Novartis expands targeted radioligand therapy pipeline

By Jane Byrne contact

- Last updated on GMT

© GettyImages/Rasi Bhadramani
© GettyImages/Rasi Bhadramani

Related tags: Cancer, Oncology

Novartis has obtained exclusive worldwide rights to develop and commercialize therapeutic applications for a library of Fibroblast Activation Protein (FAP) targeting agents.

The deal with iTheranostics, Inc, an affiliate of SOFIE Biosciences, Inc, sees the Swiss pharma giant acquiring compounds such as FAPI-46 and FAPI-74, among others.

Terms of the agreement are undisclosed but include upfront consideration along with milestone payments and royalties,”​ a spokesperson for Novartis told this publication. 

The FAP assets in this deal were originally developed at the University of Heidelberg.

The compounds are quinoline-based small molecules, which may be labelled with radioisotopes appropriate for therapeutic applications. The assets may also be labelled with radioisotopes appropriate for imaging, but this is not the primary focus of the Novartis program, said the spokesperson. iTheranostics will focus on development of imaging agents, she added.

Cancer-associated fibroblasts constitute a vital subpopulation of the tumor stroma and are present in more than 90% of epithelial carcinomas, according to a study​ by researchers at the University of Heidelberg.

That team outlined how the overexpression of FAP allows a selective targeting of a variety of tumors by inhibitor-based radiopharmaceuticals (FAPIs).

FAP is a cell-surface protein expressed at low levels in most normal adult tissues, but over-expressed in common cancers, particularly on cancer-associated fibroblasts that form the tumor stroma, which is essential for growth. 

FAP expression has been documented in the microenvironment of many epithelial cancers, including breast, lung, colorectal, pancreatic and ENT (ear, nose and throat) carcinomas, among others.

High FAP expression on cancer-associated fibroblasts is generally associated with worse prognosis in solid tumors due to promotion of tumorigenesis and progression.

The results of the University of Heidelberg research saw that chemical modification of the FAPI framework enabled enhanced FAP binding and improved pharmacokinetics in most of the derivatives, resulting in high-contrast images. "Moreover, higher doses of radioactivity can be delivered while minimizing damage to healthy tissue, which may improve therapeutic outcome."

Novartis sees agents such as FAPI-74 and FAP1-46 as fitting in well with its targeted radioligand therapy pipeline. “FAPI-46, FAPI-74, and other assets are preclinical for therapeutic use; however, several of these assets have been used in early clinical studies for imaging.We are preparing a clinical development plan [in relation to the compounds],”​ said the spokesperson.

Once radiolabelled, these compounds would work in a similar fashion to other radioligand therapies.

"These targeted drugs bind to markers or proteins (in this case FAP) over-expressed by certain tumors, or in this case tumor-associated tissue, such as stroma. Once bound, the radioactive isotope causes DNA damage that inhibits tumor growth and replication. Due to the high-affinity of these agents for specific tumor cells or associated tumor tissue, surrounding healthy tissue is less affected,"​ explained the spokesperson.

Related topics: Bio Developments

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