Research programme: infectious keratoconjunctivitis nanoparticle therapies - NanoViricides
Alternative Names: EkC-Cide™; EKC-Cide™-ILatest Information Update: 26 Jul 2019
At a glance
- Originator NanoViricides
- Developer Keio University School of Medicine; NanoViricides
- Class Antivirals; Polymers
- Mechanism of Action Virus internalisation inhibitors
-
Orphan Drug Status
No
Orphan designation is assigned by a regulatory body to encourage companies to develop drugs for rare diseases.
- New Molecular Entity Yes
Highest Development Phases
- No development reported Infectious keratoconjunctivitis
Most Recent Events
- 26 Jul 2019 No development reported - Preclinical for Infectious keratoconjunctivitis in USA (Ophthalmic)
- 09 Apr 2019 NanoViricides expects to submit documents regarding pre-IND meeting to US FDA, by April 2019
- 09 Apr 2019 NanoViricides plans to initiate GLP safety and toxicology study in USA, in the second week of May 2019
Development Overview
Introduction
The company Nanoviricides is creating special purpose nanomaterials as antiviral therapy. The EkCCide™ programme uses nanoparticles to target viruses that cause eye diseases such as epidemic kerato-keratoconjunctivitis (infectious conjunctivitis in development table). EkCCide particles seek out and attach to the invading virus particle, engulfing it and destroying it in the process. Preclinical development is underway in the US to determine the potential of the drugs in treating infectious conjunctivitis.
Nanoviricide particles are created chemically by attaching a ligand molecule that binds to the virus naturally and which is derived from the binding site of its cell surface receptor. This is then attached to a nanomicelle flexible polymer. Even when the virus particle mutates, the binding site does not change significantly, meaning that the effectiveness of the particles is not reduced. According to the company, by being able to tailor make the virus-binding ligand and the nanomicelle separately, drug candidates can be rapidly optimised against different viruses and for different routes of administration.
Company Agreements
In November 2019, NanoViricides completed the process of licensing the VZV (shingles and chickenpox virus) field for drug development and commercialization from TheraCour Pharma. Under this Agreement, NanoViricides has obtained a world-wide, exclusive, sub-licensable, license to use, promote, offer for sale, import, export, sell and distribute drugs that treat Varicella Zoster Virus infections, using TheraCour's proprietary as well as patented technology and intellectual property. The discovery of ligands and polymer materials as well as formulations, the chemistry and chemical characterization, as well as process development and related work will be performed by TheraCour under the same compensation terms as prior agreements between the parties. In February 2019, NanoViricides and TheraCour reached an agreement on the terms of the license for the drug development against varicella zoster virus (VZV) and shingles. Subject to a definitive agreement between the two, TheraCour will not receive any payment upon signing of a license agreement and that TheraCour will receive no cash but 750,000 shares of the company's series A Preferred Stock as a milestone payment when an IND (investigational New Drug Application) becomes effective. Additionally, if the NanoViricides completes phase I human clinical trials, then, upon completion, TheraCour will receive a milestone payment of $US1.5 million in cash. Further, if the Company completes phase II human clinical trials, then, upon completion, TheraCour will receive a milestone payment of $US2.5 million in cash and upon completion of phase III trial $US5 million from NanoViricides. TheraCour will receive . Other compensation terms will be consistent with the company's existing license agreements with TheraCour, including a 15% royalty on sales (net of costs) and 15% of sub-licensing revenues. As of May 2012, NanoViricides has an exclusive licence in perpetuity for technologies developed by TheraCour Pharma for the five virus types of HIV, hepatitis B and C, herpes simplex virus, avian influenza and influenza, dengue viruses, rabies virus, Ebola/Marburg viruses, Japanese encephalitis virus as well viruses causing viral conjunctivitis and ocular herpes. NanoViricides shall have no obligation to continue clinical trials beyond phase I. [1] [2]
Key Development Milestones
NanoViricides' drug candidate EKC-Cide™ has shown activity in animal studies of EKC, a viral infection of the eye that is caused by an adenovirus [3] .
In April 2009, NanoViricides released preclinical data for EKC-Cide [3] .
In July 2008, NanoViricides released preclinical data for EKC-Cide [4] .
As of May 2008, confirmatory studies are being performed in Japan [5] [6] [7] .
Financing information
In February 2019, NanoViricides announced a $US2.5 million financing as part of a registered offering, by entering into a securities purchase agreement with various institutional investors. The proceeds from this financing are expected to contribute to the advancement of NanoViricides' preclinical programmes, into clinical development [8] .
In January 2014, NanoViricides secured approximately $US20 million from a registered direct offering, raising the company's available funds to approximately $US40 million. NanoViricides believes that the available cash in hand will be sufficient to fund the phase I and II trials of injectable FluCide™ and initial clinical trials of DengueCide™ . The additional capital will also expedite the development of oral FluCide™, HerpeCide™, HIVCide™, and EKCCide™ toward IND filings and the FDA approval process, as well as support the development of additional nanoviricide™ drug candidates against rabies virus, Ebola/Marburg viruses and MERS-CoV [9] [10] .
NanoViricides reported in September 2013 that it had secured net funds of $US9.66 million from a registered direct offering, bringing the company's total available funds to $US22 million. NanoViricides believes it now has adequate funds to carry out phase I and II trials of injectable FluCide, and to expedite the development of oral FluCide™, HerpeCide™, HIVCide™, and EKCCide™, as well as to rapidly advance the development of its nanoviricide dengue therapeutic for clinical trials [11] .
Financing information
In February 2019, NanoViricides announced a $US2.5 million financing as part of a registered offering, by entering into a securities purchase agreement with various institutional investors. The proceeds from this financing are expected to contribute to the advancement of NanoViricides' preclinical programmes, into clinical development [8] .
Patent Information
As of October 2012, NanoViricides licensed patents from TheraCour® technology underlying nanoviricides® drugs. The patent covers the polymeric micelles composition, structure and uses was issued in the USA with substantially broad claims [12] .
In May 2012, NanoViricides was granted US Patent No. 8 173 764 for "Solubilisation and Targeted Delivery of Drugs with Self-Assembling Amphiphilic Polymers". The patent covers a broad range of claims to a large number of families of chemical structure compositions, pharmaceutical compositions, methods of making the same, and uses of the same. The disclosed structures enable self-assembling, biomimetic nanomedicines. This patent is due to expire on 1 October, 2026. Corresponding patents have also been issued in New Zealand, South Africa, and as a regional patent valid in 16 other African states. Additional patents are expected to be issued in Europe and other countries around the world. These patents are based on the international PCT application No. WO 2007/1084126 filed in 2006 [1] .
Drug Properties & Chemical Synopsis
- Route of administration Intravitreous, IV, Ophthalmic, Parenteral, PO, SC, Topical
- Formulation Drops
- Class Antivirals, Polymers
- Target Virus internalisation
- Mechanism of Action Virus internalisation inhibitors
-
WHO ATC code
J05 (Antivirals for Systemic Use)
J07B-X (Other viral vaccines)
S01X (Other Ophthalmologicals)
-
EPhMRA code
J5 (Antivirals for Systemic Use)
J5B1 (Viral hepatitis products)
J5B3 (Herpes antivirals)
J7E (Viral Vaccines)
S1X (Other Ophthalmologicals)
Development Status
Summary Table
| Indication | Qualifier | Patient Segment | Phase | Countries | Route / Formulation | Developers | Event Date |
|---|---|---|---|---|---|---|---|
| Infectious keratoconjunctivitis | - | - | No development reported (Preclinical) | USA | Ophthalmic / Drops | NanoViricides | 26 Jul 2019 |
| Infectious keratoconjunctivitis | - | - | No development reported (Preclinical) | Japan | Ophthalmic / Drops | Keio University School of Medicine | 04 Nov 2017 |
Commercial Information
Involved Organisations
| Organisation | Involvement | Countries |
|---|---|---|
| NanoViricides | Originator | USA |
| NanoViricides | Owner | USA |
| TheraCour Pharma | Technology Provider | Unknown |
| Keio University School of Medicine | Collaborator | Japan |
Scientific Summary
Pharmacodynamics
Data from the first animal study in EKC, demonstrated a rapid clinical response (within 3 days post-treatment with nanoviricides) as indicated by a statistically significant increase in prevention of conjunctival injection (redness, dilation and prominence of conjunctival blood vessels) and blepharitis (crusting, discharge and inflammation of the eyelid margins) when compared with the control group which received an inactive drop preparation [4] . These results have been confirmed by additional results, indicating that both of the nanoviricide drug candidates evaluated in its pilot study were found to be clinically highly effective against EKC caused by an adenovirus in a rabbit model. Both nanoviricides significantly reduced conjunctival injection (severe redness of the eye) as well as blepharitis (exudate, swelling, matting of fur). The best nanoviricide drug candidates showed excellent long-term results. There were no sub-epithelial infiltrates (SEIs) in animals treated with this nanoviricide (0% incidence). In contrast, 83% incidence of SEIs was seen in vehicle-treated animals, and a 100% incidence of SEIs occurred in untreated infected animals. SEIs are caused by local T cell-mediated immune response to the adenovirus, leading to hazy spots in the cornea. Occurrence of SEIs in the human eye can lead to decreased visual acuity for as long as 2 years [3] .
Future Events
| Expected Date | Event Type | Description | Updated |
|---|---|---|---|
| 14 May 2019 | Trial Update | NanoViricides plans to initiate GLP safety and toxicology study in USA, in the second week of May 2019 [13] | 15 Apr 2019 |
| 29 Apr 2019 | Regulatory Status | NanoViricides expects to submit documents regarding pre-IND meeting to US FDA, by April 2019 [13] | 22 Apr 2019 |
Development History
| Event Date | Update Type | Comment |
|---|---|---|
| 26 Jul 2019 | Phase Change - No development reported(Preclinical) | No development reported - Preclinical for Infectious keratoconjunctivitis in USA (Ophthalmic) Updated 26 Jul 2019 |
| 09 Apr 2019 | Regulatory Status | NanoViricides expects to submit documents regarding pre-IND meeting to US FDA, by April 2019 [13] Updated 22 Apr 2019 |
| 09 Apr 2019 | Trial Update | NanoViricides plans to initiate GLP safety and toxicology study in USA, in the second week of May 2019 [13] Updated 15 Apr 2019 |
| 04 Nov 2017 | Phase Change - No development reported | No recent reports of development identified for preclinical development in Infectious keratoconjunctivitis in Japan (Ophthalmic, Drops) Updated 04 Nov 2017 |
| 17 Oct 2012 | Licensing Status | NanoViricides in licenses patents for development of NanoViricide from TheraCure [12] Updated 26 Jul 2019 |
| 07 May 2012 | Patent Information | NanoViricides has patent protection for NanoViricides technology in USA [1] Updated 26 Jul 2019 |
| 07 May 2012 | Licensing Status | NanoViricides and TheraCour Pharma enter into a licensing agreement to develop drug against Retinal disorders [2] Updated 01 Mar 2019 |
| 21 Apr 2009 | Scientific Update | Pharmacodynamics data from a preclinical trial in epidemic keratoconjunctivitis released by NanoViricides [3] Updated 27 Apr 2009 |
| 16 Jul 2008 | Scientific Update | Interim pharmacodynamics data from a preclinical study in Epidemic keratoconjunctivitis released by NanoViricides [4] Updated 16 Jul 2008 |
| 19 May 2008 | Phase Change - Preclinical | Preclinical trials in Infectious keratoconjunctivitis in Japan (Ophthalmic, Drops) Updated 30 Oct 2009 |
| 19 May 2008 | Phase Change - Preclinical | Preclinical trials in Infectious keratoconjunctivitis in USA (Ophthalmic) Updated 21 May 2008 |
References
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NanoViricides Announces Issuance of a Fundamental Patent in the USA
Media Release -
NanoViricides Reaches an Agreement on Terms of License for Shingles Virus Drug Development.
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NSLIJ Scientists to Present EKC-Cide(TM) Study Results at the GTC-Bio Conference on Ocular Diseases and Drug Discovery.
Media Release -
NanoViricide's EKC Eye Drug Candidate Stopped Clinical Conjunctivitis Pathology.
Media Release -
NanoViricides' Anti-EKC Drug Candidate to Be Studied in Japan.
Media Release -
NanoViricides' EKC Eye Drug Demonstrates Significant Therapeutic Efficacy in Initial Animal Trials.
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NanoViricides Platform Enables Rapid Development of Robust Nanomedicines Against Influenza and HIV.
Media Release -
NanoViricides Announces $2.5 Million Financing in a Registered Direct Offering.
Media Release -
NanoViricides, Inc. Files Quarterly Report - Reports a Strong Cash Position Sufficient for Clinical Trials of its First Two Drug Candidates.
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NanoViricides Announces that It Has Raised $20 Million in a Registered Direct Offering.
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NanoViricides Announces that It Has Raised approximately $10.33 Million in the Registered Direct Offering Announced Recently and Discusses Shareholder Issues since the Reverse Split.
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NanoViricides Files Annual Report - Reports Having Sufficient Funds for Current Goals and For Advancing Its Robust Drug Pipeline.
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NanoViricides Provides Update on Pre-IND Meeting with the US FDA, GLP Safety/Toxicology Studies to Begin Soon, Multiple Kg Scale Drug Production Accomplished at Its Own Facility.
Media Release
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