Radiopharmaceuticals

for

Fibrogenesis Targets

Molecular Imaging and Targeted Radiotherapy

of Organ Fibrosis and Fibrotic Cancer

 

who we are

BiOrion is a clinical-stage biopharmaceutical company developing imaging diagnostics and targeted radiotherapeutics for fibrotic diseases such as pulmonary fibrosis, cardiac fibrosis, hepatic fibrosis, renal fibrosis and cancers with fibrotic stroma, with a special focus on advanced colon cancer.

The company is advancing its first generation tracer BOT5035 through phase 1/2  clinical PET-imaging trials targeting PDGFRB-expressing fibrotic cells in patients with pulmonary or cardiac fibrosis.

Clinical trials with our second generation BOT1712 targeting PDGFRB-expressing cells in hepatic fibrosis and colon cancer are expected to start in 2023.

BiOrion’s technology platform is based on the screening and selection of single domain antibodies (also known as nanobodies) for myofibroblast-specific membrane proteins and receptors such as PDGFRA, PDGFRB, EGFR, IGF-2R and FAP. Eventually the platform allows for a theranostic approach using the same single domain antibody for patient identification, targeted therapy and disease monitoring.

What is fibrosis

Fibrosis is the consequence of chronic cycles of tissue injury and repair leading to the accumulation of scar tissue in affected organs and disruption of normal tissue architecture and function. Fibrosis is the final common pathway in virtually all forms of chronic organ failure. The cellular and molecular biology of fibrosis is similar across multiple organs and multiple sources of tissue injury, including fibrotic stroma in many solid cancers. Fibrotic stroma can make up to 80% of tumor mass and is a suitable target for cancer treatment.

Diagnostic imaging of fibrosis

Diagnostic imaging of fibrosis is nowadays primarily focusing on major tissue density differences caused by scar tissue, mainly collagen. This could work for identification of patients with established fibrosis.  But resolution of scar tissue after a potentially successful antifibrotic intervention may take many years. Therefore, todays’ diagnostic imaging of fibrosis is not suitable for disease monitoring in patients. Moreover, lack of sensitive and reliable diagnostic options hamper the development of novel antifibrotic therapies. There is a growing demand for molecular imaging diagnostics allowing early-stage detection of fibrotic chronic diseases and help minimize costs of treating these diseases. 

“Fibrosis is not a molecular target,  Fibrogenesis is”

why targeting fibrogenesis

Fibrogenesis is a far better target as it reflects fibrosis activity. Fibrogenesis is the mechanism of wound healing and repair. Upon scarring, there is migration, proliferation and differentiation of fibrogenic cells towards activated myofibroblasts, the key pathogenic cells, followed by deposition of extracellular matrix proteins, including collagen. PDGF and TGF-beta are the main drivers of fibrosis and are validated targets for fibrosis treatment. Activated myofibroblasts express specific types of membrane receptors that distinguish them from quiescent fibroblasts.

When targeting fibrogenesis, one targets the pathogenic cells of the active disease itself. Irrespective of the amounts of deposited collagen in the fibrotic organ and how fast it will disappear.

This is the area where BiOrion, as a fibrogenesis targeting company, has made fast progress in developing tracers for these specific membrane receptors, reflecting fibrosis activity.

our technnology

BiOrion’s discovery engine is based on proprietary myofibroblast-specific receptor-binding peptides and single domain antibodies. Targeting these receptors allow targeted imaging and targeted therapy of active fibrosis. Our peptides and single domain antibodies  can be conjugated to functional groups such as a NOTA or DOTA chelators, capturing radionuclides, among others.

our focus areas

Fibrosis ranks among the top 3 clinical indications with high unmet medical need and high mortality. As a targeted radiopharmaceuticals company we do not only focus on pulmonary fibrosis, cardiac fibrosis and hepatic fibrosis. Since many solid cancers rely on fibrotic stroma, we have also included colon cancer in our areas of focus.

our PIPELINE

BiOrion’s 2 lead products are based on proprietary PDGFRB-binding peptides and single domain antibodies. PDGFRB is expressed by activated myofibroblast, the key pathogenic cells that cause fibrosis. 68Ga-BOT5035 is in phase 1/2 PET-imaging clinical trials  for cardiac fibrosis and pulmonary fibrosis. 68Ga/177Lu-BOT1712 is development for hepatic fibrosis and advanced colon cancer.

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