Celgene与OncoMed签署$33亿协议开发6种抗-癌症干细胞产品
2013-12-04 09:54:54   来源：生物谷 作者：tomato    

2013年12月3日讯 /生物谷BIOON/ --新基（Celgene）和OncoMed制药12月2日联合宣布，双方已达成了一项高达33亿美元的协议，共同开发和商业化OncoMed生物制剂研发管线中的6种抗-癌症干细胞（cancer stem cell，CSC）候选产品，包括单抗药demcizumab（OMP-21M8，Anti-DLL4）。

OncoMed将控制并开展初步的临床研究，Celgene拥有这6种新颖抗-癌症干细胞（anti-CSC）候选药物全球授权的选择权。OncoMed保留其中5种药物的全球共同开发权利和美国的联合商业化权利，同时美国利润将以50/50平分，此外，OncoMed还将获得产品在其他地区销售的特许权使用费。Celgene也将拥有研究、开发和商业化小分子化合物的权利，用于一种未披露的癌症干细胞信号通路。

Celgene将获得OncoMed在临床开发中走的最远的药物demcizumab的独家选择权利。目前，demcizumab正处于3个临床Ib期试验中，与标准护理药物联合用药，其中一项试验，正评估demcizumab用于晚期胰腺癌的一线治疗。

除了demcizumab，该项合作还包括多达5种临床前或发现阶段的生物制剂项目：抗DLL4/VEGF双特异性抗体，以及靶向RSPO-LGR CSC通路或一个未披露的CSC通路的4种生物制剂项目。在OncoMed完成这些项目的I期临床后，Celgene将获得这些项目的独家选择权利。

根据协议条款，OncoMed将获得一笔1.55亿美元的预付款，同时Celgene将以每股15.13美元的价格买入约2225万美元由OncoMed新发行的定向增发（即私募，private placement）普通股。

同时OncoMed还将有资格获得总额高达30亿美元的期权行使付款（option exercise payments）及实现开发、监管、商业化里程碑付款。对于demcizumab，这些款项总额高达7.9亿美元。对于抗-DLL4/VEGF双特异性抗体，这些款项总额可能高达5.05亿美元。对于其他4种生物制剂，每个项目将有资格获得的款项总额高达4.4亿美元。此外，OncoMed还有可能从小分子项目中获得超过1亿美元的款项。

关于癌症干细胞（Cancer Stem Cells，CSCs）：

癌症干细胞是肿瘤中的一个细胞亚群（subpopulation），负责驱动肿瘤的生长和转移。癌症干细胞也称为肿瘤起始细胞，显示出某些特性，包括：通过自我更新的过程分裂并产生新的CSCs，分化或转变成能形成肿瘤实质的其他细胞。常见的抗癌药物，靶向于肿瘤实质细胞（bulk tumor cells），但对CSCs的作用十分有限，从而为肿瘤复发提供了途径。OncoMed已将5种独特的抗CSC靶向候选产品推进至临床试验，其中包括demcizumab（OMP-21M18）。这些候选产品，与目前的新一代化疗和靶向制剂不同，有望显著影响癌症的治疗，并改善癌症患者的临床善后。

关于demcizumab (OMP-21M18)：

demcizumab是一种人源化的单克隆抗体，能够抑制Notch信号通路中的Delta样配体4（Delta-Like Ligand 4，DLL4）。目前正在开展2个Ib期组合试验，将demcizumab与标准护理联合用于晚期胰腺癌的一线治疗，以及将demcizumab与标准护理药物卡铂和培美曲唑联合用于晚期非小细胞肺癌（NSCLC）的一线治疗。此外，在MD安德森癌症中心开展的一项Ib/II期试验，正评价将demcizumab与紫杉醇联合用于铂类耐药性卵巢癌的治疗。

关于OncoMed制药：

OncoMed是一家临床阶段的制药公司，专注于发现和开发靶向癌症干细胞的新颖疗法。该公司有5个抗癌候选产品处于临床开发阶段，包括demcizumab (Anti-DLL4, OMP-21M18)、OMP-59R5 (Anti-Notch2/3)、OMP-52M51 (Anti-Notch1)、vantictumab (Anti-Fzd7, OMP-18R5)、OMP-54F28 (Fzd8-Fc)，这些候选产品，靶向于癌症干细胞的关键信号通路，包括Notch信号通路和Wnt信号通路。

OncoMed还有另外2种抗体处于临床前开发阶段，分别为Anti-DLL4/Anti-VEGF双特异性抗体和Anti-RSPO3，该公司计划于2014年初提交相关的研究性新药申请。此外，OncoMed也一直致力于发现额外的新颖抗CSC候选产品。

目前，OncoMed已与新基（Celgene）、拜耳（Bayer）、葛兰素史克（GSK）达成战略联盟。（生物谷Bioon.com）

英文原文：OncoMed and Celgene Announce Strategic Collaboration Advancing Multiple Anti-Cancer Stem Cell Therapeutics to Offer Potential Benefits to Cancer Patients

Celgene Invests in OncoMed's Demcizumab and up to Five Additional Preclinical Biologics Programs; OncoMed Leads Early Clinical Trials and Retains Co-Development, Co-Commercialization and Profit-Sharing Rights

OncoMed to Receive $177.25 Million Upfront, Including a $22.25 Million Equity Investment

OncoMed to Host a Conference Call This Morning for Investors at 8:30 a.m. ET

REDWOOD CITY, Calif., Dec. 3, 2013 (GLOBE NEWSWIRE) -- OncoMed Pharmaceuticals, Inc. (Nasdaq:OMED) and Celgene Corporation (Nasdaq:CELG) today announced an agreement to jointly develop and commercialize up to six anti-cancer stem cell (CSC) product candidates from OncoMed's biologics pipeline, including demcizumab (OMP-21M18, Anti-DLL4).

OncoMed will control and conduct initial clinical studies at which point Celgene has an option to license worldwide rights to up to six novel anti-CSC therapeutic candidates. OncoMed retains global co-development and U.S. co-commercialization rights for five of the six anti-CSC product candidates with 50/50 U.S. profit sharing, and royalties to be received in other territories. Celgene will also have research, development and commercialization rights to small molecule compounds in an undisclosed cancer stem cell pathway.

Celgene obtains an exclusive option on one of OncoMed's most advanced clinical candidates, demcizumab, during or after the completion of certain future planned Phase II clinical trials to be conducted by OncoMed. Demcizumab is currently in three Phase Ib clinical studies in combination with standard-of-care therapeutics, including a trial in patients with first-line advanced pancreatic cancer. Subsequent to option exercise, the parties will co-develop demcizumab, sharing global development costs on a 1/3 OncoMed and 2/3 Celgene basis. The companies will co-commercialize demcizumab in the United States with 50/50 profit sharing. Outside the United States, Celgene would lead development and commercialization, with OncoMed eligible to receive milestones and tiered double-digit royalties on sales outside the United States.

In addition to demcizumab, the collaboration includes up to five preclinical- or discovery-stage biologics programs: OncoMed's anti-DLL4/VEGF bispecific antibody and up to four additional biologics programs targeting either the RSPO-LGR CSC pathway or an additional undisclosed CSC pathway. Celgene obtains exclusive options on these programs during or after completion of certain Phase I clinical trials to be conducted by OncoMed. For the anti-DLL4/VEGF bispecific antibody and three of the four additional biologics programs, OncoMed retains 50/50 U.S. profit sharing and co-commercialization terms, plus 1/3 OncoMed and 2/3 Celgene global development cost-sharing and mid-single digit to mid-double digit royalties outside the profit-sharing territory. On the fourth biologics program, Celgene would receive an exclusive worldwide license, with OncoMed receiving high-single digit to mid-double digit royalties on worldwide sales. Celgene also obtains an option to conduct small molecule research, development, and commercialization in an undisclosed CSC pathway, with OncoMed eligible to receive milestones and low- to mid-single digit royalties on any resulting small molecule anti-cancer product candidates.

Under the terms of the agreement, OncoMed will receive an upfront payment of $155 million, and Celgene will also purchase approximately $22.25 million in a private placement of newly issued shares of OncoMed's common stock at a price of $15.13 per share.

The collaboration also includes option exercise payments and payments for achievement of development, regulatory and commercial milestones, paid on a per-program basis. For demcizumab, these payments could total up to approximately $790 million, and include an undisclosed payment for achievement of pre-determined safety criteria in Phase II clinical trials. For the anti-DLL4/VEGF bispecific antibody, option exercise, development, regulatory and commercial payments could total up to $505 million. For the other four biologics, each program is eligible for approximately $440 million of option exercise, development, regulatory and commercial payments. OncoMed could also receive more than $100 million in option exercise, development and regulatory approval payments for the small molecule program. Such total payments include milestones for regulatory approvals in multiple indications per program. OncoMed retains worldwide rights to certain targets in multiple pathways that do not become collaboration programs with Celgene.

"Through this major alliance with Celgene, we gain substantial resources that will enable us to continue to discover and develop new therapeutics independently while positioning OncoMed for substantial potential downstream value and profits. Importantly, by retaining co-development and co-commercialization rights to up to five biologic product candidates in our pipeline, we expect to add commercial capabilities to our core research and development competencies as we continue to build a premier oncology biotherapeutics company," said Paul J. Hastings, OncoMed's Chairman and CEO. "Celgene is a preeminent biopharmaceutical innovator with a successful track record of translating unique science into disease-altering therapies that benefit patients, healthcare and society. We can greatly benefit from their expertise and look forward to many years of successful collaboration."

Tom Daniel, President, Global Research & Early Development, of Celgene said, "We are very pleased to enter into this broad based collaboration with OncoMed, one that holds great promise for cancer patients.  Demcizumab's substantial early clinical activity warrants aggressive yet careful evaluation in several indications where we have strength, including non-small cell lung cancer and pancreatic cancer. The earlier partnerships in the RSPO-LGR and another, undisclosed cancer stem cell pathway provide us complementary and strategically valuable targeting opportunities across both biologic and small molecule modalities in the cancer stem cell arena where OncoMed has provided leadership and great strength."

Latham & Watkins LLP and Leerink Swann LLC acted as advisors to OncoMed for this transaction.

OncoMed Conference Call

OncoMed management will host a conference call today beginning at 8:30 a.m. ET/5:30 a.m. PT to discuss today's announcement regarding this strategic collaboration with Celgene Corporation.

Analysts and investors can participate in the conference call by dialing (855) 420-0692 for domestic callers and (484) 756-4194 for international callers. The live conference call will also be webcast and available on the Investor Relations page of OncoMed's website at [url]www.oncomed.com.[/url] Please access the webcast at least 10 minutes prior to the start of the call to ensure time for any software downloads that may be required. A telephone replay will be available following the conclusion of the call by dialing (855) 859-2056 for domestic callers and (404) 537-3406 for international callers using the passcode 19812706.

About Cancer Stem Cells

Cancer stem cells, or CSCs, are the subpopulation of cells in a tumor responsible for driving growth and metastasis of the tumor. CSCs, also known as tumor-initiating cells, exhibit certain properties which include the capacity to divide and give rise to new CSCs via a process called self-renewal and the capacity to differentiate or change into the other cells that form the bulk of the tumor. Common cancer drugs target bulk tumor cells but have limited impact on CSCs, thereby providing a path for recurrence of the tumor. OncoMed has advanced five distinct anti-CSC targeting product candidates into clinical trials, including demcizumab (OMP-21M18). OncoMed believes its product candidates are distinct from the current generations of chemotherapies and targeted therapies, and have the potential to significantly impact cancer treatment and the clinical outcome of patients with cancer.

About Demcizumab (OMP-21M18)

Demcizumab is a humanized monoclonal antibody that inhibits Delta-Like Ligand 4 (DLL4) in the Notch signaling pathway.  Two Phase Ib combination trials of demcizumab are ongoing: demcizumab with standard-of-care in first-line advanced pancreatic cancer patients, and demcizumab with standard-of-care carboplatin and pemetrexed (Alimta™) in first-line advanced non-small cell lung cancer (NSCLC) patients. In addition, a Phase Ib/II trial of demcizumab and paclitaxel in patients with platinum-resistant ovarian cancer is ongoing at MD Anderson Cancer Center. Demcizumab is part of OncoMed's collaboration with Celgene Corporation.

About OncoMed Pharmaceuticals

OncoMed Pharmaceuticals is a clinical-stage company focused on discovering and developing novel therapeutics targeting cancer stem cells.  OncoMed has five anti-cancer product candidates in clinical development, including demcizumab (Anti-DLL4, OMP-21M18), OMP-59R5 (Anti-Notch2/3), OMP-52M51 (Anti-Notch1), vantictumab (Anti-Fzd7, OMP-18R5), and OMP-54F28 (Fzd8-Fc), which target key cancer stem cell signaling pathways including Notch and Wnt. OncoMed has two other antibodies in preclinical development, Anti-DLL4/Anti-VEGF bispecific and Anti-RSPO3, with Investigational New Drug filings planned for as early as 2014. OncoMed is also pursuing discovery of additional novel anti-CSC product candidates.  OncoMed has formed strategic alliances with Celgene Corporation, Bayer Pharma AG and GlaxoSmithKline (GSK).