8:20 am Chair’s Opening Remarks

Highlighting Research Efforts in Novel Cytokines

8:30 am A Novel Design of Procytokines for Improvement of Product Manufacturability and the Therapeutic Window for Cancer Immunotherapy

Synopsis

  • Design and Optimization ProIL-2 and ProIL-15 Platforms
  • Strategies for Optimizing Drug Exposure, Improving Potency, and
  • Minimizing toxicity
  • Case Studies on PD-1 Targeted Procytokines

9:00 am Targeting Delivery of IL-15 to PD-L1 Expressing Tumors With An Anti- PD-L1 IgM Antibody

Synopsis

  • IGM-7354 is an anti-PD-L1 pentameric high affinity, high avidity IgM engineered with an IL-15 fused to the joining chain designed to deliver IL-15 to PD-L1 expressing tumors to enhance anti-tumor immune responses
  • Properties include more potent PD-L1 binding and blockade of PD-1 than an IgG antibody, potent proliferation of NK, CD8+ T cells, reversal of T cell exhaustion, dose-dependent cytotoxicity of cancer cells in vitro, and additivity and/or potential synergy with antibodies mediating ADCC.
  • In vivo, IGM-7354 dose-dependently increased circulating NK and CD8+ T cells which correlated with tumor regressions. IGM-7354 was well tolerated in cynomolgus monkeys and dose dependently induced the proliferation of peripheral NK, CD8+ and γδ T cells.

9:30 am Targeting Biological Synergy At the Receptor Level – Multi-specific Cytokine Inhibitors

Synopsis

• Design and Development of multi-specific cytokine inhibitors
• Importance of targeting biological synergy to optimize therapeutic outcomes
• Advancing candidates into the clinic and beyond

10:00 am
Refreshment Break

11:00 am IL-7, the great forgotten

Synopsis

  • IL-7 biology and therapeutic potential
  • IL-7 clinical development
  • NT-I7; the next-generation long-acting IL-7

Optimizing Dose & Scheduling Strategies

11:30 am XTX301, A Half-Life Extended, Tumor-Selective IL-12, Exerts Potent Anti-Tumor Activity in Mice & has the Potential To Widen the Therapeutic Index of IL-12 Treatment.

  • Ekta Patel Director - Translational Biomarkers, Xilio Therapeutics Inc.

Synopsis

• mXTX301 potently inhibits tumor growth in a syngeneic mouse model.
• XTX301 is well-tolerated in a repeat dose non-GLP non-human primate study.
• XTX301 may exert potent anti-tumor activity while widening the potential
therapeutic index of IL-12 treatment.

12:00 pm
Lunch & Networking Break

Exploring Combination Therapy Approaches

1:00 pm SOT201 is a novel targeted IL-15RBy agonist to alleviate PD-1- mediated immune cell suppression and potentiate anti-tumor efficacy

Synopsis

  • SOT201 is a novel immunocytokine consisting of a monoclonal humanized, Fc silenced antibody against PD-1 fused to a covalent RLI-15 complex of a human IL-15 mutein linked to the high-affinity binding site of the IL-15R, the sushi+ domain developed for immunotherapeutic treatment of various types of cancers.
  • The activity of SOT201 is based on spatiotemporal reinvigorating of anti-tumor immune responses by disrupting co-inhibitory T-cell signaling by blocking PD-1 and synergistically activating adaptive as well as innate immunity by IL-15- mediated signaling via the IL-2/IL-15 receptor on T cells, NK, NKT, and γδ T cells.
  • SOT201 currently being prepared for Phase I clinical trial approval displays favorable pharmacodynamic and pharmacokinetic properties and induces strong anti-tumor immunity in various tumor mouse models.

1:30 pm Antibody-cytokine fusion proteins against Fibroblast Activation Protein (FAP)

Synopsis

  • A novel fully human monoclonal antibody against FAP has been isolated
  • The antibody was fused to a cytokine payload
  • The therapeutic activity was evaluated in mouse models of cancer

2:00 pm
Afternoon Break

Better Understanding Cytotoxicity to Improve Safety & Efficacy

2:30 pm Engineering IL-12 for tumor specific cytotoxicity results in enhanced therapeutic window

  • Lucas Donigian Senior Director Business Development & Alliance Management, Zymeworks

Synopsis

  • Multiple attenuating components help to mask IL-12 off-tumor mediated cytotoxicity
  • Tumor specific activation of IL12-Fc elicits a potent anti-tumor activity in xenograft models
  • No dose limiting toxicity observed in cynomolgus monkeys at levels well above expected therapeutic doses

3:00 pm T Cell Targeted Cytokines: Redefining Biodistribution to Improve Safety and Efficacy

Synopsis

  • CD8 targeting drives efficient biodistribution of cytokine payloads on target cells and reduces systemic exposure
  • In vivo efficacy and pharmacology of CD8 targeted cytokines
  • Preclinical development of a first-in-class CD8 targeted IL-12 for oncology

3:30 pm Selective Cell Type Targeting Improves Anti-tumor Activity and Safety of Cytokines

Synopsis

  • Asher Bio’s cis-targeting platform generates cell type selective immunomodulators
  • Selective activation of CD8+ T cells by a CD8-targeted IL-2 results in enhanced anti-tumor activity and safety
  • CAR-targeted IL-2 drives selective CAR-T cell expansion and improves anti-tumor activity

4:00 pm Chairs Closing Remarks

4:10 pm End of Day 2