Ann: Half Yearly Report and Accounts, page-3

BIOTRON LIMITEDDIRECTORS' REPORT3 REVIEW OF OPERATIONSBiotron has completed several significant milestones during the first half of the 2020-2021 financial year. These include:•Continued the expanded screening program of Company compounds for activity against SARS-CoV-2, the causative agent of Covid-19, fol lowing the reported identification of compounds in Biotron’s proprietary library of small molecule drugs with in vitro activity against SARS-CoV-2. •Continued the design, synthesis and testing of new compounds under its HIV-1 program, with the aim of identifying a next-generation lead anti-HIV-1 drug.•Publication of a peer-reviewed scientific paper on its lead anti-HIV-1 drug BIT225 in a prestigious international scientific journal.•Continued the design, synthesis and testing of new compounds under its Hepatitis B program.SARS-CoV-2 During the half-year in review, Biotron announced the first round of results from the testing program to screen compounds from its proprietary small molecule compound library for antiviral activity against SARS-CoV-2, the causative agent of the Covid-19 outbreak.As explained previously, Biotron had a number of compounds in its library that have previously shown good activity against a range of coronaviruses, dating back to studies undertaken at the time of outbreak of severe acute respiratory syndrome (SARS-1), a coronavirus, in 2002–2004 when several of Biotron’s compounds showed antiviral activity against SARS-1. As reported on 7 September 2020, several compounds have been shown in laboratory cell-culture studies to have antiviral activity against SARS-CoV-2. The assays were run under contract by an Australian NATA accredited clinical trial speciality laboratory, 360biolabs, based in Melbourne, Victoria.Since September 2020 the Company has expanded its screening program to include a new series of recently designed and synthesised compounds. These additional new compounds are progressing through a panel of cell-based screening assays which are designed to identify the most potent, druggable compound(s) in the series. The screening is progressing well and it is anticipated that a subset will soon be identified for progression to an animal model of the Covid-19 disease.HIV-1 ProgramDuring the half-year in review, Biotron has continued to undertake cell culture-based assays to further elucidate the mechanism of action of BIT225. This follows on from Biotron’s demonstration that BIT225 directly modifies immune responses to HIV-1 infection.In October 2020, a manuscript containing data from its Phase 2 trial of BIT225 in HIV-1-infected subjects was accepted for publication following peer-review in a prestigious international journal. The paper, entitled “Human immunodeficiency virus type-1 Vpu inhibitor, BIT225, in combination with 3-drug antiretroviral therapy modulates inflammation and immune cell function” has been published in the Journal of Infectious Diseases.The Company has also continued to design, synthesise and screen new chemical entities with the aim of identifying a follow-on, next-generation lead.As previously advised to the market on 12 March 2020, the Phase 2 clinical trial demonstrated that BIT225 induced statistically significant changes to key immune cell populations. These changes had not previously been reported for any HIV-1 therapeutics. The results open the possibility that BIT225 may play a key role in restoring immune function, leading to improved health outcomes and elimination of residual virus.Biotron is finalising the design of the next stage of clinical development of this important new anti-HIV class of compounds in consultation with the Company’s Chief Medical Officer and international Scientific Advisory Board. The completion of long-term toxicology studies of BIT225 in 2020 was an important milestone as they support long-term dosing of BIT225 in the next stage of clinical development and beyond
The Company is focused on achieving a commercial outcome for its promising antiviral programs whilst continuing to progress its clinical HIV-1 program to prepare for more advanced clinical trials. The current pandemic highlights the importance of novel approaches such as Biotron’s viroporin compounds which have the potential to target a broad range of existing and emerging viruses.Hepatitis B Program Hepatitis B Virus (HBV) is another important early stage program for Biotron. The Company continues to design, synthesise and test new compounds with the aim of identifying a lead candidate.Like HIV-1, HBV can be treated with drugs that stop the virus replicating, but these do not eradicate the virus. Chronic infection with HBV can lead to complications such as cirrhosis and liver cancer, which cause close to one million deaths worldwide each year.In pre-clinical studies in cell culture models, Biotron’s compounds have demonstrated significant anti-viral activity against HBV, reducing levels of cccDNA (covalently closed circular DNA), as well as other key viral markers. Biotron’s compounds have a unique mechanism of action and are expected to generate significant interest from potential partners in Biotron’s family of compounds.Biotron is working with other experienced groups to access key assays to characterise the mechanism of action of its HBV compounds and continues to make good progress in its pathway to identification of a lead compound to progress to safety studies.