8:00 am Check-In & Coffee
Overcoming In Vivo Toxicity Challenges to Improve Prediction of Toxicities to the Clinic
8:50 am Chair’s Opening Remarks
9:00 am Comparing the Safety Profiles of two NaPi2b ADCs Produced using Different Platforms
Synopsis
- Optimizing an ADC platform to minimize platform off-target toxicity
- Comparing two NaPi2b ADCs produced using two different platforms, improving safety and efficacy both pre-clinically and clinically
- Leveraging the rat versus NHPs, for investigative mechanistic studies
9:30 am Unveiling the Differences in Toxicity in NHPs when Using an Identical Linker and Payload but Harnessing Different Targets
Synopsis
- Evaluating toxicities in rodents and NHPs with two different linkers
- Determining the difference in toxicity in NHP for identical linker and payload but different targets
- Comparing the highest non severely toxic dose of a vcMMAE against b-GLU exatecan in NHP on a high expression target
10:00 am Targeting Sortilin (SORT1) to Unlock the Potential of Peptide Drug Conjugates (PDCs) in Oncology: Rapid Internalization Within Minutes with Unique Multimodal MOA and Safety Profile
Synopsis
- Understand the rationale for targeting the SORT1 receptor in cancer
- Discuss the unique toxicity profile of sudocetaxel zendusortide (TH1902), the lead PDC from Theratechnologies’ SORT1+ Technology™ platform, that differs substantially from the safety profile of taxanes, due to the multimodal MOA of the conjugate and the low levels of free circulating docetaxel
- Discuss how this multifaceted MOA with improved safety profile can lead to prolonged regression of disease and enable combinations with ADCs, PDCs and other anti-cancer therapies
- Discuss the ongoing phase I clinical development of sudocetaxel zendusortide, focusing on dose optimization
10:30 am Morning Break & Networking
Synopsis
This session is an opportunity to connect with peers working within the ADC Toxicity world, to have important conversations to overcome shared challenges, and plot paths to see future successes within the field
Mitigating & Managing ADC Toxicites In the Clinic to Reduce Patient Burdens
11:30 am Looking into Ocular Challenges: Mitigating and Managing ADC Ocular Surface Toxicity
Synopsis
- Overview of ocular surface toxicities associated with ADCs
- Case study: clinical presentation and management of corneal adverse events associated with a maytansine ADC
- Evaluating preclinical models to evaluate ADC ocular toxicity
12:15 pm Discussing the Clinician Perspectives on Tolerating, Mitigating, & Managing ADC-Related Toxicities
Synopsis
- Clinic experience on identifying side effects related to ADC early on during treatment in order to avoid severe toxicities
- Frequent vs rare side effects: how to manage ADC related AEs in our clinic patients
- Is it possible to re-challenge ADC after important toxicity? When can we safely continue ADC?
12:45 pm Investigating the Possibility of Biomarkers in Order to Correctly Prescribe ADCs Dependent on Individual Patient Response to Toxicities
Synopsis
Discovering the possibility of biomarkers to understand amount/application of ADC dosing dependent on patient screening results
Looking at patient-dependent liabilities to toxicities to decide on whether the prescription of an ADC would be beneficial
Identifying which biomarkers are indicative of higher toxicity levels
1:15 pm Lunch & Networking
Showcasing Cutting-Edge In Vitro Assays to Facilitate Higher ADC Toxicity Prediction
2:15 pm Development of in vitro Assays for Off-Target ADC Hematotoxicity
Synopsis
- Summarizing potential mechanisms driving off-target ADC hematotoxicity
- Developing in vitro approaches to differentiate ADCs based on toxicity to neutrophils and megakaryocytes
- Investigating mechanisms of off-target hematotoxicity including the role of FC receptor mediated uptake
2:45 pm High-throughput Functional and Morphological Neurotoxicity Screening in Human NerveSim®
Synopsis
- Valuable in-vitro model for sensitively studying potential compound induced functional and morphological toxicities in the peripheral nervous system
- 24-well format to provide high-throughput electrophysiological characterization amenable to testing multi-drug panels for neurotoxicity on a clinically relevant nerve model
- Case study – A multidimensional assessment of toxicity for chemotherapeutic compounds and ADCs
3:00 pm Afternoon Break
Assessing Novel Approaches for Toxicity Prediction to Overcome NHP Supply Chain Challenges
3:30 pm Optimizing Non-Clinical Safety Strategies for Use of NHPs: Facilitating Internal Decision Making and Regulatory Acceptance
Synopsis
- Refining platform toxicity study designs due to limited availability of NHPs
- Leveraging internal and external information to maximize data outputs to support Go/No Go decisions and select/advance candidate ADCs toward GLP toxicity
4:00 pm Differentiating Between a Healthy Monkey & Humans, What Role Does the Immune System Have to Play?
Synopsis
- Understand the immune factors that need to be taken into account when translating ADC toxicities from pre-clinical to clinical
- Decipher why inflammatory changes seen clinically could be different from preclinical NHP models
- Delving into ways to increase the predictability of toxicities through understanding immunological responses
4:40 pm End of Scientific Program Day One
