MorphoSys, a German biotechnology company, and Emergent BioSolutions, a global specialty biopharmaceutical company, announced the initiation of a phase 1 clinical study to evaluate the safety, tolerability, and clinical activity of MOR209/ES414 in patients with metastatic castration-resistant prostate cancer (mCRPC). Under the terms of the companies' co-development and commercialisation agreement, the achievement of this milestone triggers a payment of US$ 5 million by MorphoSys to Emergent.
MOR209/ES414 is an immunotherapeutic protein developed by Emergent using its proprietary ADAPTIRTM (modular protein technology) platform. Preclinical in vitro and in vivo studies have shown MOR209/ES414 redirects T-cell cytotoxicity towards cells expressing prostate specific membrane antigen (PSMA), an antigen commonly found on prostate cancer cells.
Arndt Schottelius, Chief Development Officer of MorphoSys, said: "MOR209/ES414 has the potential to address a clear unmet medical need in prostate cancer. We are thus delighted to see this compound moving into the clinic as expected in early 2015. This is the fourth clinical candidate in our growing proprietary portfolio of compounds and increases the total number of clinical programs in our pipeline to 23."
Barry Labinger, Executive Vice President and President Biosciences Division at Emergent BioSolutions added: "Emergent is pleased to announce the dosing of our first patient in this Phase 1 clinical study. Prostate cancer is the most common cancer in men, and there is a significant need for improved treatment options. We believe that the immunotherapeutic approach represented by MOR209/ES414 offers the promise of meaningfully improved outcomes for patients with mCRPC. We are excited to work with our partner MorphoSys, to evaluate the potential of MOR209/ES414 in the clinic."
The study will be conducted in two stages. The primary objective of stage 1 is to identify the maximum tolerated dose (MTD) of MOR209/ES414 administered intravenously, with weekly dosing for three months and bi-weekly thereafter, to patients with mCRPC. The secondary objectives are to evaluate the tolerability, pharmacokinetics (PK), pharmacodynamics (PD), immunogenicity, cytokine response, and clinical activity of MOR209/ES414. Within stage 2, the primary objective is to evaluate clinical activity in patients that have or have not received prior chemotherapy, while secondary objectives are to further characterize the safety profile, PK, PD, and immunogenicity of MOR209/ES414.
This open-label phase 1 clinical study will be conducted in the US and Australia, with a planned enrollment of up to 130 patients.
MOR209/ES414 is a targeted immunotherapeutic protein, which activates host T-cell immunity specifically against cells expressing Prostate Specific Membrane Antigen (PSMA), an antigen commonly overexpressed on prostate cancer cells. The MOR209/ES414 molecule was constructed using Emergent's ADAPTIR technology platform and selectively binds to the T-cell receptor on cytotoxic T-cells and PSMA on tumour cells.
MOR209/ES414 contains two pairs of binding domains, each targeting a unique antigen, linked to opposite ends of an immunoglobulin Fc domain to extend the half-life and enable use of a purification process typical of lg-based molecules. In preclinical studies, MOR209/ES414 has been shown to redirect T-cell cytotoxicity towards prostate cancer cells expressing PSMA.
ADAPTIR bispecific proteins are modular, single chain polypeptides that comprise two separate binding domains, a hinge segment, and an effector domain (huFc). They have a differentiated structure from monoclonal antibodies and can generate a unique signaling response. Some ADAPTIR molecules, like MOR209/ES414, may mediate T-cell cytotoxicity by redirecting T-cells against tumour cells. In addition, monospecific ADAPTIR proteins may mediate complement dependent cytotoxicity and Fc dependent cytotoxicity, similar to monoclonal antibodies.
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Prostate cancer is the most common cancer in men with approximately 230,000 new cases annually in the United States or 900,000 new cases annually worldwide. Screening, radiation, surgery and hormone ablation therapy have greatly improved the detection and treatment of early stage prostate cancer. However, the new therapies only improve life expectancy by a few months for patients with metastatic castration-resistant prostate cancer.