Cortalix Nanobody Pipeline
Our Focus
At Cortalix we are developing an internal and growing VHH pipeline of targeted multispecific therapeutics, radiopharmaceuticals, CAR-T immunotherapeutics, and bioanalytical tools based on VHH antibodies. Our internal programs center on three closely related disease areas: fibrosis, fibrotic stroma in solid cancers, and inflammation. We target fibrogenesis-related membrane receptors and proteins that occur in early-stage fibrotic diseases, such as pulmonary fibrosis, cardiac fibrosis, and liver fibrosis; in solid cancers with fibrotic stroma, such as colon cancer and pancreatic cancer; and in the chronic inflammatory processes that drive fibrogenesis in the first place.
Our Internal Programs
The current Cortalix VHH pipeline includes internal programs, and consortium-based subsidy programs, in targeted multispecific therapeutics, molecular imaging, radiotherapeutics and CAR-T immunotherapies targeting PDGFRA (CD140a), PDGFRB (CD140b), EGFR, IGF-2R (CD222), and FAP. Some of these programs are built on our expanded VHH discovery platform, which integrates both synthetic and immune libraries, but also off-patent (FTO-free) VHHs to generate high-affinity binders and constructs across diverse target classes.
A growing part of our portfolio consists of bispecific and trispecific VHH antibodies, engineered to simultaneously engage multiple disease markers or to combine target recognition with albumin binding for improved plasma halflife. While some of these constructs are built around our core targets such as PDGFR, EGFR and FAP, many additional targets are also included, depending on the specific application and modality. Most of our VHH constructs include a functional moiety for site-specific chelation of radionuclides such as 68-Ga and 18-F for PET imaging or 177-Lu and 225-Ac for targeted radiotherapy.
This versatile platform supports a theranostic strategy, using the same nanobody backbone for patient selection, targeted intervention, and longitudinal monitoring, all within a single molecular construct.
Ready for Partnering: Access Our Validated VHH Libraries
Behind every internal program lies a deep, well-characterized library of VHH binders against fibrogenesis, fibrotic stroma, and inflammation targets, including PDGFRA, PDGFRB, EGFR, IGF-2R, FAP, and additional undisclosed markers. A selection of these binders have already been discovered, screened, and validated through our FC8TM platform and immune library programs, and many are ready to be engineered (CDR grafting, humanization, multimerization, conjugation) into clinical-ready leads.
If your organization is developing a diagnostic or therapeutic program in fibrosis, fibrotic cancer stroma, or inflammatory disease, and one of these targets overlaps with your interests, you don’t need to start discovery from scratch. Cortalix can grant access to existing VHH binders against these targets through a license, exclusive or non-exclusive, saving months to years of early discovery work and giving you a validated, engineering-ready starting point.
Contact us to discuss which targets are available, and how a license could fit into your development program.
Fibrosis, fibrogenesis and cancer stroma
Fibrosis is the consequence of chronic cycles of tissue injury and repair leading to the accumulation of scar tissue, mainly collagen, 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.
Fibrogenesis is the mechanism of fibrosis and is reflecting fibrosis activity.
Why targeting fibrogenesis, and Where Inflammation Fits In
Consequently, 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 Cortalix has made fast progress in developing tracers for these specific membrane receptors, reflecting fibrosis activity.
Molecular imaging of fibrogenesis, and cancer stroma
Molecular 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 screening and 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.
CTX001
At its core, CTX001 combines a PDGFRB-binding nanobody with a second, non-disclosed nanobody, engineered to enhance target specificity and increase avidity. This bispecific format reflects Cortalix’s broader strategy to engineer next-generation VHH constructs with improved functional performance.
CTX001 has been optimized for use in both molecular imaging and targeted radiotherapy. Its imaging version is conjugated to a NOTA chelator for 68-Ga-based PET imaging, enabling precise detection of fibrotic and tumor-associated PDGFRB expression. A fluorine-18-labeled variant can also be provided to support wider clinical adoption.
For therapeutic use, CTX001 is developed as a trispecific VHH construct: the two target-binding nanobodies are combined with an AlbuFlexTM albumin-binding domain to extend circulation time and optimize its pharmacokinetic profile. This 177-Lu- or 225-Ac-DOTA-labeled ImmunoRadiotherapy agent has an initial focus on metastatic colorectal cancer, where targeting the PDGFRB-rich tumor stroma may offer new opportunities for microenvironment-directed treatment.
BOT5035 (Thorascan®)
BOT5035 (Thorascan®) was a first-generation diagnostic imaging agent based on a dimeric bicyclic peptide targeting the PDGF-β receptor. In its original format, BOT5035 was conjugated to a NOTA chelator for Gallium-68 PET imaging, with a fluorine-18 version also under development. The compound was evaluated for disease monitoring in cardiac fibrosis (including HFpEF and atrial fibrillation), pulmonary fibrosis (ILD and IPF), and liver fibrosis.
The BOT5035 program was acquired from BiOrion Technologies and progressed through multiple clinical PET imaging studies. While the compound showed promising biological targeting, its peptide-based architecture ultimately limited its further development potential.
Importantly, BOT5035 served as a blueprint for the design of next-generation nanobody-based tracers, influencing the development of VHH constructs like CTX001 and CTX004. Given the superior pharmacological properties and modularity of nanobodies, Cortalix has discontinued BOT5035 in favor of advancing its FC8TM nanobody platform for both diagnostic and therapeutic applications.
Other Candidates
In addition to PDGFRB-binding CTX001, we are advancing a series of next-generation diagnostic imaging and radiotherapy candidates, whether or not developed through our FC8TM discovery platform, targeting PDGFRA, IGF-2R, EGFR, FAP, and additional undisclosed markers. These constructs increasingly leverage our expertise in bispecific and trispecific VHH formats, designed to enhance targeting precision, signal clarity, and in vivo stability.
Our upcoming candidate CTX004, for example, is a fibrosis targeted Interferon gamma agent that will be developed for treatment of active hepatic fibrosis.
Other tracers in our pipeline follow similar principles, combining multi-target recognition with flexible labeling strategies, and will be aligned with our broader focus in fibrosis, fibrotic cancer stroma, and inflammation.
Interested in One of Our Targets?
Many of the VHH binders behind these programs are available for licensing, whether you’re looking for a validated starting point for a fibrosis, oncology, or inflammatory disease program. Get in touch to discuss target availability and licensing options.