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01.12.2020

Funding for the development of an inhibitor against hospital germs

HZI joint project receives funding from CARB-X to further develop advanced drugs against bacterial pneumonia

Hospital-acquired bacterial pneumonia is the most frequent nosocomial infection. It is mostly caused by the bacterium Staphylococcus aureus, which in many cases is already resistant to commonly used antibiotics and is therefore difficult to treat. A team from the Helmholtz Centre for Infection Research (HZI) in cooperation with the Lead Discovery Center GmbH (LDC), a spin-off of Max Planck Innovation and the Max Planck Society e.V., aims to further develop a drug that prevents staphylococci from colonizing the lungs. The research team will now receive milestone-dependent funding of initially 1.33 million US dollars from the non-profit organization CARB-X (Combating Antibiotic-Resistant Bacteria Biopharmaceutical Accelerator), with CARB-X anticipating a further 7.44 million US dollars depending on the progress of the project.

Bacteria of the species Staphylococcus aureus are among the most common pathogens associated with hospital-acquired pneumonia worldwide. Multi-resistant strains of this pathogen have spread worldwide and constitute a major threat for health care, especially in countries with high antibiotic use. Hospital-acquired bacterial pneumonia has a high mortality rate of over 20 percent even with adequate antibiotic therapy - regardless of whether the patient requires artificial respiration or not.

A research team from the HZI and LDC led by Prof Mark Brönstrup has recently discovered highly potent first-in-class small molecule drugs that can inhibit the colonisation of the lung by S. aureus. Brönstrup heads the department “Chemical Biology” at the HZI and holds a professorship at the German Center for Infection Research (DZIF) that is based at the Leibniz University Hannover. In the project now funded by CARB-X, the scientists intend to optimise the discovered compounds in preclinical studies and subsequently transfer them into clinical trials on humans. “We are very pleased about the funding of CARB-X and the international recognition of our drug research at the HZI,” says Prof Dirk Heinz, Scientific Director of the HZI.

For Mark Brönstrup, the support provided by CARB-X is an important step: “We urgently need better treatment options for patients with pneumonia caused by S. aureus. In the long term, however, we will not achieve this by killing the pathogens with antibiotics alone. Instead, we need preventive or accompanying therapies that prevent damage to the lungs by bacterial toxins.” A highly promising approach, already validated by preclinical and clinical data with monoclonal antibodies, is to disarm the bacteria rather than kill them. For this purpose, the scientists are blocking the bacteria's most important toxin that causes damage of lung tissue and immune cells - the virulence factor α-hemolysin. In this way, the progression of the infection can be halted until the immune system or a suitable antibiotic therapy eliminates the bacteria. During the first project phase, which was financed by the Helmholtz Association's Validation Fund, the research team of the HZI and LDC had already identified highly effective small molecule inhibitors of α-hemolysin. In the now funded project, these inhibitors are intended to be further developed for the prophylaxis and treatment of lung infections with S. aureus and optimised up to a first human use in clinical phase 1 studies.

“The CARB-X funding enables the continued successful translation of excellent academic research into application. We look forward to the next phase in our close cooperation with the HZI, in which we will be advancing the α-haemolysin inhibitor project as rapidly as possible with the goal of developing a new drug for the treatment of patients with resistant S. aureus infection,” says Dr Bert Klebl, CEO & CSO of LDC.

“Pneumonia caused by S. aureus is a significant health threat around the world, particularly for patients whose immune systems are compromised,” said Erin Duffy, R&D Chief of CARB-X, a non-profit partnership led by Boston University, and dedicated to funding and supporting the development of innovative products targeting antibiotic-resistant bacteria. “The HZI project is an innovative approach that, if successful, has the potential to offer improved treatment of S. aureus infections around the world, particularly in low- and middle-income countries (LMICs), and to save lives.”

This news release is supported by the Cooperative Agreement Number IDSEP160030 from ASPR/BARDA and by awards from the Wellcome Trust, Germany’s Federal Ministry of Education and Research (BMBF), and the UK Global Antimicrobial Resistance Innovation Fund (GAMRIF). The contents are solely the responsibility of the authors and do not necessarily represent the official views of the HHS Office of the Assistant Secretary for Preparedness and Response, or other CARB-X funders.

ABOUT CARB-X:

Combating Antibiotic-Resistant Bacteria Biopharmaceutical Accelerator (CARB-X) is a global non-profit partnership dedicated to accelerating early development antibacterial R&D to address the rising global threat of drug-resistant bacteria. CARB-X is led by Boston University and funding is provided by the Biomedical Advanced Research and Development Authority (BARDA), part of the Office of the Assistant Secretary for Preparedness and Response (ASPR) in the US Department of Health and Human Services, the Wellcome Trust, a global charity based in the UK working to improve health globally, Germany’s Federal Ministry of Education and Research (BMBF), the UK Department of Health and Social Care’s Global Antimicrobial Resistance Innovation Fund (GAMRIF), the Bill & Melinda Gates Foundation, and with in-kind support from National Institute of Allergy and Infectious Diseases (NIAID), part of the US National Institutes of Health (NIH). CARB-X is investing up to $480 million from 2016-2022 to support innovative antibiotics and other therapeutics, vaccines, and rapid diagnostics. CARB-X supports the world’s largest and most innovative pipeline of preclinical products against drug-resistant infections. CARB-X is headquartered at Boston University School of Law. https://carb-x.org/

Germany is supporting the CARB-X Initiative with 39 million euros over a period of four years. In addition to direct funding, the BMBF is providing one million Euros for the so-called "CARB-X Accelerator" on a national scale. The German Center for Infection Research (DZIF), the Federal Institute for Drugs and Medical Devices (BfArM), and the Paul Ehrlich Institute (PEI) are cooperating within this project. DZIF actively advises and accompanies German academic groups on their way to successful CARB-X funding and takes on an advisory function for international companies or working groups in the already existing CARB-X portfolio. BfArM and PEI provide support especially in regulatory issues. In 2020, two German research projects were nominated for CARB-X funding for the first time.

ABOUT LDC:

Lead Discovery Center GmbH was established in 2008 by the technology transfer organization Max Planck Innovation of the German Max Planck Gesellschaft e.V., as a novel approach to capitalize on the potential of excellent basic research for the discovery of new therapies for diseases with high medical need. The Lead Discovery Center takes on promising early-stage projects from academia and transforms them into innovative pharmaceutical leads and antibodies that reach initial proof-of-concept in animals as well as candidate nomination. In close collaboration with high-profile partners from research and industry, the Lead Discovery Center is building a strong and growing portfolio of lead and candidate compounds with exceptional medical and commercial potential. The Lead Discovery Center sustains a long-term partnership with the Max Planck Society, KHAN-I GmbH & Co.KG and has formed alliances with Apeiron, AstraZeneca, Bayer, Boehringer Ingelheim, Merck KGaA, Daiichi Sankyo and Qurient, e.g.In addition, LDC also works with leading translational drug discovery centers and with various investors to provide its assets for company creation financed by venture capital firms, like Arix Bioscience and Medicxi, e.g.: www.lead-discovery.de

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