Science &
Technology

We’re here to make an impact. At Ocugen, we approach drug development with a sense of urgency, resolve, ingenuity, and boldness. We consider patients in everything we do. Courageous innovation means driving science in new directions and breaking new ground.

PIPELINE

PRECLINICAL
IND-Enabling
PHASE 1
PHASE 2
PHASE 3
  • Vaccine

    Asset/ Program
    COVAXIN™ (BBV152)
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    Whole-Virion Inactivated Vaccine

    Therapeutic Area

    Covid-19

    Phase

    Phase 2/3

    Phase 2/3

    The COVID-19 vaccine candidate BBV152, known as COVAXIN™ outside the United States, is a whole-virion inactivated COVID-19 vaccine candidate that applies the same vero cell manufacturing platform used in the production of polio vaccines for decades. It has been granted Emergency Use Listing by the World Health Organization, based on a submission by partner, Bharat Biotech.

    Unique to COVAXIN™ (BBV152) is its novel, Algel-IMDG (TLR 7/8) adjuvant, which together with the inactivated virus is designed to elicit an immune response against multiple antigens (S1, N and RBD) and generate memory T-cell responses against several epitopes. IMDG is a novel immunomodulator developed in collaboration with the National Institutes of Health. It can be stored at 2-8 °C for up to two years, and is stable for six months at room temperature (25°C).

    COVAXIN™ (BBV152) was co-developed with Bharat Biotech, in collaboration with the Indian Council of Medical Research (ICMR) – National Institute of Virology (NIV).

    COVAXIN™ (BBV152) is a two-dose vaccine given at Days 0 and 28. COVAXIN™ (BBV152) demonstrated a vaccine efficacy in mild, moderate, and severe COVID-19 disease of 77.8% with efficacy against severe COVID-19 disease alone of 93.4%. Adverse events reported were similar to placebo, with 12.4% of subjects experiencing commonly known side effects and less than 0.5% of subjects feeling serious adverse events. It is under clinical investigation in the U.S. for use in adults 18+ based on a Phase 3 clinical trial conducted in India and whose results were published in The Lancet.

    An additional study has shown how the candidate vaccine generates neutralizing antibodies against the Omicron and Delta variants.

    Learn more about our candidate vaccine.

    Publications:

    Preclinical Product Development
    https://www.biorxiv.org/content/10.1101/2020.09.09.285445v2

    Animal Challenge Studies – Hamsters
    https://www.researchsquare.com/article/rs-76768/v1

    Animal Challenge Studies – Rhesus Macaques
    https://www.nature.com/articles/s41467-021-21639-w

    Human Clinical Trials – Phase I
    https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(20)30942-7/fulltext

    Human Clinical Trials – Phase II
    https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(21)00070-0/fulltext

    Inactivated COVID-19 vaccine BBV152/COVAXIN effectively neutralizes recently emerged B 1.1.7 variant of SARS-CoV-2
    https://ocugen.com/wp-content/uploads/2021/05/Inactivated-COVID-19-vaccine-BBV152COVAXIN-effectively-neutralizes-recently.pdf

    COVAXIN effectively neutralizes B.1.617 variant of SARS-CoV-2
    https://ocugen.com/wp-content/uploads/2021/04/BioRxIv-Neutralization-of-variant-under-investigaton-B.1.617-with-sera-of-BBV152-vaccinees.pdf

    Neutralization of B.1.1.28 P2 variant with sera of natural SARS-CoV-2 infection and recipients of BBV152 vaccine
    https://ocugen.com/wp-content/uploads/2021/05/Neutralization-of-B.1.1.28-P2-variant-with-sera-of-natural-SARS-CoV-2-infection-and.pdf

    Efficacy, safety, and lot to lot immunogenicity of an inactivated SARS-CoV-2 vaccine (BBV152): a, double-blind, randomised, controlled phase 3 trial
    https://www.medrxiv.org/content/10.1101/2021.06.30.21259439v1.full.pdf

    Efficacy, safety, and lot-to-lot immunogenicity of an inactivated SARS-CoV-2 vaccine (BBV152): interim results of a randomised, double-blind, controlled, phase 3 trial
    https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)02000-6/fulltext

    Inactivated virus vaccine BBV152/Covaxin elicits robust cellular immune memory to SARS-CoV-2 and variants of concern
    https://www.medrxiv.org/content/10.1101/2021.11.14.21266294v1

  • Ocugen’s modifier gene therapy platform is a cutting-edge technology licensed from the Schepens Eye Research Institute of Massachusetts Eye and Ear (Harvard Medical School) and involves delivery and expression of one or more nuclear hormone receptor genes (NHRs) in the disease tissues. NHRs play a vital role in regulating retinal cell progression, maturation, metabolism, visual cycle function, survival, and maintaining the cellular and molecular homeostasis in retinal tissues. In multiple animal models, expression of NHRs within the retina stabilized retinal cells and suppressed/prevented the development of inherited diseases and dry age-related macular degeneration, demonstrating proof of concept for their modifier function.

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  • Asset/ Program
    OCU400
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    AAV-NR2E3
    Received orphan drug designation

    Therapeutic Area

    Treatment of NR2e3 and Rhodopsin mutations

    Phase

    Phase 1/2

    Phase 1/2

    OCU400 (AAV-NR2E3) is a novel gene therapy product candidate with the potential to be broadly effective in restoring retinal integrity and function across a range of genetically diverse inherited retinal diseases (“IRDs”). It consists of a functional copy of a nuclear hormone receptor (“NHR”) gene, NR2E3, delivered to target cells in the retina using an adeno-associated viral (“AAV”) vector. As a potent modifier gene, expression of NR2E3 within the retina may help reset retinal homeostasis, potentially stabilizing cells and rescuing photoreceptor degeneration.

    In 5 unique mouse models of RP, treatment with the AAV-NR2E3 gene by subretinal injection rescued multiple genetically diverse IRDs by protecting photoreceptors from further damage after disease onset. The five RP models tested were rd1 (PDE6β associated RP), Rho-/- and RhoP23H (both Rhodopsin associated RP), rd16 (Leber Congenital Amaurosis) and rd7 (Enhanced S-cone Syndrome). The study, published in Nature Gene Therapy, demonstrates the potential of a novel modifier gene therapy to elicit broad-spectrum therapeutic benefits in early and intermediate stages of RP and Leber Congenital Amaurosis (LCA) based on animal models, showing the potential for a mutation-agnostic treatment.

    Currently, Ocugen is developing OCU400 for the treatment of multiple IRDs encompassing RP and LCA.

    Publications:

    Li, S., Datta, S., Brabbit, E. et al. Nr2e3 is a genetic modifier that rescues retinal degeneration and promotes homeostasis in multiple models of retinitis pigmentosa. Gene Ther (2020). https://doi.org/10.1038/s41434-020-0134-z 

    Haider, N. B. et al. Mapping of genetic modifiers of Nr2e3rd7/rd7 that suppress retinal degeneration and restore blue cone cells to normal quantity. Mammalian Genome 19, 145-154, https://pubmed.ncbi.nlm.nih.gov/18286335/ (2008).

    Cruz NM, Yuan Y, Leehy BD, Baid R, Kompella U., et. al. (2014)
    Modifier Genes as Therapeutics: The Nuclear Hormone Receptor Rev Erb Alpha (Nr1d1) Rescues Nr2e3 Associated Retinal Disease, PLoS ONE 9(1): e87942.

    Olivares, A. M. & Haider, N. B. Role of Nuclear Receptors in Central Nervous System Development and Associated Diseases. 9, 93-121, https://journals.sagepub.com/doi/10.4137/JEN.S25480  (2015).

    Mollema, N. & Haider, N. B. Focus on Molecules: Nuclear hormone receptor Nr2e3: Impact on retinal development disease. Experimental Eye Research 91, 116-117, doi:10.1016/j.exer.2010.04.013 (2010).

    Cheng, H. et al. In vivo function of the orphan nuclear receptor NR2E3 in establishing photoreceptor identity during mammalian retinal development. Hum Mol Genet 15, 2588-2602, https://academic.oup.com/hmg/article/15/17/2588/852398 (2006).

    Haider, N. B. et al. The transcription factor Nr2e3 functions in retinal progenitors to suppress cone cell generation. Visual Neuroscience 23, 917-929, https://www.cambridge.org/core/journals/visual-neuroscience/article/abs/transcription-factor-nr2e3-functions-in-retinal-progenitors-to-suppress-cone-cell-generation/467BD0AFF1A683B45D9028EE2C50C027  (2006).

    Schorderet, D. F. & Escher, P. NR2E3 mutations in enhanced S-cone sensitivity syndrome (ESCS), Goldmann-Favre syndrome (GFS), clumped pigmentary retinal degeneration (CPRD), and retinitis pigmentosa (RP). Human Mutation 30, 1475-1485, https://onlinelibrary.wiley.com/doi/10.1002/humu.21096  (2009).

  • Asset/ Program
    OCU410
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    AAV-hRORA

    Therapeutic Area

    Dry Age-Related Macular Degeneration


    Phase

    IND-Enabling

    IND-Enabling

    OCU410 (AAV-RORA) is a modifier gene therapy product candidate being developed for the treatment of dry age-related macular degeneration (Dry AMD). OCU410 utilizes an AAV delivery platform for the retinal delivery of the RORA (RAR Related Orphan Receptor A) gene. Various genes associated with AMD are regulated by RORA. The RORA protein plays an important role in lipid metabolism and demonstrates an anti-inflammatory role, which we believe could be a potential therapeutic candidate for dry AMD based on in-vitro and in-vivo (animal model) studies.

    Publications:

    Olivares, a. M. et al. Multimodal Regulation Orchestrates Normal and Complex Disease States in the Retina /631/114/2114. Scientific Reports 7, 1-16, doi:10.1038/s41598-017-0788-3 (2017).

    Jun, G. et al. Influence of ROBO1 and RORA on Risk of Age-Related Macular Degeneration Reveals Genetically Distinct Phenotypes in Disease Pathophysiology. PLoS ONE 6, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0025775 (2011).

    Katie L. Pennington and Margaret M. DeAngelis. Epidemiology of age-related macular degeneration (AMD): associations with cardiovascular disease phenotypes and lipid factors. Eye Vis (Lond). 2016; 3: 34.

    Xiaoyan Ding, Mrinali Patel, and Chi-Chao Chana. Molecular pathology of age-related macular degeneration. Prog Retin Eye Res. 2009 Jan; 28(1): 1-18.

    Silveira, AC. et al. Convergence of linkage, gene expression and association data demonstrates the influence of the RAR-related orphan receptor alpha (RORA) gene on neovascular AMD: a systems biology based approach. Vision Res. 2010 Mar 31;50(7):698-715.

    Sun, Y et al. Nuclear receptor RORα regulates pathologic retinal angiogenesis by modulating SOCS3-dependent inflammation. Proc Natl Acad Sci U S A. 2015 Aug 18;112(33):10401-6.

  • Novel Biologic

    Asset/ Program
    OCU200
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    Transferrin-Tumstatin

    Therapeutic Area

    Diabetic Macular Edema
    Diabetic Retinopathy
    Wet Age-Related Macular Degeneration (Wet AMD)

    Phase

    IND-Enabling

    IND-Enabling

    OCU200 is a biologic product candidate in preclinical development for treating severely sight-threatening diseases like Diabetic Macular Edema (DME), Diabetic Retinopathy (DR), and Wet Age-Related Macular Degeneration (Wet-AMD). Patients affected by these diseases share common symptoms, such as blurriness in vision and progressive vision loss as the disease progresses. The formation of fragile and leaky new blood vessels leads to fluid accumulation in and around the retina, causing damage to vision.

    OCU200 is a novel fusion protein consisting of two human proteins, tumstatin and transferrin, that are already present normally in retinal tissues. OCU200 unique features which we believe will enable it to (a) efficiently target leaky blood vessels, (b) regress the existing abnormal blood vessels, and (c) inhibit the growth of new blood vessels in the retina and choroid. Tumstatin, which acts as an anti-VEGF, anti-inflammatory and anti-oxidative agent, is the active component of OCU200. It binds to integrin receptors, which play a crucial role in disease pathogenesis. Transferrin facilitates the targeted delivery of tumstatin into the retina and choroid and potentially helps increase the interaction between tumstatin and integrin receptors.

    In preclinical studies, OCU200 demonstrated efficacy in different animal models of neovascularization. In an animal model for DME and DR (Oxygen-induced retinopathy in mice), OCU200 demonstrated comparable efficacy at significantly lower dose compared to existing approved anti-VEGF therapy in preventing disease manifestation and progression. In animal models for wet AMD (laser induced CNV in mice and rats), OCU200 demonstrated superior activity compared to anti-VEGF control groups in preventing the formation and growth of new leaky blood vessels and subsequent disease symptoms.

    OCU200 Demonstrated Efficacy in Animal Models for DME, DR, and Wet-AMD

    Publications:

    Friedlander M, Theesfeld CL, Sugita M, Fruttiger M, Thomas MA, Chang S, Cheresh DA. Involvement of integrins alpha v beta 3 and alpha v beta 5 in ocular neovascular diseases. Proc Natl Acad Sci U S A. 1996 Sep 3;93(18):9764-9.

    Maeshima Y, Colorado PC, Torre A, Holthaus KA, Grunkemeyer JA, Ericksen MB, Hopfer H, Xiao Y, Stillman IE, Kalluri R. Distinct antitumor properties of a type IV collagen domain derived from basement membrane. J Biol Chem. 2000 Jul 14;275(28):21340-8.

    Raquel Lima e Silva, Yogita Kanan, Adam C. Mirando, Jayoung Kim, Ron B. Shmueli, Valeria E. Lorenc, Seth D. Fortmann, Jason Sciamanna, Niranjan B. Pandey, Jordan J. Green, Aleksander S. Popel, Peter A. Campochiaro. Tyrosine kinase blocking collagen IV-derived peptide suppresses ocular neovascularization and vascular leakage. Sci Transl Med. 2017 Jan 18;9(373). pii:eaai8030. https://www.science.org/doi/10.1126/scitranslmed.aai8030 

    Venugopal Gunda and Yakkanti A Sudhakar. Regulation of Tumor Angiogenesis and Choroidal Neovascularization by Endogenous Angioinhibitors. J Cancer Sci Ther.;5(12): 417-426. https://www.hilarispublisher.com/open-access/regulation-of-tumor-angiogenesis-and-choroidal-neovascularization-by-endogenous-angioinhibitors-1948-5956.1000235.pdf 

    Maeshima Y, Colorado PC, Kalluri R. Two RGD-independent alpha v beta 3 integrin binding sites on tumstatin regulate distinct anti-tumor properties. J Biol Chem. 2000 Aug 4;275(31):23745-50.

    http://www.modernretina.com/modern-retina/news/anti-pdgf-inhibitor-development-continues-despite-negative-results 

    https://lowvision.preventblindness.org/2017/06/29/anti-vegf-treatment-should-not-be-expected-to-improve-vision/ 

    Maguire, MG et al. Five-Year Outcomes with Anti-Vascular Endothelial Growth Factor Treatment of Neovascular Age-Related Macular Degeneration: The Comparison of Age-Related Macular Degeneration Treatments Trials. Ophthalmology. 2016 Aug; 123(8):1751-1761. https://www.aaojournal.org/article/S0161-6420(16)30092-6/fulltext 2016 May 2.

    Patel, PJ et al. Aflibercept treatment for neovascular AMD beyond the first year: consensus recommendations by a UK expert roundtable panel, 2017 update. Clin Ophthalmol 11, 1957-1966, https://www.dovepress.com/aflibercept-treatment-for-neovascular-amd-beyond-the-first-year-consen-peer-reviewed-fulltext-article-OPTH (2017).