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Research programme: viral budding inhibitors - Biotron

Drug Profile

Research programme: viral budding inhibitors - Biotron

Alternative Names: BIT 009; Next-generation viroporin inhibitors - Biotron

Latest Information Update: 28 Mar 2020

At a glance

  • Originator Biotron
  • Developer Biotron; ImQuest BioSciences; National Institutes of Health (USA)
  • Class Small molecules
  • Mechanism of Action Hepatitis C virus p7 protein inhibitors; Hepatitis C virus replication inhibitors; HIV replication inhibitors; Human immunodeficiency virus 1 vpu protein inhibitors; SARS coronavirus E protein inhibitors; Viral protein inhibitors; Virus replication inhibitors
  • Orphan Drug Status

    Orphan designation is assigned by a regulatory body to encourage companies to develop drugs for rare diseases.

    No
  • New Molecular Entity Yes
  • Available For Licensing Yes - Coronavirus infections; Dengue; Hepatitis C; HIV infections

Highest Development Phases

  • No development reported Coronavirus infections; Dengue; Hepatitis C; HIV infections; Zika virus infection

Most Recent Events

  • 28 Mar 2020 No recent reports of development identified for research development in Zika-virus-infection in Australia
  • 04 Nov 2017 No recent reports of development identified for preclinical development in Hepatitis-C in Australia
  • 04 Nov 2017 No recent reports of development identified for preclinical development in HIV-infections in Australia

Development Overview

Introduction

Biotron is developing small-molecule antiviral compounds that target viroporins (i.e. small, virus-encoded polypeptides that interact with membranes comprising at least one transmembrane segment) for the treatment of viral infections, including dengue, coronavirus, hepatitis C (HCV) and HIV infections. Viroporins are proteins that 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, E protein of coronaviruses such as sudden acute respiratory syndrome (SARS), the p7 protein of HCV and the Vpu of HIV. Development of therapies for HCV and HIV are at the preclinical stage of development, while therapies for dengue and zika virus fever are at the research stage. No recent development for treatment of coronavirus infections has been reported.

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 November 2017, no recent reports of development had been identified for preclinical development in Hepatitis-C in Australia, preclinical development in HIV-infections in Australia, research development in Dengue in Australia, USA.

As at March 2020, no recent reports of development had been identified for research development in Zika-virus-infection in Australia.

Key Development Milestones

As of May 2013, Biotron indicated in its pipeline that development of therapies for HCV and HIV are at the preclinical stage of development, while therapies for dengue are at the research (discovery) stage. No recent development for treatment of coronavirus infections has been reported. In June 2013, Biotron reported in an Asia Biotech investor presentation that its next generation HCV therapies are ready for IND enabling preclinical studies.

Biotron has been able to demonstrate that its virion technology has the potential to treat viruses such as the sudden 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 [1] .

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 [2] .

Patent Information

By August 2009, Biotron's intellectual property portfolio contained two patents generally covering its antiviral therapeutics. Patent No. WO04112687 entitled "Antiviral compounds and methods" has been granted in South Africa, India and Singapore, and is under examination elsewhere. Patent No. WO6135978 entitled "Antiviral compounds and methods" has entered into the national phase [3] .

Drug Properties & Chemical Synopsis

  • Formulation unspecified
  • Class Small molecules
  • Target Hepatitis C virus p7 protein; Hepatitis C virus replication; HIV replication; Human immunodeficiency virus 1 vpu protein; SARS coronavirus E protein; Viral protein; Virus replication
  • Mechanism of Action Hepatitis C virus p7 protein inhibitors; Hepatitis C virus replication inhibitors; HIV replication inhibitors; Human immunodeficiency virus 1 vpu protein inhibitors; SARS coronavirus E protein inhibitors; Viral protein inhibitors; Virus replication 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
Coronavirus infections - - No development reported (Preclinical) USA unspecified / unspecified National Institutes of Health (USA) 05 Jun 2013
Coronavirus infections - - No development reported (Preclinical) Australia unspecified / unspecified Biotron 05 Jun 2013
Dengue - - No development reported (Research) USA unspecified / unspecified National Institutes of Health (USA) 04 Nov 2017
Dengue - - No development reported (Research) Australia unspecified / unspecified Biotron 04 Nov 2017
HIV infections - - No development reported (Preclinical) Australia unspecified / unspecified Biotron 04 Nov 2017
Hepatitis C - - No development reported (Preclinical) Australia unspecified / unspecified Biotron 04 Nov 2017
Zika virus infection - - No development reported (Research) Australia unspecified / unspecified Biotron, ImQuest BioSciences 28 Mar 2020

Commercial Information

Involved Organisations

Organisation Involvement Countries
Biotron Originator Australia
Biotron Owner Australia
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 Coronavirus infections, Dengue, Hepatitis C, HIV infections 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 [4] .

Development History

Event Date Update Type Comment
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 preclinical development in Hepatitis-C in Australia Updated 04 Nov 2017
04 Nov 2017 Phase Change - No development reported No recent reports of development identified for preclinical development in HIV-infections 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 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 Active Status Review Preclinical development is ongoing for HCV and HIV infections in Australia Updated 05 Jun 2013
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
13 Sep 2010 Active Status Review Preclinical development is ongoing for HCV and HIV infections in Australia Updated 13 Sep 2010
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 [4] 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

  1. Independent Tests Verify Biotron's Hiv Compound to be Effective and Non-toxic in the Treatment of Aids.

    Media Release
  2. ZIKA VIRUS PROGRAM UPDATE.

    Media Release
  3. Re: Year End Accounts and Preliminary Final Report.

    Media Release
  4. 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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