SOUTH SAN FRANCISCO, Calif.–(BUSINESS WIRE)–Centivax Inc, the therapeutics spin-out of Contract Research Organization Distributed Bio Inc, announced a significant advance in their mission to develop an optimized antibody therapeutic to treat COVID-19.
Today, three independent laboratories have confirmed that multiple Centivax antibody therapeutic candidates are potent neutralizers of the pandemic coronavirus. Viral neutralization directly demonstrates that the antibodies are able to completely block the novel coronavirus from infecting human cells. “Independent validation is a cornerstone of good science,” says Dr. Jacob Glanville, Founder, CEO, and President of Centivax and Distributed Bio. “We sent our antibodies out to three world-class laboratories to ensure that independent groups, using different people, samples, equipment, and experimental designs, would all come to the same robust conclusion: that we had generated highly potent neutralizing antibodies that could be used to treat the novel coronavirus.”
Dr. Alex Bukreyev at the University of Texas Medical Branch and the Galveston National Laboratory reports, “Our lab tested a panel of antibodies against a real SARS-CoV-2 in biocontainment. We were pleased to see very good neutralizing activity for some antibodies. We are working on their testing in vivo, and I hope to see protection soon.”
Dr. Peter S. Kim, the Virginia & D.K. Ludwig Professor of Biochemistry at Stanford University and Lead Investigator of the Infectious Disease Initiative at the Chan Zuckerberg Biohub, agreed, “We are pleased to find that the Centivax antibodies prevent infection by lentiviruses pseudotyped with the SARS-CoV-2 Spike protein and hope that these antibodies will assist in the development of therapeutics and vaccines.”
Scientists at the U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID) are testing the antibodies for their ability to prevent the novel coronavirus from infecting human cells. “We are still in the early stages of evaluating these monoclonal antibodies, but the preliminary results are promising,” said Dr. Jay Hooper, who is leading the USAMRIID effort. “The plaque reduction neutralization test, or PRNT, data indicate a subset of these antibodies have potent neutralizing activity against live SARS-CoV-2. I look forward to further evaluation of these lead candidates in cell culture and in animal models.”
Centivax would like to thank the community effort of over 1,200 people across 44 nations who donated to help make the discovery and characterization of these antibodies possible.
Centivax was able to successfully engineer these potent therapeutic antibodies in less than 9 weeks by leveraging Distributed Bio’s breakthrough computational antibody engineering technologies: Tumbler and SuperHuman2.0. “We had refined these technologies on over 50 antibody discovery and optimization programs with partners across the biotechnology industry. When the pandemic struck, we were ready,” notes Sarah Ives, Director of Contract Research at Distributed Bio and cofounder of Centivax.
The Distributed Bio Tumbler technology was used to adapt 5 previously proven potently neutralizing and protective anti-SARS antibodies to target the novel pandemic COVID19-causing SAR-CoV-2 coronavirus. “These were well-established, super-potent anti-SARS antibodies that could neutralize SARS and completely protect animals from SARS. We just needed to adapt them to the new coronavirus,” explains Shahrad Daraeikia, Senior Scientist at Distributed Bio and cofounder of Centivax. “By using Tumbler to create and search through billions of mutant variants of these anti-SARS antibodies, we succeeded in evolving them in under 7 weeks to be potent weapons in the fight against the COVID-19 pandemic.”
Centivax also used the Distributed Bio SuperHuman2.0 technology to rapidly identify fully human, novel therapeutic antibodies against the viral “spikes” including broad-spectrum antibodies that blocked both SARS and SARS-CoV-2.
Sindy Liao Chan, Director of Biosensing/High Throughput Protein Interactions at Distributed Bio and cofounder of Centivax, summarizes the discovery process: “In 2 weeks, we screened thousands of anti-SARS-CoV-2 antibodies that we generated with our technologies for binding kinetics, affinity, and epitope specificity. We were successful in identifying high-affinity IgG candidates from all 5 Tumbler programs as well as the SuperHuman2.0 program to the receptor binding domain of the spike glycoprotein of SARS-CoV-2 that blocks the human ACE2 cellular receptor required for viral entry and infection.”
In addition to high affinity and potent neutralization, the antibodies have been engineered for optimal therapeutic properties. “These antibodies represent the cutting edge of modern antibody engineering. They are optimized for enhanced potency, thermostability, reduced immunogenicity, extended half-life, and enhanced safety. This makes them ideal therapeutic candidates for treating the novel pandemic coronavirus in both the hospital as well as prophylactic settings,” reports Dr. Jacob Glanville. “We have designed these molecules to fight the pandemic where it is needed most. Emergency COVID-19 patients. Medical staff. The elderly. The immunocompromised. Warfighters. From Ebola to Rabies, antibody therapeutics have repeatedly proven to be a powerful medicine to treat dangerous viruses, and with this new neutralization data, we can move forward with increased confidence that they will be effective to help end this viral threat as well.”
The therapeutic property engineering has already shown results. “My teams have confirmed that the molecules have superior stability, expression, and are specific to the viral target without any binding to human cells,“ describes Dr. Sawsan Youssef, Chief Science Officer and immunologist at Distributed Bio and cofounder of Centivax, “These are all important properties to ensure that the drug can be produced inexpensively, is shelf-stable, can be concentrated for easier delivery, and has a clean safety profile and half-life.” Centivax Director of Virology, Professor David Gangemi, reviews the clinical opportunities for these engineered molecules: “Because of their exceptional physical properties including neutralization potency, affinity, and stability, these antibodies will be highly effective in reducing SARS-CoV-2 replication and dissemination, and can be concentrated and delivered in smaller doses that may be suitable for the more convenient subcutaneous route of administration and for prophylaxis of at-risk individuals.”
Going forward, the best antibodies are being progressed for safety assessment with Charles River Laboratories. “We are encouraged by the neutralizing effect seen thus far,” said Birgit Girshick, Corporate Executive Vice President at Charles River. “As a strategic partner of Distributed Bio, we’re proud to support this innovative program and are excited by the potential it holds.” Centivax aims to complete pre-clinical development and initiate a clinical study for COVID-19 patients by the end of summer, and remains open to any collaborative opportunities to further accelerate rapid global access to the medicine to follow. “This will likely be the fastest I’ve ever taken a therapeutic antibody into the clinic,” explains Dr. Sawsan Youssef, “but the world needs this therapy now.”
The combination of Centivax’s focus on anti-pandemic therapeutic discovery and Distributed Bio’s advanced computational immunoengineering technologies was well-suited to rapidly respond to the novel coronavirus outbreak. “For 8 years leading up to the COVID-19 pandemic, my teams had been preparing for a crisis such as this one, developing therapeutic technologies uniquely well-suited to fight pandemics,” explains Dr. Jacob Glanville. “Beyond industry, the Distributed Bio technology platforms were recognized for their ability to rapidly generate therapeutics against challenging pathogens by multiple agencies in the armed forces, resulting in Cooperative Research and Development Agreements (CRADAs) with USAMRIID, the Naval Medical Research Center (NMRC), and Walter Reed Army Institute of Research (WRAIR) prior to the coronavirus outbreak.” In 2019, Centivax’s universal vaccine technology had been awarded a Gates Foundation Grand Challenge “End the Pandemic Threat” award and was featured in the Netflix documentary series Pandemic: How to Prevent an Outbreak.
[The information contained in this press release does not necessarily reflect the position or policy of the Government and no official endorsement should be inferred.]
Centivax is a therapeutics company founded to treat, cure and eradicate complex pathogens of the 21st century. This goal is executed by combining computationally-guided therapeutic engineering to efficiently make break-through medicines, with a unique business strategy to make sure that we have the freedom to pursue medicines that matter and sell those medicines at a price that the world can afford. Centivax is spun out of a series of internally incubated technology projects run at Distributed Bio. These technologies were made possible by the emerging field of computational immunology and developed by pioneers of that field over the course of 8 years at Distributed Bio. From our unique vantage point as the creators of these technologies, we were able to see that the true consequence of computational immunoengineering went far beyond disrupting the biologics discovery services market, and had broken open pathways to victory against many of the major outstanding druggability challenges in our generation of medicine. Central to Centivax’s DNA is a commitment to making all of our medicines available at close to cost in the developing world, and to run a lean business that keeps our medicines affordable. We focus on common-sense rapid product creation as a means of ensuring a sustainable R&D budget while reducing our reliance on external funding and ensuring that our incentives are always aligned with making medicines that matter.
About Distributed Bio
Distributed Bio is a biologics discovery contract research organization and a field leader in advanced computational immunoengineering of biomedicines. Our mission is to create breakthrough technologies to drug previously challenging targets (GPCRs, ion channels, pMHC complexes, condition-specific binders, anti-idiotypes, and broadly neutralizing viral epitopes), engineering IgGs, CAR-Ts, VHHs, bi-specifics and other biologic modalities to suit any therapeutic area. Distributed Bio SuperHuman 2.0 computationally optimized antibody library contains more than 76 billion unique fully human and computationally diversified antibodies, enabling rapid recovery of high-affinity, therapeutic-quality antibodies against novel therapeutic targets like SARS-CoV-2. SuperHuman2.0 has been licensed by numerous pharmaceutical companies and can be accessed through Distributed Bio discovery services to generate antibodies against any target. In addition, the Distributed Bio Tumbler platform is another industry-standard antibody optimization technology, licensed by multiple pharmaceutical partners to optimize the developability and potency of biologic medicines. Distributed Bio has been profitable since day one in 2012 with no venture capital investment.