FMR LLC

12/31/2009

6,462,538

4,691,940

264.99%

$74,901

SAC CAPITAL ADVISORS...

12/31/2009

3,624,420

(1,260,580)

(25.81%)

$42,007

BARCLAYS GLOBAL INVE...

12/31/2009

2,517,638

(2,741,860)

(52.13%)

$29,179

MORGAN STANLEY

12/31/2009

862,199

(1,803,803)

(67.66%)

$9,993

GOLDMAN SACHS GROUP ...

12/31/2009

861,489

(585,560)

(40.47%)

$9,985

CITADEL ADVISORS LLC

12/31/2009

153,516

(2,754,704)

(94.72%)

$1,779

Seattle Genetics与葛兰素签署许可协议

　　新浪财经讯 北京时间周二凌晨消息，生物技术公司Seattle Genetics Inc(SGEN)表示，将授权葛兰素史克公司(GSK)使用其抗癌技术。

　　作为回报，该公司将获得1200万美元的前期金。

　　Seattle Genetic的抗体药物偶联技术旨在瞄准并杀死特殊细胞，包括癌细胞。该公司还将有权获得至多3.90亿美元的里程碑付款，以及权利金。

　　Seattle Genetics表示，目前已为此项技术达成了超过9项许可交易。

胰岛素肺部吸入远景迷茫

时间:2009-11-30

　　

　　继辉瑞Exubera撤市之后，诺和诺德也终止了吸入性胰岛素的开发，那么，是什么原因导致Exubera撤市，这一切对通过肺部给药的蛋白类药物的远景毕竟意味着什么?

　　最近，诺和诺德公司终止其处于Ⅲ期临床阶段的速效吸入胰岛素产品AERx iDMS研发的消息正式传出，而此前辉瑞公司也发布了全球首个获得批准的吸入胰岛素Exubera撤市。这些利空的消息，使那些热切盼望能用吸入制剂代替注射用胰岛素的患者顿感扫兴。

　　难负众望

　　AERx iDMS是诺和诺德从Aradigm公司处获得的产品，是继辉瑞公司Exubera之后肺部吸入制剂研究领域中的又一新产品。此前，分析家们曾对 Exubera寄予厚望，他们估计，这一产品的年销售额将达到50亿美元。因为辉瑞公司和Nektar Therapeutics合作开发的Exubera能更容易地把持糖尿病患者的血糖程度，故被视为糖尿病治疗领域的一大创举。但是，撤市的事实却让分析家 大跌眼镜，Exubera没能实现研发商和分析师们的厚望。

　　那么，是什么原因导致Exubera这只“盼望之星”败走麦城呢?专家们给出的答案各不雷同。曾经参加了Exubera早期临床实验的洛杉矶查 尔斯德鲁大学(Charles R. Drew University)医学教授Mayer Davidson说：“从一开端，我就感到Exubera不是糖尿病治疗领域的重要突破，” 他说：“Exubera的体积比较大，应用起来不方便。患者不能将Exubera放到钱包里隐蔽应用。另外，应用Exubera的患者还需要应用长效胰岛 素来保持血糖的程度，并需要定期进行肺功效检测。”

　　Davidson还称，患者仍然需要刺破手指来测定血糖。总之，这些种种不便，掩盖了Exubera能避免注射给药的优势。他说，由于体积越来越小、应用更加方便且用完即可丢弃，胰岛素笔应用不便的毛病已经有了明显改良。这一点对吸入型胰岛素显然是不利因素。

　　仅仅是奢望?

　　美国圣弗朗西斯科的投资银行汉博银行(WR Hambrecht and Co.,)的制药业分析师Andrew Forman认为，Exubera的问题不在产品本身，是辉瑞公司的销售方法不当。辉瑞公司的营销方案缺乏创新，没有更好的、能用于餐后应用的包装。“另 外，辉瑞公司没能供给足够的产品，人们是不愿意应用供给没有保障的产品的。”他说。

　　尽管肺部吸入胰岛素存在上述的这些毛病，但是包含MannKind和 Alkermes在内的公司仍然在持续开发自己的吸入胰岛素产品。他们盼望自己采用下一代设计方案和创新给药道路的产品能在Exubera失败之后获得成 功。即使如此，开发出安全、有效、应用方便的肺部吸入产品能使注射制剂相形见绌的产品仍然是一种奢望。

　　MannKind 公司的首席履行官Dick Anderson 说，“目前已经很明确，还没有一种产品能完整代替注射用胰岛素;一种新的治疗方法必须比现有的产品安全性更高，疗效更好。” MannKind公司的吸入胰岛素制剂产品Technosphere与电话一样大小，临床实验已经证实，该产品起效更快。他说：“这种治疗方法与餐后胰岛 素分泌的正常模式非常吻合。”

　　弗吉尼亚联邦大学药学院 (Virginia Commonwealth University, School of Pharmacy)气雾剂专家Peter Byron认为，当前利用肺部进行肽类、蛋白质类药物给药面临的最大寻衅是吸入给药比注射给药更加不稳固。“许多更简略的给药道路是经嘴，而不是经肺。但 是考虑到每个人的嘴和喉咙的尺寸各不雷同，因此，这种给药道路的不稳固性更大。”

　　后有来者

　　为了克服上述的障碍，研究者们正在对包含粉末、结晶和液体在内的辅料进行筛选，从而设计出应用更方便、更有效的吸入产品。例 如，Alkermes正在开发一种尺寸比Exubera小的胰岛素吸入制剂，这种产品的胰岛素粒子尺寸比较大，但是密度轻。Byron说：“与 Exubera不同，这种胰岛素粒子体积比较大，密度比较轻，因此流动性更好，疏散更容易。”

　　MannKind的Technosphere同样采用了粉末技巧。但是该公司用吸收增进剂代替了体积比较大、密度比较轻的粒子技巧。Byron说：“通过使药物吸收更快，可以解决生物利用度的问题。这个想法是好的，但是目前的问题是吸收增进剂是否真的无毒。”

　　肺并不是唯一的用来传递目前通过注射给药的肽类、蛋白质类药物的器官。麻省理工学院(Massachusetts Institute of Technology)的生物工程师Robert Langer说：“差不多身材的每一部分都可以用来给药。”

　　例如，美国Nastech Pharmaceutical正在开发一种降钙素鼻腔吸入制剂，降钙素重要是预防妇女由于骨质疏松导致的骨质减少。包含了Dutch pharmaceutical、Echo 和强生公司在内的多家公司正在通过超声和电子技巧进行透皮制剂的开发。通过类似于用于治疗哮喘的吸入制剂RapidMist，加拿大制药企业 Generex进行口腔给药制剂的开发。目前正在开发用来治疗急性疼痛的吗啡和芬太尼的复方口腔喷雾制剂，治疗深部静脉血栓形成的低分子量肝素口腔喷雾制 剂。

　　据Langer表现，目前还很难断定口腔喷雾和肺部吸入制剂孰优孰劣，因为口腔喷雾还处于早期的研究阶段。他说：“许多东西需要通过临床实验来 证实，我认为一种给药道路并不能实用于任何一个人。不同的给药方法都有其自身的优势，你需要逐一解决如下的问题——重现性、生物利用度、免疫原性和费 用。”

　　德克萨斯大学医学部副主席兼FDA、内分泌和代谢类药物顾问委员会委员William Calhoun表现，生物利用度是产品获得批准的金标准，对任何一只产品都是相当重要。以Exubera来说，虽然其生物利用度比注射用胰岛素低，但是这 一事实并没有吓倒顾问委员会，其原因有以下两条：其一，患者可以采用另一种给药道路来获得正确的剂量;其二，该药物是用来把持血糖的峰值，而不是完整代替 注射用胰岛素。

　　Calhoun说，FDA最初的疑虑是Exubera有可能导致肺功效异常。后来的事实证明FDA是对的。临床数据显示，该药物确实导致患者肺功效的中度损伤，虽然损伤没有持续向下发展。

　　这些创造都在强调，正在开发新型给药道路药物的研究者们必须面临的寻衅是：药物有可能会对肺或其他器官产生生物效应，这些效应并不是研究者所需 要的。Calhoun说，“如果你以肺作为给药道路来治疗肺部疾病，治疗的靶标正好是药物传输的组织。这个时候肺才是一种很方便、最好的给药道路。但我们 将对通过肺部给药带来的潜在的、我们所不需要的生物效应表现关注。”

INCY discuss 2

Looks like the LLY pick was a bit of a surprise, as they really don't have an RA franchise, and therefore an RA focused salesforce.

Mgmt came out upfront saying they picked LLY because of deal terms (option to copromote) and pick and choose between 3 different buckets for various 050 inflam indications.

BUT, still how will LLY be able to market such an RA drug with no real RA distribution experience? This requires thousands of RA people! The only mitigating factor, from my viewpoint, is that LLY will have a number of years to work on this. But LLY does NOT have the deep pockets of a PFE or MRK or NVS or Roche. So, that is now a known unknown.

Friedman also indicated a number of times that INCY will get to bring their JAK science expertise to the table and be able to participate fully in the development of 050 and have 50% rep on a joint committee.

My gut tells that that LLY not having a huge RA team that could shunt aside, or suppress, INCY R&D and development staff in the joint effort in a perverse way was seen actually as a plus from the INCY standpoint!

Is this the way shareholders would also see it? I know from speaking with INCY Investor Relations head in the past year+ that INCY staff was always concerned that these big pharma R&D people thought they had the superior answers and would not value INCY scientists as much. So, my guess is that the LLY pick might have, to a significant extent, been driven by the R&D staff not being comfortable on this score with the other large pharma who were competing on this deal. LLY was the least threating and most cooperative? They need INCY more than the other large pharma?

Finally, Friedman/Rich Levy confirmed that the current Phase IIa RA trial is fully recruited, and 3 month results (before unblinding) will come out in April '09.

AND, that neither LLY nor INCY have any idea how the RA Phase IIa trial is doing since it is still double blinded.

INCY discuss 1

I'm in this for the long haul. However, you seem to have overlooked a few items in your price comparison vs. early 2009.

1. INCY has issued about 25% common equity since then. They raised 22 million shares at $6.75/share recenlty, but in the ensuing 15 months they have used cash for their operation of over $130 million.

2. INCY issued new convertible debt to replace the old one, but with a lower conversion strike price. The difference between the old ($11+/share), vs. current conversion strike price of $8.75/share is $2.25/share. On a base of $11+, this is a 20% INCREMENTAL dilution on an apples-to-apples basis that amounts to about another 10 million shares.


The big difference though is the $210 million + $90 million in upfront payments from the 2 deals.

So, there is a lot of cloudiness in the quantitative waters on this stock and I would submit that there are many who see what they want to see.

I believe we are seriously, or significantly undervalued, but a comparison of just the price in early '09 vs. now, in my view, misses a lot of the different elements.

I expect the next catalysts will be:

1) Jan 12th INCY presentation at Chase investor meeting,

2) Feb's annual investor update, including projections for full year '10 (which I expect will be outstanding) and in currentlu underappreciated,

3) the Phase 2 050 data in April '10,

4) Early data on Phase III for 424 in MF (assuming it is unblinded early), sometime in May/June '10, and

5) Potential start of Phase 3 PV trials in late 1H'10.

Incyte sells autoimmune therapies to Lilly

Mon, Dec 21 2009

* To get $90 mln upfront, up to $665 mln in milestone payments

* Incyte retains co-development, co-promotion rights

* Eli Lilly sees Q4 charge of $0.05/shr

* Eli Lilly reconfirms FY adj EPS view

* Incyte shares rise 6 pct (Adds conference call details, analyst comment; updates share movement)

By Vidya L Nathan

BANGALORE, Dec 21 (Reuters) - Incyte Corp sold global rights to its oral anti-inflammatory and autoimmune therapies (口服消炎和自身免疫疗法) to Eli Lilly and Co for up to $755 million, the companies said.

Under the deal, Eli Lilly will pay Incyte $90 million upfront and up to $665 million in potential performance-based payments for the therapies, including its lead compound for rheumatoid arthritis(类风湿关节炎), INCB28050, they said in a joint statement.

Incyte shares rose 6 percent to $9.00 early Monday morning, before shedding some gains to trade up 5 percent at $8.90 on Nasdaq.

Leerink Swann analyst Joshua Schimmer and Cowen & Co's Ziad Bakri said a deal was partly built into Incyte stock, which has risen 174 percent in the last six months.

The analysts expect the deal to strengthen Incyte's balance sheet, and said that at least some investors had expected the company to sign an agreement.

Eli Lilly gains world-wide rights to the product, INCB28050, while Incyte retains co-development and co-promotion rights, the companies said.

"The earliest we expect to consider exercising the co-development option would be in the second half of 2010, concurrent with the potential initiation of a mid-stage trial with INCB28050 in rheumatoid arthritis," Incyte Chief Financial Officer Dave Hastings said in a call with analysts.

Other oral compounds in development as a treatment for the same indication are Pfizer Inc's CP-690,550; Rigel Pharmaceuticals Inc's R788 and Lexicon Pharmaceutical Inc's LX2931.

"To say that (the deal) represents an entry-point for Eli Lilly in the potential multi-billion-dollar oral rheumatoid arthritis market is justified," Cowen & Co's Bakri said.

Eli Lilly, which expects to take a transaction-related charge of 5 cents per share in the fourth quarter, stood by its full-year profit view of $3.90 to $4.00 per share on a pro-forma basis.

Eli Lilly shares were up 2 percent $36.28 on the New York Stock Exchange. (Reporting by Vidya L Nathan in Bangalore; Editing by Gopakumar Warrier and Aradhana Aravindan)

© Thomson Reuters 2009. All rights reserved. Users may download and print extracts of content from this website for their own personal and

Dendreon Prices Offer

Dendreon Corporation (NasdaqGM: DNDN - News) announced recently that it has priced its common stock at $24.75 per share in its public offering to sell 15 million shares of common stock. The offer is underwritten by JP Morgan Securities, a division of JP Morgan Chase & Co (NYSE: JPM - News) along with Deutsche Bank (NYSE: DB - News). The underwriters will have a 30-day option to purchase up to a further 2.25 million shares of common stock to cover any over-allotments. The offer, which is expected to realize a net amount of approximately $356 million which can extend to $409.5 million in the event of the underwriters exercising the over-allotment option fully, is expected to close on Dec 15, 2009.

The company intends to use the proceeds from the offer to accelerate the construction of new facilities in Atlanta, Georgia and Orange County, California and build-out of the remaining capacity at its facility in Morris Plains, New Jersey.

Furthermore, the money raised from the offering will be utilized to fund investment in information technology infrastructure and product support systems coupled with the hiring of manufacturing, sales and marketing and other related personnel in preparation for marketing Provenge, a therapeutic vaccine for the treatment of prostate cancer in men.

The U.S. Food and Drug Administration (FDA) has assigned a Prescription Drug User Fee Act (PDUFA) date of May 1, 2010, to the company’s amended biologics license application (BLA) for Provenge.

Provenge would be the first product to be launched in a new therapeutic class known as active cellular immunotherapies on approval. The candidate boosted survival rates in men with advanced prostate cancer beyond any currently available treatments in clinical trials.

Unlike traditional vaccines that prevent diseases, Provenge acts by stimulating the body's own immune system to attack cancer cells. Dendreon plans to market Provenge in the U.S. on its own and is seeking partners for ex-U.S territories.

Prostate cancer is the most common non-skin cancer in the United States and the third most common cancer worldwide as per data from the American Cancer Society. We believe that approval of Provenge is critical for the financial performance of Dendreon since the product has blockbuster potential and its successful commercialization could drive the company to strong profitability.

诺华与Incyte公司达成药物授权协议

时间: 2009-12-04

药物开发商Incyte日前表示，已将2款潜在药物的许可权授予瑞士制药商诺华，其中包括一款骨髓纤维化治疗药物。

根据协议，诺华与Incyte公司将合作开发并营销INCB18424，该产品正作为一款骨髓纤维化治疗药物接受后期试验。骨髓纤维化能够引发骨髓衰竭、脾脏肿大，以及其他健康问题。Incyte公司将拥有该药的美国营销权。

另外一项产品是INCB28060，是一款试验性抗癌药物，即将进入人类试验阶段。诺华将拥有该产品的全球营销权。

总部位于美国特拉华州的威尔明顿的Incyte公司，将获得一笔1.50亿美元的前期付款，此外还将获得6000万美元的里程碑付款。如果 INCB18424在欧洲开始后期试验，并且该药达到销售及开发里程碑，那么诺华还可能额外支付给Incyte公司约11亿美元。Incyte公司还将获 得超过销售额10%的权利金。

如果INCB28060获得批准，诺华也将根据该药的销售额向Incyte公司支付权利金。

阿斯利康和Targacept公司就抗抑郁药TC-5214达成12亿美元协议

英国阿斯利康公司（AstraZeneca）12月3日表示，其已经就严重抑郁性障碍在研治疗药物 TC-5214与美国Targacept公司达成协议。据了解，TC-5214为Targacept公司研发末期产品，此次交易总价超过12亿美元，阿斯 利康公司将获得本品的全球研发及销售推广权。

根据协议规定，阿斯利康公司将支付Targacept公司一笔价值2亿美元的首付款，以及累计达5.40亿美元的审批和销售里程金。 Targacept公司保有在美国地区与阿斯利康公司共同推广本品的权利。此外，如果本品作为烟碱通道阻滞剂通过审批，Targacept公司将获得5亿 美元特定销售里程金收入，以及销售版税收入。

据了解，Targacept公司2009年7月曾经表示，TC-5214在Ⅱb期临床研究（本品作为严重抑郁障碍患者的附加疗法研究）中达到主要及次要临床终点。公司计划于2010年中期着手进行本品的Ⅲ期临床研究，并于2012年提交美国上市申请。