7:00 am Registration & Morning Coffee
7:40 am Chair’s Opening Remarks
Discovering the Next Generation of Biomarkers for Effective Translation of Preclinical Dry AMD Models to the Clinic
7:50 am
Translation to the Clinic: Role of Preclinical Models & Biomarkers to Optimize Dry AMD Clinical Trials
Remote
Synopsis
- Translatability and considerations of preclinical models for dry AMD
- Lessons learned from the clinic – how can we maximally de-risk preclinical assets prior to initiation of clinical trials?
- Role of molecular and imaging biomarkers for early POC clinical trials
8:20 am Reviewing the Key Lessons Learned from Phase 2 GA Trials
Synopsis
- Review of lessons learned from our IVT complement Factor P inhibitor GA Phase 2 trial
- Data on how geographic atrophy is measured – the importance of patient level data vs summed data
- Fundus autofluorescence measure vs OCT measurements – functional outcomes including chart-based tests vs microperimetry
8:50 am Identification of DKK3 as an Ocular Pharmacodynamic Biomarker for Anti-HtrA1 in a Clinical Trial for Geographic Atrophy Secondary to Agerelated Macular Degeneration
Synopsis
- Identification of HtrA1 substrates enabled the development of a clinical PD biomarker for evaluating anti-HtrA1 Fab activity
- Enzyme activity–based PD assay (reduction in cleaved-DKK3 fragments) suggests potential for 8-week target inhibition at higher doses
- Analysis of cleaved DKK3 in patient aqueous humor provided evidence of anti-HtrA1 activity and information on duration of activity in phase 1
9:20 am Dry AMD Therapeutics, iPSC to the Rescue
Synopsis
- Patient-derived RPE cells and unique phenotypic assays
- Linking genetics to RPE cells response to AMD stress
- High-throughput platform to screen new neuroprotective agents with no a
priori on targets
9:30 am How Vision is Impaired from Aging to Intermediate AMD: Insights from ALSTAR2 Baseline
Synopsis
- Structure/function endpoints for AMD should be motivated by the pathobiology of the disease. RMDA has a strong history in outer retina neurophysiology and psychophysics
- Using z-scores to standardize vision measures – greatest difference between visual function in normal and intermediate AMD eyes
- Delayed rod-mediated dark adaptation in normal eyes doubles the risk for incident AMD
10:00 am A Complement Alternative Pathway Inhibitor Delivered by Gene Therapy in Mouse Models of Age-Related Macular Degeneration
Synopsis
- Discover how the eye generates its own complement
microenvironment, which is composed of RPE/choroid-derived
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?
10:30 am Data Solutions for Imaging Biomarker Discovery and Clinical Endpoint Validation
Synopsis
- Meaningful prognostic biomarkers and clinical outcome measures are essential
to the development of treatments for degenerative retinal disease - Biomarkers and endpoints are not born, they are discovered and validated
- Clinical standards of care are often insufficient, and must be supported with
emerging imaging modalities and analyses - TII integrates clinical and research data, data flow automations, and advanced
analytics to accelerate the discovery and validation of biomarkers and endpoints
11:00 am Round-Table Discussion: Discussing Regulatory Challenges Across Different Stages of Dry AMD Therapeutics Development
Synopsis
Some of the biggest challenges when developing drug for dry AMD is understanding the regulatory landscape for all stages of drug development. This session facilitates discussions on a range of regulatory checkpoints including:
- Pre-IND
- Endpoint Designation
- Recruiting & Phase I
- Phase II & Phase III
11:30 am Morning Break
Reviewing Therapeutic Modalities for Dry AMD & Geographic Atrophy to Fully Gauge the Treatment Landscape
12:00 pm Phase 2 Trial of ALK-001 in Stargardt Disease and Treatment Indications for Dry AMD/GA
Synopsis
- ALK-001 is a first in class inhibitor of vitamin A dimerization
- Results of a randomized, placebo-controlled, clinical trial indicates that
- ALK-001 has disease modifying ability on the progression of Stargardt Disease
- ALK-001 is also being tested in Geographic Atrophy associated with dry-AMD in a fully enrolled Phase 3 study.
12:30 pm IONIS-FB-LRx, an Investigational Antisense Oligonucleotide to Treat AMD Associated Geographic Atrophy
Synopsis
- Developing a non-invasive therapeutic option with novel mechanism of action
targeting complement Factor B (FB) - Preclinical and clinical data demonstrating reduction in systemic FB and
excellent safety profile - Phase 2 clinical trial (GOLDEN) baseline study characteristics
1:00 pm A Modifier Gene Therapy Approach for Treatment of Dry-AMD
Synopsis
- Dry-AMD disease pathophysiology and risk factors
- Modifier gene therapy, an innovative therapeutic approach for treatment of complex multifactorial diseases
- In vitro and In vivo preclinical studies demonstrating potential of OCU410 gene therapy for dry-AMD
1:30 pm Lunch Break
2:30 pm Small molecule-driven endogenous regeneration of RPE cells: a novel approach to treating Geographic Atrophy
Synopsis
- The therapeutic concept: inducing endogenous regeneration
- In vitro GA models for testing the regenerative effect of potential therapeutics
- In vivo POC: lessons learned from different animal models
3:00 pm Exploring a Novel Approach Using a Glyco-Immune Therapy Targeting Both Complement and Macrophages
Synopsis
- A discussion of how macrophages/microglia are involved in the pathobiology of AMD
- What are Siglecs and self-associated molecular patterns and how do they modulate immune responses?
- A novel glyco-engineered nanoparticle that inhibits over-activation of complement and macrophages
3:30 pm ReCLAIM-2: Phase 2 Trial of Subcutaneous Elamipretide in Patients with Noncentral Geographic Atrophy
Synopsis
- Elamipretide is a first in class mitochondrial restorative compound
- Review results of phase 2 trial demonstrating positive secondary endpoints and possible path to phase 3 enrichment
- Cover ellipsoid zone endpoint and how it relates to mitochondrial health
4:00 pm Afternoon Break
4:30 pm Targeting the Sigma-2 Receptor (S2R) for Dry AMD with an Oral Small Molecule Approach: Preclinical & Clinical Biomarker Support
Synopsis
- Background on target and rationale for dry AMD
- Preclinical data support a unique mechanism of action to restore RPE homeostatic function
- Proteomic biomarker evidence that the S2R modulator CT1812 can alter dry AMD relevant protein and pathways in an aged population
Understanding the Patient Perception in the Clinic & Appropriate Delivery Modalities to Better Understand Clinical Processes
5:00 pm
Hearing Patient Reception of Long Term & Invasive Treatments for Dry AMD to Understand Patient Experience
Remote
Synopsis
- Viewing patient testimonies to understand key desires and thoughts of the recipients
- What is the patient reception of current clinical trials?
- How can the industry meet the needs of their patients?
5:30 pm Routine Suprachoroidal Drug Administration: the Role in Intermediate AMD/GA Therapies
Synopsis
- Choroidal administration of therapies in intermediate AMD/GA
- Novel principle of targeted routine drug suprachoroidal administration
- Case studies: Use of the suprachoroidal Oxulumis® illuminated microcatheter in back-of-the-eye disorders