UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
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FORM 8-K
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CURRENT REPORT
Pursuant to Section 13 OR 15 (d)
of The Securities Exchange Act of 1934
Date of Report (Date of Earliest Event Reported): August 16, 2022
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(Exact Name of Registrant as Specified in its Charter)
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| (State or Other Jurisdiction of Incorporation) | (Commission File Number) | (I.R.S. Employer Identification Number) | ||||||||||||
(484 ) 328-4701
(Address, including zip code, and telephone number, including area code, of principal executive office)
N/A
(Former Name or Former Address, if Changed Since Last Report)
Check the appropriate box below if the Form 8–K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions (see General Instruction A.2. below):
Securities registered pursuant to Section 12(b) of the Act:
| Title of each class | Trading Symbol(s) | Name of each exchange on which registered | ||||||||||||
(The Nasdaq Capital Market) | ||||||||||||||
Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§240.12b-2 of this chapter).
Emerging growth company ☐
If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. ☐
Item 8.01 Other Events.
Attached as Exhibit 99.1 hereto and incorporated herein by reference is a presentation that Ocugen, Inc. may use from time to time in presentations or discussions with investors, analysts, and other parties.
Item 9.01 Financial Statements and Exhibits.
The following exhibits are being filed herewith:
(d) Exhibits
| Exhibit No. | Document | |||||||
| 99.1 | ||||||||
| 104 | Cover Page Interactive Data File (embedded within the Inline XBRL document). | |||||||
1
SIGNATURE
Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.
Date: August 16, 2022
| OCUGEN, INC. | ||||||||
| By: | /s/ Shankar Musunuri | |||||||
| Name: Shankar Musunuri | ||||||||
| Title: Chief Executive Officer and Chairman | ||||||||
2
Courageous Innovation August 2022 NASDAQ: OCGN
Forward Looking Statements 2 This presentation contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995, which are based on the beliefs and assumptions of Ocugen, Inc. and on information currently available to management. All statements contained in this presentation other than statements of historical fact are forward- looking statements. We may, in some cases, use terms such as “predicts,” “believes,” “potential,” “proposed,” “continue,” “estimates,” “anticipates,” “expects,” “plans,” “intends,” “may,” “could,” “might,” “will,” “should,” or other words that convey uncertainty of future events or outcomes to identify these forward-looking statements. Such statements are subject to numerous important factors, risks, and uncertainties that may cause actual events or results to differ materially from our current expectations. These and other risks and uncertainties are more fully described in our periodic filings with the Securities and Exchange Commission (SEC), including the risk factors described in the section entitled “Risk Factors” in the quarterly and annual reports that we file with the SEC. Forward- looking statements that we make in this presentation are based on a combination of facts and factors currently known to us and speak only as of the date of this presentation. Except as required by law, we assume no obligation to update forward-looking statements contained in this presentation whether as a result of new information, future events, or otherwise, after the date of this presentation.
We’re Here to Make an Impact Through Courageous Innovation 3 Mission: At Ocugen, we are developing novel solutions to medical challenges, approaching healthcare innovation with purpose and agility to deliver new options for people facing serious disease and conditions Pioneering a breakthrough modifier gene therapy for several vision impairment diseases Innovating a novel biologic to treat eye diseases that can lead to vision loss for millions of people Co-developing a COVID-19 vaccine Creating a restorative cell therapy (RCT) platform to treat serious conditions like articular cartilage lesions
4 Pipeline Overview Asset/Program Indication Status Vaccine COVAXIN™ (BBV152) SARS-CoV-2 virus COVID-19 • EUA for adults in Mexico; EUA for 2 to 18-year-olds pending* • U.S. Phase 2/3 Immuno-bridging and broadening clinical trial in-progress • Health Canada NDS under review* Cell therapy NeoCart® (Autologous chondrocyte- derived neocartilage) Treatment of Articular Cartilage Defects in the Knee U.S. Regenerative Medicine Advanced Therapy (RMAT) designation; Phase 3 clinical trial under development Modifier Gene Therapy Platform OCU400 *** AAV-hNR2E3 Gene mutation-associated retinal degeneration** NR2E3 Mutation Phase 1/2 RHO Mutation Phase 1/2 CEP290 Mutation To be submitted OCU410 AAV-hRORA Dry Age-Related Macular Degeneration (Dry AMD)** Preclinical Novel Biologic OCU200 Transferrin – Tumstatin Diabetic Macular Edema Preclinical Diabetic Retinopathy Preclinical Wet Age-Related Macular Degeneration (Wet AMD) Preclinical * Based on Bharat Biotech-sponsored clinical trials in India ** No approved therapies exist https://www.aao.org/eye-health/diseases/retinitis-pigmentosa-treatment | https://www.aao.org/eye-health/diseases/amd-treatment *** ORPHAN DRUG DESIGNATION in the US; Broad ORPHAN MEDICINAL PRODUCT DESIGNATION by the EC for the treatment of retinitis pigmentosa (RP) and Leber congenital amaurosis (LCA)
5 MODIFIER GENE THERAPY PLATFORM Breakthrough technology designed to address many rare diseases as well as complex diseases that affect millions
~2 million >250 genes IRD ~1.5 million >100 genes RP ~100,000 25 genes LCA ~100,000 ~8,200~400,000 • Only one approved gene therapy for LCA associated with RPE65 mutation: Luxturna® (Voretigene Neparvovec) • Electronic Smart Glasses are used to enable low vision aid in retinitis pigmentosa (RP) patients –IrisVision is a Class I medical device FDA approved for RP • No treatment options are available for RP Gong et al, 2021 Heterogeneous disease with many gene mutations involved Prevalence of IRDs and Associated Genes 6
7 Our Vision: Inherited Retinal Diseases Modifier Gene Therapy vs Traditional Gene Augmentation Normal gene X Gene Augmentation: Transfer functional version of a non-functional gene into the target cells Modifier Gene Therapy: Designed to introduce a functional gene to modify the expression of many genes/gene networks, and regulate basic biological processes in retina Traditional approach that targets one individual gene mutation at a time Regulatory pathway focused on specific product for one disease Longer time to recoup development costs Novel approach that targets nuclear hormone genes (NHRs), which regulate multiple functions within the retina Smoother regulatory pathway due to ability to target multiple diseases with one product Ability to recoup development costs over multiple therapeutic indications Traditional Gene Therapy OCU400 NR2E3 Mutation-Associated Retinal Disease Rhodopsin Mutation-Associated Retinal Disease CEP290 Mutation-Associated Retinal Disease Broad Spectrum Therapy for RP ONE Disease GENE X cell GENE X Cell with mutated/nonfunctioning gene X GENE X GENE X cell GENE X GENE X cell GENE X cell GENE M Cell with mutated/nonfunctioning gene(s) other than modifier gene GENE X GENE M Modifier gene M Cell with normal function cell We plan to address several diseases using the same modifier gene product cell
8 Our Focus: Nuclear Hormone Receptor Genes (NHRs) *References: https://pubmed.ncbi.nlm.nih.gov/28556246/ | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5409218/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4339951/ | https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0183526 NHRs in the retina are modulators of retinal development & function, acting as “master genes” in the retina Molecular reset of key transcription factors and associated gene networks – retinal homeostasis Gene modifier concept, including its impact on clinical phenotypes, is well known in other disease areas, such as cystic fibrosis and spinal muscular atrophy
OCU400, NR2E3 gene within the AAV5 capsid RP /L C A E ye H ea lth y Ey e N R2E3 NR2E3 modifier gene therapy to restore retinal homeostasis Ocugen’s Modifier Gene Therapy Regulates Gene Networks 9
10 Proof of Principle: Published in Nature Gene Therapy OCU400 NR2E3 Mutation-Associated Retinal Disease CEP290 Mutation-Associated Retinal Disease ONE Disease GENE X GNE X https://www.nature.com/articles/s41434-020-0134-z Important milestone for development of therapy; demonstrated proof of principle Protection elicited in multiple animal models of degeneration caused by different mutations Potential to represent first broad-spectrum g e agnostic therapy and provide rescue even after disease onset Efficacy results shown in five unique mouse models of RP Technology developed at Harvard Medical School, Dr. Neena Haider’s Lab Study suggests potency of modifier gene therapy to elicit broad- spectrum therapeutic benefits in early and advanced stages of RP Results suggest evidence of vision rescue in early & advanced stages of disease
OCU400 Pharmacological Studies Wert et al., J. Vis. Exp. (69), 2012 OCU400 administered subretinally Mouse Model RhoP23HRho-/-rd1 Untreated rd7rd16B6 AAV8-Nr2e3 Treated Human Disease Control PDE6β associated RP Rhodopsin associated adRP Rhodopsin associated adRP Leber Congenital Amaurosis (CEP290) NR2E3 associated RP OCU400 rescues retinal degeneration in different RP and LCA mouse models Li et al., Gene Therapy 28(5), 2020 Untreated AAV8-Nr2e3 Treated INL – Inner nuclear layer, ONL - Outer nuclear layer, GCL – ganglion cell layer OCU400 was tested in five different mouse models of retinal degeneration 11
OCU400 Biodistribution, Safety and Toxicity Studies NR2E3 protein expression in the retina following OCU400 administration Retina Vitreous Humor RPE/Choroid Aqueous Humor Iris/Ciliary Body Sclera Lateral Geniculate Nucleus Optic Nerve Optic Tract Relative tissue distribution Image: Charles River Laboratories OCU400 distribution in ocular tissues at six months post-dosing 12
OCU400 Well Tolerated and Not Immunogenic No toxic effects related to OCU400 No ADA response in serum or aqueous humor No immunogenic response in PBMCs or lymphocytes Center Image: Enrico et al., Clinical Cancer Research 26(4), 2020 13
14 OCU400 Phase 1/2 Clinical Trial Progress ⌛ OCU400 A Phase 1/2 Study to Assess the Safety and Efficacy of OCU400 for Retinitis Pigmentosa Associated with NR2E3 (Nuclear Receptor Subfamily 2 Group E Member 3) and RHO (Rhodopsin) Mutations NCT: 05203939 Study Type: Interventional (Clinical Trial) Estimated Enrollment: 18 participants Clinical Trial Sites: Seven Allocation: Non-randomized Intervention Model: Sequential assignment Masking: None (Open Label) Primary Purpose: Treatment Dosing: Escalation study involving low, medium, high doses Just 30 days to receive FDA clearance for Phase 1/2 gene therapy clinical trial Enrollment expected to conclude by YE 2022 Cohort 1 Cohort 2 Cohort 3 Low dose First dose March 2022 No serious adverse events reported Medium dose First dose planned for August 2022 Initiated dosing based on DSMB recommendation High dose To be initiated Completed In-progress Pending
15 OCU400 Pathway to Phase 3 Clinical Trials RP LCA Proposed Indication RP & LCA
16 OCU410 Modifier Gene Therapy Platform
Phase 1/2 clinical trial 17 OCU410 (AAV-RORA) Dry Age-Related Macular Degeneration 30 Dry AMD • Leads to irreversible blindness due to degeneration of the retina • ~9-10M patients in the U.S. • Currently no approved treatment for Dry AMD • Contributing factors: aging, genetics, environmental factors We believe OCU410 has the potential to address this disease through its multi-factor approach RORA Inflammation Lipid Peroxidation Oxidative Stress Sources https://www.brightfocus.org/macular/article/age-related-macular-facts-figures https://www.uniprot.org/uniprot/P35398#function https://pubmed.ncbi.nlm.nih.gov/21998696/ https://pubmed.ncbi.nlm.nih.gov/19786043/ We are executing pre-IND studies to support a planned 2023
OCU410 (RORA) A Potential Modifier Therapeutic for Dry-AMD • Genetic modifiers are genes like Nuclear Hormone Receptors (NHR) that can: a) Significantly affect disease outcomes such as onset, rate of progression, and severity b) Enhance or suppress disease phenotypes c) Regulate cellular homeostasis • The Retinoic Acid Related (RAR) Orphan Receptor Alpha (RORA) is a member of the NR1 subfamily of NHRs and regulates several gene networks OCU410 is an adeno- associated virus-based vector containing Human RORA (isoform 1) 18
OCU410 Reduces Drusen in Abca4 -/- Mice, Improves Function • ABCA4 is a retina-specific protein localized in outer segment disk edges of rod photoreceptors • Mutations in ABCA have been linked to: a) Age-related macular degeneration (AMD) b) Stargardt macular dystrophy (STGD) c) Recessive RP d) Recessive cone-rod dystrophy • OCU410 reduces drusen in Abca4 -/- mice and improves retinal function 19
OCU410 Restores Cd59 Expression in Abca4-/- mice IV - Intravitreal; SR-Subretinal; B6 - C57BL/6mice INL - Inner nuclear layer, ONL - outer nuclear layer RPE – Retinal Pigment Epithelium ONL RPE INL • Abca -/- mice show very low CD59 expression in their retinas • CD59 prevents the formation of the complement membrane attack complex (MAC) • OCU410 administered by intravitreal or subretinal routes restores CD59 expression in the RPE cells in the retina 20
21 OCU200 Novel biologic for treating Diabetic Macular Edema (DME), Diabetic Retinopathy (DR) and Wet Age-Related Macular Degeneration (Wet AMD)
22 OCU200 Potential to Treat DME, DR & Wet AMD 30 DME DR Wet AMD OCU200 is a Transferrin-Tumstatin Fusion Protein • Tumstatin: Multiple Mechanisms of Action (MOAs) for treatment and prevention of macular edema and neovascularization • Transferrin: Targets the site of action and improves uptake (better target engagement) Integrin Targeting provides hope to these patients who are non-responders to current therapies Distinct MOA through targeting Integrin pathways can potentially also help reduce number of injections for patients who do respond to Anti-VEGF & corticosteroids therapies We are executing pre-IND studies to support a planned 2023 Phase 1 clinical trial 2 OCU200 Provides hope to ALL patients with DME, DR, or Wet AMD (*) https://www.gene.com/stories/retinal-diseases-fact-sheet https://www.brightfocus.org/macular/article/age-related-macular-facts- figures ~50% of Patients DO NOT Respond to Anti- VEGF/Corticosteroids Therapies ~0.7m ~7.7m ~1.1m patients in the U.S.* patients in the U.S.* patients in the U.S.*
23 OCU200 Demonstrated Superior Efficacy Compared to Existing Anti-VEGF Therapies 30 DME DR 2 Effect of OCU200 intravitreal treatments on Neovascularization (NV). Data are presented as mean± SD. Filled circles represent data points from individual eyes * P < 0.05, ** P < 0.01 (n = 9-10 eyes per group) * indicates p<0.05 when compared to PBS and/or tumstatin treatment † indicates p<0.05 when compared to Avastin; CNV lesions measured on day 14 after treatment Data expressed as percentage of CNV lesions on Day 10 after treatment. Laser induction & treatment start on Day 0 -50 0 50 100 150 N V (% of co nt ro lr et in aN V) Neovascular area (normalized) * ** ** V e h i c le E y l e a O C U 2 0 0 O C U 2 0 0 + E y l e a 4 0 6 0 8 0 L e a k y C N V le s io n s (% ) DME/DR Oxygen-Induced Retinopathy (OIR) Mouse Model Wet AMD In-Vivo Laser-Induced Rat CNV Model Wet AMD In-Vivo Laser-Induced Mouse CNV Model PBS Tumstatin OCU200 Avastin
24 Ocugen™ Vision Fully integrated, patient-centric biotech company focused on vaccines in support of public health and gene and cell therapies targeting unmet medical needs through Courageous Innovation
August 2022 NASDAQ: OCGN Thank you!