Infections under fire

AiCuris, Max Planck Institute look to natural products for new weapons against viral, bacterial infections

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WUPPERTAL & DORTMUND, Germany—Antibiotic resistance is one of the biggest and most pressing health issues today, both in the United States and worldwide. While some antibiotic resistance is a natural occurrence—vulnerable bacteria are killed by antibiotics, while resistant strains survive to reproduce, making them the predominant forms—it is exacerbated these days due to factors such as international travel and the overprescription of antibiotics. The U.S. Centers for Disease Control and Prevention (CDC) estimates that in up to 50 percent of cases, antibiotics are not optimally prescribed or are prescribed when not needed. According to the CDC, some two million illnesses and 23,000 deaths are attributed to antibiotic resistance, with a majority of infections and deaths occurring in hospital settings.
In the latest installment of an ongoing partnership, AiCuris Anti-infective Cures GmbH and the Max Planck Institute of Molecular Physiology (MPI) announced a collaborative agreement in the second quarter of 2018 to address the issue of antibiotic resistance. The organizations will work together for the identification of novel compounds for treating viral and bacterial infections.
Per the terms of the deal, AiCuris will be granted access to the MPI’s proprietary collection of natural product-inspired substances and, together with the research group of Dr. h.c. Waldmann, will investigate and optimize compounds that prove active against bacteria or viruses and could be developed into anti-infective drugs. No financial details were disclosed.
“Novel antibiotics are in high demand due to the global rise of resistance to existing drugs,” Waldmann noted in a press release. “Natural products have been an invaluable source of novel antibiotics, and the concepts developed at MPI Dortmund for the design and synthesis of novel natural product-inspired compounds could pave the way to the discovery of new drugs. The expertise of MPI scientists in chemical biology partnered with AiCuris’ proven experience in drug development could result in the discovery and development of innovative approaches to fight bacterial and viral resistance.”
Waldmann’s research group, as noted on the MPI website, focuses on “the organic chemistry-biology interface. Grounded in chem- and bioinformatic charting of biologically relevant chemical space, we develop novel strategies for the synthesis of natural product-inspired compound collections and use them for the study of biological phenomena. Natural products and their structural scaffolds represent the biologically relevant and prevalidated regions of chemical structure space explored by nature.”
In January, the World Health Organization (WHO) shared surveillance data from its Global Antimicrobial Surveillance System, detailing some sobering specifics with regards to antibiotic resistance across the globe. In patients with suspected bloodstream infections, those with resistance to at least one commonly used antibiotic ranged from zero to as high as 82 percent. Penicillin resistance fell between zero and 51 percent, and individuals with E. coli bacteria associated with urinary tract infections showed resistance to ciprofloxacin anywhere between 8 and 65 percent of the time.
WHO issued a 2017 report titled “Antibacterial agents in clinical development—an analysis of the antibacterial clinical development pipeline, including tuberculosis” that showed there is a critical lack of new antibiotic being advanced clinically. The report found 51 new antibiotics and biologicals meant to treat priority antibiotic-resistant pathogens, but only eight were defined by WHO as “innovative treatments that will add value to the current antibiotic treatment arsenal.” The majority “are modifications of existing classes of antibiotics and are only short-term solutions,” as noted in a WHO press release.
“We strongly believe the development of new antibacterial drugs is crucial to combat antibiotic-resistant bacteria that is killing around 25,000 people every year in Europe,” commented Dr. Holger Zimmermann, CEO of AiCuris Anti-infective Cures GmbH. “One way to develop a resistance-breaking drug is to disregard well-trodden paths and explore new opportunities. We are very excited to be working with the MPI and its proprietary library of nature-derived compounds, as nature has often proven to be the perfect blueprint for innovative concepts.”
This isn’t the only news from AiCuris on the topic of infections and collaborations. The second quarter of the year also saw the company announce that the Japanese Ministry of Health, Labor and Welfare had granted MSD (known as Merck & Co. in the United States and Canada) marketing authorization for PREVYMIS for the prevention of cytomegalovirus infections in allogeneic hematopoietic stem cell transplant patients. AiCuris licensed the drug, a first-in-class non-nucleoside CMV inhibitor, to MSD in 2012, and per AiCuris’ agreement with MSD, it receives milestone payments and royalties on net sales of PREVYMIS. Securing Japanese marketing approval triggered a €15-million payment to AiCuris.

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