S100A4

OSLO, Norway & BOSTON--(BUSINESS WIRE)--Calluna Pharma AS (Calluna), a clinical stage biotechnology company pioneering first-in-class antibodies to treat inflammatory and fibrotic diseases, today announced that the company will present three posters related to both of its pipeline programs at the American Thoracic Society (ATS) 2025 International Conference (ATS 2025). ATS 2025 is being held May 16 – 21, 2025 at the Moscone Center in San Francisco. The following abstracts are now available through the ATS 2025 itinerary planner. CAL101 - Targeting S100A4 Title: Therapeutic Potential of CAL101: A S100A4 Neutralizing Antibody for Fibrotic and Inflammatory Pulmonary Diseases Session: B28 - Transcriptional and Molecular Signatures in Pulmonary Fibrosis Poster: 124 Date and Time: Monday May 19, 2025, 9:15 AM-11:15 AM PT Presenter: Ian Holyer, PhD, Pharmacology Project Director Calluna Pharma Title: Evaluating the Safety, Tolerability and Target Engagement Profile of CAL101, A Novel S100A4 Neutralizing Antibody, for Progression into Idiopathic Pulmonary Fibrosis Session: B36 - Repair my Broken Lungs Poster: P528 Date and Time: Monday May 19, 2025,11:30 AM-1:15 PM PT Presenter: Jonas Hallen, MD PhD, Chief Medical Officer Calluna Pharma CAL103 - Addressing Oxidized Phospholipids Title: Anti-OXPL Antibodies Modulates Pathways Driving COPD Pathophysiology Session: A71 - Epithelial Dysfunction, Inflammation and Cigarette Smoke: Drivers of COPD and CF Pathogenesis Poster: P418 Date and Time: Sunday May 18, 2025, 11:30 AM-1:15 PM PT Presenter: Ian Holyer, PhD, Pharmacology Project Director Calluna Pharma About Calluna Pharma www.callunapharma.com Calluna Pharma is a global clinical stage company pioneering a breakthrough approach to treating inflammatory and fibrotic diseases by leveraging the body’s innate immune system. The Company’s therapeutic approach targets upstream amplifiers of disease, offering potential applicability across a diverse array of medical conditions. Calluna has a robust pipeline of selective antibodies targeting immunological diseases with enhanced efficacy, including multiple first-in-class drug candidates. Calluna was formed in 2023 following the merger of Oxitope Pharma and Arxx Therapeutics. Calluna is incorporated in Oslo, Norway and operates globally.

OSLO, Norway I October 23, 2024 I Calluna Pharma AS (Calluna), a clinical stage biotechnology company pioneering first-in-class antibodies to treat inflammatory and fibrotic diseases, today announced the completion of Phase 1 clinical study for CAL101, Calluna’s lead product candidate. The study demonstrated a favorable safety, pharmacokinetic (PK) and immunogenicity profile for the mAb. CAL101 is a first-in-class mAb that targets S100A4, a damage-associated molecular pattern (DAMP) protein implicated in serious and life-threatening diseases, such as idiopathic pulmonary fibrosis and systemic sclerosis. Preclinical studies have demonstrated the ability of CAL101 to prevent and treat fibrosis and modify the disease-specific activation of fibroblasts – the key effector cells driving progression of fibrosis 1 . Jonas Hallén M.D., Ph.D., Co-Founder and Chief Medical Officer of Calluna Pharma, commented: “We are encouraged by the findings from the Phase 1 study. These results are an important step forward in the development of our lead asset, CAL101, particularly for fibrotic and fibro-inflammatory diseases where there remains a critical need for innovative therapeutic options. We are excited as we now move into the next phase of clinical development.” The first-in-human, randomized, double-blind, placebo-controlled Phase 1 study in 57 subjects was designed to evaluate safety, tolerability, immunogenicity and PK, and was led by Professor Dave Singh at the Medicines Evaluation Unit in Manchester, UK 2 . The study tested single ascending doses of CAL101 in healthy volunteers and multiple ascending doses in patients with mild to moderate chronic plaque psoriasis. Summary of key CAL101 Phase 1 study results: In early 2025, Calluna plans to advance CAL101 into Phase 2 studies in fibrotic and fibro-inflammatory indications. For more information about Calluna Pharma, please visit: www.callunapharma.com SOURCE: Calluna Pharma

Harnessing nanoparticles to deliver drugs precisely to a surgically repaired tendon is a promising new approach that reduced scar tissue formation and improved mechanical function. Harnessing nanoparticles to deliver drugs precisely to a surgically repaired tendon is a promising new approach that reduced scar tissue formation and improved mechanical function in a study appearing in Science Advances. Researchers' success in pinpointing a drug therapy inside the body, at the cellular level, proved to be a highly efficient delivery method that could be used to treat other injuries. Whether it's a season-ending Achilles rupture by pro footballer Aaron Rodgers or an everyday workplace accident, tendon injuries are common and can be life-changing. They require 300,000 surgeries per year and often result in lost work time and permanent impaired physical function. Typically, traumatic tendon injuries are surgically repaired with sutures, but optimal healing is often impaired by the tendon's propensity to heal with scar tissue that restricts tendon movement and function. Researchers at the University of Rochester and University of Oregon combined their expertise in tendon cell biology and drug delivery systems to find a better way to deliver therapies that can reduce scar tissue and facilitate improved healing. "There are very few effective drug regimens to assist the tendon healing process, despite the high number of these injuries and the poor outcomes that often result," said Alayna Loiselle, PhD, associate professor at the University of Rochester's Center for Musculoskeletal Research. "Systemic drug treatments delivered orally or via injection show poor tendon homing; in some cases, less than 1 percent of a systemically delivered medication reaches the healing tendon. Local administration of drugs directly to the tendon has disadvantages as well, including potential tissue damage from the injection and poor control over drug concentrations at the point of injury." "We want to pivot from using suturing alone to incorporating therapeutics," said Emmanuela Adjei-Sowah, a Biomedical Engineering PhD student at the University of Rochester, who has spent the past several years working with co-authors Loiselle, Danielle S.W. Benoit, PhD, and others to develop the nanoparticle delivery system to improve healing in tendon injuries. "Advances in multiomics and drug delivery using nanoparticles open up new possibilities in treatment." The challenge for researchers was to identify which substances could assist tendon healing. Molecular 'map' of healing process charts a new therapeutic path "The fundamental cellular and molecular mechanisms that drive scar-mediated tendon healing are really only just beginning to be well-defined," Loiselle said. "Our prior work used spatial transcriptomic profiling to define a molecular map of the healing tendon. In subsequent analysis of this data, we found that the area right at the injury site had high levels of Acp5 gene expression, which was both surprising and exciting." The Acp5 gene produces a protein called Tartrate Resistant Acid Phosphatase (TRAP); both are known to occur as injured bones recover and rebuild. High TRAP activity within the healing tendon allowed researchers to employ a peptide that binds with TRAP to deliver medication directly to the healing tendon site. "While Benoit's lab has previously used TRAP-binding peptide nanoparticles (TBP-NP) for targeted drug delivery to bone, high TRAP activity in the healing tendon opened up an entirely new research direction," Loiselle said. Prior to initiating studies with therapeutic agents, the team completed a series of dose and timing studies, using a mouse model of complete transection and surgical repair of the flexor tendon, to define the window in which their drug delivery system could most effectively target the healing tendon. "Defining an optimal treatment window is critical to successfully developing an innovative and effective drug delivery system that improves tendon healing by encouraging a more regenerative, rather than fibrotic, healing cascade," said Benoit, the Lorry Lokey Department Chair and Professor in the Department of Bioengineering at the University of Oregon. "In addition, by defining the optimal therapeutic window for this drug delivery system, we can mitigate the unwanted side effects that typically accompany the high doses or multiple doses required to achieve sufficient drug accumulation in the tissue." As a therapeutic, the team chose Niclosamide, which inhibits S100a4, a protein that Loiselle's lab already identified as contributing to scar formation. Previous work from Loiselle's lab demonstrated that genetic knockdown of S100a4 improved mechanical and functional outcomes in this mouse tendon healing model. S100a4 has been implicated in scar formation in many tissues, including the liver, heart, lung, and oral submucosa; Loiselle's discovery that it complicates tendon healing gave them a therapeutic target for this study, where they used their TRAP-binding peptide nanoparticle drug delivery system to precisely affect the injured tendon. As a comparison, they delivered Niclosamide systemically; it did slightly reduce the amount of S100a4 in the healing tendon but it had no beneficial impact on the healing process. In contrast, delivery of the same dose of Niclosamide using the nanoparticle system resulted in robust inhibition of S100a4 mRNA and protein levels in the healing tendon. This targeted drug delivery method also significantly benefited the tendon healing process. TBP-NP delivery of Niclosamide improved both functional range of motion recovery and increased the mechanical integrity of the healing tendon across both short- and longer-term timepoints. Importantly, these sustained effects occurred with just a single treatment. Researchers will continue their work to define how broadly the system can be used for other tendon injuries and disease, as well as other types of tissue injury that result in scar formation. "The beauty of this system is that it can be loaded with different kinds of drugs to target different molecular processes or pathways," said Adjei-Sowah.