Molecular Insight Pharmaceuticals, Inc. (MIPI) presented positive data from a completed phase 2a clinical study of Azedra, (Ultratrace iobenguane I 131 or Ultratrace I-131-MIBG), the company's lead oncology therapeutic that targets neuroblastoma, a common childhood cancer. Phase 2a data presented at the Advances in Neuroblastoma Research (ANR) Conference in Stockholm, Sweden, on June 23, 2010, reported that the study successfully provided safety, toxicity and response data.

Data from the phase 2a study were presented in an abstract titled A phase IIa Trial of Ultratrace (no-carrier added) Iobenguane I-131 (MIBG): A New Approaches to Neuroblastoma Therapy (NANT) Study (Abstract 1906390) and in an oral presentation by lead investigator Katherine K. Matthay, M.D., the Mildred V. Strouss Professor of Translational Cancer Research and Chief, Pediatric Hematology-Oncology in Department of Pediatrics at the University of California, San Francisco. Key conclusions from Dr. Matthay's presentation, which included data on an additional seven patients enrolled since the abstract was submitted, include: (a) doses of 12 to 18mCi/kg of Ultratrace iobenguane were tolerated without dose limiting toxicity (DLT); and (b) Ultratrace iobenguane is active in tumours, without significant toxicity, with promising responses as shown by a preliminary observed response rate, using International Neuroblastoma Response Criteria (INRC), in 5 of 13, or 38 percent of currently evaluable patients. The data support proceeding to a pivotal Phase 2 study utilizing the 18 mCi/kg administered therapeutic dose.

Currently, I-131-MIBG is used to treat neuroblastoma, with a response rate greater than 30 percent in relapsed disease. The presence of non-radioactive "carrier" MIBG molecules may inhibit uptake of I-131-MIBG, resulting in less tumour radiation and increased risk of cardiovascular side effects. Azedra consists of the iobenguane molecule radiolabeled with iodine-131 using the company's proprietary Ultratrace technology platform, a technique that avoids large quantities of cold (non-radioactive) iobenguane in the formulation of the product. In previous animal studies, the lack of cold iobenguane suggested two significant clinical benefits: greater tumour uptake and reduced pharmacological toxicity or side effects.

Dr Matthay noted: "The primary aim of this Phase 2a study was to establish the maximum tolerated dose (MTD) of Ultratrace iobenguane I-131 with autologous hematopoietic stem cell (AHSC) support. We showed that Ultratrace iobenguane I-131 with AHSC support is feasible at 18 mCi/kg without significant toxicity and with promising partial and complete responses that support proceeding to a pivotal Phase 2 study at18 mCi/kg."

The primary objectives of the study were to determine MTD and toxicity graded by Common Terminology Criteria for Adverse Events (CTCAE) of Azedra in patients with refractory high-risk neuroblastoma; estimate radiation absorbed doses to measurable lesions and to a standard set of normal organs following a 0.1 mCi/kg intravenous administration of Azedra; and assess objective tumour response following treatment. Secondary objectives include evaluation of objective tumour response by INRC.

Eligible patients were age 1 to 30 years old with resistant neuroblastoma, MIBG uptake, and cryopreserved AHSC. A diagnostic dose of Ultratrace iobenguane (1-5 mCi) was followed by 3 dosimetry scans. The administered therapeutic dose was then adjusted based on absorbed dose estimates and normal organ tolerance limits. AHSC were infused 14 days post therapy. Response and toxicity were evaluated at day 60. The Ultratrace iobenguane was escalated in 3mCi/kg increments from 12-21 mCi/kg using 3+3 design. Dose limiting toxicity was defined as failure to engraft or grade 3 or 4 non-haematologic toxicity except grade 3 pre-defined exclusions. No DLT was observed and there were no related serious adverse events reported. Most commonly reported adverse events (AE) included myelosuppression, gastrointestinal (nausea/vomiting, salivary gland pain/swelling, increased liver function tests, headache and fever. Nearly 80 percent of the reported AEs were Grade 1 and 2 by CTCAE criteria.

Azedra, a novel, targeted radiotherapeutic, recognizes the norepinephrine transporter molecular target that is over-expressed in neuroendocrine tumour cells allowing targeted accumulation at these tumour sites. Azedra, developed using Molecular Insight's proprietary Ultratrace technology, permits more efficient and high specific activity labelling with the therapeutically active 131-Iodine isotope which could result in maximum delivery of the therapeutic potential of iobenguane I 131, a radiotherapeutic currently marketed in Europe to treat neuroendocrine tumours. At a given therapeutic dose, Azedra minimizes the amount of non-radioactive iobenguane molecules administered to the patient, potentially reducing pharmacologic toxicities, especially cardiovascular events or toxicity, and possibly enabling better tolerated and effective treatment.

Azedra is currently in advanced clinical trials for the treatment of malignant pheochromocytoma, a rare, hard-to-access neuroendocrine tumour that develops in the core of an adrenal gland.

Neuroendocrine Tumours Neuroendocrine Tumors (NETs) are rare tumours of the nervous and endocrine systems. Until becoming metastatic, they are typically slowly growing and difficult to diagnose. Functional NETs secrete excess hormone, leading to a variety of clinical syndromes, some life threatening and all adversely affecting quality of life.

A type of NET, neuroblastoma is the most common extracranial solid cancer in childhood and the most common cancer in infancy, with an annual incidence of about 650 new cases per year in the US. Neuroblastoma comprises six to ten percent of all childhood cancers, and fifteen percent of cancer deaths in children. Close to 50 percent of neuroblastoma cases occur in children younger than two years old. This type of malignant tumour arises from any neural crest element of the sympathetic nervous system or SNS. Neuroblastoma most frequently originates in one of the patient's adrenal glands, but can also develop in nerve tissues in the neck, chest, abdomen or pelvis.

Molecular Insight Pharmaceuticals is a clinical-stage biopharmaceutical company and pioneer in molecular medicine. The company is focused on the discovery and development of targeted therapeutic and imaging radiopharmaceuticals for use in oncology.