Conference Day Two
Thursday, October 10, 2024
8:30 am Check In & Registration
9:25 am Chair’s Opening Remarks
Evolving Preclinical & Translational Strategy With Novel Conjugates to Better Inform Dosing in the Clinic
9:30 am Discussing Key ADME Attributes Determining ADC Disposition & Conjugation Stability
Synopsis
- Investigate impact of payload physico-chemical properties and site of conjugation on ADC disposition
- Assess Maleimide-thiol conjugation stability
- Review the impact of on-target off tissue and off-target uptake on toxicity
10:00 am Delving into DMPK Considerations for ADCs
10:30 am Morning Break & Speed Networking
11:30 am Understanding & Characterizing the Impacts Of High Drug-to-Antibody Ratio (DAR) on ADC Behaviour in the Early Development Phase
12:00 pm Roundtable Discussion: Incorporating Animal Data to Better Inform FIH Dosing in ADCs
Synopsis
- Improving bioanalytical data from MS/in vivo studies to understand how an ADC will behave in humans
- Designing studies to better inform dose prediction from in vivo models
- Discussing examples of how to make animal models more predictive across different indications
1:00 pm Lunch
Exploring PK Modeling Insights to Better Predict Clinical Outcomes
2:00 pm Physiology Based Pharmacokinetic Models for Whole-Body Disposition of Antibody-Drug Conjugate
Synopsis
- Understanding and predicting how conjugation to antibody can affect distribution of a drug
- Utilizing PBPK models as a platform for translational and clinical investigations of ADCs
- Discussing future directions for PBPK modeling for ADCs
2:30 pm PBPK Modeling & Simulation Predicts Low Drug-Drug Interaction Liability & No Significant Impact of Hepatic Impairment for An ADC With the Payload AF-HPA
Synopsis
- Case study describing a PBPK modeling and simulation approach to predict the impact of drug-drug interactions (DDI) and hepatic impairment on clinical PK of an ADC with an auristatin-based payload (auristatin F-hydroxypropylamide [AF-HPA])
- Model development and verification using a combination of in vitro, pre-clinical, and clinical ADME/PK data using mixed ‘bottom-up’ and ‘top-down’ approaches
- Overview of model simulations to predict the liability of unconjugated AF-HPA as a victim or perpetrator of clinical DDI and to predict the impact of hepatic impairment on the exposure of unconjugated AF-HPA
3:00 pm Afternoon Break
Delving into Clinical Strategy to Set Up an ADC Study for Success
3:30 pm Utilizing Population Pharmacokinetic Analysis & Exposure-Response (ER) Analysis to Better Inform Dosing
Synopsis
- Enhancing characterization of doses prior to registration trials to maximize the efficacy and safety of oncology drugs
- Assess the impact of Covariates (Intrinsic and Extrinsic factors) on ADC exposure and on optimal dose
- PopPK and Quantitative Medicine-based Optimal Dose and Schedule for ADCs and combinations
4:00 pm Preclinical Journey of anti-Claudin18.2 ADC for Effective Translation Into Clinical Pharmacokinetics
Synopsis
- Introducing anti-Claudin18.2 ADC, preclinical studies, bioanalytical strategy and assay design for PK analysis
- Utilizing preclinical pharmacology, toxicology and animal PK data to determine safe human starting dose
- Reviewing clinical PK and correlation with human PK predictions
4:30 pm The Application of Modeling & Simulations to Support Late-Stage ADC Development
Synopsis
- Utilizing modeling and simulations to support ADC material comparability
- Assessing ethnic comparability
- Exploring indication expansion to allow wider patient access