MIPI Molecular Insight Pharmaceuticals (MM)

Molecular Insight Pharmaceuticals, Inc. (NASDAQ: MIPI) announced today the publication of a preclinical study describing the synthesis and initial evaluation of two series of radiolabeled small molecules that target prostate-specific membrane antigen (PSMA), a validated molecular marker for prostate cancer. The lead compounds, MIP-1072 and MIP-1095, demonstrated high affinity and specific binding to PSMA on human prostate cancer cells, and the radiolabeled analogs provide the foundation for the Company�s Trofex prostate cancer molecular imaging program, which is currently undergoing an exploratory Phase 1 clinical trial in patients with histological confirmed prostate cancer and evidence of recurrent disease. The goal of the clinical trial is to select the more promising of the two compounds for further clinical development and commercialization. The study was published as a manuscript in the Journal of Medicinal Chemistry, a leading peer-reviewed scientific journal. In the manuscript, Molecular Insight reported on the structure activity relationship of two series of heterodimeric small molecules based on the glutamate-urea-lysine pharmacophore; the benzyl-lysine series, which includes MIP-1072, and the phenylureido-lysine series, which includes MIP-1095. The study examined the nature and position of the halogen atom on the aryl ring in each of the classes of compounds. The manuscript can be found through this link: http://dx.doi.org/10.1021/jm800994j. An abstract is presented below. Prostate cancer is the second leading cause of cancer-related deaths in men in the United States, and research shows that approximately 1 in 6 men will be affected by this disease in his lifetime. Molecular Insight�s Trofex program is designed to fill an important need in prostate cancer disease management by identifying and staging tumors, particularly in metastatic disease where patients have no obvious symptoms other than increasing levels of the established biomarker, prostate specific antigen (PSA). Detection and staging are important in designing appropriate treatment regimens for patients. MIP-1072 and MIP-1095 both target PSMA, a protein that is highly expressed by prostate tumors. �The discovery and characterization of these novel small molecule radiopharmaceuticals targeting PSMA represents a milestone in the battle against prostate cancer. It is extremely challenging to detect recurrent disease despite the availability of several imaging modalities, and no single technique is effective in simultaneously detecting both soft tissue and bony metastases. Trofex has the potential to fill a critical unmet medical need and aid in the management of patient care,� said Daniel George, M.D., Associate Professor of Medicine and Surgery, and co-Director of the Duke Prostate Center at Duke University Medical Center. Dr. George is a nationally-recognized physician and researcher in the field of clinical urological oncology. �The results of this study support Molecular Insight�s small molecule approach to the discovery and development of molecular imaging radiopharmaceuticals,� said John W. Babich, Ph.D., Chairman and Chief Executive Officer of Molecular Insight, and an author on the study. �The Trofex program is currently undergoing an exploratory Phase 1 clinical trial to determine which compound, MIP-1072 or MIP-1095, to progress into further clinical development, and we plan to complete this trial in the first half of 2009. In addition to Trofex, our molecular imaging radiopharmaceutical pipeline also includes Zemiva�, which is in clinical development for the detection of cardiac ischemia in the emergency department setting.� The study published in the Journal of Medicinal Chemistry is titled �A Series of Halogenated Heterodimeric Inhibitors of PSMA as Radiolabeled Probes for Targeting Prostate Cancer.� Authors on the study include: Kevin P. Maresca, Shawn M. Hillier, Frank J. Femia, Donna Keith, Chris Barone, Craig N. Zimmerman, John A. Barrett, William C. Eckelman, John L. Joyal and John W. Babich of Molecular Insight Pharmaceuticals, Inc., Cambridge, MA; and Allan P. Kozikowski of the Department of Medicinal Chemistry and Pharmacognosy at the University of Illinois at Chicago, Chicago, IL. The Trofex preclinical data were also presented as a poster, entitled �The Development of an SAR with Small Molecule Inhibitors of Prostate Specific Membrane Antigen (PSMA),� in June 2008 at the Society of Nuclear Medicine (SNM) 55th Annual Meeting. About Molecular Insight Pharmaceuticals, Inc. Molecular Insight Pharmaceuticals (NASDAQ: MIPI) is a biopharmaceutical company specializing in the emerging field of molecular medicine, applying innovations in the identification and targeting of disease at the molecular level to improve healthcare for patients with life-threatening diseases. The Company is focused on discovering, developing and commercializing innovative molecular imaging radiopharmaceuticals and targeted molecular radiotherapeutics with initial applications in the areas of cardiology and oncology. Molecular Insight�s lead molecular imaging radiopharmaceutical product candidate, Zemiva, is being developed for the diagnosis of cardiac ischemia, or insufficient blood flow to the heart. The Company�s imaging candidate, Trofex, is in development for the detection of metastatic prostate cancer. Molecular Insight�s lead molecular radiotherapeutic product candidates, Azedra� and Onalta�, are being developed for detection and treatment of cancer. In addition, the Company has a growing pipeline of product candidates resulting from application of its proprietary platform technologies to new and existing compounds. Molecular Insight Pharmaceuticals is based in Cambridge, Massachusetts and its website address is: www.molecularinsight.com. Forward-Looking Statements Statements in this release that are not strictly historical in nature constitute "forward-looking statements." Such statements include, but are not limited to, statements about the development of AzedraTM, OnaltaTM, ZemivaTM, Trofex� and our other product candidates. Such forward-looking statements involve known and unknown risks, uncertainties, and other factors that may cause the actual results of Molecular Insight to be materially different from historical results or from any results expressed or implied by such forward-looking statements. These factors include, but are not limited to, risks and uncertainties related to the progress, timing, cost and results of clinical trials and product development programs; difficulties or delays in obtaining regulatory approval for product candidates; competition from other pharmaceutical or biotechnology companies; and the additional risks discussed in filings with the Securities and Exchange Commission (SEC). The Company�s SEC filings are available through the SEC�s Electronic Data Gathering Analysis and Retrieval system (EDGAR) at www.sec.gov. Press releases for Molecular Insight Pharmaceuticals, Inc. are available on our website:�www.molecularinsight.com. If you would like to receive press releases via email, please contact: investor@molecularinsight.com. All forward-looking statements are qualified in their entirety by this cautionary statement, and Molecular Insight undertakes no obligation to revise or update this release to reflect events or circumstances after the date hereof. A Series of Halogenated Heterodimeric Inhibitors of PSMA as Radiolabeled Probes For Targeting Prostate Cancer K. P. Maresca1, S. M. Hillier1, F. J. Femia1, D. Keith1, C. Barone1, J. L. Joyal1, C. N. Zimmerman1, A. P. Kozikowski2, J. A. Barrett1, W. C. Eckelman1, and J. W. Babich1*. 1 Molecular Insight Pharmaceuticals, Inc., 160 Second Street, Cambridge, MA 02142, USA. 2 Department of Medicinal Chemistry J. Med. Chem., Article Publication Date (Web): December 29, 2008 Copyright � 2008 American Chemical Society Abstract: Prostate specific membrane antigen (PSMA) is a validated molecular marker for prostate cancer. A series of glutamate-urea (Glu-urea-X) heterodimeric inhibitors of PSMA were designed and synthesized where X ) ?-N-(o-I, m-I, p-I, p-Br, o-Cl, m-Cl, p-Cl, p-F, H)-benzyl-Lys and ?-(p-I, p-Br, p-Cl, p-F, H)-phenylureido-Lys. The affinities for PSMA were determined by screening in a competitive binding assay. PSMA binding of the benzyllysine series was significantly affected by the nature of the halogen substituent (IC50 values, Cl < I) Br , F ) H) and the ring position of the halogen atom (IC50 values, p-I < o-I , m-I). The halogen atom had little affect on the binding affinity in the para substituted phenylureido-Lys series. Two lead iodine compounds were radiolabeled with 123I and 131I and demonstrated specific PSMA binding on human prostate cancer cells, warranting evaluation as radioligands for the detection, staging, and monitoring of prostate cancer.