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Products are filtered by different dates, depending on the combination of live and on-demand components that they contain, and on whether any live components are over or not.
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  • Contains 3 Component(s) Includes a Live Web Event on 11/19/2024 at 11:00 AM (EST)

    This symposium/webinar is intended to educate ADME scientists on MPS technology and its potential to generate clinically translatable data.

    Despite billions in annual investment, most drugs never reach the market because preclinical experiments fail to predict human effects. In this webinar, we will cover why in vivo models only deliver an approximation of what is likely to happen in the human body and why building more predictive, human-relevant models is key to reducing drug attrition. During the webinar we will introduce ADME scientists to the field of microphysiological systems (MPS), also known as organ-on-a-chip (OOC).

    We will explore how MPS technology can be implemented to create human-specific tissue models such as the gut and liver and interconnect them into systems that generate clinically translatable data. We will demonstrate how a deeper and earlier knowledge of human drug ADME profiles enables issues to be addressed prior to costly preclinical studies.

    The webinar will conclude by highlighting how the complementary use of MPS bridges the human-relevance gap, facilitating the confident selection of safer and more effective drug candidates, whilst also reducing costs.

    This webinar is sponsored by CN Bio Innovations.

  • Contains 3 Component(s) Includes a Live Web Event on 11/12/2024 at 9:00 AM (EST)

    In this webinar we will discuss efforts for improving the global underrepresentation of African genetics in science. We will further explore the current landscape and challenges in realizing an African hepatic modeling platform - with a specific focus on the development of hiPSC models that can better recapitulate hepatic function.

    The African continent harbors unparalleled genetic diversity yet remains largely underrepresented in  pharmaceutical  research  and  development.  Pharmacogenomics  is  fundamental  to  precision medicine strategies, and although to date largely absent from implementation, representing the genetic diversity of the African population within the laboratory is critical to the democratization of stratified  and  effective  healthcare  in  Africa.  Afrocentric  preclinical  resources  could  support precision  medicine on  the  continent  and  reshape  the  global  underrepresentation  of  African genetics  in  science. Models  which  could  begin  to  address  this  include  primary  human hepatocytes,  immortalized  hepatic  cell  lines,  and human induced  pluripotent  stem  cell  (hiPSC)derived hepatocyte-like cells – derived from individuals of African genetic ancestry. The feasibility of an African hepatic modeling platform is slowly being realized due to the convergence of several technologies and methodologies which have traditionally been siloed on the continent.

  • Contains 3 Component(s) Includes a Live Web Event on 07/09/2024 at 11:00 AM (EDT)

    This webinar is intended to provide education and updates of this evolving area to scientists and graduate students.

    This webinar is organized by ISSX M&S and transporter FG jointly. It will cover from in vitro to the human PK prediction for transporter substrates with focus on the current challenge and possible solutions related to:

    1) Critical In vitro methods /parameters needed for a reliable PBPK model predictions, data quality, gaps and how to overcome the limitations of in vitro system; 

    2) Key model structure and population parameters (including special populations) for transporter substrates - gaps in addressing multiple transporter involvement and interplay with enzymes; 

    3) Status of model validation for index substrates, applications in regulatory interaction and filing -challenges and future direction.

    The webinar will include sufficient time for Q&A with invited field expert as panelists.

    Xiaomin Liang

    Xiaomin Liang, Ph.D., is a Senior Scientist II in the Department of Drug Metabolism at Gilead Sciences Inc. She obtained her B.S. degree in molecular toxicology from the University of California, Berkeley in 2011, and her Ph.D. degree in pharmaceutical sciences with a focus on membrane transporters, transporter-mediated drug disposition, and pharmacokinetics (PK) from the University of California, San Francisco in 2016. Following a brief fellowship at the Office of Clinical Pharmacology at the FDA, she joined Gilead in 2017. Her primary research interests are in the applications of transporter biology, in vitro methodologies, and mechanism-based PK/PBPK modeling to understand the ADME of compounds and translate preclinical data to predict human PK.

    Ying-Hong Wang

    Dr. Ying-Hong Wang is a senior reviewer in the Division of Pharmacometrics, Office of Clinical Pharmacology, Office of Translational Sciences (OTS)/CDER. Prior to joining the FDA, she worked for 14 years at Merck, where she was responsible for preclinical and clinical development of numerous compounds in multiple therapeutic areas. She chaired the Quantitative Prediction of Drug Interaction Working Group and developed the internal guidelines for DDI prediction. Her modeling work on predicting and characterizing enzyme and transporter-mediated DDI and hepatic impairment contributed to the NDA approvals of grazoprevir/elbasvir and letermovir. Dr. Wang earned her Ph.D. from the Oregon Health Science University and completed her Clinical Pharmacology Fellowship training at the Indiana University-Purdue University Indianapolis. Her current research focuses on applications of PBPK modeling in CYP induction, transporter-mediated DDI, and hepatic impairment.

    Kunal Taskar

    Kunal Taskar, Ph.D., is currently working as Director, Global Head of PBPK Modelling at GSK. Kunal completed his doctorate more than a decade ago and postdoctoral research at Texas Tech University Health Sciences department, USA, in Quentin Smith’s lab with research focused on Neuropharmacokinetics and role of transporters in drug delivery across the blood-brain barrier (BBB).

    Kunal’s experience and research focus include: PBPK modeling of small/large molecules and new modalities for PK and dose predictions, drug-drug interaction predictions and mechanistic understanding of the clinically occurring drug–drug interactions; and application of PBPK modeling in special populations including pediatrics, pregnancy, and organ impairment. His expertise also includes transporter mediated drug delivery and intracellular drug concentrations, especially the role of uptake and efflux transporters in drug pharmacokinetics-pharmacodynamics in disease and toxicology; novel transporters and role in drug disposition and use of endogenous probes and modeling for drug mediated transporter modulations.

    Kunal is a member of American Society of Clinical Pharmacology and Therapeutics (ASCPT), International Society for the Study of Xenobiotics (ISSX) and the International Brain Barriers Society. Kunal is a member of several IQ consortiums including MIDD Pilot Program WG, Transporters, Induction PBPK and Pediatric PBPK. He is the founder member and Chair of the ASCPT QP PBPK Community. He received the 2014 AAPS Pharmaceutical Research Meritorious Manuscript Award for a manuscript that was published in the same journal in 2012. He has actively published and given invited talks and conducted workshops at international conferences.

  • Contains 3 Component(s)

    This webinar is intended to share knowledge regarding development of a quantitative assay for siRNA using ddPCR.

    Background: siRNA is a promising therapeutic modality highlighted by several US FDA approvals since 2018, with many more oligonucleotide assets in clinical development. To support siRNA discovery and development, robust and sensitive quantitative platforms for bioanalysis must be established to assess pharmacokinetic/pharmacodynamic relationships and toxicology. Droplet digital PCR offers improved sensitivity and throughput, as well as reduced susceptibility to matrix effects, compared with other analytical platforms. Methodology: The authors developed a stem-loop reverse transcription droplet digital PCR method to measure siRNA in mouse plasma and liver extract using bioanalytical method qualification guidelines. Conclusion: This newly developed assay has been demonstrated to be a superior alternative to other platforms, with the added benefit of greater sensitivity, with dynamic range from 390 to 400,000 copies/reaction and readiness for FDA investigational new drug-enabling applications.

    Megan Turski

    Megan Turski received her B.A. in Biology from University of Wisconsin-Madison. She has over 10 years of experience in bioanalysis working in the pharmaceutical industry. She began her career working in an FDA-regulated bioanalytical laboratory using LC-MS/MS and continued on to quantitative method validation and development for ligand binding assays and qPCR. She is currently a Scientist in the Drug Metabolism and Pharmacokinetics group at Takeda Pharmaceuticals in San Diego, CA. She primarily supports the bioanalysis for oligonucleotide drug candidates as well as the delivery platform development. Her current research focuses on developing PCR methods for oligonucleotides to determine pharmacokinetics and biodistribution of these drug candidates.

  • Contains 3 Component(s)

    This webinar aims to introduce the use of various tools to elucidate transporter function and consequently, in vivo exposure to transporter substrates. This includes the use of proteomics to inform an efflux ratio-relative expression factor enabling prediction of fetal exposure across the placenta, a novel metabolomics approach to identify biomarkers of renal OAT1/3 and MRP2/4 and lastly, a case study highlighting the importance of elucidating both the pharmacokinetics and pharmacodynamics of a P-gp substrate in determining its efficacy as CNS drug. The present webinar also aims to recognize graduate students and postdoctoral fellows from academia who carried out transporter-related research and presented their work in the form of a poster in 2023 North American ISSX annual meeting.

    This ISSX webinar will feature three presentations! The webinar will also recognize graduate students and postdoctoral fellows from academia who carried out transporter-related research and presented their work in the form of a poster at the 2023 North American ISSX meeting. The graduate student presenters will be introduced by their mentors, who will also participate in the question and answer portion of the webinar.

    PREDICTION AND VERIFICATION OF FETAL EXPOSURE TO DUAL BCRP/P-GP DRUG SUBSTRATES USING THE PROTEOMICS INFORMED EFFLUX RATIO-RELATIVE EXPRESSION FACTOR (ER-REF) APPROACH AND PBPK MODELING AND SIMULATION

    To inform fetal drug safety, it is important to determine or predict fetal drug exposure throughout pregnancy. The former is not possible in the first or second trimester. In contrast, at the time of birth, fetal drug exposure, relative to maternal exposure, can be estimated as Kp,uu (unbound fetal umbilical venous (UV) plasma area under the curve (AUC)/unbound maternal plasma (MP) AUC), provided the observed UV/MP values, spanning the dosing interval, are available from multiple maternal-fetal dyads. However, this fetal Kp,uu cannot be extrapolated to other drugs. To overcome the above limitations, we have used an efflux ratio-relative expression factor (ER-REF) approach to successfully predict the fetal Kp,uu of P-gp substrates. Because many drugs taken by pregnant people are also BCRP substrates, here, we extend this approach to drugs that are effluxed by both placental BCRP and P-gp or P-gp alone. To verify our predictions, we chose drugs for which UV/MP data were available at term: glyburide and imatinib (both BCRP and P-gp substrates) and nelfinavir (only P-gp substrate). First, the ER of the drugs was determined using Transwells and MDCKII cells expressing either BCRP or P-gp. Then, the ER was scaled using the proteomics-informed REF value to predict the fetal Kp,uu of the drug at term. The ER-REF predicted fetal Kp,uu of glyburide (0.43), imatinib (0.42), and nelfinavir (0.40) fell within two-fold of the corresponding in vivo fetal Kp,uu (0.44, 0.37, and 0.46, respectively). These data confirm that the ER-REF approach can successfully predict fetal drug exposure to BCRP/ P-gp and P-gp substrates, at term.

    METABOLOMICS-BASED BIOMARKER APPROACH FOR IDENTIFICATION AND VALIDATION OF CLINICAL ENDOGENOUS BIOMARKERS OF RENAL ORGANIC ANION TRANSPORTERS

    Endogenous substrates of drug transporters can be used as phenotypic biomarkers to predict transporter-mediated drug-drug interactions (DDIs), drug toxicity, and inter-individual variability in transport function. Inhibition of renal organic anion transporter (OAT) 1 and 3-mediated uptake and multidrug resistance-associated protein (MRP) 2 and 4-mediated efflux can increase plasma concentration and decrease urine amount of endogenous substrates, respectively, which can be used as clinical biomarkers. We identified and validated clinically relevant biomarkers of OAT1/3 and MRP2/4 using a state-of-the-art metabolomics-based DMET biomarker discovery (MDBD) approach. Untargeted metabolomics of the plasma and urine samples collected from a clinical furosemide/probenecid pharmacokinetic DDI study (n=16) yielded >10,000 features (m/z values) that were either increased or decreased in plasma and urine samples in the presence of probenecid (dual OAT/MRP inhibitor). Features that were significantly increased in plasma (1.5 to 10-fold) and were either decreased or non-significantly increased in urine samples were characterized as putative OAT1/3 biomarkers. Similarly, identification of putative MRP2/4 biomarkers included features that were significantly decreased in urine (by >45%) with non-significant change in plasma. Putative OAT1/3 biomarkers (m/z range, 130-384) belonged to the following pathways: tryptophan metabolites, steroids, peptides, glucuronide conjugates, and fatty acids. MRP2/4 biomarkers (m/z range, 110-510) were majorly bile acids, fatty acids, steroids, glycosides, and peptides. In vitro validation of the identified OAT1/3 biomarkers confirmed 12 putative OAT1 substrates as OAT1 biomarkers (>1.4-fold uptake in transporter over-expressing cells, p-value <0.05), 17 as OAT3 biomarkers and 21 as dual OAT1/3 biomarkers. This high-throughput and robust MDBD approach to identify and validate biomarkers is applicable beyond transporters.          

    HOW MUCH IS ENOUGH? BI-907828: A MDM2-P53 ANTAGONIST WITH LIMITED BBB PENETRATION BUT POTENT EFFICACY IN GLIOBLASTOMA MDM2–p53 inhibition may be effective in glioblastoma (GBM). This study evaluates the pharmacokinetics/pharmacodynamics of BI-907828, a potent antagonist of MDM2, in GBM, and demonstrates a translational paradigm with a focus on a unified “Delivery – Potency – Efficacy” relationship in drug development for central nervous system(CNS) tumors. BI-907828 was tested for cytotoxicity and MDM2–p53 pathway inhibition. Systemic pharmacokinetics and transport mechanisms controlling CNS distribution were evaluated in mice. BI-907828 free fractions in cell media, mouse and human specimens were measured to determine “active” unbound concentrations. Efficacy measures, including overall survival and target expression were assessed in mouse orthotopic GBM xenografts. BI-907828 exhibited potent inhibition of MDM2–p53 pathway and promoted cell death in GBM TP53 wild-type cells. MDM2-amplified cells are highly sensitive to BI-907828, with an effective unbound concentration of 0.1 nmol/L. The CNS distribution of BI-907828 is limited by blood–brain barrier (BBB) efflux mediated by P-gp, resulting in a Kp,uu_brain of 0.002. Despite this seemingly “poor” BBB penetration, weekly administration of 10 mg/kg BI-907828 extended median survival of orthotopic GBM108 xenografts from 28 to 218 days (P < 0.0001). This excellent efficacy can be attributed to high potency, resulting in a limited, yet effective, exposure in the CNS. These studies show that efficacy of BI-907828 in orthotopic models is related to high potency even though its CNS distribution is limited by BBB efflux. Therefore, a comprehensive understanding of all aspects of the “Delivery – Potency – Efficacy” relationship is warranted in drug discovery and development, especially for treatment of CNS tumors.

  • Contains 1 Component(s)

    The ISSX New Investigator Group will present this Fireside Chat with Dr. Eric Chan, an influential scientist in the field. This chat session will be moderated by a member of the group and the discussion will include wide-ranging topics such as current scientific trends, leveraging your network, and thinking strategically about your career in industry, academia, and/or government.

    The ISSX New Investigator Group will present this Fireside Chat with Dr. Eric Chan, an influential scientist in the field. This chat session will be moderated by a member of the group and the discussion will include wide-ranging topics such as current scientific trends, leveraging your network, and thinking strategically about your career in industry, academia, and/or government.

    About the Speaker:

    Dr. Eric Chan is a professor at the Department of Pharmacy and Pharmaceutical Sciences, National University of Singapore. He received his Ph.D. from the same department and was a postdoctoral research scientist at S*BIO Pte Ltd, a joint venture between the Economic Development Board of Singapore and Chiron Corporation at Emeryville, California. As professor, his research interests are (1) metabolism-driven systems biology modelling of diseases, pharmacology, toxicology and mammalian host-bacteria interactions and (2) xenobiotic-derived reactive metabolite research with specific focus on interaction with biological proteins and physiological-based pharmacokinetics-pharmacodynamics (PBPK-PD) modelling of pharmacology and toxicology. He advocates #LearningWithoutBarrier and has been sharing his knowledge generously via his #WeeklyDoseOfPK in LinkedIn. 

    Eric Chan

    Dr. Eric Chan is a professor at the Department of Pharmacy and Pharmaceutical Sciences, National University of Singapore. He received his Ph.D. from the same department and was a postdoctoral research scientist at S*BIO Pte Ltd, a joint venture between the Economic Development Board of Singapore and Chiron Corporation at Emeryville, California. As professor, his research interests are (1) metabolism-driven systems biology modelling of diseases, pharmacology, toxicology and mammalian host-bacteria interactions and (2) xenobiotic-derived reactive metabolite research with specific focus on interaction with biological proteins and physiological-based pharmacokinetics-pharmacodynamics (PBPK-PD) modelling of pharmacology and toxicology. He advocates #LearningWithoutBarrier and has been sharing his knowledge generously via his #WeeklyDoseOfPK in LinkedIn.

  • Contains 3 Component(s)

    Selective inhibitors of drug metabolizing enzymes are critical for reaction phenotyping to characterize clearance pathways. New selective inhibitors have been identified to enable more effective understanding of mechanisms involved in metabolism and drug-drug interactions. Learning the characteristics of these new selective inhibitors will allow researchers to apply them readily to characterize new drug candidates.

    Selective chemical inhibitors are critical for reaction phenotyping to identify drug-metabolizing enzymes that are involved in the elimination of drug candidates. Although relatively selective inhibitors are available for the major cytochrome P450 enzymes (CYP), they are quite limited for the less common CYPs and non-CYPs. To address this gap, we developed a multiplexed high throughput screening (HTS) assay using 20 substrate reactions of multiple enzymes to simultaneously monitor the inhibition of enzymes in a 384-well format. Four 384-well assay plates can be run at the same time to maximize throughput. This is the first multiplexed HTS assay for drug-metabolizing enzymes reported. The HTS assay is technologically enabled with state-of-the-art robotic systems and highly sensitive modern LC-MS/MS instrumentation. Virtual screening is utilized to identify inhibitors for HTS based on known inhibitors and enzyme structures. Screening of ~4000 compounds generated many hits for many drug-metabolizing enzymes. This webinar will highlight the characterization of selective inhibitors of CYP3A5 (loteprednol etabonate) and AO (erlotinib and dibenzothiophene). We encourage colleagues from other organizations to explore their proprietary libraries using a similar approach to identify better inhibitors that can be used across the industry.

    Li Di

    Dr. Li Di has ~30 years of experience in the pharmaceutical indus­try including Pfizer, Wyeth and Syntex. She is currently a DMPK fellow at Recursion Pharmaceuticals. Her research interests include the areas of drug metabo­lism, pharmacokinetics, drug-drug interactions, absorption, transporters, blood–brain barrier and PBPK modeling and simulation. She has 200 publications including two books and presented over 100 invited lectures. She is a recipient of the Thomas Alva Edison Patent Award, the New Jersey Association for Biomedical Research Outstanding Woman in Science Award, the Wyeth President’s Award, Peer Award for Excellence, Pfizer’s top 14 articles in 2023 and ISSX Distinguished Accomplishments in Drug Discovery and Development of Paxlovid Team Award.

  • Contains 3 Product(s)

    This virtual workshop will bring together scientists from academia, industry, and regulatory agencies to share their research findings, experience, and expert views on endogenous biomarkers for drug transporters, an active research area with rapid advances in recent years.

    This workshop is organized through the efforts of the ISSX Transporters Focus Group and is organized by Drs. Aleksandra Galetin, Xinning Yang, Bhagwat Prasad, Xiaoyan Chu, Hong Shen, Pei Feng Shawn Tan (student member), Mitesh Patel, Eva Gil Berglund, and Chitra Saran.

    This virtual workshop will bring together scientists from academia, industry, and regulatory agencies to share their research findings, experience, and expert views on endogenous biomarkers for drug transporters, an active research area with rapid advances in recent years. 

    The three-day workshop will cover several important topics in these areas: 

    -application of transporter biomarker in drug development,
    -understanding transporter function changes in specific populations facilitated by biomarker assessment, 
    -methods to identify transporter biomarkers, and 
    -emerging biomarkers of efflux transporters.  

    Each session of the workshop consists of presentations from several expert speakers followed by roundtable discussions, with case study presentations incorporated into one session to showcase the experience and advances in using transporter endogenous biomarkers during drug development. In addition, there will be an interactive virtual poster session, which will be selected from the pool of abstracts from trainees and industry attendees.

    Your workshop registration includes access to all presentation slides and recordings.

  • Contains 3 Component(s)

    This webinar is intended to highlight and discuss: The Process of Drug Discovery to Clinic.

    Drug discovery and development can be described as the sum of multiple steps taken by biotech and pharmaceutical companies to identify and study new chemical or biological entities and convert these into approved marketed medical products. The entire process takes, on average, more than 10 years and over $1-2B, to bring a product to market.

    During this process the attrition rate at all stages of drug discovery and early development are high; hence, sponsors are seeking ways to conduct early-stage drug development studies in the most cost-effective manner. The other consideration is the timeline needed to reach first in human (FIH) studies– the faster we can conduct these studies, the better it is for companies seeking to advance these leads further into development or sell the promising assets to potential buyers who are prepared to conduct additional clinical trials beyond Phase 1 studies. 

    The elements of drug development leading to IND submission and the conduct of FIH studies include: Drug Metabolism & Pharmacokinetics (DMPK), Safety/Tox, Bioanalytical (GLP/non-GLP) and CMC. With limited and dwindling resources in biotech/pharmaceutical companies, a significant portion of the task of advancing lead compounds to clinical are now conducted by Contract Research organizations (CROs) who are very well equipped to conduct these early development studies. Very often study sponsors struggle to outsource studies, often in small pieces, to reliable CROs. 

    Managing the costs and tracking timelines/samples/reports at multiple CROs often become a very inefficient and costly task. It is important to seek CROs that can provide a one stop shop option to drive cost-savings and efficiency, including accelerated timelines to reach FIH studies. Furthermore, proper project management, resolving issues with the best available science, and ability to provide proper/relevant regulatory guidance, are essential components of this one stop shop facilities. To keep the prices manageable (especially with the high attrition rate), many sponsors are also seeking more cost-effective alternatives overseas, including conducting studies in countries such as China (second largest economy in the world).

    Frontage Labs has been engaged in R & D activities over the last 20+ years, with substantial investments in facilities in both USA and China. Over the years, it has built a full-service science-driven organization that has participated in bringing products to the market for numerous clients. With its dual presence in USA and China, and being a strong science and issue driven organization, Frontage is now offering end to end services to advance clients’ lead candidates to FIH at very reasonable cost (estimated to be 50% less than what it costs to conduct these studies internally or outsource to multiple vendors) and with constricted timelines. 

    In this presentation we will describe the complete package that Frontage offers to clients seeking to advance their lead candidates to FIH and beyond.


    This webinar is sponsored by Frontage.

  • Contains 3 Component(s)

    This symposium is intended to provide perspectives on the impact that the ICH M12 guideline will have on the in vitro DDI studies required for drug development.

    In June 2022, the ICH released the first draft of its harmonized Drug Interaction Studies Guideline (M12). The guideline is the result of several meetings of the Expert Working Group since 2018 with the goal of harmonizing member regulatory agencies' guidelines to create a single guideline that will be used across all member countries. After a review period, the guideline will be adopted in early 2024. This presentation will offer perspectives on the differences between current in vitro drug-drug interaction guidance from the relevant US FDA, EMA and PMDA guidance documents, and how to plan drug development strategies to meet the ICH M12 guideline.

    This webinar is sponsored by BioIVT.