On Wednesday, August 6th and Thursday, August 7th, the World Health Organization (WHO) held an Emergency Committee teleconference to determine whether the current outbreak of Ebola Virus Disease (EVD) in West Africa constitutes a Public Health Emergency of International Concern. After discussion and deliberation, the Committee advised that the Ebola outbreak in West Africa constitutes an ‘extraordinary event’ and a public health risk to other States, and that possible consequences of further international spread of the disease are particularly serious in view of the virulence of the virus, intensive community and health facility transmission patterns, and the weak health systems in currently affected and most at-risk countries.
Ebola virus has human case fatality rates as high as 90 percent, and is responsible for some 1,800 cases and approaching 1,000 deaths in the current West African outbreak affecting Guinea, Sierra Leone, Liberia, and the latest — Nigeria, over the past several months. Between August 5 – 6th, 68 new cases (laboratory-confirmed, probable, and suspect cases) of EVD and 29 deaths were reported from the main four countries affected thus far. In addition to being a global health concern, the U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID) also considers Ebola a potential biological threat agent.
The WHO committee determined that a coordinated international response is deemed essential to stop and reverse the international spread of Ebola, and it was the Committee members’ unanimous view of the that conditions for a Public Health Emergency of International Concern (PHEIC) have been met.
On Friday, WHO Director-General, Dr Margaret Chan gave a press briefing to the international media from WHO Headquarters, and will give an additional briefing on the situation of the outbreak and the ongoing response in the region to the Permanent and Observer Missions to the United Nations and other international organizations in Geneva on Tuesday, August 12th.
On Monday, August 11th, WHO will convene a panel of medical ethics experts to review and discuss experimental treatments in the ongoing West African EVD outbreak. Currently there are no registered medicines or vaccines against EVD, although several experimental options are under development. Two seriously ill health workers from US faith-based aid organizations were flown from Liberia to Atlanta under heavy quarantine this week. American medical missionaries Dr. Kent Brantly of the Samaritan’s Purse non-denominational evangelical Christian International Relief organization based in Boone North Carolina, and Nancy Writebol — an aid worker also from North Carolina who works with Serving in Mission (SIM), were transferred under heavy security to the Emory University hospital’s special isolation unit for voluntary treatment with the experimental monoclonal antibody (mAb) cocktail drug ZMapp — a product of Mapp Biopharmaceutical of San Diego, in collaboration with also San Diego-based Leaf Biopharmaceutical Inc.
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The experimental use of ZMapp therapy on Dr. Brantly and Ms. Writepol has raised ethical questions about whether medicines that have never been tested or shown to be safe in humans should be used in outbreak situations. In the case of Ebola experimental drugs, supplies are extremely constrained, raising even more questions about who should receive it, if it’s used.
There are several programs underway to develop medicines to combat EVD, most, like ZMapp, being focused on deployment of monoclonal antibodies. A study resulting from a widespread scientific collaboration has shown promising preliminary results, preventing disease in infected nonhuman primates using mAbs.
In an article published in the online edition of the Proceedings of the National Academy of Sciences (PNAS), the study research team describes a proof-of-concept for using a “cocktail” of mAbs to prevent lethal disease in rhesus macaque primates. When administered one hour after infection, all animals survived. Two-thirds of the animals were protected even when the treatment, known as MB-003, was administered 48 hours after infection.
The work is culmination of more than a decade of effort between government and industry partners. According to lead investigator Gene Olinger, Ph.D., a virologist at USAMRIID, the consortium of investigators took very distinct technologies and combined them to develop a cutting-edge medical countermeasure against a lethal viral disease.
“It is rare that an antiviral compound prevents Ebola virus infection with limited to no morbidity in treated animals at any point of treatment following infection by this lethal virus,” comments Dr. Olinger in a USAMRIID release. “Until recently, attempts to utilize antibodies to provide protection against Ebola virus have been met with failure. The level of protection against disease that we saw with MB-003 was impressive.”
Caliber Biotherapeutics Ramps Up Readiness For Ebola Fight
Earlier this week, BioNews Texas reported that the Texas A&M Center for Innovation in Advanced Development and Manufacturing has been cited as a potential mass-production center for ZMapp medicine. The TAMU Center is one of just three facilities in America equipped to standardize a treatment and geared to accelerate research and development of vaccines and therapeutics for a virus such as Ebola , with the goal of shepherding these products through pre-clinical and clinical development to licensure and production as quickly as possible consistent with due diligence, according to Dr. Scott R. Lillibridge, a professor of epidemiology and assistant dean with the Texas A&M Health Science Center School of Rural Public Health in Houston.
Also this week, The New York Times‘ Andrew Pollack cited R. Barry Holtz chief science and technology officer at Bryan, Texas based biotechnology company Caliber Biotherapeutics, LLC , which was established with Defense Department funding to be able to respond to biological threats, saying Caliber has received inquiries from government officials about whether it could help manufacture ZMapp.
Caliber Biotherapeutics Project Manager Lan H. Ly, Ph.D commented to BioNews Texas today via email that “Caliber Biotherapeutics is the largest plant-made pharmaceutical operation in the United States. We have shown that we can make commercial quantities of vaccines and biotherapeutics in plants cost-effectively and quickly and stand ready to help in this crisis should we be asked.”
Read more about Caliber Biotherapeutics in the News:
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Caliber Biotherapeutics also has a strategic alliance with G-Con Manufacturing of College Station, Texas for comprehensive Good Manufacturing Practice (GMP) solutions. G-Con’s mission is to revolutionize the biomanufacturing industry by providing comprehensive GMP manufacturing solutions that are flexible, less expensive to build and maintain, and easier to operate than any existing solution.
Dr. Holtz is also President and Co-Founder of G-CON,LLC, and was Senior Vice President of Biopharmaceutical Development for Large Scale Biology Corporation (LSBC) for 15 years, and was responsible for product development, long-term regulatory strategy, clinical development, and manufacturing compliance of the company’s proprietary therapeutics portfolio. He has been awarded 23 U.S. patents, and has published more than 50 scientific papers.
Caliber Biotherapeutics’ stated mission is to develop and commercialize protein-based therapeutic agents that improve outcomes for patients with cancer and other diseases. The Company utilizes technological innovations in biological research, product development, and manufacturing to create treatments with increased safety and effectiveness — while reducing both costs and development time.
Caliber says it has created a pipeline of “biobetter” products, applying its expertise in the Nicotiana benthamiana plant-based expression and manufacturing of recombinant proteins. Caliber operates what it claims is the world’s largest N. benthamiana expression based protein manufacturing facility in College Station, Texas. Under a DARPA challenge, the company has demonstrated the ability to rapidly produce substantial quantities of influenza vaccine antigen using this facility. Caliber’s technologies are being supported by the Cancer Prevention and Research Institution of Texas (CPRIT), DARPA and several Texas based life sciences investors.
Regarding mAb research, in late 2012, Caliber Biotherapeutics and Thousand Oaks, CAlifornia based ImmunGene, Inc. announced the launch of Valor Biotherapeutics, LLC, a joint venture focused on clinical development and commercialization of monoclonal antibody-interferon (mAb-IFN) fusion protein therapeutics targeting certain cancers and other diseases. The mAb-IFN fusion protein technology was invented in Professor of Microbiology, Immunology & Molecular Genetics Sherie Morrison’s laboratory at the University of California, Los Angeles and licensed exclusively to ImmunGene. This technology is being used to enable the precise targeting of tumor cells with monoclonal antibodies and their destruction by interferon.
ImmunGene technology allows fusing cytotoxic cytokines to antibodies to selectively target disease causing cells and tissues while reducing the systemic toxicity of the cytokines. This versatile fusion system genetically links IFNa, a clinically validated tumor killing cytokine, with monoclonal antibodies. ImmunGene is also advancing its own pipeline of next-generation antibody-based candidates.
Through the joint venture, Caliber has gained access to the mAb-IFN fusion protein platform — a new class of therapeutics produced by fusing antibodies to tumor cell-killing cytokines (e.g. IFN). These fusion proteins offer potential advantages because several important properties can be built into a single, genetically engineered molecule. They are thought to kill tumor cells mainly by stimulating apoptosis, in an ADCC (antibody-dependent cell-mediated cytotoxicity)-independent manner. Consequently, these molecules have the potential to be efficacious in patients with defective ADCC mechanisms. In addition, they have the potential to be cytotoxic to tumor cells with low density of targeted surface antigens. The fusion proteins retain the properties of conventional, non-fused antibody therapeutics in stimulating ADCC and complement-dependent cytotoxicity (CDC) functions.
“This joint venture will allow us to accelerate the development of ImmunGene’s antibody interferon fusion drug candidates into human proof-of-concept studies in cancer patients,” commented Sanjay D. Khare, Ph.D., CEO of ImmunGene, at the 2012 announcement. “We believe our technology has the potential to improve the treatment of certain cancers and that Caliber’s unique experience in cancer research will help us realize the clinical and commercial potential of our pipeline through this promising joint venture.”
PMP Based Monoclonal Antibodies (mAb) Candidates
Caliber has created a series of Rituximab biobetter candidates using the company’s proprietary N. benthamiana expression system. The project is being supported by CPRIT with the larger goal of enabling the industrialization of the N. benthamiana expression technology leveraging Caliber’s massive production facility. Caliber says it is using additional technologies to enhance the power of its N. benthamiana production system to design multiple biobetter mAb candidates.
Monoclonal Antibody – Interferon (mAb-IFN) Fusion Proteins
mAb-IFN fusion proteins are a new class of biotherapeutics produced by fusing antibodies to tumor cell-killing cytokines (e.g. IFN). These fusion proteins offer potential advantages because several important properties can be built into a single, genetically engineered molecule. They are thought to kill tumor cells mainly by stimulating apoptosis, in an ADCC (antibody-dependent cell-mediated cytotoxicity)-independent manner. Consequently, these molecules have the potential to be efficacious in patients with defective ADCC mechanisms. In addition, they have the potential to be cytotoxic to tumor cells with low density of targeted surface antigens. The fusion proteins retain the properties of conventional, non-fused antibody therapeutics in stimulating ADCC and complement-dependent cytotoxicity (CDC) functions. Valor Biotherapeutics says such mAb-IFN fusion proteins have demonstrated superior efficacy and safety in preclinical studies, validating the therapeutic potential of this technology.
The World Health Organization
Texas A&M University
University of California, Los Angeles
Caliber Biotherapeutics LLC
Valor Biotherapeutics LLC
U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID)
Proceedings of the National Academy of Sciences (PNAS)
The New York Times