Anand Giddabasappa
Head and Research Fellow, AMI - Global Discovery, Investigative & Translational Sciences Pfizer
Seminars
As autoimmune T-cell engagers rapidly advance into clinical development, one of the field’s greatest challenges remains the ability to accurately predict clinical efficacy, durability, and safety before large-scale patient studies. Traditional preclinical models often fail to capture the complexity of autoimmune disease biology, creating urgent demand for more predictive translational tools, mechanistic biomarkers, and early human readouts that can de-risk development and accelerate patient benefit. This interactive session will discuss how the industry can improve translational predictability and shorten the path from discovery to clinical success by:
- Building more predictive translational models for autoimmune T-cell engagers, evaluating how advanced in vitro systems, humanized models, patient-derived assays, and mechanistic immune profiling can better predict efficacy, cytokine release syndrome risk, tissue depletion, and long-term immune reconstitution.
- Identifying the biomarkers that matter most for early clinical decision-making, discussing how pharmacodynamic biomarkers, cytokine signatures, immune-cell depletion kinetics, tissue-level readouts, and translational immune-monitoring strategies can support dose optimization, patient selection, and earlier validation of therapeutic activity
- Integrating early human data to accelerate development and reduce clinical risk, exploring how first-in-human studies, adaptive trial designs, and translational datasets can be leveraged to refine therapeutic hypotheses, improve safety management, and establish clearer pathways toward durable patient benefit and regulatory success
T-cell engager programs are advancing toward the clinic, but developers face an important challenge in demonstrating efficacy and safety in a therapeutic class where traditional preclinical models often fail to predict human responses. Unlike oncology, where tumor killing can be readily measured, autoimmune TCEs must balance selective immune-cell depletion, cytokine control, and long-term disease modification in heterogeneous patient populations. This workshop will explore innovative approaches to generating more predictive translational data and overcoming bottlenecks in both preclinical and clinical development by:
- Advancing ex vivo and human-derived testing platforms to improve clinical predictability, exploring the use of patient-derived samples, diseased tissue models, organoid systems, and immune-cell co-culture assays to evaluate pharmacodynamic activity in settings that better reflect autoimmune biology
- Establishing translational frameworks for assessing efficacy and safety before firstin-human studies, examining which biomarkers, functional assays, and immunemonitoring approaches are most predictive of clinical outcomes
- Innovating patient recruitment and trial design for emerging autoimmune TCE programs, exploring approaches to identify appropriate patient subsets, leverage biomarker-driven enrolment strategies, and recruit patients with specific immunecell signatures most likely to benefit from targeted depletion therapies
