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罗氏签订$5.25亿协议—进军表观遗传学领域

  1. LSD1
  2. ORY-1001
  3. 甲基化
  4. 罗氏
  5. 表观遗传学

来源:生物谷 2014-04-09 18:49

罗氏签订首个表观遗传学交易,开发和商业化赖氨酸特异性脱甲基酶-1(LSD1)抑制剂ORY-1001,此次交易超过$5.25亿。

2014年4月7日讯 /生物谷BIOON/ --罗氏(Roche)和Oryzon Genomics公司4月7日宣布,双方已达成了一项全球性合作,研究、开发和商业化赖氨酸特异性脱甲基酶-1(LSD1;KDM1A)抑制剂。LSD1是一种表观遗传学调节器,能够调节基因的表达。此次合作,是罗氏签订的首个表观遗传学交易,获得了Oryzon Genomics公司的癌症阻滞剂ORY-1001的相关权利,ORY-1001能够阻断LSD1酶。

此前,欧洲药品管理局(EMA)已于2013年8月授予ORY-1001孤儿药地位,目前该药正处于I/II期临床调查用于急性髓性白血病(AML)的治疗。罗氏将全权负责ORY-1001和/或其备份化合物的开发和商业化。

根据协议条款,罗氏将支付一笔2100万美元的预付款和近期里程碑款项,在未来还将支付横跨血液学、肿瘤学、非恶性疾病(non-malignant)的开发、商业化、销售里程碑款项,总额可能超过5亿美元,同时还将支付销售相关的特许权使用费。

关于表观遗传学(epigenetics):

表观遗传学是一个术语,用于描述基因组功能上相关的变化,不涉及核苷酸序列的变化。表观遗传学机制的例子包括DNA甲基化或组蛋白修饰,这2种情况均能够改变基因如何表达,但不改变DNA序列。即使不涉及DNA变化,但表观遗传学变化却可能通过细胞分裂在细胞生命周期中持续,并可能持续数代。表观遗传学是癌症研究的一个热门领域。赖氨酸特异性脱甲基酶1(LSD1)能够使组蛋白脱甲基化,LSD1是一种不可或缺的表观遗传学调节器,调控关键的细胞过程,包括增殖和分化。LSD1也与其他恶性肿瘤如实体瘤和其他血液病疾病相关。

关于ORY-1001

ORY-1001是一种高度选择性、强劲的LSD1抑制剂,可通过口服给药,该药能够作用于AML干细胞。在急性淋巴细胞白血病小鼠模型中,ORY-1001能够显著减少肿瘤细胞负荷,并延长存活时间。(生物谷Bioon.com)

英文原文:Roche and Oryzon announce collaboration to develop epigenetics-based medicines

Collaboration spans research, development and commercialization of LSD1 inhibitors  for oncology, haematology and non-malignant conditions

Lead agent ORY-1001 currently in phase I/IIa study in AML

Roche (SIX: RO, ROG; OTCQX: RHHBY) and Oryzon Genomics SA today announced they have entered into a worldwide collaboration to research, develop and commercialize inhibitors of Lysine Specific Demethylase-1 (LSD1; KDM1A), an epigenetic modulator that regulates gene expression.

The lead molecule, ORY-1001, was granted orphan drug status by EMA in August 2013 and is currently in phase I/IIA for acute myeloid leukaemia (AML). Roche will have sole responsibility for developing and commercializing ORY-1001 and/or its backup compounds. The agreement includes the licensing of two patent families that Oryzon has created in its pioneering research in LSD1, and includes options for other Oryzon programs to be incorporated in future. The agreement also includes an initial two-year collaborative research program between Oryzon and Roche’s New York-based Translational Clinical Research Center (TCRC), Roche’s hub for research and early development activities in North America, to better understand the potential of LSD1 inhibitors in oncology and haematology.

John Reed, Roche’s Head of Pharma Research and Early Development, commented, “Oryzon is working at the leading edge of LSD1 inhibition, a technology with great potential to bring genuine patient benefit. Our TCRC in New York has been launched with a mandate to identify partnerships that drive innovation, providing an industry-leading conduit between sources of breakthrough science and the broader Roche organization. This collaboration on LSD1 inhibition with Oryzon fulfils that mandate perfectly.”  

Carlos Buesa, CEO of Oryzon, added, “We are excited to work with Roche in developing ORY-1001 to make a significant difference for patients with AML and, hopefully, for patients in other disease areas as well. Roche is the global leader in oncology and haematology, with a tremendous expertise in clinical development; this was the primary reason to prioritize this alliance. The collaboration is recognition of our cutting-edge science and our experience in epigenetics, an approach that we believe holds great promise for many patient groups.”

Under the terms of the agreement, Oryzon will receive an upfront payment and near-term milestones totalling $21 million, plus potential development, commercial and sales milestone payments across haematology, cancer and non-malignant indications that could exceed $500 million, together with tiered royalties on sales which range up to mid-double digits. 

About epigenetics

Epigenetics is a term used to describe functionally relevant changes to the genome that do not involve a change in the nucleotide sequence. Examples of epigenetic mechanisms include DNA methylation or histone modification, each of which alters how genes are expressed and consequently read or not read without altering the underlying DNA sequence. These epigenetic changes may last through cell divisions for the duration of the cell's life, and may also last for multiple generations even though they do not involve changes in the underlying DNA sequence. Epigenetics is an active field of cancer research. The lysine-specific demethylase 1 (LSD1), which demethylates a histone, is an indispensible epigenetic governor involved in regulation of key cellular processes including proliferation and differentiation.

About LSD1 inhibition

LSD1 is also called an “eraser”, for it removes signals in the histone, provoking changes in the reading context of the chromosome and turning off genes. Aberrant “erasing” activity may lead to disease. In mixed lineage leukaemia (e.g., AML, ALL) LSD1 has been identified as playing a pivotal role. Drugs inhibiting LSD1 produced changes in gene expression leading to differentiation of leukemic blasts cells into normal differentiated cells, reducing proliferation and reducing viability of leukemic stem cells.

About ORY-1001

ORY-1001 is a highly selective and potent LSD1 inhibitor which can be orally administered to patients. ORY-1001 affects AML stem cells, a sub-population of cancer cells that has been proposed to be responsible for frequent relapses of the disease. ORY-1001 also significantly reduces tumour cell load and increases survival time in mouse models of Acute Lymphoblastic Leukaemia. LSD1 has been also related with other malignancies such as solid tumours and other haematological diseases.

About the Translational and Clinical Research Center (TCRC)

The TCRC is Roche’s hub for research and early development activities in North America, underscoring the center’s importance to Roche. The TCRC staff comprises some 250 highly experienced drug developers who are focused on early clinical development of Roche drug candidates. In addition to advancing Roche’s existing portfolio, the TCRC experts aim to access external innovation by identifying collaborations ranging from very early discovery platforms through advanced stage molecules.

About Oryzon

Founded in 2000 in Barcelona, Spain, Oryzon (www.oryzon.com) is a privately held, clinical stage biotechnology company considered as the European champion in Epigenetics with a strong portfolio in the field. Its LSD program is currently covered by 18 patent families. The company has a second program in LSD1 inhibition devoted to Alzheimer’s and Huntington′s disease that is expected to enter in Clinical trials in 2015. The company has also a strong technological platform for biomarker identification. With a core in genomics, the company performs biomarker and target validation for a variety of malignant and neurodegenerative diseases. Under our current business model, Oryzon develops new drugs against these targets till Phase II.

About Roche

Headquartered in Basel, Switzerland, Roche is a leader in research-focused healthcare with combined strengths in pharmaceuticals and diagnostics. Roche is the world’s largest biotech company, with truly differentiated medicines in oncology, immunology, infectious diseases, ophthalmology and neuroscience. Roche is also the world leader in in vitro diagnostics and tissue-based cancer diagnostics, and a frontrunner in diabetes management. Roche’s personalised healthcare strategy aims at providing medicines and diagnostics that enable tangible improvements in the health, quality of life and survival of patients. Founded in 1896, Roche has been making important contributions to global health for more than a century. Twenty-four medicines developed by Roche are included in the World Health Organisation Model Lists of Essential Medicines, among them life-saving antibiotics, antimalarials and chemotherapy.

In 2013 the Roche Group employed over 85,000 people worldwide, invested 8.7 billion Swiss francs in R&D and posted sales of 46.8 billion Swiss francs. Genentech, in the United States, is a wholly owned member of the Roche Group. Roche is the majority shareholder in Chugai Pharmaceutical, Japan.

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