Abstract
GSK said its existing vaccine technology will be complemented by Okairos's platform, which delivers genetic material using deactivated chimpanzee-derived adenoviruses that target the immune system's CD8 T cells and aims to protect against and treat infectious diseases and cancer. The potential of Okairos's technology has been tested in clinical studies, in which more than 700 subjects have been vaccinated, including Phase II programs for hepatitis C and malaria.
As part of the deal, GSK will acquire full ownership of Okairos, including what it called a “small number” of the company's early-stage assets for hep C, malaria, and diseases that include respiratory syncytial virus, tuberculosis, ebola, and HIV. In addition to developing its platforms, Okairos was pursuing therapeutic vaccines to treat cancer.
“This is a fantastic opportunity for patients and our research organization as it is expected to contribute to the development efforts for an exciting new generation of vaccines, building on the excellent science and expertise of both companies,” Christophe Weber, GSK vaccines president, said in a statement.
The companies also said they are “committed to an innovative collaboration and will work together over the next few months to develop ways of working that will maintain the autonomy, spirit, and agility of this unique small biotech firm which will be strengthened by the support and advantages that GSK can provide.”
Okairos was formed in 2007 as a spinout of Merck & Co. and supported by investments from BioMedInvest, the Boehringer Ingelheim Venture Fund, LSP, Novartis Venture Funds, and Versant Ventures.
If the dissolution plan is approved by shareholders, GenVec said, it plans to file a certificate of dissolution with the Delaware Secretary of State, complete a liquidation of company assets already underway, satisfy remaining obligations, and distribute any available liquidation proceeds to stockholders.
The board approved a dissolution plan on May 24 “after extensive and careful consideration of the Company's strategic alternatives,” concluding that the plan “is in the best interests of the Company and its stockholders,” according to an 8-K filing with the U.S. Securities and Exchange Commission.
“The Company may abandon the Plan of Dissolution if the Board of Directors determines that, in light of new proposals presented or changes in circumstances, liquidation and dissolution pursuant to the Plan of Dissolution are no longer advisable and in the best interests of the Company and its stockholders,” GenVec added.
Despite winning a conditional approval last June for its first approved product—a vaccine intended to treat foot-and-mouth disease in cattle—from the U.S. Department of Agriculture's Animal and Plant Health Inspection Service, GenVec has largely struggled to develop successful gene therapy treatments. Two months later, in September, GenVec cut 30% of its workforce, or 23 positions, to save cash, saying the reduction would allow it to fund operations through the third quarter of 2014, even without any milestone payments it may receive through an ongoing collaboration with Novartis. At the time, GenVec reported about $20.9 million in cash, cash equivalents, and short-term investments at the end of the second quarter 2012.
That number fell 6 months later to $15.3 million in cash, cash equivalents, and short-term investments as of the end of the fourth quarter, during which it lost $3.2 million, down from a $2.5 million net loss in Q4 2011, on revenues of just $1.5 million, down more than half from $3.4 million a year earlier.
GenVec ended 2012 with a 47% revenue loss down to $9.4 million, a slide the company blamed on year-over-year declines of $5.6 million in its hearing loss and balance disorders program, $1.5 million in its HIV program, and $1.2 million in its foot-and-mouth disease program.
The company in 2010 halted a Phase III trial on its lead drug for patients with locally advanced pancreatic cancer, TNFerade, after concluding that the trial would not meet the goal of demonstrating persuasive evidence of clinical effectiveness. GenVec then announced it would explore strategic alternatives that included a possible sale of the company.
Four years earlier in 2006, GenVec ended development of a peripheral vascular disease treatment in 2006, following its failure in a midstage trial.
“The broad spectrum of efficacy in two relevant animal models of influenza suggests that intranasal delivery of AAV9.FI6 should be seriously considered for further development as a rapid and effective prophylaxis for influenza,” the investigators concluded in findings published online May 31 in Science Translational Medicine (Limberis et al., 2013).
Investigators in the Gene Therapy Program at the University of Pennsylvania's Perelman School of Medicine joined with colleagues at the Public Health Agency of Canada; the University of Manitoba; and the University of Pittsburgh in a study designed to assess in animals a new gene therapy approach to thwarting potential flu pandemics.
UPenn's gene therapy program is directed by James M. Wilson, M.D., Ph.D., editor-in-chief of Human Gene Therapy. Dr. Wilson was a co-corresponding author on the study with Maria P. Limberis, Ph.D., director of the animal models core with the Penn gene therapy program.
“The experiments described in our paper provide critical proof-of-concept in animals about a technology platform that can be deployed in the setting of virtually any pandemic or biological attack for which a neutralizing antibody exists or can be easily isolated,” says Wilson. “Further development of this approach for pandemic flu has taken on more urgency in light of the spreading infection in China of the lethal bird strain of H7N9 virus in humans.”
Investigators used a novel approach to gene therapy that did not require elicitation of an immune response, as with conventional approaches to fighting flu that are useful only on the strain of flu for which they are designed. The research team cloned into a vector a gene that encodes an antibody effective against several flu strains and engineered cells lining the nasal passages of the mice and ferrets in order to express the antibody, since the virus usually enters the body and replicates in the nasal and oral mucosa.
One key challenge was to design vectors capable of delivering antibody genes to the nonlymphoid respiratory cells of the nasal and lung passages as well as express functional antibody protein, since antibodies are normally expressed from B lymphocytes. The vector that was used, primate virus-based AAV9, was discovered in Dr. Wilson's laboratory.
Investigators said two near-term applications of the gene therapy platform for flu infections should be considered: seasonal flu infections in high-risk individuals; and emerging flu pandemics, most of which can be controlled with the FI6-expressing AAV9 vector that has shown effectiveness against a broad range of group 1 and 2 influenza A viruses: “The product can be stockpiled and rapidly deployed, with efficacy realized only days after dosing.”
A pair of studies released in recent weeks examines the severe effects of infection with the H7N9 avian flu virus in humans and ferrets. In one study, a team of 45 Chinese investigators examined clinical, epidemiologic, and virologic data from three Chinese patients who died following exposure to H7N9 flu. While two of the patients had a history of recent exposure to poultry, all three developed severe and fatal respiratory disease—namely coughing, dyspnea, and fever, as well as complications that included acute respiratory distress syndrome and multiorgan failure.
“All three cases of H7N9 infection reported here were virulent, with the patients' conditions deteriorating rapidly with the development of severe pneumonia and ARDS, and ultimately resulted in death,” the Chinese investigators reported in findings published in The New England Journal of Medicine (Gao et al., 2013).
All the patients had preexisting medical conditions, and two had a history of direct contact with poultry. The research team added: “Two patients presented with rhabdomyolysis, which has rarely been reported in patients infected with H1N1 or H5N1 influenza viruses. Encephalopathy, which is normally more common in pediatric patients with influenza, was observed in two patients.”
Investigators from the Chinese Center for Disease Control and Prevention and its National Institute for Viral Disease Control and Prevention joined in the study with colleagues from the Beijing Institute of Respiratory Diseases at Beijing Chao-Yang Hospital; Peking University People's Hospital; Shanghai Public Health Clinical Center at Shanghai Medical College of Fudan University; Shanghai Municipal Center for Disease Control and Prevention; the Fifth People's Hospital of Shanghai at Fudan University; Institute Pasteur of Shanghai, Chinese Academy of Sciences; the Anhui Provincial Center for Disease Control and Prevention; Zhongda Hospital, Southeast University; Jiangsu Provincial Center for Disease Prevention and Control; and Chuzhou Center for Disease Control and Prevention. Yuelong Shu, Ph.D., of the National Institute for Viral Disease Control and Prevention served as co-corresponding author on the study with Zhenghong Yuan, Ph.D., of the Shanghai Medical College of Fudan University.
In the other study, researchers from China, the United States, and Canada used a ferret model to evaluate the infectivity and transmissibility of A/Shanghai/2/2013 (SH2), a human H7N9 virus isolate from a patient who died of the fatal index case. They concluded that human-to-human transmission of the H7N9 virus may be possible under appropriate conditions, according to findings the team published on May 31 in Science (Zhu et al., 2013).
“If this virus acquires the ability to efficiently transmit from human-to-human, extensive spread of this virus may be inevitable, as quarantine measures will lag behind its spread,” the researchers cautioned.
The researchers found that the H7N9 virus replicated in the upper and lower respiratory tracts of the ferrets and was shed at high titers for 6 to 7 days, with the ferrets showing relatively mild clinical signs. SH2 was transmitted more efficiently via direct contact than by airborne exposure.
“Ferrets can be infected by SH2 and shed virus that could transmit to direct contact and airborne exposed animals, resulting in productive infections. Shedding of this virus occurred before the development of the majority of clinical signs,” the researchers wrote.
Because the domesticated pig is a major mammalian host of influenza A viruses, and may have played a key role in facilitating the emergence of human pandemic influenza viruses, the researchers evaluated the infectivity and transmissibility of SH2 in pigs. They found that while pigs could be productively infected by SH2 and shed virus for 6 days, they were unable to transmit the virus to other animals.
Investigators from the Joint Influenza Research Centre and Joint Vaccine Research Centre at China's Shantou University Medical College (SUMC) joined in the study with colleagues at State Key Laboratories of Emerging Infectious Diseases based at Shenzhen Third People's Hospital and the University of Hong Kong (HKU) Centre of Influenza Research; the National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention; Canada's University Health Network; University of Toronto; and St. Jude Children's Research Hospital in the United States. Dr. Shu and Yi Guan, Ph.D., of the Joint Influenza Research Centre (SUMC/HKU) served as co-corresponding authors.