浩鼎300萬美金購 OBI-3424 (TH-3424,Threshold)開花待果：未含中/日/印/新/馬/泰/土

Threshold Pharma completes sale of TH-3424 to OBI Pharma for $3M，Jun. 22, 2017 Threshold Pharmaceuticals (NASDAQ:THLD) finalizes the sale certain rights to cancer candidate TH-3424, a small molecule prodrug, to Taiwan's OBI Pharma for total consideration of $3M.

Eighteen months after being poleaxed by the failure of its lead drug, Threshold Pharma's recovery efforts—including a planned merger—are looking brighter thanks to a licensing deal with Taiwan biotech OBI Pharma. OBI is buying rights to TH-3424—billed by Threshold as a first-in-class drug targeting cancers that overexpress the enzyme aldo-keto reductase 1c3 (AKR1C3)—for an undisclosed, one-off payment. The Taiwan firm gets rights to the drug in all world markets, but excluding several Asian countries including China, Japan and India. The drug, which will be renamed OBI-3424, is a prodrug that releases a tumor cell-killing alkylating agent in the presence of AKR1C3, seen in a number of hard-to-treat cancers, including liver and prostate cancer as well as T-cell acute lymphoblastic leukemia. OBI says it plans to file for approval to start trials in the U.S. early next year. In December 2015, Threshold was hit by the failure of its lead cancer drug evofosfamide (TH-302)—formerly partnered with Merck KGaA—in two phase 3 trials, and the following year a second candidate called tarloxotinib flunked a phase 2 proof-of-concept study in skin cancer and was dropped. Threshold still hasn't wholly given up on the drug, as it maintains it saw an improvement in overall survival among a subset of Asian patients in Merck's MAESTRO study. Discussions with the Japanese authorities about the possibility of a marketing application based on the data came to naught, however, and the company has been informed it has to carry out another trial. For now, its focus on evofosfamide is on a clinical trial looking at the drug in combination with Bristol-Myers Squibb's checkpoint inhibitor Yervoy—which is being carried out in collaboration with MD Anderson Cancer Centre—and on investigator-led trials of the drug alongside angiogenesis inhibitor drugs. In a recent SEC filing, Threshold said it had resources on hand for another 12 months or so of operations and was looking at partnering TH-3424 and possibly another early-stage candidate—PET imaging agent HX4—to help fund future development of evofosfamide. The embattled biotech called in strategic advisers in the wake of the phase 3 failure to work out which way to turn, and in March agreed a merger with Molecular Templates, pooling their respective cancer pipelines with a $20 million venture cash injection pledge from Longitude Capital. That deal hasn't yet gone through, but if it comes to fruition will see the two companies operate under the Molecular Templates banner, adding the latter's lead candidate MT-3724, an anti-CD20 drug in a phase 1 trial that has shown activity in heavily pre-treated non-Hodgkin lymphoma (NHL) patients, to their joint pipeline. With the OBI licensing deal in hand, Threshold's appeal to its would-be merger partner looks likely to have gone up.

Threshold Pharmaceuticals and National Cancer Institute to Collaborate on Drug Candidate TH-3424 December 19, 2016 08:02 ET | Source: Threshold Pharmaceuticals, Inc.-- Preclinical studies will explore the effects of TH-3424 against T-cell acute lymphoblastic leukemia cancer cell lines with high AKR1C3 expression --SOUTH SAN FRANCISCO, Calif., Dec. 19, 2016 (GLOBE NEWSWIRE) -- Threshold Pharmaceuticals, Inc. (NASDAQ:THLD), a clinical-stage biopharmaceutical company developing novel therapies for cancer, today announced that it has entered into a collaboration with the National Cancer Institute (NCI), part of the National Institutes of Health (NIH), to study TH-3424, the company's new drug candidate for the treatment of cancer. The collaboration will explore the effects of TH-3424 against T-cell acute lymphoblastic leukemia (T-ALL) xenograft cell lines with high AKR1C3 expression. The studies will be conducted through the NCI-funded Pediatric Preclinical Testing Consortium (PPTC). Under this collaboration, Threshold will supply TH-3424, and the NCI will fund the studies that will be conducted at the PPTC leukemia research program led by Professor Richard Lock of Children's Cancer Institute (Sydney, Australia). TH-3424 is a novel, small-molecule compound invented at Threshold with potentially broad anticancer properties. TH-3424 is activated by the enzyme AKR1C3, which is over-expressed in a number of different cancers, to release a cytotoxic agent directly to the tumor. Preclinical results showed that TH-3424 is effective in a variety of human xenograft models of cancer, as initially presented at the American Association for Cancer Research Annual Meeting in April 2016."TH-3424 is designed to be activated by AKR1C3 inside tumor cells and spare healthy tissue," said Barry Selick, Ph.D., CEO of Threshold Pharmaceuticals. "Evaluating this compound in collaboration with the NCI enables us to expand the scope of our investigations to better inform our strategy for potential future clinical studies for this molecule."

About TH-3424 TH-3424 is a small-molecule drug candidate being evaluated for the potential treatment of hepatocellular cancer (HCC), castrate 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). Tumors overexpressing AKR1C3 can be resistant to radiation therapy and chemotherapy and immunotherapy. TH-3424 is a prodrug that selectively releases a potent DNA cross-linking agent in the presence of AKR1C3. Investigational New Drug (IND)-enabling toxicology studies are being done in collaboration with Ascenta Pharmaceuticals, Ltd.

OBI-3424(TH-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。根據雙方合約，Threshold將會移轉OBI-3424所有權。及臨床前和製造相關數據予浩鼎；浩鼎將支付Threshold一次性款項，未來則不需要另行支付Threshold任何款項或權利金。這項轉讓除了亞洲區部份國家（不包括大陸、香港、澳門、台灣、日、韓、新加坡、馬來西亞、泰國、土耳其及印度）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。

延伸一窺: 深圳艾衡昊医药(仙瞳资本)+台灣浩鼎: 癌藥AST-3424（OBI-3424）: FDA准進臨床I/II期 !

深圳艾衡昊医药(仙瞳资本)+台灣浩鼎: 癌藥AST-3424（OBI-3424）: FDA准進臨床I/II期 !

迎接生技月行情 類股族群再啟航 2018-07-09 16:14中央社 台北9日電美國那斯達克生技類股指數NBI大漲3.72%，創1月30日來收盤新高，加上生技月將在18日登場，台股生技族群重捨活力，今天由保瑞、寶齡富錦、科妍漲停領軍，帶動生技股再度啟航。不畏美中貿易大戰，觀察最能代表生技業表現的美國那斯達克生技類股指數(NASDAQ BiotechnologyIndex，簡稱NBI)，從4月底的3254.85點來到7月6日的3656.5點，2個多月以來漲幅逾12%，7月6日NBI更跳空大漲3.72%、收3656.50點，創1月30日以來收盤新高。其中，美國生技製藥公司Biogen Inc.與日本製藥商衛材株式會社(Eisai Co.)宣布，攜手開發的阿茲海默藥物在中期試驗階段展現不錯的臨床結果，消息傳來激勵Biogen暴衝19.63%、收357.48美元，創10多年來最大單日漲幅。美國生技類股指數亮眼，加上生技展即將登場，台灣生技類股也開始蘊釀生技月行情。觀察今天盤面表現，高價生技個股精華、大江股價休息，資金轉向先前表現活潑的保瑞、寶齡富錦、科妍等個股點火，3檔人氣指標股分別攻抵115.5元、86.5元及69.3元漲停價，帶動生技股人氣。上櫃生技指數今天成交比重為11.95%，漲幅為1.53%，僅次於觀光類股。上市生技股指數漲幅1.8%，表現同樣不俗。台灣兩大新藥廠浩鼎及智擎陸續於上週末傳出喜訊，浩鼎抗癌新藥OBI-3424獲FDA孤兒藥資格，智擎胰腺癌新藥於歐盟第三國上市，獲300萬美元里程碑授權金，合約新台幣9000萬元，可挹注智擎每股盈餘(EPS)約0.61元。浩鼎及智擎今天表現相對強勢，浩鼎尾盤收在157.5元，上漲8.5元，漲幅5.7%；智擎以132元作收，上漲4元，漲幅3.13%。另外一檔大型股晟德重要孫公司蘇州東曜藥業完成新一波募資，成功引進策略投資夥伴，除使股東結構更加多元外，依IFRS規定，也將認列處分投資利益約14.91億元，影響EPS約為4.65元。今天股價漲幅高達6.45%，以72.6元作收重新站上所有均線之上。晟德表示，新一輪資金將有助於東曜持續專注於高端抗腫瘤藥物的開發，並打造抗腫瘤藥物研發技術平台，其中包括生物藥技術、溶瘤病毒技術及特殊劑型藥物等技術。

艾衡昊抗癌新药AST-3424（OBI-3424）获得FDA核准进入 I/II期临床试验04-23,2018深圳艾衡昊医药科技有限公司（以下简称"艾衡昊"，是仙瞳资本投资企业）今天宣布，美国食品暨药物管理局（FDA）已核准该公司和台湾浩鼎生技公司（以下简称浩鼎）共同开发的新药AST-3424 （OBI-3424），针对醛酮还原酶（AKR1C3）有高度表达的实体瘤展开的I/II期临床试验。该试验已选定在全美癌症学术居于领导地位研究机构：德州大学MD安德森癌症中心(M.D. Anderson Cancer Center）、俄亥俄州立大學的The James Cancer Hospital and Solove Research Institute进行。AST3424是由艾衡昊董事长段建新博士首创研发的抗癌新药，其具有针对多种肿瘤，特别是耐药肿瘤微环境中醛酮还原酶（AKR1C3）高度表达作为靶向，精准高选择释放强效DNA烷基化剂杀死肿瘤细胞的特点。AST-3424另一特点是，可用免疫染色法来测量AKR1C3表现量，籍此选择AKR1C3高度表现的病人。目前向中国CFDA申报I/II期临床试验的准备工作已完成，即将递交申请。中国的临床试验将在广谱的醛酮还原酶（AKR1C3）高度表达瘤种中，选择中国高发并临床急需安全有效药物，同时这一瘤种中绝大多数患者的醛酮还原酶（AKR1C3）高度表达的肝癌、T-细胞白血病和T细胞淋巴瘤最先进入临床试验。中国的临床试验预计将在2018年底展开，秦叔逵教授和李进教授将主持肝癌等实体瘤的临床研究，马军教授将主持T-细胞白血病和T-细胞淋巴瘤的临床研究。艾衡昊董事长段建新博士表示，公司有多个技术平台研发针对肿瘤或疾病微环境，精准投放治疗药物，目前产品管线布局已完成，AST-3424作为第一个进入临床试验的药物，标志着公司的产品开始进入临床研发阶段。艾衡昊已经取得AST-3424亚洲专利权，如中国、香港、澳门、台湾、日本、韩国、新加坡、马来西亚、泰国、土耳其及印度等。

浩鼎抗癌新藥OBI-3424 獲FDA孤兒藥資格認定  2018年07月08日 17:48 工商 杜蕙蓉 台灣浩鼎生技(4174）今(8)日宣布，該公司積極研發的抗癌新藥OBI-3424，已獲美國食品和藥物管理局（FDA）肝細胞癌（HCC）治療的孤兒藥資格認定。OBI-3424是以醛酮還原酶（AKR1C3）為標靶的DNA烷化首創型癌症治療藥物，它對於過度表現醛酮還原酶（AKR1C3）的腫瘤，可選擇性釋放強效DNA烷化劑，達到抗癌目的。OBI-3424在今年四月獲FDA核准展開臨床試驗(IND)，以肝細胞癌（HCC）和去勢抵抗性前列腺癌（CRPC）等固體腫瘤患者為對象的第一/二期臨床試驗，已在美國德克薩斯大學安德森癌症中心開始收案。浩鼎總經理黃秀美指出，OBI-3424獲FDA認定為孤兒藥，是該藥開發重要的里程碑。由於標靶性肝癌治療方式極其有限，研發OBI-3424目的在尋求新的治療選擇。OBI-3424獲得孤兒藥資格認定，顯示FDA認為對開發新型標靶治療藥物有迫切的需求，希望未來OBI-3424在這些癌症治療能發揮效果。

艾衡昊医药在2017年国际分子标靶与癌症治疗大会上 发布旗下新药AST-3424研究成果 仙瞳资本 2017-11-22 研究成果显示，AST-3424在有AKR1C3还原酶表达的T细胞急性淋巴性白血病（T-ALL）的患者来源肿瘤异种移植（PDX）模型中表现出优异的抗肿瘤活性。深圳艾衡昊医药科技有限公司（以下简称"艾衡昊"、'ASCENTA'或"公司"）于美国东部时间2017年10月29日在美国费城召开的由美国癌症研究学会-美国国家癌症研究院-欧洲癌症研究与治疗组织(AACR-NCI-EORTC)主办的国际分子标靶和癌症治疗大会上，报告AST-3424在T细胞急性淋巴性白血病（T-ALL）的患者来源肿瘤异种移植（PDX）模型研究结果。该报告由澳洲雪梨的Lowy癌症研究中心的儿童癌症研究所白血病生物学计划负责人Richard B. Lock教授发布。此研究经费来源为美国国家癌症研究院(NCI)，经费CA199222及CA199000，并由美国国家研究院儿科临床前试验联合会执行。研究显示，AST-3424耐受性良好，仅有2.8%的接受药物治疗组的受试者出现毒性反应。AST-3424在可评估PDX模型上，在所有接受药物治疗的无事件存活率（EFS）分布，与控制组相比，都有显著的差别（治疗组样本数为9，比率为百分之百）。肿瘤生长延迟值(T-C values)分布在17.1至65.2(T/C 2.3-14.0)，在9个治疗组样本中，有8个出现客观缓解(objectiveresponses) (2个完全缓解, CRs；6个维持客观缓解, MCRs)。在6个可评估的T-ALLPDX样本中，有4个样本的28天骨髓浸润为显著降低(P<0.0001)。AKR1CR酶素在ALL PDX模型的生体内反应的重要性，在以B细胞前驱的ALL PDX模型(ALL-11)验证，此为以慢病毒载体传染稳定过度表现的AKR1C3 (ALL/11/1C3)，并与空载体控制组比较(ALL-11/EV)。植入ALL-11/1C3的小鼠，其MCR T-C值>37.3天，T/C>3，相较之下ALL-11/EV之CR为T-C 21.1 天, T/C 2.5。AST-3424治疗组的ALL-11/1C3细胞对鼠骨髓浸润的程度，与控制组小鼠相比，显著下降(P<0.0001)，但植入ALL-11/EV的小鼠并无显示此现象。此次研究成果的报告人、澳洲儿童癌症研究所白血病生物学计划负责人Richard B. Lock教授表示:"AST-3424是我们12年来在澳洲儿童癌症研究所做的临床前侵略性儿童ALL研究中，对T-ALL治疗最有效的药物之一。对于AST-3424改善这种侵略性癌症病人的治疗以及生活品质的潜力，我们感到非常地兴奋，并期待人体临床试验来评估这个药物的潜力。」"艾衡昊亚洲地区以外的合作伙伴浩鼎研发长游丞德博士暨临床药学士表示:"我们期待看到AST-3424的进一步开发，以满足表现AKR1C3癌症病人的治疗需求。此外，AST-3424的临床试验申请(IND) 预计于2018年早期，向美国食品药物管理局 (FDA) 提出。"与此同时，艾衡昊计划在2018年初向中国食品药物管理局（CFDA）提出AST-3424临床申請(IND)。