Research programme: viral budding inhibitors - Biotron
Alternative Names: BIT 009; Next-generation viroporin inhibitors - BiotronLatest Information Update: 28 Sep 2023
At a glance
- Originator Biotron
- Class Antivirals; Small molecules
- Mechanism of Action Viral protein 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
- Available For Licensing Yes
Highest Development Phases
- Preclinical COVID 2019 infections
- Research Ebola virus infections; Hepatitis B; Influenza virus infections
- No development reported Dengue; Severe acute respiratory syndrome; Zika virus infection
Most Recent Events
- 28 Sep 2023 No recent reports of development identified for preclinical development in Severe acute respiratory syndrome in Australia
- 28 Sep 2023 No recent reports of development identified for preclinical development in Severe acute respiratory syndrome in USA
- 28 Sep 2023 No recent reports of development identified for research development in Dengue in Australia
Development Overview
Introduction
Small-molecule antiviral compounds targeting viroporins is being developed by Biotron, for the treatment of viral infections, including dengue, severe acute respiratory syndrome; COVID-2019 infections, influenza virus infections, Zika virus infections, Ebola virus infections and hepatitis B. Viroporins are virus-encoded polypeptides that interact with membranes comprising at least one transmembrane segment. Viroporins participate in several viral functions, including the promotion of release of viral particles from cells. By blocking the ion channel activity of viroporins, potentially therapeutic compounds are able to inhibit viral budding and replication. Viral proteins targeted under Biotron's programme included M protein of Dengue virus and E protein of coronaviruses such as severe acute respiratory syndrome (SARS). Preclinical development for the treatment of severe acute respiratory syndrome and COVID-2019 infections is underway in the US and Australia. Early research for the treatment of Dengue, Ebola virus infections, Zika virus infections, Hepatitis B and Influenza virus infections is underway in the US and Australia.
Biotron is currently focussing on advancement of its HCV and HIV programmes in clinical trials. A lead candidate from this programme, BIT 225, has advanced into clinical development [see RDI profile 800026501].
Biotron is seeking partnership for the clinical development of its viroporin inhibitors.
As at September 2023, no recent reports of development had been identified for preclinical development in Severe acute respiratory syndrome in Australia, USA, research development in Dengue in USA, Australia, research development in Zika-virus-infection in Australia.
Key Development Milestones
As of September 2021, non-clinical development of small molecules for the treatment of influenza, dengue, Zika virus infections, Ebola virus and Severe acute respiratory syndrome (SARS) is underway in the US and Australia (Biotron pipeline, September 2021).
As of June 2021, Biotron is developing a lead series of compounds for the treatment of COVID-19 infections. The company has identified three most active compounds on the basis of inhibiting SARS-CoV-2 replication in three different cell culture models of SARS-CoV-2 virus infection. The assays were performed by collaborators at the Scripps Research Institute, La Jolla, California, USA. The animal studies are expected to be completed during the third quarter of 2021 [1] .
As of June 2021, Biotron continues to design, synthesise and test new compounds with the aim of identifying a lead candidate for the treatment of Hepatitis B. The company is working with other experienced groups to access key assays and to identify a lead series to progress to preliminary safety studies and assessment in animal models of HBV infection [1] .
Biotron has been able to demonstrate that its virion technology has the potential to treat viruses such as the severe acute respiratory syndrome (SARS) coronavirus, dengue virus and a wide range of other virus-related diseases. Preclinical antiviral testing against a broad range of diseases was being conducted in conjunction with researchers at the National Institute of Health (NIH) in the US.
Prior to the advancement of BIT 225 into clinical development, Biotron had identified BIT 009 as a lead candidate for the treatment of HIV-1 infections. Preclinical studies in human white blood cells infected with HIV demonstrated that BIT 009 significantly reduced the level of virus released by the cells and almost wholly prevented viral replication. Additionally, the compound caused no harm to human cells. However, it appears that development of BIT 009 was discontinued in favour of BIT 225 [2] .
Biotron announced in September 2016 that it had earlier identified two lead candidates to be active against Zika virus. The company had further identified additional compounds that are able to inhibit Zika virus activity, with greater potency against the virus than the first two compounds. Biotron entered into an agreement with the US National Institute of Allergy and Infectious Diseases (NIAID), wherein, the company will utilise the nonclinical and pre-clinical services programme offered by NIAID [3] .
Patent Information
By August 2009, Biotron's intellectual property portfolio contained two patents generally covering its antiviral therapeutics. Patent No. WO 041 126 87 entitled "Antiviral compounds and methods" has been granted in Australia, Canada, China, India, Japan, Korea, New Zealand, Singapore and South Africa, and is under examination in Brazil, Europe, Hong Kong, and USA. Patent No. WO 613 597 8 entitled "Antiviral compounds and methods" is granted in Granted in Austria, Australia, Belgium, Canada, Switzerland, China, Germany, Denmark, Spain, Finland, France, United Kingdom, Hong Kong, Ireland, Italy, Japan, Korea, Luxembourg, Monaco, The Netherland, New Zealand, Poland, Portugal, Sweden, Singapore, Turkey, South Africa and USA and under examination in Brazil and India [4] .
Drug Properties & Chemical Synopsis
- Formulation unspecified
- Class Antivirals, Small molecules
- Target Viral protein
- Mechanism of Action Viral protein inhibitors
-
WHO ATC code
J05A (Direct acting antivirals)
-
EPhMRA code
J5 (Antivirals for Systemic Use)
J5B (Antivirals, excluding anti-HIV products)
J5C (HIV antivirals)
- SMILES C1=C2C(=C(C=C1)C1=CN(N=C1)C)C=CC(=C2)C(NC(N)=N)=O
-
Chemical Structure
Development Status
Summary Table
| Indication | Qualifier | Patient Segment | Phase | Countries | Route / Formulation | Developers | Event Date |
|---|---|---|---|---|---|---|---|
| COVID 2019 infections | - | - | Preclinical | Australia, USA | unspecified / unspecified | Biotron | 30 Jun 2021 |
| Dengue | - | - | No development reported (Research) | Australia, USA | unspecified / unspecified | Biotron | 28 Sep 2023 |
| Ebola virus infections | - | - | Research | Australia | unspecified / unspecified | Biotron | 14 Sep 2021 |
| Hepatitis B | - | - | Research | Australia | unspecified / unspecified | Biotron | 30 Jun 2021 |
| Influenza virus infections | - | - | Research | Australia | unspecified / unspecified | Biotron | 14 Sep 2021 |
| Severe acute respiratory syndrome | - | - | No development reported (Preclinical) | Australia, USA | unspecified / unspecified | Biotron | 28 Sep 2023 |
| Zika virus infection | - | - | No development reported (Research) | Australia | unspecified / unspecified | Biotron | 28 Sep 2023 |
Commercial Information
Involved Organisations
| Organisation | Involvement | Countries |
|---|---|---|
| Biotron | Originator | Australia |
| Biotron | Owner | Australia |
| The Scripps Research Institute | Collaborator | USA |
| National Institutes of Health (USA) | Collaborator | USA |
| National Institute of Allergy and Infectious Diseases | Collaborator | USA |
| ImQuest BioSciences | Collaborator | USA |
Licensing Availability
| Licensing Organisation | Available Indication | Available Phase | Region | Date |
|---|---|---|---|---|
| Biotron | - | Preclinical | - | 28 Jun 2004 |
Scientific Summary
Antimicrobial Activity
Heaxmethyleneamiloride (HMA) inhibited release of new HIV-1 virions from monocyte-derived macrophages (MDM). In this study, MDM grown in culture were infected with laboratory adapted HIV-1BaL strain and then cultured in the presence or absence of HMA for periods up to 28 days. HMA , in the range of 1 to 10 µmol/L was found to inhibit the release of new virions from the cells. No cell toxicity was observed at concentrations below 10 µmol/L [5] .
Development History
| Event Date | Update Type | Comment |
|---|---|---|
| 28 Sep 2023 | Phase Change - No development reported | No recent reports of development identified for preclinical development in Severe acute respiratory syndrome in Australia Updated 28 Sep 2023 |
| 28 Sep 2023 | Phase Change - No development reported | No recent reports of development identified for preclinical development in Severe acute respiratory syndrome in USA Updated 28 Sep 2023 |
| 28 Sep 2023 | Phase Change - No development reported | No recent reports of development identified for research development in Dengue in Australia Updated 28 Sep 2023 |
| 28 Sep 2023 | Phase Change - No development reported | No recent reports of development identified for research development in Dengue in USA Updated 28 Sep 2023 |
| 28 Sep 2023 | Phase Change - No development reported | No recent reports of development identified for research development in Zika-virus-infection in Australia Updated 28 Sep 2023 |
| 14 Sep 2021 | Active Status Review | Early research for Dengue is ongoing in USA and Australia (Biotron pipeline, September 2021) Updated 14 Sep 2021 |
| 14 Sep 2021 | Active Status Review | Early research for Zika virus infections is ongoing in Australia (Biotron pipeline, September 2021) Updated 14 Sep 2021 |
| 14 Sep 2021 | Active Status Review | Preclinica development for Severe acute respiratory syndrome is ongoing in USA and Australia (Biotron pipeline, September 2021) Updated 14 Sep 2021 |
| 14 Sep 2021 | Patent Information | Biotron has patent protection for Antiviral compounds in multiple countries worldwide, before September 2021 (Biotron website, September 2021) Updated 14 Sep 2021 |
| 14 Sep 2021 | Patent Information | Biotron has patents pending for Antiviral compounds in multiple countries worldwide, before September 2021 (Biotron website, September 2021) Updated 14 Sep 2021 |
| 14 Sep 2021 | Phase Change | Early research in Ebola virus infections in Australia (unspecified route), before September 2021 (Biotron pipeline, September 2021) Updated 14 Sep 2021 |
| 14 Sep 2021 | Phase Change | Early research in Influenza virus infections in Australia (unspecified route), before September 2021 (Biotron pipeline, September 2021) Updated 14 Sep 2021 |
| 30 Jun 2021 | Phase Change | Early research in Hepatitis B in Australia (unspecified route), before June 2021 [1] Updated 14 Sep 2021 |
| 30 Jun 2021 | Phase Change - Preclinical | Preclinical trials in COVID-2019 infections in Australia (unspecified route), before June 2021 [1] Updated 14 Sep 2021 |
| 30 Jun 2021 | Phase Change - Preclinical | Preclinical trials in COVID-2019 infections in USA (unspecified route). before June 2021 [1] Updated 14 Sep 2021 |
| 28 Mar 2020 | Phase Change - No development reported | No recent reports of development identified for research development in Zika-virus-infection in Australia Updated 28 Mar 2020 |
| 04 Nov 2017 | Phase Change - No development reported | No recent reports of development identified for research development in Dengue in Australia Updated 04 Nov 2017 |
| 04 Nov 2017 | Phase Change - No development reported | No recent reports of development identified for research development in Dengue in USA Updated 04 Nov 2017 |
| 16 Feb 2016 | Phase Change | Early research in Zika virus infection in Australia (unspecified route) Updated 19 Feb 2016 |
| 03 Dec 2014 | Active Status Review | Early research is ongoing for Dengue Updated 05 Dec 2014 |
| 05 Jun 2013 | Phase Change - No development reported(Preclinical) | No development reported - Preclinical for Coronavirus infections in Australia (unspecified route) Updated 05 Jun 2013 |
| 05 Jun 2013 | Phase Change - No development reported(Preclinical) | No development reported - Preclinical for Coronavirus infections in USA (unspecified route) Updated 05 Jun 2013 |
| 09 Sep 2010 | Licensing Status | Research programme: viral budding inhibitors - Biotron is available for licensing http://www.biotron.com.au/profile.htm Updated 09 Sep 2010 |
| 06 Mar 2009 | Active Status Review | Preclinical development is ongoing for dengue and coronavirus infections in Australia and the US Updated 06 Mar 2009 |
| 26 Aug 2005 | Active Status Review | Profile reviewed with information available at the BIO-2005 conference Updated 26 Aug 2005 |
| 28 Jun 2004 | Phase Change | Investigation in Dengue in USA (unspecified route) Updated 06 Mar 2009 |
| 28 Jun 2004 | Phase Change - Preclinical | Preclinical trials in Coronavirus infections in USA (unspecified route) Updated 06 Mar 2009 |
| 28 Jun 2004 | Phase Change | Investigation in Dengue in Australia (unspecified route) Updated 28 Jun 2004 |
| 28 Jun 2004 | Phase Change - Preclinical | Preclinical trials in Coronavirus infections in Australia (unspecified route) Updated 28 Jun 2004 |
| 28 Jun 2004 | Phase Change - Preclinical | Preclinical trials in Hepatitis C treatment in Australia (unspecified route) Updated 28 Jun 2004 |
| 24 Sep 2003 | Scientific Update | Data presented at the 43rd Annual Meeting of the Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC-2003) have been added to the Viral Infections antimicrobial activity section [5] Updated 24 Sep 2003 |
| 21 Aug 2003 | Phase Change - Preclinical | Preclinical trials in HIV infections treatment in Australia (unspecified route) Updated 21 Aug 2003 |
References
-
Biotron Q 2 report 2021. Internet-Doc 2021;.
Available from: URL: https://www.biotron.com.au/wp-content/uploads/2021/07/Report-on-Activities-for-the-Quarter-Ended-30-June-2021.pdf -
Independent Tests Verify Biotron's Hiv Compound to be Effective and Non-toxic in the Treatment of Aids.
Media Release -
ZIKA VIRUS PROGRAM UPDATE.
Media Release -
Re: Year End Accounts and Preliminary Final Report.
Media Release -
Ewart G, Nasr N, Naif H, Cox GB, Cunningham AL, et al. Hexamethyleneamiloride and new anti-HIV-1 compounds targeting virus budding and release. 43rd-ICAAC-Late 2003;14.
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