Drug-Resistant Tuberculosis

ProteinLogic and Stellenbosch University receive $1.3 million grant to develop blood test to monitor response to TB antimicrobial chemotherapy ProteinLogic, Cambridge, UK and Stellenbosch University, South Africa collaboration study funded by Bill & Melinda Gates Foundation.ProteinLogic extends ImmiPrint® Technology to address TB antimicrobial chemotherapy response monitoring.ProteinLogic ImmiPrint® diagnostic pattern of soluble immune proteins in blood and other body fluids portfolio defined using machine learning.ImmiPrint® off-the-shelf diagnostics and disease progression monitoring tests address multiple disease areas including infectious diseases and oncology.ImmiPrint® technology applicable to resource-rich and emerging economy clinical settings. CAMBRIDGE, UK (2024-01-22) – ProteinLogic, a biomarker discovery and commercialization company and Stellenbosch University, today announced that they have received a $1.35 million grant from the Bill & Melinda Gates Foundation to accelerate the development of ImmiPrint® Technology to monitor treatment responses to TB antimicrobial chemotherapy. The collaborative project was conceived and developed with the assistance of PTNG Consulting, a specialised science consultancy. PTNG Consulting will oversee the project management of this undertaking. ProteinLogic has forged a partnership with Stellenbosch University, South Africa, renowned for their significant contributions to global TB research. The non-dilutive funding from the Gates Foundation will allow ProteinLogic and Stellenbosch University to determine whether the use of ImmiPrint® technology can be extended to the monitoring of clinical responses to TB antimicrobial therapy. Tuberculosis is one of the world’s deadliest diseases, killing about 3600 people per day in 2022. For people living with HIV, it is a major risk, accounting for one-third of deaths among this community. While global health efforts made steady progress against TB, the COVID-19 pandemic caused major disruptions to essential TB services, effectively reversing much of the progress made. Additionally, the rise of drug-resistant strains of the bacterium causing TB has led to a sense of urgency to develop new treatments and prevention methods. Current treatments are lengthy (6 months treatment regimen) and diagnostic methods are complicated and costly. New treatments that are safer, shorter, simpler, and more affordable are urgently needed. ProteinLogic’s ImmiPrint® Technology is a sensitive, specific, and minimally invasive precision medicine technology that uses high-throughput immunoassays to measure the levels of multiple immune system proteins in body fluids. They are comprised principally of soluble cluster of differentiation (CD) proteins as well as cytokines. These play a key role in immune responses and provide the basis for the identification of disease-specific patterns in blood and other body fluids. Patterns of these proteins can be used to define diagnostic proteomic fingerprints that are able to detect the presence of multiple different disease types sensitively and specifically. ProteinLogic’s ImmiPrint® Technology was developed by the Company’s scientific co-founders, the inventor of monoclonal antibodies and Nobel Prize winner Dr César Milstein and Dr Adrian Woolfson. ImmiPrint® technology has been extensively clinically validated as a rule-out test for active Tuberculosis (TB) in prospective clinical cohorts of patients from around the world and meets or exceeds the WHO-mandated active TB rule-out test criteria. The ability to monitor clinical responses to TB antimicrobial chemotherapy and the potential to predict TB antimicrobial chemotherapy responses at an early timepoint, will have a significant impact on the duration of clinical trials for new TB antimicrobial chemotherapies. Reducing the cost of research and development and enabling physicians to determine treatment outcomes in a timely manner will aid directly in the development of novel anti-TB chemotherapies. Peter Klimt, Chairman of ProteinLogic, commented: “ProteinLogic’s ImmiPrint® technology provides the basis of a universal protein based search engine for the rapid, efficient, and cost-effective discovery of diagnostic biomarker signatures that address multiple disease categories. The non-dilutive funding received from the Bill & Melinda Gates Foundation will allow the Company to continue to explore the use of ImmiPrint® technology in the TB therapeutic area. We are immensely grateful to the Bill & Melinda Gates Foundation and our investors for supporting ProteinLogic’s vision for the future of disease diagnostics, which includes a focus on the development of high-impact and affordable diagnostics and disease monitoring systems accessible to both industrialised nations and developing economies.” Professor Novel Chegou, Head of the Diagnostic Biomarker Research Laboratory, Stellenbosch University, South Africa stated: “Our colleagues and ourselves at Stellenbosch University have been fortunate to lead several clinical trials researching TB diagnostic biomarkers as part of the African-European Tuberculosis Consortium (AETBC), ScreenTB, TriageTB and other multicentred studies. Through this experience we have access to a large number of samples from a diverse range of clinical trials, collected in South Africa and other African sites. Tuberculosis to this day kills more people globally than HIV/AIDS and is the number one killer when it comes to deadly infectious diseases. Multidrug-resistant TB remains a public health crisis and we are in desperate need for new tools that may assist in the control of the disease. We are very grateful and excited to be using the funding from the Bill & Melinda Gates Foundation to work together with ProteinLogic to determine the suitability of their biomarker signature and our own biomarkers for TB treatment monitoring. Our laboratory, as it is situated in a high burden African country and works closely with other laboratories across Africa is uniquely positioned to answer this question.” About ProteinLogicProteinLogic is a biomarker discovery and exploitation company developing a novel diagnostic platform and diagnostic products that address key unmet medical needs in infection and inflammatory diseases. The Company has developed a proprietary biomarker technology (ImmiPrint®) with potential to diagnose and predict early onset of diseases, and to provide information as to how a disease is likely to develop and respond to particular drug treatments. The technology is based upon the profiling of a discrete subset of immune system proteins (‘sCD’) found in the blood and other body fluids. In addition to the TB and hepatitis B diagnostic tests there are several potential follow-on products in the Company’s pipeline.ProteinLogic is headquartered in Cambridge, UK. For further information please visit https://www.proteinlogic.com. About Stellenbosch UniversityStellenbosch University (SU) is a proudly African knowledge hub that serves our country and continent through excellent education, research, and innovation. Our vision is to be Africa’s leading research-intensive university, globally recognised as excellent, inclusive and innovative, where we advance knowledge in service of society. With our 32 000 students, 3 300 staff and world-class academic environment, we not only count among South Africa’s leading higher education institutions, but among the top universities in the world. Our ten faculties – AgriSciences, Arts and Social Sciences, Economic and Management Sciences, Education, Engineering, Law, Medicine and Health Sciences, Military Science, Science, and Theology, as well as the School for Climate Studies, the School for Data Science and Computational Thinking and the Stellenbosch Business School – are located across five campuses in the Western Cape province of South Africa. About PTNG ConsultingPTNG Consulting is a specialised science consultancy that supports biotech and pharma companies - as well as academia - in all their protein-based endeavours. In addition to the planning and management of multi-partner international projects, PTNG Consulting provides computational biology and protein engineering services. The company’s highly experienced scientists use cutting-edge computational tools in combination with decades of experimental knowledge to de-risk clients’ projects and improve their chances for clinical success. https://www.ptngconsulting.com Contacts: ProteinLogic Peter Klimt, non-executive Chairmaninfo@proteinlogic.com Stellenbosch UniversityWilma Stassen, News and Media Coordinatorwstassen@sun.ac.za PTNG ConsultingSimona John von Freyend, Managing Directorsimona@ptngconsulting.com

A research team has detected various substances that have a dual effect against tuberculosis: They make the bacteria causing the disease less pathogenic for human immune cells and boost the activity of conventional antibiotics. A research team has detected various substances that have a dual effect against tuberculosis: They make the bacteria causing the disease less pathogenic for human immune cells and boost the activity of conventional antibiotics. In cooperation with research partners in Germany and France, the infectious disease specialist Dr Jan Rybniker and his team at University Hospital Cologne and the University of Cologne's Faculty of Medicine have identified new, antibiotic molecules that target Mycobacterium tuberculosis and make it less pathogenic for humans. In addition, some of the discovered substances may allow for a renewed treatment of tuberculosis with available medications -- including strains of the bacterium that have already developed drug resistance. The research has been published in the article 'Discovery of dual-active ethionamide boosters inhibiting the Mycobacterium tuberculosis ESX-1 secretion system' in Cell Chemical Biology. Tuberculosis (TB) -- or 'consumption', as it used to be called -- mainly affects the lungs, but can also damage other organs. If diagnosed early and treated with antibiotics, it is curable. Although the disease is relatively rare in most western European countries, it still ranks among the infectious diseases that claim the most lives worldwide: According to the World Health Organization (WHO), only Covid-19 was deadlier than TB in 2022. The disease also caused almost twice as many deaths as HIV/AIDS. More than 10 million people continue to contract TB every year. This is mainly due to insufficient access to medical treatment in many countries. Limited targets Multidrug-resistant tuberculosis is emerging especially in eastern Europe and Asia. That is of particular concern to researchers because like all bacteria that infect humans, Mycobacterium tuberculosis possesses only a limited number of targets for conventional antibiotics. That makes it increasingly difficult to discover new antibiotic substances in research laboratories. Working together with colleagues from the Institute Pasteur in Lille, France, and the German Center for Infection Research (DZIF), the researchers at University Hospital Cologne have now identified an alternative treatment strategy for the bacterium. The team utilized host-cell-based high-throughput methods to test the ability of molecules to stem the multiplication of bacteria in human immune cells: From a total of 10,000 molecules, this procedure allowed them to isolate a handful whose properties they scrutinized more closely in the course of the study. Double attack Ultimately, the researchers identified virulence blockers that utilize target structures that are fundamentally distinct from those targeted by classical antibiotics. "These molecules probably lead to significantly less selective pressure on the bacterium, and thus to less resistance," said Jan Rybniker, who heads the Translational Research Unit for Infectious Diseases at the Center for Molecular Medicine Cologne (CMMC) and initiated the study. In deciphering the exact mechanism of action, the researchers also discovered that some of the newly identified chemical substances are dual-active molecules. Thus, they not only attack the pathogen's virulence factors, but also enhance the activity of monooxygenases -- enzymes required for the activation of the conventional antibiotic ethionamide. Ethionamide is a drug that has been used for many decades to treat TB. It is a so-called prodrug, a substance that needs to be enzymatically activated in the bacterium to kill it. Therefore, the discovered molecules act as prodrug boosters, providing another alternative approach to the development of conventional antibiotics. In cooperation with the research team led by Professor Alain Baulard at Lille, the precise molecular mechanism of this booster effect was deciphered. Thus, in combination with these new active substances, drugs that are already in use against tuberculosis might continue to be employed effectively in the future. The discovery offers several attractive starting points for the development of novel and urgently needed agents against tuberculosis. "Moreover, our work is an interesting example of the diversity of pharmacologically active substances. The activity spectrum of these molecules can be modified by the smallest chemical modifications," Rybniker added. However, according to the scientists it is still a long way to the application of the findings in humans, requiring numerous adjustments of the substances in the laboratory. This research was made possible with the support of the German Center for Infection Research (DZIF) and other funding institutions.

TB kills 1.3 million people a year and sickens more than 10 million people annually. A new TB vaccine is needed to reach the global End TB goals. MTBVAC is a highly promising vaccine candidate that has the potential to be used as an alternative to BCG vaccination in infants and for prevention of TB disease in adolescents and adults. Grant from the Bill & Melinda Gates Foundation to IAVI will support efficacy trial. NEW YORK, NY and PORRIÑO, SPAIN / ACCESSWIRE / December 18, 2023 / IAVI, a global nonprofit scientific research organization, and Spanish biopharmaceutical company Biofabri, a subsidiary of Zendal, today announced that the Bill & Melinda Gates Foundation has awarded IAVI US$55 million to conduct a Phase IIb trial assessing the safety and efficacy of the tuberculosis (TB) vaccine candidate MTBVAC to prevent active TB lung disease in adolescents and adults. This funding has been made possible in part through a grant provided by Open Philanthropy, a grant-making organization that aims to use its resources to help others as much as it can. This trial is also supported by additional funding provided by the German Federal Ministry of Education and Research (BMBF) through the KfW Development Bank, which provides funding to IAVI and partners in support of developing MTBVAC. It is anticipated that the trial will begin enrolling participants in mid-2024. "We're thrilled to have secured the investment needed to advance this promising vaccine candidate into an efficacy study," said Mark Feinberg, M.D., Ph.D., president and CEO of IAVI. "The world urgently needs a new, effective vaccine that can prevent TB disease in adults and adolescents, and we are hopeful that MTBVAC will be part of the solution to finally end the TB epidemic. We are grateful to the Bill & Melinda Gates Foundation for their support of our late-stage development work on MTBVAC and to Open Philanthropy, whose visionary investment could accelerate the availability of MTBVAC by several years, if it is shown to be safe and efficacious in the upcoming efficacy trial." "This is a historic opportunity to learn whether this promising TB vaccine candidate, MTBVAC, can prevent active TB disease in adolescents and adults, the population among whom most TB disease and transmission occurs," said Lewis Schrager, M.D., senior leader of TB vaccine development efforts at IAVI. "If MTBVAC were shown to safely prevent TB disease in this population, this vaccine could prove to be critically important in global strategies to suppress the TB pandemic given its ease of use, low cost, and anticipated widespread availability." Previous Phase Ib/IIa dose-ranging studies of MTBVAC in adults and neonates demonstrated favorable immunogenicity and safety pro In addition to this Phase IIb trial, Biofabri is conducting a Phase III trial of MTBVAC (NCT04975178) in neonates in South Africa, Madagascar, and Senegal, with support from the European & Developing Countries Clinical Trials Partnership (EDCTP). Biofabri and the HIV Vaccine Trials Network are planning a Phase IIa trial (NCT0547890) evaluating the safety and immunogenicity of MTBVAC in people living with HIV whose viral loads are well controlled on antiretroviral therapy, scheduled to begin in South Africa in mid-January 2024. Only a handful of TB vaccine candidate efficacy trials have ever been conducted. This study of MTBVAC to prevent TB disease will be conducted in approximately 4,300 people who have latent TB infection. Participants will be between the ages of 14 and 45, living in South Africa and select other sub-Saharan African countries in areas with high TB burden. Participants at 15-20 trial sites will receive either a single dose of MTBVAC or placebo and be observed for two to three years. Kundai Chinyenze, M.D., MPH, IAVI Africa director, said, "We are gratified to be able to begin working on this efficacy trial in a region of the world where TB is a leading contributor to morbidity and mortality, especially for people living with HIV. IAVI's long history in conducting clinical trials in Africa and our strong network of regional and global partners provide a solid foundation for the successful conduct of this important trial." MTBVAC, designed by the Spanish researcher Carlos Martin, Ph.D., from the University of Zaragoza, and Brigitte Gicquel, Ph.D., of Institut Pasteur, was in-licensed by Biofabri (Zendal Group). The only available TB vaccine, bacille Calmette-Guérin (BCG), is derived from Mycobacterium bovis, a bacterium that causes a TB-like disease in cows. BCG is largely ineffective in preventing TB in adolescents and adults. MTBVAC is the only live, attenuated vaccine derived from Mycobacterium tuberculosis, the bacterium that causes TB disease in humans, in the pipeline. Given its derivation from the human, rather than the bovine, TB-causing organism, MTBVAC has the potential to generate a broad protective immune response against TB. The vaccine is administered as a single dose via intradermal delivery and does not require the use of an adjuvant. Esteban Rodriguez, CEO, Biofabri, said, "We are delighted by the fantastic opportunity - through the tremendous efforts of IAVI, and the valuable support provided by the Bill & Melinda Gates Foundation, Open Philanthropy, and the German Federal Ministry of Education and Research (BMBF) through the KfW Development Bank - to now evaluate the efficacy of MTBVAC in adolescents and adults. The outcome of the efficacy studies in neonates as well as those in adolescents and adults will provide us with a pathway to license MTBVAC for all age groups." Should MTBVAC be shown to be safe and efficacious, Biofabri, in partnership with IAVI and other collaborators, will ensure that MTBVAC is manufactured and supplied in sufficient quantities globally and is accessible at affordable prices in low- and middle-income countries. TB Since the COVID-19 emergency has ended, TB is on track once again to be the deadliest infectious disease in the world. TB killed an estimated 1.3 million people in 2022, about 16% of whom were children. Around 10.6 million people fell ill with TB in 2022, and the disease is one of the 10 leading causes of death worldwide. Drug-resistant/multi-drug resistant TB (DR/MDR TB) is becoming an increasing threat, with about 410,000 cases in 2022. Treating DR/MDR TB is lengthy and expensive, often causes debilitating side effects, and is not always successful. A vaccine that prevents TB disease would play an important role in reducing the incidence of DR/MDR TB, by reducing the transmission of DR/MDR TB and reducing the use of TB drugs and the emergence of drug-resistant strains. MTBVAC MTBVAC is being developed for two purposes: as a more effective and potentially longer-lasting vaccine than BCG for newborns, and for the prevention of TB disease in adults and adolescents, for whom there is currently no effective vaccine. Two Phase II trials have been completed, one supported by EDCTP and sponsored by Biofabri in infants in South Africa, and one sponsored by IAVI and supported by the U.S. National Institutes of Health and the U.S. Department of Defense through its Congressionally Directed Medical Research Program. Results are expected to be published in early 2024. IAVI. IAVI is a nonprofit scientific research organization with headquarters in the U.S. and locations in Europe, Africa, and India that develops vaccines and antibodies for HIV, tuberculosis, emerging infectious diseases (including COVID-19), and neglected diseases, with the goal of providing global access. It has contributed to efforts to evaluate most of the leading TB vaccine candidates now in clinical development and has a highly experienced TB vaccine clinical research team in South Africa. Biofabri. Biofabri is a biopharmaceutical company created in 2008 with the aim of researching, developing, and manufacturing vaccines for humans. Biofabri has a solid technical and scientific capacity in vaccines and immunotherapy. Biofabri belongs to the Zendal group, a Spanish pharmaceutical business group made up of six companies specialised in the development, manufacture and marketing of vaccines and other biotechnological products for human and animal health. UNIZAR. The University of Zaragoza in Spain is the main center for technological innovation in the Ebro Valley. It participates in different exchange programs, collaborating with universities and research centers in Europe, Latin America, and the United States. Microbiologists from the university associated with Centro de Investigación Biomédica en Red Enfermadades Respiratorias (CIBERES) led the research and subsequent discovery of the experimental vaccine MTBVAC. Within the TuBerculosis Vaccine Initiative (TBVI) consortium, the MTBVAC discovery phase has included rigorous clinical characterization by independent laboratories and research groups. IAVI Media Contact Karie Youngdahl +1 212 847 1051 kyoungdahl@iavi.org Zendal Media Contact Beatriz Díaz Lorenzo +34 619 085 074 b.diaz@zendal.com SOURCE: IAVI View the original press release on accesswire.com