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SYMPOSIUM ABSTRACTS & BIOS
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GLOBALGATORS GLOBAL GATORS
GLOBALGATORS GLOBAL GATORS
Jan Schlender, Ph.D.
Jan Schlender is Director and Site Head for Modeling & Simulation at Novartis in Basel, where he leads a multidisciplinary team encompassing Quantitative Systems Pharmacology (QSP), Translational PK/PD, Biophysical, and PBPK modeling His work focuses on integrating mechanistic modeling approaches to support drug development and regulatory interactions across various therapeutic areas Prior to Novartis, he spent ten years at Bayer Pharmaceuticals, holding various positions of increasing responsibility within the Modeling & Simulation and Pharmacometrics department He studied pharmacy at the University of Bonn, National Taiwan University, and the University of Florida, and earned his PhD in Clinical Pharmacy from the University of Bonn in collaboration with Bayer Technology Services.
Bridging PK–PD in Older Adults: Overcoming Data Gaps for Evidence-Based Labeling through In Silico Approaches
Abstract:
Older adults, particularly those ≥80 years, remain consistently underrepresented in clinical trials despite carrying a disproportionate disease burden, leading to uncertainty in dose selection and limited actionable information in drug labeling This gap is compounded by age-dependent physiological changes affecting ADME, increased multimorbidity, and polypharmacy, all of which challenge direct extrapolation from younger populations
This presentation integrates findings from IQ Consortium working groups on geriatric PBPK and clinical trial representation to highlight disconnects between PK changes, PD outcomes, and label recommendations. Despite evidence that a substantial proportion of drugs show PK and/or PD differences in older adults, labeling rarely reflects differentiated dosing guidance. It will be discussed how in silico approaches, particularly PBPK and PBPK/PD modeling, can bridge this gap by mechanistically incorporating age-related physiological changes and supporting extrapolation of exposure–response relationships
Learning Objectives:
Understand key drivers of uncertainty in geriatric labeling, including underrepresentation in trials and disconnects between PK, PD, and clinical outcomes
Recognize how age-related physiological changes impact PK–PD relationships and complicate direct extrapolation from younger adults
Evaluate the role of in silico approaches (PBPK, PBPK/PD) to support dose selection, trial design, and regulatory decision-making in older populations.
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S Van Fleet Endowed Professorship in Pharmaceutics Dr Meibohm received his pharmacy degree and doctorate in pharmaceutics from Technical University CaroloWilhelmina, Braunschweig, Germany After completion of a clinical pharmacology research fellowship at the University of Florida, he joined in 1999 the University of Tennessee
Dr. Meibohm’s scientific interests include bacterial and viral infections, pediatric pharmacotherapy and the application of pharmacometrics techniques in preclinical and clinical drug development, with specific focus on therapeutic proteins. His
Inhaled Tigecycline against Non-Tuberculous Mycobacterial infections, a Rapidly Growing Danger for Older Women research has resulted in over 230 scientific papers (>15,000 citations; h-index 57), three textbooks, and over 250 invited scientific presentations to national and international audiences
Learning Objectives:
To appreciate the role ofMycobacterium abscessusin opportunistic pulmonary infections
To understand the potential of inhaled tigecycline for the treatmentMycobacterium abscessuspulmonary infections
To acknowledge the role of PBPK modeling in establishing a human dose rationale for inhaled tigecycline
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GLOBALGATORS GLOBAL GATORS
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establishing pathways of drug-resistance, and identifying agents to overcome resistance to standard chemotherapy Some seminal discoveries from our group include CD33 polymorphisms of significant clinical relevance to gemtuzumab response (JCO, 2017) which holds promise in utilizing preemptive genotype to select patients most likely to benefit from CD33 directed therapy We have developed novel antibodies recognizing different CD33 isoforms for development of novel therapeutic agents Another clinically relevant discovery includes development of a pharmacogenetics-based polygenic score that not only provides prognostic
significance by predicting poor outcome in acute myeloid leukemia to standard therapy, but suggests that alternative augmented induction 1 regimens with either high-dose ara-C, or clofarabine/Ara-C combination or addition of gemtuzumab are more suitable strategies for patients with detrimental score (JCO, 2022). Throughout this, we built a strong team of clinical investigators across multiple institutes with expertise in genetics and bioinformatics allowing trainees in the group to gain skills at multiple levels Research in my lab has been funded by NCI since 2008 and other foundations such as Leukemia Lymphoma Society, American Cancer Society, St Baldrick’s Foundation, Live like Bella foundation etc Our ongoing work is focused on novel therapeutics in AML, primarily driven by multiomics findings as well as ongoing CRISPR/cas9 synthetic lethal screening of AML cell lines and primary patient samples
Abstract:
Pharmacogenomics for Tailoring Induction Chemotherapy for Acute Myeloid Leukemia
AML is a heterogeneous disease with dismal outcome Cytarabine (also known as ara-C) has been the backbone of acute myeloid leukemia (AML) chemotherapy for more than five decades that is given in combination with anthracyclines However, this standard regimen fails to induce remission in roughly 10%-15% of children and among those who achieve remission, approximately 40% relapse. Ara-C is a prodrug requiring activation to ara-C triphosphate (ara-CTP) which blocks DNA/RNA synthesis and causing leukemic cell death. Interpatient variation in art-CTP activation impacts the response. Thus we established a patient-specific polygenic score (ACS10) derived from cytarabine pathway pharmacogenomic evaluation to personalize acute myeloid leukemia (AML) treatment. We show low ACS10 (≤0) is associated with poor outcomes in over 2000 patients with AML treated with standard chemotherapy across 4 clinical trials Further we show that intensification of chemotherapy such as high dose areC or combination of clofarabine/Ara-C or addition of another agent improves outcome significantly We are currently preparing a clinical trial to personalize AML chemotherapy using ACS10 score at University of Florida
Learning Objectives:
Understand the role of pharmacogenomics in predicting outcome in AML
Gain knowledge on how pharmacogenomics discoveries can personalize AML chemotherapy to maximize efficacy and reduce toxicity
Learn about an example where pharmacogenomics discovery can enhance drug development
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How to quantify the host-drug-drug-disease interplay: Modelling approaches to support development of novel treatment strategies in resistant bacterial infections
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Pharmacokinetic-pharmacodynamic modeling of malaria and opioid overdose utilizing Human-on-a-Chip microphysiological systems
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