Explore the Agenda
8:20 am Check In & Coffee
8:50 am Chair’s Opening Remarks
Advancing Combinations & Novel Targets to Expand Therapeutic Horizons in Solid Tumors
9:00 am Combining Tarlatamab with Chemo-immunotherapy to Kick-Start a New Era in Small Cell Lung Cancer Treatment
- Tracing the breakthrough journey of tarlatamab from discovery to development, showcasing the scientific insights that enabled a first‑in‑class T‑cell–engager approach for SCLC
- Revealing the synergistic potential of pairing T‑cell engager molecules with checkpoint inhibitors and chemotherapy, supported by compelling preclinical evidence that demonstrates enhanced anti‑tumour activity and immune activation
- Highlighting emerging clinical data on tarlatamab and chemo‑immunotherapy combinations, illustrating how this strategy may unlock deeper, more durable responses for patients with limited treatment options
9:30 am Session Reserved for Alloy Therapeutics
10:00 am Exploring the De novo Design and Hypothesis-Driven exploration of Potent T-cell Engagers with JAM-2
- Exploring how generative design enables the rational construction of multispecifics
- Rapid generation of developable TCEs by designing in developability
- Exploration of new target space for TAAs including complex multipass membrane proteins
- Rationale design of TCEs that optimize the immune synapse
10:30 am Morning Refreshments & Networking
Discovery, Design & Engineering
Advancing Bispecific & Multi-Specific T-Cell Engagers to Maximize Tumor-Specific Engagement for More Potent Therapeutics
11:30 am Discovery, Engineering & Optimization of a Bispecific T-Cell Engager Against a Novel Low Copy Number Tumor Antigen
- Discovery of the novel tumor antigen, focusing on the identification strategies used to validate its high tumor selectivity and the challenges associated with targeting a protein with such a low-copy-number expression profile
- Rational engineering of the bispecific scaffold, detailing the optimization of the CD3 and tumor-binding domains to ensure a stable immunological synapse can form even when target density is minimal
- Optimization of the therapeutic window, highlighting how binding affinities were fine-tuned to maximize T-cell mediated killing of tumor cells while mitigating the risks of off-tumor toxicity and systemic cytokine release.
12:00 pm Building Multi‑Specific T‑Cell Engagers for Heterogeneous, Hard‑to‑Treat Tumors
- A purpose‑built approach addresses the limiting challenges of narrow therapeutic windows and target heterogeneity by extending T‑cell engager success to pMHC targets
- Trackers, small soluble TCR‑derived binding elements, leverage the natural pMHC–TCR interaction to drive precise tumor cell killing while maintaining antibody‑like developability
- The Broadcast platform identifies optimal target pairs, discovers and optimizes novel Trackers with drug‑like properties, and designs multi‑specific formats that expand tumor coverage and increase the number of patients with potential to benefit
Preclinical, Translational & Clinical Development
Evaluating Preclinical Strategies for Robust Translation of T-Cell Engagers into the Clinic with Improved Safety & Activity Assessment
11:30 am Advancing T‑Cell Engagers Targeting Driver Mutations for Solid Tumors
- Discovery and engineering approaches for generating highly selective pHLA-targeted binders.
- Preclinical evaluation strategies, including functional activity, specificity, and safety assessment.
- Key learnings from advancing pHLA-targeted therapies from nonclinical development into the clinic, and implications for next-generation programs
12:00 pm A PSMA-Targeted, CD2-Costimulating T-Cell Engager with Strong Preclinical Efficacy & a Favorable GLP Toxicology Profile
- PSMA is highly expressed in prostate cancer, and single‑cell RNA sequencing of metastatic tumor‑infiltrating lymphocytes identifies CD2 as a broadly expressed co‑stimulatory receptor, particularly on CD8⁺ T cells
- QL535, a trispecific PSMA × CD3 × CD2 molecule (2+1+1 TECOS format), delivers CD3 activation and CD2 co‑stimulation to enhance cytotoxicity while limiting cytokine release compared with benchmark T‑cell engagers
- QL535 demonstrates superior PSMA‑dependent killing in vitro, sustained activity under repeated stimulation, dose‑responsive tumor regression in PSMA⁺ PDX models, and a favorable GLP toxicology profile in non‑human primates, supporting its clinical development for PSMA‑positive prostate cancer
12:30 pm Lunch & Networking
Discovery, Design & Engineering
Utilizing Advanced Platforms & Avidity Driven Approaches to Engineer the Next Generation of Curative T-Cell Engagers
1:30 pm XmAb819: Avidity-Driven Selectivity in T-Cell Engagers Using Xencor’s 2+1 Platform
- Discussing different T-Cell Engager configurations such as 1+1 and 2+1 as strategies for selectivity
- Examining how dual-antigen engagement enables simultaneously binding that increases functional avidity and exploring factors that impact avidity
- Presentation of pre-clinical and clinical data in RCC
2:00 pm Roundtable Discussion: Utilizing Discovery Platforms to Hunt for the Perfect Target and Advance T-Cell Engager Efficacy in Solid & Liquid Tumors
- Discussing the methodologies currently used to identify antigens in multiple myeloma and B-cell lymphoma
- Debating whether therapeutic failure in hematologic cancers stems from T-cell exhaustion or from a lack of high-density, specific antigens to target
- Identifying shared antigens vs personalized neoantigens in solid tumor populations
Preclinical, Translational & Clinical Development
Navigating Early Clinical Development & Dosing Strategiesof TCE Therapies for Long‑Term Success
1:30 pm Standardizing Step-Up Dosing Escalation Protocols to Master Early-Phase Safety and Maximize the Therapeutic Window of T-Cell Engagers
- Implementing evidence-based step-up dosing regimens to reduce the cytokine response, allowing for higher target doses while minimizing the risk of severe CRS and ICANS
- Transitioning to Modified MABEL models that utilize real-time PD markers to identify the optimal biological dose
- Ensuring escalation decisions are based on anti-tumor activity rather than just circulating drug levels
2:00 pm Rational Target Selection, Combination Design & Early Clinical Responses for TCEs
- How antigen density, tumor heterogeneity, and safety considerations guide the rational selection of TCE targets to maximize efficacy while minimizing off‑tumor toxicity
- Rationale for pairing TCEs with agents such as cytokine modulators, checkpoint inhibitors, and targeted therapies to enhance T‑cell activation, durability, and tumor penetration
- Emerging patterns in efficacy, safety, and biomarkers from first‑in‑human TCE studies, and what they reveal about translational design decisions
2:30 pm Afternoon Refreshments & Networking
Utilizing Immune Effector Cells to Unleash Next-Generation Precision Targeting & Overcome Traditional T-Cell Limitations
3:00 pm Unlocking Intracellular Targets Through Synapse-Optimised T cell Engagers
- Discover and validate novel MHC presented targets
- Optimize, in parallel, our TCR-Ab binders, our anti-CD3, and our format for optimal synapse formation and therapeutic window
3:30 pm Conditionally Active Costimulatory T Cell-Engager Programs for Autoimmunity & Solid-Tumor Indications
- Shifting from oncology’s maximum potency mindset to a safety-first model by optimizing immune thresholds for chronic B-cell or T-cell depletion
- Leveraging lessons from oncology to eliminate high-grade CRS and ICANS, ensuring a benign safety profile suitable for non-malignant, chronic indications
- Utilizing tissue-restricted targeting and refined dosing to achieve long-term immune reset while preserving overall patient safety