Research programme: siRNA therapeutics - OliX Pharmaceuticals
Alternative Names: asiRNA therapeutics - OliX Pharmaceuticals; BMT 101; cp-asiRNA therapeutics - OliX Pharmaceuticals; OLX 10020; OLX 103; OLX 201; OLX 301; OLX 401; OLX 701Latest Information Update: 10 May 2022
At a glance
- Originator BioMolecular Therapeutics
- Developer OliX Pharmaceuticals; University of Virginia School of Medicine
- Class Analgesics; Antifibrotics; Antivirals; Eye disorder therapies; Skin disorder therapies; Small interfering RNA
- Mechanism of Action Connective tissue growth factor inhibitors; RNA interference
-
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
- Preclinical Brain disorders; Neuropathic pain
- Research COVID 2019 infections
- No development reported Age-related macular degeneration; Atopic dermatitis; Hepatic fibrosis; Idiopathic pulmonary fibrosis
- Discontinued Cancer; Herpes simplex virus infections
Most Recent Events
Development Overview
Introduction
siRNA therapeutics are being developed by OliX Pharmaceuticals (formerly BioMolecular Therapeutics) for the treatment of dermatological, ophthalmic, pulmonary disorders, COVID-2019 and CNS diseases, such as neuropathic pain and degenerative brain disorders. Company's proprietary cell penetrating asymmetric siRNA (cp-asiRNA) compounds are different from traditional siRNA. These are based on asymmetric shorter-duplex siRNA (asiRNA), which is a 15-16 bp sense strand paired to a 19-21 bp antisense strand. Asymmetric siRNA is designed to specifically target implicated disease gene(s) and silence them. The siRNA therapeutic potentially avoids triggering the innate immune system, an unwanted off-target effect, which is often a problem associated with conventional siRNA therapies. cp-asiRNA compounds have shown to efficiently induce gene silencing in animal models and can deliver into hard to transfect cells including primary and suspension cells, without requiring special formulation or instrument. Lead molecules from connective tissue growth factor (CTGF) targeting programmes include, OLX 201 which is being developed as an aerosol formulation in collaboration with Korea Institute of Toxicology for idiopathic pulmonary fibrosis. Another candidate, OLX 301 (OLX 10020) that targets an undruggable gene involved in both wet and dry age-related macular degeneration is being developed in collaboration with University of Virginia. OLX 301 is a first-in-class therapeutic with potential to treat both wet and dry age-related macular degeneration. OLX 701 is being developed for liver fibrosis. These molecules target CTGF, whose increased expression in injuries leads to scarring and fibrosis. OliX Pharmaceuticals is also developing OLX 103 for atopic dermatitis, OLX 401 for neuropathic pain and OLX 402 for brain disorders. Preclinical development in underway in South Korea and the US. Early research for COVID-19 is underway in South Korea.
OliX Pharmaceuticals was developing siRNA therapeutics for herpes simplex virus infections, and cancer however as at January 2018, these indications are not listed on company's pipeline and hence the development has been discontinued.
The company is also developing siRNA technology for cosmetic use including skin whitening, hair loss and anti-wrinkle treatments.
In September 2014, Biomolecular Therapeutics changed its name to OliX Pharmaceuticals (OliX Pharmaceuticals Website, January 2018).
OLX 401A [see AdisInsight drug profile800068462] and OLX 402 [see AdisInsight drug profile800068463] have emerged from this research programme.
OLX 10010 [see AdisInsight drug profile800052077] and OLX 304A [see AdisInsight drug profile800054779] have emerged from this research programme.
As at February 2022, no recent reports of development had been identified for preclinical development in Age-related-macular-degeneration in South Korea, preclinical development in Atopic-dermatitis in South Korea (Topical), preclinical development in Hepatic-fibrosis in South Korea, and preclinical development in Idiopathic-pulmonary-fibrosis in South Korea (Inhalation, Aerosol).
Company Agreements
In March 2019, OliX Pharmaceuticals entered into a license and collaboration agreement with Thea Open Innovation, to develop and commercialize OLX 301A. Under the agreement, OliX receives a non-refundable and non-creditable upfront payment of €2 million [Adis conversion ≈ $US2.26 million] and is eligible to receive milestone payments upon achievement of clinical milestones, plus royalty for the development and commercialisation. Thea has been granted licensing rights for OLX 301A program in EU countries, Middle East and Africa. OliX continues to hold the rights of OLX 301A program for US and Asia. In October 2020, OliX Pharmaceuticals expanded the agreement granting Thea worldwide rights, with the exclusion of Asia-Pacific, for OLX 301A and OLX 301D, for the treatment of dry/wet AMD and wet AMD/subretinal fibrosis, respectively. Additionally OliX granted Thea an option to nominate two more ophthalmic pipeline programmes. Thea will pay a total of €8.8 million [Adis conversion ≈ $US10.38 million] to OliX, inclusive of upfront payments for OLX 301A and OLX 301D, an option fee for the two additional ophthalmic programmes, along with prospective development and commercialisation milestones, should the option be exercised. Thea possesses global rights to these four programmes, excluding Asia-Pacific. [1] [2]
In January 2012, BioMolecular Therapeutics announced it had entered a research collaboration with Samyang, a Korean-based company, for the development of RNAi therapeutics. As part of the agreement BioMolecular Therapeutics will conduct validation studies regarding the use of the RNAi technology against targets identified by Samyang.
Key Development Milestones
In January 2019, OliX Pharmaceuticals reported its intention to submit an IND application to the US FDA for OLX 301 for initiation of a phase I trial in dry age-related macular degeneration (geographic atrophy) in 2019. OliX Pharmaceuticals completed preliminary safety studies of OLX 301 and initiated GLP toxicology studies [3] .
In May 2022, OliX Pharmaceuticals announced that it has identified effective inhibition of target gene expression in rodent brain tissues for its central nervous system (CNS) treatment program. With a single intrathecal injection of its optimized therapeutic candidate, the company identified up to 90 percent knockdown of gene expression in a rodent study. The siRNA was delivered not only to the spinal cord but also to multiple areas of the brain [4] .
In preclinical trials, OLX 301 demonstrated efficacy in animal models of both wet and dry-age related macular degeneration [3] .
In October 2010, BioMolecular Therapeutics reported research on the immune stimulation effect of asymmetric shorter-duplex siRNA [5] .
Financing information
In July 2018, Olix Pharmaceuticals raised a capital of KRW43 billion ($US38 million) in the Korea Securities Dealer Automated Quotation (KOSDAQ) listing, which would be used for research and development of therapeutic programs including idiopathic pulmonary fibrosis (OLX 201), and age-related macular degeneration (OLX 301A and OLX 301D) [6] .
In April 2015, Olix Pharmaceuticals secured a grant from The Small and Medium Business Administration, Korea for the development of OLX 103, for atopic dermatitis (Olix Pharmaceuticals website, January 2018).
In October 2014, Olix Pharmaceuticals received a three years funding of $US1.8 million from A*STAR, Singapore and Korea Health Industry Development Institute, for the development of OLX 201 for the treatment of idiopathic pulmonary fibrosis (Olix Pharmaceuticals website, January 2018).
Patent Information
In May 2021, Olix Pharmaceuticals received a notice of allowance from the United States Patent and Trademark Office (USPTO) for its enhanced platform technology that aims to improve the potency of RNAi therapeutics by increasing delivery of siRNA to target cells [7] .
In February 2020, Olix Pharmaceuticals filed a provisional patent application covering composition of matter claims to more than 30 small interfering RNAs (siRNAs) designs that target available genomes of the COVID virus [8] .
Olix Pharmaceuticals holds patent tiRNA (PCT/KR2010/000678) issued in South Korea, Europe, Japan and is under review in the US (Olix Pharmaceuticals website, May 2021).
Olix Pharmaceuticals holds patent for cp-asiRNA (PCT/KR2013/004463) issued in South Korea, the US, Europe, Japan and China (Olix Pharmaceuticals website, May 2021).
Olix Pharmaceuticals holds patent for asiRNA (PCT/KR2008/007530) issued in South Korea, Europe, Japan, Australia and China (Olix Pharmaceuticals website, May 2021).
Olix Pharmaceuticals holds patent lasiRNA (PCT/KR2011/006632) issued in South Korea, the US, Europe, Japan and China (Olix Pharmaceuticals website, May 2021).
Olix Pharmaceuticals holds patent bg-asiRNA (PCT/KR2010/007771) issued in South Korea and the US (Olix Pharmaceuticals website, May 2021).
Drug Properties & Chemical Synopsis
- Route of administration Inhalation, Intrathecal, Topical
- Formulation Aerosol, Injection, unspecified
- Class Analgesics, Antifibrotics, Antivirals, Eye disorder therapies, Skin disorder therapies, Small interfering RNA
- Target Connective tissue growth factor
- Mechanism of Action Connective tissue growth factor inhibitors; RNA interference
-
WHO ATC code
A05B-A (Liver therapy)
D03A (Cicatrizants)
D11 (Other Dermatological Preparations)
J05 (Antivirals for Systemic Use)
L01 (Antineoplastic Agents)
N02 (Analgesics)
N07 (Other Nervous System Drugs)
R07 (Other Respiratory System Products)
S01 (Ophthalmologicals)
-
EPhMRA code
A5B (Hepatic Protectors, Lipotropics)
D11 (Other Dermatological Preparations)
D3 (Wound Healing Agents)
J5 (Antivirals for Systemic Use)
L1 (Antineoplastics)
N2 (Analgesics)
N7 (Other CNS Drugs)
R7 (Other Respiratory System Products)
S1 (Ophthalmologicals)
Table of Contents
Development Status
Summary Table
| Indication | Qualifier | Patient Segment | Phase | Countries | Route / Formulation | Developers | Event Date |
|---|---|---|---|---|---|---|---|
| Age-related macular degeneration | - | - | No development reported (Preclinical) | South Korea | unspecified / unspecified | OliX Pharmaceuticals, University of Virginia School of Medicine | 28 Feb 2022 |
| Atopic dermatitis | - | - | No development reported (Preclinical) | South Korea | Topical / unspecified | OliX Pharmaceuticals | 28 Feb 2022 |
| Brain disorders | - | - | Preclinical | South Korea | Intrathecal / Injection | OliX Pharmaceuticals | 04 May 2022 |
| COVID 2019 infections | - | - | Research | South Korea | unspecified / unspecified | OliX Pharmaceuticals | 20 Mar 2020 |
| Cancer | - | - | Discontinued (Preclinical) | South Korea | unspecified / unspecified | OliX Pharmaceuticals | 22 Jan 2018 |
| Hepatic fibrosis | - | - | No development reported (Preclinical) | South Korea | unspecified / unspecified | OliX Pharmaceuticals | 28 Feb 2022 |
| Herpes simplex virus infections | - | - | Discontinued (Preclinical) | South Korea | unspecified / unspecified | OliX Pharmaceuticals | 22 Jan 2018 |
| Idiopathic pulmonary fibrosis | - | - | No development reported (Preclinical) | South Korea | Inhalation / Aerosol | OliX Pharmaceuticals | 28 Feb 2022 |
| Neuropathic pain | - | - | Preclinical | South Korea | Intrathecal / Injection | OliX Pharmaceuticals | 22 Jan 2018 |
Commercial Information
Involved Organisations
| Organisation | Involvement | Countries |
|---|---|---|
| BioMolecular Therapeutics | Originator | South-Korea |
| OliX Pharmaceuticals | Owner | South-Korea |
| Hugel | Licensee | Asia |
| Thea Open Innovation | Licensee | Africa, European Union, Middle East |
| AM Chemicals | Technology Provider | USA |
| Small and Medium Business Administration | Funder | South-Korea |
| Korea Health Industry Development Institute | Funder | South-Korea |
| A STAR | Funder | Singapore |
| Korea Drug Development Fund | Funder | South-Korea |
| Samyang Biopharmaceuticals Corporation | Collaborator | South-Korea |
| Korea Institute of Toxicology | Collaborator | South-Korea |
| University of Virginia School of Medicine | Collaborator | USA |
Future Events
| Expected Date | Event Type | Description | Updated |
|---|---|---|---|
| 30 Jun 2020 | Trial Update | Olix Pharmaceuticals plans to initiate preclinical study for COVID-2019 infections within three months [8] | 10 May 2022 |
| 31 Dec 2019 | Regulatory Status | OliX Pharmaceuticals intends to file an IND application for OLX 301 with the US FDA for Dry age-related macular degeneration in 2019 [3] | 22 Jan 2019 |
| 31 Dec 2019 | Trial Update | OliX Pharmaceuticals plans a phase I trial for OLX 301 for Dry age-related macular degeneration in USA in 2019 [3] | 22 Jan 2019 |
| 01 Aug 2019 | Trial Update | Hugel plans a phase II trial for Hypertrophic scars in South Korea in August 2019 (NCT04012099) | 10 Jul 2019 |
Development History
| Event Date | Update Type | Comment |
|---|---|---|
| 10 May 2022 | Active Status Review | Preclinical development in Neuropathic-pain is ongoing in South Korea [4] Updated 10 May 2022 |
| 04 May 2022 | Phase Change - Preclinical | Preclinical trials in Brain disorders in South Korea (Intrathecal) [4] Updated 10 May 2022 |
| 28 Feb 2022 | Phase Change - No development reported | No recent reports of development identified for preclinical development in Age-related-macular-degeneration in South Korea Updated 28 Feb 2022 |
| 28 Feb 2022 | Phase Change - No development reported | No recent reports of development identified for preclinical development in Atopic-dermatitis in South Korea (Topical) Updated 28 Feb 2022 |
| 28 Feb 2022 | Phase Change - No development reported | No recent reports of development identified for preclinical development in Hepatic-fibrosis in South Korea Updated 28 Feb 2022 |
| 28 Feb 2022 | Phase Change - No development reported | No recent reports of development identified for preclinical development in Idiopathic-pulmonary-fibrosis in South Korea (Inhalation, Aerosol) Updated 28 Feb 2022 |
| 28 Feb 2022 | Phase Change - No development reported | No recent reports of development identified for preclinical development in Neuropathic-pain in South Korea Updated 28 Feb 2022 |
| 28 May 2021 | Patent Information | Olix Pharmaceuticals has patent protection for asiRNA technology in South Korea, Europe, Japan, Australia and China (Olix Pharmaceuticals website, May 2021) Updated 28 May 2021 |
| 28 May 2021 | Patent Information | Olix Pharmaceuticals has patent protection for bg-asiRNA technology in South Korea and USA (Olix Pharmaceuticals website, May 2021). Updated 28 May 2021 |
| 28 May 2021 | Patent Information | Olix Pharmaceuticals has patent protection for cp-asiRNA technology in South Korea, USA, Europe, Japan and China (Olix Pharmaceuticals website, May 2021) Updated 28 May 2021 |
| 28 May 2021 | Patent Information | Olix Pharmaceuticals has patent protection for lasiRNA technology in South Korea, USA, Europe, Japan and China (Olix Pharmaceuticals website, May 2021). Updated 28 May 2021 |
| 28 May 2021 | Patent Information | Olix Pharmaceuticals has patent protection for tiRNA technology in South Korea, Europe and Japan (Olix Pharmaceuticals website, May 2021). Updated 28 May 2021 |
| 28 May 2021 | Patent Information | Olix Pharmaceuticals files for patent protection with USPTO for tiRNA technology in USA (Olix Pharmaceuticals website, May 2021) Updated 28 May 2021 |
| 24 May 2021 | Patent Information | Olix Pharmaceuticals receives patent allowance for RNAi technology in USA [7] Updated 28 May 2021 |
| 20 Mar 2020 | Trial Update | Olix Pharmaceuticals plans to initiate preclinical study for COVID-2019 infections within three months [8] Updated 10 May 2022 |
| 20 Mar 2020 | Phase Change | Early research in COVID-2019 infections in South Korea (unspecified route) [8] Updated 30 Mar 2020 |
| 25 Feb 2020 | Patent Information | Olix Pharmaceuticals has patents pending for composition of matter patent for siRNAs for COVID-2019 [8] Updated 30 Mar 2020 |
| 09 Jul 2019 | Trial Update | Hugel plans a phase II trial for Hypertrophic scars in South Korea in August 2019 (NCT04012099) Updated 10 Jul 2019 |
| 18 Mar 2019 | Licensing Status | OLX 301A licensed to Thea Open Innovation in European Union, Middle East and Africa [1] Updated 25 Mar 2019 |
| 17 Jan 2019 | Regulatory Status | OliX Pharmaceuticals intends to file an IND application for OLX 301 with the US FDA for Dry age-related macular degeneration in 2019 [3] Updated 22 Jan 2019 |
| 17 Jan 2019 | Trial Update | OliX Pharmaceuticals plans a phase I trial for OLX 301 for Dry age-related macular degeneration in USA in 2019 [3] Updated 22 Jan 2019 |
| 22 Jan 2018 | Patent Information | Olix Pharmaceuticals has patent pending for cp-asiRNA technology in USA, Europe, Japan and China (Olix Pharmaceuticals website, January 2018) Updated 22 Jan 2018 |
| 22 Jan 2018 | Patent Information | Olix Pharmaceuticals has patent protection for cp-asiRNA technology in South Korea (Olix Pharmaceuticals website, January 2018) Updated 22 Jan 2018 |
| 22 Jan 2018 | Phase Change - Discontinued(Preclinical) | Discontinued - Preclinical for Cancer in South Korea (unspecified route) Updated 22 Jan 2018 |
| 22 Jan 2018 | Phase Change - Discontinued(Preclinical) | Discontinued - Preclinical for Herpes simplex virus infections in South Korea (unspecified route) Updated 22 Jan 2018 |
| 22 Jan 2018 | Phase Change - Preclinical | Preclinical trials in Age-related macular degeneration in South Korea (unspecified route) (Olix Pharmaceuticals pipeline, January 2018) Updated 22 Jan 2018 |
| 22 Jan 2018 | Phase Change - Preclinical | Preclinical trials in Atopic dermatitis in South Korea (Topical) (Olix Pharmaceuticals pipeline, January 2018) Updated 22 Jan 2018 |
| 22 Jan 2018 | Phase Change - Preclinical | Preclinical trials in Hepatic fibrosis in South Korea (unspecified route) (Olix Pharmaceuticals pipeline, January 2018) Updated 22 Jan 2018 |
| 22 Jan 2018 | Phase Change - Preclinical | Preclinical trials in Idiopathic pulmonary fibrosis in South Korea (Inhalation) (Olix Pharmaceuticals pipeline, January 2018) Updated 22 Jan 2018 |
| 22 Jan 2018 | Phase Change - Preclinical | Preclinical trials in Neuropathic pain in South Korea (unspecified route) (Olix Pharmaceuticals pipeline, January 2018) Updated 22 Jan 2018 |
| 16 Jul 2016 | Phase Change - No development reported | No recent reports of development identified for preclinical development in Age-related-macular-degeneration in South Korea Updated 16 Jul 2016 |
| 01 Sep 2014 | Company Involvement | BioMolecular Therapeutics is now called OliX Pharmaceuticals Updated 16 Jan 2018 |
| 24 Apr 2012 | Company Involvement | Boston Biomedical has been acquired by Dainippon Sumitomo Pharma Updated 27 Apr 2012 |
| 03 Jan 2012 | Phase Change - No development reported(Preclinical) | No development reported - Preclinical for Cancer in South Korea (unspecified route) Updated 03 May 2012 |
| 03 Jan 2012 | Phase Change - No development reported(Preclinical) | No development reported - Preclinical for Herpes simplex virus infections in South Korea (unspecified route) Updated 03 May 2012 |
| 20 Jan 2009 | Phase Change - Preclinical | Preclinical trials in Cancer in South Korea (unspecified route) Updated 28 Oct 2010 |
| 20 Jan 2009 | Phase Change - Preclinical | Preclinical trials in Herpes simplex virus infections in South Korea (unspecified route) Updated 28 Oct 2010 |
| 20 Jan 2009 | Phase Change - Preclinical | Preclinical trials in Age-related macular degeneration in South Korea (unspecified route) Updated 26 Oct 2010 |
References
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Tha and OliX Announce Collaboration to Develop RNAi Therapies for the Treatment of AMD.
Media Release -
OliX Pharmaceuticals Announces Expansion of Collaboration with Laboratoires Tha to Develop siRNA Therapeutics for Ophthalmic Diseases.
Media Release -
OliX Announces Clinical Candidate Nomination for the Treatment of Geographic Atrophy.
Media Release -
OliX Pharmaceuticals Identifies Effective Inhibition of Target Gene Expression and Delivery of Candidate to Brain for CNS Therapeutics.
Media Release -
BioMolecular Therapeutics, a New Global Player in RNAi Therapeutics, Launches Company and Adds Key Advisors.
Media Release -
OliX, a RNAi therapeutics developer, gets approval for KOSDAQ listing.
Media Release -
OliX Pharmaceuticals Receives Notice of Allowance from U.S. Patent and Trademark Office for Improved Intracellular Delivery Platform Technology for RNAi Therapeutics.
Media Release -
OliX Pharmaceuticals Advances RNAi Approaches to Target Highly Conserved Regions of Coronavirus RNAs.
Media Release
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