Novartis Expands Targeted Radioligand Therapy Pipeline with In-License of Fibroblast Activation Protein (FAP)-Targeting Agent Portfolio

March 31, 2021 /BioValleyBIOON/ -- Novartis recently announced that, through molecular imagingDiagnosisand a transfer agreement with iTheranostics, an affiliate of technology developer SOFIE Biosciences, through which it obtained the global exclusive rights to develop and commercialize therapeutic applications of a library of fibroblast activation protein (FAP)-targeting agents, including FAPI-46 and FAPI-74. The FAP assets were initially developed by Heidelberg University. The agreement also includesNovartisJoint ownership of the rights to develop imaging applications for these assets.

Fibroblast Activation Protein (FAP) is a cell surface protein expressed at low levels in most normal adult tissues but overexpressed in common cancers, particularly on cancer-associated fibroblasts that form the tumor stroma, which is essential for tumor growth. High expression of FAP on cancer-associated fibroblasts is often associated with poor prognosis in solid tumors because it promotesTumorthe occurrence and development.

NovartisTumorNovartis CEO Dr. Susanne Schaffert stated, “We continue to invest in radioligand therapy as aNovartisOne of the four unique platforms in oncology. We believe that working across multiple modalities is key to reimagining cancer care. FAP is an exciting target, and these agents are well-suited for our radioligand therapy pipeline. Currently, we are actively investigating multipleTumortype. We believe this technology has the potential to transform the lives of many patients.”

Image source: vitusprostate.com

Targeted Radioligand Therapy is a precision medicine that combines two key elements: a targeting compound or ligand and a radioactive isotope, which can cause DNA damage and inhibit tumor growth and replication. These targeted drugs bind to markers or proteins overexpressed in certain tumors or tumor-associated tissues (such as the stroma). Due to these drugs' specificity for particular tumor cells or relatedTumorHigh tissue affinity, with minimal impact on surrounding healthy tissues.

NovartisGlobal expertise, specialized supply chains, and manufacturing capabilities have been established across a network of four radioligand therapy production sites, further enhancing supply capacity to ensure the delivery of radioligand therapies to patients in need.

It is worth noting that,NovartisIt is the only pharmaceutical company currently building four distinct cancer treatment platforms, including radioligand therapy, cell and gene therapy, targeted therapy, and immunotherapy, positioning it to integrate these platforms and deliver optimal outcomes for each cancer patient.

¹⁷⁷Lu-PSMA-617 (Image source: embs.org)

Just recently,NovartisAnnounced the first interpretable results from the Phase III VISION study evaluating the targeted radioligand therapy 177Lu-PSMA-617 in patients with PSMA-positive metastatic castration-resistant prostate cancer (mCRPC). The study enrolled 831 patients with mCRPC who had disease progression after prior treatment with taxanes and androgen receptor-directed therapies (ARDTs) and who were PSMA-PET scan-positive. It assessed the efficacy and safety of 177Lu-PSMA-617 (administered as a 7.4 GBq intravenous infusion every 6 weeks for up to 6 cycles) in combination with best standard of care (BSC) selected by the investigators, compared with BSC alone. The surrogate primary endpoints of the study were radiographic progression-free survival (rPFS) and overall survival (OS).

The results demonstrated that the study met its two primary endpoints: compared with best supportive care (BSC) alone, 177Lu-PSMA-617 plus BSC significantly improved overall survival (OS) and radiographic progression-free survival (rPFS) in patients with PSMA-positive metastatic castration-resistant prostate cancer (mCRPC). These findings bring us closer to the goal of providing an innovative targeted therapy for more than 80% of patients with advanced prostate cancer. The safety profile was consistent with data reported in previous clinical studies. The results of the VISION trial will be presented at the upcoming medicalMeetingpublished above and will be included in the regulatory submission documents for the United States and the European Union.

Prostate Cancer (Image source: hopkinsmedicine.org)

Prostate cancer is a type of cancer that occurs in the prostate, a small walnut-shaped gland in the male pelvis. In castration-resistant prostate cancer (CRPC), tumors show signs of growth, such as elevated prostate-specific antigen (PSA) levels, despite hormone therapy aimed at lowering testosterone. In metastatic CRPC (mCRPC),TumorSpread to other parts of the body, such as adjacent organs or bones, remains unresponsive to hormone therapy. The 5-year survival rate for patients with mCRPC is approximately 15%.

Despite advances in the treatment of prostate cancer, there remains a very high unmet medical need for new targeted therapeutic options in patients with metastatic castration-resistant prostate cancer (mCRPC). More than 80% of prostate cancersTumorHigh expression of a phenotypic biomarker known as prostate-specific membrane antigen (PSMA), making it a promisingDiagnosisTargets (visualized via positron emission tomography [PET] imaging) and therapeutic targets for radioligand therapy.

177Lu-PSMA-617 is a PSMA-targeted radioligand therapy developed for the treatment of metastatic castration-resistant prostate cancer (mCRPC). This drug is a precision cancer treatment that combines a targeting compound (ligand) with a therapeutic radioisotope (radionuclide). After injection into the bloodstream, 177Lu-PSMA-617 binds to prostate cancer cells expressing PSMA (a transmembrane protein), resulting in higher drug uptake by tumors compared to normal tissues. Once bound, radiation (beta particles) emitted from the radioisotope damagesTumorcells, impairing their replicative capacity and/or triggering cell death. The radiation emitted by radioisotopes acts only over very short distances, thereby limiting damage to surrounding cells. (Bioon.com)

Original Source: Novartis expands targeted radioligand therapy pipeline with in-license for compounds targeting Fibroblast Activation Protein (FAP)