2015年2月25日讯 /生物谷BIOON/ --当前，PD-1/PD-L1肿瘤免疫疗法领域竞争异常激烈，该领域的佼佼者——百时美施贵宝、默沙东、罗氏、阿斯利康均在火速推进各自的临床项目，同时也正通过广泛的合作及收购交易进一步扩充各自的资产。继今年1月中旬与礼来达成临床合作之后，该领域公认的领导者——百时美施贵宝（BMS）近日又爆出大动作，将以12.5亿美元重金收购美国私人生物技术公司Flexus BioSciences，进一步扩充其免疫肿瘤学资产。该笔交易包括8亿美金的前期付款及高达4.5亿美金的研发里程碑款项。目前，该笔交易已获双方董事会及Flexus股东一致批准，预计将于2015年第一季度完成。
此次收购，将使百时美获得Flexus临床前小分子IDO1抑制剂F001287的全部权利，同时也将获得Flexus广泛的IDO/TDO开发项目，包括IDO选择性、IDO/TDO双选择性、TDO选择性化合物文库。百时美表示，通过收购Flexus，将充分发掘IDO/TDO靶向免疫疗法与自身免疫肿瘤学资产（包括Yervoy和Opdivo）组合疗法的最大潜力。
此前，百时美已先后与生物技术巨头新基（Celgene）、FivePrime、日本小野制药（Ono Pharmaceutical）、协和发酵麒麟（Kyowa Hakko Kirin）、礼来（Eli Lilly）就明星肿瘤免疫疗法Opdivo达成了广泛的临床合作协议。
值得一提的是，错过这场游戏的美国巨头辉瑞（Pfizer），在去年1200亿美元收购阿斯利康未能如愿的背景下，也开始重金打造自己的免疫肿瘤学资产，该公司去年11月与德国制药巨头默克（Merck KGaA）签订28.5亿美元合作协议宣布进入免疫肿瘤学领域。之后与比利时生物技术公司iTeos Therapeutics签署全球独家授权协议，获得了数个免疫肿瘤学早期资产，其中就包括靶向IDO/TDO的抑制剂。
关于IDO和TDO：
吲哚胺2,3-双加氧酶（IDO）和色氨酸2,3-加氧酶（TDO）是分解色氨酸（tryptophan）的2种重要酶，在多种肿瘤细胞及周围微环境细胞中表达，可局部降解色氨酸，钝化免疫系统的肿瘤监视作用及防止肿瘤排斥。针对这2种酶的特异选择性抑制剂，能够解放机体的防御系统，并帮助T细胞更好地攻击肿瘤，因此具有治疗广泛类型肿瘤的潜力。另外，在肿瘤中通常只表达其中一种酶，而对于同时表达IDO和TDO的肿瘤，联合利用IDO抑制剂和TDO抑制剂具有互补的优势，有望用于癌症的个性化治疗。
Flexus BioSciences成立于2013年，位于美国加州圣卡洛斯( San Carlos )，，是一家私人持有的生物技术公司，致力于发现、开发和商业化靶向调节性T细胞的小分子肿瘤免疫疗法——肿瘤免疫抑制逆转疗法（ARTIS）。
英文原文：Bristol-Myers Squibb To Expand Its Immuno-Oncology Pipeline with Agreement to Acquire Flexus Biosciences, Inc.
-Gains full rights to Flexus’ lead preclinical IDO1 inhibitor F001287 and the company’s broad IDO/TDO discovery program
-Enables Bristol-Myers Squibb to fully explore the potential of IDO/TDO targeted immunotherapies in combination with its immuno-oncology portfolio
NEW YORK & SAN CARLOS, Calif.--(BUSINESS WIRE)--Bristol-Myers Squibb Company (NYSE: BMY) and Flexus Biosciences, Inc. announced today the companies have signed a definitive agreement under which Bristol-Myers Squibb will acquire all of the outstanding capital stock of Flexus, a privately held biotechnology company focused on the discovery and development of novel anti-cancer therapeutics. The transaction has a potential total consideration of $1.25 billion, including $800 million upfront and development milestones that, upon achievement, could total up to $450 million. The transaction has been approved by the boards of directors of both companies and by the stockholders of Flexus.
The acquisition will give Bristol-Myers Squibb full rights to F001287, Flexus’ lead preclinical small molecule IDO1-inhibitor targeted for IND filing in the second half of 2015. In addition, Bristol-Myers Squibb will acquire Flexus’ IDO/TDO discovery program which includes its IDO-selective, IDO/TDO dual and TDO-selective compound libraries. A newly formed entity established by the current shareholders of Flexus will retain, from and after the closing, all non-IDO/TDO assets of Flexus including those related to Flexus’ Phase 1 FLT3 and CDK4/6 inhibitor, its earlier stage small-molecule Treg cancer immunotherapy programs, and its current personnel and facilities.
“Bristol-Myers Squibb is committed to leading scientific advances in immuno-oncology and our acquisition of Flexus will expand our innovative pipeline with an important approach to enhancing immune responses in cancer,” said Francis Cuss, MB BChir, FRCP, executive vice president and chief scientific officer, Bristol-Myers Squibb. “With the addition of a potentially best-in-class IDO1 inhibitor and the broad IDO/TDO programs, Bristol-Myers Squibb will accelerate its ability to explore numerous immunotherapeutic approaches across tumor types, including combinations with our biologic checkpoint and co-stimulatory agents that target different and complementary pathways.”
“Bristol Myers Squibb is a recognized leader in the cancer immunotherapy field, and we are delighted with the opportunity to have their organization advance the development of our potentially best-in-class IDO/TDO inhibitors and to bring more innovative cancer immunotherapies to patients,” said Terry Rosen, Ph.D., Chief Executive Officer of Flexus Biosciences. “With the consummation of this acquisition, we will continue to advance our oncology and immuno-oncology pipeline of Agents for Reversal of Tumor Immunosuppression (ARTIS) in the newly created spin-off, with the strong support of our committed group of investors.”
Bristol-Myers Squibb and Flexus anticipate the transaction will close during the first quarter of 2015. Closing of the transaction is subject to customary closing conditions, including clearance under the Hart-Scott-Rodino Antitrust Improvements Act.
Citi acted as exclusive advisor to Flexus on the transaction and Gunderson Dettmer acted as legal counsel. Kirkland & Ellis LLP is serving as legal advisor to Bristol-Myers Squibb in connection with the transaction.
About IDO/TDO
IDO and TDO are enzymes expressed by many tumor cells and cells in the surrounding microenvironment that suppress T-cell function by producing a potent immunosuppressive factor, kynurenine, thus inhibiting the immune system from identifying and destroying certain types of tumors. IDO/TDO inhibitors reduce kynurenine production enabling the immune system to attack tumors more effectively. Given the immuno-modulatory effects of IDO/TDO inhibitors, strong scientific rationale supports exploring combination regimens with immunotherapies where synergistic activity may enhance long-term survival benefits for patients.