*All times Eastern Daylight Time*

8:00 am Opening Address from Chair

BISPECIFIC ANTIBODY APPROACHES FOR IMPROVED AND SELECTIVE IMMUNE CHECKPOINT BLOCKADE

8:10 am CD5 x TGFbR2 Bispecific Antibodies Provide A Novel Strategy To Suppress TGFb By Selective Blockade Of TGFbR2 On T cells

Synopsis

  • We engineered bispecific antibodies that simultaneously engage CD5 and TGFbR2 using Xencor’s XmAb® platform
  • CD5 x TGFbR2 bispecific antibodies selectively block TGFb signaling on T cells with activity in vitro and in vivo
  • CD5 x TGFbR2 bispecific antibodies employ a novel strategy for suppression of TGFb activity on tumor T cells that may enhance their anti-tumor activity while avoiding the toxicity associated with systemic blockade

8:35 am A Novel Bispecific Checkpoint Inhibitor Antibody To Preferentially Block PD-1 And LAG-3 On TILs Whilst Sparing Treg Activation

Synopsis

  • Improved targeting to tumor-reactive T cells rather than Tregs due to the selectivity gain and different expression patterns of PD-1 and LAG-3 on these two T cell types
  • Reduced internalization
  • Fc silent-mediated resistance to drug-shaving by macrophages,
  • Increased in vitro T cell effector functions even in the presence of Tregs, and
  • Superior in vivo tumor control/eradication in several mouse models compared to a combination of monospecific anti-PD1 and anti-LAG3 antibodies

9:00 am Chair led Speaker Q&A

9:10 am Panel Discussion: Targeting Checkpoint Inhibitors – PD-1/PD-L1

Synopsis

  • Identifying which anti-PD-1-refractory cancers to target?
  • What we know so far in treatment strategies to simultaneously block PD-1/PD-L1 and other pro tumor signals (e.g. TGF-β) to try and enhance the effect patient response rates
  • Cytokine and co-stimulation combination approaches
  • Combinations with checkpoint inhibitors

9:55 am PD-1-engaging Bispecific DART® molecules: Early Clinical Data Highlights Antitumor & Pharmacodynamic Activity

  • Bradley Sumrow Senior Director - Clinical Research & Development, MacroGenics, Inc.

Synopsis

  • Tebotelimab (PD-1 x LAG-3) and MGD019 (PD-1 x CTLA-4) purposefully designed to enact dual checkpoint inhibition while maintaining full PD-1 blockade
  • Phase 1 evaluations demonstrate safety, antitumor activity in various solid and hematologic malignancies, pharmacodynamic evidence of dual checkpoint inhibition, and associations between clinical response and baseline biomarkers
  • Preclinical rationale supports the ongoing tebotelimab combination with margetuximab (Fc-engineered anti-HER2 monoclonal antibody), yielding encouraging clinical activity in patients with refractory advanced HER2+ neoplasms

10:20 am Networking Break

Expanding the Boundaries of Biotherapeutics with Tri and Multispecific Antibodies

11:00 am Developing Next-Generation CD3-Engaging Multispecifics Through Tumor- Specific Activation and Checkpoint Modulation

  • Tony Polverino Executive Vice President, Early Development and Chief Scientific Officer , Zymeworks

Synopsis

  • ProTECT™: A Novel Antibody Platform for Integrating Tumor-Specific Immune Modulation And Enhancing the Therapeutic Window of Targeted Multispecific Biologics
  • ProTECT™ is a transferable platform to engineer antibodies for tumor-specific activity by masking with functional immunomodulatory pairs
  • Protease activation in the tumor recovers target binding while conferring additional synergistic anti-tumor activity from a remaining immunomodulatory domain
  • Differentiated trispecific mechanism of action and improved potency demonstrated in a ProTECT™ HER2/CD3/PD-1 program

11:30 am Modulating Cancer Immunity with Tri-specific & Multi-Specific Antibodies

Synopsis

  • Evaluate the latest platforms increasing therapeutic index via through tri and multi-specific approaches
  • Evaluation of targets for Tri and multi-specific approaches
  • Tri and multi-specific approaches to overcome traditional T-cell engager toxicities

12:00 pm Multispecific Biotherapeutics Beyond Immune Cell Engagers

  • Xiaotian Zhong Senior Principal Scientist & Laboratory Head , Pfizer

Synopsis

  • New designs, new technologies, and new mechanistic understandings for multispecific immune cell engagers have been coming of age
  • Novel therapeutic modes of action for multispecific biotherapeutics beyond immune cell engagers are emerging and coming into play
  • New modalities and new molecular designs have presented new opportunities as well as challenges for therapeutic applications

12:30 pm Conditional Tumor-Restricted Activation of Multi-specific-Cell Engagers

  • Liat Dassa Senior Director, Head of R&D , Immunorizon

Synopsis

  • First-in-class Multi-specific conditional activation of T-and NK-cell engagers at the tumor
    microenvironment
  • Ability to locally unleash both the innate and adaptive immune system at the TME
  • Unique scaffolds designed to enhance target specific anti-tumor response with minimal off-target activity

1:00 pm Lunch

T-Cell Based Approaches For Oncology Therapeutics

1:45 pm Protease Dependent COBRA Activity Regresses Established Solid Tumors in Mice

  • Chad May Senior Vice President, R&D, Maverick Therapeutics

Synopsis

  • Will review the pre-clinical characterization of the T cell engagers MVC-101, targeting EGFR, and MVC-280, targeting B7H3
  • COBRAs are engineered to be administered as prodrugs which are preferentially activated in the tumor microenvironment
  • COBRA design increases the therapeutic index in mice with established solid tumors

2:15 pm Optimization Of Bispecific T Cell Engager With Reduced Cytokine Release

  • Li Zhou VP Cell Therapy & Antibody Research , Boan Boston

Synopsis

  • Optimization on CD3 activity
  • Unique format that support bivalent tumor antigen binding and monovalent CD3 binding
  • Case studies

CMC Strategies & Scale-up Production for Clinical Applications

11:00 am TriTAC: A T Cell Engager Platform Optimized To Treat Solid Tumors

  • Bryan Lemon Director Protein Sciences , Harpoon Therapeutics

Synopsis

  • Designed to be small, stable, and half-life extended
  • Engineered for improved manufacturability and developability
  • Bryan Lemon, Executive Director Protein Sciences, Harpoon Therapeutics

11:30 am A Robust And Modular Heterodimeric Fc Platform Engineered For Efficient Development Of Bispecific And Fc Fusion Therapeutics

Synopsis

  • XmAb – A multiformat platform engineered for rapid development of next generation biotherapeutics with new functionalities, extended half-life and increased stability
  • Design allows for improved manufacturability using standard process and analytical tools
  • Stability of the platform enables rapid pipeline generation with streamlined preclinical and clinical development

12:00 pm CMC Development of Therapeutic Bispecific Antibodies Generated By Harbour HBICE Platform

  • Amy Que Chief Technology Officer, Harbour Biomed

Synopsis

  • HBICE Platform allows for favourable developability profiles
  • HBICE Platform is optimised for maximum manufacturability

12:30 pm This Track has now come to a close please join us after lunch for the next set of presentations

  • Umesh Muchhal Senior Director Protein Sciences , Xencor
  • Amy Que Chief Technology Officer, Harbour Biomed

1:00 pm Lunch

Scale-Up, Optimizing Production And Expression Of Bispecific Molecules

1:45 pm Scaling Up A Cost-effective kl-bodyä Purification Process For Phase I Clinical Applicatio

  • Yves Poitevin Head of Bioprossessing , Light Chain Bioscience – Novimmune SA

Synopsis

  •  Downstream purification of bispecific mAbs
  • Development of a robust and scalable kl body platform purification process
  • Clinical Phase I opportunity to scale up a new 2 affinity step kl body purification approach

2:15 pm Cell Line Development Strategies To Improve The Purity Of CD3 Bispecific Antibodies

  • Yanjing Li Senior Scientist - Cell Line Development / CMC Lead , Boan Boston

Synopsis

  • Overview of the cell line development strategies and challenges in the development of
    Bispecific antibody
  • Tuning bsAb productivity and heterodimer content by modulating chain-to chain ratio
  • Early screening of purity profile allows the identification of pools containing the highest proportion of bsAb heterodimer form

2:45 pm Break

INVESTIGATING NOVEL APPROACHES IN THE BISPECIFIC LANDSCAPE

3:15 pm Preclinical Development of a Bispecific Antibody for Neuroblastoma with Improved Efficacy and Reduced Pain

Synopsis

  • Current standard of care antibody treatment for the childhood cancer neuroblastoma causes excruciating and doselimiting pain, due to expression of the target on peripheral nerves.
  • Invenra uses our bispecific antibody platform to create SNIPERs(tm), which increase the specificity of targeted cells by requiring two different targets to be present.
  • We are developing a SNIPER that retains or increases the efficacy of the standard of care, but avoids peripheral nerve
    binding and therefore reduces pain

3:45 pm A Bispecific Antibody Targeting CD40 For Optimized Synthetic Peptide Delivery To Antigen-Presenting Cells

  • Sara Mangsbo Associate senior lecturer, and Co-founder , Uppsala University, Strike pharma AB

Synopsis

  • Antibody-drug conjugates (ADCs) targeting CD40 have shown to enable delivery of tumor antigens in the form of peptides or proteins to dendritic cells and thereby improve antigen presentation
  • This talk will feature an opportunity to use bispecific antibodies and a high-affinity interaction between the peptide and the entibody, to deliver peptide therapeutics to dendritic cells via CD40
  • Data presented on the resulting in vitro and in vivo immune activation (dendritic cell/Tcell activation) but also how the bispecific delivery entity improves the pharmacokinetic properties of the peptide drug part

4:15 pm Small Molecule Bispecifics For Targeted Protein Degradation

  • Ryan Potts Executive Director & Head of IPP , Amgen

Synopsis

  • Induced Proximity Medicines are an emerging new drug modality to expand the solution space for difficult to drug therapeutic targets
  • Targeted Protein Degradation approaches including PROTACs and molecular GLUEs have tremendous potential to change the landscape for drug discovery
  • Here, I will explore the use of induced proximity medicines for targeted degradation of proteins where traditional inhibition has been difficult

EXPLORING THE USE OF IMMUNOCYTOKINES FOR ONCOLOGY INDICATIONS

4:45 pm BiCKI: An Optimized Anti-PD1 Bispecific Platform In Particular For Immunocytokine Such As With IL-7.

Synopsis

  • The BiCKI monovalent anti-PD1 platform has been optimized for manufacturing and pharmacokinetics of innovative bispecific fusion proteins
  • Key roles of the valency and affinity of fused cytokines
  • Significant preclinical efficacy of anti-PD1/IL-7 bispecific in syngeneic immunocompetent or humanized mice models

5:15 pm Xencor’s Pipeline Of Novel Cytokine Fc-Fusions Engineered For Improved Exposure, Selectivity, And Tolerability

Synopsis

  • We have created a pipeline of engineered cytokine Fc-fusions built using a bispecific (heterodimeric) Fc domain backbone
  • Cytokine Fc-fusions for IL-15, IL-2, and IL-12 have been engineered for optimal PK and PD using our potency reduction and Xtend™ technology
  • Candidate molecules have significantly improved exposure, selectivity, and tolerability compared to native cytokines or native cytokine Fc-fusions

5:45 pm A Bispecific Antibody Agonist Of The IL-2 Heterodimeric Receptor Promotes In Vivo Expansion Of CD8 And NK Cells

Synopsis

  • Development and activity of bispecific antibodies that simultaneously bind and activate IL-2Rβγ.
  • Bispecific IL-2Rβγ antibodies avoid IL-2Rα and toxicities associated with the trimeric receptor.
  • IL-2Rβγ agonist antibodies expand T and NK effector cells both in vitro and in vivo and avoid preferential expansion of Tregs.

 

 

6:15 pm Chair’s Closing Remarks

6:30 pm End of Conference