In November 2010, NexBio reported positive results from in vitro and in vivo models, showing that independent of its antiviral activity, and by a different mechanism of action, DAS 181 may provide benefit in patients with airway diseases such as asthma and COPD  . The results build on previous studies of DAS 181 in three animal models of asthma. DAS 181 inhibited airway hyperreactivity, and also decreased the number of inflammatory and mucous-secreting cells in the respiratory tract. The drug was considered to be as effective as a bronchodilator or a steroid (used as antiasthma drugs in the marketplace) in the animal models  . However, no recent development in this indication has been reported.
Coronovirus infections (COVID-19)
In April 2020, Ansun Biopharma initiated and enrolled fist patient in a randomised, double-blind, placebo-controlled proof-of-concept trial, to assess the safety and efficacy of DAS 181, for the treatment of severe COVID-19 pneumonia. The two-stage trial is a randomised, double-blind study and intends to initially enrol approximately 22 patients in the US, and further expansion will be undertaken to initiate a second stage of this adaptive design trial, enrolling approximately 60 more patients in the US and Europe, following an interim review of data    .
In April 2020, Ansun Biopharma in collaboration with Renmin Hospital of Wuhan University, completed a compassionate use phase II study to assess the safety and efficacy of DAS 181 in patients with COVID-19 infections (NCT04324489; DAS181-SARS-CoV-2). The open-label trial initiated in March 2020, enrolled four patients in China. Favourable preliminary data from the trial were released in April 2020   .
Influenza virus infections
Ansun Biopharma, in April 2020, reported that the phase IIb STOP-Flu trial was underway, to assess the efficacy, safety and pharmacokinetics of DAS 181 in the treatment of severe hospitalised influenza virus infections, inclusive of SAD-RV Infection and COVID-19 infections (NCT04298060; DAS181-2-07). The randomised, double-blinded, placebo-controlled trial intends to recruit approximately 280 patients in China. Earlier, in October 2019, National Medical Products Administration approved the IND application for the trial    .
In January 2014, Ansun completed a phase IIb trial that evaluated safety and efficacy of DAS 181 in patients with naturally acquired influenza (NCT01740063; DAS181-2-04). The randomised, double-blind, placebo-controlled trial, initiated in November, enrolled 423 patients in the US  .
In August 2011, NexBio reported the completion of a phase II trial of DAS 181 in 297 subjects with laboratory-confirmed influenza, including influenza A virus H1N1 and H3N2 subtypes and influenza B strains (NCT01037205). Topline results showed that the trial had met its primary endpoint of reduction in viral load. The trial, which began in January 2010, ran through two Northern Hemisphere influenza seasons and one Southern Hemisphere influenza season and assessed the effect of DAS 181 on influenza viral load as measured by the amount of viral shedding in the upper respiratory tract. Patients were recruited at sites in the US and Mexico    .
In July 2015, Ansun Biopharma reported that the viral load, in the patient with ill cystic fibrosis, was not cleared on treated with tamilfu and then with relenza IV. The patient cleared viral load on treating with DAS 181, under an IND emergency use  .
The National Institute of Allergy and Infectious Diseases (NIAID) completed a single- and multiple-dose phase I trial of DAS 181 in healthy volunteers (NCT01173224). This investigator-sponsored trial investigated inhaled single drug doses of 20mg and 30mg, as well as a total dose of 200mg over 10 consecutive days. A total of 18 subjects were recruited  .
In August 2011, Ansun Biopharma in collaboration with National Institutes of Health completed a phase I trial that evaluated the safety of DAS 181 in adult patients with well-controlled asthma or bronchiectasis (DAS181-1-04; 10-I-0085; NCT01131286; NCT01113034). The randomised, double-blind, placebo-crossover trial was initiated in July 2010 and enrolled 11 patients in the US  .
In December 2008, NexBio completed a phase Ia trial of DAS 181 in approximately 36 healthy volunteers (NCT00527865). The drug was found to be well tolerated at all dose levels tested  . This trial evaluated four different doses of DAS 181 (0.5mg, 1.0mg, 2.25mg and 4.5mg)  .
A second phase I trial was completed in December 2009 in the US in 45 healthy adults (NCT00876161). This trial evaluated three doses of DAS 181 (5mg, 10mg and 20mg) for safety, tolerability and pharmacokinetics  .
Following the declaration of an influenza A virus H1N1 subtype (swine flu) pandemic in June 2009, NexBio had been testing DAS 181 against this current pandemic strain of influenza. The company had also conducted previous investigations in collaboration with the US Centers for Disease Control and Prevention (CDC) during the avian influenza (bird flu) outbreak from about 2004 onwards  .
DAS 181 has shown potent inhibitory activity against multiple human influenza strains, including the 2009 influenza A/H1N1 (Novel H1N1 or "Swine flu"), oseltamivir-resistant influenza virus and the H3N2 strain     .
Parainfluenza virus infections
In October 2017, the US FDA awarded breakthrough therapy designation to DAS 181 for parainfluenza virus infections  .
In July 2015, fast track designation status was granted to DAS 181 by the US FDA. The US FDA also granted an orphan drug designation to DAS 181 (ParaDase™)   .
In May 2019, Ansun Biopharma initiated and enrolled the first patient in the phase III STOP PIV trial designed to assess the safety and efficacy of DAS 181 in immunocompromised patients with lower respiratory tract parainfluenza infection (NCT03808922; DAS181-3-01). The randomised, placebo-controlled trial intends to enrol approximately 132 patients in the US and might expand to Europe and Asia including Chin   . In October 2019, NMPA approved the IND for DAS 181 phase III trial in China  .
Ansun, in May 2017, completed a phase II trial that examined effects of DAS 181 administered either as a dry powder inhalation or a nebulised formulation in immunocompromised patients with parainfluenza virus infections (NCT01924793; DAS181-2-06). The primary outcome of the trial was the cumulative incidence and severity of adverse events over two years. The trial, initiated in August 2013, enrolled 23 patients in the US  .
In December 2016, Ansun completed a phase II trial that assessed the safety and tolerability of DAS 181 in immunocompromised patients with parainfluenza virus infections, on supplemental oxygen (NCT01644877; DAS181-2-05). The randomised, double-blind, placebo-controlled trial, initiated in March 2014, enrolled 111 patients in the US. In October 2018, Ansun Biopharma presented results from this trial at the IDWeek 2018. Results showed that DAS 181 was well tolerated and showed a signal for clinical efficacy in immunocompromised patients with parainfluenza virus lower respiratory tract infection   .
In October 2015, Ansun announced successful treatment with DAS 181 in a transplant patients on a respirator who were co-infected with influenza and parainfluenza. The drug was used under an emergency IND  .
NexBio reported in August 2011 that DAS 181 had been used, under an emergency IND (eIND) granted by the US FDA, to treat four patients who were severely immunocompromised and experiencing parainfluenza pneumonitis. Significant improvement in clinical symptoms was noted in all cases after administration of DAS 181. The company stated that this outcome justified conducting controlled clinical trials of DAS 181 in this indication. NexBio declared that it was executing a broad clinical development plan for DAS 181 that included the aim of showing activity against influenza as well as parainfluenza  .
Positive preclinical results were presented at the 52nd Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC-2012)  .
Ansun, in September 2015, reported positive efficacy of DAS 181 against enterovirus 68 in in vitro studies which suggest clinical evaluation of the candidate against enteroviral infections  .
In a preclinical study, DAS 181 showed activity against JC and BK viruses, two viruses that occur in immunocompromised patients  .
Respiratory Syncytial Virus (RSV)
Lower concentrations of DAS 181 exhibited of RSV compared with ribavarin in in vitro studies. DAS 181 showed activity against various respiratory pathogens based on the same host-directed antiviral mechanism   .
DAS 181 exhibited potent in vitro inhibition of MPV. DAS 181 blocked infection of human MPV strains A2, B1 and B2 at low concentrations. Pre-incubation of Hep-2 cells with DAS 181 exhibited inhibition of binding of MPV G protein to Hep-2 cells  .
Financing information: In May 2018, Ansun BioPharma announced the completion of an $US85 million Series A financing round, the proceeds from which will fund a phase III trial of DAS 181  .