Please Note: Times Are Listed As ET
8:00 am Pre-Conference Virtual Networking
8:40 am Chair’s Opening Remarks
Reviewing the State of Play of Complement-Targeted Therapeutics
8:50 am SWOT Analysis Panel Discussion Topics to be Addressed
Synopsis
- Where are we now with complement-based therapeutics?
- What are the untapped clinical areas where complement-based therapeutics have not yet been investigated or reached their potential?
- What is the therapeutic and commercial opportunity of shifting the market focus from rare to mainstream diseases?
- Where is the greatest unmet patient clinical need that can be addressed by emerging complement-targeted therapies?
- How have competing drug modalities reached late-stage clinical testing, particularly in the mainstream disease setting, and how must be done so that complement-targeted therapies can achieve the benchmarks set by standards of care in mainstream disease settings?
9:20 am Overcoming Challenges for Accurate Real World Complement Analysis
Synopsis
- Complement analytes are unstable
- Current best practice for complement sample management is based on healthy normal donor samples – patient samples are different
- Reliable testing is possible by tightly controlling or eliminating the clinical sample workflow from draw to analysis
Leveraging Complement Biomarkers to Evaluate Disease, Predict and Monitor Treatment Response
9:30 am A Precision Medicine Approach to Classical Complement Mediated Diseases: Identifying the Right Patients to Achieve Better Outcomes
Synopsis
- Autoimmune diseases are clinically and biologically heterogeneous; in certain diseases complement drives pathology in the whole population
while in others a subset of patients have complement-mediated disease - Complement proteins and activation products, especially upstream components of the classical cascade, can be leveraged as patient selection biomarkers
- Normalization of complement activity is associated with reduced disease activity and can serve as a monitoring tool that is linked to treatment response
10:00 am Update on the Machaon Study of 1,000 Patients’ aHUS Genetics, Clinical Outcomes, Clinical Presentation and Laboratory Results in the US (MAC Plus Study)
Synopsis
- Physicians have ordered >2000 aHUS/TMA genetic tests for their patients
- We have initiated a retrospective study to further characterize this cohort and publish the clinical and genetic data together
- Who is ordering this test and why?
- Additionally, soluble C5b-9 is emerging as a marker of complement involvement
10:30 am Virtual Speed Networking & Break
Stream A – Revealing Complement Biology to Facilitate Discovery of Novel Targets
Chair: Scott Rottinghaus, VP Clinical Development Hematology/Nephrology, Alexion
Chair: Scott Rottinghaus, VP Clinical Development Hematology/Nephrology, Alexion
Investigating the Intricacies of Complement Signaling to Identify Novel Targets in Neurodegenerative Diseases
11:30 am Complement in Neurological Diseases: Roles in Pathology and Target for Therapy
Synopsis
- Complement contributes to pathology in diverse brain diseases
- Terminal pathway likely a critical contributor to damage
- Strong case for testing brain penetrant anticomplement drugs in brain diseases
12:00 pm Complement-Mediated Synapse Loss: A Viable Therapeutic Target in Multiple Sclerosis
Synopsis
- Synapse loss can occur early and as an independent pathology in multiple sclerosis (MS)
- Synapse loss occurs as a consequence of complement C3 deposition at synapses and microglial synapse engulfment
- Targeting C3 at synapses is a promising therapeutic target to preserve synapse structure and circuit function in MS
12:30 pm Complement in the Central Nervous System During Normal Development and Diseases
Synopsis
- Complement components are locally produced in the brain by various cell types with spatial heterogeneity
- The expression pattern of the complement system is developmentally regulated
- The complement pathway affects neuronal development and its overactivation can induce Schizophrenia-like symptoms in a mouse model
Stream B – Advancing Complement Inhibitors into the Clinic
Chair: Michael Storek, Head of Complement Cluster, Sanofi
Chair: Michael Storek, Head of Complement Cluster, Sanofi
Insights & Learnings from Clinical Trials Investigating Complement Inhibitors
11:30 am Roles of Systemic vs Local Complement Activation in Macular Degeneration
Synopsis
- Implications for clinical trials
- Further details to be announced
12:00 pm Genetic Technology Applications in Complement Therapy Development
12:30 pm Supplementing Complement Factor I as a Therapeutic Strategy in Age-Related Macular Degeneration
1:00 pm Lunch Networking Break
Exploring Complement Targets in the Cancer Setting
2:00 pm Complement Targeting Therapies: A Promising Approach for the control of Graft-versus-host Disease and Tumor Relapse
Synopsis
- Alternative Complement Pathway contributes to Graft-versus-host Disease (GVHD) but not graft-versusleukemia (GVL) function
- Site-specific Targeting complement activation is critically to control GVHD and tumor relapse after allogeneic bone marrow transplant
- Complement regulate GVHD and GVL effect via regulating immune cell metabolism
2:30 pm Complement Factor H as a Novel Drug Target for Cancer
Synopsis
- CFH is a novel tumor specific target
- Human-derived antibodies against CFH cause complement activation and tumor specific cytotoxicity
- Complement activation by the CFH Ab promotes an adaptive immune response
Under Appreciated Areas of Complement Crosstalk & Interface with Innate Immunity & Other Systems
3:00 pm More Complement Crosstalk: The Ins and Outs of Sublytic MAC
Industry Developments of Complement Inhibition in the Neurodegenerative Disease Setting
2:00 pm Classical Pathway Activation in Neurodegenerative Disease
Synopsis
- Activated glial cells express classical complement pathway components during neuroinflammation
- C1Q or C3 knockout provide similar protection against neurodegeneration in Alzheimer’s disease and frontotemporal dementia mouse models
- Elevated levels and increased activation of the classical pathway is found in the central nervous system of neurodegeneration patients
2:30 pm Complement C5 Inhibition in Immune- Mediated Necrotizing Myopathy (IMNM)
Synopsis
- IMNM is a disease with high complement levels in muscle
- Non-clinical data supporting pathogenic role of complement in IMNM
- Proof of concept trial results will be shared
3:00 pm Terminal Pathway Inhibitors for Neurodegenerative Disorders
Synopsis
- Terminal pathway inhibition facilitates regeneration
- CP010, a humanized C6 antibody, is an effective C6 blocker in vivo
- Systemic administration of CP010 prevents relapse in experimental autoimmune encephalomyelitis
3:30 pm Afternoon Networking Break
Understanding How Engineered Nanoparticles Can Activate the Complement System & Inform Drug Delivery
4:00 pm Use of Complement Inhibitors to Block Opsonization and Immune Uptake of Nanoparticles
Synopsis
- Nanoparticles including those used for drug delivery and therapy and imaging activate complement
- Complement activation leads to immune uptake in blood
- Use of soluble complement regulators can effectively block the uptake
Considering How to Use Complement Inhibitors as Part of Novel Combination Strategies to Improve Patient Outcomes
4:00 pm Validating Robust Combination Strategies Within the Context of the Patient Continuum of Care
Synopsis
- When is the right time to use a complement inhibitor?
- Given that the complement system is a multifactorial system, should we be exploring multi-points of intervention?
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.
Complement Pathophysiology – Targeting C5a Receptor
Roundtable Leader:
Roundtable Leader:
Complement Biomarkers, the Utility of Complement Assays & Evaluating the Best Methods to Accurately Quantify Complement Activation
Roundtable Leader:
Roundtable Leader: