HiFiBiO Therapeutics, a multinational biotechnology company with unique expertise in immune modulation and single-cell science, today announced a publication in Nature Communications with its collaborators at Xinhua Hospital and Nankai University on the preclinical data for its SARS-CoV-2 neutralizing monoclonal antibody, HFB30132A1 (P4A1-2A in the manuscript). The manuscript entitled “A SARS-CoV-2 neutralizing antibody with extensive Spike binding coverage and modified for optimal therapeutic outcomes” was released online ahead of publication in Nature Communications.
HFB30132A is a unique antibody that binds to the majority of the amino acids in the receptor binding domain (RBD) that interact with the human ACE2 receptor. In vitro studies show that HFB30132A potently binds to mutant variants of the Spike protein and efficiently neutralizes mutant pseudoviruses, including the highly prevalent B.1.1.7 variant first isolated in UK. As part of this study, scientists were able to demonstrate the engineered antibody’s optimized pharmacokinetic and safety profile by showing how a single administration of HFB30132A into rhesus monkeys infected with the SARS-CoV-2 virus results in complete viral clearance. The comprehensive characterization of this antibody provides strong evidence for its promising potential to effectively treat and prevent COVID-19 in humans.
HFB30132A was engineered as an Fc modified IgG4 with minimized binding to the human FcγRs, which leads to reduction of risk for antibody-dependent enhancement (ADE) of coronavirus infection, an increased affinity for human FcRn, and an extended half-life. Its profile allows this antibody to be positioned for both therapeutic and prophylactic applications.
HFB30132A is currently in a Phase 1 dose-ranging study in healthy volunteers (NCT04590430). HFB30132A is well tolerated at all doses tested in humans, displays an excellent pharmacokinetic profile, and distributes to the respiratory mucosa.
“Our HFB3013 program is a combination of our deep knowledge in the molecular mechanisms of disease, our expertise in single-cell technology and antibody engineering, and our commitment to curing disease. The rapid progression from discovery to Phase 1 underscores this commitment,” said Liang Schweizer, PhD, President and CEO of HiFiBiO Therapeutics. “The excellent tolerability and sustained plasma exposures in the Phase 1 study along with the extensive preclinical characterization of HFB30132A makes us confident in its potential to treat and prevent COVID-19 in humans. We look forward to additional partnerships to continue the development of HFB30132A, including combination approaches to help address COVID-19.”
“Monoclonal antibodies developed from convalescent patients may represent some of the most effective anti-viral weapons in the fight against SARS-CoV-2 infection. We are happy to be part of this productive collaboration and excited to see that our initial contribution has made it possible for HiFiBiO to engineer and advance the molecule into the clinic so quickly,” said Kun Sun, MD, PhD, one of the corresponding authors and President of Xinhua Hospital in affiliation with Shanghai Jiaotong University. “It is our hope that this neutralizing antibody will be available to benefit patients soon, including those who cannot benefit from or have access to vaccines such as young children, the elderly, and certain immunocompromised individuals. Neutralizing antibodies such as HFB30132A can not only protect them from serious complications, but also curb the spread of COVID-19.”
Zihe Rao, PhD the last corresponding author, member of the Chinese Academy of Sciences and former Chancellor of Nankai University, also stated, “Deep understanding of structural biology has been playing important roles in anti-viral drug development for many years. The development of HFB30132A showcases how this knowledge can be leveraged to make potent anti-viral therapies. Our work continues to demonstrate our dedication towards combating SARS-CoV-2 and other viruses that cause severe diseases in humans.”
To read the full manuscript, please visit here.
HFB30132A is an anti-SARS-CoV-2 recombinant antibody engineered with specific sequences identified from the B cells of a COVID-19 convalescent patient. The antibody binds the viral spike protein with high affinity and has demonstrated potent neutralization of live virus infections in vitro and in vivo. HFB30132A also efficiently neutralizes a panel of SARS-CoV-2 S protein variants including the dominant D614G and the most prevalent RBD mutations such as N501Y and S477N. In an on-going clinical trial in healthy volunteers (NCT04590430), HFB30132A is well tolerated and non-immunogenic at all doses tested, exhibits extended half-life, and distributes to the respiratory mucosa. With a longer half-life, HFB30132A is expected to provide prolonged protection against SARS-CoV-2 infection.
About HiFiBiO Therapeutics
HiFiBiO Therapeutics is transforming the field of immunotherapy by combining proprietary single-cell profiling technologies with advanced data intelligence and deep knowledge of immune system biology. This approach enables the development of novel antibody therapies that are paired with biomarkers to predict patient response. HiFiBiO Therapeutics is working actively to address unmet medical needs around the world through its own innovative pipeline programs and open-innovation partnerships with world-renowned industrial and academic leaders. The company’s global footprint features cutting-edge laboratories on three continents, in Cambridge, Mass., Paris, Shanghai, Hangzhou, and Hong Kong. To learn more, please visit www.hifibio.com.
1 HFB30132A is an investigational agent. Safety and Efficacy have not been established. There is no guarantee that HFB30132A will become approved and commercially available anywhere globally.