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 Structured Speed Networking Break
11:00 am 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
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
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
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
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
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