SEATTLE -- The Bill & Melinda Gates Foundation announced today an $82.9 million grant to the Aeras Global TB Vaccine Foundation to support development of new vaccines to prevent tuberculosis, a disease that kills nearly two million people every year. The grant, the largest ever for TB vaccine development, will allow Aeras to fund human trials of promising TB vaccines and early research on the next generation of vaccines.

Dr. Richard Klausner, former executive director of the Gates Foundation's Global Health program, announced the grant at the opening session of the American Association for the Advancement of Science annual meeting in Seattle. The grant will more than double the amount spent annually on TB vaccine research worldwide.

"It's unacceptable that TB continues to kill someone every 15 seconds when we have the ability to discover new tools to stop it," Klausner said. "Through accelerated research and development, a new vaccine could permanently change the trajectory of the epidemic and save millions of lives every year."

Two billion people—one out of every three people on earth—are infected with the TB pathogen. TB is the leading killer of people infected with HIV. Fueled by the HIV/AIDS epidemic, TB is resurgent in the developing world, and the World Health Organization projects that 36 million people could die of the disease over the next 20 years. 

New TB Vaccine Urgently Needed

A new vaccine is the key to controlling TB, an airborne, contagious bacterial disease that begins with a cough but can rapidly spread to the lungs, bones and brain.  While TB can be treated, the basic treatment regimen takes at least six months to complete and requires as many as four different drugs, which are often unavailable in developing countries.  Modeling studies show that a modestly effective vaccine (50%-70% effective) used in combination with drug therapy could save tens of millions of lives, and a highly effective vaccine could eventually control the disease.

The existing TB vaccine, BCG (Bacille Calmette-Guerin), has been in use since the early 1900s and is administered to millions of newborns around the world. BCG appears to reduce the risk of serious childhood forms of TB. However, the high incidence of TB in developing countries where infant BCG immunization is widely practiced indicates that BCG is not highly efficacious over the many years that people are at risk for the disease.

Dr. Jerald Sadoff, President and CEO of the Aeras Global TB Vaccine Foundation and the former Clinical Director for Vaccine Development at Merck, was optimistic about the prospects for a new TB vaccine.

"Our goal—and we believe it is achievable—is to license and deliver a more effective TB vaccine within 10 years," Sadoff said.  "About 90% of people infected with the TB pathogen never get sick, which indicates that there is some natural immunity against the disease. This grant allows us to develop leading vaccine candidates today and explore new research paths that could lead to even better vaccines in the future."

Grant to Advance Research on Promising TB Vaccines

Aeras will use the grant announced today to support research in three major areas:

• - Vaccine trials:  Aeras will sponsor Phase II trials of a combination of two promising TB vaccines. The first vaccine, known as rBCG30, is an enhanced version of the BCG vaccine that has been genetically engineered to stimulate a stronger immune response.  Aeras began a Phase I clinical trial of rBCG30 in the U.S. in January 2004. The second, a fusion protein, is a new vaccine that combines two proteins from the TB pathogen that are primary targets of the immune system.  rBCG30 will be used to "prime" the immune system to control TB, and  the fusion protein will provide an additional "boost" to the body’s response to infection.  Previous research has demonstrated that this "prime-boost" approach often results in enhanced protection in animal models.

• - Improved animal models:  Aeras will also study the ability of animal models to predict vaccine effectiveness in humans. Finding such predictive models will greatly accelerate future TB vaccine research.

• - Next-generation vaccines:  Aeras will also support early research on the next generation of TB vaccines. Researchers will construct and evaluate several leading candidates, and prepare the most promising ones for human trials.

Aeras, which is based in Bethesda, Maryland, will implement this research in partnership with scientists, academic institutions, governments, and companies in the U.S., Europe, South Africa, and other developing countries.  Aeras has already established a clinical research site in Cape Town, South Africa, where more than 9,000 volunteers are enrolled in a clinical trial, and other sites are being considered in Peru and India.  Aeras is also partnering with The Biovac Institute in Cape Town to manufacture vaccines for future Phase I and II clinical trials.  Following an "industrial model" of vaccine development, Aeras will prioritize the vaccine pipeline into primary and back-up candidates, and adhere to strict timelines and predetermined "go/no go" criteria.

Sadoff emphasized that more resources are needed to support TB vaccine research efforts.  "We hope that the Gates Foundation grant will leverage much-needed support from other donors, both in the U.S. and worldwide," he said.

Klausner stressed that as TB vaccine research moves forward, it is also important to increase research on TB drugs and diagnostics, and expand global access to existing TB prevention and treatment efforts. The World Health Organization has estimated that total resources for TB research and control from 2001-2005 will fall about $3.8 billion short of the need. To date, the Gates Foundation has provided a total of $217 million in grants to TB research and control programs.

###

The Aeras Global TB Vaccine Foundation works through public-private partnerships to develop new tuberculosis vaccines and ensure that they are distributed to all who need them. Aeras is led by Dr. Jerald Sadoff, who has licensed five vaccines commercially and developed numerous other vaccine candidates while at Merck and the Walter Reed Army Institute of Research.

NEW YORK – OCTOBER 1, 2018 – The International AIDS Vaccine Initiative (IAVI) and Aeras, a nonprofit organization dedicated to developing tuberculosis (TB) vaccines, today announced the transfer to IAVI of Aeras’ TB vaccine clinical research programs and assets, consisting of certain clinical staff, clinical programs, biorepository, funding commitments, and other assets.

The transaction, effective today, will enable the continuity of Aeras’ core TB vaccine clinical programs and will expand IAVI’s clinical development capabilities and network, incorporating an experienced clinical team and South African clinical partner network with a strong track record in later-stage clinical trials and work with adolescent and adult populations.

This agreement comes as the New England Journal of Medicine (NEJM) published the results of a clinical study conducted by Aeras in collaboration with GSK, evaluating GSK’s investigational TB vaccine candidate, M72/AS01E. The Phase IIb efficacy study showed that the vaccine protected against active pulmonary TB disease, with an overall vaccine efficacy of 54 percent. This finding, if confirmed in follow-up studies, would represent a breakthrough in the decades-long quest to develop an effective TB vaccine. The study involved 3,573 HIV-negative adults in three countries in Africa (Kenya, South Africa, and Zambia).

These results follow another Aeras Phase II study recently published in the NEJM showing the potential to prevent sustained TB infection among high-risk adolescents. The study involved the currently available bacille Calmette-Guerin (BCG) vaccine and an experimental subunit vaccine candidate, H4:IC31®, which uses the IC31® adjuvant available under license from Valneva. The study was conducted through a partnership between Aeras and Sanofi.

Mark Feinberg, M.D., Ph.D., president and CEO, IAVI, said, “Aeras’ contributions to these two important studies have built excitement in the field, demonstrating that an effective TB vaccine may be achievable. The transfer of Aeras research capabilities to IAVI will enable this important work to continue.” Dr. Feinberg continued, “There is extensive overlap among individuals and communities hit hardest by TB and HIV/AIDS; TB is the single biggest killer of people living with HIV, and, in some parts of the world, the HIV pandemic has fueled the spread of TB. The expertise of the Aeras clinical operations team and South African network will enable IAVI to strengthen its clinical development capacity and enhance its ability to address HIV, TB, and other important global health challenges. We are looking forward to working with public and private sector partners to develop new technologies and programs to help control the TB pandemic.”

Jacqueline Shea, Ph.D., CEO, Aeras, said, “Aeras is proud of the contribution it has made to the field of TB vaccine research and development and the role that it has played in two recent groundbreaking clinical efficacy trials. For more than two decades, Aeras has formed partnerships with commercial biopharmaceutical companies, other nonprofits, researchers, funders, and global health experts in its mission to advance TB vaccines for the world. We believe that the time is right to join the expertise within Aeras and IAVI to build on the recent findings and accelerate progress toward new, more effective TB vaccines. We believe such progress will also require additional partnerships among like-minded and committed organizations.”

Eric Goosby, M.D., U.N. Secretary-General’s Special Envoy on Tuberculosis and board chair, IAVI, said, “Following the first-ever United Nations high-level meeting on TB, it is important to emphasize that a vaccine is necessary to achieve control over TB on a global level. Without vaccines to both prevent and treat the disease, the pandemic will continue. These recent studies bring us one step closer to a solution.”.

###

• About TB
  • • Tuberculosis (TB) is the world’s deadliest infectious disease and is increasingly characterized by antimicrobial resistance. In 2017, there were 1.6 million deaths and 10 million new cases of TB disease. The World Health Organization (WHO) estimates that nearly one-quarter of the world’s population has latent TB infection, meaning that they are infected with TB bacteria that could develop into active TB disease. Teens and adults are most at risk for developing and spreading TB.
    • An estimated 19 percent of TB-related deaths, and 9 percent of new TB cases, were among people living with HIV. The risk of developing TB disease is estimated to be 20 times higher among the 37 million people living with HIV than it is for those without, and TB accounts for about one in three AIDS-related deaths.
• About IAVI
  • • The International AIDS Vaccine Initiative (IAVI) is a nonprofit scientific organization whose mission is to develop vaccines and other biomedical innovations that prevent HIV infection. Since its founding in 1996, IAVI has provided scientific, research and development, and policy leadership to address the needs of communities and key populations at risk for HIV infection around the world. IAVI works with more than 100 academic, industry, government, civil society, clinical, and community partners in more than 25 countries. IAVI is committed to supporting the broad field of HIV vaccine research and to fostering collaborations that accelerate the development and availability of new prevention tools. In pursuit of our goals, we work to catalyze and support novel partnership models that engage partners from both the public and private sectors across the product development continuum.
    • IAVI’s global reach, including its clinical research network in five countries in sub-Saharan Africa and in India, has allowed IAVI to make fundamental contributions to understanding of the epidemiology, transmission, natural history, virology, and immunology of HIV infection. This work played a key role in facilitating the structure-based design of promising HIV vaccine candidates as well as the discovery of “broadly neutralizing antibodies” that are now being advanced as promising approaches for HIV prevention. IAVI’s integrated capabilities in vaccine discovery, development, and clinical research take advantage of biopharmaceutical industry expertise to accelerate the development and testing of novel HIV vaccine candidates.
    • In addition to its core HIV vaccine effort, IAVI is working to amplify its global health impact by working with partners to address other urgent unmet public health needs – such as vaccines for other infectious diseases – where our existing technologies, assets, and experience can add unique value.
• About Aeras
  • Aeras is a nonprofit organization advancing the development of new TB vaccines for the world in partnership with other biotech, pharmaceutical, and academic organizations. Aeras is primarily funded by the Bill & Melinda Gates Foundation, the U.K. Department for International Development (DFID), and other parties committed to ending the tuberculosis epidemic. Aeras also receives support from the U.S. government and through partnerships and collaborations with universities and biopharmaceutical companies around the world. Aeras is headquartered in Rockville, Maryland (USA), with a clinical development and operations office in Cape Town, South Africa. For more information, please visit www.aeras.org.

Shares of [Inovio Pharmaceuticals, Incorporated] are down more than 22% in premarket trading after the company announced a leadership change at the helm and the discontinuation of a Phase III COVID-19 vaccine study.

Pennsylvania-based Inovio announced Tuesday that Chief Executive Officer [Dr. Jong Joseph Kim (born 1969)] has resigned from his position, as well as from his role as president and a member of the company board of directors. [Jacqueline Elizabeth Shea, Ph.D. (born 1965)], who has served as the chief operating officer of [Inovio Pharmaceuticals, Incorporated] since 2019, will take over the company's reins in his stead. 

Before coming to Inovio, Shea served as COO and later as CEO of tuberculosis-focused  [AERAS Global TB Vaccine Foundation], a not-for-profit drug development organization. She also previously held leadership roles at Emergent BioSolutions.

Not only has the company made a change in the C-suite, but in its quarterly financial report on Tuesday, Inovio announced plans to discontinue its Phase III Innovate trial in order to prioritize its heterologous booster strategy for COVID-19. The late-stage study was assessing INO-4800, the company's DNA vaccine candidate for COVID-19. The vaccine candidate is an intradermally-injected DNA plasmid vaccine designed to control the virological spread of COVID-19. 

In its announcement, changes in infection rates across the globe indicate the company will need to increase the trial size and cost of the INNOVATE study. In contrast, the heterologous booster market offers greater opportunities due to the endemic phase of COVID-19. So, instead of assessing INO-4800 as a two-dose vaccine, Inovio and its developmental partner Advaccine will examine the drug candidate as a heterologous booster to an inactivated COVID-19 vaccine. 

Earlier clinical data from a study conducted by Advaccine showed positive T cell immune response. In that study, interim immunogenicity data showed that using INO-4800 as a booster after six months resulted in a 6.3-fold increase in T cell immune response. 

In a separate Advaccine study examining a third dose of a COVID-19 vaccine, the cellular response increased by 1.7-fold. The highest booster effect of INO-4800 was observed with a 2 mg dose of INO-4800 delivered 6 months after a primary series with an inactivated vaccine.

With this understanding, Inovio said INO-4800 has the potential to play an important role in reducing the incidence of severe COVID-19 cases, particularly of viral mutations. The company is discussing this option with regulatory agencies across the globe.

New CEO Shea said the company believes in the potential of its DNA medicines and vaccines. In order to achieve the goals of being able to combat infectious diseases and other indications, Inovio had to "strategically prioritize" its resources to "capitalize on its demonstrated ability to generate functional T-cell and antibody immune responses."

As Inovio moves forward, the company intends to expand its partnership with Advaccine beyond INO-4800 to include heterologous boosters and vaccine candidates covering future COVID-19 variants. The expanded partnership will allow both companies to share data, leverage Advaccine's multiple manufacturing sites in China, and access opportunities globally.

Additionally, Inovio announced a change in plans regarding its therapy for HPV-associated cervical high-grade squamous intraepithelial lesions, VGX-3100. Following input from the U.S. Food and Drug Administration, Inovio will shift its focus to a biomarker study after the regulatory agency said data from the Phase III REVEAL2 study will not be sufficient for approval. 

The FDA recommended that data from Reveal2 could be used as an exploratory study to evaluate a biomarker-selected population. Then, Inovio can conduct one or two additional trials in the biomarker-positive population in order to provide enough evidence to support the approval of a marketing application.

In response, Inovio will amend the Reveal2 trial to revise the primary analysis population from the all-comers population to the biomarker-positive population. The change in regulatory guidance, though means that Inovio no longer anticipates filing a Biologics License Application for VGX-3100 in 2023.