7:30 am Registration & Morning Coffee

8:30 am Chair’s Opening Remarks

State of Play of the Complement-Targeted Drug Development Field

8:40 am Complement Industry Leaders’ Chat – 2021/22 in Review & Looking Ahead

Synopsis

This panel will discuss the key breakthroughs that have happened this year, the key challenges that have been overcome and where the biggest excitement remains:

  • How do you perceive the complement drug development space? How has this changed in the past 12 months?
  • What is missing from complement drug discovery and translation into the clinic?
  • What are the gaps that both investors and drug developers must see, that we need to bring from other areas of biotech R&D?
  • How are complement-targeted therapeutics going to compete against other drugs in the field?

Leveraging Innovation in Assay Development & Defining Therapeutic Windows of Drugs Across Complement Pathways to Elevate Drug Design

9:10 am Overcoming Challenges for Accurate Real World Complement Analysis

Synopsis

  • Review why complement analytes are unstable
  • Current best practice for complement sample management is based on healthy normal donor samples – patient samples are different
  • Understand how reliable testing is possible by tightly controlling or eliminating the clinical sample workflow from draw to analysis

9:20 am Complement Inhibitory Drugs: Dose Selection & Schedule for Different Indications Based Upon Disease Mechanism, Pharmacokinetics & Pharmacodynamics

Synopsis

  • Assess how magnitude and clinical impact of complement activation in different diseases may differ significantly
  • The optimal doses and schedules of administration of the same drug in different diseases may differ substantially
  • Examine how the determination of optimal dosing in different diseases depends upon mechanism of complement activation and may be facilitated by pharmacokinetics and pharmacodynamics

9:50 am Panel Discussion: Defining the Therapeutic Windows of Drugs to Ensure Patient Safety Whilst Maintaining Drug Efficacy

Synopsis

  • Balancing the therapeutic index versus safety in targeting complement
  • Discussing this in the context of disease versus healthy complement inhibition
  • Reviewing the therapeutic window when you target classical, lectin or alternative pathways
  • Discussing pharmacokinetics of targeting complement
  • Specifying inclusion/exclusion criteria put in place specifically due to safety considerations e.g. avoiding comorbidities or infections

10:20 am Importance of Complement Assays in Drug Development

Synopsis

  • Complement is a necessary pathway to monitor in any drug development – not only when the pathway is directly targeted
  • Discuss how functional and quantitative assays are equally important and will provide a more wholesome image of the situation
  • Learn from Svar’s long experience with complement assays with special expertise in functional assay setups

10:30 am Speed Networking & Morning Coffee Break

Track A – Discovery & Preclinical Validation of Emerging Strategies
Chair: Nirmal K. Banda, Professor, School of Medicine. University of Colorado Anschutz Medical Campus

Revealing Complement Dysregulation in Disease to Identify Novel Therapeutic Targets

11:30 am Therapeutic Targeting C5AR1 to Diagnosing & Preventing Early Rheumatoid Arthritis as a New Pathway to Precision Medicine

  • Nirmal K. Banda Professor, University of Colorado Anschutz Medical Campus

Synopsis

  • Recently RNAi therapeutic using siRNAs are almost replacing antibody therapeutics
  • CR5AR1 gene is expressed high, correlated with disease activity score 28 and a valid therapeutic target in Early Rheumatoid Arthritis
  • Highlighting how single targeting of C5-C5AR1 axis is not sufficient but double targeting of C5 and C5AR1 expression with a new conjugate of anti-C5AR1-C5siRNA is effective in reducing arthritis

12:00 pm Complement Inhibitor for the Treatment of Age-related Macular Degeneration: Target, Location of Delivery & Timing?

Synopsis

  • Discover how the eye generates its own complement microenvironment, which is composed of RPE/choroidderived proteins and those delivered by the liver (circulation), and set up in part by differential permeability of Bruch’s Membrane to complement proteins
  • Complement activation appears to occur outside of the Blood Retina Barrier (basal side of RPE, BrM and CC)
  • As the goal is to identify a treatment for dry AMD that can be used early in disease, to prevent conversion from early to intermediate AMD (i.e., in the presence of a presumably intact BRB), how do we deliver the therapeutics accordingly?

12:30 pm In Vitro Neuromuscular Junction Models to Functionally Dissect Anti-AChR Pathogenic Mechanism in Myasthenia Gravis

Synopsis

  • Exploring three mechanisms of neurotransmission impairment by anti-acetylcholine receptor (AChR) autoantibodies in myasthenia gravis, including complement activation, antigenic modulation, and functional blockade
  • In vitro NMJ (neuromuscular junction) models may offer an opportunity to dissect the contribution of pathogenic autoantibodies and may allow a tailored therapeutic strategy
  • Sharing how Zilucoplan, an investigational macrocyclic peptide inhibitor of complement C5, prevented functional impairment induced by AChR+ myasthenia gravis patient sera in an in vitro neuromuscular junction model

Track B – Clinical Development & Commercialization Considerations
Chair: Michael Storek, Head of Complement Cluster, Sanofi

Clinical Update on Complement Therapeutics in the Clinic, Key Learnings & Future Directions

11:30 am RLS-0071: Dual Target Inhibition in Support of Hypoxic Ischemic Encephalopathy

Synopsis

  • RLS-0071 is a novel, dual-targeting peptide with upstream control of inflammatory pathways. Mutually supportive inhibition of complement and cellular inflammatory processes support lead candidate RLS- 0071 development in hypoxic ischemic encephalopathy
  • Discussing the Phase 2 clinical trial in progress assessing safety, pharmacokinetics and pharmacodynamic biomarkers planned in HIE
  • Demonstrating a clean safety profile in Phase 1 human trial with encouraging target engagement data

11:40 am A Phase 1 Study of CAN106: A Novel, Long-Acting, Anti-C5 Monoclonal Antibody in Development for Complement-Mediated Diseases

  • Gerry Cox Interim Chief Medical Officer, Chief Development Strategist, CANbridge Pharmaceuticals

Synopsis

  • Exploring data supporting anti-C5 mechanism of action
  • Sharing Phase 1 single ascending dose clinical trial data in healthy volunteers
  • Progressing into the clinic for paroxysmal nocturnal hemoglobinuria and other complement-mediated diseases

12:10 pm Safety, Efficacy, Pharmacokinetics & Pharmacodynamics of ARGX-117, a Therapeutic Antibody Targeting Complement Factor 2

Synopsis

  • Evaluating how the ARGX-117 antibody has been engineered to have a long half life
  • Demonstrating that administration of ARGX-117 in healthy volunteers is safe and well-tolerated
  • ARGX-117 is being studied in adults with multifocal motor neuropathy in a Phase 2 clinical study

1:00 pm Lunch & Networking Break

2:00 pm Stop the Start: The Effect of Anti-C1q Inhibitors on Neurodegeneration

Synopsis

  • C1q tags membranes for elimination via classical complement activation by microglia or macrophages
  • Anti-C1q inhibitors provide synaptic and neuronal protection in multiple mouse models
  • Annexon has developed fit-for-purpose C1q inhibitors for Ophthalmology and Neurodegeneration that have demonstrated proof of biology

2:30 pm Targeted Inhibition of Intracellular Complement Activation to Control Tissue Injury

  • Abhigyan Satyam Assistant Professor, Harvard Medical School, Harvard University

Synopsis

  • Examining the role of intracellular complement activation in tissue damage
  • Highlighting the development of in-vitro models to study complement activation
  • Optimizing delivery of complement inhibitors to a target organ

3:00 pm Precision Antibody-Based Therapeutics for Complement Regulation

Synopsis

  • Targeting critical components of the complement pathway can impact diseases that are initiated or
    exacerbated by complement dysregulation
  • Antibody based therapeutics can be used to precisely target and potently inhibit complement activation
  • Visterra has developed novel antibodies for targeting complement activation

2:00 pm Treatment of Critically Ill COVID-19 Patients with Vilobelimab, a First-in-Class Anti-C5a Antibody

Synopsis

  • C5a/C5aR axis plays an essential role in COVID-19 pathogenesis
  • C5a-indued neutrophil activation is a driving force in the development of severe COVID-19
  • Understand how Vilobelimab treatment improves survival in critically ill COVID-19 patients

2:30 pm An Update & Analysis of the Macular Degeneration Complement Landscape

  • Stephen Poor Director External Opportunities & Translational Biomarkers, Novartis Institutes for Biomedical Research

Synopsis

  • Assessing the current status of complement therapeutics in clinical development
  • What are the implications of month 24 Phase 3 data from APELLIS and Month 12 Phase 3 data from IVERIC for geographic atrophy treatment ( intravitreal C3 and C5 therapy)?
  • What is the potential of gene therapy and systemic approaches in clinical development vs intravitreal therapies for macular degeneration?

3:00 pm Phase 3 Data in Generalized Myasthenia Gravis

  • Petra Duda Head of Development – Zilucoplan, UCB

Synopsis

  • Exploring complement involvement in myasthenia gravis pathophysiology
  • Outlining the design and conduct of the zilucoplan Phase 3 study in gMG
  • Evaluating phase 3 data of zilucoplan in gMG

3:30 pm Afternoon Networking Break

Breakout Roundtable Discussions

4:30 pm Uncover the story behind leaps and setbacks from the movers and shakers of complement research and drug development. Each roundtable will be hosted by a complement R&D leader who will share a challenge, question or case study to discuss:

1. Complement Biomarkers, the Utility of Complement Assays & Evaluating the Best Methods to Accurately Quantify Complement Activation

2. Overcoming Challenges with Next Generation Complement Drug Development

5:00 pm Chair’s Closing Remarks

5:10 pm End of Conference Day One