Avellino Labs

THE FUTURE OF PRECISION MEDICINE

Eric Bernabei Chief Sales and Marketing Officer Avellino Labs Genetic services provider specializing in data, diagnostics, and therapies.

‘08 1st PCR genetic test to detect corneal dystrophy

2015 ‘15 Named Technology Pioneer - World Economic Forum

Partnered with Ulster University to develop novel 2016 ‘16 gene editing treatments

‘19 Launch AvaGen NGS test for KC Risk Factors /TGFBI CD

8 Avellino Labs

Pioneering Precision Medicine for Eye Care and Beyond Proven Scientific Leadership & Clinical Advisors

Terry Kim, MD Dick Lindstrom, MD John Marshall, PhD, MBE Edward Holland, MD Eric Donnenfeld, MD Board Member Director of Scientific and Medical Affairs

David Hwang, MD Andrea Cusumano, MD Elizabeth Yeu, MD Vance Thompson, MD

Tara Moore, PhD Professor of Personalized Medicine, Ulster Univ, Chief R&D Officer

11 Burkhard Dick, MD EK Kim, MD, PhD Shigeru Kinoshita, MD Aaron Lech,OD Introducing AvaGen

After 10 years of development, the first and only NGS test combining CD Testing and KC Risk Scores

2014 2015 2017

11 5 70 CD TGFBI mutations 2 1,000 variants across 75 1 + Test for Test for Universal 5 R&D Identified 6 more TGFBI genes associated with 1 TGFBI mutation 2 TGFBI mutations GCD1, GCD2, LCD1, mutations Over 1,000 variants across 75 TBCD,RBCD (GCD2) (GCD1, GCD2) LCD I/IIIA, 2 vt LCD, Keratoconus variant TBCD, GCD, RBCD genes associated with KC

2008 2019

5 Join Us Sunday Evening!

Eric Donnenfeld, MD Dick Lindstrom, MD

Terry Kim, MD

Edward Holland, MD Elizabeth Yeu, MD

6 Why a Genetic Test for Keratoconus?

Don’t we already know the etiology?

Eye Rubbing Observable and actionable: • Topography • Tomography • Behavior changes • Relies on patient memory Family • Medications • May not be accurate or relevant Environmental History

There is no one gene responsible for the development of keratoconus but there is a strong genetic component or link within each group.1

1. Gordon-Shaag A, et al. BioMed Res Int. Volume 2015, Article ID 795739, 19 pages. 7 Understanding the Natural Progression of Keratoconus Systematic review and meta-analysis of 11,529 eyes with untreated keratoconus to identify predictors of progression

Patients with greater Middle Eastern Younger patients populations Kmax at baseline

▪ Patients were predicted to • experienced significantly ▪ Patients were predicted to have a 1 D greater K greater K increase have 0.8 D less Kmax max max steepening for every 5 D than Europeans and East steepening over 12 months greater baseline K Asians for every 10-year increase in max age ▪ Patients with >55 D Kmax at 1.23 D (95% CI: –0.33 to 2.80) vs baseline are likely to 0.75 D (95% CI: –0.15 to 1.66; ▪ Patients <17 years old are P=0.01) and 0.16 D (95% CI: –0.34 to likely to have more than 1.5 progress by at least 1.5 D 0.66; P=0.01), respectively K at 12 months D of Kmax progression over 12 max months

Ferdi AC, et al. Ophthalmology. 2019; 126(7):935-945. 8 Global Keratoconus Risk 2019 Millions of patients are at risk based on corneal curvature alone

309,000,000 90% Patients with >46D corneal Live in Asia-Pacific Countries curvature or >2D cylinder 60% in India and China

1,700,000 4,000 Between ages 15-30 yrs old, Cornea Specialists

21 Keratoconus Risk in US & Canada 2019 Identifying At Risk Patients 2019 Patients with higher than normal risk for triggering or natural progression of disease

Patients with >47D cc and/or >2D astigmatism

Contact Lens and Orthokeratology Candidates

Refractive Surgery Candidates

Family History of Keratoconus

21 Using Genetic Testing to Identify Patients at Risk

Testing Process:

Extraction Sequencing Referencing and Patient Report Variant Risk Scores

12 Reading Results

Individual variants receive risk scoring for KC, description for TGFBI CD • 98% Accuracy in detecting targeted genes and variants – Proven in CLIA validation, September 2019 • All variants carry a risk. If it’s on the report, some level of risk is identified. • Negative result = no risk variants found. • Genetic counselors perform interpretation and will be made available for physicians and patients

13 Positive Disruption: Next Gen Testing, Big Data, and AI 2019 AI Driven Molecular Network Mapping and Pairwise Risk Scores

21 AvaGen Capability Pipeline 2019 Continuous addition of detection capabilities will make AvaGenTHE genetic eye test. Front Middle Back

2008 - 2019 2020+

Corneal Dystrophies Retinitis Pigmentosa Keratoconus AMD Stargardt’s Disease 2019 - 2020

Fuchs ECD EBMD Fleck CD 2021+ Macular CD Schnyder CD Glaucoma Cataract Myopia Uveitis Presbyopia Hyperopia 21 Avellino: Delivering The Value of Genetic Testing in Eye Care 2019

• Early detection of risk factors and diseases

• Education about monitoring and treatment options

• Empowering physicians and patients Avellino Labs

THANK YOU