Recently, the Wall Street Journal introduced a small, 25-person San Diego-based biotech called Ansun Biophrma (Ansun) reporting on recent success of a drug that cleared COVID-19 symptoms in a small study involving four Chinese patients. With a strong background in influenza research, the company sought to investigate whether its drug called DAS181, a recombinant sialidase with broad antiviral properties, could address COVID-19. The experimental drug has been designed in a novel way so it doesn’t directly target the virus but rather the host cell to help thwart penetration by invading virus. The investigational drug actually removes the host cell-surface component used by various influenza viruses to penetrate the human’s respiratory cells. The company now initiates and plans imminent clinical trials in the U.S. and beyond targeting SARS-CoV-2, the virus behind the COVID-19 pandemic.
The COVID-19 Medical Challenge
Presently, the only approved treatment (for emergency use) for COIVID-19 is remdesivir, which only has been shown to reduce the duration of sick days by about 30%. Much innovation is needed, and U.S. President Donald Trump recently launched Operation Warp Speed to drive the drug industry forward. Moreover, there is absolutely no approved treatments available to patients with severe SARS-CoV-2-induced pneumonia. The only treatment course of action presently is to offer supportive care, such as supplementary oxygen and mechanical ventilatory support.
The Chinese Study Shows Promise
Ansun launched a small, single group assignment, open-label study with four patients over this spring. In collaboration with Renmin Hospital of Wuhan University, the sponsor treated the eligible patients with the investigational DAS181 and monitored them for 28 days upon administration of the drug. These patients were afflicted with severe bilateral viral pneumonia and hypoxemia. The team administered DAS181 once to twice per day—for ten consecutive days—a total of 9 mg (7ml) nebulized DAS181. In the cases where they treated the patient with DAS181 twice per day, it involved one vial containing 4.5 mg (3.5 ml) each—delivered ideally in about 12-hour intervals. The study ran from March 6, 2020 through the end of April.
The primary outcome measures included, 1) Improved clinical status by day 14 (% of patients with improved clinical status), and 2) Return to room air by day 14 (% of patients return to room air).
By April, the sponsor issued a press release indicating positive results for the investigator-initiated study of DAS181. Highlighting the positive results, principal investigators Dr. Zuojiion Gong and Dr. Ke Hu from Renmin Hospital, commented, “These results are highly encouraging, as they demonstrate that DAS181 may potentially help reduce or eliminate some of the most significant symptoms associated with COVID-19.” They continued, “In the first 14 days of our study, the first two patients no longer required supplemental oxygen, and showed stabilized vital signs, increased oxygen saturation, and resolution of infiltrates on chest CT scans. The third patient, who had been a persistent SARS-CoV-2 carrier for more than 33 days, was completely virus-free before the end of the 10-day DAS181 regimen and met all discharge criteria, and the fourth is currently undergoing treatment and showing positive trends.”
The Proof-of-Concept Study to America
The company also announced the initiation of an additional randomized, double-blind, placebo-controlled proof-of-concept trial in a quest to investigate the safety and efficacy of DAS181 for the treatment of severe COVID-19 pneumonia. The two-stage clinical trial will initially enroll approximately 20 patients at medical centers across America. The company expects to expand enrollment after an interim review of the data.
Other Disclosed Studies
Ansun has disclosed other studies in the U.S. government’s Clinicaltrials.gov data repository where the sponsor assesses the investigational DAS181 for immunocompromised patients currently hospitalized with lower respiratory tract parainfluenza virus and a Phase IIb for patients hospitalized with influenza.
In a published Phase II/III study in Italy, the first stage of a two-staged design includes a proof-of-concept (POC) including 22 patients with COVID-19 and clinically significant impairment of respiratory function. The sponsor seeks to evaluate and determine the safety and efficacy, and if these objectives are achieved, the study moves to Stage 2 expanding enrollment with an additional 60 patients (or more) to provide adequate power to potentially demonstrate statistically significant therapeutic efficacy. The research sites involved include Milan’s Fondazione IRCC Ca Granda Osperdale Maggiore Policlinico and A.O.U Policlinico Di Modena (government hospital in Modena Italy). This study centers on patients with significant impairment of respiratory function.
Additionally, in April, the sponsor launched a Phase II study in China involving two cohorts of what equals 280 patients. The Phase IIb focuses on the efficacy, safety and pharmacokinetics of DAS181 in IFV (influenza) infection with Ruijin Hospital—part of Shanghai Jiao Tong University School of Medicine—serving as the clinical investigational site.
In the United States, the sponsor opened up a 250-patient Phase III study initially targeting lower tract parainfluenza infection and now including a stub-study enrolling patients with severe COVID-19. Commencing May 23, 2020, the study is planned to run through till April 30, 2021. The San Diego-based sponsor has recruited 32 sites to conduct the study.
The Company Profile
Ansun Biopharma, founded in 2002, identifies themselves as a “small team of approximately 25 scientists, doctors, and visionaries” devoted to the inventing, testing and delivering of recombinant therapeutic proteins to treat dangerous diseases affecting the most vulnerable patents.” Founded by virologists and molecular biologists who realized that targeting viruses was a difficult task as the actual targets have the ability to mutate and avoid the treatments. Because viruses can mutate, they can evade vaccines. So rather than hit the target, why not target the host instead of the virus? Hence, the premise behind the development of DAS181.
Note, DAS181 received FDA Fast Track and Breakthrough Therapy designation status in 2017. The company has somewhat, as CEO Nancy Chang reported to Biospace, “quietly been developing DAS181 to treat severely ill patients infected with PIV and other respiratory infectious diseases, including influenza, for a number of years.”
Who leads the Charge?
Ansun’s CEO, Dr. Nancy Chang, is an internationally renowned biochemist and drug developer who co-founded Tanox and guided the company through one of the most successful biotech IPOs in history. The company was acquired by Genentech in 2007 for just under $1 billion reports the Ansun website. Interestingly, Ansun’s board includes Dr. Allan Chao, the founder of Watson Pharmaceuticals. Dr. Stanley Lewis, Chief Medical Officer, worked at Genentech as Medical Director; while Dr. Jennifer Ho serves Ansun as VP of Clinical Development—she was a professor at Taiwan’s prestigious Wan Fang Medical Center University and other prominent stops in an impressive career.
Who are its Investors?
According to Crunchbase, the venture has raised over $183 million. Among their investors is YuanMing Capital—and recently Dr. Tian Yuan, Vice President of the Wuhan University Alumni Association and founder of the investment firm, emphasized his feeling about the investment: “I am honored to have an opportunity to leverage my decades of experience and resources to help Ansun achieve this significant milestone, and even more importantly to help explore potentially effective treatment options for COVID-19.”
Round A investors included 3E Biventures, YuanMing Capital, Viventures and Oceanpine Capital. B round investors included Lilly Asia Ventures, Junson Capital, 3E Bioventures, Matrix Partners China, Korea Investment Partners.