlights of preclinical and translational PK/PD challenges, and knowledge gaps in advancing these therapies to the clinic. Regulatory and industry perspectives will be provided. Preclinical and translational PK/PD strategies for implementation in cell and gene therapies will be presented through case studies.
Wednesday, Oct. 28 9:30 am – 10:00 am
Symposium: Regulatory Considerations and Expectations for Translational Pkpd Aspects of Cell and Gene Therapies
Wednesday, Oct. 28 10:30 am – 11:00 am
Symposium: Selecting FIH Starting Dose for Adoptive T Cell Therapies and PK/PD Considerations
This presentation will detail pharmacokinetic and pharmacodynamic (PK/PD) approaches to establish the first-in-human starting dose and efficacious or threshold dose projections for chimeric antigen receptor (CAR)-T cell therapies. It is also imperative to execute quantitative assessments from dose-escalation studies for CAR-Ts already in the clinic including PK/PD correlations. Multiscale semi-mechanistic PK/PD modeling approaches that account for the engagement of CAR-T with tumor to drive response can be used for human starting and efficacious dose projections.
Wednesday, Oct. 28 11:00 am – 11:30 am
Symposium: Preclinical PKPD and Biodistribution of Luxturna and Translation to Clinic
Wednesday, Oct. 28 11:30 am – 12:00 pm
Symposium: Considerations in Design and Development of RNA Therapy Products: A Translational PKPD Perspective
Gene therapies are a promising and rapidly evolving approach for treatment of rare diseases. This session will focus on the emerging field of gene therapy development with a focus on preclinical to clinical translation of adeno-associated virus-mediated liver-directed gene therapy. An understanding of preclinical evaluations that support clinical development of gene therapies will be discussed. The session will also highlight opportunities and challenges in translating gene therapy products.
Wednesday, Oct. 28 12:00 pm – 12:30 pm
Keynote: Translational Sciences in Car T-Cell Therapies: Staying The Course for Success
Joseph Melenhorst,
University of Pennsylvania
Wednesday, Oct. 28 2:00 pm – 3:00 pm
INNOVATION AND ACCELERATION OF PRECLINICAL DEVELOPMENT
Prologue: Introduction to Local Delivery of Biopharmaceuticals
This presentation will introduce local delivery strategies applied for the development of biopharmaceuticals. An overview of physiological and pharmacological aspects that drive the design and selection of biopharmaceuticals for local administration will be presented. Additionally, formulation and device considerations that are important for efficient delivery of biopharmaceuticals will be discussed. Pharmacokinetic and pharmacodynamic approaches that can incorporate these different aspects to support design, development, and dosing of biopharmaceuticals through local delivery will be discussed.
Monday, Nov. 2 9:30 am – 10:00 am
Symposium: Important Development Considerations in The Delivery of Nucleic Acids and Proteins to The Respiratory Tract
Monday, Nov. 2 10:30 am – 11:00 am
Symposium: Recent Progress in Oral Delivery of Biopharmaceuticals
Oral delivery of biologics is highly desirable given the expansion of biologics. However, development of oral biologics is a notoriously challenging task given the physiological barriers of the gastrointestinal tract, which severely limit oral bioavailability. The field has made considerable progress thanks to innovative materials, leading to novel delivery technologies.
Monday, Nov. 2 11:00 am – 11:30 am
Symposium: Smart Devices for Oral Delivery of Biologic
Monday, Nov. 2 11:30 am – 12:00 pm
Symposium: Delivery of Biologics to The Brain
With recent success of biologic modalities in neuroscience (antibodies, RNA therapeutics, and gene therapy), there is a need to further optimize brain delivery of biologics. This talk will outline local brain delivery approaches and discuss recent findings on cerebrospinal fluid delivery of biologics.
Monday, Nov. 2 12:00 pm – 12:30 pm
Keynote: Quantitative Systems Pharmacology to Guide Translational Research of Novel Biological Modalities
Clinical development of novel biotherapeutic modalities is challenging, including selecting relevant starting and efficacious doses. Multiple factors contribute to variability in the clinic, including differences in functional affinity due to avidity, receptor expression, effector to target cell ratio, and presence of soluble target. Mechanistic modeling approaches are a powerful integrative tool to understand the complexities and aid in clinical translation, trial design, and prediction of regimens and strategies to reduce dose limiting toxicities of innovative biologicals.
Piet H. van der Graaf, Ph.D., Pharm.D., Certara
Monday, Nov. 2 2:00 pm – 3:00 pm
Rapid Fires
Monday, Nov. 2 3:30 pm – 4:30 pm
ADVANCES IN PRECLINICAL DEVELOPMENT OF IMMUNO-THERAPEUTICS
Prologue: Translational and Functional Considerations for Bi-Specifics
Wednesday, Nov. 4 9:30 am – 10:00 am
Symposium: Model-Based Approach to Design Bi-Specific Modalities in Early Discovery
This case study will show a tiered model-based approach to determine feasibility of a bi-specific antibody to appropriately cover multiple antigen pairs. Once feasibility was assessed, further modeling determined ideal affinity ranges for each target in bi-specific format at the site of action. Sensitivity analysis was performed to understand each parameter and its impact on predicted target coverage. This approach provided guidance for informed antibody design, prioritization of experiments, and triaging of challenging antigen pairs.
Wednesday, Nov. 4 10:30 am – 11:00 am
Symposium: Next-Generation of T-Cell Redirecting Antibodies
Harnessing the immune system has revolutionized how cancer is treated. Revitope is developing two-component systems composed of conditionally activated T-cell engaging antibody circuits that initiate and focus cytotoxic immunity accurately on the tumor. This discussion will cover protein engineering considerations and in vitro as well as in vivo activity. How quantitative systems pharmacology modeling approaches aid mechanistic understanding will also be discussed.
Wednesday, Nov. 4 11:00 am – 11:30 am
Symposium: Mathematical Model to Elucidate The Bio-Distribution of T-Cell-Dependent Bispecific Molecules
This presentation will outline a mathematical model that describes the bio-distribution of T-cell dependent bispecific molecules (TDBs) in preclinical solid tumor xenograft mouse models. Overall, the TDB bio-distribution platform serves as a robust tool for candidate molecule selection and design of optimal in vivo pharmacology experiments in mouse efficacy models to support translational efforts.
Wednesday, Nov. 4 11:30 am – 12:00 pm
Symposium: What Next After Your FIH Dose for T-Cell Bispecifics
Wednesday, Nov. 4 12:00 pm – 12:30 pm
Keynote: Preclinical Validation of T-Cell Bispecific Antibodies
T-cell bispecific antibodies have demonstrated striking efficacy in hematologic cancers, including non-Hodgkins lymphoma and multiple myeloma. While the concept is simple, the design and validation of these potent T cell redirecting molecules require careful attention to ensure both their safety and efficacy. Understanding the detailed mechanisms by which T-cell bispecifics lead to anti-tumor activity will be required to build upon the successes seen in hematologic cancers.
Stephen Gould Ph.D., Genentech, Inc.
Wednesday, Nov. 4 2:00 pm – 3:00 pm
Rapid Fires
Wednesday, Nov. 4 3:30 pm – 4:30 pm
Prologue: Advancements in Antibody Engineering and Applications
Bispecific antibodies (bsAb) are a large family of molecules designed to recognize two different epitopes or antigens. Landmark advances in the engineering and development of bsAbs are enabling unprecedented versatility in therapeutic antibody concepts. More than 20 different commercialized technology platforms are available for bsAb creation and development, two bsAbs are marketed, and more than 85 are in clinical development. bsAbs have the potential for novel functionalities; that is, activities that do not exist in mixtures of the parental or reference antibodies. This presentation will discuss the design, function, and potential of these so-called obligate bsAbs.
Monday, Nov. 4 8:30 am – 9: 00 am
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CHEMICAL
PRECLINICAL DEVELOPMENT OF NOVEL THERAPEUTIC MODALITIES AND APPROACHES
Prologue: Introduction to Novel Roles of Emerging Transporters
Transporter biology is a rapidly changing field in pharmaceutical research. Many drugs, nutrients and metabolites undergo facilitated or active transport not only through the plasma membrane but also among subcellular organelles including the endoplasmic reticulum, lysosomes and mitochondria. Thus, transport proteins remain one of the most underestimated fields for drug targets. This symposium will address specific examples of transporters as novel therapeutic targets for the treatment of disease.
Tuesday, Oct. 27 9:30 am – 10:00 am
Symposium: OCT1 As An Emerging Transporter
Tuesday, Oct. 27 10:30 am – 11:00 am
Symposium: Novel Roles of Multidrug-Resistance Proteins in Cancer
We have focused on identifying and developing modulators of MRP1 that selectively deplete glutathione from cells with high MRP1 expression as well as investigating how these modulators interact with MRP1 and how they might be best combined with existing drugs to treat cancer. This presentation will cover the rationale for these approaches, the challenges of safely and effectively targeting MRP1 and our progress to date toward realizing the potential of MRP1 modulators.
Tuesday, Oct. 27 11:00 am – 11:30 am
Symposium: Regulation of The Peptide/Histidine Transporter in Macrophages
There is increasing evidence that proton-coupled oligopeptide transporters (POTs) can transport bacteria-derived chemotactic peptides and, therefore, reside at the critical interface of innate immune responses and regulation. This symposium discusses the (sub)cellular expression and functional activity of POTs in macrophages derived from mouse bone marrow and evaluates the effect of specific POT deletion on the production of inflammatory cytokines in wildtype, Pept2 knockout and Pht1 knockout mice.
Tuesday, Oct. 27 11:30 am – 12:00 pm
Symposium: SLC13A5/Sodium-Coupled Citrate Transporter In Metabolic Diseases
The human transporter NaCT (gene symbol SLC13A5) mediates the sodium-coupled uptake of citrate and intermediates of the tricarboxylic acid cycle into hepatocytes and is important for human brain development, brain function and energy metabolism. This presentation summarizes the current knowledge on the role of this transporter for human metabolism.
Tuesday, Oct. 27 12:00 pm – 12:30 pm
Keynote: The Continued Evolution of ‘Synthetics’ as Therapeutics
Percy Carter MBA., Ph.D., Janssen Research and Development, LLC
Tuesday, Oct. 27 2:00 pm – 3:00 pm
Rapid Fires
Tuesday, Oct. 27 3:30 pm – 4:00 pm
INNOVATION AND ACCELERATION OF PRECLINICAL DEVELOPMENT
Prologue: Challenging Species Dependent PK/ADMET and Implications of Emerging Tools for Preclinical Development
When species dependent PK/ADMET is observed, it poses significant challenge in predicting human PK with higher certainty. It becomes essential to mechanistically understand factors responsible for the PK/ADMET disconnect between preclinical species. This analysis helps to devise strategies to explore in-silico, in-vitro or in-vivo tools and/or models that take these differences into account for translation to human. Some of these tools will be briefly introduced in prologue followed by detailed discussions by speakers.
Thursday, Oct. 29 9:30 am – 10:00 am
Symposium: Ridging The Gap Between in Vitro, Animal, and Human via Modeling and Simulation
Thursday, Oct. 29 10:30 am – 11:00 am
Symposium: Human-On-A-Chip Systems for Use in Therapeutic Index Determination and Systemic Toxicity in Pre-Clinical Drug Discovery Application
This presentation discusses the results of six workshops held at NIH to explore what is needed for validation and qualification of new systems for selecting drug candidates for human clinical trials. Upon completion, participants will understand how the construction and function of human-on-a-chip systems, and their application to opioid research. In addition, participants gain understanding of overdose models in a multi-organ system and evaluate the effects of overdose treatments.
Thursday, Oct. 29 11:00 am – 11:30 am
Symposium: New Kids On The Block: Genetically Altered Animal Models and Their Utility in Investigating Drug Distribution, Clearance and Induction
Preclinical species are not useful in estimating human PK parameters, in part, because there can be striking species differences in the expression and activity of drug metabolizing enzymes and drug transporters, as well as their regulatory pathways. To address this, genetically modified animal models have been developed with the hope of bridging the gap between the preclinical models to the clinic. This presentation will showcase several genetically modified animal models and demonstrate how they have been used to elucidate the mechanism of ADME-related phenomenon, as well as their potential utility in complementing current drug research.
Thursday, Oct. 29 11:30 am – 12:00 pm
Symposium: Human Liver Chimeric Mice for Drug Metabolism
Thursday, Oct. 29 12:00 pm – 12:30 pm
Keynote: The Next Frontier in Adme Science: Predicting and Verifying Tissue Drug Concentrations
Understand the challenges in predicting systemic and tissue drug exposure in humans based on preclinical data with special emphasis on transporters. Attendees will learn about how predictions of systemic and tissue drug exposure can be verified through non-invasive imaging (e.g., PET). Once this approach has been verified with additional probe substrates, it can be used to routinely predict tissue concentration of drugs under development. It is supported by UWRAPT funded by Genentech, Merck, Biogen, Gilead, BMS, Pfizer and Takeda.
Jashvant Unadkat Ph.D., University of Washington
Thursday, Oct. 29 2:00 pm – 3:00 pm
Rapid Fires
Thursday, Oct. 29 3:30 pm – 4:30 pm
ADVANCES IN PRECLINICAL DEVEOPMENT OF IMMUNO-THERAPEUTICS
Rapid Fires
Tuesday, Nov. 3 9:00 am – 10:00 am
Prologue: PK/PD, Dosing Regimen and Therapeutic Index Considerations in Design and Development of TCIS and Protein Degraders
Understanding aspects of target biology through PK/PD-based approaches is critical to inform the design of drug candidates on the intrinsic inactivation or degradation potency, pharmacokinetic half-life, et al. In addition, PK/PD understanding of target biology may aid dosage regimen selections in mitigating potential target toxicities associated with these compounds. In this presentation, theoretical considerations and practical examples will be provided to highlight the importance of PK/PD in guiding drug designs and dosage regimen selections for these novel classes of molecules.
Tuesday, Nov. 3 9:30 am – 10:00 am
Symposium: Covalent Drug Discovery
Covalent and irreversible inhibition has now become a critical small molecule drug modality used to discover clinical candidates and therapies for a wide range of diseases, including for some previously undruggable targets. As a result, this modality will grow. In this talk, both data and theory are used to illustrate how a kinact/KI can be used to interpret SAR, better define selectivity, and translate target engagement across all types of preclinical assays.
Tuesday, Nov. 3 10:30 am – 11:00 am
Symposium: Clinical Pharmacology Considerdations for Targeted Covalent Inhibitors
This presentation will provide an overview of clinical pharmacology of selected approved covalent binders and use carfilzomib, a covalent inhibitor of proteasome, as an example to illustrate the use of pharmacokinetic/pharmacodynamic data to select an optimal dosing regimen. Upon completion, participants will have a general overview of clinical pharmacology of approved covalent binders and gain a broad understanding of key pharmacokinetic/pharmacodynamic factors that drive selection of optimal clinical dosing regimens (dose and dosing interval).
Tuesday, Nov. 3 11:00 am – 11:30 am
Symposium: Discovery and Development of Selective Estrogen Receptor Degraders (SERD)
When guided by assays and cocrystal structures, chemists are fully capable of multi-parameter optimization that led to identification of a best-in-class SERD, with full antagonist profile across ER+ cell lines, excellent ADME profiles, and high safety margin preclinically. With GDC-9545, there is an ability to discover novel biology, not through ER degradation, but by decreasing mobility of ER in nucleus. Participants gain understanding about how small molecules can induce target degradation, without linker or attached E3 ligase ligand.
Tuesday, Nov. 3 11:30 am – 12:00 pm
Symposium: Mechanistic Modeling Framework for Bispecific Protein Degraders
Bispecific protein degraders are an emerging therapeutic modality that can engage the ubiquitin-proteasome pathway to catalytically degrade intracellular proteins through the formation of ternary complexes with the target proteins and E3 ubiquitin ligases. This “event-driven” pharmacology challenges traditional drug development paradigms and requires a novel approach. This presentation provides an overview of this model framework along with examples to illustrate how it can be used to understand the impact of system- and drug-specific parameters on the dynamics of induced protein degradation both in vitro and in vivo.
Tuesday, Nov. 3 12:00 pm – 12:30 pm
Keynote: Use of Small Molecules to Make Giant Leaps in Immuno-Oncology
Bayard Huck, EMD Serono
Tuesday, Nov. 3 2:00 pm – 3:00 pm
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BIOMOLECULAR
TO BOLDLY GO WHERE NO ASSAY HAS GONE BEFORE!
Rapid Fires
Tuesday, Oct. 27 3:30 pm – 4:30 pm
Wednesday, Oct. 28 9:00 am – 10:00 am
Prologue: Bold Advances in Biomolecular Bioanalysis
Wednesday, Oct. 28 9:30am - 10:00 am
Symposium: Strategies for Regulated Cell and Gene-Therapy Based Enzyme Activity Assays
We present an overview of our experiences with regulated enzyme activity assay bioanalysis, recommendations for enzyme assay characterization, and life cycle management. Enzyme activity assays generally use a non-detectable molecule that is specifically cleaved by the enzyme of interest into a detectable subunit of the parent molecule. Participants will be able to understand the unique challenges associated with CGT-based enzyme bioanalysis, have statistical models for how to monitor enzyme assays over time under variable operational conditions, and have robust discussions on best practices.
Wednesday, Oct. 28 10:30 am – 11:00 am
Symposium: Biodistribution and Shedding of Viral Gene Therapies
Wednesday, Oct. 28 11:00 am – 11:30 am
Symposium: Anti-Aav6 Antibody Assay for Detecting Gene Therapy Treatment-Induced Antibody Response
This session discusses anti-AAV6 total antibody assay to monitor patients’ antibody responses post-treatment in clinical studies. As commercial human anti-AAV6 antibodies are currently not available, we generated the positive control antibody by purifying IgG from human sera with pre-existing antibodies to AAV6. Understand how to develop and optimize an immunogenicity assay, including preparation of the negative control serum, selection of the detection antibody, and generation of the positive control antibody.
Wednesday, Oct. 28 11:30 am – 12:00 pm
Symposium: Nab Assays for Oncolytic Virus
Wednesday, Oct. 28 12:00 pm – 12:30 pm
Keynote: Taking Vaccine Bioanalytical Assays Into a New Frontier, Boldly Going Where No One Has Gone Before
If you are looking for current challenges in the field of bioanalytical assays look no further. This session will provide opportunities for scientists, managers, clinicians, regulatory scientists to learn about the bio analytical area of clinical vaccine development. The presentation will cover the differences in assay development for vaccines and biologics, detailed aspects of vaccine assays/methodologies, and case studies and describe unique opportunities and challenges for vaccine development.
Roy Helmy, Ph.D., Merck & Co., Inc.
Wednesday, Oct. 28 2:00 pm – 3:00 pm
WILL THE CONTEXT OF USE FOR EACH ASSAY PLEASE STAND UP?
Prologue: Applying Context of Use in Biomolecular Assays
Monday, Nov. 2 9:30 am – 10:00 am
Symposium: Do You Know What You Are Measuring? Developing Biomarkers That Have Clinical Impact
The bioanalytical community has developed a solid understanding of developing and validating accurate, robust, and enduring PK and ADA assays to characterize protein therapeutics in clinical studies. Specific case studies that illustrate strategies for developing biomarkers that transition from research studies into clinical development and the corresponding challenges will be presented. Determine key considerations for COU-driven assay characterization and validation and evaluate existing assays for their suitability for proposed COUs.
Monday, Nov. 2 10:30 am – 11:00 am
Symposium: Bioanalytical Challenges in Oncology Patients with Prior Exposure to Biotherapeutics
Learn about assessing potential risk of rising ADA from prior exposure of similar biologics in same (re-treated) oncology populations and special considerations when assessing ADA assay cut-points in IO patients with prior exposure to biologics and evolving biotherapeutics landscape in oncology space. Discuss bioanalytical challenges associated with the use of same-class of biotherapeutics in IO space Adapting a “fit for purpose” bioanalytical strategy for selecting the most apt assay format and immunogenicity assessment in IO clinical trials.
Monday, Nov. 2 11:00 am – 11:30 am
Symposium: An Enzymatic Neutralizing Antibody Assay for Gene Therapy Clinical Enrollment
This presentation will address these unique challenges pertinent to the development of an enzymatic NAb assay against a transgene-encoded protein expressed from a liver-tropic rAAV, to potentially inform clinical enrollment. Learn the importance of transgene immunogenicity assays for determining potential efficacy of gene therapy explain key concepts and strategies on how to develop a clinically relevant enzymatic neutralizing antibody assay. Elaboration on the use of immunogenicity assays to screen patients for enrollment; as opposed to the typical utility of determining antibody incidence post treatment.
Monday, Nov. 2 11:30 am – 12:00 pm
Symposium: Development of Technology for Expanded Newborn Screening of Inborn Errors of Metabolism: Lysosomal Enzymes, Biomarkers and Beyond
Monday, Nov. 2 12:00 pm – 12:30 pm
Keynote: Biomarkers of Muscle and Nerve Health: in and Out of The Box
Attendees will receive a basic introduction to biomarkers for assessing the health of nerve and muscles in order to monitor progression of a variety of disorders and to assess the effect of therapy. R relative advantages and disadvantages will be reviewed. Attendees will have a deeper understanding of the challenges and advantages of various biomarkers for monitoring therapeutic intervention in a wide range of neuromuscular disorders, including amyotrophic lateral sclerosis, muscular dystrophies, peripheral neuropathies, and spinal muscular atrophy.
Seward B. Rutkove M.D., Harvard Medical School
Monday, Nov. 2 2:00 pm—3:00 pm
Rapid Fires
Monday, Nov. 2 3:30 pm – 4:30 pm
ARE YOU READY FOR THE LABORATORY OF THE FUTURE?
Prologue: A Look Into The Future of The Biomolecular Laboratory
This presentation provides an introduction to an exciting topic of Biomolecular Bioanalytical Laboratory of The Future. Together we will review challenges and opportunities facing bioanalytical scientists today and in the upcoming years. Discussion questions related to complexities of immunogenicity assays will include potential solutions for the lack of ability to compare study data between biotherapeutic compounds and growing need in a more detailed alignment of analytical methods.
Thursday, Oct. 29 9:30 am – 10:00 am
Symposium: Comparability of Immunogenicity Assays. Wishful Thinking Or Achievable Goal?
Immunogenicity testing constitutes a critical step in the development of therapeutic proteins. It is very important for internal and regulatory decision making and in the selection of optimal treatment options in clinical practice. We will use the “cut-point anti-drug antibody reagents complex” (CP-ARC) amount, as a clearly defined assay parameter that enables a technical assay comparison and reflect on how the current way of ADA assay development limits our understanding of the true performance of ADA assays.
Wednesday, Nov. 4 10:30 am – 11:00 am
Symposium: Universal Sample Pretreatment Method: Dream to Reality?
Assays that measure the immunogenicity of therapeutics are a critical component of bioanalysis. We propose the idea of a universal sample pretreatment method that would be employed across multiple assay formats, including both ELISA and cell-based assays. Participants will understand the importance of sample pretreatment in immunogenicity assays, describe common methods of sample pretreatment, and have a clear idea of the challenges involved in developing a universal sample pretreatment method, as well as the considerable benefits for such a bioanalytical strategy.
Wednesday, Nov. 4 11:00 am – 11:30 am
Symposium: Bioanalysis of Biosimilars—Leveraging The Past to Shape The Future
The past decade has witnessed discussion, debate, and ultimately an evolution in best practice around the bioanalysis of biosimilars and best practices have slowly emerged. Attendees will be able to better articulate the relationship and importance between a sound bioanalytical strategy and its role in achieving success of a biosimilar development program, understanding of the current hurdles limiting efficiency in development and introduction of biosimilars to the marketplace.
Wednesday, Nov. 4 11:30 am – 12:00 pm
Symposium: Biomolecular Assay Automation: The Past, The Present, and The Future
Wednesday, Nov. 4 12:00 pm – 12:30 pm
Keynote: Crypto for Healthcare: Transparent End-to-End Data Integrity with Blockchain
The emergence of COVID-19 has demonstrated the need for immediate, transparent access to data to guide policy and clinical care. The use of emerging cryptographic technologies, such as blockchain, can offer efficient methods to assess the source of data assets. We will discuss the benefits and limitations of blockchain technology and review a proof-of-concept application that leverages a public/private blockchain to validate data lineage and highlight its potential applications for pharmaceutical sciences.
Wade L. Schulz M.D., Ph.D., Yale School of Medicine
Wednesday, Nov. 4 2:00 pm – 3:00 pm
Rapid Fires
Wednesday, Nov. 4 3:30 pm – 4:30 pm
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CHEMICAL
TO BOLDLY GO WHERE NO ASSAY HAS GONE BEFORE
Prologue: To Boldy Go Where No Assay Has Gone Before
Tuesday, Oct. 27 9:30 am – 10:00 am
Symposium: Cuts to the Bone: Bioanalytical Considerations for an Atypical Matrices
Bioanalysts are challenged with addressing the cutting edge of analysis. Sometimes this requires novel technologies, unique troubleshooting approaches, reanalysis of validation requirements and introductions to analysis of new tissues. Sometimes it involves all of these. This presentation discusses the need to develop a cleaning protocol for homogenization equipment between samples; the suitability of samples for analysis and potential impact to quantitation, as well as the establishment of the correct matrix for stability establishment.
Tuesday, Oct. 27 10:30 am – 11:00 am
Symposium: Cell Surface, Intracellular, Extracellular PD-1 Determination Using Cell Surface Labeling
A methodology was developed for the isolation of cell surface, intracellular and extracellular PD-1 with cell surface labeling technique using mouse T cell line 3A9 transfected with human PD-1. The presentation describes the methodology to isolate cell surface, extracellular, and intracellular proteins for hybrid LC-MS/MS analysis and considerations to further optimize the methodology to isolate and quantify cell surface, extracellular and intracellular proteins.
Tuesday, Oct. 27 11:00 am – 11:30 am
Symposium: Clinical Study Support—Bioanalytical Monitoring of Transient Drug-Target-Drug Complexes
Ligand binding assays (LBAs) are the gold-standard tool for the bioanalysis of therapeutic proteins owing to their high sensitivity, robustness and capability to meet the high-throughput demands of routine sample analyses. This presentation will cover an alternative calibration function for SEC based on the morphology of the protein complexes confirmed by atomic force microscopy. We will reflect on the limitations of current bioanalytical approaches to analyze large protein complexes but will be able to develop appropriate methods for accurate successful bioanalytical support of a clinical trial.
Tuesday, Oct. 27 11:30 am – 12:00 pm
Symposium: Immunocapture-LC-MS/MS Assays for Interleukin-8 Target Engagement Evaluation in Tissue Biopsies
Using IL-8 as an example, we will discuss strategies for the development of the sensitive hybrid LC-MS/MS assays for target engagement evaluation in tissue samples. Participants will have in-depth understanding of the strategy for target engagement evaluation in tissue biopsies using immunocapture LC-MS/MS assays. This presentation describes the methodology, including the challenges and issues, for immunocapture LC-MS/MS assay development for total drug, total and free target, and target-drug complex measurement in tissue samples.
Tuesday, Oct. 27 12:00 pm – 12:30 pm
Keynote: Samples That Convey Both Identity and Drug Use: Rapid and Non-Invasive Sampling From Single Fingerprints
This session explores the chemical information that can be left behind in a fingerprint and detected using mass spectrometry imaging and profiling techniques to improve the recovery of fingermarks at crime scenes and explore the possibility of using fingerprints as a drug testing matrix. This talk will describe our work on exploring the significance of detecting cocaine and heroin in a fingerprint. Attendees will understand the challenges and opportunities associated with fingerprint-based drug testing.
Melanie J. Bailey Ph.D., University of Surrey
Tuesday, Oct. 27 2:00 pm – 3:00 pm
Rapid Fires
Tuesday, Oct. 27 3:30 pm – 4:30 pm
ARE YOU READY FOR THE LABORATORY OF THE FUTURE?
Prologue: A Look into the Future of the LC/MS/MS Bioanalytical Laboratory
Thursday, Oct. 29 9:30 am – 10:00 am
Symposium: Update on Bioanalytical Method Validation for Hybrid Assays in Regulated Studies
This session summarizes the discussion topics and consensus reached between the industry and FDA colleagues. An abstract will be prepared after the workshop. Better understand the requirement for bioanalytical method validation for biotherapeutics by LC-MS/MS. Make an assessment of what additional experiments may be needed to support hybrid assays develop or update their SOPs on performing validations and the subsequent samples analysis for large molecules by LC-MS/MS.
Thursday, Oct. 29 10:30 am – 11:00 am
Symposium: An Industry Perspective of Evolving Strategies and Key Focus Areas in Metabolite Bioanalysis
The presentation(s) will include case examples of metabolite measurements in various biological matrices to support drug development and for regulatory submission (e.g., IND and NDA) including the level of validation needed for in vitro metabolism support. understand when metabolites should be measured in support of drug development describe what level of data quality is needed for metabolite measurement. Have a more clear picture of the definition of “validation” for in vitro metabolite testing.
Thursday, Oct. 29 11:00 am – 11:30 am
Symposium: Strategy to Replace Quantitation of Nucleoside Phosphates in Pbmcs by Indirect Quantitation in Human Dried Blood Using Volumetric Absorptive Microsampling
Islatravir (MK-8591), ISL is a nucleoside reverse transcriptase translocation inhibitor in phase 2 clinical trials and designed to treat and prevent HIV infection. Intracellular Islatravir-triphosphate (ISL-TP) is the active metabolite, and its concentration levels are measured in peripheral blood mononuclear cells (PBMCs) samples. In this session, we describe development strategy and assessments to measure free or total Islatravir (ISL-DP + ISL-TP) in VAMS blood and identify bioanalytical issues in the analysis of unstable compounds in dried blood.
Thursday, Oct. 29 11:30 am – 12:00 pm
Symposium: Bioanalytical Laboratory Automation: Where We Came From, Where We Are, and Where We Are Going?
Thursday, Oct. 29 12:00 pm – 12:30 pm
Keynote: Is Your Protein Biomarker Mass Spectrometry Lab Ready for The Next Horizon?
Significant efforts are spent in the biopharmaceutical industry to execute translational pharmacology strategies aiming to reduce costly compound attrition in phase 2 clinical trials. A key element is developing an understanding of the properties of human drug targets in discovery phases as well as to predict and measure how targets are engaged by biotherapeutics. Using case studies, this session illustrates how next horizon challenges can be tackled and discusses opportunities for protein biomarker mass spectrometry.
Hendrik Neubert Ph.D., Pfizer Inc.
Thursday, Oct. 29 2:00 pm – 3:00 pm
Rapid Fires
Thursday, Oct. 29 3:30 pm – 4:30 pm
WILL THE CONTEXT OF USE FOR EACH ASSAY PLEASE STAND UP?
Rapid Fires
Tuesday, Nov. 3 9:00 am – 10:00 am
Prologue: Applying Context of Use in Chemical and LC/MS/MS Assays
Tuesday, Nov. 3 9:30 am – 10:00 am
Symposium: What’s the Context of Use for Generic Biomarker Panels?
This discussion features a reactive oxygen species panel originally designed to monitor levels of glutathione, cysteine, N-acetyl cysteine and homocysteine as free and total concentrations utilizing LC/MS/MS. The session describes various contexts of use for which a single multiplex assay may be suitable and highlights differences between a validation to address a pharmacokinetic context of use compared to validation requirements for biomarker contexts of use.
Tuesday, Nov. 3 10:30 am – 11:00 am
Symposium: Journey of Biomarker from Discovery to Qualification (Renal Biomarker)
This session discusses the development of the renal biomarker from discovery to qualification process from the developer and regulator point of view. We will discuss essential components required for the biomarker development process and promote an understanding of criteria to go through the qualification process.
Tuesday, Nov. 3 11:00 am – 11:30 am
Symposium: Development/validation of an Endogenous Compound in Accordance with ICH-M10
Aminolevulinic acid (5-ALA) is an endogenous, non-proteinogenic amino acid. It is a key component of the porphyrin synthesis pathway. Attendees will gain an understanding of how to apply ICH M10 draft guidelines to validation of a bioanalytical method for measurement of endogenous compounds, straightforward benzoyl chloride derivatization-based extraction for measurement of 5-ALA, and how to apply a straightforward derivatization-based extraction to differentiate 5-ALA from structurally similar compounds that may be present in study samples.
Tuesday, Nov. 3 11:30 am – 12:00 pm
Symposium: Quantitative Analysis of Protein Biomarkers in the Tumor Microenvironment Using High Resolution LC/MS/MS
With the advent of cancer immunotherapy (CIT), the number of clinical targets and opportunities for oncology treatment has grown rapidly. The focus of the present talk will be on the role and advantages of non-imaging analysis of FFPE by high-resolution LC/MS/MS for multiplexed protein quantification in the TME. MS detection of specific metal ions occurs following sample ablation using a laser or other means. Insights from this comparative analysis will be provided along with discussion on the emerging role of MS for protein quantification in the TME.
Tuesday, Nov. 3 12:00 pm – 12:30 pm
Keynote: Evaluating the Safety and Efficacy of Cell and Gene Therapies in Development
Cell and gene therapies are emerging as important treatments for various diseases. Particularly, for rare diseases, these therapies may hold the only option for long term treatment or even cure. Efficient methods for manufacturing, conduct of clinical trials evaluating safety and efficacy in small populations, and ensuring availability are issues that all need to be addressed. This session describes potential development pathways for evaluating safety and efficacy of cell and gene therapies for bespoke therapies.
Peter W. Marks, M.D., Ph.D., U.S. Food and Drug AdministrationTuesday, Nov. 3 2:00 pm – 3:00 pm
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BIOMOLECULAR
MODEL INFORMED DRUG DEVELOPMENT: 2020 AND BEYOND
Prologue: The Role of MIDD in Drug Development for Clinical Bridging and Alternate Dosing
Tuesday, Oct. 27 9:30 am – 10:00 am
Symposium: PK/PD Relationships and Pharmacometric with Immunotherapy for Combinatorial Strategies
Combinatorial strategies are considered as the future of immunotherapy in oncology. A rising number of clinical trials have thus tried to combine immune checkpoint inhibitors with cytotoxics, targeted therapies or radiation therapy, as an attempt to turn once “cold” tumors into “hot” ones. Quite notably, most of these combinations have been tested on an empirical basis so far. Participants will understand the current challenges of combinatorial strategies with immune checkpoint inhibitors, and why dosing, scheduling and sequencing of the combined treatments could matter eventually.
Tuesday, Oct. 27 10:30 am – 11:00 am
Symposium: Pembrolizumab Q6-Week Dosing: Model-Informed Selection and Approval of an Extended Dosing Regimen in Immuno-Oncology
Tuesday, Oct. 27 11:00 am – 11:30 am
Symposium: IO Combinations
Combinatorial strategies are considered as the future of immunotherapy in oncology. A rising number of clinical trials have thus tried to combine immune checkpoint inhibitors with cytotoxics, targeted therapies or radiation therapy, as an attempt to turn once “cold” tumors into “hot” ones. Quite notably, most of these combinations have been tested on an empirical basis so far. Participants will understand the current challenges of combinatorial strategies with immune checkpoint inhibitors, and why dosing, scheduling and sequencing of the combined treatments could matter eventually.
Tuesday, Oct. 27 11:30 am – 12:00 pm
Symposium: Beyond Unstudied Doses Aided by MIDD
This presentation is intended to provide some examples of model informed drug development (MIDD) which reflects the nature of application of exposure-based, biological and statistical models to facilitate drug development and decision making. We expect to understand the application of MIDD in dose selection, individualization, and optimization, the usage of MIDD in new drug development and health care, and the regulatory programs of MIDD.
Tuesday, Oct. 27 12:00 pm – 12:30 pm
Rapid Fires
Tuesday, Oct. 27 3:30 pm – 4:30 pm
Wednesday, Nov. 4 3:30 pm - 4:30 pm
NOVEL THERAPEUTIC MODALITIES - CLINICAL PHARMACOLOGY CONSIDERATIONS
Prologue: Clinical Pharmacology of Novel Modalities
Oligonucleotides, modified mRNA therapeutics have great potential to treat diseases and are expanding to chronic disease areas. These molecules have unique pharmacokinetic and pharmacodynamic properties that raise challenges in dose selection and utility of population pharmacodynamic approaches rather than population pharmacokinetic approaches for therapeutic individualization. Attendees will learn about unique pharmacokinetic/pharmacodynamic characteristics of oligonucleotides and small interfering RNAs, regulatory challenges in development of novel modalities, and unique pharmacokinetic/pharmacodynamic characteristics of some gene therapy products.
Thursday, Oct. 29 9:30 am – 10:00 am
Symposium: PK/PD Modeling for Development of CAR-T Therapies
Thursday, Oct. 29 10:30 am – 11:00 am
Symposium: A Mechanistic PKPD Model to Guide siRNA Therapy Design
Efficacy in siRNA therapies depend on the mechanisms that drive the delivery of siRNA to target cell, the interactions of siRNA with RNA interference machinery, and the downstream effects of the reduction in target mRNA. This symposium discusses the key processes that contribute to the variability and uncertainty in target mRNA suppression and downstream target reduction during siRNA therapy, the impact of dosing regimen on efficacy, and target mRNA and protein in defining the therapy limitations.
Thursday, Oct. 29 11:00 am – 11:30 am
Symposium: The Clinical Pharmacology of siRNA Therapy: Is DDI a Concern - A Case Study of Givosiran
RNAi therapeutics rarely interact with drug metabolizing enzymes or drug transporters and therefore have low liability for drug-drug interactions. This presentation presents a case study of Givosiran, a RNAi therapeutic for treatment of Acute Hepatic Porphyria, where a pharmacological drug-drug interaction on the heme pathway was evaluated. Attendees will understand the DDI perspectives for novel therapeutics such as RNAi and explore new mechanisms for DDIs.
Thursday, Oct. 29 11:30 am – 12:00 pm
Symposium: Payload-mediated DDI Framework for Antibody-drug Conjugates: An IQ Consortium Perspective
Antibody-drug conjugates (ADCs) are an important class of biotherapeutics in oncology. An IQ ADC working group was formed to collect data and develop a risk-based payload-mediated DDI strategy. The objective of this presentation is to share the overall findings and provide a recommendation for a payload-mediated DDI strategy for ADCs. Learn the risk-based DDI strategy of clinical development of ADCs, how to assess payload-mediated DDI of ADCs, and the IQ pharma industry perspective on DDI framework for ADCs.
Thursday, Oct. 29 12:00 pm – 12:30 pm
Keynote: Clinical Pharmacology Challenges in Global Drug Development
The presentation will highlight the challenges in developing an appropriate clinical pharmacology development strategy in order to establish the right dose for the right patient. An overview of the clinical pharmacology studies required to meet regulatory requirements will be presented including the timing of studies and how the incorporation of quantitative methodologies can help to facilitate dose selection. Examples of how the information generated in a clinical pharmacology program could impact global product labeling will be presented in the context of global regulatory requirements.
Nolan D. Wood Ph.D., Certara
Thursday, Oct. 29 2:00 pm – 3:00 pm
Rapid Fires
Thursday, Oct. 29 3:30 pm – 4:30 pm
CLINICAL PHARMACOLOGY DRIVING INNOVATIVE TRIAL DESIGN
Prologue: Clinical Pharmacology Driving Innovative Trial Design
This session provides an overview for the audience on how big data, ranging from -omics to data generated from wearables and other outpatient sampling technologies to electronic medical records, is currently being used to transform drug discovery, development, and utilization. Learn about how high throughput technologies have led to the creation of large and diverse datasets for drug discovery, development, and utilization. Gain an understanding of the challenges and opportunities in translating big data to improve healthcare.
Tuesday, Nov. 3 9:30 am – 10:00 am
Symposium: Real World Evidence to Inform Precision Medicine
Precision Oncology is transforming Cancer Care. This talk will discuss recent challenges and opportunities in precision oncology drug development, with a focus on real world evidence.
Tuesday, Nov. 3 10:30 am – 11:00 am
Symposium: Real World Evidence for Drug Interactions
Using myopathy as a case example, the use of electronic health databases, such as the FDA Adverse Event Reporting System (FAERS), will be used to identify clinically significant drug-drug interactions. Using electronic health records, attendees will explore the risk of drug-drug interactions that produce myopathy and demonstrate how mechanistic pharmacokinetic modeling can support bioinformatic analyses of real-world drug interaction data. Attendees will gain the use of big data resources for drug-drug interaction prediction.
Tuesday, Nov. 3 11:00 am – 11:30 am
Symposium: Wearables and Outpatient Sampling in the Time of COVID-19
The session will discuss the use of wearable devices for clinical research during the COVID-19 pandemic. The use of wearables, also known as biometric monitoring technologies, has increased dramatically as medical appointments and clinical trial study visits moved to a remote mode. These devices present a feasible opportunity for remote data collection. Learn about considerations and decision models for transitioning from traditional in-person clinical measurements to a remote at-home data collection in the time of COVID-19 pandemic.
Tuesday, Nov. 3 11:30 am – 12:00 pm
Symposium: Regulatory Perspective on Integrating Big Data and RWE into the Drug Development and Regulatory Framework
This presentation will share case studies and discuss the regulatory considerations on the use of real world data (RWD) to facilitate drug development and precision medicine, with a focus on clinical pharmacology issues. Attendees will learn what RWD is and how it can be used to facilitate drug development and precision medicine.
Tuesday, Oct. 3 12:00 pm – 12:30 pm
Keynote: Will Clinical Pharmacology Follow the Dinosaurs?
Clinical pharmacology is changing. Twenty years ago companies were small molecule focused; today, small molecules represent a small proportion of many companies portfolios. These new modalities, like CAR-T and gene therapy, challenge the concept of what is clinical pharmacology and the roles and responsibilities of a clinical pharmacologist. This talk will discuss these changes, provide a glimpse into what the future might hold, and how a clinical pharmacologist can remain relevant to drug development.
Dr. Peter Bonate
Tuesday, Nov. 3 2:00 pm – 3:00 pm
Rapid Fires
Wednesday, Oct. 28 9:00 am – 10:00 am
Tuesday, Nov. 4 9:00 am - 10:00 am
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CHEMICAL
CLINICAL PHARMACOLOGY DRIVING INNOVATIVE TRIAL DESIGN
Rapid Fires
Tuesday, Oct. 27 3:30 pm – 4:30 pm
Symposium: Artifical Intelligence for Clinical Trial Design
Wednesday, Oct. 28 10:30 am - 11:00 am
Symposium: Computer-aided Drug Repositioning for COVID-19, An Iterative Exercise in Patience and Due Diligence
Reliable computer-aided drug repositioning (CADR) technologies require accurate data science and machine learning (ML) support. With integration of clinical and experimental data for SARS-CoV-2 drugs into a CADR workflow specifically tailored for COVID-19 (“CADR19”) in order to rapidly identify drugs that may be effective in the incubation and symptomatic phases of COVID-19. Attendees will learn about computational technologies and artificial intelligence for drug repositioning and discuss the merits of various anti-SARS-CoV-2 drugs in an effective manner.
Wednesday, Oct. 28 10:30 am – 11:00 am
Symposium: Adaptive Clinical Trials: Changing the Face of Medical Research
Wednesday, Oct. 28 11:00 am – 11:30 am
NOVEL APPROACHES INFORMING UNDERSTUDIED POPULATIONS
Prologue: Novel Approaches Informing Understudied Populations
With rapid advances in personalized healthcare and technology, the importance of representative populations in clinical trials and biomedical research is paramount. This presentation will focus on the scientific and clinical relevance of racial/ethnically representative patient populations in clinical research and strategies for addressing disparities in understudied populations and identify approaches to ensure all eligible patients have access to clinical research and the benefits of personalized healthcare.
Monday, Nov. 2 9:30 am – 10:00 am
Symposium: An FDA Perspective: Advancing Racial and Ethnic Minority Participation in Clinical Trials
This symposium provides an overview of the U.S. Food and Drug Administration’s (FDA) Office of Minority Health and Health Equity and discusses the FDA Policy strategies to support diverse participation in clinical trials. We will describe communication & outreach strategies to improve diverse participation in clinical trials.
Monday, Nov. 2 10:30 am – 11:00 pm
Symposium: Increasing Diversity in Clinical Research
Advancing Inclusive Research is a corporate initiative at Genentech and Roche focused on broadening inclusion of historically underrepresented groups in clinical research and ensuring personalized healthcare tools are designed for all patients. The healthcare industry can shine a spotlight on disparities and address barriers to clinical access, particularly for underrepresented racial and ethnic minorities. Genentech and Roche believe that data representative of real-world patient populations is required to improve clinical outcomes for patients.
Monday, Nov. 2 11:00 am – 11:30 am
Symposium: Pediatric Dosing Considerations Based on Two Case Studies
One of the key challenges in pediatric drug development is defining an optimal dose for pediatric patients. The objective of this presentation is to highlight the importance of using model-informed drug development to design efficient dosing strategies for pediatric patients, based on two case examples, a monoclonal antibody and a small molecule. Upon completion, participants will be able to appreciate the application of clinical pharmacology expertise in pediatric dose selection.
Monday, Nov. 2 11:30 pm – 12:00 pm
Symposium: Predicting Human Milk-plasma Concentration Ratios of Small-molecule Drugs and Antibodies
This presentation introduces the new IVIVE approach and compared its prediction performance with five literature in vitro prediction approaches. Attendees will gain understanding of the factors which affect drug or biologic transfer from a lactating woman’s blood to milk and potential risks to infants caused by therapeutic biologics in human milk. We will discuss challenges in human M/P ratio prediction, especially for transporter substrates and the IVIVE model for the prediction of M/P ratios for small-molecule drugs.
Monday, Nov. 2 12:00 pm – 12:30 pm
Keynote: From Ebola to COVID-19—The Global Impact of Clinical Pharmacology in the Development of Investigational Drugs during Infectious Disease Outbreaks
During an infectious disease outbreak, decisions about therapeutics must balance the urgent need for treatments with a thorough evaluation of safety and efficacy. Due to the immediate need for therapy, drugs used during infectious disease outbreaks are typically repurposed. We will describe clinical pharmacology considerations that are important when developing drugs to address an infectious disease outbreak, factors to consider, and a list lessons from previous infectious disease emergencies.
Kellie S. Reynolds, PharmD, Division of Infectious Disease Pharmacology, OTS, CDER, FDA
Monday, Nov. 2 2:00 pm – 3:00 pm
Rapid Fires
Monday, Nov. 2 3:30 pm – 4:30 pm
MODEL INFORMED DRUG DEVELOPMENT: 2020 AND BEYOND
Prologue: The Role of MIDD in Drug Development for COVID
Wednesday, Nov. 4 9:30 am – 10:00 am
Symposium: MIDD to Inform Drug Repurposing for Global Pandemics
This session features a discussion on viral dynamic models used to predict the antiviral efficacy of candidate treatments against SARS-CoV-2 and optimize their use. We will discuss how in vitro and data from non-human primates have also been used to elaborate more sophisticated models that integrate the immune response, pathogen, and treatments. We will address how to learn from this outbreak regarding how to improve the use and the dissemination of their models in a context of public health crisis.
Wednesday, Nov. 4 10:30 am – 11:00 am
Symposium: Precision Dosing for COVID-19, Combining M&S and Real-World Data to Optimize Dosing for All Patients
Potential treatments for COVID-19 are being investigated at an unprecedented speed. To ensure safe and effective use in patents, it is essential to develop optimal dosing information for all patient subgroups. Success will require immediate collaboration between drug developers, academics and regulators. Learn how M&S and real-world data can potentially be leveraged to accelerate understanding of dose individualization for safe use in emerging treatments for COVID-19.
Wednesday, Nov. 4 11:00 am – 11:30 am
Symposium: An Integrative Modeling Approach to Optimizing Hydroxychloroquine Dosing for Patients with COVID-19
Hydroxychloroquine (HCQ) was a promising candidate for the treatment of 2019’s coronavirus disease (COVID-19). Via timely analysis integrating historic and emerging pharmacological and toxicological data, the Laboratory of Dr. Rada Savic helped to understand safe and efficacious HCQ dosing strategies for COVID-19 treatment.
Wednesday, Nov. 4 11:30 am – 12:00 pm
Symposium: The Role of MIDD in Drug Development for COVID: Regulatory Perspective
COVID-19 has triggered a wave of model-based analyses to support various decisions related to potential treatments. This symposium will focus on the in vitro and in vivo correlation for hydroxychloroquine (HCQ) to evaluate if approved dosing regimens are sufficient to have any potential anti-viral effect. The role of this analysis in the FDA’s decision to revoke the Emergency Use Authorization for HCQ will also be discussed.
Wednesday, Nov. 4 12:00 pm – 12:30 pm
Keynote: The Next Decade in Clinical Pharmacology: Do We Reinvent Ourselves?
Dr. Vikram Sinha
Wednesday, Nov. 4 12:00 pm – 12:30 pm
Rapid Fires
Wednesday, Nov. 4 3:30 pm – 4:30 pm
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BIOMOLECULAR
NEXT GENERATION MANUFACTURING ENABLING SPEED TO PATIENT
Rapid Fires
Wednesday, Oct. 28 9:00 am – 10:00 am
Prologue: Next Generation Manufacturing Enabling Speed to Patient
Wednesday, Oct. 28 9:30 am – 10:00 am
Symposium: Evolution of Standards and The Pharmacopeia Advancing Drug Product Quality
This presentation will describe the evolving compendium used to address key new paradigms for ensuring pharmaceutical quality and the need for novel approaches to develop pharmacopeial standards. It will also review recent advances in the pharmacopeial science and strategy framework in conjunction with the current technological and regulatory trends. The presentation will also include examples of the new USP processes and strategies supporting novel excipients, over the counter drugs, biological standards, and general chapters.
Wednesday, Oct. 28 10:30 am – 11:00 am
Symposium: Efficient Biologics Production Platform with Advanced Control to Enhance Product Quality and Titer Consistency
This presentation will provide an overview of the challenges, barriers, and opportunities of process analytical technology (PAT) adoption in the pharmaceutical and biotechnological industries. It will also define the critical challenges in bioprocessing that are potentially solvable by deploying proper PAT tools.
Wednesday, Oct. 28 11:00 am – 11:30 am
Symposium: Developing a Fed-Batch Cell Culture Platform for Process Intensification
BMS has established a robust and scalable next-generation cell culture platform for high-productivity manufacturing of monoclonal antibodies (mAbs) by recombinant Chinese hamster ovary (CHO) cells. This presentation will focus on key strategies to develop the intensified fed-batch platform, including perfusion operation at N-1 seed culture step, optimization of basal and feed media, and other process parameters in the production bioreactor. The process has been successfully scaled up to both pilot and manufacturing scales for multiple assets.
Wednesday, Oct. 28 11:30 am – 12:00 pm
Symposium: Rapid Adventitious Agent Testing—Accelerating Clinical Timelines / Speed to Patient
Industry and regulators are evaluating the use of rapid adventitious virus detection methods, i.e., next generation sequencing (NGS), to replace or supplement current test methods. A targeted NGS viral safety assay can useful for in-process testing, to enable forward processing decisions, and to mitigate the business risk of a facility contamination. BMS participates in an early access study, evaluating a targeted NGS-based adventitious virus test specific for viral contaminants of Chinese hamster ovary cell cultures, developed by Thermo Fisher Scientific.
Wednesday, Oct. 28 12:00 pm – 12:30 pm
Keynote: Increasing Speed to Clinic—Whether for Covid-19 Or Not
This presentation will focus on increasing speed to clinic, including historical trends over the last 30 years in the time required to go from DNA sequence to phase 1 human clinical trials. Data for monoclonal antibodies will be presented, with some discussion on how the lessons learned apply to other products. The impact of new technologies, as well as changing regulatory requirements and industry learnings, will be covered.
Matt Croughan, Ph.D., Matthew S. Croughan Consulting Services
Wednesday, Oct. 28 2:00 pm – 3:00 pm
ADVANCES IN PROCESS CONTROL, MODELING, AND ANALYTICS
Prologue: Advances in Process Control, Modeling, and Analytics
Monday, Nov. 2 9:30 am – 10:00 am
Symposium: Glycosylation in a Cho Culture: Characterization, Optimization, and Control
We will present a multivariate analysis approach (MVDA) to combine metabolomics analysis with culture performance parameters as a means to predict critical quality attributes (CQAs) related to glycosylation. This approach provides us with a comprehensive understanding of how culture conditions impact the glycosylation CQAs which will be used as a diagnosis tool during scale-up and technology transfer of cell culture process.
Monday, Nov. 2 10:30 am – 11:00 am
Symposium: Real Time Monitoring of Cell Health, Apoptosis and Aggregation in Biopharmaceutical Development
This presentation will cover the development of advanced biomanufacturing technologies, including the challenges, opportunities, and potential solutions. Data-rich enabling process analytical technology method development and implementation for process control will be described.
Monday, Nov. 2 11:00 am – 11:30 am
Symposium: Systematic Assessment of Pat Applications to Biomanufacturing: Benchmarking and Current Status
This presentation will benchmarking and current status of systematic assessment of process analytical technology (PAT) applications to biomanufacturing.
Monday, Nov. 2 11:30 am – 12:00 pm
Symposium: Machine Learning & Statistical Analyses for Formulation Design, Manufacturing, and Quality Control
This presentation will cover machine and deep learning applications for pharmaceutical data analysis automation, big data mining, predictive sciences, as well as defect detection and quality control monitoring.
Monday, Nov. 2 12:00 pm – 12:30 pm
Keynote: Advances in Process Control, Modeling, and Analytics for Biomanufacturing
This keynote will discuss process control, mechanistic modeling, data analytics and machine learning, the implementation of PAT, and real-time release testing (RTRT). The effective application of advanced statistics and process modeling approaches, performance monitoring, and deployment of automated feedback/feedforward control will be discussed. The technologies, methodologies, and key points will be illustrated through applications to monoclonal antibody, viral vaccine, and gene therapy manufacturing in collaboration with university and industrial partners.
Richard D. Braatz, Ph.D., Massachusetts Institute of Technology
Monday, Nov. 2 2:00 pm – 3:00 pm
Rapid Fires
Monday, Nov. 2 3:30 pm – 4:30 pm
MANUFACTURING AND ANALYTICAL CHALLENGES OF EMERGING THERAPEUTIC MODALITIES AND NOVEL DELIVERY SYSTEMS
Rapid Fires
Tuesday, Nov. 3 9:30 am – 10:00 am
Prologue: Manufacturing and Analytical Challenges of Emerging Therapeutic Modalities and Novel Delivery Systems
Wednesday, Nov. 4 9:30 am – 10:00 am
Symposium: Manufacturing Cell and Gene Therapies—Cmc Considerations
This talk will cover the main components and chemistry, manufacturing, and controls considerations for development and manufacturing of current good manufacturing practices (cGMP)-compliant cell and gene therapy products, particularly as it relates to CD19/CD22 bi-specific CAR-T and other T cell based therapies. This presentation intends to provide an insight into the development of cGMP-compliant manufacturing processes for “bench to bedside” cell and gene therapies.
Wednesday, Nov. 4 10:30 am – 11:00 am
Symposium: Critical Quality Attributes: Establishing Biologically Relevant Thresholds/Controls During Process Development
The manufacturing and process development associated with novel biologics has led to new questions around quality attributes and strategy to establish adequate controls. This presentation uses a nanobody-based case study to demonstrate how to establish controls for an out-of-specification post-translational quality attribute.
Wednesday, Nov. 4 11:00 am – 11:30 am
Symposium: Statistical Solutions for Cell and Gene Therapy Data Challenges
The proposed symposium will focus on the main aspects of chemistry, manufacturing, and controls (CMC) such as characterization and analytical components and serve as a platform to develop and share knowledge in ways to surmount such challenges. The proposed symposium will cover delivery mechanisms, manufacturing technologies, analytical and quality control, and regulatory agencies.
Wednesday, Nov. 4 11:30 am – 12:00 pm
Symposium: Manufacturing Facility Design Considerations for ATMPs
Between new products, strategic partnerships, and acquisitions in the advanced therapy medicinal product (ATMP) market, companies are racing to find the capacity for plasmids, viral vectors, gene modified cell therapies, and fill finish products. Companies are considering building multi-product or multi-modal ATMP facilities, but a dedicated manufacturing facility can be costly and limits future. Why not have a facility that can produce multiple product types and allows for adaptability to an evolving product pipeline?
Wednesday, Nov. 4 12:00 pm – 12:30 pm
Keynote: Allogeneic Car-Ts: Promises, Challenges and Analytics in The Development of a Next Generation Platform
Mike Bowen, Allogene Therapeutics
Wednesday, Nov. 4 2:00 pm – 3:00 pm
Rapid Fires
Wednesday, Nov. 4 3:30 pm – 4:30 pm
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CHEMICAL
NEXT GENERATION MANUFACTURING ENABLING SPEED TO PATIENT
Prologue: Next Generation Manufacturing Enabling Speed to Patient
Tuesday, Oct. 27 9:30 am – 10:00 am
Symposium: Additive Manufacturing to Speed Drug Development
Tuesday, Oct. 27 10:30 am – 11:00 am
Symposium: Continuous Manufacturing to Enable Speed of Development and Commercialization
Tuesday, Oct. 27 11:00 am – 11:30 am
Symposium: Continuous Manufacturing and Other Approaches to Remove Tech Transfer / Upscaling
Tuesday, Oct. 27 11:30 am – 12:00 pm
Keynote: Flexible Manufacturing in a Rigid Regulatory Environment
This presentation will discuss several emerging pharmaceutical manufacturing technologies and approaches, explore what are actual versus perceived regulatory barriers to implementation of new pharmaceutical manufacturing technology, and help attendees understand how to approach regulators in U.S., Europe, and Japan for discussion on new technology.
Christine Moore, Ph.D., Merck & Co., Inc.
Tuesday, Oct. 27 2:00 pm – 3:00 pm
Rapid Fires
Tuesday, Oct. 27 3:30 pm – 4:30 pm
ADVANCES IN PROCESS CONTROL, MODELING, AND ANALYTICS
Prologue: Advances in Process Control, Modeling, and Analytics
Thursday, Oct. 29 9:30 am – 10:00 am
Symposium: Digital Lab—A Human Centric Design Approach to Enable Modeling and Predictive Analytics
This presentation session will cover talks focused on the topic of innovative control strategy approaches for application of continuous manufacturing to low dose (high potency) tablets, where conventional spectroscopic process analytical technologies have proven challenging to measure tablet content.
Thursday, Oct. 29 10:30 am – 11:00 am
Symposium: Implementation Considerations for PAT in Manufacturing and Novel PAT Beyond NIR
Thursday, Oct. 29 11:00 am – 11:30 am
Symposium: DoE with Process Automation: New Approach to Quality By Design
Despite the benefits of design of experiment (DoE), the execution of planned experiments is often a major challenge. Even with statistically optimized planned experiments, many still must be executed. We propose to perform such experiments with a high automation level. Processes can be better understood by applying a combination of automation and DoE. This presentation will describe the method for capsule filling and tablet compression, with examples and results from formulation development, process optimization, and continuous manufacturing line.
Thursday, Oct. 29 11:30 am – 12:00 pm
Symposium: Process Modeling for Robust Drug Product Manufacturing
Modeling is a powerful tool for manufacturing process development and routine control. Various models can be created for a single process, varying from local models for individual unit operations/steps, to the overall model that describes the entire process. These models will require different approaches to development, validation, and life-cycle maintenance. This presentation will address regulatory aspects of various process models in drug product manufacturing.
Thursday, Oct. 29 12:00 pm – 12:30 pm
Keynote: Towards A Digital Twin: Advances in Process Modeling and Integration of Pharmaceutical Manufacturing
Recent developments toward Industry 4.0 have led to a focus on cyber-physical systems, internet of things, and smart manufacturing that, combined with data generated for the manufacturing cycle, could lead to complete transformation of product manufacturing. This is the first step toward a Digital Twin, which is a virtual construct that mirrors physical system behavior completely. This talk will present our work toward developing process systems engineering approaches, supported by different applications from pharmaceutical manufacturing, focusing on continuous integration and production facilities.
Marianthi Ierapetritou, Ph.D., University of Delaware
Thursday, Oct. 29 2:00 pm – 3:00 pm
Rapid Fires
Thursday, Oct. 29 3:30 pm – 4:30 pm
MANUFACTURING AND ANALYTICAL CHALLENGES OF EMERGING THERAPEUTIC MODALITIES AND NOVE DELIVERY SYSTEMS
Prologue: Manufacturing and Analytical Challenges of Emerging Therapeutic Modalities and Novel Delivery Systems
Tuesday, Nov. 3 9:30 am – 10:00 am
Symposium: Designing Large Scale Oligonucleotide Manufacturing for Long Term Viability
Current oligonucleotide manufactures have long and complex supply chains covering amidite synthesis, oligo assembly, purification, isolation, and formulation. The current state of the art in oligonucleotide production has an associated cost and waste burden that is unsustainable in the future. This presentation will describe interactions between control strategy, cost, and sustainability across substance and product. Considering these interactions, the presentation will describe how long-term viability can be built into the design of manufacturing and supply.
Tuesday, Nov. 3 10:30 am – 11:00 am
Symposium: Meeting The Challenge: A Road Map to Progress From Milligrams to Tons in Oligonucleotide Manufacturing
Oligonucleotide synthesis generally follows the established and widely available solid phase phoshoramidite synthesis process, which is the basis for virtually all current oligonucleotides. However, this process has certain limitations that require companies to develop clever scale-up strategies for registration and market entry and innovative synthesis options. This presentation will describe a scale-up and manufacturing strategy to support a rapid launch, as well as on life-cycle management options to support predicted high volume market demands.
Tuesday, Nov. 3 11:00 am – 11:30 am
Symposium: Terminal Sterilization of Oligonucleotide Drug Products—Challenge, Considerations and Opportunities
Tuesday, Nov. 3 11:30 am – 12:00 pm
Symposium: Analytical Challenges for siRNA—Trials and Tribulations of Externalizing Method Development and Testing
Externalization of early phase work within the pharmaceutical industry is becoming more routine. Oligonucleotides and siRNA appear to be the exception. Oligonucleotides are uniquely excluded from many ICH guidelines, which complicates the regulatory pathway. This talk will focus on the challenges of externalizing the active pharmaceutical ingredient manufacture and release testing for this class of molecule while gaining alignment to bend the internal processes set up for the release and filing of a small molecule.
Tuesday, Nov. 3 12:00 pm – 12:30 pm
Keynote: New Modalities, Transitions in Routes of Administration and Needs in Drug Delivery & Analytics
This presentation will describe the reasons why pharma R&D productivity has decreased over the last ten years, from 10% to 1.9%, which is not sustainable. It will also cover innovative solutions that are being explored by pharma companies to address R&D productivity issues by offering transformative medicines with more significant patient outcomes. These include new modalities, drug delivery, and new routes of administration. Lastly, we will provide an overview of new modality druggability and developability spaces.
Manuel Sanchez-Felix, Ph.D., Novartis Institutes for BioMedical Research, Inc.
Tuesday, Nov. 3 2:00 pm – 3:00 pm
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BIOMOLECULAR
ADVANCES AND INNOVATION FOR FORMULATION DEVELOPMENT
Prologue: Advances in Formulation and Delivery for Vaccines
Tuesday, Oct. 27 9:30 am – 10:00 am
Symposium: Technology for Rapid Deployment of Vaccines During Global Pandemic Emergencies
This will be a case study showing how principles of immunology and formulation development enhanced the potency and physical stability of an Ebola vaccine. Using this example, I will provide insight through lessons learned to demonstrate how pharmaceutical scientists can rapidly adapt drug delivery platforms during pandemic situations to effectively formulate newly discovered vaccines for rapid disbursement to hot spots of infection.
Tuesday, Oct. 27 10:30 am – 11:00 am
Symposium: Formulation and Optimization of mRNA Vaccines
Tuesday, Oct. 27 11:00 am – 11:30 am
Symposium: Formulation Challenges of Protein-Based Vaccines
Tuesday, Oct. 27 11:30 am – 12:00 pm
Symposium: Cmc Regulatory Considerations for Accelerated Vaccine Development
Tuesday, Oct. 27 12:00 pm – 12:30 pm
Keynote: Formulation Development Challenges for New Vaccine Candidates Targeted for Use in Low- and Middle-Income Countries
David Volkin, University of Kansas
Tuesday, Oct. 27 2:00 pm – 3:00 pm
Rapid Fires
Tuesday, Oct. 27 3:30 pm – 4:30 pm
Drug Delivery and Device Development
Prologue: Can You Handle It? Post Production Handling and Administration of Biologics
Thursday, Oct. 29 9:30 am – 10:00 am
Symposium: Shocking Data On Parcel Shipments of Protein Solutions
This presentation will show data obtained from shipments of liquid protein formulations. This data will include information on the number and magnitude of shock events that can occur during transportation. Furthermore, the effect of these shock events on critical quality attributes like subvisible particle numbers of different liquid protein formulations will be discussed. An overview of the potential mechanisms that can cause stability problems after shock events and mitigation strategies will conclude the talk.
Thursday, Oct. 29 10:30 am – 11:00 am
Symposium: Role of Cstds in Post Production Handling of Biologics
This presentation will describe the reasons for the broader use of closed system drug transfer devices (CSTDs) with biologics. The differences in the design and materials of different devices will also be explained. Further, experimental data showing the effect of various features of CSTDs on protein drug quality attributes will be presented. An overview of potential sources of issues during the use of CSTDs for biologics and strategies for risk mitigation will conclude the talk.
Thursday, Oct. 29 11:00 am – 11:30 am
Symposium: Drug Delivery in Cell Therapy: Dealing with a Living Active Drug Substance
This presentation will give an overview of the different types of advanced therapy medicinal products (ATMPs) and the outstanding challenges related to the development and handling of these products. The advantages and disadvantages of storing ATMPs in the frozen state will be discussed. Furthermore, the talk will provide insights about optimal strategies for the handling of fresh or frozen ATMPs before administration.
Thursday, Oct. 29 11:30 am – 12:00 pm
Symposium: Wearable Injectors and Their Potential to Address The Growing Needs of The Pharmaceutical Industry
Thursday, Oct. 29 12:00 pm – 12:30 pm
Keynote: Advances in Dosage Form for Biologics
Donna French, AstraZeneca
Thursday, Oct. 29 2:00 pm – 3:00 pm
Rapid Fires
Thursday, Oct. 29 3:30 pm – 4:30 pm
FORMULATION DEVELOPMENT CHALLENGES FOR EMERGING MODALITIES
Prologue: Formulation Development Challenges of Emerging Modalities
New therapeutic modalities such as new protein formats, viral and cell therapy are emerging that are providing new challenges for Formulation Development. This prologue aims to introduce into the topic.
Tuesday, Nov. 3 9:30 am – 10:00 am
Symposium: Development of Low-Dose Drug Products of Potent Novel Protein Modalities
Protein aggregation is a critical quality attribute that is closely monitored during biologic candidate selection and process development. Aggregation is often observed under accelerated stress conditions such as thermal stress, agitation and freeze-thaw processes. This talk will delve into the relatively rare stability issues encountered during long-term storage of proteins in the frozen state.
Tuesday, Nov. 3 10:30 am – 11:00 am
Symposium: Strategies in Formulation Development of Novel Biologics Modalities
Increasing numbers of potent therapeutic protein modalities with extremely low first-in-human doses (< 0.1 ug/kg ) have been under development in recent years. Developing a robust drug product strategy that enables accurate delivery of these potent drugs is critical for patient safety and product efficacy. This presentation discusses the pharmaceutical development challenges, from formulation to product in-use, encountered in development of potent biologics drug products. The strategies implemented may guide development of similar products requiring ultra-low clinical doses.
Tuesday, Nov. 3 11:00 am – 11:30 pm
Symposium: Advances and Challenges in Gene Therapy Formulation Development
A systematic screening of formulation attributes (pH, buffer, and excipients) using current Pfizer gene therapy (GTx) candidates provides valuable information toward developing a platform formulation for GTx. To facilitate this process, a biophysical characterization toolkit was assembled to retrospectively assess the biophysical attributes that drive the biological function of adeno-associated viruses. In addition to the update on the formulation development, this presentation will also cover the current challenges and capabilities for early and late stage drug product.
Tuesday, Nov. 3 11:30 am – 12:00 pm
Symposium: Formulation Development of Cell Therapy Products
Tuesday, Nov. 3 12:00 pm – 12:30 pm
Keynote: Dosage Form Development Challenges for Advanced Therapeutic Medicinal Products
Nicholas Warne, Pfizer Inc.
Tuesday, Nov. 3 2:00 pm – 3:00 pm
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CHEMICAL
ADVANCES AND INNOVATION IN FORMULATION DEVELOPMENT
Rapid Fires
Wednesday, Oct. 28 9:00 am – 10:00 am
Prologue: Poor Solubility—Where Do We Stand 25 Years After The “Rule of Five”
This presentation will cover historical context of poor solubility; the “Rule of Five” and its limitations; what we can do to overcome poor water solubility; and the advantages and disadvantages of different formulation options.
Wednesday, Oct. 28 9:30 am – 10:00 am
Symposium: Mechanistic Insights Into Amorphous Drug Delivery Systems—A Computational Modelling Exploration
Today, most drug candidates are poorly water-soluble; this has led to greater emphasis on screening more complex formulation technologies such as spray dried dispersions (SDD). This presentation will provide case studies demonstrating how recent advances and applications in the use of mechanistic modeling can represent an opportunity for formulation/experimental scientists to explore these advanced techniques in designing and/or screening SDD formulations, thereby leading to more rational drug development.
Wednesday, Oct. 28 10:30 am – 11:00 am
Symposium: A Novel Architecture for High Drug-Loaded Amorphous Solid Dispersion Tablets
A high-loaded dosage form (HLDF) architecture for amorphous solid dispersions (ASDs) was developed, in which a drug is first spray-dried with a high glass transition temperature dispersion polymer to facilitate high drug loading while maintaining physical stability. The ASD is then granulated with concentration-sustaining polymers to extend supersaturation in solution. This presentation will describe case studies highlighting the HLDF architecture, including physical stability, in vitro and in vivo performance, and manufacturability.
Wednesday, Oct. 28 11:00 am – 11:30 am
Symposium: Strategies to Formulate High Drug-Load Amorphous Dispersions to Reduce Pill-Burden
This talk will provide overview of amorphous solid dispersions (ASDs), followed by a description of their dissolution behavior. Different strategies to increase drug loading without compromising dissolution will be discussed, including exploiting ionization behavior of the drug to enhance drug loading in the ASD and incorporating additives to improve dissolution of ASDs. Finally, the talk will summarize observations and how this topic has addressed the need for developing high drug load ASD formulations.
Wednesday, Oct. 28 11:30 am – 12:00 pm
Symposium: Counterions Facilitate High Drug Loading in Amorphous Solid Dispersion
High drug loading of amorphous solid dispersions (ASDs) challenges physical stability and drug release. In this research, counterions were incorporated with API model compound indomethacin to ionize the API and influence the pH of the diffusion layer. Improvement of dissolution rate was systemically studied to show the facilitating effect of counterions in high drug load ASDs. These findings can help better design high drug load ASDs using counterions for ionizable drugs.
Wednesday, Oct. 28 12:00 pm – 12:30 pm
Keynote: Integrating Multi-Disciplinary Science for The Hot Melt Extrusion (Hme) Process and Product: Towards a Fast Track Road Map From Design to Clinical Batch
Amrit Paudel, Graz University of Technology
Wednesday, Oct. 28 2:00 pm – 3:00 pm
DRUG DELIVERY AND DEVICE DEVELOPMENT
Prologue: Drug Transporter Small Molecules
Monday, Nov. 2 9:30 am – 10:00 am
Symposium: Overview of Kasa and Risk to Quality and Structured Product Assessment Initiatives
Monday, Nov. 2 10:30 am – 11:00 am
Symposium: Risk to Quality and Structured Biopharmaceutics Assessment
Monday, Nov. 2 11:00 am – 11:30 am
Symposium: Risk to Quality and Structured Manufacturing Assessment
Monday, Nov. 2 11:30 am – 12:00 pm
Symposium: Industrial Perspective
Monday, Nov. 2 12:00 pm – 12:30 pm
Keynote: As Drug Modalities Evolve So Must Our Development Strategies
Mike Hagemen, University of Kansas
Monday, Nov. 2 2:00 pm – 3:00 pm
Rapid Fires
Monday, Nov. 2 3:30 pm – 4:30 pm
FORMULATION DEVELOPMENT CHALLENGES FOR EMERGING MODALITIES
Prologue: CMC to Product Bio
Wednesday, Nov. 4 9:30 am – 10:00 am
Symposium: Gi Physiology and Condition to in Vitro Dissolution
This presentation will discuss why compendial dissolution apparatuses cannot predict in vivo dissolution profiles in certain drug products and how gastrointestinal (GI) physiology should be incorporated into the dissolution apparatuses. The idea of how to translate GI functionality and conditions into in vitro study will be discussed.
Wednesday, Nov. 4 10:30 am – 11:00 am
Symposium: in Vivo Predictive in Vitro Dissolution Methodologies (Current and Newer Methods)
Wednesday, Nov. 4 11:00 am – 11:30 am
Symposium: Pharmaco-Imaging in Early Drug Development
This presentation will discuss different microscopy and spectroscopy techniques used in regulatory settings or otherwise to better understand the microstructure of a dosage form. The presenter will also discuss how these techniques have been used to understand the release of active ingredient(s) from the dosage form, the delivery of the active ingredient to the intended local site of action, and the role of inactive ingredients in the drug delivery process. Current limitations will also be discussed.
Wednesday, Nov. 4 11:30 am – 12:00 am
Symposium: Predicting Performance in Paediatrics with PBPK Modelling and Biorelevant Data
The presentation will focus on the use of in vitro biopredictive testing and physiologically-based pharmacokinetic modeling for the prediction of in vivo performance in paediatrics.
Wednesday, Nov. 4 12:00 pm – 12:30 pm
Keynote: Regulatory Perspectives On Drug-Device Combination Products
Kristina Lauritsen, U.S. Food and Drug Administration
Wednesday, Nov. 4 2:00 pm – 3:00 pm
Rapid Fires
Wednesday, Nov. 4 3:30 pm – 4:30 pm
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HOT TOPICS
DISCOVERY AND BASIC RESEARCH
3D Printing in Pharmaceutical/Biomedical Applications
This symposium is comprised of four 30 minute talks regarding aspects of advanced 3D printing optimization and engineering for personalized medicines and bio-materials, formulation compositions, advanced drug delivery, materials properties, and characterizations of 3D printed pharmaceuticals, and more. Participants will learn and understand key engineering aspects of 3D printing processes and instrumentation and explore advanced pharmaceutical and biomedical applications of 3D printing technologies.
Monday, Oct. 26 2:00 pm – 3:00 pm
The Future of Space Medicine, Plant Molecular Foundries for Biotherapeutics in Space
One of the biggest challenges for deep space missions is ensuring crew health for both anticipated and unanticipated medical conditions, particularly when drug resupply and medical evacuations are not feasible. Plants are likely to serve multiple purposes in these missions including providing bioregenerative life support, a fresh food source, and psychological benefits. This presentation will describe how plants can also be used as molecular foundries to produce biotherapeutics, and more.
Thursday, November 5 10:50 am – 11:10 am
The Future of Space Medicine, New Stabilization Matrices for Medications During Space Travel
Thursday, November 5 11:10 am – 11:30 am
PRECLINICAL DEVELOPMENT - BIOMOLECULAR
COVID-19 Therapeutics Using DNA and RNA Based Vaccines
Monday, Oct. 26 2:00 pm – 3:00 pm
Rapid Advancement of a COVID-19 Vaccine into Phase 1 Clinical Testing: Leveraging a Platform Technology
Monday, Oct. 26 2:00 pm – 2:30 pm
PRECLINICAL DEVELOPMENT - CHEMICAL
Be Proactive: Know Your Active Metabolites!
Thursday, Nov. 5 9:00 am – 9:30 am
A Practical Example: The Ozanimod Experience
Thursday, Nov. 5 9:30 am – 10:00 am
BIOANALYTICS - BIOMOLECULAR
Is Your Bioanalytical Lab Ready for a Pandemic?
This panel will describe the importance of the supply chain in bioanalytical labs and address how the pandemic impacts rapid assay development for testing, how to maintain GLP compliance, and the economic and supply chain impact. Attendees will understand current testing for viruses and understand how to improve the testing during a pandemic.
Tuesday, Nov. 3 3:30 pm – 4:30 pm
BIOANLYTICS - CHEMICAL
Artificial Intelligence/Machine Learning: An Emerging Bioanalytical Solution
This panel discussion features colleagues sharing their experiences with bioanalysis. Panelists will describe current trends and techniques in AI/ML techniques and identify possible learning routes to start the AI/ML journey in your research.
Friday, Oct. 30 10:30 am – 11:30 am
CLINICAL PHARMACOLOGY - BIOMOLECULAR
Dose Selection Strategies for Rare Pediatric Diseases
This presentation focuses on the key features that discriminate dosing rationales for pediatric rare diseases from other pediatric and adult indications. Initial dosing rationale for first-time-in pediatrics (FTIP) dosing in rare diseases along with guidance for final dose selection will be discussed. Recent examples will be presented along with methodologies that facilitate these selections and garner regulatory confidence. Finally, a road-map for a streamlined approach consistent with a model-informed drug development (MIDD) paradigm will be proposed.
Thursday, November 5 10:30 am – 11:30 am
CLINICAL PHARMACOLOGY - CHEMICAL
Role of Modeling and Simulation in Biopharmaceutics
This case study addresses the use of PBPK/PBBM modeling to conduct virtual bioequivalence simulations to assess the impact of in vitro release characteristics between two drug products. We include a description of mechanisms of dissolution, absorption, distribution, and elimination of a drug in the human body with a discussion of how specific properties of the active pharmaceutical ingredient affects in vivo absorption.
Tuesday, Nov. 3 3:30 pm – 4:30 pm
MANUFACTURING AND ANALYTICAL CHARACTERIZATION - BIOMOLECULAR
Mass Spectrometry as a Disruptive Technology for CGT Analytics
Cell and gene therapies promise to become revolutionary curative treatments, yet realization of this potential requires advances in biomolecular understanding to be on par with quality standards of today’s state-of-the art treatments (e.g. monoclonal antibodies). This talk will describe translation of principles of the multi-attribute mass spectrometry method (MAM) toward 1) identification and control of viral vector quality attributes and 2) adaptation of these principles toward comprehensive proteome characterization of CAR-T cells.
Wednesday, Oct. 28 3:30 pm – 4:30 pm
MANUFACTURING AND ANALYTICAL CHARACTERIZATION - CHEMICAL
Flexible Manufacturing for Pediatric Patients
Friday, Oct. 30 9:00 am – 10:00 am
FORMULATION AND DELIVERY - BIOMOLECULAR
Challenges and Opportunties, Oral Delivery of Monoconal Antibodies
Friday, Oct. 30 10:30 am – 11:00 am
Novel Devices for Oral Delivery of Macromolecules
Friday, Oct. 30 11:00 am – 11:30 am
FORMULATION & DELIVERY - CHEMICAL
QbD for Inhaled Products: Parameters & Considerations for Development
Trending development requests for capsules and the aspects of customization of the drug container will all build the case for why a QbD initiative is necessary. The session will close with a look at what specific analytics should be built around an inhalation QbD program.
Wednesday, Oct. 30 3:30 pm – 4:30 pm
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WORKSHOPS
PRECLINICAL DEVELOPMENT - BIOMELCULAR
Drug Transporters 2020: Old Challenges and New opportunities
The goals of this workshop are 1) to bring together experts in the transporter field from academia, industry, and regulatory agencies, 2) to enhance interaction and communication between these three entities, and 3) to inform the audience about existing challenges and new opportunities in the transporter field. Session topics will include: transporter animal models, predicting human PK/IVIVE, transporters as drug targets, and an update on DDI guidances.
Monday, Nov. 9–Tuesday, Nov. 10, 2020
10:30 am – 12:00 pm and 2:00 pm – 3:30 pm each day
Gene Therapy: Inserting Old Genes Into a New Modality!
This workshop will provide a more comprehensive look at the discovery and development of gene therapy, including basic transgene and gene editing target selection, delivery mechanisms, quality testing, immunogenicity, clinical pharmacology and biomarker responses. Presentations will cover dose projections, gene delivery, and manufacturing challenges.
Wednesday, Nov. 11 – Thursday, Nov. 12, 2020
10:30 am – 12:00 pm and 2:00 pm – 3:30 pm each day
BIOANALYTICS - BIOMELECULAR
Introduction to Vaccine Clinical Development
This workshop will provide key concepts in vaccine process development and vaccine clinical development. Case study examples will be used to illustrate vaccine process development, clinical development, and regulatory strategy for vaccine licensure. The lectures will set the foundation for a COVID-19 roundtable discussion. Participants will have multiple opportunities to engage the expert panel to deepen understanding of what is needed to develop and license a novel vaccine and how we may adapt the traditional development process during a pandemic to meet the global need.
Monday, Nov. 9 – Tuesday, Nov. 10, 2020
10:30 am – 12:00 pm and 2:00 pm – 3:30 pm each day
Be Specific—Biomarker Assay Validation In Context
This workshop will provide foundational ideas of concept of context of use (COU), including clarification on what differentiates a biomarker category from a biomarker endpoint from the biomarker’s COU. Furthermore, we will demonstrate how to craft specific COU statements to address these scenarios. Lastly, we will highlight managing situations where COU is not forthcoming, but an assay is being requested. Examples of COUs with attendant validation considerations / requirements or assay characterizations and the COUs they may support will be provided.
Wednesday, Nov. 11 – Thursday, Nov. 12, 2020
10:30 am – 12:00 pm and 2:00 pm – 3:30 pm each day
MANUFACTURING AND ANALYTICAL CHARACTERIZATION - CHEMICAL
Strategic Approaches to Develop Phase-Appropriate Organic Impurity Control Strategies
This workshop will describe best practices for development of early phase control strategies for organic impurities and extractable/leachables in small molecule drug products. We will also discuss robust and phase-appropriate strategies to ensure that packaging supports the quality and efficacy throughout shelf life. This program will provide case studies and real-world examples of how appropriate control strategies can be successfully applied throughout the drug development for these impurity topics. It will also provide a forum to discuss new and innovative technologies that can be applied to the detection, isolation, identification, control, and monitoring of impurities throughout a product lifecycle.
Wednesday, Nov. 11 – Thursday, Nov. 12, 2020
10:30 am – 12:00 pm and 2:00 pm – 3:30 pm each day
Latest Developments in Excipients That Are Relevant to Formulation, Analytical and Manufacturing
There is a growing need to control critical excipient material properties that contribute to excipient variability in dosage forms. This presentation will highlight both challenges and opportunities for USP in collaboration with key stakeholders to provide up-to-date USP-NF monograph standards and chapters helpful in qualifying an excipient for its intended pharmaceutical use, providing a better understanding of excipient composition and impurities that may help in the selection of excipients for pharmaceutical use, and developing a toolbox approach to supplier qualification to help mitigate associated risks.
Wednesday, Nov. 11 – Thursday, Nov. 12, 2020
10:30 am – 12:00 pm & 2:00 pm – 3:30 pm each day
View the full program, and add sessions to your schedule today!
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