USAMRIID, GNL confirm efficacy of COVID-19 antibody therapy in hamsters

Centivax Inc, the therapeutics spinout of Contract Research Organization Distributed Bio Inc, announced today that their antibody therapeutic protects hamsters from SARS-CoV-2, the COVID-19-causing coronavirus. Confirmed simultaneously at two independent national laboratories, these results provide critical support for the antibody to move to clinical studies to protect and treat human patients.

At the U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID) in the Department of Defense (DoD), the Centivax lead antibody was administered to hamsters preventatively to protect against future exposures. The researchers found that the antibody protected the hamsters from COVID-19 symptoms and radically reduced the amount of the pathogenic virus in hamster lungs, even in immunocompromised hamsters. At the University of Texas Medical Branch/Galveston National Laboratory (UTMB/GNL) the Centivax lead antibody was administered as a therapeutic to previously infected hamsters: within 48 hours, the hamsters had a 97% reduction of virus in the lungs and significantly reduced lung damage.

“Hamsters, like humans, can become infected and fall ill after exposure to SARS-CoV-2, the virus that causes COVID-19. This is why hamsters are considered the gold standard to evaluate the effectiveness of therapeutics to treat and prevent the novel coronavirus in humans,” explains Dr. Sawsan Youssef, Chief Science Officer of Distributed Bio and Centivax.

“This is a watershed moment for a COVID-19 therapy,” said Dr. Jacob Glanville, founder, CEO and President of San Francisco-based Centivax and Distributed Bio. “These two world-class laboratories came to the same robust conclusion: that we had generated neutralizing antibodies that successfully protected hamsters from the novel coronavirus. Independent validation of this kind is a cornerstone of good medical science. We move forward now with confidence into rapid clinical development of our human therapy.”

Therapeutic applications

Dr. Alex Bukreyev’s laboratory led the protective hamster model research at UTMB/GNL, where hamsters already infected with COVID-19 were administered the Centivax lead antibody.

“We tested the Centivax lead antibody in the hamster model of COVID-19 and observed a significant reduction of the viral load in the lungs and reduced pathology,” said Bukreyev, a professor of pathology and microbiology & immunology at the university.

Preventive applications

The positive preventative results indicate that the Centivax antibody could be used as a prophylactic to protect vulnerable populations such as the elderly, the immunocompromised, and frontline care workers from the symptoms of COVID-19. Dr. Jay Hooper’s laboratory led the prophylactic model research at USAMRIID, where hamsters were first administered the Centivax antibody and then exposed to the novel coronavirus. “

Two monoclonal antibodies that showed promise in our neutralization assay were tested in two Syrian hamster models of COVID-19 — both antibodies showed evidence of protective efficacy,” said Hooper, chief of the molecular virology branch at USAMRIID. His laboratory confirmed that the Centivax lead antibodies provided protection in both healthy as well as immunocompromised hamsters. A similar effect in humans could protect high-risk and immunosuppressed populations from COVID-19.

Coronavirus neutralization

These results expand on previous findings by five independent laboratories across 3 nations that the Centivax antibodies were able to potently neutralize the novel coronavirus SARS-CoV-2. In addition to previous reports of neutralization of the virus by USAMRIID, UTMB/GNL, and Dr. Peter S. Kim’s lab at Stanford University, two additional partners confirmed potent neutralization: Dr. Nigel Temperton’s laboratory, Viral Pseudotype Unit at the University of Kent in the UK, and Sino Biological in China.

“The Viral Pseudotype Unit evaluated a panel of Centivax/Distributed Bio antibodies for their ability to neutralize SARS-CoV-2 Spike-pseudotyped HIV vectors. Many were found to be potent neutralizers in our sensitive assay,” Temperton said. “We evaluated a panel of 50 antibodies from Centivax/Distributed Bio: we identified multiple potent neutralizers in our assay,” added Dr. Zie Zhang, President of Sino Biological.

“Best-in-class” therapeutic optimization

“While neutralization of the coronavirus is necessary, there are many other factors that influence the performance of a therapeutic antibody,” said Sarah Ives, Director of Contract Research at Distributed Bio. “By leveraging the advanced bioengineering capabilities at Distributed Bio, we have enhanced the potency, thermostability, safety, half-life, and manufacturability of the Centivax lead candidates.”

Centivax was able to successfully engineer these potent therapeutic antibodies in less than 9 weeks by implementing Distributed Bio’s breakthrough computationally optimized antibody engineering technologies: Tumbler to adapt antibodies previously proven to neutralize SARS-CoV-1 from 2002 to target the related but novel SARS-CoV-2, and SuperHuman 2.0 to discover new antibodies de novo. For both technologies, the discovery process included optimization engineering for affinity, thermostability, humanness, specificity, safety, half-life, non-immunogenicity, and manufacturability.

“Such optimizations have very practical consequences, as they enable Centivax antibodies to have outstanding safety profiles, be manufactured more easily and less expensively, be more shelf-stable, and possibly be delivered more conveniently, such as through subcutaneous injection outside a hospital environment,” said Dr. David Gangemi, Director of Virology at Centivax. “

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