From Immunophysiology to Immunotherapy
Ilya Pharma evolved from the internationally recognized research conducted by the laboratories of the co-founders Mia Phillipson, Professor of Physiology at Uppsala University, Sweden, and Stefan Roos, Professor at the Swedish University for Agricultural Sciences. By combining the discoveries of the Phillipson laboratory focusing on how the immune system protects and repairs mucosal surfaces and injured tissues, with the know-how of the Roos laboratory on characterization and engineering of various lactobacilli strains, they designed and genetically engineered a strain of L. reuteri expressing the human chemokines CXCL12 (ILP100) and CXCL17 (ILP101), now developed as pharmaceuticals by Ilya Pharma.
Much of Dr Phillipson’s research has focused on macrophages, which are immune cells found throughout the body that are best known for eliminating pathogens but, as Phillipson has shown, also play a crucial role in tissue repair and maintaining healthy organs.
“I’ve always been interested in what the immune system does beyond fighting viruses and bacteria,”
she says.
“Immune cells are essential for healing, maintaining normal tissue function, and preserving the protective barriers that keep harmful microbes away from our skin and mucosal surfaces.”
Her laboratory works at the intersection of physiology and immunology, investigating how immune cells interact with blood vessels, mucosal tissues, and the microbiome. Her group demonstrated that certain proteins, including CXCL12 could enhance restorative functions of macrophages when delivered directly to damaged tissue. The challenge was that these particular proteins are rapidly broken down in the body. To overcome this, the researchers engineered non-colonizing probiotic bacteria capable of producing the therapeutic protein CXCL12 exactly where it was needed, and for as long as benfits were seen, by repeated administration. The drug candidate was proved to be both safe and effective in an initial human study on wound healing (Öhnstedet 2023 eClinicalMedicine) and had strong antimicrobial effects when co-cultured with different multi-resistant pathogens (Lofton-Tomenius 2025 Infectious Diseases and Therapy).
“That was when we began asking whether the concept could work in the lungs,”
Phillipson says.
“Cystic Fibrosis (CF) immediately came to mind because chronic infection and inflammation are such fundamental features of the disease.”
Mia has recently been awarded funding from the Swedish Cystic Fibrosis Association Research Fund (RfCF) for a proof-of-concept study investigating ILP101s effects in experimental animals with genetic charactiristics similar to CF and chronic lung infections with muti-drug-resistant (MDR) pseudomonas aerginuosa.
Amplifying Endogenous Immune Responses
The focus of the new project is CXCL17, a chemokine naturally produced by the epithelium of healthy airways.
“CXCL17 is part of the mucosal immune system’s first line of defence. Healthy lungs produce it in response to both inflammation and infection, and we believe it helps regulate both and immune cells and kill bacteria within the airway.”
Phillipson explains.
In CF, however, that protective balance is disrupted. Thick mucus allows disease-causing bacteria to establish persistent infections, driving a cycle of chronic inflammation and progressive lung damage.
Rather than stimulating an aggressive immune response, the researchers hypothesize that L. reuteri delivered CXCL17 will reinforce the lungs’ own healing and protective mechanisms.
“Our hypothesis is that CXCL17 can help restore the mucosal balance in the airway by limiting the recruitment of inflammatory immune cells, while driving resolution of inflammation to support maintenance of the mucosal barrier.”
Living Medicine with Multimodal Mechanism of Action
To deliver CXCL17, the team is taking an unconventional approach: using genetically engineered probiotic bacteria as microscopic protein factories inside the lung.
“Using bacteria as a therapeutic platform is still a relatively new concept. But the principle is quite simple. The bacteria produce CXCL17 exactly where it’s needed, within the mucosal lining of the airways.”
Phillipson says.
The bacterial chassi used in the ILP101 is a lactic acid-producing species originally isolated from rats. Because it is poorly adapted to humans, it survives for only a few hours after administration and does not spread beyond the site of administration—a key aspect of the treatment’s safety profile.
Although the therapeutic L. reuteri delivered CXCL17 is temporary, bioavailibility is longer than if delivered as a recombinat protein. In addition, other reserachers have published that L. reuteri delivered to the lungs significantly limit inflammation as it reduces the recruitment of neutrophils. Phillipson therefor believes that the drug candidate initiates a multimodal and long-lasting biological response.
“Our theory is that even a short exposure can trigger a cascade of healing processes that continues long after the bacteria themselves have disappeared.”
Next Steps
The RfCF funded study aims to demonstrate that the approach is safe and that it produces measurable and meaningful biological effects. In this project, mice carrying the same CF mutation found in most people with cystic fibrosis will inhale aerosolised droplets containing the engineered bacteria.
The researchers will investigate whether treatment can reduce pathogenic bacteria, strengthen the airway barrier, and improve immune function without provoking harmful inflammation.
“We need clear evidence that CXCL17 behaves the way we expect. Only then can we begin thinking about the next steps towards clinical development.”
Phillipson says.
Could Stimulating the Immune System Make Things Worse?
The idea of inhaling bacteria into lungs already affected by chronic inflammation may initially sound counterintuitive.
Phillipson understands the concern.
“It’s an entirely reasonable question.”
However, she stresses that the probiotic bacteria are not intended to activate the immune system in a way that intensifies inflammation.
Instead, the researchers believe the treatment may actually help resolve inflammation by killing pathogens and restoring healthier immune regulation within the airway.
Even if the results are more modest than hoped—for example, reducing multidrug-resistant bacteria without broader improvements—the project would still generate valuable knowledge.
“Negative results are informative too. Every well-designed study teaches us something.”
Research Funded by EU and Swedish Cystic Fibrosis Foundation
The program was initated by funding from the EU Marie Sklodowska-Curie Actions in 2024 by the B-ACTIVE consortia where both Ilya Pharma and Uppsala University are Partners. Academic collaborations and multidisciplinary teams including Inductrial PhD students are key to bringing new concepts to proof-of concept. Ilya Pharma holds the patents, the know-how and the platform to take drug candidates to the next validation milestone.
Engaging with patient organisations involving them as stakeholder derisks the whole program.
For companies developing new medicines, support from patient organisations provides valuable external validation—not only of the underlying science but also of its importance to the people the treatment is ultimately intended to help. Such endorsement and engagement derisks the whole program, also for investors, regulators, and industrial partners.
“The CF community is remarkably knowledgeable and engaged. Working with patient organisations from the very beginning helps ensure we’re focusing on research that has genuine relevance.”
For Phillipson, funding from the RfCF grant represents more than financial support.It is also an endorsement that the project has been independently evaluated and recognised as both scientifically rigorous and meaningful from a patient perspective.
“Receiving this grant tells us that patients, phycisions and other scientists believe this research is worth pursuing. That kind of confidence is incredibly important and helps us take the work forward.”