Global health & Local efforts: A silent pandemic

According to the World Health Organization (WHO), Antimicrobial resistance (AMR) is directly responsible for an estimated 1.14 million deaths a year and contributes to an additional 4.71 million deaths annually. Today we call AMR a silent pandemic and the main driver behind this pandemic is the misuse and overuse of antimicrobials in humans, animals, and plants – leading to the development of drug-resistant pathogens. This silent pandemic also has economic consequences. The World Bank estimates that AMR could result in USD 1 trillion additional healthcare costs by 2050, and USD 1 trillion to USD 3.4 trillion gross domestic product losses per year by 2030.

Many things at once

Important advances have been made in recent years to tackle AMR on an international level, including most recently the launch of the Gram-Negative Antibiotic Discovery Innovator (Gr-ADI) program. The USD 50 million investment by philanthropic partners Novo Nordisk Foundation, the Gates Foundation, and Wellcome, will focus on combatting AMR caused by a specific range of bacteria that are among the leading contributors to AMR-associated deaths. 

By sharing data in a consortium structure and maintaining a very specific research focus, we hope to make quick and real progress in a relatively short time.

“We want to work together in a new way when it comes to the Gr-ADI and use data-sharing to pool the resources and efforts of our three foundations, participating research institutions, and industry partners from around the globe. We also want to focus on finding new antibiotics against a very particular, but also very dangerous, strain of bacteria called Klebsiella spp. By sharing data in a consortium structure and maintaining a very specific research focus, we hope to make quick and real progress in a relatively short time,” says Marianne Holm, Vice President, Infectious diseases, Novo Nordisk Foundation.

Marianne Holm, VP, Infectious Diseases, Novo Nordisk Foundation

The problem with AMR is that we need to do many things at once, Holm emphasizes. “We must develop new antibiotics, vaccines, and diagnostics, but we also need to create a lot more public awareness and push for better policies that prevent AMR in the first place,” she says.

“Additionally, we need to ensure equitable access to antibiotics and new treatments and foster responsible antimicrobial stewardship (AMS) to prevent misuse and overuse. We also need broad industry and political support for a better financial model behind antibiotic drug discovery.”

Another global initiative underway is the AMR Action Fund of USD one billion, launched in 2020 by several pharmaceutical companies and foundations. The aim of this initiative is to bring two to four new antibiotics to patients by 2030 by investing in small and medium-sized biotech companies focused on developing innovative antibacterial treatments that address the most dangerous and resistant bacteria.

In the Nordics, a new Danish AMR alliance was formed in 2023, initiated by Pfizer Denmark, Pharmadanmark and the Novo Nordisk Foundation, and Sweden has the world’s first AMR ambassador, Malin Grape. Her task is to promote the visibility of the government’s priority issues in the field of AMR on the international arena and to drive a stronger global dialogue. Through Grape, Sweden was also a catalyst in the drafting of the European Roadmap on AMR, adopted in 2023, listing 53 measures, ranging from improved hygiene and vaccination to the use of whole genome sequencing, to improve monitoring of antibiotics and resistance in the environment.

Nordic efforts

On a local business level, there are several Nordic companies developing products, therapies, and preventive measures with the aim of tackling AMR. Danish company SNIPR Biome, previously interviewed by Ellen Delisio in NLS, is one such company. Christian Grøndahl, co-founder and CEO, and his colleagues are engineering microbiomes using CRISPR technology. They have a drug candidate designed to target E. coli infections, developed as an oral prophylactic treatment to reduce the risk of blood stream infections for blood cancer patients undergoing hematopoietic stem cell transplantations. They have completed Phase 1 clinical trials in the US and have now moved into Phase 1b/2a.

My experience is that there is a gap between both the global and local ambitions for curbing AMR and what I see, hear, and read is being implemented.

Also based in Sweden, Evelina Vågesjö, co-founder and CEO of Ilya Pharma, was recently selected for the Eisenhower Fellowship, encompassing six weeks of intensive travel across the US where fellows meet with experts in their respective fields. For her, the program can create a collaborative stakeholder strategy for MDR pathogen testing, treatment, and policy reform. 

“My experience is that there is a gap between both the global and local ambitions for curbing AMR and what I see, hear, and read is being implemented,” she says. “Through the Eisenhower Fellowship I get support to cast a wide net, reach out to several hundred leaders and decision-makers in the field, and meet all the relevant organizations, investors, researchers, healthcare providers, and other stakeholders. I aim to find those islets or clusters that are high performers and doing meaningful and impactful work. And I want to learn and collaborate in the relevant way to potentially leverage data use and intellectual property developed by Ilya Pharma.

Evelina Vågesjö, co-founder and CEO, Ilya Pharma

Ilya Pharma develops local-acting immunotherapies and the company’s proprietary platform uses lactic acid bacteria as vectors to deliver human therapeutic factors to the afflicted site. The lead asset, ILP100, is a non-human strain of L. reuteri that delivers the human chemokine CXCL12. 

“One feature of the ILP-drug candidates is that they per default also have a strong antibiotic effect against pathogens, especially MDR pathogens. The antibiotic potency has recently been shared in a preprint and is on par with approved traditional chemical antibiotics. Their antimicrobial effect of ILP100 in doses used in clinical studies were assessed against six different infectious bacterial species that are highly resistant isolated in Ukraine; Pseudomonas aeruginosa, Acinetobacter baumannii, Enterobacter cloacae, Klebsiella pneumoniae, Proteus mirabilis, and Staphylococcus aureus. This additional product feature is most relevant for our company’s work related to skin wounds and lungs,” explains Vågesjö.

I also ask her what she believes are the key efforts needed to slow this silent pandemic down.

“What gets measured can be improved. Transparent reporting from all healthcare providers and relevant use of the data to both curb the spread of resistance and also in some way market good and responsible sites that reward meaningful progress. I believe in testing healthcare personnel and introducing accountability on the part of the care-provider and employer for patients and staff,” she says. 

“I also believe in point-of-care susceptibility testing covering the relevant MDR strains at each time-point in each region, allowing same-day results and same day decisions on treatment or other actions. The technologies needed seem to already be available,” she adds.

Further to the west, Norwegian AdjuTec’s novel antibiotic resistance breakers may also facilitate a reduction in the use of antibiotics. Their antibiotic product is an enzyme inhibitor that works on gram negative bacteria, listed by the WHO as the leading cause of deadly bacterial infections in the world. Bacteria defend themselves by producing enzymes that destroy antibiotics. AdjuTec’s product inhibits these enzymes and thereby protects the antibiotic.

“It can be combined with different broad-spectrum antibiotics, including carbapenems and cephalosporins. After intravenous administration, it should preferably have comparable pharmacokinetics, meaning plasma profile, distribution, and route of elimination from the human body as the antibiotic. There should be no interactions between the compounds,” says Bjørn Klem, CEO, AdjuTec.

The company is now ready to test its product in humans. The final product will be administered intravenously to severely ill patients infected with bacteria resistant to existing treatments. The first results are expected in early 2025. The phase IB trial starting in 2025 will then investigate how the APC148 works in combination with a broad-spectrum antibiotic.

Even in the small country of Iceland, efforts are being made in the fight against AMR. One example is Akthelia Pharmaceuticals which is part of the EU-project IN-ARMOR (with a budget of EUR 95.5 billion)aiming to introduce a novel class of immune system inducers able to enhance the body’s own innate microbial defense mechanisms to combat infections. This mechanism should work on all pathogens and is multi-factorial. Resistance is therefore unlikely to develop, describes Egill Másson, CEO, Akthelia Pharmaceuticals.

“A broad-spectrum therapeutic based on these inducers would be an alternative and addition to direct-acting antibiotics and might even potentiate current antibiotics to be active against resistant pathogens. A secondary goal is to develop the inducers as therapeutics for inflammatory disorders, such as Crohn’s disease,” he adds.

Akthelia’s therapeutic platform is based on novel compounds that mimic and amplify the immunomodulation of epithelial surfaces by natural metabolites of our microbiomes. Akthelia and the other participants have explored the chemical space and screened over 130 novel compounds to define a shortlist of 20 compounds with powerful innate immune induction that are now undergoing further in vitro screening, describes Másson.

By running these activities simultaneously, we can speed up progress and stay on track to begin IND-enabling studies at the end of the project, which runs until summer 2027.

“We expect to select three lead candidates and specific pathogens for in vivo studies which start later this year. In parallel, nano-formulation work has already started to develop targeted drug delivery to the GI tract, and the scale-up of one compound will start ahead of the in vivo studies. By running these activities simultaneously, we can speed up progress and stay on track to begin IND-enabling studies at the end of the project, which runs until summer 2027,” he says.

Last but not least, Finnish company Solu is building the world’s most extensive pathogen DNA library, enabling more efficient bacterial data processing and real-time monitoring of changes in pathogens.

Finnish company Solu is building the world’s most extensive pathogen DNA library.

“I got terrified by the idea of resistant bacteria running rampart at an event about antibiotic resistance in April 2022. After studying the topic for a week or two, I started to realize the potential of DNA sequencing as a way to cope with the problem. Sequencing could be used to monitor outbreaks, trace phylogenetic relationships, determine the effectiveness of therapies, and refine the accuracy of antibiotics,” states Sam Sihvonen, co-founder and CEO on the company’s website.

“Almost every clinical microbiology doctor supports the idea of sequencing becoming routine in 5-10 years. It will be the next big thing in diagnostics, and the data from the genomes is the key to preventing epidemics, developing new drugs, and treating patients,” he states further on the website.

The company started its first pilots in the fall of 2022 and so far their software has been able to provide relief to overworked scientists. One of Solu’s earliest clients in the US look for antimicrobial resistance genes and susceptibility predictions in, for example, cystic fibrosis patient bacterial genome samples. The company has also entered a collaboration with Hopital de La Tour, a healthcare institution in Geneva, Switzerland. Through this collaboration, Hopital de la Tour will implement Solu’s genomic surveillance technology to improve its infectious disease monitoring, antimicrobial resistance tracking and outbreak prevention efforts. “Through this partnership we will showcase how genomic surveillance can significantly improve public health and strengthen healthcare systems,” stated Sihvonen at the time of the announcement.

“Our product has the potential to reinvent diagnostics, pandemic control and therapies. Its application extend beyond bacteria to include viruses, fungi, drug development, bacteriophages, phage therapies, and anti-toxin therapies – all stored in real-time databases,” states Sihvonen.