Conference Day 1, May 22
8:00 am Check-In & Coffee
8:45 am Chair’s Opening Remarks
Tricky Terrain: Tackling Solid Tumors with Cell Engagers to Address Unmet Need & Mitigate Toxicity
9:00 am Bench to Bedside: Tebentafusp, the Story of the First Approved TCR Therapeutic
Synopsis
- A historical overview exploring the context of building a novel pipeline and platform
- Developing and characterizing transformative medicines to address unmet needs in cancer
9:30 am Understanding Cell Recruitment to Solid Tumors to Localize Targeting & Enhance Immune Response
Synopsis
- Localizing immune cell recruitment to minimize systemic toxicity
- Amplify anti-tumor activity and triggering of cytotoxic factors while combating immune evasion
- Explore induction of immunological memory towards tumor-specific antigens
10:00 am Novel Dual Targeting T Cell Engager With Selective Tumor Activity in Solid Tumors
Synopsis
- Engineering strategy to increase the therapeutic index of T cell engager molecules
- Improving tumor selectivity to avoid on-target off-tumor toxicity
10:30 am Speed Networking
Synopsis
The ideal opportunity to get face-to-face with many of the brightest minds working in the cell engager field and introduce yourself to the attendees that you would like to have more in-depth conversations with your peers.
Balancing on Toxicity Tightropes for Cell Engager Therapies
11:30 am How to Enhance Translatability of Immunotherapies in Preclinical Models?
Synopsis
- Focus on BRGSF-HIS hCD34+ reconstituted mice featuring human lymphoid and myeloid compartments and syngeneic humanized mouse models
- Characterization of the immune response in the mice
- Assessment of efficacy and safety induced by cell engagers
12:00 pm Roundtable Discussion: Resistance Risks? Comparing Cell Engagers to Alternate Cancer Treatments Such as ADCs & Cell Therapies to Evaluate Potential Risks
Synopsis
- Question the learnings from alternate therapeutic strategies such as how CAR T developers manage CRS
- Balance how cell engagers can fit into the standard of care or following patient treatment with these therapies
- Discuss future directions and the looming risk of resistance. Can we prevent it ever developing?
From Discovery to Manufacturing: End-to-End T Cell Engager Development
12:30 pm KeywayTM TCRm T-cell Engagers Discovery and Engineering: Fully Integrated Workflow from Target Idea to Development Candidate
Synopsis
- TCRm antibody enable the targeting of intracellular proteins that have not been addressed by conventional cancer immunotherapies while avoiding the manufacturing and regulatory challenges of other TCR-based modalities
- Keyway TCRm Discovery is the industry leading service to deliver fully functional and highly-specific lead TCRm T cell engagers by integrating high quality pMHC generation, best-in-class antibody discovery capabilities, comprehensive AI/ML enabled specificity screening, and therapeutically-tailored functional testing
- Keyway TCRm Discovery is led by pioneering minds in the field of TCR-based therapies and the team has successfully executed many partner projects across a variety of targets and HLA alleles.
1:00 pm Lunch & Networking
Engineering Improved Delivery, Stability, Affinity & Avidity for Enhanced Efficacy
2:00 pm Engineering & Assembling Novel Formats to Fine-Tune Affinity & Avidity
Synopsis
- Revolutionizing protein structure of BITEs to boost selectivity, ensuring binding to tumor cells while sidestepping any unwanted interactions with healthy tissue
- Achieving a balance between affinity and risk of CRS
- Building robust translational and bioanalytical strategies to safely and effectively treat more cancers
2:30 pm Quantitative Systems Pharmacology Modeling to Facilitate Translations Between Bench & Bedside: Forward & Back & Branching Out
Synopsis
- Quantitative systems pharmacology (QSP) modeling integrates in vitro data, in vivo PK and PD data, mechanism of action of the drug and biological understanding of the disease. I will demonstrate in my talk how QSP modeling is a powerful tool for translation to clinical as well as back translation from clinical to bench.
- For T cell engager first-in-human studies, we developed a QSP model that captures the CD3:drug:TAA cross-linking complex formation to support higher starting dose than an exposure-based MABEL approach. It has also been used to guide efficacious dose selection since bispecific molecules can have bell-shaped dose responses where a higher dose could lead to reduced efficacy.
- In addition to translation, QSP modeling can also be used early in R&D to guide novel platform design and perform in silico proof-of-concept simulations.
3:00 pm Mitigate Toxicity by Engineering & Assembling Novel Formats to Mitigate Toxicity
Synopsis
- Optimizing protein structure of BITEs to achieve increased selectivity of binding to tumor cells to minimize interactions with healthy tissue
- Navigating reducing affinity to reduce risk of CRS and toxicity, compared to decreased potency and risk reducing efficacy
- Explore the promise of tri- and multi-specific cell engagers for dual targeting
3:30 pm Afternoon Break
3:45 pm Achieving Strong Avidity & Durability
Synopsis
- Utilizing the natural features of immunoglobulins to achieve strong binding
- Looking into the overall developability strengths and weaknesses of IGM based modalities