浩鼎 擴大研發主力 收購臨床前小分子新藥 (TH-3424/ OBI-3424: Threshold Pharmaceuticals)/ Ascenta Pharmaceuticals合作pre-IND動物毒理測試

浩鼎 發言日期106/06/01 發言時間 發言人黃秀美 發言人職稱總經理 發言人電話(02)2786-6589 主旨 說明本公司宣布收購首創抗癌新藥OBI-3424 將開發為治療AKR1C3酵素高度表現癌症之潛力療法 符合條款 第51款 事實發生日106/06/01 說明1.事實發生日:106/06/01 2.公司名稱:台灣浩鼎生技股份有限公司 3.與公司關係(請輸入本公司或子公司):不適用 4.相互持股比例:不適用 5.傳播媒體名稱:中時電子報 6.報導內容:浩鼎生技 (4174)宣布與美國加州Threshold Pharmaceuticals 簽訂合約，取得小分子首創新藥 (first-in-class) TH-3424全球智財權和專利權（但不包括中國、香港、澳門、台灣、日、韓、新加坡、馬來西亞、泰國、土耳其及印度），並重新命名OBI-3424，將開發為治療AKR1C3酵素高度表現癌症之潛力療法，成為浩鼎產品線的新生力軍...。 7.發生緣由:本公司今日宣布與美國加州Threshold Pharmaceuticals 簽訂合約，收購小分子首創新藥 (first-in-class) TH-3424，並重新命名OBI-3424，成為浩鼎產品線的新生力軍。OBI-3424為一化療前驅型新藥，它會選擇性地在AKR1C3酵素作用下，釋出強效DNA烷基化劑；這種選擇性的啟動機制﹐OBI-3424與傳統烷基化藥物，如cyclophosphamide 與ifosfamide有很大區別。根據文獻，AKR1C3在多種抗藥性及難治癌症的腫瘤細胞中均有過度表現，舉例來說，大多數肝細胞癌病人即有AKR1C3高度表現。OBI-3424在臨床前動物試驗中﹐展現了高度抗癌活性，並且對肝細胞癌標準治療藥物sorafenib有抗藥性的動物也有效果。AKR1C3的表現量會在接受去勢療法後上升，因此去勢抗性攝護腺癌亦為OBI-3424的開發方向。另外，美國國家癌症研究院 (National Cancer Institute)也正進行臨床前試驗，研究OBI-3424用於治療T細胞急性淋巴性白血病的效果。此產品另一個特色是，可用免疫染色法測量AKR1C3表現量；亦即試驗將可選擇AKR1C3高度表現的病人，以辨識出最可能對OBI-3424藥物治療產生良好抗癌反應的病人，有利於依此制定相對精準的臨床發展有效策略。根據雙方合約，Threshold將移轉OBI-3424所有權，以及臨床前及製造相關數據予浩鼎；浩鼎將支付Threshold一次性款項，未來則不需另行支付Threshold任何款項或權利金。這項轉讓除了亞洲區部份國家(見註一)外，浩鼎將取得OBI-3424的全球智慧財產及其商務、開發與生產權利。註一: 浩鼎取得全球智財權和專利權，但不包括下列國家/地區:中國、香港、澳門、台灣、日本、韓國、新加坡、馬來西亞、泰國、土耳其及印度。 8.因應措施:無 9.其他應敘明事項:無

浩鼎宣布收購首創抗癌新藥OBI-3424  2017年06月01日彭暄貽 浩鼎生技 (4174)宣布與美國加州Threshold Pharmaceuticals簽訂合約，取得小分子首創新藥 (first-in-class) TH-3424全球智財權和專利權（但不包括中國、香港、澳門、台灣、日、韓、新加坡、馬來西亞、泰國、土耳其及印度），並重新命名OBI-3424，將開發為治療AKR1C3酵素高度表現癌症之潛力療法，成為浩鼎產品線的新生力軍。浩鼎總經理黃秀美表示，將持續臨床前開發﹐並希望發展OBI-3424為表現AKR1C3癌症的優秀治療方案。這個首創新藥強化了浩鼎產品線﹐也引領浩鼎朝世界級癌症生技公司目標更邁進一步。目前規劃加速OBI-3424開發腳步，將在2018年初向美國食品藥物管理局(FDA)提出臨床試驗申請(IND)。浩鼎指出，OBI-3424為一化療前驅型新藥﹐它會選擇性地在AKR1C3酵素作用下﹐釋出強效DNA烷基化劑；這種選擇性的啟動機制﹐OBI-3424與傳統烷基化藥物，如cyclophosphamide 與ifosfamide有很大區別。據雙方合約，Threshold將移轉OBI-3424所有權。及臨床前及製造相關數據予浩鼎；浩鼎將支付Threshold一次性款項，未來則不需另行支付Threshold任何款項或權利金。這項轉讓除了亞洲區部份國家(見註一)外，浩鼎將取得OBI-3424的全球智慧財產及其商務、開發與生產權利。根據文獻，AKR1C3在多種抗藥性及難治癌症的腫瘤細胞中均有過度表現，舉例來說﹐大多數肝細胞癌病人即有AKR1C3高度表現。OBI-3424在臨床前動物試驗中﹐展現高度抗癌活性﹐並且對肝細胞癌標準治療藥物sorafenib有抗藥性的動物也有效果。在去勢動物中﹐AKR1C3的表現量會提升﹐因此去勢抗性攝護腺癌亦為OBI-3424的開發方向。另美國國家癌症研究院 (National Cancer Institute)也正進行臨床前試驗﹐研究OBI-3424用於治療T細胞急性淋巴性白血病的效果。此產品另一個特色是可用免疫染色法測量AKR1C3表現量；亦即試驗將可選擇AKR1C3高度表現的病人﹐以辨識出最可能對OBI-3424藥物治療產生良好抗癌反應的病人，有利於依此制定相對精準的臨床發展有效策略。(工商)

THRESHOLD IS EVALUATING TH-3424, FOR TUMORS THAT OVEREXPRESS AN ENZYME, AKR1C3, THAT MAKES THEM RESISTANT TO RADIATION THERAPY AND CHEMOTHERAPY.  TH-3424 is a novel small-molecule that targets cancers that overexpress high levels of the enzyme aldo-keto reductase 1C3 (AKR1C3). Tumors overexpressing AKR1C3 can be resistant to radiation therapy and chemotherapy. TH-3424 is a prodrug that selectively releases a potent DNA cross-linking agent in the presence of AKR1C3.  TH-3424 is being evaluated for the potential treatment of hepatocellular (liver) cancer (HCC), castration-resistant prostate cancer (CRPC), T-cell acute lymphoblastic leukemias (T-ALL), and other cancers expressing high levels of aldo-keto reductase family 1 member C3 (AKR1C3). Preliminary nonclinical toxicology studies suggested an adequate therapeutic index that the Company believes warrants continued development. The Company is conducting Investigational New Drug (IND)-enabling toxicology studies of TH-3424 in collaboration with Ascenta Pharmaceuticals, Ltd.    

HAROLD E. "BARRY" SELICK, PH.D. CHIEF EXECUTIVE OFFICER  Harold E. "Barry" Selick, Ph.D. joined Threshold as Chief Executive Officer in June 2002. Between June 2002 and July 2007, Dr. Selick was a Venture Partner of Sofinnova Ventures, Inc., a venture capital firm. From January 1999 to April 2002, he was Chief Executive Officer of Camitro Corporation, a biotechnology company. From 1992 to 1999, he was at Affymax Research Institute, the drug discovery technology development center for Glaxo Wellcome plc, most recently as Vice President of Research. Prior to working at Affymax he held scientific positions at Protein Design Labs, Inc. and Anergen, Inc. As a staff scientist at Protein Design Labs, he co-invented the technology underlying the creation of fully humanized antibody therapeutics and applied that to PDL's first product, Zenapax, which was developed and commercialized by Roche for treating kidney transplant rejection. Dr. Selick received his B.S. and Ph.D. from the University of Pennsylvania and was a Damon Runyon-Walter Winchell Cancer Fund Fellow and an American Cancer Society Senior Fellow at the University of California, San Francisco. 

TILLMAN PEARCE, M.D. CHIEF MEDICAL OFFICER  Tillman Pearce, M.D. joined Threshold as Chief Medical Officer in February 2012. From April 2007 until March 2011, Dr. Pearce served as Chief Medical Officer at KaloBios Pharmaceuticals, Inc. Dr. Pearce has approximately 15 years of experience in the biopharmaceutical industry in both Europe and the United States. Prior to joining KaloBios, he was at Protein Design Labs in Paris, France, where he held the position Senior Director, Clinical Research and directed their European office. Between 1997 and 2002, Dr. Pearce was Medical Director at Sanofi-Synthelabo, S.A. in Paris, France, in their Oncology Business Unit. Prior to that, he held the position of Director, Clinical Research at Novartis Pharma AG in Basle, Switzerland. Dr. Pearce received his M.D. from the Medical College of Georgia and is board-certified in both internal medicine and hematology. 

JOEL A. FERNANDES, C.P.A SENIOR VICE PRESIDENT, FINANCE AND CONTROLLER  Joel Fernandes was appointed Threshold's Senior Vice President, Finance and Controller in March 2016. Previously, he served as Threshold's Vice President, Finance and Controller since May 2011 having held roles of increasing responsibility in finance and accounting since joining the company in 2006. Prior to joining Threshold, Mr. Fernandes served as Associate Director of Finance at Theravance Inc., Senior Manager of Corporate Finance at KLA-Tencor, and Assistant Controller of ALZA Corporation. Mr. Fernandes holds a CPA and a Masters in Accountancy from Manchester College, Indiana. 

CHARLES P. HART, PH.D. SENIOR VICE PRESIDENT, BIOLOGY  Charles Hart, Ph.D., was appointed Threshold's Vice President, Biology in 2008. He joined the company as Senior Director, Biology in 2004. Dr. Hart is responsible for in vitro and in vivo preclinical translational studies. Prior to joining Threshold, Dr. Hart was Senior Director, Biology at Galileo Pharmaceuticals, Director of Drug Discovery at Signature Bioscience, and a Research Unit Director at Affymax (a Glaxo company). Dr. Hart holds an A.B. from UC Berkeley, an M.S. from Stanford University, and a Ph.D. in Molecular Biology and Genetics from Yale University. Dr. Hart completed a postdoctoral fellowship at the University of Strasbourg, France. 

ERIC D. MALEK, M.B.A. SENIOR VICE PRESIDENT, CORPORATE DEVELOPMENT  Eric Malek was appointed Threshold's Senior Vice President, Corporate Development in March 2016. Mr. Malek joined Threshold as Vice President, Corporate Development in 2010 and led negotiations for the TH-302 co-development and co-commercialization partnership with Merck KGaA. Prior to joining Threshold, he led corporate development at BiPar Sciences where he initiated the partnering effort that led to BiPar's acquisition by Sanofi-Aventis. Prior to BiPar, Mr. Malek was Vice President, Corporate Development at Allos Therapeutics, where he led the acquisition and product planning efforts for FOLOTYN®, indicated for the treatment of patients with relapsed or refractory peripheral T-cell lymphoma. Before Allos, Mr. Malek held business development positions at Gilead Sciences, NeXstar Pharmaceuticals, Ilex Oncology and Research Corporation Technologies as well as research positions at Janssen Pharmaceuticals. Mr. Malek holds a B.A. in Biochemistry from the University of Arizona and an M.B.A. from the University of Michigan. 

MARK HOPKINS, J.D., PH.D. VICE PRESIDENT OF INTELLECTUAL PROPERTY AND ASSISTANT GENERAL COUNSEL  Mark Hopkins, J.D., Ph.D., joined Threshold as Vice President of Intellectual Property and Assistant General Counsel in July 2015. Dr. Hopkins is responsible for advising the company on a variety of legal issues both domestically and internationally. Dr. Hopkins has more than 16 years of legal experience in the pharmaceutical industry. Prior to joining Threshold, Dr. Hopkins was a partner at Kilpatrick Townsend and Stockton LLP where he led a team of legal professionals providing legal opinions and securing patents for pharmaceutical companies on their key drugs. Dr. Hopkins began his career as a senior scientist and patent agent with the Dow Chemical Company, where he led a multidisciplinary team responsible for lead generation in several novel chemical applications. Dr. Hopkins was an American Cancer Society postdoctoral fellow at Northwestern University, has a J.D. from the John Marshall Law School, a Ph.D. in Chemistry from the University of California, Irvine, and is the author of multiple legal and scientific publications.

KRISTEN QUIGLEY, B.A. VICE PRESIDENT OF CLINICAL OPERATIONS  Kristen Quigley was appointed Vice President of Clinical Operations in October 2016. Ms. Quigley has over 20 years of experience in the pharmaceutical/CRO industry in both Europe and the United States. She joined Threshold in June 2014 as Senior Director of Clinical Operations, leading cross-functional process-improvement initiatives and several successful CRO collaborations on the TH-302 program. Prior to joining Threshold, Ms. Quigley held various Project Management and Clinical Trial Management roles during a 12-year tenure with ICON Clinical Research, the most recent of which was Project Management Senior Director in ICON's Oncology and Hematology Division From 2013-2014. Between 2010-2011, Ms. Quigley was stationed in Stockholm, Sweden as co-Director of ICON's Nordic region. Prior to joining ICON, she held Project Management and Clinical Research Associate roles during a 5-year tenure at Kendle International. Kristen received her B.A. from Washington University in St. Louis.