*All times Eastern Daylight Time*

DEVELOPING A ROBUST BISPECIFIC PLATFORM

7:45 am Opening Remarks

  • Carston Wegner Professor of Medicinal Chemistry , University of Minnesota

7:55 am Review Of The Clinical Development Landscape For Bispecifics

Synopsis

  • What are the emerging bispecific platforms and approaches which are being developed today?
  • How has innovative designs, novel formats enabled investigational bispecifics to address the unmet clinical need?
  • Contrasting bispecific development in solid tumor and hematological indications
  • Evaluating the bispecific clinical landscape
  • Learning from successful and failed bispecific biologics

8:20 am Enhancing Quality By Design For Bispecific Molecules

  • Regis Cebe Principal Scientist II, Novartis Biologic Center, NIBR Novartis Pharma AG

Synopsis

  • Description of a robust IgG like bispecific discovery platform
  • Investigating format diversity based on biological needs
  • Improving developability to complement manufacturing
  • Enhancing effector functions with a mosaic IgG/A approach

8:50 am Mechanistic Strategies for Modeling Avidity: Application in the Design of Tumor Selective Bispecific Antibodies in Oncology

  • Alison Betts Vice President of Scientific Collaborations and Fellow of Modeling & Simulation , Applied Biomath

Synopsis

  • Definition of avidity and why it is important in the design of tumor-selective bispecific antibodies
  • Use of modeling to help understand avidity, including interpreting dose titration curves and optimizing single-site binding affinities
  • Extrapolating avidity from in vitro to in vivo conditions
  • Case study examples: optimizing design of a 2+1 tumor-selective T cell engager bispecific antibody for binding selectivity to tumor cells.

9:20 am Combining Building Blocks To Bispecifics

  • Eva Hansbauer Associate Director of Protein Analytics , Pieris Pharmaceuticals

Synopsis

  • Analyzing single building blocks in order to select the best ones
  • Combination of antibodies and anticalin® proteins to bispecific
  • Preclinical characterization of bispecifics

9:50 am Networking Break

10:25 am Panel Discussion: Strategies To Improve The Developability Of Novel Bispecific Antibodies

Synopsis

  • Format analysis to improve developability
  • Investigating which cell line platforms are best
  • Bioassays and other tools for characterisation
  • How to improve biophysical properties of a bispecific antibody scaffold to aid developability
  • Supply reliable antibody molecules for fundamental research, and potentially deliver safer drugs treating different diseases.

10:40 am Addressing the Complexity of Manufactuiring Biologics from Early Stage to Commercial

10:50 am Networking break

Enhancing Bispecific Product Design and Early Development

11:30 am BEAT 2.0: A Robust Platform Technology To Engineer Optimized Bispecific And Trispecific Antibodies

Synopsis

  • Bispecific and trispecific antibodies engineered in the natural antibody format based on common light chain Fabs.
  • Multimodal platform that allows the design of T-cell engagers, NK engagers and Macrophage modulators
  • Optimized designs with favorable developability profiles.

12:00 pm Next Generation Engineering Approaches For Bispecific T Cell Engager (Bite®) Molecules

Synopsis

  • Bispecific T cell engager (BiTE®) molecules have demonstrated clinical benefit in hematological malignancies and there is growing evidence of activity in solid tumors
  • This presentation will highlight key findings from recent trials along with observations from nonclinical studies that inform on BiTE® molecule mechanism of action and new engineering approaches to address clinically observed challenges

Late-Stage Development And Scale Up For Clinical Application / Platforms Driving Efficacy In Solid Tumours

11:30 am ReSTORE T Cell Engagers: Maintaining Immune Activation and Controlling CRS via Depletion of MDSC

Synopsis

  • AMV564, a bivalent T cell engager that targets MDSC, has shown monotherapy activity in solid tumor patients with limited evidence CRS
  • Consistent with these clinical findings, the cytokine profile in patients treated with AMV564 shows strong induction of IFNγ and cytokines and chemokines driving T cell trafficking and activation, with limited IL6
  • ReSTORE pipeline molecules provide additional specificity for tumor targets to address non-immunogenic solid tumors

12:00 pm Tumor Micro-Environment Features Associated With Response To Tebentafusp, A Gp100-Targeted T Cell Receptor-CD3 Bispecific

Synopsis

  • T cell receptor-CD3 bispecifics are a new class of therapeutics that can re-direct any T cell to kill tumor cells that present specific peptide-HLA complexes
  • Tebentafusp, a gp100-directed T cell receptor-CD3 bispecific, has demonstrated survival benefit in uveal melanoma
  • Using tebentafusp as a case study, I will describe how understanding the tumor micro-environment can inform development of TCR-CD3 bispecifics

1:00 pm Networking Lunch

1:30 pm Bioanalytical Strategies for Bispecific Antibodies During Clinical Development

Synopsis

  • Showcasing the development of the next generation of therapeutic proteins such as Bi specific antibodies
  • Discussing their pharmacokinetic and pharmacodynamic properties, including their immunogenic potential, that is closely related to their unique structural features and ability to interact simultaneously with two different targets
  • Overview of the bioanalytical strategies, challenges, and solutions of PK and Immunogenicity assays used for clinical development of Bispecific antibody therapeutics

Enhancing Bispecific Product Design and Early Development

2:00 pm Bispecific T Cell Engagers: Biomarkers of Synthetic Immunity for Cancer Immunotherapy

Synopsis

  • Biomarkers of TCE activity and toxicity
  • Dose/schedule selection
  • Determinants of T cell fitness

2:30 pm Translational Biomarker Strategies Supporting Clinical Stage Bi-specific DART® Molecules

  • Paul Moore VP Immunology & Cell Biology , MacroGenics

Synopsis

  • Various pharmacodynamic and biomarker based approaches to characterize the biological activity of DART molecules administered to patients will be discussed in the context of programs designed for either redirected T-cell killing (eg flotetuzumab) or dual checkpoint blockade (eg tebotelimab)
  • Methods to confirm target engagement and desired biological mechanism of action
  • Correlations of baseline biomarkers with clinical response
  • Leveraging learnings to guide future clinical development paths

3:00 pm Immunogenicity Assessment for Multi-Functional Biotherapeutics

  • Yanchen Zhou Sr. Scientist, Clinical Immunology, Translational Medicine , Amgen, Inc.

Synopsis

• Immunogenicity risk assessment
• Clinical monitoring strategies
• Case examples

1:30 pm Novel Bispecific EGFR/Met Antibody To Combat Resistance To EGFR Inhibition

Synopsis

  • Selection of the bispecific Ab from a panel of parental EGFR and cMet mAbs
  • Description of the epitopes of the lead EGFR and cMet binding arms
  • Bispecific Ab design to control inhibition of receptor-ligand interactions, receptor phosphorylation inhibition, and ADCC

Late-Stage Development And Scale Up For Clinical Application / Platforms Driving Efficacy In Solid Tumours

2:00 pm Use Of ADAPTIRTM And ADAPTIR-FLEX Platformtm Technologies To Generate Immuno-Modulatory Bispecific Therapeutic Candidates For The Treatment Of Hematologic And Solid Tumors

  • Jane Gross Chief Scientific Officer , Aptevo Therapeutics

Synopsis

  • Advantages of the ADAPTIR and ADAPTIR-FLEX bispecific and multi-specific platform technologies will be provided
  • Advances made in the development of APVO436, a CD3-based T-cell engager targeting CD3 and CD123 will be reviewed
  • Utility of the ADAPTIR-FLEX platform technology in the development of APVO442, a novel bispecific targeting CD3 with low-affinity and PSMA with high avidity will be provided

2:30 pm IGM-2323 Is A High Avidity Igm-Based CD20xCD3 Bispecific Antibody For Enhanced T-Cell Dependent Killing With Minimal Cytokine Release

Synopsis

  • Current bispecific antibodies are largely based on IgG-like scaffolds and though some early success has been seen in the clinic, adverse events related to cytokine release remain a major concern
  • IGM-2323 is an IgM-based bispecific that uses an anti-CD20 IgM to provide high avidity binding to CD20, an scFv fused to the N-terminus of J-chain to provide monovalent engagement of CD3 on T-cells, and human serum albumin (HSA) fused to the C-terminus of J-chain to improve pharmacokinetics
  • Our preclinical data demonstrate IGM-2323 is highly effective at complement dependent cytotoxicity and T-cell dependent cellular cytotoxicity killing of tumor cells with minimal cytokine release and is currently in a Phase I clinical trial in Non-Hodgkin’s Lymphoma

3:00 pm Program Partner Presentation from Asimov

3:30 pm Panel discussion: Reducing The Risk Of Immunogenicity For Bispecifics

  • Regis Cebe Principal Scientist II, Novartis Biologic Center, NIBR Novartis Pharma AG
  • Jane Gross Chief Scientific Officer , Aptevo Therapeutics
  • Tatiana Novobrantseva Chief Scientific Officer , Verseau Therapeutics
  • Samuel Pine Head of Bioanalysis & Immunogenicity , Ablynx
  • Darshana Jani Director, Global Bioanalysis, Agenus inc

Synopsis

• Detecting Immunogenicity including assays and next-generation methodologies to test this
• Go/ no go criteria for immunogenicity assessments
• Strategies to reduce immunogenicity risk
• How can we predict immunogenicity (In silico vs In vitro testing)?
• Which drugs failed due to immunogenicity and lessons

4:10 pm Networking Break

Bispecifics Beyond Oncology Applications

4:40 pm Tissue Localized Inhibition of Complement Activation

  • Kelly Fahnoe Associate Director – Protein Science , Q32 Bio

Synopsis

  • Delivery of targeted bispecific fusion proteins are intended to drive a high local concentration of complement inhibitors in the tissue while reducing systemic complement blockade
  • Bispecific fusion proteins were designed, expressed, and characterized in vitro to show modulation of complement activation over a broad potency range.
  • In vivo studies in rodent preclinical models demonstrate targeting-dependent distribution and durable inhibition of complement activation in disease tissues
  • These data demonstrate the potential to address autoimmune and inflammatory diseases that are driven by dysregulation of complement

5:10 pm Bispecific antibodies for infectious and metabolic diseases

Synopsis

  • Safety and efficacy of T cell engagers in preclinical models of Chronic Hepatitis B
  • Preclinical efficacy of a biepitopic antibody against CD38 for the treatment of metabolic disorders

5:40 pm End of Tracked Session

Mitigating Against On-Target Off-Tumor Toxicities

4:40 pm A Biological Rationale For Toxicity Mitigation With CD3 Bispecifics

  • Teemu Junttila Principal Scientist - Translational Oncology Genentech, Genentech

Synopsis

  • I will discuss the relationship of cytokine release and activity of CD3 bispecific
  • We have further characterized the cellular and molecular mechanism of CD3 bispecific-induced cytokine release
  • Optimal mitigation strategies for CRS

5:10 pm An Industry Perspective on CD3 Bispecifics Starting Doses & Efficacious Dose Projections

Synopsis

  • Strategies for selection of starting doses to balance patient safety and minimize patient’s exposure to subtherapeutic doses
  • Approaches for predicting efficacious doses
  • Challenges and opportunities for defining optimal biological doses for CD3 bispecifics

5:40 pm Overcoming On-Target Off-Tumor Toxicities of Bispecifics

  • Anthony Stein Director, Leukemia Program Codirector , Gehr Family Center for Leukemia Research, City of Hope

Synopsis

  • Etiology of CRS: Discuss causes of cytokine release syndrome and review current grading system
  • Preventative Measures: Discuss methods to try and reduce severity of CR
  •  Treatment of CRS: Discuss current treatment options of CRS

6:10 pm Closing Remarks

6:20 pm End of Day One