PRCS Praecis Pharmaceuticals (MM)

PRAECIS PHARMACEUTICALS INCORPORATED (NASDAQ: PRCS) today announced that it is presenting interim clinical data from an ongoing phase 1 trial of its investigational compound, PPI-2458, at the 18th EORTC-NCI-AACR Symposium on �Molecular Targets and Cancer Therapeutics� being held from Tuesday, November 7 to Friday, November 10, 2006 at the Prague Congress Centre in Prague, Czech Republic. The data being presented is entitled �A Phase 1 Dose Escalation Safety & Tolerance Study of PPI-2458 in Subjects with Non-Hodgkin�s Lymphoma or Solid Tumors� (Abstract #139). Additionally, PRAECIS is presenting research on the potential role of PPI-2458 in melanoma in a poster entitled �Effects of PPI-2458, an inhibitor of methionine aminopeptidase type-2 on growth of melanoma and expression of MITF� (Abstract #349). The posters may be viewed on the Company�s website (http://www.praecis.com) in the �Investors� section, under �Presentations.� PPI-2458 - Interim Clinical Data: PPI-2458 is a novel, proprietary, orally available small molecule that specifically targets methionine aminopeptidase-2 (MetAP-2). MetAP-2 has previously been demonstrated to be overexpressed in certain human cancers, including non-Hodgkin�s lymphoma (NHL). Study 2458-04-01 is a multi-center, open-label, dose-escalation study designed to determine the maximum tolerated dose (MTD) of PPI-2458 in patients with NHL or solid tumors. PPI-2458 is administered to subjects orally every other day (QOD) for two 28 day cycles. Subjects are allowed to continue treatment, in the absence of unacceptable toxicity, until evidence of disease progression. The primary endpoint of the study is safety, with disease response being evaluated as a secondary endpoint. Additional secondary endpoints include pharmacokinetic and pharmacodynamic data. Interim results presented include data for 32 subjects that have been treated across 4 dose cohorts ranging from 2 mg to 8 mg. Data to date suggests that PPI-2458 is well tolerated at doses up to 8 mg. The maximum tolerated dose has not been determined and treatment is currently ongoing in a fifth cohort of subjects receiving a 12 mg dose. Results reported for this trial also include investigation of pharmacokinetics, pharmacodynamics and tumor assessments. The pharmacodynamic endpoint is assessed using PRAECIS� proprietary MetAP-2 assay. Results reported show that MetAP-2 in white blood cells is substantially inhibited by PPI-2458 in patients across each cohort. In addition, 7 subjects across the first 4 cohorts have been reported by the clinical investigators to have stable disease at the end of the first 2 cycles of treatment. �Based on study results to date, PPI-2458 appears to be an agent with unique and exciting�mechanisms (MetAP-2 and microphthalmia-associated transcription factor (MITF) protein), and as the Phase 1 study proceeds, there is growing data to support a focused Phase 2 clinical development plan,� stated Dr. J. Paul Eder, Principal Investigator for the Phase 1 clinical trial and Clinical Director of Translational Pharmacology at the Dana-Farber Cancer Institute in Boston, Massachusetts. Dr. Eder continued, �There is indication of substantial target inhibition in a surrogate tissue and we plan to determine the effects of PPI-2458 in patient tumor samples in future cohorts. As the dose has escalated, we have been encouraged by the increased duration of treatment without clinically�significant toxicity that has been observed for these otherwise treatment refractory patients." �We are pleased to see the encouraging safety and tolerability data in this Phase 1 trial and we continue to believe that PPI-2458 holds promise for the treatment of a wide range of cancer types,� stated Kevin F. McLaughlin, President and Chief Executive Officer of PRAECIS. Additional information about the Company�s ongoing clinical trial for PPI-2458 can be accessed on the Internet at www.clinicaltrials.gov. The Company is currently planning Phase 2 clinical development protocols in oncology. PPI-2458 - Preclinical Research in Melanoma: One tumor type of particular interest for PPI-2458 treatment is melanoma. In a poster presented by Gerhard Hannig, Ph.D., Director of Cellular and Molecular Pharmacology, PRAECIS describes data on research of the growth inhibitory effects of PPI-2458 on human melanoma cell lines. These data demonstrate the selective growth inhibition of melanoma cell lines both in cell-based studies and in animal models and illustrate a novel mechanism of action for PPI-2458 in melanoma. This inhibition of melanoma growth appears to be directly linked to MetAP-2 inhibition in these studies. In addition, PRAECIS reports that PPI-2458 decreases the cellular level of microphthalmia-associated transcription factor (MITF) protein, a master regulator of the melanocyte lineage, in melanoma cell lines. Recently, MITF has been shown to be a novel melanoma survival oncogene and this protein may play a potentially important role in the development and progression of melanoma in humans. Melanoma patients with metastatic disease and high MITF expression in tumor tissue tend to have worse overall outcomes than patients with lower levels of this protein in tumor tissue as described in a recent publication in the journal Nature. (Nature 436, 2005, 117) As part of its current planning for further clinical development of PPI-2458 in oncology, PRAECIS will consider this preclinical data on melanoma as well as preclinical and clinical data with respect to several other cancer types. About PRAECIS PRAECIS PHARMACEUTICALS INCORPORATED is a biopharmaceutical company focused on utilizing its proprietary technologies for the discovery and development of novel compounds that have the potential to address unmet medical needs or improve existing therapies. PRAECIS has a novel MetAP-2 inhibitor, PPI-2458, in clinical development for cancer indications, including non-Hodgkin�s lymphoma and solid tumors, an innovative drug discovery technology, DirectSelect�, which enables the generation and practical use of ultra-large libraries for the discovery of orally active compounds for drug development, and a research and development program aimed at identifying one or more selective S1P-1 agonist compounds to take forward into clinical testing. This news release contains forward-looking statements regarding the Company�s continued development of PPI-2458 for cancer and autoimmune disorders. These statements are based on the Company�s current beliefs and expectations as to future outcomes and are not guarantees of such outcomes or of future performance. These statements are subject to numerous risks, uncertainties and assumptions that could cause actual events and results to differ from those expected or anticipated, including, but not limited to, the Company�s ability to continue development of and successfully partner or otherwise obtain funding for its PPI-2458 program, the Company�s ability to continue to manage operating expenses and to retain key employees, unexpected expenditures, the timing and content of decisions made by the FDA, unexpected results in ongoing and future clinical or preclinical trials, and the need for additional research and testing, including as a result of unanticipated determinations by regulatory authorities, as well as the risks set forth from time to time in the Company�s filings with the Securities and Exchange Commission, including but not limited to the various risks discussed in the Company�s Quarterly Report on Form�10-Q for the quarter ended June 30, 2006. The Company undertakes no obligation to update any forward-looking statement made in this press release to reflect new information, events or circumstances after the date of this release. PRAECIS PHARMACEUTICALS INCORPORATED (NASDAQ: PRCS) today announced that it is presenting interim clinical data from an ongoing phase 1 trial of its investigational compound, PPI-2458, at the 18th EORTC-NCI-AACR Symposium on "Molecular Targets and Cancer Therapeutics" being held from Tuesday, November 7 to Friday, November 10, 2006 at the Prague Congress Centre in Prague, Czech Republic. The data being presented is entitled "A Phase 1 Dose Escalation Safety & Tolerance Study of PPI-2458 in Subjects with Non-Hodgkin's Lymphoma or Solid Tumors" (Abstract #139). Additionally, PRAECIS is presenting research on the potential role of PPI-2458 in melanoma in a poster entitled "Effects of PPI-2458, an inhibitor of methionine aminopeptidase type-2 on growth of melanoma and expression of MITF" (Abstract #349). The posters may be viewed on the Company's website (http://www.praecis.com) in the "Investors" section, under "Presentations." PPI-2458 - Interim Clinical Data: PPI-2458 is a novel, proprietary, orally available small molecule that specifically targets methionine aminopeptidase-2 (MetAP-2). MetAP-2 has previously been demonstrated to be overexpressed in certain human cancers, including non-Hodgkin's lymphoma (NHL). Study 2458-04-01 is a multi-center, open-label, dose-escalation study designed to determine the maximum tolerated dose (MTD) of PPI-2458 in patients with NHL or solid tumors. PPI-2458 is administered to subjects orally every other day (QOD) for two 28 day cycles. Subjects are allowed to continue treatment, in the absence of unacceptable toxicity, until evidence of disease progression. The primary endpoint of the study is safety, with disease response being evaluated as a secondary endpoint. Additional secondary endpoints include pharmacokinetic and pharmacodynamic data. Interim results presented include data for 32 subjects that have been treated across 4 dose cohorts ranging from 2 mg to 8 mg. Data to date suggests that PPI-2458 is well tolerated at doses up to 8 mg. The maximum tolerated dose has not been determined and treatment is currently ongoing in a fifth cohort of subjects receiving a 12 mg dose. Results reported for this trial also include investigation of pharmacokinetics, pharmacodynamics and tumor assessments. The pharmacodynamic endpoint is assessed using PRAECIS' proprietary MetAP-2 assay. Results reported show that MetAP-2 in white blood cells is substantially inhibited by PPI-2458 in patients across each cohort. In addition, 7 subjects across the first 4 cohorts have been reported by the clinical investigators to have stable disease at the end of the first 2 cycles of treatment. "Based on study results to date, PPI-2458 appears to be an agent with unique and exciting mechanisms (MetAP-2 and microphthalmia-associated transcription factor (MITF) protein), and as the Phase 1 study proceeds, there is growing data to support a focused Phase 2 clinical development plan," stated Dr. J. Paul Eder, Principal Investigator for the Phase 1 clinical trial and Clinical Director of Translational Pharmacology at the Dana-Farber Cancer Institute in Boston, Massachusetts. Dr. Eder continued, "There is indication of substantial target inhibition in a surrogate tissue and we plan to determine the effects of PPI-2458 in patient tumor samples in future cohorts. As the dose has escalated, we have been encouraged by the increased duration of treatment without clinically significant toxicity that has been observed for these otherwise treatment refractory patients." "We are pleased to see the encouraging safety and tolerability data in this Phase 1 trial and we continue to believe that PPI-2458 holds promise for the treatment of a wide range of cancer types," stated Kevin F. McLaughlin, President and Chief Executive Officer of PRAECIS. Additional information about the Company's ongoing clinical trial for PPI-2458 can be accessed on the Internet at www.clinicaltrials.gov. The Company is currently planning Phase 2 clinical development protocols in oncology. PPI-2458 - Preclinical Research in Melanoma: One tumor type of particular interest for PPI-2458 treatment is melanoma. In a poster presented by Gerhard Hannig, Ph.D., Director of Cellular and Molecular Pharmacology, PRAECIS describes data on research of the growth inhibitory effects of PPI-2458 on human melanoma cell lines. These data demonstrate the selective growth inhibition of melanoma cell lines both in cell-based studies and in animal models and illustrate a novel mechanism of action for PPI-2458 in melanoma. This inhibition of melanoma growth appears to be directly linked to MetAP-2 inhibition in these studies. In addition, PRAECIS reports that PPI-2458 decreases the cellular level of microphthalmia-associated transcription factor (MITF) protein, a master regulator of the melanocyte lineage, in melanoma cell lines. Recently, MITF has been shown to be a novel melanoma survival oncogene and this protein may play a potentially important role in the development and progression of melanoma in humans. Melanoma patients with metastatic disease and high MITF expression in tumor tissue tend to have worse overall outcomes than patients with lower levels of this protein in tumor tissue as described in a recent publication in the journal Nature. (Nature 436, 2005, 117) As part of its current planning for further clinical development of PPI-2458 in oncology, PRAECIS will consider this preclinical data on melanoma as well as preclinical and clinical data with respect to several other cancer types. About PRAECIS PRAECIS PHARMACEUTICALS INCORPORATED is a biopharmaceutical company focused on utilizing its proprietary technologies for the discovery and development of novel compounds that have the potential to address unmet medical needs or improve existing therapies. PRAECIS has a novel MetAP-2 inhibitor, PPI-2458, in clinical development for cancer indications, including non-Hodgkin's lymphoma and solid tumors, an innovative drug discovery technology, DirectSelect(TM), which enables the generation and practical use of ultra-large libraries for the discovery of orally active compounds for drug development, and a research and development program aimed at identifying one or more selective S1P-1 agonist compounds to take forward into clinical testing. This news release contains forward-looking statements regarding the Company's continued development of PPI-2458 for cancer and autoimmune disorders. These statements are based on the Company's current beliefs and expectations as to future outcomes and are not guarantees of such outcomes or of future performance. These statements are subject to numerous risks, uncertainties and assumptions that could cause actual events and results to differ from those expected or anticipated, including, but not limited to, the Company's ability to continue development of and successfully partner or otherwise obtain funding for its PPI-2458 program, the Company's ability to continue to manage operating expenses and to retain key employees, unexpected expenditures, the timing and content of decisions made by the FDA, unexpected results in ongoing and future clinical or preclinical trials, and the need for additional research and testing, including as a result of unanticipated determinations by regulatory authorities, as well as the risks set forth from time to time in the Company's filings with the Securities and Exchange Commission, including but not limited to the various risks discussed in the Company's Quarterly Report on Form 10-Q for the quarter ended June 30, 2006. The Company undertakes no obligation to update any forward-looking statement made in this press release to reflect new information, events or circumstances after the date of this release.