Trial Initiated to Evaluate Compound for Molecular Imaging of Apoptosis

New imaging compounds have shown selective uptake in apoptotic cells in a variety of disease models, including solid tumors undergoing radio- and chemotherapy, different ischemic and inflammatory conditions, neurodegenerative disorders, atherosclerosis, acute myocardial infarction and others.

NST NeuroSurvival Technologies, Ltd. (NST; Petach Tikva, Israel), a clinical phase company developing molecular imaging agents and drugs that identify and target cells undergoing apoptosis, recently announced that the U.S. Food and Drug Administration (FDA) issued a "safe to proceed” letter for the company's Aposense [18F]-ML-10 Investigational New Drug Application (IND).

[18F]-ML-10 is a member of the Aposense family of molecules, a novel class of small molecular probes that detect and accumulate within cells undergoing apoptosis from its early stages. Apoptosis is a genetically controlled process of cell death, associated with most medical disorders, in multiple clinical areas including oncology, neurology, and cardiology. Upon recognizing apoptosis-specific changes on the cell membrane, Aposense molecules undergo a change enabling them to enter and accumulate within the dying cell from the early stages of the death process, while being excluded from viable or necrotic cells. The [18F]-ML-10 is labeled with the radioisotope 18F(fluorodeoxyglucose) for molecular imaging of programmed cell death in real time with positron emission tomography (PET).

Molecular imaging is an emerging field that aims to visualize noninvasively biologic processes in vivo. The ability to image disease-related biologic processes might allow physicians to detect disease early, characterize the disease better, and to personalize treatment by real-time monitoring of therapeutic effect. Molecular imaging depends on special molecules (probes) that can selectively target these biologic processes, while carrying an imaging moiety for visualization, such as 18F or other positron-emitting radioisotopes that can be visualized by PET imaging.

Apoptosis is a genetically controlled program of cell death, inherent in any nucleated cell in the body, and therefore, frequently referred to as "cell suicide.” Upon activation, the apoptotic program executes a well-characterized sequence of events by which the cell undergoes fragmentation and elimination by macrophages, without damaging the surrounding tissue. Apoptosis is a universal process of cell death and it plays a role in most medical disorders, making it one of the important processes of cell biology. For example, apoptosis has important roles in oncology, both in the process of tumor growth, as well as in treatment with most therapies that aim to induce death in cancer cells. Targeting cells undergoing apoptosis, for imaging or delivering therapy, can therefore have broad clinical applications.

"This is a major step for our company as we now can expand our Aposense clinical program into the largest healthcare market in the world,” said Yoram Ashery, CEO of NST NeuroSurvival Technologies. "Initial clinical data for our [18F]-ML-10 compound for molecular imaging of apoptosis suggest that we may be able to deliver on the promise of personalized medicine by using real-time images of cell death to monitor disease activity and patient response to treatment.”

Pre-clinical studies with [18F]-ML-10 and other Aposnese compounds showed selective uptake in apoptotic cells in a variety of disease models. A phase I clinical study conducted in Europe evaluated the safety, dosimetry, and biodistribution of [18F]-ML-10 in normal healthy volunteers, and its suitability for imaging of cell death in the region of the infarct in patients with acute ischemic cerebral stroke. In both parts of the study, [18F]-ML-10 manifested an excellent safety profile and efficacy in imaging cell death. A phase IIa study was recently initiated in Israel in patients with metastatic brain tumors, a serious complication found in up to 25% of patients with advanced cancer. The study evaluates [18F]-ML-10 in early assessment of response to radiotherapy, compared to magnetic resonance imaging (MRI), which typically can evaluate response only two months or longer after treatment has been completed.

Following the FDA's safe-to-proceed letter for the [18F]-ML-10 IND, NST will expand its clinical programs in neurovascular disorders and cancer into the U.S. The first protocol already submitted to the FDA evaluates [18F]-ML-10 in visualizing apoptosis and neurovascular damage in patients with relapsing-remitting multiple sclerosis, as well as the safety of administering [18F]-ML-10. NST intends to submit additional protocols in the near term for evaluating [18F]-ML-10 in detecting and monitoring tumor response to anticancer therapy.

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NST NeuroSurvival Technologies