BIT 225 / Biotron - LARVOL DELTA

Current status of the small molecule anti-HIV drugs in the pipeline or recently approved. (PubMed, Bioorg Med Chem) - "These compounds include analogues of nucleoside reverse transcriptase inhibitors (NRTIs) - islatravir and censavudine; non-nucleoside reverse transcriptase inhibitors (NNRTIs) - Rilpivirine, elsulfavirine and doravirine; integrase inhibitors namely cabotegravir and dolutegravir and chemokine coreceptors 5 and 2 (CC5/CCR2) antagonists for example cenicriviroc. Also, fostemsavir is being developed as an attachment inhibitor while lenacapavir, VH4004280 and VH4011499 are capsid inhibitors. Others are maturation inhibitors such as GSK-254, GSK3532795, GSK3739937, GSK2838232, and other compounds labelled as miscellaneous (do not belong to the classical groups of anti-HIV drugs or to the newer classes) such as obefazimod and BIT225. There is a considerable progress in the development of new anti-HIV drugs and the effort will continue since HIV infections has no cure or vaccine till now. Efforts are needed to reduce the toxicity of available drugs or discover new drugs with new..."

Journal • Review • Human Immunodeficiency Virus • Infectious Disease • CCR2

An open-label study of the safety and efficacy of 12 weeks treatment with BIT225 and Combination Antiretroviral Therapy (cART) in patients with Human Immunodeficiency Virus-1 (HIV-1) with only partial immune reconstitution. (ANZCTR) - P2 | N=20 | Completed | Sponsor: Biotron Limited | Active, not recruiting ➔ Completed

IO biomarker • Trial completion • Human Immunodeficiency Virus • Infectious Disease • CD4 • CD8 • IFNG • IL10 • IL17A • IL1B • IL22 • IL6 • NCAM1 • PTPRC • TNFA

A study of the safety and efficacy of 6 months treatment with BIT225 and Combination Antiretroviral Therapy (cART) in patients with Human Immunodeficiency Virus-1 (HIV-1) compared to cART alone, including measurement of BIT225 in the blood, antiviral activity and immune markers. (ANZCTR) - P2 | N=27 | Completed | Sponsor: Biotron Limited | Active, not recruiting ➔ Completed

IO biomarker • Trial completion • Human Immunodeficiency Virus • Infectious Disease • CD4 • CD8 • IFNG • IL10 • IL15 • IL17A • IL1B • IL21 • IL22 • IL2RA • IL6 • ISG20 • PD-1 • TNFA

Post-infection treatment with the E protein inhibitor BIT225 reduces disease severity and increases survival of K18-hACE2 transgenic mice infected with a lethal dose of SARS-CoV-2. (PubMed, PLoS Pathog) - "Treatment efficacy was dependent on BIT225 dose and was associated with significant reductions in lung viral load (3.5 log10), virus titer (4000 pfu/ml) and lung and serum cytokine levels. These results validate viroporin E as a viable antiviral target and support the clinical study of BIT225 for treatment and prophylaxis of SARS-CoV-2 infection."

Journal • Preclinical • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

SARS-CoV-2 E-PROTEIN VIROPORIN INHIBITOR BIT225 ACTIVE IN hACE2 TRANSGENIC MICE (CROI 2023) - "BIT225 is an inhibitor of SARS-CoV-2 E-protein viroporin activity. In the K18 model BIT225 protected mice from weight loss and death, inhibited virus replication and reduced inflammation. These effects were noted when treatment with BIT225 was initiated before or 24-48 hours after infection and validate viroporin E as a viable antiviral target and support the clinical study of BIT225 in treatment of SARS-CoV-2."

Preclinical • Human Immunodeficiency Virus • Immunology • Infectious Disease • Inflammation • Novel Coronavirus Disease • Respiratory Diseases • IL1B • IL6 • TGFB1 • TNFA

".@BiotronLimited : @US_FDA BIT-225 #Covid_19 Guidance - subscribe to Biotech Daily https://t.co/4E9331THtC" (@biotech_daily)

Infectious Disease • Novel Coronavirus Disease

An open-label study of the safety and efficacy of 12 weeks treatment with BIT225 and Combination Antiretroviral Therapy (cART) in patients with Human Immunodeficiency Virus-1 (HIV-1) with only partial immune reconstitution. (ANZCTR) - P2; N=20; Not yet recruiting; Sponsor: Biotron Limited

Clinical • IO biomarker • New P2 trial • Human Immunodeficiency Virus • Immunology • Infectious Disease • CD4 • CD8 • IFNG • IL10 • IL1B • IL21 • IL22 • IL6 • NCAM1 • PTPRC • TNFA

Biotron (ASX:BIT) reflects on busy quarter (The Market Herald) - "Biotron has continued to further explain the mechanism of action for its flagship compound BIT225....In the recent quarter, a manuscript containing data from its phase two trial was published in a prestigious international journal. Biotron is now mapping out the next stage of clinical development for the drug."

Clinical • P2 data • Human Immunodeficiency Virus • Infectious Disease

Human immunodeficiency virus type-1 Vpu inhibitor, BIT225, in combination with 3-drug antiretroviral therapy modulates inflammation and immune cells functions. (PubMed, J Infect Dis) - "A phase II trial enrolled 36 HIV-1-infected, treatment-naïve participants in Thailand to receive standard of care antiretroviral therapy (ART) Atripla®, with 100 mg or 200 mg of BIT225 or placebo for 12 weeks. These findings are consistent with inhibition of the known effects of HIV Vpu, and may reflect clinically important modulation of inflammatory and immune function. Further clinical study is planned to both confirm and extend these important findings in treatment naïve, and treatment experienced individuals."

Combination therapy • Journal • Human Immunodeficiency Virus • Immunology • Infectious Disease • Inflammation • CD8 • IL21

[VIRTUAL] Vpu inhibitor BIT225 alters T cell activation and homing plasma membrane receptor expression on CD4+T cells (CD28 and CCR7) and monocyte-derived macrophages (CD80 and CD86) (AIDS 2020) - No abstract available

Late-breaking abstract

Biotron phase 2 hepatitis C trial success (PRNewswire) - P2, N=30; "Biotron Limited...confirms positive outcomes from its Phase 2 study of its first-in-class antiviral drug BIT225...BIT225 was safe and well-tolerated with none of the HCV G1 patients withdrawing due to BIT225-related adverse events...The trial has provided key data on the performance of the capsule formulation of BIT225...Analysis of the trial data is ongoing, and the Company aims to present detailed data at a scientific conference later in 2016."

Anticipated conference • P2 data • Hepatitis C Virus

BIT 225 enhances anti- viral activity in HIV/HCV genotype 3 coinfected patients; Phase 2 data to be presented at leading International Liver Meeting (Biotron Press Release) - P2, N=12; Biotron today announced preliminary headline data from its Phase 2 open-label pilot study of BIT225 in patients co-infected with Hepatitis C virus (HCV) and HIV. The data will be detailed in a late-breaking poster at the American Association for the Study of Liver Diseases (AASLD) 2013....Interim analysis of virus levels in the treated patients indicates that all six HCV Genotype 3 subjects who completed 28 days of BIT225 therapy had undetectable levels of HCV 12 weeks into the study."

Anticipated P2 data • P2 data • Hepatitis C Virus

Update on BIT225 HCV program (Biotron Press Release) - P2, N=60; BIT225-008; "A Phase 2 study (BIT225-008) of BIT225 is currently in progress at key teaching hospitals in Thailand.....A second site in Khon Kaen, has recently been initiated following receipt of ethics approval from Khon Kaen University. Ethics approval has now been received from two additional sites - one in Chiang Mai and an additional site in Bangkok....The addition of new sites will speed up recruitment and we expect the trial to be fully enrolled by mid-2014, with data anticipated in the second half of the year.' 

Anticipated P2 data • Enrollment status • Hepatitis C Virus

[VIRTUAL] PHASE II TRIAL OF VPU INHIBITOR BIT225 IN COMBINATION WITH ANTIRETROVIRAL THERAPY (CROI 2020) - "HIV-1 infected individuals recruited from two sites in Thailand were treated with either BIT225 or placebo in addition to ART (Atripla) for 12 weeks.Individuals were randomized 2:1 (BIT225: placebo). Vpu has been associated with reducing cell surface expression/function of numerous cellular proteins/receptors involved in viral antigen presentation to CD4+, CD8+ T cells and NK cells. The production of IL-21 by Tfh, Th17, and/or NK cells is a unique immunological consequence of addition of BIT225 to ART and offers the potential for treatment targeting different HIV-1 compartments during standard therapy."

Combination therapy • P2 data • CD8 • IFNG • IL6