User:Oceanflynn/sandbox/Timeline VSV-EBOV

A timeline of selected events related to VSV-EBOV

VSV-EBOV
file=7042 lores-Ebola-Zaire-CDC Photo.jpg VSV-EBOV or rVSV-filovirus-GP type of vaccine, is an experimental vaccine for the Ebola filovirus, 'viral hemorrhagic fever (VHF), developed by a team of scientists at the National Microbiology Laboratory of the Public Health Agency of Canada (PHAC) in c.2003. The vaccine contains a gene for the Ebola surface protein stitched into a livestock pathogen known as vesicular stomatitis virus (VSV). According to Dr. Gregory Taylor of the PHAC, "This vaccine, the product of many years of scientific research and innovation, could be an important tool in curbing the outbreak." VSV-EBOV vaccine was found to be 100% effective in protecting Nonhuman primates (NHP) from Ebola and is now being rushed through human trials - "after sitting unused on a lab shelf for ten years. The VSV-EBOV vaccine had its results "published in a respected journal," and "health officials called them exciting."

VSV-EBOV uses an Ebola virus protein spliced into a weakened strain of a different virus, vesicular stomatitis virus (VSV), which typically afflicts cattle. The weakened viral strain is modified to express an Ebola virus protein to help trigger an immune response to Ebola."

It costs a few million dollars for academic researchers to "develop a prototype drug or vaccine that works in animals." But "tests in humans and scaling up production can cost hundreds of millions, and bringing a new vaccine all the way to market typically costs $1 billion to $1.5 billion."

"While vaccines normally are preventatives, the VSV-EBOV vaccine has shown effectiveness in studies on animals after they were exposed to the virus. It may be used soon after someone was exposed to infection, similar to the way rabies shots are used now, said Gary Kobinger, chief of special pathogens for the Public Health Agency of Canada."

By 2014 there were several experimental ebola vaccines considered by WHO but the VSV-EBOV is considered to be the most promising as it requires only one injection.

The U.S. National Institutes of Health is planning a larger, human study in early 2015 to test another experimental Ebola vaccine co-developed by the NIH and GlaxoSmithKline PLC GSK, -0.03%.

Johnson & Johnson JNJ, -0.17%  also is developing an experimental vaccine in partnership with Bavarian Nordic of Denmark.

Ebola
The family Filoviridae include Ebola virus and Marburg virus. The Ebola virus was first identified in 1976. Since then "no previous Ebola outbreak has been as large or persistent as the current epidemic." The most widespread epidemic of Ebola virus disease in history which emerged again in 2013 is ongoing in 2014 in several West African countries. According to the World Health Organization, by October 2014, the Ebola outbreak in West Africa had already killed more than 4,500 people.

Public Health Agency of Canada
The Public Health Agency of Canada holds the patent associated with the rVSV-filovirus-GP type of vaccine.

National Microbiology Laboratory
From 1999 to 2008, Dr. Feldmann held the position of chief of the special pathogens program of the National Microbiology Laboratory, Public Health Agency of Canada. At a conference in Germany in 2000 Dr. Thomas Geisbert of University of Texas Medical Branch and Dr. Heinz Feldman of the highest level containment required to safely work with deadly viruses, Biosafety level four (BSL-4) at the National Microbiology Laboratory in Winnipeg, decided to work together to develop an Ebola vaccine. They tested the vaccine on monkeys with a 100% success rate and published their findings in 2005 and 2011. The "Galveston National Laboratory at the University of Texas Medical Branch also has a Biosafety level four (BSL-4) facility.

"The development of the vaccines started in 2001 at the National Microbiology Laboratory (NML) in Winnipeg, in partnership with the then-Faculty of Medicine at the University of Manitoba (it’s now the College of Medicine in the Faculty of Health Sciences). At the time, Jones was professor of immunology and Feldmann, a professor of medical microbiology. The research was supported by a Canadian Institutes of Health Research grant through the U of M. Following initial trials, work was carried out in partnership with the U.S. Army Medical Research Institute of Infectious Diseases in what was being considered a landmark in international scientific collaboration." The VSV-EBOV "vaccine went into non-human primate (monkey) trials in late 2003. The monkeys were 100 percent protected." In 2003 scientists from the Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland and the United States Army Medical Research Institute of Infectious Diseases reported on the results of an experimental vaccine which successfully protected non-human primates (cynomolgus macaques) against ebola. At that Thomas W. Geisbert was associated with the United States Army Medical Research Institute of Infectious Diseases in Maryland and he co-authored a paper entitled Accelerated vaccination for Ebola virus haemorrhagic fever in non-human primates with eight fellow scientists at  the Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland and the United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland.

In 2005 Steven M Jones, Heinz Feldmann, Ute Ströher, Joan B Geisbert, Lisa Fernando, Allen Grolla, Hans-Dieter Klenk, Nancy J Sullivan, Viktor E Volchkov, Elizabeth A Fritz, Kathleen M Daddario, Lisa E Hensley, Peter B Jahrling & Thomas W Geisbert published the results of their very successful vaccine trials on monkeys in the journal Nature Medicine. A single injection of the "EBOV or MARV vaccine elicited completely protective immune responses in nonhuman primates against lethal EBOV or MARV challenges." In 2005 Dr. Kobinger moved back to Canada in 2005 bringing his Ebola research with him. The Public Health Agency of Canada provided start-up funds and provided space for Kobinger's team. Financial support came the Canadian Department of National Defence's Chemical, Biological, Radiological and Nuclear Research and Technology Initiative.

The central role in ebola research played by National Microbiology Laboratory in Winnipeg is credited to Heinz Feldmann, the lab's first special pathogens chief and Gary Kobinger, his successor and the current branch chief. The National Microbiology Laboratory produced "ZMapp, the most promising of the current experimental treatments", an Ebola vaccine that may be useful both to prevent infection and stop it in its tracks" and "a mobile diagnostic lab that has changed the way outbreak testing is done."

Dr. Frank Plummer was director of NML from 2000 to March 2014 when he stepped down for health reasons. Plummer has been battling health problems over the past year; he finished his final term in the job at the end of March. According to Canadian Press journalist Branswell, scientific and public health leaders were "very concerned about the way the government is going about filling the job and the job posting itself." There was only a "[t]he three-week window to apply, the lack of attention drawn to the opening, and the salary scale offered — starting at $132,600 — suggested to a number of people that the federal government might be seeking a bureaucrat, not a top-notch scientist, to replace Plummer, who is a world-renowned HIV researcher."

""The posting did not stipulate that candidates must be experienced scientists, nor did it ask that they have published scientific papers. It calls for experience managing the delivery of health-related programs, providing strategic scientific advice and representing an organization nationally and internationally. The wording of the posting even suggests someone could be named to the job without having either a medical degree or a PhD.""

- Branswell 2014d

The National Microbiology Laboratory in Winnipeg and the "Galveston National Laboratory at the University of Texas Medical Branch [are facilities] with the highest level containment required to safely work with deadly viruses, Biosafety level four (BSL-4)."

Dr. Heinz Feldmann
From 1999 to 2008, Dr. Feldmann held the position of chief of the special pathogens program of the National Microbiology Laboratory, Public Health Agency of Canada.

Dr. Gary Kobinger
In 2005 Dr. Kobinger moved back to Canada in 2005 bringing his Ebola research with him. The Public Health Agency of Canada provided start-up funds and provided space for Kobinger's team. Financial support came the Canadian Department of National Defence's Chemical, Biological, Radiological and Nuclear Research and Technology Initiative.

"The vaccine was produced in Winnipeg by the Public Health Agency of Canada, and is the product of more than 10 years of scientific research by Public Health Agency of Canada scientists at the National Microbiology Laboratory. The Canadian government patented it, and 800 to 1,000 vials of the vaccine were produced.

By September 2007 Dr. Gary Kobinger was working at the mobile field laboratory that the National Public Health Agency of Canada had in Mweka, Congo.

By 2012 funding for the Kobinger's research was a concern. Their major financial source, the Defence Research and Development Canada, was "hit hard by cuts in March 2012 federal budget; microbiology research is not high on its agenda." Marc Fortin, CEO of Defence Research and Development Canada, said that "areas of highest priority" for the organization are cyber security and the Arctic. "Other areas now require less DRDC support."

"The Canadian research was done under the leadership of Dr. Gary Kobinger who heads the special pathogens research program at the national laboratory. His team had developed a cocktail of three monoclonal antibodies called ZMApp, the rights to which were recently acquired by LeafBio of San Diego, Calif." In the 1990s as a youth in Montreal during the AIDS epidemic Kobinger watched documentaries that became catalysts for his career which led him from medical school in Montreal to research in Philadelphia. In Philadelphia he focused on the Ebola virus. "Ebola binds strongly to these cells, so Gary Kobinger at the University of Pennsylvania in Philadelphia tried adding a surface protein from Ebola to HIV. Initial tests on mice showed the hybrid virus was very efficient: the gene it carried was active in 24 per cent of airway cells after two months, a far better proportion than achieved by other delivery methods. ZMapp is a hybrid of two earlier monoclonal cocktails, one made by Kobinger’s team and the other by scientists at the U.S. Army Medical Research Institute of Infectious Diseases in Frederick, Md. Gary Kobinger is the "chief of special pathogens at Winnipeg’s National Microbiology Laboratory and the scientist who led the development of the vaccine." According to a Globe and Mail article published August 2014,

""Dr. Kobinger and his colleagues at the Winnipeg lab also developed two of the three mono-clonol antibodies that form the basis of an experimental Ebola treatment known as ZMapp, which received widespread scrutiny after limited doses were offered to two U.S. health-care workers and a Spanish priest, but not to Africans..."

In July 2014 Dr. Kobinger and his team were involved in ebola-related work in Sierra Leone. When he returned to Canada he told the Canadian Press that the use of the experimental drugs would be too risky.

""These are all experimental drugs that have not met the requirements … even for a Phase 1 [trial] right now in humans. So they have to pass all the toxicity [tests], they have to pass the safety trials."

- Dr. Kobinger July 2014

Thomas W. Geisbert


In an interview with the Boston Globe, Thomas W. Geisbert, a a virologist and "Ebola expert at the University of Texas, Galveston and one of the developers of the vaccine, made a statement,"

"'There's never been a big market for Ebola vaccines... So big pharma, who are they going to sell it to?... It takes a crisis sometimes to get people talking. 'OK. We've got to do something here.'"

At a conference in Germany in 2000 Dr. Thomas Geisbert of University of Texas Medical Branch and Dr. Heinz Feldman of the Level 4 Containment Laboratory at the National Microbiology Laboratory in Winnipeg, decided to work together to develop an Ebola vaccine. They tested the vaccine on monkeys with a 100% success rate and published their findings in 2005 and 2011. Nonhuman primate (NHP)

John Eldridge, chief scientific officer for Profectus BioSciences Inc., based in Baltimore.

Amir Attaran
"University of Ottawa professor Amir Attaran published a letter in the British medical journal The Lancet calling for Canada to withdraw from its agreement with NewLink."

Attaran is calling on the Ottawa to change the licensing agreement, which now says that Canada should get a commercial return on the vaccine, to make sure commercial considerations play no role in the fight against Ebola.

In an interview on 20 November 2014, Professor Attaran argued that the existing licensing agreement between NewLink and the Government of Canada needed to be changed to ensure that commercial considerations are not part of the decisions made to combat ebola. He said,

""The arrangements have to ensure that very poor people, the poorest in the world, get this vaccine without paying a price they can’t afford.... So far, the Government of Canada has demanded a maximum commercial return. That will have to change for that to succeed.""

- Professor Attaran 20 November 2014

NewLink Genetics Corporation
Iowa-based NewLink Genetics acquired the commercial license to develop rVSV-ZEBOV in 2010 for use in humans, in its wholly owned subsidiary BioProtection Systems at the Iowa State University Research Park in Ames, Iowa.

BioProtections Systems
BioProtections Systems, an emerging biotechnology company, is a wholly-owned subsidiary of GenLinks Corporation, located in the ISU Research Park in Ames, Iowa. ""BioProtection Systems Corporation (BPSC) is an emerging biotechnology company located in the Iowa State University Research Park in Ames, Iowa. The company is developing innovative vaccine solutions to increase the United States’ biodefense capabilities. BioProtection Systems Corporation is collaborating with NewLink Genetics’ experienced biomedical and bioinformatics professionals to exploit new vaccine technologies.""

- ISU Research Park 2014

Iowa-based NewLink Genetics has the license to develop rVSV-ZEBOV for use in humans, in its wholly owned subsidiary BioProtection Systems at the Iowa State University Research Park in Ames, Iowa. In this work, BioProtection Systems is supported by the U.S. Defense Threat Reduction Agency, of the United States Department of Defense. The role of Newlink Genetics appears to be mainly the organization of clinical trials in the U.S., as it has no production facilities for the vaccine. Canada had roughly 1,500 vials of vaccine made for clinical trials before the 2014 Ebola outbreak began in West Africa. The license with Newlink has come under criticism. Amir Attaran, a professor of law and population health at the University of Ottawa, has urged that the license be cancelled because of the limitations of such a small company with little experience in this area. The license was awarded when there seemed to be no urgency for an Ebola vaccine, and hence little interest from large pharmaceutical companies.

Timeline

 * 1987 The ISU Research Park in Ames, Iowa was created in 1987 to provide space and resources to technology-based firms and research organizations.

"Between 1994 and the present, there have been many Ebola virus outbreaks, caused by 4 different strains of the virus, affecting mostly people living in central Africa, and the health care providers trying to treat them. Ebola viruses are members of the filoviridae virus family, which also includes the dangerous Marburg virus. It causes severe and often deadly infection called a viral hemorrhagic fever, characterized by organ failure, bleeding, and death."
 *  1994 NewLink Genetics, an Iowa-based biopharmaceutical company, that focuses on "discovering, developing, and commercializing novel immunotherapeutics to improve treatment options for patients with cancer" acquired the commercial license for $200,000 in 2010 for an ebola vaccine developed by Canadians. They did not begin to work on developing the the vaccine until there was a crisis. In their registration of their first clinical trial using the ebola vaccine on human subjects in October 2014, they contextualized their study.

- NewLinks Genetics 2014


 * 2000 At a conference in Germany in 2000 Dr. Thomas Geisbert of University of Texas Medical Branch and Dr. Heinz Feldman of the Level 4 Containment Laboratory at the National Microbiology Laboratory in Winnipeg, decided to work together to develop an Ebola vaccine.


 * 2000 The VHF viruses are considered by military medical planners to have a potential for aerosol dissemination, weaponization, or likelihood for confusion with similar agents that might be weaponized.


 * 11 September 2001 There was more funding after the terrorist attacks and Geisbert and Feldman were able to make progress on the vaccine. The vaccine "used vesicular stomatitis virus, a pathogen employed in other vaccines, and subbed in an Ebola gene. Thus, the host animal would produce atibodies to Ebola but not contract the disease."


 * 2001 "The development of the vaccines started in 2001 at the National Microbiology Laboratory (NML) in Winnipeg, in partnership with the then-Faculty of Medicine at the University of Manitoba (it’s now the College of Medicine in the Faculty of Health Sciences). At the time, Jones was professor ofimmunology and Feldmann, a professor of medical microbiology. The research was supported by a Canadian Institutes of Health Research grant through the U of M. Following initial trials, work was carried out in partnership with the U.S. Army Medical Research Institute of Infectious Diseases in what was being considered a landmark in international scientific collaboration."


 * 2003 The VSV-EBOV "vaccine went into monkey trials in late 2003. The monkeys were 100 percent protected."


 * 2003 Scientists from the Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland and the United States Army Medical Research Institute of Infectious Diseases reported on the results of an experimental vaccine which successfully protected non-human primates (cynomolgus macaques) against ebola. At that Thomas W. Geisbert was associated with the United States Army Medical Research Institute of Infectious Diseases in Maryland.


 * 2005 Steven M Jones, Heinz Feldmann, Ute Ströher, Joan B Geisbert, Lisa Fernando, Allen Grolla, Hans-Dieter Klenk, Nancy J Sullivan, Viktor E Volchkov, Elizabeth A Fritz, Kathleen M Daddario, Lisa E Hensley, Peter B Jahrling & Thomas W Geisbert published the results of their very successful vaccine trials on monkeys in the journal Nature Medicine. A single injection of the "EBOV or MARV vaccine elicited completely protective immune responses in nonhuman primates against lethal EBOV or MARV challenges."


 * 10 August 2005 BioProtection Systems Corporation, NewLink Genetics'swholly owned subsidiary, signed a lease with Iowa State University Research Park Corporation.


 * 27 April 2007 Nicholas N. Vaharian, Chief Medical Officer signed a Confidentiality Agreement on behalf of Bioprotection Systems Corporation (NewLinks its wholly owned subsidiary) and Frank A. Plummer, Scientific Director General of the National Microbiology Laboratory, Canadian Science Centre for Human and Animal Health Canada, signed on behalf of the Public Health Agency of Canada in Winnipeg, Manitoba. The Minister of Health signed an agreement with Bioprotection Systems Corporation, an incorporated company under the laws of Delaware with its registered office at Iowa State University Research Park, through which it was acknowledged that Canada had developed the vaccine and that the company would "develop and commercialize the technology." Bioprotection Systems Corporation is affiliated with Iowa-based NewLink Genetics Corporation. Carl Langren, Chief Financial Officer also signed the document. Bioprotection Systems Corporation is affiliated with Iowa-based NewLink Genetics Corporation. Primary representatives were Dr. Steven Jones and Dr. Dorothea Blandford and Dr. Nicholas Vahanian.


 * 28 September 2007 The National Public Health Agency of Canada installed a mobile field laboratory in Mweka, Congo. Gary Kobinger worked at this field lab.


 * 1 November 2008 The Nondisclosure Agreement came into effect.


 * 14 April 2010 Nicholas N. Vaharian, Chief Medical Officer signed a sole commercial license agreement through its wholly owned subsidiary Bioprotection Systems Corporation and Frank A. Plummer, Scientific Director General of the National Microbiology Lab, Canadian Science Centre for Human and Animal Health Canada, signed on behalf of the Public Health Agency of Canada in Winnipeg, Manitoba. It is affiliated with Iowa-based NewLink Genetics Corporation. [T]he Canadian government licensed Iowa company NewLink Genetics to carry out clinical trials and be the sole producer of an ebola vaccine, rVSV-ZEBOV.

""Canada surrenders its commercial self-interest to the Company; and In exchange, in good faith, the Company uses its discretion and experience in product development and regulatory affairs, its commercial resources and business savvy and, assuming that any relevant statutory, regulatory or administrative authorizations or permits for a vaccine product are obtained, its marketing, sale and distribution savvy for the benefit of both Parties.""

- SEC 2010


 * 4 May 2010 The SEC notes 10.67 *(4) refers to, "Sole License Agreement executed May 4, 2010 by and between Her Majesty the Queen in Right of Canada and BioProtection Systems Corporation." Through this agreement NewLink licensed the vaccine for a mere $200,000. They received some funding from the United States government but NewLink Board of Directors "didn’t see much commercial potential in it." They waited until there was a crisis and then began to work on the vaccine.

""BPS is a party to a license agreement dated May 4, 2010, or the Canada License, with the Her Majesty the Queen in Right of Canada, or Canada. The Canada License grants BPS a worldwide, personal, non-transferable, sole, revocable, royalty-bearing license for commercialization of specified Canada patent rights relating to technology based on rVSV. The license is subject to Canada's retained right to use the Canada patent rights and technology to improve the patent rights, carryout educational purposes, and development of the patent rights where BPS cannot obtain regulatory approval or meet demand. BPS may grant sublicenses under the Canada license, provided that each sublicense is consistent with the terms and conditions of the Canada License and contain certain mandatory sublicensing provisions. In consideration of the license grant, BPS must pay to Canada a specified patent and signing fees, annual license maintenance fees, patent prosecution costs, potential milestone payments in an aggregate amount up to approximately C$205,000 per licensed product, and royalties as a low single-digit percentage of the sales price of the licensed products sold by BPS, which royalty rate varies depending on the type of licensed product. In addition, if BPS grants a sublicense under the licenses granted by Canada, BPS is required to pay to Canada a percentage of certain consideration BPS receives from the sublicensee. BPS is obligated to use commercially reasonable efforts to develop and market the licensed products. If BPS breaches its obligations and fails to cure the breach, Canada may terminate the Canada License. Unless terminated earlier, the Canada License will remain in effect until the expiration of the last of the Canada patent rights. Pending the status of certain patent applications and the payment of appropriate maintenance, renewal, annuity or other governmental fees, we currently expect the last patent will expire under this agreement in 2023, excluding any patent term adjustments or patent term extensions or additional patents issued that are included under the license. Canada may terminate this agreement for BPS's failure to use commercially reasonable efforts to commercialize, failure to pay, breach of confidentiality, cessation of business, criminal conviction or other breach of its obligations under the agreement. BPS may not assign the Canada License to a third party without the prior written consent of Canada, not to be unreasonably withheld. This agreement will terminate automatically if BPS assigns the Canada License without prior written consent or if BPS files for bankruptcy or similar proceedings.""


 * 23 November 2010 NewLink Genetics Corporation in City of Ames, State of Iowa, filed a Certificate of Incorporation.


 * 26 October 2011 NewLink Genetics Corporation applied to the NASDAQ Global Market under the under the symbol NLNK, now NLNK.O. Their initial public offering of 5,500,000 shares of their common stock was registered with the Securities and Exchange Commission with an anticipated initial public offering price of between $10.00 and $12.00 per common share. Charles J. Link, Jr. an oncologist who worked at the National Cancer Institute (NCI) from 1991-93, is CEO; Gordon H. Link, Jr is Chief Financial Officer and Thomas A. Raffin, Ernest J. Talarico III? (who is also senior VP at Mesirow Financial, Chicago), David J. Lundquist, Sarah Alexander, Joseph Saluri and Paul R. Edick on the Board of Directors.


 * 2011 The major source of income for NewLink Genetics is "research and development being performed by their wholly owned subsidiary BioProtection Systems Corporation, or BPS, under contracts and grants with the Department of Defense, or DOD, and the National Institutes of Health, or NIH."


 * March 2012By 2012 funding for the Kobinger's research was a concern. Their major financial source, the Defence Research and Development Canada, was "hit hard by cuts in March 2012 federal budget; microbiology research is not high on its agenda." Marc Fortin, CEO of Defence Research and Development Canada, said that "areas of highest priority" for the organization are cyber security and the Arctic. "Other areas now require less DRDC support."


 * 4 October 2012 The Secretary of the Department of Health representing the Government of the United States took out a patent on "Human Ebola Virus Species and Compositions and Methods Thereof", a process which began on 26 November 2007, according an accession number 200706291.


 * 7 October 2012 There was an outbreak of Ebola haemorrhagic fever (EHF) in the Democratic Republic of Congo (DRC) and by early October 24 people had died. The Centre for Disease Control (CDC) "established a field laboratory in Isiro from the beginning of the outbreak and Public Health Agency of Canada (PHAC) is continuing to provide support on rapid diagnosis in the field with their mobile laboratory facilities in Isiro."


 * July 2013 Dr. Kobinger explained that scientists behind VSV-EBOV began researching VSV-EBOV's safety since 2013. Testing for efficacy and safety are measured separately.


 * 6 March 2014 Dr. Thomas Geisbert, a professor at University of Texas Medical Branch, and researcher at its Galveston National Laboratory received a five-year grant from the National Institutes of Health funds that will be used toward fighting bioterrorism. The grant of up to $26 million will be used by Dr. Geisbert in "collaboration with UTMB, Maryland-based Profectus Biosciences Inc., Tekmira PharmaceuticalsCorp. (Nasdaq: TKMR) of British Columbia and the Vanderbilt University Medical Centeradvance" to advance treatments of the highly lethal hemorrhagic fever viruses known as Ebola and Marburg.


 * July 2014 In July 2014 Dr. Kobinger and his team were involved in ebola-related work in Sierra Leone. When he returned to Canada he told the Canadian Press that the use of the experimental drugs would be too risky.

""These are all experimental drugs that have not met the requirements … even for a Phase 1 [trial] right now in humans. So they have to pass all the toxicity [tests], they have to pass the safety trials.""

- Dr. Kobinger July 2014

""NewLink Genetics Corporation, through its wholly owned subsidiary, BioProtection Systems Corporation announced that they had secured a letter contract with the United States Defense Threat Reduction Agency (DTRA) for studies that will bring an Ebola vaccine licensed from the Public Health Agency of Canada closer to human clinical trials. The letter contract is for $1.0 million with additional funding subject to final negotiation and will fund Investigational New Drug (IND)-enabling pre-clinical toxicology studies and includes the manufacture of clinical materials.""
 * 5 August 2014 NewLink announced that it had secured a $1.0 million contract with Defense Threat Reduction Agency (DTRA) to fund development regarding the investigational new drug (IND),

- Marketwired 2014


 * 5 August 2014 In their announcement of the DTRA contract, NewLink CEO Charles Link noted that there was an,

""...an urgent need for a medical countermeasure against the deadly Ebola virus...This Ebola vaccine has been 100% effective in preventing lethal infection when given to non-human primates before they are infected with the virus. The vaccine also acts rapidly enough to have significant efficacy even when given to animals that have recently received a typically lethal dose of Ebola virus.""

In the same announcement NewLink President and Chief Medical Officer, Nicholas Vahanian noted that there was an, ""Advancing this vaccine into a human Phase I safety study is a major priority for NewLink and our partners, whose ongoing support will be critical for moving the project forward.""

- Vahanian CFO 2014


 * 5 August 2014 The World Health Organization's panel of experts approved the use of experimental vaccines with conditions because of the urgency of the ebola outbreak in Guinea, Liberia, Nigeria and Sierra Leone with 1,013 deaths by October 2014. WHO's Marie-Paule Kieny, warned that supplies were low for one of the experimental drugs known as ZMapp made by San Diego-based U.S. biotech company Mapp Biopharmaceutical and partly developed at Canada's National Microbiology Laboratory in Winnipeg.

vaccine developed by Canadians, is being donated to the WHO by the Canadian government "for use in the West African outbreak response." NewLink, a partner with Canada, is also working “around the clock” to start trials. NewLink president Nicholas Vahanian said in a telephone interview with Bloomberg journalists that they has reserved enough of the vials for human trials "and made a joint decision with the Canadian government to donate the rest."
 * 5 August 2014 Dr. Gregory Taylor, deputy head of the Public Health Agency of Canada announced on 5 August 2014 that the 800 to 1,000 vials of VSV-EBOV


 * 8 August 2014


 * 12 August 2014 Two American aid workers in Liberia during the ebola crisis were given the experimental unlicensed drug, ZMapp. "is made of three monoclonal antibodies, disease fighting proteins that target a specific part of an invading pathogen, in this case the Ebola Zaire virus. That is the specific strain of Ebola responsible for this outbreak...Two of the monoclonal antibodies are the product of years of research done at the Public Health Agency of Canada's National Microbiology Laboratory in Winnipeg, the agency confirmed in an email late Monday."


 * 13 August 2014 Health Minister Rona Ambrose announced the Phase 1 trial in which 20 vials of the VSV-EBOV vaccine was tested at the Walter Reed Army Institute of Research in Maryland on 40 healthy volunteers. The trial was designed to "determine if VSV-EBOV is safe for human use" and to determine the "right dosage for humans and to look out for any side effects."




 * 29 September 2014 Science reporter Kupferschmidt interviewed virologist Heinz Feldmann, who helped develop the vaccine while he was working at PHAC, who expressed his concern that doses of the vaccine "are lying around ... while people are dying in Africa." A consortium of scientists including, Stephan Becker, virologist at the University of Marburg, Germany are waiting for vials of the vaccine that are in Canada to test on healthy human subjects in Germany. Becker and other scientists told Kupferschmidt that negotiations with NewLink Genetics have needlessly delayed the start of the trial.


 * September 2014 Clinical trials "started in the United States on a Canadian-made Ebola vaccine, with results expected in December."


 * 8 October 2014 Canadian Ebola vaccine safety trials move ahead, NewLink Genetics says.


 * 8 October 2014 Thomas Eric Duncan from Liberia, was the first Ebola patient in the Texas Health Presbyterian Hospital Dallas. Duncan was visiting family in Texas after being in Liberia, one of the countries hit by the Ebola epidemic. He was seen by health officials at the Texas Health Presbyterian Hospital on 25 September 2014, but was discharged too soon. He had to be taken back by ambulance on 28 September 2014. The hospital apologized for their error and later compensated the family.


 * 9 October 2014 The U.S. National Institute of Allergy and Infectious Diseases (NIAID) was recruiting healthy human volunteers for a "Phase 1 Randomized, Double-Blind, Placebo Controlled, Dose-Escalation Study to Evaluate the Safety and Immunogenicity of Prime-Boost VSV Ebola Vaccine in Healthy Adults".


 * 10 October 2014 NewLink registered its the first clinical trial under the government identifier NCT02269423. and began to recruit participants in a study "to test how safe the vaccine is in humans and how well it makes the human immune system cause an immune, or defense response to Ebola virus. This vaccine BPSC-1001 will be studied at different doses." The sponsor was listed as NewLink Genetics Corporation and collaborators included the BioProtection Systems Corporation and the Department of Defense. The study's primary completion date is July 2015 and a completion date is January 2016.


 * 10 October 2014 Canadian Federal Health Minister Rona Ambrose announced that Canada would take targeted temperature screens at the border to try to prevent an Ebola importation to this country.


 * 13 October 2014 As the number of ebola cases was rising exponentially in the "three hardest-hit countries, Guinea, Liberia, and Sierra Leone," World Health Organisation director-general Margaret Chan warned that the "the world is ill-prepared to respond to any severe, sustained, and threatening public health emergency". WHO claims that the ebola outbreak "most severe acute health emergency in modern times."


 * 13 October 2014 At the Walter Reed Army Institute of Research in Silver Spring, Md., NewLink Genetics began clinical trials of rVSV-ZEBOV on healthy human subjects to evaluate the immune response, identify any side effects and determine the appropriate dosage.


 * 18 October 2014 In a news release the Canadian government announced that the Public Health Agency of Canada would begin shipping the first of three separate shipments for a total of 800 vials of the experimental vaccine to the "UN body in Geneva in its role as the international co-ordinating body for the Ebola outbreak in West Africa."


 * 20 October 2014 NewLink entered into a $1 billion deal with Genentech, a unit of Switzerland's Roche Holding AG to develop a cancer immunotherapy. NewLink's shares rose 62 percent in October after the announcement.


 * 20 October 2014On October 20, the Public Health Agency of Canada began air shipment of 800 doses of the VSV-EBOV vaccine to the WHO in Geneva.

""This vaccine is intended to be used in Phase I clinical trials, to start in late October or early November. This will determine if the vaccine is safe to use in humans and if so, determine the appropriate dosage. The WHO has recruited 250 volunteers ready to begin clinical trials in four locations: Switzerland, Germany, Gabon and Kenya. If results of this and following trials are positive, the deployment of this vaccine in environments such as West Africa would be facilitated by the expected requirement of only a single dose. Also, its effectiveness in nonhuman primates when administered even after exposure to the virus could help to protect health-care workers after a suspected exposure.""


 * 20 October 2014 By 20 October, Canada had pledged 65.4 million Canadian dollars to the fight against Ebola. As part of its contribution, Canada has deployed two mobile diagnostic laboratories in Sierra Leone, and shipped the first batch of an experimental Ebola vaccine to the WHO in Geneva.


 * 23 October 2014 NewLink registered its second clinical trial under the government identifier NCT02280408.


 * 23 October 2014 "The vaccine is in the hands of two companies," NewLink and Maryland-based Profectus Biosciences Inc."


 * 29 October 2014 On 29 October, the Wellcome Trust announced that multiple trials on a potential ebola vaccine, rVSV-ZEBOV developed by the Public Health Agency of Canada, were set to begin in healthy volunteers in Europe, Gabon, Kenya, and the USA.  This is the latest of several international commitments to fast-track early tests of candidate Ebola vaccines so they could be available for trial in West Africa by the end of 2014, and if successful deployed more widely in 2015.


 * 29 October 2014 In an interview with Science NewLink Charles Link Jr. explained that


 * c. 11-15 November 2014 Charles Link confirmed in an interview Wednesday that a representatives of NewLink Genetics, Merck and the Public Health Agency of Canada met in in Ottawa to discuss a new arrangement. Sylwia Krzyszton, a spokeswoman for Health Canada, said the government is "committed to support its international partners’ efforts to control the Ebola outbreak and hopes that the experimental vaccine will be able to help address this global crisis. We are working with NewLink Genetics to assure the best approach to achieve this objective."


 * 19 November 2014 "University of Ottawa professor Amir Attaran published a letter in British medical journal The Lancet calling for Canada to withdraw from its agreement with NewLink."


 * 20 November 2014 Thursday, In the House of Commons Health Minister Rona Ambrose said the government is working with international partners "to bring all of their influence to bear to support this Canadian vaccine, which we should all be proud of, to make sure that it gets to market safely and effectively." In an interview on 20 November 2014, Professor Amir Attaran said that a deal with Merck would be good news and that Canada needed to "find a partner that is capable of replacing NewLink and Merck is an outstanding partner with the ability and the facilities to do so.”

In response to concerns about perceived delays in testing and manufacturing on the part of his company NewLinks, Charles Link explained that NewLink succeeded in the almost impossible task of getting through regulatory requirements in record time. "The vaccine is now being tested on human subjects in five separate trials, including one in Halifax. The company has been clearing very challenging regulatory hurdles with unprecedented speed... To get the trials going in the space of about 10 days, a team of people working 16 to 18 hours a day, through the week, through the weekend,” managed to get FDA approval within four days."


 * November 2014 NewLink is "manufacturing vaccine at a high-tech plant in Germany. It hopes to have 50,000 high-concentration doses ready in December. Depending on the results of human trials, the vaccine could be diluted as much as 100 times, which could mean that five million doses would be ready early in 2015." According to Link, that would amount to a vaccination for "every single person in all three countries (where the outbreak is ongoing) with that drug supply." He added that, "NewLink is proud of the work it has done to try to stop Ebola, and won’t profit from it." He claimed that NewLink's intention was "to help the crisis... Commercial considerations to us are secondary, and a distant secondary thought."


 * 24 November 2014


 * 24 November 2014 Merck & Co. obtained the rights to rVSV-EBOV, an experimental Ebola vaccine. NewLink will be paid "$30 million upfront, plus an additional $20 million when new clinical trials to test the vaccine’s efficacy get under way, which is expected by the first quarter of 2015. Merck MRK, +0.15%  also will pay royalties to NewLink NLNK, +2.44%  on sales of the product if it is approved for sale, excluding Africa and certain low-income countries."  NewLink paid $205,000 for the license to VSV-EBOV vaccine and will get $30 million up front, with $20 million more when the vaccine enters efficacy testing, plus royalties if the vaccine is approved and cleared for marketing, the Canadian Press reported today. NewLink will not "receive royalties on doses sold to African countries and other low-income nations."

President of Merck Vaccines, Julie Gerberding, said,

"", "Merck is committed to applying our vaccine expertise to address important global health needs and, through our collaboration with NewLink, we hope to advance the public health response to this urgent international health priority.""

- Julie Gerberding 2014


 * January 2015 The U.S. National Institutes of Health is planning a larger, human study in early 2015 to test rVSV-EBOV.