5th Ocular Diseases & Drug Development
 Register 2, the 3rd goes free with the coupon code rcdvb!
Day 1 Day 2
Day 1 - Thurday, March 21, 2013
7:00 Continental Breakfast & Registration
7:55 Welcome & Opening Remarks
Moderator: Barbara Wirostko, Jade Therapeutics; University of Utah
KEYNOTE PRESENTATION
8:00 A Phase 2b Study of FovistaTM, a Platelet Derived Growth Factor (PDGF) Inhibitor in Combination with a Vascular Endothelial Growth Factor (VEGF) Inhibitor for Neovascular Age-Related Macular Degeneration (AMD)




Samir Patel
President, CEO
Ophthotech

Purpose/Methods: To assess the safety and efficacy of FovistaTM in combination with ranibizumab compared to ranibizumab monotherapy, 449 patients with neovascular AMD were randomized in a prospective, controlled, superiority trial to receive one of the following treatment regimens administered every 4 weeks for 24 weeks: FovistaTM 0.3 mg in combination with ranibizumab 0.5 mg; FovistaTM 1.5 mg in combination with ranibizumab 0.5 mg; or sham in combination with ranibizumab 0.5 mg.

Results: The combination of FovistaTM (1.5 mg) with ranibizumab met the pre-specified primary endpoint of superiority in mean visual acuity gain compared to ranibizumab monotherapy (10.6 ETDRS letters at week 24, compared to 6.5 letters, p=0.019). An additional 62% benefit from baseline was noted in the FovistaTM (1.5 mg) combination therapy arm over ranibizumab monotherapy. A classic dose-response curve was observed. Enhanced visual outcomes for FovistaTM 1.5 mg combination therapy compared to ranibizumab monotherapy were present at every monthly timepoint. The relative magnitude of visual benefit increased over time, implying a benefit to continued combination therapy. The superiority of FovistaTM 1.5 mg combination therapy over ranibizumab monotherapy was consistent across all subgroups including those analyzing baseline vision, lesion size, and central retinal thickness. FovistaTM 1.5 mg combination was superior to ranibizumab monotherapy across multiple treatment endpoints including 3, 4 and 5 lines of vision gain (ETDRS chart). OCT and fluorescein angiography analysis showed patients receiving FovistaTM 1.5 mg combination therapy had greater reduction in neovascular size compared to those receiving ranibizumab monotherapy. No significant safety issues were observed for either treatment group in the trial.
Session: Novel Targets, Developments and Technologies
FEATURED PRESENTATION
8:35 Lipoprotein-associated Phospholipase A2 Inhibition Regulates Retinal Vasopermeability During Experimental Diabetes



Peter Adamson
Vice President and Head of Research, GSK Ophthalmology
GlaxoSmithKline
Diabetic macular edema is recognized to have an inflammation-linked etiology. It is hypothesized that inhibition of lipoprotein-associated phospholipase A2 (Lp-PLA2) is protective against hyperglycemia-related compromise of the blood retinal barrier (BRB). Lp-PLA2 was localized to the vascular endothelium of human retinal capillaries,and in parallel, brown Norwegian rats had diabetes induced and maintained for 4 weeks with treatment using vehicle or SB435495 (a specific inhibitor of Lp-PLA2). A different group of hyperglycemic animals were maintained treatment free for 4 weeks prior to initiating the 4 wk treatment regimen with SB435495. A group of non-diabetic BN rats were used as controls. BRB function was determined by retinal fluorescein angiography, Evan’s blue (EB) leakage and immunohistochemical detection of intravascular and extravasated rat albumin in the retina.

SB435495-treatment during initiation of diabetes resulted in less vascular leak when compared to the vehicle-treated diabetic controls. EB leakage was elevated in the vehicle-treated diabetic group when compared to non-diabetic counterparts. 4 weeks treatment with SB435495 significantly prevented this response after either 4 or 8 weeks of prior diabetes. In vehicle-treated diabetic rats, albumin immunoreactivity was apparent in the retina from both superficial and deep capillary plexi. In SB435495-treated diabetic rats, albumin was co-localized with blood vessels with a pattern similar to non-diabetic controls.

This data indicates that inhibition of Lp-PLA2 in a preclinical model of hyperglycemia induced retinal vascular leak can prevent breakdown of the inner BRB. Lp-PLA2 may thus be a useful target for treatment of DME.

1. Understanding pre-clinical models of hyperglycemia-induced retinal vascular permeability.
2. Treatment for DME
3. Role of inflammation in DME
4. Blood-brain barrier vs Blood-retinal barriers
9:10 Intrinsic Lipid Circuits: Key Regulators of Innate Immunity and Ocular Inflammatory-Reparative Responses
Karsten Gronert, Associate Professor, Ophthalmology, University of California, Berkeley
Inflammation, a frequent and self-resolving response, is essential for protection and integrity of tissues and is intimately linked to wound healing. Healthy execution of inflammatory/reparative responses requires activation of conserved resolution programs. Distinct classes of lipoxygenase (LOX)-derived eicosanoids and their w-3 PUFA homologs establish a tone of anti-inflammatory signals, are early response signals to injury or infection and key regulators of resolution and healing. Our research efforts are focused on elucidating function and regulation of these protective lipid circuits in the eye. We have discovered intrinsic lipid circuits in the cornea and retina that control inflammation, leukocyte function, wound healing and angiogenesis. These protective lipid circuits are regulated by dietary w-3 PUFA that amplify the generation of specific docosahexaenoic acid-derived autacoids. Sex-specific differences in ocular inflammatory/reparative responses and estrogen’s role in ocular diseases are not well understood. Our ongoing work has uncovered that estrogen receptors selectively regulate protective lipid circuits, which correlates with estrogen-driven and sex-specific differences in wound healing and inflammation.

In addition, we recently discovered that eicosanoids are an early and obligatory effector function of inflammasomes, which are critical intracellular sensor for infection/stress and activators of essential cellular innate immune responses. The lecture will present our current understanding of the formation, regulation and mechanism of action of intrinsic lipid circuits and their potential role in the pathogenesis of ocular inflammatory diseases.
9:35 Early Detection of Amblyopia in the Primary Care Setting: A Cost Effective Alternative to Vision Screening
Justin Shaka, Chief Executive Officer, REBIScan
Amblyopia (“lazy eye”) and strabismus (misaligned eyes) are medical eye conditions that combine as the leading causes of preventable monocular vision loss in children, and are major contributors to worldwide blindness. Amblyopia, which effects 5% of the population, is fully treatable if caught early, yet millions of children suffer permanent vision loss every year because of lack of detection.

The failure to detect amblyopia has become a public health catastrophe; however, REBIScan has developed a hand-held device that has shown unprecedented accuracy at detecting disease. Using patented technology based out of Johns Hopkins University and Boston Children’s Hospital, clinical trials have shown the Pediatric Vision Scanner (PVS) to be 98% accurate in children as young as the age of 2. The PVS uses retinal birefringence scanning to analyze the nerve fibers of the fovea, and, in under 3 seconds, provides an objective, binary output.

By supplying this technology into primary care settings, we can catch amblyopia when it starts, and reduce the inefficient spending that goes toward detecting risk factors and false referrals to specialists. The combined cost of amblyopia screening and strabismus surgery in the US is estimated to be $800 million annually, while the cost to society from loss of function is estimated at well over $20 billion. REBIScan’s solution to this problem will give access to a newly developed technology to all children, thereby eliminating vision loss from amblyopia, while introducing a cost-effective payment model.

Benefits of the talk:
1. Understanding the shortcomings of vision screening and how retinal birefringence scanning solves those problems
2. Cost-effective methods to detecting disease over risk-factors
3. Realistic approach to eradicating vision loss as a result of amblyopia
10:00 Morning Networking Break
10:30 Sustained Delivery of Proteins and Antibodies
  Hong Guo, PhD, Vice President of Research, pSivida
Sustained Delivery of Proteins and Antibodies – A drug delivery technology that may provide opportunities
One of the many challenges to pharmaceutical industry is to develop effective delivery systems for protein and antibody drugs. pSivida’s new approach is using biocompatible and biodegradable structures of meso-porous silicon to provide sustained delivery of therapeutics. The primary focus with this technology is the delivery of large biologic molecules, including proteins and antibodies. The pore diameter and surface area of meso-porous silicon materials can be adjusted to enable the adsorption of specific classes of proteins and antibodies. Adsorbed agents are then released on a sustained basis over time. These materials are also being evaluated for the delivery of smaller molecules.

• What are the challenges of deliver protein and antibody drugs
• pSivida’s drug delivery systems
• Meso-porous silicon properties and scientific background
• Sustained delivery will bring new life to protein and antibody drugs
• Promising research results
10:55 Utility of a Mouse Model for Evaluation of Potential Therapies for Age-related Macular Degeneration
Chi-Chao Chan, Chief, Immunopathology Section; Laboratory of Immunology; Head, Histopathology Core, National Eye Institute, National Institutes of Health
We use the Ccl2-/-/Cx3cr1-/- on rd8 background (DKO/rd8) mouse as a model for age-related macular degeneration (AMD). These mice develop progressive focal retinal degeneration characterized by photoreceptor and RPE atrophy, elevated ocular A2E and immune dysfunction, plus retinal dystrophy from the rd8 background. We examined the effect of feeding AREDS2 formulation to DKO/rd8 mice: one group was fed the AREDS2 diet with lutein, zeaxanthin and DHA/EPA, the other group was fed an isocaloric diet. After three months, 75% of control DKO/rd8 mice had retinal lesion progression, compared to 19% of AREDS2-treated mice. Ocular A2E levels were significantly lower and the mean outer nuclear layer was also significantly thicker in AREDS2-treated mice compared to the controls. Retinal expression of iNos, Tnf-?, Cox-2, and Vegf were lower in AREDS2-treated eyes. The data suggest that oxidative inflammatory damage was counteracted early enough to halt RPE damage and photoreceptor loss, and thus support a beneficial effect of AREDS2 formulation for AMD. While the identification of rd8 and rd8-associated retinal phenotype impacts the power of DKO/rd8 as an AMD model, the use of the model as self-control by treating one eye as the control allows for appropriate experimental interventional studies. In intervention studies on DKO/rd8, treatment is shown to alleviate photoreceptor and RPE lesions that can be attributed to Ccl2 and Cxcr3 null while showing little or no effect on rd8 lesions. Therefore, DKO/rd8 may still serve as a suitable and relevant model for compound screening on focal retinal degenerative diseases including AMD.
FEATURED PRESENTATION
11:20 A Novel Approach to Treat Corneal Defects


Barbara Wirostko
Chief Scientific Officer and Co-Founder
Jade Therapeutics
Clinical Adjunct Associate Professor, Ophthalmology
University of Utah
Jade Therapeutics develops locally administered, sustained-release formulations of already-approved drugs for use in poorly served ophthalmic indications. This approach could enable improved therapeutic outcomes along with increased patient compliance to therapy and decreased frequency of administration and office visits – ultimately resulting in better visual function with enhanced quality of life.

The Company’s initial focus is on a novel, bioresorbable topical ocular product that elutes recombinant human growth hormone (rHGH) over a period of approximately 1-2 weeks to help address persistent corneal epithelial defects (PCED). PCED can result from injury to the eye (such as chemical or blast trauma), disease of the eye (including ocular infections, severe dry eye, neurotrophic keratitis, diabetic neuropathies, and neurologic palsies), and various ocular surgeries. Practitioners report that today’s therapeutic options are quite limited as there are currently no approved drugs designed to help heal the ocular surface in general or to resolve corneal defects in particular.

Commercially available, systemically administered rHGH has been used safely for decades by thousands of patients for various non-ophthalmic indications, where it has been shown broadly to activate epithelial and other cell types in order to repair and build tissue. Jade’s own studies have demonstrated promising results in accelerating corneal healing in various rabbit models.

Aims of the presentation:
• Better characterize PCED as a disease and the associated unmet need
• Share the MOA/rationale for rHGH in treating PCEDs
• Discuss the data that exist for non-ocular wound healing
• Share the preclinical data to date for Jade’s product
11:55 Lunch on Your Own
Moderator: Abraham Scaria, Senior Scientific Director, Genzyme
Session: Novel Drug Delivery Methods to the Anterior and Posterior Segments
1:30 Gene Therapy for the Treatment of Neovascular AMD
Abraham Scaria, Senior Scientific Director, Genzyme
VEGF plays a critical role in neovascular age-related macular degeneration and proliferative diabetic retinopathy. VEGF antagonists are useful for treating such disorders; however current treatments require monthly intravitreal injections. We have designed a soluble anti-VEGF molecule (sFLT01) and delivered it by intravitreal injection of an adeno-associated viral (AAV) vector since AAV vectors are capable of long-term gene expression. AAV2-sFLT01 inhibited retinal neovascularization in the murine oxygen-induced retinopathy model and in the laser-induced choroidal neovascularization (laser-CNV) model in mice. In the eyes of rodents and cynomolgus monkeys, AAV2-sFLT01 gives expression levels persistent for at least one year. We also performed laser-CNV experiments 5 months after vector administration in non-human primates and showed that sFLT01 is effective at inhibiting neovascularization in this model. Results of our 12-month safety study of AAV2-sFLT01 administered intravitreally in cynomolgus monkeys will be discussed. In summary, we have demonstrated long-term efficacy with minimal side effects following intravitreal delivery of AAV-sFLT01 in rodents and non-human primate models. These results suggest an alternate method for the long-term treatment for diseases of ocular neovascularization, without the need for repeated intraocular injections. A Phase I clinical trial is under way at four clinical sites in the USA.
1:55 PRINT Technology for Ocular Drug Delivery
Kenneth J. Mandell, Vice President, Early Development, Liquidia Technologies, Inc.
As many as 285 million people suffer from disease-related visual impairments and blindness wordlwide. Unfortunately, the safety and effectiveness of many medical therapies for ocular disorders are limited due to poor ocular drug uptake, non-specificity to target tissues, systemic side effects, and poor adherence to therapy. To address these critical unmet needs, Liquidia is using its proprietary PRINT technology platform to rationally design and manufacture micro- and nano-particle systems for the treatment of ocular diseases. The PRINT particles, which can consist of both small molecule and biologic therapeutics, are designed and manufactured with the goal of improving the delivery, safety and efficacy of medicines used to treat ocular disease. The technology can be used to precisely engineer particles of virtually any size, shape and chemistry and finely tune them to perform as highly targeted therapeutics with enhanced effectiveness and safety. Additionally, the ability to engineer therapeutic particles with tunable release kinetics could significantly reduce dosing requirements and increase patient compliance. The PRINT technology platform can be applied to topical therapies to achieve a highly homogenous distribution on the ocular surface with the potential for increased retention and tolerability. Such advancements could allow for the delivery of ocular therapies with improved therapeutic index using fewer doses and result in improved patient compliance and therapeutic outcomes.

Benefits of the talk
1. Discussion of unmet needs in ophthalmic drug delivery
2. Presentation of novel nano- and microfabrication technology
3. Discussion of applications of novel nano- and microparticles for drug delivery
2:20 Suprachoroidal Drug Delivery: Clinical and Pre-Clinical Experience
Samirkumar Patel, Director, Research and New Product Development, Clearside Biomedical
Treating diseases that affect the posterior segment of the eye is primarily done by direct injection of drugs into the vitreous. Currently doctors have very few viable options to deliver a drug directly to the choroid and retina where the pathology of many posterior segment diseases occurs. Direct injection into the suprachoroidal space with a microneedle can accomplish this and be done in a minimally invasive manner. This talk will focus on how injecting drugs into the suprachoroidal space using Clearside’s proprietary microneedle, has demonstrated efficacy in posterior inflammation (uveitis) in animal models and early human clinical safety experience.

Benefits/topic covered:
- An understanding of the microinjection technology
- An understanding of the suprachoroidal space anatomy and benefits of drug administration to this space
- Safety and efficacy data on suprachoroidal delivery in animal models
- Early clinical safety experience with Clearside’s suprachoroidal microinjection technology in human subjects
2:45 Recent Developments in Drug Delivery for Anterior and Posterior Segment
Eugene de Juan, Founder & Vice-Chairman, ForSight Labs
3:10 Afternoon Networking Break
3:40 Polyesteramides: Materials, Formulation and Processes for Ocular Drug Delivery
John Zupancich, Staff Scientist, DSM Biomedical
The incorporation of amino acid-based units into resorbable, biodegradable polymers introduces not only metabolisable building blocks within the polymer, but also one or more functional groups along the polymer chain. This allows modification of the polymer to tailor its physicochemical properties, bio-erosion and performance as drug eluting matrices. DSM is developing a portfolio of polyesteramide polymers (“PEAs”) based on a-amino acids, aliphatic dicarboxylic acids and aliphatic a-w diols. A main advantage of PEAs is that by design, they predominantly degrade via an enzymatic mechanism and consequently due to exclusive surface erosion, drug release follows nearly zero-order kinetics.

Recently, significant advances have been made in optimizing the delivery of drugs to target tissues within the eye. Although topical administration remains the most common method, application of injectable, degradable ocular delivery devices provide better control over dosage, reduces amounts of formulated drug required and offers the opportunity to delivery drug more efficiently to the posterior segment of the eye.

In this presentation we will present DSM’s portfolio of PEAs and address various topics on ocular biocompatibility, degradation, processing and utility as a 6+ month sustained release delivery vehicle using latanoprost and dexamethasone as examples.
4:05 Drug-Eluting Contact Lenses
Joseph B. Ciolino, Assistant Professor, Ophthalmology, Mass. Eye & Ear Infirmary, Harvard Medical School
Purpose: To the report the in vitro and in vivo results in the development of a latanoprost-eluting contact lens designed for the treatment of glaucoma.

Methods: Drug-eluting therapeutic contact lenses (TCL) were created by encapsulating drug-polymer films in methafilcon A by ultraviolet light polymerization. TCLs were placed in phosphate buffered solution at 37°C with continuous rotation. The release media was sampled and changed daily. Drug concentrations were measured with an enzyme-linked immunosorbent assay (ELISA). TCLs were inserted on the left eye of New Zealand white rabbits for 4 weeks. The eyes were examined under an operating microscope and the anterior chamber (AC) fluid was collected during 28 days of continuous wear. For comparison, latanoprost 0.005% solution (drops) was topically applied and the AC fluid was sampled after drop administration (1, 3, 6, 12, and 24 hrs). Each sample was collected on a different day and the AC drug concentration was measured by ELISA. The 24-hr area under the curve (AUC) for latanoprost drops was calculated and compared to the AC concentration measured during 28 days of TCL wear.

Results: In vitro, TCLs demonstrated an initial burst and then eluted a sustained and therapeutic daily amount of latanoprost for 4 weeks. In vivo, the TCLs demonstrated no signs of toxicity. Through 28 days of continuous wear, the TCLs delivered a therapeutic level of latanoprost to the anterior chamber without any signs of toxicity.

Conclusions: This contact lens design can potentially be used as a treatment for glaucoma and as a platform for ocular drug delivery with widespread applications.

“Benefits”
-Highlight potential future therapeutics
-Discuss the potential of contact lens drug delivery
-Discuss advantages and disadvantages of contact lenses as a means of drug delivery
Session: Safety Assessment and Regulatory Landscape in Ocular Drug Development
FEATURED PRESENTATION
4:30 Thirty Years of Developing New Therapeutic Ophthalmic Drugs – Some Simple Principles



Gary Novack
President
PharmaLogic Development
The author has been involved in the development of scores of ophthalmic products over the past 30 years. In this talk, he will present a brief list of basic principles of pharmacology, the scientific method, and communication and their application to ophthalmic product development. As well, he will discuss how these product development perspectives align with regulatory laws, regulations and guidances.
Moderator: Kenneth J. Mandell, Massachusetts Institute of Technology (MIT)
Panel Discussion: Safety and Regulatory in Ocular Development
5:05 Panelist: Gary Novack, President, PharmaLogic Development
Panelist: Judy F. Gordon, Founder and President, ClinReg Consulting Services
Panelist: Hal Patterson, Vice President of Quality and CMC, Ora
5:50 Networking Reception and Poster Session
Day 1 Day 2
Day 2 - Friday, March 22, 2013
7:30 Continental Breakfast
Moderator: Barbara Wirostko, Jade Therapeutics; University of Utah
Session: Novel Drug Delivery Methods to the Anterior and Posterior Segments
8:00 Replenish Ophthalmic MicroPumps
  Sean Caffey, Chairman, CEO and Co-Founder, Replenish
Moderator: Emmett Cunningham, Clarus Ventures
Panel Discussion: BD, Investments and Potential for Collaborations
8:25 Panelist: Quinton Oswald, Chief Executive Officer, SarCode
Panelist: Baldo Sforzolini, Vice President, Global Drug Development, Bausch & Lomb
Panelist: K. Angela Macfarlane, President & CEO, ForSight Labs
Panelist: Susan Orr, Sr. Director, R&D Alliances, Alcon
Panelist: Charles Warden, Managing Director, Versant Ventures

Panel to discuss drug delivery from the perspectives of both investors and industry.
Session: Short Presentations
9:10 Advances in High Precision Low Dose Drug Delivery Technology
Timothy Sullivan, President & CEO, Mystic Pharmaceuticals
  Recent advances in the development of novel ophthalmic delivery device technology will provide pharmaceutical manufacturers with the capability to develop drug/device combination products precisely deliver a drug to the front of eye at a discreet volume that can be calibrated between five and 30 microliters. This same technology will enable self administration by the patent at the targeted discreet volume on a repeatable basis. This session will provide an overview of a new ophthalmic delivery system under development by Mystic that has achieved this level of performance and discuss potential implications on patient safety, tolerance and compliance.
9:20 Catalyst's Preclinical Dry AMD Program
Ed Madison, Chief Scientific Officer, Catalyst Biosciences
9:30 Evolution of Business Models of Chinese CRO– Advancing Your Breakthroughs
  Mingzhu Zhang, Vice President and Head of US Business Development, Shanghai Medicilon
  The global outsourcing industry is undergoing a paradigm shift with the rise in outsourcing capabilities in China over the past decade. Increase in R&D capabilities and access to highly-educated low-cost talent pool are driving outsourcing to China. Outsourcing has become a long-term trend.

Shanghai Medicilon is the pioneer in integrated pharmaceutical R&D services in China that offers chemistry, biology and structural biology, DMPK/PD, toxicology (GLP, non-GLP) services to pharmaceutical and biotech companies around the world since 2004. This presentation, taking Shanghai Medicilon as an example, illustrates development trends and strategies of Chinese CROs, which are gradually shifting their roles from traditional service providers to strategic partners.
9:40 Applying Primate Ophthalmic Models to Realize Clinical Objectives
  Matthew Lawrence, CSO & CEO, RxGen
  Navigating the path from basic science discovery or clinical observation to new approved therapeutic strategy is demanding, requiring careful consideration of preclinical and clinical strategy, resources, time, talent and the quality of data and analysis applied. Before setting off on that path, and along that path, many decisions are required, not least of which is the validity of the preclinical models employed and the manner in which they are applied, and their interpretation with respect to the specific clinical indication being pursued. In ophthalmology, non-human primate models represent an important, and in some instances, essential test system in which to evaluate pharmacology, efficacy and/or safety, both to de-risk a program in the early stages of development, and at a later stage, given the significant investment of time and resources required for clinical trials, to provide confidence in safely and effectively pursuing the proposed clinical strategy. The rationale and practical considerations for why, when, how and where to extend preclinical modeling into non-human primates is not always clear without balanced attention to comparative medicine, regulatory, technical, and cost considerations. This can be achieved by early engagement with groups routinely implementing and refining validated, clinically predictive models. Where such models do not exist, goals can be met by pursuing collaborative and consortia approaches to expand the model portfolio available for immediate development needs, and ultimately to the broader ophthalmic research community and the clinical challenges we collectively address. The objectives of effective and efficient translational development will be discussed in this context.
  Oral Presentations from Submitted Abstracts
9:50 Human Photosynthesis or the Real Role of Melanin in the Pathophysiology of AMD, Diabetic Retinopathy and Glaucoma
Arturo Solis Herrera MD, PhD., Human Photosynthesis Study Center, SC. Aguascalientes, Mexico
10:00 Inhibition of Multiple Pathogenic Pathways by Histone Deacetylase Inhibitor SAHA in a Corneal Alkali-Burn Injury Model
Shusheng Wang, Assistant Professor, Cell and Molecular Biology & Ophthalmology, Tulane University
10:10 A Preclinical Model of dry AMD
Shelley Boyd BSc, MD, FRCS(C), Assistant Professor, University of Toronto
10:20 Morning Networking Break
Moderator: Kenneth J. Mandell, Massachusetts Institute of Technology (MIT)
Session: Clinical Development Advances & Updates
10:50 Dark Adaptation: A Functional Clinical Trial Endpoint for Age-related Macular Degeneration
Gregory Jackson, Associate Professor, Ophthalmology, Penn State University
Age-related macular degeneration is a progressive chronic retinal disease. AMD causes the deterioration of the Bruch’s membrane/retinal pigment epithelium cell complex which compromises photoreceptor function and health. Disruption of retinal pigment epithelium function alters the retinoid cycle which primarily governs the speed of dark adaptation. Slowed dark adaptation is a prominent deficit of visual function in patients with early AMD. Cone recovery is slower. The rod-cone break and rod intercept are delayed, and the slope of the second component of rod-mediated dark adaptation is shallower. Studies of dark adaptation in AMD patients report increasing impairment of DA with increasing disease severity. This relationship suggests that there is a progressive loss of dark adaptation with disease progression. A significant change in DA parameters within one year might be a useful marker of disease progression which could be modified by therapeutic intervention. To address this possibility, we have conducted a 12-month natural history study of DA in patients with mild to intermediate AMD. We found that nearly 20% of patients with AMD exhibited a significant change in dark adaptation while maintaining stable acuity and AREDS severity grade. This study suggests that dark adaptation may be a suitable functional endpoint for early clinical studies evaluating novel treatments for early to intermediate AMD.

Benefits
1. A framework for the validation of novel functional clinical trial endpoints will be presented
2. Data will be presented supporting dark adaptation as a clinical trial endpoint for age-related macular degeneration
3. The 12-month natural history of dark adaptation in early to intermediate AMD will be described
11:15 New Advances in the Development of Rho Kinase Inhibitors for the Treatment of Glaucoma
Casey Kopczynski, Chief Scientific Officer, Aerie Pharmaceuticals
The objective of Aerie’s development program is to bring new, more effective treatment options to patients with glaucoma or ocular hypertension. Aerie's glaucoma pipeline includes novel inhibitors of Rho kinase (ROCK) that lower intraocular pressure (IOP) through a new mechanism of action, improving the outflow of aqueous humor through the trabecular meshwork (TM).

AR-12286 is a first-in-class ROCK inhibitor that has demonstrated an excellent safety and efficacy profile in Phase 2 clinical studies as a once-daily eye drop. Aerie has developed the first fixed-dose combination (FDC) of a ROCK inhibitor plus a prostaglandin agonist, PG286 (AR-12286 plus travoprost), and evaluated the efficacy and safety of this FDC vs. travoprost monotherapy in a 7-day Phase 2a clinical study. PG286 was well tolerated and reduced 8 AM IOP by 12.2 mmHg (46%) compared to 9.1 mmHg (34%) for travoprost. PG286 has the potential to become the most effective once-daily combination product for treating glaucoma.

AR-13324 is the first of a new class of glaucoma drugs that lowers IOP through a unique dual mechanism of action, increasing TM outflow through ROCK inhibition while also decreasing the production of aqueous humor. A first-in-human Phase 2a study evaluating AR-13324 0.01%, 0.02% and 0.04% dosed once-daily in the morning has been completed. All dose levels produced large reductions in IOP. AR-13324 0.02% defined the top of the dose response curve and was well tolerated. The results suggest peak efficacy is achieved >8 hours after dosing, and that maximal efficacy will be achieved with evening dosing.

Benefits:
1. Learn how ROCK inhibitors differ from currently marketed glaucoma drugs.
2. Hear an update on the clinical development of the first-in-class ROCK inhibitor, AR-12286.
3. Learn about a new dual mechanism class of glaucoma drugs discovered at Aerie.
4. Hear how the dual mechanism inhibitor AR-13324 differs from other ROCK inhibitors.
11:40 Advancing the State of the Art...the True Path for Innovation in Clinical Development
Philip G. Ralston, Chief Executive Officer, MacuCLEAR
Challenging conventional wisdom can be an uphill battle when innovating, especially in clinical development of a drug. The payoffs can be huge. A leader must demonstrate passion, tenacity, creativity, and perhaps a stubborn streak. Learn about MacuCLEAR’s aggressive clinical program for The Chiou Syndrome, its novel drug MC-1101 for treating dry AMD, and how it resulted in a pivotal trial design using novel endpoints. Understand how they are championing uncharted territories with the FDA and in a cost effective way.
The attendee should come away with:
• Guidelines for working with FDA
• Getting functionally relevant novel endpoints considered for novel targets
• Managing risk in clinical development
• A “passing attack” approach to technology development that leads to truth seeking and cost efficiency.
12:05 GTC Sponsored Lunch
2:30 Conference Concludes
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