
Our Science
A differentiated approach to the development of transformative therapies for the treatment of chronic inflammatory and fibrotic diseases
Upstream targeting
Leveraging over 30 years’ research by our co-founders, we have unlocked a groundbreaking therapeutic concept that allows us to tackle the root causes of inflammation and fibrosis.
Targeting upstream innate immune amplifiers, our first-in-class therapeutics modulate a wide range of disease-associated signaling pathways while ensuring a favorable safety profile.
Using these principles, our robust pipeline of therapeutics fulfils unmet clinical needs across a spectrum of diseases driven by acute or chronic inflammation and fibrosis.



Targeting S100A4
S100A4 is a Damage Associated Molecular Pattern protein predominantly confined to the intracellular space under physiological conditions. Upon tissue injury or stress, S100A4 is released into the extracellular environment alerting the surrounding cells to danger by engaging with Pattern Recognition Receptors. These receptors in turn trigger a broad repertoire of inflammatory and fibrotic responses including release of inflammatory mediators from macrophages and other immune cells, activation and differentiation of fibroblasts, and attraction of additional immune and stromal cells to the site of injury.
In chronically diseased tissue, S100A4 is inappropriately upregulated which switches self-limiting tissue repair responses into chronic activation of inflammatory signalling pathways and sustained fibrogenesis. Elevated levels of S100A4 are a hallmark of pathological tissue fibrosis and chronic inflammation and is seen in a wide range of diseases such as systemic sclerosis, idiopathic pulmonary fibrosis, liver cirrhosis, dermatomyositis, psoriasis, rheumatoid arthritis and metastatic cancer.

S100A4 – Treating Idiopathic
Pulmonary Fibrosis
Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease where an inappropriately activated wound-healing response causes the lung tissue to become thickened and scarred, making it difficult to breathe. The exact triggers of IPF are unknown, but it is believed to be a combination of genetic and environmental factors. Over time, the scarring in the lungs worsens, leading to respiratory failure and ultimately death.
Disease epidemiology
Prevalence
- Approx 150,000 people suffering from IPF in the US
- Population is growing at ~ 6% per year
Patient demographics
- Disease primarily affects older adults
Scientific rationale
- Targeting S100A4 has the potential to re-establish tissue homeostasis by switching off the downstream pathways involved in the persistent and maladaptive scar tissue formation characteristic of IPF
OxPL – Addressing Oxidized Phospholipids
Oxidative stress-induced oxidized phospholipids (oxPLs) are key drivers of harmful inflammation, contributing to surrounding tissue damage across a wide range of immunological indications with unmet medical needs, including reperfusion injury, rheumatoid arthritis, osteoarthritis, IBD and a range of severe respiratory indications.
Calluna Pharma is focused on developing novel therapeutics that neutralize the effects of oxPLs, reduce immune system activation, and improve clinical outcomes and patient quality of life.

References
Neutralization of S100A4 induces stabilization of atherosclerotic plaques: role of smooth muscle cells.
Sakic A, Chaabane C, Ambartsumian N, Klingelhöfer J, Lemeille S, Kwak BR, Grigorian M, Bochaton-Piallat ML.
Cardiovasc Res. 2020 Nov 2:cvaa311. doi: 10.1093/cvr/cvaa311.
Anti-S100A4 Antibody Therapy Is Efficient in Treating Aggressive Prostate Cancer and Reversing Immunosuppression: Serum and Biopsy S100A4 as a Clinical Predictor.
Ganaie AA, Mansini AP, Hussain T, Rao A, Siddique HR, Shabaneh A, Ferrari MG, Murugan P, Klingelhöfer J, Wang J, Ambartsumian N, Warlick CA, Konety BR, Saleem M.
Mol Cancer Ther. 2020 Dec;19(12):2598-2611. doi: 10.1158/1535-7163.MCT-20-0410.
Oligomeric S100A4 Is Associated With Monocyte Innate Immune Memory and Bypass of Tolerance to Subsequent Stimulation With Lipopolysaccharides.
Neidhart M, Pajak A, Laskari K, Riksen NP, Joosten LAB, Netea MG, Lutgens E, Stroes ESG, Ciurea A, Distler O, Grigorian M, Karouzakis E.
Front Immunol. 2019 Apr 15;10:791. doi: 10.3389/fimmu.2019.00791.
S100A4-neutralizing antibody suppresses spontaneous tumor progression, pre-metastatic niche formation and alters T-cell polarization balance.
Grum-Schwensen B, Klingelhöfer J, Beck M, Bonefeld CM, Hamerlik P, Guldberg P, Grigorian M, Lukanidin E, Ambartsumian N.
BMC Cancer. 2015 Feb 12;15:44. doi: 10.1186/s12885-015-1034-2.
A link between inflammation and metastasis: serum amyloid A1 and A3 induce metastasis, and are targets of metastasis-inducing S100A4.
Hansen MT, Forst B, Cremers N, Quagliata L, Ambartsumian N, Grum-Schwensen B, Klingelhöfer J, Abdul-Al A, Herrmann P, Osterland M, Stein U, Nielsen GH, Scherer PE, Lukanidin E, Sleeman JP, Grigorian M.
Oncogene. 2015 Jan 22;34(4):424-35. doi: 10.1038/onc.2013.568.
A generally applicable translational strategy identifies S100A4 as a candidate gene in allergy.
Bruhn S, Fang Y, Barrenäs F, Gustafsson M, Zhang H, Konstantinell A, Krönke A, Sönnichsen B, Bresnick A, Dulyaninova N, Wang H, Zhao Y, Klingelhöfer J, Ambartsumian N, Beck MK, Nestor C, Bona E, Xiang Z, Benson M.
Sci Transl Med. 2014 Jan 8;6(218):218ra4. doi: 10.1126/scitranslmed.3007410.
Anti-S100A4 antibody suppresses metastasis formation by blocking stroma cell invasion.
Klingelhöfer J, Grum-Schwensen B, Beck MK, Knudsen RS, Grigorian M, Lukanidin E, Ambartsumian N.
Neoplasia. 2012 Dec;14(12):1260-8. doi: 10.1593/neo.121554.
The metastasis promoting protein S100A4 is increased in idiopathic inflammatory myopathies.
Cerezo LA, Kuncová K, Mann H, Tomcík M, Zámecník J, Lukanidin E, Neidhart M, Gay S, Grigorian M, Vencovsky J, Senolt L.
Significance of the S100A4 protein in psoriasis.
Zibert JR, Skov L, Thyssen JP, Jacobsen GK, Grigorian M.
J Invest Dermatol. 2010 Jan;130(1):150-60. doi: 10.1038/jid.2009.206
Metastasis-inducing S100A4 protein is associated with the disease activity of rheumatoid arthritis.
Oslejsková L, Grigorian M, Hulejová H, Vencovsky J, Pavelka K, Klingelhöfer J, Gay S, Neidhart M, Brabcová H, Suchy D, Senolt L.
Rheumatology (Oxford). 2009 Dec;48(12):1590-4. doi: 10.1093/rheumatology/kep316.