2019 - Emmett Cunningham, Jr., M.D., Ph.D., M.P.H. Senior Managing Director Blackstone Life Sciences HEATHEGY TEAM CRAIG SIMAK CRAIG SIMAK DANIELLE SILVA MAUREEN LINNEMANN 1200 OIS@AAO 24 Meetings > 1,150 1000 ~ 13,500 Attendees 800 OIS@ASCRS 600 > 650 400 OIS@ASRS 200 > 300 0 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018 2019 2020 Registrants 3% 10% OIS@AAO 2019 ( > 1,150) 8% Academia, Government, or Association 41% Adviser, Consultant, or Service Provider Finance/Investment Firm Large Multi-National Corporation Physician/Healthcare Provider 25% Press/Media Start-up/Emerging Growth Company 3% 25 Countries 10% 32 US States Record Number of CDER NME NDA/BLA Approvals in 2018 70 BLA 59 60 NDA 50 45 46 Number 39 41 of 40 35 36 Drugs 30 30 30 27 27 24 26 22 24 21 20 21 22 20 17 18 10 0 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018 Source: FDA 1998 - 2018 High Innovation Record Number of • 31 (53%) Orphan CDER NME NDA/BLA Approvals in 2018 • 26 (44%) Priority Review • 16 (27%) Fast Track • 12 (20%) Break Through Designation 59 • 18 (30%) Oncology • 1 (0%) Ophthalmology Cenegermin-bkbj Ophthalmic Solution, (OXERVATE®) Ophthalmic Drugs Streamlined Reporting of Ophthalmology Clinical Group CDER As of January, 2018 Ophthalmology Clinical Group Reported Directly & Independently to Deputy Director Office of New Drugs Peter Stein, MD Five Additional Office of Offices of Drug Antimicrobial Evaluation (ODEs) Products Division of Division of Division of Transplant and Anti-Infective Anti-Viral Ophthalmology Products Products Dr. Wiley A. Chambers Products Supervisory Medical Officer Division of Transplant and Ophthalmology Products (DTOP) Re-Org Officially Approved September 26, 2019 https://www.fda.gov/drugs/regulatory-science-research-and-education/reorganization-office-new-drugs-corresponding-changes-office-translational-sciences-and-office Original NDA/BLA Approvals – 1988 to 2019 Center for Drug Evaluation and Research 2019 160 129 140 120 100 80 60 • Range: 0 – 9 • Mean: 4.4 40 Ophthalmic / Year • Median: 4 20 7 0 1988 1989 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018 2019 Ophthalmic Approvals Total Approvals Linear (Ophthalmic Approvals) Linear (Total Approvals) Data provided by : Wiley A. Chambers, MD Gary Novack, PhD Supervisory Medical Officer Pharma . Logic Consulting, Inc. Division of Transplant and Ophthalmology Products Original NDA/BLA Approvals Center for Drug Evaluation and Research - FY2019 140 7 5.4% Ophthalmic 122 October 1, 2018 thru September 30, 2019 120 • Fluocinolonide acetonide intravitreal implant (YUTIQ®), 0.18mg, a corticosteroid implant indicated for the treatment of chronic non-infectious uveitis affecting the posterior segment of the eye, October 12, 2018 (NDA) – Eyepoint 100 Pharmaceuticals, Inc. •Dexamethasone Ophthalmic Insert (DEXTENZA®), 0.4mg, a corticosteroid insert indicated for the treatment of ocular pain associated with ophthalmic surgery. November 30, 2018 (NDA) – Ocular Therapeutix, Inc. 80 •Loteprednol etabonate ophthalmic gel (LOTEMAX SM®), 0.38% in new formulation to treat post-operative inflammation and pain following ocular surgery, February 22, 2019 (NDA) – Bausch & Lomb, Inc. • Tetracaine hydrochloride ophthalmic solution, 0.5% , local ophthalmic anesthetic – March 12, 2019 (NDA) – 60 Bausch & Lomb, Inc. • Netarsudil / Latanoprost (ROCKLATAN®), 0.02%/0.005%, fixed dose combination for the reduction of elevated intraocular pressure in patients with open-angle glaucoma or ocular hypertension, March 12, 2019 (NDA) – Aerie 40 Pharmaceuticals, Inc. • Acyclovir Ophthalmic Ointment (AVACLYR®), 3.0%, indicated for the treatment of acute herpetic keratitis (dendritic ulcers) in patients with herpes simplex (HSV-1 and HSV-2) virus, March 29, 2019 (NDA) – Fera Pharmaceuticals, LLC. 20 •Brolucizumab (Beovu®), 6mg/0.05mg, indicated for the treatment of wet age-related macular degeneration, October 8, 2019, Novartis AG 0 Ophthalmic Non-Ophthalmic Data provided by : Wiley A. Chambers, MD Gary Novack, PhD Supervisory Medical Officer Pharma . Logic Consulting, Inc. Division of Transplant and Ophthalmology Products FDA Approved October 12, 2018 YUTIQTM SHAM Fluocinolone acetonide intravitreal implant, 0.18 mg (YUTIQ™), contains a corticosteroid and is indicated for the Fluocinolone Acetonide treatment of chronic non-infectious uveitis affecting the Intravitreal Implant posterior segment of the eye. FDA Approved November 30, 2018 First FDA Approved Punctal Plug Delivery System Dexamethasone Ophthalmic Insert (DEXTENZA®), 0.4mg A corticosteroid insert indicated for the treatment of ocular pain associated with ophthalmic surgery. November 30, 2018 (NDA) FDA Approved February 22, 2019 Proportion of Patients with Complete Resolution of ACC at Day 8 (Pooled Analysis) 60% LOTEMAX® SM (n=371) P<0. 40% 0001 30% 20% 15% 0% Day 8 Loteprednol etabonate ophthalmic gel (LOTEMAX SM®), 0.38% in new formulation to treat post-operative inflammation and pain following ocular surgery FDA Approved - March 12, 2019 Launched – May, 2019 First Fixed-Dose Combination Containing a PGA First Once-Daily Fixed-Dose Combination Netarsudil / Latanoprost (ROCKLATAN®), 0.02%/0.005%, is a fixed-dose combination indicated for the reduction of elevated intraocular pressure in patients with open-angle glaucoma or ocular hypertension “Beovu® is the first to offer less frequent dosing in the first year of therapy while maintaining its effectiveness.” October 8, 2019 Brolucizumab (Beovu®), 6mg/0.05mg “More than half of patients on brolucizumab (56% indicated for the treatment of wet in HAWK, 51% in HARRIER) age-related macular degeneration were able to maintain a 3-month dosing interval” Number of CDER NME NDA/BLA Approvals, 2015-2019* 59 60 All Indications 60 Ophthalmology 50 50 45 46 40 40 30 30 30 22 20 20 10 10 3 0 1 1 1 0 0 2015 2016 2017 2018 2019* 2015 2016 2017 2018 2019* * 2019 Through October 8, 2019; FDA Global Ophthalmic Pharmaceutical Market Revenues by Specialty 50 Total ($B) 42.14 40 6.9 Total ($B) 29.04 6.5 30 6.2 6.3 20 4.9 Revenues ($B) Revenues 4.9 Anti-VEGF 10 22.4 13.0 Largest 0 2019 2024 IVT Anti-VEGF (AMD, DME, RVO, Etc.) Glaucoma Pharmaceuticals Dry Eye All Other Source: Market Scope Estimates 2019; Courtesy Market Scope. http://market-scope.com/ Market Scope ® IVT Injections…. Courtesy Dr. Peter Karth and Dr. Marc Blumenkranz Global Anti-VEGF Injections (M) Global 25 24.4M 20 Ex-US 17.5M 15 10 IVT Injections Injections IVT (M) US 5 6.9M 0 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018 2019 United States Outside United States Global Source: Market Scope Estimates 2019; Courtesy Market Scope. http://market-scope.com/ Market Scope ® Wet AMD OPT-302-1002 – Mean Change in VA Over Time Additive benefit of OPT-302 evident from 8-weeks Mean Gains in Visual Acuity From Baseline Benefit of Pan-VEGF Inhibition (A + C + D) +14.2 *p = 0.0107 +10.8 +9.4 Sham + Lucentis® (0.5 mg) OPT-302 (0.5 mg) + Lucentis® (0.5 mg) OPT-302 (2.0 mg) + Lucentis® (0.5 mg) (n = 119) (n = 122) (n = 121) OPT-302-1002 clinical trial (NCT03345082). Graph represents observed data and standard error of the mean (SEM). Modified Intent-to-treat study population. BCVA, Best Corrected Visual Acuity; ETDRS, Early Treatment Diabetic Retinopathy Study. * Difference in Least Square Means, using Model for Repeated Measures (MRM) analysis. Control of Type I error via the Hochberg Procedure. GB-102 – Small Molecule TKI (Sunitinib – Pan VEGFR Antagonist) • Best performing dose • ~90% of patients rescue-free at 6 Months • ~60% of patients rescue-free at 8 months • Excellent safety profile • Phase 2a in Macular Edema Q3 2019 • Phase 2b in wAMD Q3 2019 Antibody Biopolymer Conjugates (ABCs): a new scientific design platform for extended durability intravitreal therapeutics • Phase 1 Data: 110+ Patients: wAMD, DME (NPDR, PDR), RVO • Safety: 300+ injections: no inflammation or other safety signals • Efficacy: strong anti-VEGF efficacy in each indication • Durability: wAMD dosing interval of 3-5 months in emerging data (Retina Society) KSI-301: anti- VEGF ABC Antibody and optically clear, branched, high molecular weight phosphorylcholine biopolymer covalently bound via single, site- specific stable linkage • New durability data in wAMD, DME, and RVO to be presented Friday 10/11 at AAO • Pivotal ‘DAZZLE’ wAMD study: KSI-301 q3-5 month vs Eylea q2mo now enrolling OPTIC Cohort 1 24-week conclusions ADVM-022 AAV.7m8 capsid • Zero rescue injections required • Consistent and sustained anatomical improvements on OCT ITR C11 aflibercept ITR Aflibercept expression cassette • BCVA stability maintained RN • ADVM-022 - safe and well tolerated A Aflibercept Day -14 to -7: Day 1: 24-week safety and 52-week safety and aflibercept ADVM-022 efficacy assessment efficacy assessment Baseline assessment Treatment evaluation Treatment evaluation Follow-up Weeks: 4 8 12 16 20 24 52 104 Rescue at any time if disease activity meets retreatment criteria† Sub – Retinal Delivery REGENXBIO ANNOUNCES EXCLUSIVE WORLDWIDE OPTION AND LICENSE AGREEMENT WITH CLEARSIDE BIOMEDICAL FOR EVALUATION OF IN- OFFICE DELIVERY PLATFORM FOR RGX-314 Ophthalmic Devices 510(k) Clearances Division of Ophthalmic and Ear, Nose and Throat Devices - FY2018 3000 2.2% of Total 2500 2348 54 2000 1500 1000 Ophthalmic 500 Non-Ophthalmic 0 Lee Kramm, MD, MSE & Judy Gordon, DVM ClinReg Consulting Services, Inc. PMA Approvals – 2004 to 2019 Division of Ophthalmic and Ear, Nose and Throat Devices 80 2019 70 60 50 49 40 30 20 10 3 0 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018 2019 Opthalmic PMA Total PMA Lee Kramm, MD, MSE & Judy Gordon, DVM ClinReg Consulting Services, Inc. PMA Approvals Division of Ophthalmic and Ear, Nose and Throat Devices- FY2018 60 5.8% of Total 3 50 49 40 October 1, 2018 thru September 30, 2019 • Visumax Femtosecond Laser, Carl Zeiss Meditec, Inc.