Drug Discovery & Development 2021

Specific biomarker assays are included in an increasing number of drug labels, with uses ranging from prediction of adverse events to providing insights on efficacy for patient populations.  More than 40 of these biomarkers fit into the category of companion diagnostics, and provide information on the safety and efficacy of the associated therapy.  The ability to develop biomarker assays in a fit for purpose manner, and then translate that development into a companion diagnostic strategy when appropriate is a key element of the delivery of precision medicine.  In this talk, will cover the key elements necessary for the delivery across this continuum of development, including partnership relationships with pharma and diagnostic companies.  Will also cover future trends include expansion of applications to new therapeutic areas, use of multi-analyte technologies and applications, artificial intelligence and machine learning analytics and algorithms, and implementation of new therapeutic modalities such as cell and gene therapies.

Learning Objectives:

1. Understanding of the key factors in the development of biomarker assays and requirements for transition to companion diagnostic applications

2. Examine future technologies and trends that impact the development of biomarker and companion diagnostic assays and their delivery of precision medicine

COVID-19 has changed the way companies operate, the way employees perform their work and the way both are adapting to the environment.  In this session, we'll cover both macro industry trends and specific changes enabling attendees to gain a holistic perspective.

Learning Objectives:

1. The current Life Sciences job market

2. Best practices in recruitment, interviewing and hiring

3. Employee and candidate sentiment

4. The "new normal" landscape

There are approximately 2000 distinct lipids which are believed to influence health and disease in humans. Their molecular interplay with genes, proteins and metabolites is strongly affected by the cellular supply of each of these lipids. A disordered lipid metabolism, system-wide or on a cellular basis, can fuel the development of diseases, including cancer. Lipidomics is the systems biology of lipids and lipid pathways and studies their role in health and disease. Here we show how lipidomics was applied in a variety of research projects ranging from basic science to clinical and industrial research, from organellar samples to tissue and body fluids, and from small scale pilot projects to population cohort analyses with several thousands of lipidomics profiles.

Learning Objectives:

1. Explain what lipidomics is

2. Identify relevant research areas for lipidomics analysis

The COVID-19 pandemic changed all of our lives in 2020.  Development of a COVID-19 vaccine required some re-thinking of the standard vaccine development paradigm.  The webinar will cover nonclinical development of the Pfizer-BioNTech CoVID-19 vaccine as well as some aspects specifically related to developing an mRNA vaccine and how that differed from a typical infectious disease nonclinical development program.

Learning Objectives: 

1. Provide brief overview of the typical approach to infectious disease vaccine development

2. Describe approach used for COVID-19 vaccine nonclinical development during a pandemic

3. Outline some points to consider in mRNA vaccine nonclinical development

As pharmaceutical companies have reduced or eliminated neuroscience drug development due to high costs and low approval rates, the economic and healthcare burden of CNS disorders in the United States costs an estimated $800 billion per year and rising. In the central nervous system, arginine vasopressin (AVP) and oxytocin (OT) are expressed in the social behavioral network (SBN), which includes connections important for parental bonding, peer relationships, social perception, cognition, and decision making. Within the SBN, AVP and OT are expressed in distinct cell populations and are associated with opposing roles in behavioral and physiological functions, with AVP exerting anxiogenic and depressive-like effects and OT exerting anxiolytic and anti-depressive effects. The mammalian OT-AVP receptor family is comprised of four G-protein coupled receptors: one canonical OT receptor (OTR) and three AVP receptors (V1a, V1b, and V2). Both OTR and V1aR are robustly expressed in the brain, and share ~85% structural homology, resulting in significant cross-reactivity between their ligands. Perturbations in the OT-VP system are associated with multiple psychopathologies, thus OT has received considerable interest as a therapeutic target. Currently, OT therapeutic applications are limited due to a relatively short efficacy, poor oral bioavailability, and poor blood-brain barrier penetrance. To address this, two OT variants (Pro8-OT and Val3-Pro8-OT) with a longer half-life are being compared to effects of the endogenous OT analog (Leu8-OT). This project evaluates the effects of OT analog-induced G-protein mediated signaling and effects on neuronal structure in human derived neuronal-like SH-SY5Y cells and murine primary hippocampal culture. Collectively, these data will provide key findings into how OT affects neuronal structure and function, so that these effects can better inform OT-mediated therapeutic development in humans.

Learning Objectives:

1. Describe the drug development process and timeline

2. Identify the challenges associated with neuropharmacological drug development

3. Differentiate between agonists, partial agonists and antagonists

4. Discuss how drug effects on cellular signaling and neuronal morphology may relate to physiological and sociobehavioral changes at the organismal level

Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disease affecting approximately 1 in 50,000 people worldwide. About 10% of these cases are found to have a hereditary component, but lack of routine genetic testing for those with family history suggests that the number could be much higher. Having better clarity into which genes play a role in disease causation, and by what molecular mechanism is the basis for precision medicine. This, coupled with an understanding of the clinical presentation of the disease based on genotype and progression, helps clinical and pharma researchers to improve patient selection for clinical trials and ultimately better diagnose and treat ALS patients. However, there has not yet been a systematic and comprehensive investigation of all genetic variants across all ALS-associated genes. However, there has not yet been a systematic and comprehensive investigation of all genetic variants across the most prevalent ALS-associated genes. To overcome this limitation, we present the most comprehensive genomic landscape of 28 ALS-associated genes and a complete characterization of all disease-causing variants, assessed to clinical standards and annotated for actionability. In this webinar, Dr. Mark Kiel will present the results of this curation effort and what it may mean for improving ALS diagnosis and treatment.

Learning Objectives:

1. Learn how the genetic heterogeneity of ALS has ramifications for clinical practice

2. See what a genomic landscape is and how a combination of A.I. and manual techniques can be used to produce one

3. Review the results of the ALS Genomic Landscape, highlighting key findings and their implications for drug development

G-protein-coupled receptors (GPCRs) remain major drug targets, despite an incomplete understanding of how they signal through 16 non-visual G-protein signal transducers (collectively named the transducerome) to exert their actions. Recent efforts in GPCR drug discovery have included the design or discovery of drugs that alter the engagement of specific subsets of these pathways—a concept termed functional selectivity or “bias.” However, traditional pharmacological tools to classify and rank the pharmacological activity of test compounds have largely depended on intracellular signaling pathways downstream of receptor activation and are heavily dependent on the intracellular milieu unique to each cell type or tissue, i.e. “system bias.” Because multiple transducers can link to common pathways, the disambiguation of specific G protein pathways can be especially laborious. To overcome this, multiple teams have developed FRET and BRET tools that directly measure ligand-mediated receptor-transducer engagement, though these have been largely incomplete or incompletely characterized. This talk will describe the development, characterization, and validation of the largest set of GPCR-G protein biosensors to date, collectively dubbed TRUPATH. Specific emphasis will be placed on the versatility of these types of tools in drug-screening and receptor-characterization efforts. These biosensors are freely and openly available to academic researchers for modification and use through an MTA with the University of North Carolina at Chapel Hill or through distribution by Addgene, the non-profit plasmid repository.