ROCKVILLE, MD. - March 22, 2002 - The Sequella Global Tuberculosis Foundation (SGTBF) has announced landmark progress in developing field-testing the first new tuberculosis (TB) vaccines in more than 80 years. Through its Tuberculosis Vaccine Collaboration (TBVC) pprogram, a program funded with $25M from the Bill and Melinda Gates Foundation, the SGTBF has entered into reached agreement on three clinical partnerships for to the development of three different TB vaccines that will intervene at three different phases of the disease. The SGTBF's TBVaccine Collaboration program is composed of several interrelated initiatives that foster dialogue between researchers, field clinicians, global regulatory and governmental agencies, and the pharmaceutical industry. These The clinical development partnerships agreements demonstrate reflect the consensus reached among public health officials that TB can will only be contained and ultimately eradicated through the synergistic efforts of public and private institutions in partnership. public-private partnerships, such as the ones the SGTBF is fostering.

Until recently, the international pharmaceutical industry did not see a sufficient profit incentive to create a new, more effective TB vaccine - despite the fact thatAccording to the World Health Organization (WHO), 2-3 million people die annually from TB and that 70-90 million people will be infected with die from the disease in the next three decades. according to the World Health Organization (WHO). As a resultDespite these dismal statistics, the world has not seen a new TB vaccine since the 1920s, 19XX, when the original BCG vaccine (currently used to vaccinate 85% of newborns in the world) was createddiscovered. The SGTBF , funded generously by the Bill & Melinda Gates Foundation, which has donated $25 million, has teamed up with three corporate partners, University of California, CLA (UCLA, Los Angeles, CA, USA), Intercell, Inc.,AG (Vienna, Austria), and Sequella, Inc.(Rockville, MD, USA), to develop new TB vaccines that use different mechanisms of action and address different disease stages and different mechanisms of action.

First, the SGTBF has reached aThe clinical development agreement with UCLA is to develop an 'improved' BCG vaccine, a recombinant BCG that over-expresses a major TB protein that has, itself, demonstrated efficacy in animal models of TB: Antigen 85. the TB vaccine currently used on infants. The research underpinning the selection of this vaccine for preparation for clinical trials was, lead by Marcus Horwitz, M.D., at UCLA, and has demonstrated in animal studies that this new vaccine has provokes a stronger immune response in vaccinated animals than BCG, and is more protective. This discovery suggests that the recombinant BCG may supplant the current vaccine as a prophylactic vaccine for children if its safety and efficacy in humans is as good as in animals. The Korean TB Institute has produced the first batch of clinical grade vaccine, and preclinical studies in preparation for Phase I safety tests in humans will commence in the next several months. , suggesting that it is much more effective than the current vaccine. This discovery is a result of a greater understanding of proteomics. today, than existed over a century ago, when the BCG vaccine was developed. This potentially more effective vaccine is slated to enter human Phase I clinical trials in Junein mid 2002 and marks the first Phase I test of a new TB vaccine in more than 80 years.

The SGTBF is will also helping to develop another pre-infection vaccine, the TransVax TB Epitope vaccine, which resulted from collaboration between EpiVax, Inc, a bioinformatics company in RI, USA, and Intercell AG, a biotechnology company in Vienna, Austria. EpiVax used its proprietary bioinformatics programs to scan using bioinformaticsTB proteins known to protect animals for regions (epitopes) of the proteins that would stimulate human immune responses from a wide variety of genetic backgrounds. Intercell, Inc. is using its proprietary bioinformatics technology to scan and identify proteins associated with a TB immune reaction.synthesized these peptides and combined them with their proprietary adjuvant, TransVax. The indication for this vaccine is as a boost to the current BCG vaccine to stimulate recall immune responses in adolescent children vaccinated with BCG as newborns. This vaccine is being manufactured by Good Manufacturing Practice (GMP) in Intercell facilities in Europe, and is expected to begin preclinical toxicity studies in late summer 2002. This technique works in a wide variety of genetic backgrounds and should improve the immune reaction to the TB virus (?). The TransVax TB vaccine will is expected to begin enter human Phase I safety and immunogenicity studies in early 2003. _______.

In a similar privatepublic-public private partnership, the SGTBF is working with Sequella, Inc. (both co-founded by Dr. Carol A. Nacy) {you need to explain the common name in a casual way} to develop a post-exposure vaccine that may decrease reactivation disease and will may decrease shorten the amount of time (currently 6-24 months) patients must must take their TB drugs. This result, demonstrated in animal models of TB, could help decrease the incidence of drug-resistant TB in humans who find it difficult to comply with the current long drug regimen, after being diagnosed with the disease.1 This vaccine is also being manufactured according to GMP in Europe, by Cobra Pharmaceuticals in the UK, and will be tested for potency in several laboratories around the world before it begins its preclinical toxicity testing. SGTBF anticipates that this vaccine could begin Phase I safety and immunogenicity tests in humans in 2003. Currently, patients must take a cocktail of four drugs daily for two months, followed by 6-24 (K - took the 24 months from our fact sheet) months of treatment with two drugs taken twice weekly, which must be adhered to strictly to be effective. Patients with HIV infection can require much longer courses of treatment. (See HYPERLINK "http://www.sequella.com/pipeline/hspvaccine.asp" http://www.sequella.com/pipeline/hspvaccine.asp for a description of the vaccine).


Strictly adhering to this multi-drug regimen is a serious problem in many less developed nations and impoverished areas, where TB is rampant. Noncompliance, i.e. stopping treatment too early, missing medication or improper drug doses, can cause TB to relapse and more seriously, can cause multi-drug resistant TB evolution, which can have a mortality rate as high as 80%. The emergence of multi-drug resistant TB is increasing at an alarming rate of _______

Through its current three clinical development agreements, SGTBF has ensured that any effective TB vaccine developed with its assistance will be marketed in all countries in which there is a need. By deceasing the length of time patients must take current TB drugs, not only will more people be cured of TB and cured quicker, but theA new and effective TB vaccine that can prevent or facilitate treatment of infectious pulmonary TB could substantially reduce the economic hardship endured by less developeding nations as a result of epidemic TB will be lessened . Thuis SGTBF contributes through its vaccine clinical development agreements to fact is evidenced in the overall theme for World TB Day 24 March 2002, - "Stop TB, fight poverty" (not sure how necessary, but wanted to tie in world tb day somehow). This theme suggests that the UN believes that tackling TB is one way of achieving greater global prosperity. Although, the SF has no interest in owning the intellectual property of these vaccines, the SF has ensured in these agreements that promising TB vaccines will be carried through development, and will be marketed in all countries in which there is a need (K - is this how you wanted to say this?).

The need for new tools to combat this global infectious disease has never been so obvious as it is today: over 2 billion people infected with the causative agent of TB, more than two million deaths each year, and a rising incidence of drug resistant TB threatens public health in every corner of the world. The strict compliance necessary in the current multi-drug Tb treatment is particularly relevant given the WHO's policy, vocal advocacy and 9.3 billion funding of their DOTS program (Directly Observed Treatment, Short-course). While While Directly Observed Therapy Short Course (DOTS) with the existing anti-TB drugs, recommended by the WHO and the cornerstone of the Stop TB movement, the DOTS program will go a long way inwill curbihelp to reduceng TB in areas where it is rigorously practiced, - new, and more effective vaccines, diagnostics and drugs must be developed to truly achieve a significant level of control over the global TB epidemic. SGTBF mission is to assist the development of new tools for the control of TB through creative partnerships with academia, governments, and industry. The three new Clinical Development Agreements for new TB vaccines with UCLA, Intercell, and Sequella represent a first step forward in the ultimate goal of TB eradication. TB. It is this development of new vaccines that the SGTBF has made significant strides towards achieving through these agreements with UCLA, Intercell, Inc. and Sequella, Inc. About the Sequella Global Tuberculosis Foundation .

The rapid rise of multi-drug resistant tuberculosis is a public-health catastrophe of the first order," says Dr. Paul Farmer, an associate professor of social medicine at Harvard Medical School, in "The Global Impact of Drug Resistant Tuberculosis" a report by Harvard Medical School's Program on Infectious Disease and Social Change and the Open Society Institute.

The heart of the TB problem lies in sub-Saharan Africa, Southeast Asia, India, and China; roughly 90% of all new cases of TB occur in these areas. Because AIDS patients are particularly susceptible to developing active, infectious forms of TB, the spread of AIDS has greatly exacerbated the spread of TB. As a result, TB is a leading cause of death for those infected with HIV; it is estimated that tuberculosis causes 30% of all AIDS-related deaths, and 60% in some sub-Saharan African nations.

According to the WHO, TB is estimated to take an annual economic toll equivalent to US$ 12 billion dollars from the incomes of poor communities. On average three to four months of work time are lost as a result of TB, resulting in an average lost potential earnings of 20 to 30% of annual household income, with mortality, there is the further loss of about 15 years of income to the family because of the premature death of the TB sufferer.