8:00 am Preconference Virtual Networking
8:55 am Chair’s Opening Remarks
9:00 am Setting the Scene: An analysis of the Challenges Facing Dry AMD Therapeutics Developers and patients
Panel Discussion: Defining the Therapeutic Journey for Dry AMD Patients
9:15 am Topics to be discussed:
Synopsis
• Understanding the continuum of care for preventing, slowing, or reversing dry AMD at various stages of
the disease – where do pharmacological, cell therapies, gene therapy approaches, light therapies and
vision prosthesis play a role in the patient’s therapeutic journey?
• Discussing the potential for sequential or combination regimens depending on stage of disease
• Providing a potential therapeutic journey framework for dry AMD patient populations from early stages,
through to advanced cases with GA secondary to dry AMD or wet AMD
10:00 am Preclinical Models for Drug Discovery in Dry AMD
Synopsis
- How to choose a preclinical model for proof-of-concept and pharmacologic efficacy studies in dry AMD?
- What imaging modalities are available to monitor dry AMD pathology in preclinical models?
- What can structure-function relationships in preclinical models for dry AMD tell us?
Applying Cell Therapy Approaches to Replace RPE Cells and Restore Vision
10:30 am Virtual Speed Networking & Break
11:00 am OpRegen, an RPE Transplant for the Treatment of Dry AMD
11:20 am Development of a Composite RPE Cell-Ultrathin Membrane Implant for the Treatment of the Dry Form of Age-Related Macular Degeneration
Synopsis
• Development of a bioengineered implant as a tissue replacement
therapy for geographic atrophy
• Selection and development of materials and manufacturing method for
the implant
• Delivery and clinical evaluation of the implant
11:40 am Adult RPE Stem Cell Transplantation as Therapy for dry AMD
Synopsis
• Adult RPE stem cells (RPESC) can be expanded extensively
• Poised to produce native RPE with stable phenotype
• Progenitor stage RPE progeny enhance engraftment and vision rescue
12:00 pm Live Presenter Q&A
Targeting the Complement & Inflammasome Systems in Dry AMD Effectively and Safely
12:15 pm Virtual Networking Break
1:00 pm Neuroprotection in Geographic Atrophy
Synopsis
• There are different types of GA
• Pseudoreticular drusen patient has extensive photoreceptor loss before
RPE loss
• Complement activation might be less important in Oriental races
• Potential keep photoreceptors from dying is the most important goal
1:20 pm Analysis of Complement in of Donor/Post-Mortem Eyes with and Without Age-Related Macular Degeneration (Amd), Implications for Future Intermediate Amd or Geographic Atrophy (Ga) Clinical Trials
Synopsis
• The majority of complement components in both healthy and AMD
donor eyes are in the Retinal pigment epithelium-choroid ( ≥ 10 fold
more than in the retina)
• Complement gene expression is upregulated in atrophic AMD retina,
Iba1 +ve microglia cells are the primary cellular source of complement
• Systemic complement inhibition should be considered for future
intermediate AMD or GA clinical trials
1:40 pm Live Presenter Q&A
1:50 pm Advancing the Targeted C3 Therapy, Pegcetacoplan, for the Treatment of Geographic Atrophy
Synopsis
• Pegcetacoplan targets the complement cascade at C3 to control and
slow the irreversible lesion growth in geographic atrophy (GA)
• Phase 2 study results showed that monthly treatment with
pegcetacoplan resulted in a 29% (p=0.008) reduction in the rate of
GA lesion growth compared to sham injections at 12 months with an
acceptable safety and tolerability profile
• Pegcetacoplan is being studied in two large, randomized global Phase 3
clinical studies
2:10 pm Zimura, Novel Complement C5 Inhibitor, Significantly Reduces the Mean Rate of Geographic Atrophy Growth in a Phase 3 Clinical Trial
Synopsis
• Robust independent imaging and prespecified statistical analysis plan
• Primary efficacy endpoint was achieved for both Zimura 2 mg and Zimura
4 mg dose, leading to a ~27% reduction in GA growth over 12 months
• Reduction in GA growth observed already at 6 months
• Increase in Absolute Difference up to 18 Months
• Sham arm performed as expected
• Both Zimura 2 mg and 4 mg were well tolerated over 18 months
• No Zimura related AE
• No endophthalmitis
• Lower rate of CNV
2:30 pm Re-imagining complement-based therapies for AMD
Synopsis
• Complement inhibition as a means of halting the progression of
geographic atrophy
• Possible Reasons for Failures and Success of Complement Based
Therapies
• Interaction of two key AMD risk factors: complement factor H and
lipoproteins
2:50 pm Live Presenter Q&A
3:05 pm Virtual Networking Break
3:40 pm Elamipretide, a Mitochondrial-Targeted Drug, in the Treatment of Dry AMD
Synopsis
- Elamipretide preclinical data showed reversal of AMD pathophysiology & improvement of vision
- A phase 1 open label safety study of elamipretide in patients with dry AMD showed improvements in multiple measures of vision
- A phase 2, randomized, double-masked, placebo-controlled clinical study of elamipreide in patients with dry AMD is on-going.
Assessing Biomarkers, Functional Outcomes & Clinically Relevant Endpoints in Dry AMD
4:00 pm Patient Selection and Monitoring for Efficacy in Dry AMD trials
Synopsis
- Use of multimodal imaging to identify patients at high-risk for
progression - New biomarkers of AMD progression
- Design of precision endpoints, tailored to specific therapeutics
4:20 pm Current Efforts to Evaluate Functional Visual Impairment and Clinically Relevant Endpoint Candidates for Intermediate Dry AMD
Synopsis
• Defining functional impairment in early and intermediate AMD in a
longitudinal prospective natural history studies
• An industry perspective on the MACUSTAR initiative – an European
Innovative Medicine Initiative (IMI2) to evaluate and validate clinical
endpoints for intermediate AMD
4:40 pm Establishing Correlations Between Functional outcomes, Imaging- and Blood-Based Biomarkers in Nonexudative AMD: Lessons Learned and Regulatory Implications
Synopsis
- Structure-function correlations in national history studies of early and intermediate AMD and learnings from other retinal degenerative diseases
- Blood-based biomarkers of disease progression (genetics, flow cytometry of monocytes, other)
- Deep learning algorithms to predict progression to geographic atrophy and visual loss on retinal imaging
5:00 pm Imaging in Dry Age-related Macular Degeneration
Synopsis
• New imaging modalities can provide information about retinal structure
and function in patients with dry AMD
• Structural measures correlate with measures of visual function
• Imaging retinal structure and function can be used to monitor disease
progression and response to therapy for patients with dry AMD
5:20 pm Clinical Implementation of an Ultrathin Stem-Cell Derived RPE Monolayer in Phase 1/2a Clinical Trial for Treatment of Advanced Dry AMD with Geographic Atrophy
Synopsis
• Review of clinical study design
• Review of methods for surgical delivery of ultrathin implant in subretinal
space and within area of GA
• Review of surgical results and preliminary study results