2009年5月8日 星期五

Vanda Pharmaceuticals 終於等到春天



Vanda,不是Panda


 


什麼產業的股票可以跌到每股只剩0.45美元的歷史低價後,因著一項產品的成功,股價再上漲到每股8美元,半年內波段漲幅接近百分之一千八百 (1780%),單日最大漲幅可達999%


 


位於美國馬里蘭州的Vanda Pharmaceuticals昨日( 2009-04-07 )收盤單日漲幅達 625.93%。除非台股解除漲跌幅限制,不然這樣的股價曲線圖大概永遠不可能在台灣股市出現。


 




 


 


Vanda這一年內的故事跟股價曲線一樣精采。


 


Vanda是一家位於美國馬里蘭州的小型生技製藥公司,主要針對CNS的疾病進行新藥開發。其關鍵藥物為iloperidone,是一個治療精神分裂的藥物,另外一個主要藥物是tasimelteon針對睡眠及情緒方面進行藥物開發。


20087月底,美國FDA針對Vandailoperidone所提出的新藥申請發出了一個non-approvable letterFDA認為Vanda必須提供更多該藥物安全方面的資料。問題是,小型生技公司的現金一般都不多,當時Vanda的現金與約當現金僅約五千萬美金,根本不可能有資金再進行任何大規模臨床實驗。這non-approvable letter對中小型生技公司而言,就像死神一樣,宣判了該公司的死刑,Vanda股價因此慘跌近八成!隨後的半年,Vanda股價隨著金融海嘯緩步趨「軟」,一直盤跌到2008年年底的歷史低點0.45每元,之後股價略有回升,但一直都在1美元以下整理。


一般生技公司的股價在壞消息出現而驟跌之後,若該公司管理階層和大股東有共識,認為公司仍有機會的話,多半不會再往下跌太多。Vanda曾於2008Q3-Q4進行組織重整,裁員15%,並停止所有臨床前實驗以節省開支。但是持有Vanda15%股權的大股東TCP (Tang Capital Partners)不看好公司營運,20092月趁著董事會改選的機會,要求撤換創辦人兼執行長 Mihael Polymeropoulos 及董事長 Argeris Karabelas,並且要求Vanda進行資產拋售換取現金,當時TCP甚至打算藉由手上持股改選董事以達到上述要求。市場派的啃骨頭行動當然遭到Vanda的悍然拒絕。Vanda的未來遭到大部分分析師與媒體的質疑,落魄的Vanda還當選了2007 年的Worst Pharma Stock!!


上帝一定會眷顧認真工作的人嗎?我不知道,但是上帝(或者說FDA就是生技業的上帝?)這次倒是相當眷顧VandaVanda針對FDAnon-approvable letter說明理由進行申訴,得到FDA的認可,FDA200957核准了Vandailoperidone的新藥申請,消息一出,股價如火箭般往上衝,結果就是單日最大漲幅高達999%


目前市場上的精神分裂藥物副作用較明顯,iloperidone勝出的原因據信是其較佳的安全性。這讓我想起前一陣子肥胖藥物開發的例子,市場所有的關注皆落在藥效(efficacy),未能達到受試組平均體重降低5%的新藥物,經常被華爾街呼風喚雨的分析師認為沒有成為明星藥的潛力而棄之如敝屣,即使該藥物安全性極佳,甚至有部分改善心血管指標的功能。明星分析師一發表看壞的評論,股價常常是像自由落體般墜落。


報派型開發有成的台灣生技公司們,天天在媒體上告訴對新藥開發外行的投資人,某某藥又獲得FDA「核可」進行第某期臨床實驗,然後股價一路推升,飆到五六十元的「天價」(註一)。問題是你要在台灣進行臨床實驗,燒你自己的錢,試你自己的人,只要Protocol合理可行,FDA幹嘛要擋你? FDA只把守最後一道關卡,就是NDA。你要在美國NDA,就要燒錢依序進行各期臨床試驗,獲得藥效與安全性皆佳的臨床測試資料。這還不保證NDA申請一定會過,如果針對該類疾病,市場上已經有藥物在販售,你還得說服FDA你的藥比起市場上現有藥物到底好在哪哩。像是Vanda這樣走到最後階段被FDA宣判出局的美國生技公司例子可謂不勝枚舉。


眾人皆濁唯我獨清,眾人皆醉唯我獨醒。只可惜真實股票市場的資本運作常常讓醒的人氣死,清的人餓死。台灣生技股何嘗不是如此?


 


註一:對藥物還在開發燒錢中,根本還沒有營收的生技股而言,藥物只有「評估價值」,並沒有真正的市場價值,這叫智財權的鑑價。在買家還沒有出現時,評估價值是不能轉換為市場價值的,因此只具有報表參考功能。如果台灣有厲害專業的生技智財權方面的鑑價師,應該盡快列入國家保護資產。


2009年5月7日 星期四

Avastin獲得FDA許可治療多發性神經膠母細胞瘤



(Photo from www.researchvegf.com)


 

在作為早期大腸癌化療輔助劑的嘗試失敗後,羅式控股終於傳來好消息,FDA核准了Avastin使用於多發性神經膠母細胞瘤(glioblastoma),相信這會讓Avastin的年銷售額由2008年的40億美金攀升到2011年的70億美金左右。


多發性神經膠母細胞瘤是 一種相當惡性的腦瘤,也稱為Glioblastoma mutiforme (GBM),大部份病人都在兩年內死亡。目前治療GBM為放射治療與化學治療併用,化療藥物主要為temozolomide (商品名:帝摩多,TemodalSchering-Plough),為一種alkylating agent (烷基化藥物),可造成DNA甲基化,進而普遍抑制癌細胞內的基因表現。早期單用temozolomide療效並不顯著,2005年在新英格蘭醫學雜誌有兩個關於temozolomide的重要研究報告:(1) 一個跨歐洲與加拿大的研究顯示,若將temozolomide與放射治療併用,腦瘤病患的存活時間與兩年存活率都有顯著增加;(2) Hegi的研究結果顯示,temozolomide的療效與癌細胞內的MGMT (methylguanine methyltransferase) 活性有關。MGMT負責甲基化DNA,若細胞的MGMTsilencing (靜默化=關閉),意味著細胞失去甲基化酵素活性。在此狀況下使用temozolomide時,其抑制效果會明顯高於MGMT仍然活化的細胞。


此次試驗中,Avastin所併用的化療藥物是Irinotecan,又稱為CPT-11 (商品名:抗癌妥,CamptosarPfizer),為Topoisomerase I inhibitor,主要用於轉移性大腸直腸癌。CPT-11是喜樹鹼(camptothecin)的半合成衍生物,水溶性較喜樹鹼更佳,且骨髓抑制等毒性較低,有研究顯示CPT-11對腦瘤也有不錯的療效。由分子生物的研究顯示,GBM是是一種相當仰賴VEGF的腫瘤,因此推測Avastin應該會對GBM有相當不錯的療效,臨床試驗的結果果然印證這個基本分生知識的推測。


看到Avastin又成功拓展腦癌的市場,不免讓我想起我在『台灣生技公司股東何時出頭天?』一文裡的感慨。一個作用標的正確的生技藥物,其價值就足以招攬眾多投資者投入資金,根本無須廠商搏命演出『搶錢大作戰』。國發基金的功能的不是幫台灣的上市櫃生技公司上大學,而是藉由國家資本的高風險承受性,尋找有潛力的早期生技公司進行投資,發堀台灣的長期價值,也藉由政府對高風險的承擔,鼓勵人才與資金進行新創事業


 


參考資料 



  • Brandes et al. (2009) Recurrence Pattern After Temozolomide Concomitant With and Adjuvant to Radiotherapy in Newly Diagnosed Patients With Glioblastoma: Correlation With MGMT Promoter Methylation Status. JCO 27: 1275-1279.
  • Oshiro et al. (2009) Efficacy of Temozolomide Treatment in Patients with High-grade Glioma. Anticancer Res 29: 911-917.
  • Goldhoff et al. (2008) Targeted Inhibition of Cyclic AMP Phosphodiesterase-4 Promotes Brain Tumor Regression. Clin. Cancer Res. 14: 7717-7725.
  • Kushner et al. (2006) Irinotecan Plus Temozolomide for Relapsed or Refractory Neuroblastoma. JCO 24: 5271-5276.
  • Reardon and Wen (2006) Therapeutic advances in the treatment of glioblastoma: rationale and potential role of targeted agents. The Oncologist 11: 152-164.
  • Paulino et al. (2005) Treatment of brain tumors.. NEJM 352: 2350-2353.
  • DeAngelis (2005) Chemotherapy for Brain Tumors — A New Beginning. NEJM 352: 1036-1038.
  • Stupp et al. (2005) Radiotherapy plus concomitant and adjuvant temozolomide for newly diagnosed glioblastoma. NEJM 352: 987-996.
  • Hegi et al. (2005) MGMT gene silencing and benefit from temozolomide in glioblastoma. NEJM 352: 997-1003.

2009年5月5日 星期二

Genentech 產品發展部門總裁 Susan Desmond-Hellmann 將出任 UCSF 校長


 


根據WSJ的消息,Genentech 明星藥 Herceptin, Rituxan 及 Avastin 的推手、產品發展部門總裁 Susan Desmond-Hellmann 將在羅式控股以每股95美金的高價收購 Genentech後,揮別一起奮鬥了14年的 Genentech ,成為加州大學舊金山分校(UCSF)校長,此項人事案將在加大2009-05-07的董事會中投票。



Susan Desmond-Hellmann 手中的 Genentech 股票超過一百萬股,市值至少30億台幣。


生技版搶錢大作戰?




『投資上市櫃公司,好比幫高中生上大學,會比幫幼稚園孩童上大學快』、『呼籲政府不宜再堅持只投資新創公司的政策,以免重複失敗』、『建議國發基金挹注資金在這些值得幫忙的公司』

 有必要為了搶這六百億,說出這麼讓人掉下巴的話來?記者有沒有訪問過創投專業人士的意見?如果國發基金投資上市公司賠錢,這些董事長或是總裁的願不願意以私有資產照價賠償?

 掛牌成功就是研發有成?生技業是這樣玩的?我看這無關生技邏輯,這叫資本邏輯,這些人玩掛牌上市遠比產品上市有興趣得多。從這樣的發言很難讓人不懷疑ao3j6z83裡面的人腦袋都是裝些什麼樣的料?


這樣的言論是因為特定品牌的shampoo洗太多,腦袋洗壞了嗎?唉!台灣的生技產業到底有沒有未來?………【謎之音:老子有錢,說了算!】


 *********************************************************************************************************



懷特生技董座:國發基金應投資上市公司

【經濟日報記者謝柏宏/即時報導】2009.03.30 09:30 pm

懷特生技新藥(4108)董事長李成家30日表示,政府透過國發基金投資生技公司,應該放寬投資範圍到上市櫃公司,而不只是侷限在風險難以評估的新創公司,他並呼籲政府應協助上市櫃生醫公司併購小型生技公司。

李成家表示,國發基金過去只對新創生技公司有興趣,但新創公司風險很難評估,目前仍未見成功案例,因此不宜再堅持只投資新創公司政策;而投資上市櫃公司,好比幫高中生上大學,會比幫幼稚園孩童上大學快。

2009/03/30 經濟日報】



生技起飛鑽石行動選題 李成家:有業界參與才能落實兆元產業
2009/03/30 19:21 鉅亨網

【鉅亨網記者葉小慧台北】 行政院擬定「生技起飛鑽石行動方案」,將成立最 大規模達新台幣 600億元的生技基金,推動生技成未來兆元產業,美吾華 1731(TW) 、懷特 4108(TW) 生技集團董事長李成家今(30)日表示,生技產業唯有擴大規模才能走進國際市場,盼國發基金扶持正成長且值得投資的上市櫃公司,在投資選題上,應納入生技產業界的意見,才能落實兆元產業,把兆元產值做出來才有用。

李成家指出,過去政府都把錢花在研究單位,但實際將產品商品化的比例不高,而國發基金過去只對新創生技公司有興趣,但這些新創公司的風險很難評估,到目前還看不到投資成功的案例,因此呼籲政府不宜再堅持只投資新創公司的政策,以免重複失敗。

美吾華總裁陳寬墀表示,國內生技產業經過10多年的努力,已有部分公司研發有成,公司股票也已成功掛 牌上市櫃,累積很多能量,但仍需要充分資金和人力, 建議國發基金挹注資金在這些值得幫忙的公司,協助產業真正踏入國際。

行政院預定由國發基金出資40%、民間投入60%的生技基金,第一期規模預估75億到 100億元,據了解最先以醫療器材為主,而據媒體報導,經濟部新藥及醫療器材選題委員會的成員,將包括醫界、金融界、會計師及 法律專家共9名,李成家認為,委員會成員應納入生技產業指標人士,才知道產業實際經營發展狀況。

陳寬墀指出,選題委員會成員須具備專業性和公平性,到底選公司或選研發項目應該明確,而政府不應擔心利益衝突就不納入業界代表,事實上台灣地域狹小,醫界、學界也無法排除利益衝突問題,而且國外的選題委員會都會有業界人士,重要的是,嚴格要求「利益迴避」,簽訂利益迴避條款。



Ernst & Young:四大趨勢將影響生技產業未來的商業運轉模式

根據 Ernst & Young 的最新報告 Beyond borders: Global biotechnology report 2009,2008年的經濟危機將撼動目前生技產業的商業模式,未來生技產業的商業運作將受到下列四項重要因素的影響:


1. 學名藥的發展:學名藥的重要性將大幅增加,尤其是目前已到期或即將到期的明星藥,由於學名藥的出現將可大幅降低公部門與保險單位的負擔,目前已到期或即將到期的明星藥未來將面臨學名藥的強力競爭。


2. 美國醫療改革:由於美國是目前世界最大的藥物市場,美國即將進行的醫療改革方案及給付制度將深深影響未來生技及醫藥產業走向。


3. 個人化醫療:個人化醫療將增加早期研發(生技公司相對於大藥廠的利基)的相對價值,也增加其談判籌碼,更有效率的藥物開發技術也將降低研發成本,增加生技公司自給自足的機會。


4. 全球化:新興市場日益倍增的重要性將促使藥廠或生技公司採取更具創造性的雙贏方案,例如將資本與美國以外的市場與具創造性競爭力的伙伴共享。同時,亞洲的商業運轉模式將會是歐美面臨困境的生技或製藥公司ㄧ個可能的解決方案。


2008年美國上市生技公司的獲利成長8.4%,雖較2007年的11.3%下滑,但2008年首次出現產業總體淨獲利4億美金。美國的生技創投並未受金融風暴影響,2008年共募集44億美金,為史上第二高,僅次於2007年的55億美金。


歐洲上市生技公司2008年的獲利成長17%,達112億歐元(非淨獲利,未計虧損)。歐洲的資本募集從2007年的55億歐元大幅衰退到2008年的20億歐元。


亞太地區2008年生技產業的獲利成長25%,主要由澳洲的強勁成長所貢獻。澳州公開的資金募集也衰退到2002年後的新低,在日本與中國僅有少量的新上市案,但印度生技業的私募部分則成長強勁。


 


2009 全球新興生技聚落 -- 還在計較學歷認證的台灣在哪裡?

Emerging Biotechnology Clusters
Experienced Management and VCs and a Serial Entrepreneurial Culture Provide Critical Keys to Success


Gail Dutton








Researchers at Scotland's University of Glasgow are working to improve the safety and efficacy of gene therapy by studying the biology of viruses.
(D. Bhella, MRC Virology Unit)


Boston, San Francisco, San Diego, and Cambridge are on everyone’s list of the top biotech clusters. Medicon Valley, straddling the border of Sweden and Denmark, Switzerland’s BioValley, Seattle, and Paris may be on that list, too, and no wonder. These are areas where biotech thrives. Biotech is so successful at attracting brainpower, related industries, and money to regions that today almost everybody is trying to get into the act.




Obviously, some regions will fare better than others. Many of these clusters have formed because of local political interest. “Consequently, many of the clusters don’t reach critical mass,” notes Willy DeGreef, secretary general, EuropaBio.




There are many great research universities throughout the world, and most regions with a nascent biotech industry have at least one. Good ideas and the scientific capital to bring them to fruition, therefore, are plentiful. It’s the business aspects of growing a biotech cluster that are often most difficult, and that can make the difference between success and mediocrity or even failure. As Glen Giovannetti, global biotech leader at Ernst & Young, points out, “The secret sauce for biotech success is experienced venture capital, experienced management, and a serial entrepreneurial culture.”




GEN talked with a number of biotech industry thought leaders to identify some of the most promising emerging biotech clusters. One point they all made is that it’s nearly impossible to choose the best, and that even the term biotech is hard to define. The term “emerging” had some challenges, too. Nonetheless, here are some of the regions that are capturing their attention.




Brazil






Belo Horizonte, São Paulo, and Rio de Janeiro are the three leading biotech clusters. Generic manufacturers are currently predominant, but they realize the need for innovative new compounds, according to Sarah Frew, Ph.D., research associate at McLaughlin-Rotman Centre for Global Health at the University Health Network and the University of Toronto.




The biotech sector is dominated by small to medium-sized companies that are focused on agriculture, although some small innovative drug firms exist. Collaborations tend to be with Brazilian universities and with foreign companies, but not with other Brazilian companies, and usually are for services like marketing or for access to information. Private financing remains challenging, and public funds are limited.




Belo Horizonte, in the northern part of the country, is the capital of Minas Gerais, and was Brazil’s first planned city. It has three universities, including the University of Minas Gerais, which is known for its science and technology. The Biominas Foundation also is located in Belo Horizonte. The Foundation has helped 33 biotech companies generate business opportunities since its inception in 1990, and its Incubator of Companies program has introduced 21 start-ups to the market since 1997. Biominas is an active lobbyist for the biotech industry, and its officers have close ties to the government and to the venture capital community.




São Paulo is home to the Butantan Institute, which is one of two vaccine suppliers to the Brazilian Program for National Immunization (PNI), universities, and to Intrials, which claims to be the largest full-service clinical trials research organization in Brazil.




Rio de Janerio has the Oswaldo Cruz Foundation, which plays a major role in developing healthcare products. The Immunobiologicals Technology Institute, known as Biomanguinhos, is the other vaccine supplier to the PNI and is located in Rio.




Canada






Both Toronto and Vancouver have good, small companies, but they’re struggling for capital. They have the benefit of government support and strong universities, particularly the University of Toronto, the University of Guelph, and the University of British Columbia. Entrepreneurship skills need to be honed, however.




In the heart of Toronto, the MaRS Center incubates a host of companies within about a mile of five teaching hospitals, the University of Toronto, the provincial parliament, and the financial district. The local government takes a close interest in the Center’s success, and several promising research projects are moving toward commercialization.




Vancouver, on Canada’s west coast, consistently ranks as a fast-growing cluster, attracting more than 90 companies, some with late-stage trials. The University of British Columbia has an active tech-transfer department that has spun out several companies.




China






The People’s Republic of China has declared the development of a vibrant biotech industry to be one of its top priorities, and several biotech parks have emerged. Shanghai and Beijing are home to the largest groupings of biotech companies, according to Dr. Frew. Both cities boast good universities.




“Shanghai is the new center of business and commerce in China, rivaling Hong Kong,” according to Zhu Shen, Ph.D., CEO of BioForesight. The Shanghai Zhangjiang Hi-tech Park, located in the Pudong New Area, is home to more than 3,600 companies focused on life sciences, software, and information technology. Of those, more than 250 are life sciences companies, employing a total of 20,000 life sciences professionals. About half the Park revenues are from life sciences, Dr. Shen adds.




The Zhangjiang Drug Valley, as that park is nicknamed, has developed 17 square kilometers of the 25 square kilometers within the park. Companies include 7 of the top 10 big pharma companies and more than 110 indigenous CRO or outsourcing firms, novel drug discovery firms, contract manufacturers, and others. Nearby organizations include the Shanghai Institute for Biological Sciences, and Shanghai University of Traditional Chinese Medicine.




About 80 kilometers west, “Suzhou BioBay is hungrier and more aggressive, and focuses on early-stage and innovative companies,” Dr. Shen says. “Government officials at Suzhou BioBay and at Suzhou Industrial Park tend to be younger, energetic, and well-versed in English and Western-style business operations.” The parks are known for consistent policies, pro-business mentalities, and large private funding networks.




Beijing is home to numerous government agencies and savvy entrepreneurs who know how to work with government. The Beijing Zhong-guan-cum Life Science Park is one of China’s older biotech parks, Genzyme and Bayer Schering both have announced plans to develop R&D centers there. The Institute of Biotechnology, Beijing Normal University, Peking University, Beijing University, and other universities are located here.




Although China in general has some cost advantages, thought leaders say they still hear concerns about intellectual property “which is getting better,” Giovanneti points out. As yet the companies and universities are doing discovery research, and clinical trials, but the industry hasn’t yet moved into late-stage research.




India






“There’s been a lot of activity here in public/private partnerships for biotech parks,” Giovannetti says. Overall, the region is still strong in generics, but some innovative companies are coming out of Genome Valley, about 20 miles from Hyderabad, and also from Bangalore. Within the next two to three years, India  expects to have about 27 biotech parks, according to Ernst & Young.




ICICI Knowledge Park was founded in 2000 on 200 acres of land. It currently is 100% occupied, with 80,000 square feet of wet labs and about 1,400 employees onsite, according to the just-released Ernst & Young study, “Biotechnology Clusters in India”.    Genome Valley also includes the Shapoorji Pallonji Biotech Park with modular wet labs, pilot plants, a business incubation center, and business support facilities. Its 140-acre phase I site is operational, and the phase II site is expected to be completed by 2015.




Hyderabad is dominated by the generics industry but has some biotech companies that are working on innovative drugs. CROs, including GVK Biosciences, are growing, spanning the gap between discovery and development. Strengths include the University of Hyderabad, which has a strong private partnership culture.




Biocon anchors the biotech industry in Bangalore. Spin-offs Syngene and Clinigene also are there, as well as the Indian Institute of Science and the Institute for Bioinformatics and Biotech. In addition, “the Biocon CEO has been a driving force for biotechnology in India,” Dr. Frew says.




“India released a biotech strategic plan last year,” Dr. Frew adds. The plan aims to streamline a confusing and bureaucratic regulatory process and, she says, “signals a willingness to work together.” The downsides to India, as well as any other developing country, Dr. Frew says, are that “tech transfer is a huge barrier,” and capital is in short supply.




France






Lille capitalizes on ties to Lille University, where Louis Pasteur developed the purification process now known as pasteurization. The Pas de Calais area around Lille has some 800 healthcare and biotech companies. The Eurasante Bio-business Park, based in Lille, currently has about 30 biotech firms employing some 3,700 people. It is growing quickly because of its proximity to major universities, seven hospitals, the Pasteur Institute, and other international institutions. The region has a well-developed infrastructure to support life science research and development.



Japan






Tokyo’s biotech cluster is patterned after the bionetworks in Chiba, Yokohama, and Tsukuba. Tokyo has a large concentration of companies focused on monoclonal research and also on stem cell research.




Universities in the city include the University of Tokyo and the Tokyo Institute of Technology, which both have graduate-level biotechnology programs. Tokyo University of Science and a long list of other schools also contribute to the scientific acumen of the city, as does its strong IT industry. The three cities comprising the Tokyo Bay Biotech cluster are close by.




Israel






In 2006, Silico Research Limited ranked Rehovot as number eight in its list of the top non-U.S. biotech clusters, citing its work in monoclonals. About 20 kilometers from Tel Aviv, Rehovot is home to the 250-acre Tamar Science Park, the Weizmann Institute of Science, as well as Hebrew University’s Faculty of Agriculture. Rehovot, which is known as Israel’s science city, has a higher than average population of university-educated citizens.




Israel has more than 900 life sciences companies. Of those, 55% are devoted to medical devices, and about 21% are focused on biotechnology. Pharmaceuticals constitute another 12% of the market, according to ILSI. Most of the pharmaceutical companies are engaged in generics, but 25% are developing new chemical entities. The country is entrepreneurial, and companies are spinning off from the universities in Tel Aviv and Jerusalem. About 14% are at clinical stage. 




Singapore






The Biopolis at the One-North corporate park has attracted some of the world’s leading researchers and also persuaded many R&D and manufacturing companies to locate facilities there. The hope is that those activities will spur local entrepreneurs. Like many emerging regions, it still needs a vibrant venture capital community. Biopolis is near the National University of Singapore and the National University Hospital.




Phase one includes seven buildings—two for the private sector and five for public institutions. Phase two, completed in 2006, brought total research space to 222,000 square meters (about 2.4 million square feet).




Biopolis is home to the Agency of Science, Technology, and Research (A*STAR), which leads the country’s scientific research and development efforts for the Ministry of Trade and Industry.




United States






Biogen Idec is one of many companies with research facilities in the San Diego area.


Home to many top biotech clusters, nearly every state is hoping to become a player in the biotech field. Thought leaders like Florida’s chances. Several leading institutes are located in the state including the Burnham Institute for Medical Research, Scripps Florida, SRI International, and the Torrey Pines Institute for Molecular Studies.




Also, East Coast researchers often are familiar with Florida, so attracting senior researchers as full-time residents isn’t difficult.  The Innovation Incentive Fund, however, was slashed at the end of fiscal 2008. The additional challenge is to grow companies through spin-offs from these and other institutions.




Colorado also has strong potential, with continued high levels of state funding for start-up companies and research intuitions. Precommercialization funding grants are capped at $250 million for companies from a five-year, $26.5 million program. Additional funding also is available.  Clusters are forming in Denver and Boulder, but the nascent firms tend to be acquired by larger companies before reaching maturity.




Also Worth a Look






In the U.S., additional emerging cluster contenders include Madison, Wisconsin; Orange County, California; and Houston, Texas. Madison is home to the University of Wisconsin, which has a strong life sciences program, and the region has a specialized job concentration in pharmaceuticals; medical devices; agricultural feedstocks, chemicals, and research; and testing and medical laboratories, according to BIO.




Orange County is known for its medical devices, but increasingly is adding biotech to its list of strengths, according to Tim Ingersoll at BioCom. Houston has more than 120 biotech organizations and is home to St. Luke’s Episcopal Hospital, a prominent neuroscience center. 




Australia has more than 400 companies, mostly clustered in Sydney and Melbourne.  Major contributions are coming out of the University of Queensland and other universities. Like many regions, it had been hit hard by the economic downturn and many sources of government funding have disappeared.




Malaysia has a growing bioinformatics sector, and industry experts say several companies there have gained funding recently from a leading U.S. capital fund. The government favors growing the biotech industry, so the industry is gaining traction.




In Europe, Barcelona, Ghent, and Montpelier, France, are benefitting from significant government interest and proximity to leading universities. And Scotland, whose biocluster is composed of more than 620 life science companies, is one of the continent’s largest and fastest-growing life science clusters—generating more than $4.4 billion (£3 billion) annually.



FDA 拒絕 Northfield Laboratories 血液替代製劑 PolyHeme 之上市許可




FDA於2009年4月底告知總部位於美國伊利諾州Evanston的生技公司Northfield Laboratories Inc.其經歷將近20年所研發的血液替代製劑PolyHeme之上市許可申請將被拒絕。此消息嚴重打擊Northfield Laboratories Inc.的股價,由前4月30日收盤的0.49美元暴跌至5月1日開盤的0.11美元,跌幅接近80%,隨後股價回升至0.25美元附近盤整,跌幅約50%。另兩家類似產品的生技公司為Enzon及Biopure,Enzon最近正在打官司對抗意圖撤換其CEO的市場派,Biopure則因FDA一直未核准其IND申請而無法進行臨床試驗。


目前血液替代製劑的研發大致上朝三個方向:


1.針對血紅素進行相關修飾或處理:此類主要針對像血紅素進行pyridoxylation、pegylation或是polymerization,基本上要維持血紅素蛋白完整性、調整血紅素的攜氧能力及終產物分子大小,以解決氧平衡及分子過小經血管滲漏的問題。此法還有一個基本障礙是vasoconstriction,也就是血紅素在血管運行時導致血管窄化及血壓上升;另外一個主要問題是誘發心臟病 (myocardial infarction, MI)。Northfield Laboratories Inc. 的PolyHeme (pyridoxylated Glutaraldehyde-polymerized human Hb)、Enzon 的 PEG-conjugated bovine Hb、Biopure 的Hemopure (Glutaraldehyde-polymerized bovine Hb)、Hemosol的hemolink都屬於這一類產品,是目前市場的主流。


2.針對紅血球進行相關修飾或處理:此類研究主要需解決血球抗原所誘發的免疫問題,一般採取覆蓋醣化修飾區的作法。


3.嘗試以化學成分取代血紅素的攜氧功能:主要以perfluorocarbon (過氟碳化合物,PFC) 為主,PFC是一種將碳以氟加以飽和的分子,目前主要應用於造影及氧氣運送。由於分子本身的鈍性,進入人體後比較沒有毒性方面的問題。此類分子水溶性不佳,使用前須以水相溶液(例如血漿)打成乳液狀,才能導入血流中,而且PFC與氧氣的結合與釋放不像血紅素的主動運輸,其氧結合曲線呈直線而非乙狀曲線,使用此類產品的患者必須同時使用高濃度氧氣以提高PFC的帶氧率。


 



 


至於PFC排除,目前認為身體內PFC的排除主要經由reticuloendothelial macrophages (RES) 對乳化顆粒的吞噬作用,再運送至肺部以氣體排出。此過程之效率與所使用PFC之蒸氣壓及親脂性成正比,而與PFC之分子量成反比。目前此方法的主要副作用有肺部過度充氣、發燒、類感冒症狀等。


目前看起來針對血紅素進行相關修飾或處理的產品似乎都未能消除FDA對產品安全的疑慮。以PolyHeme為例,其三期臨床試驗結果發表在2009年1月份的 Journal of the American College of Surgeons,其結果就統計角度而言雖未顯示PolyHeme使用組有統計上的顯著差異高於對照組,但就多重器官衰竭、一般及嚴重副作用等來看,PolyHeme組皆略高於控制組,且PolyHeme組發生冠狀動脈缺氧的比率為3%,高於對照組的1%。


 


看來,上帝把血紅素留在紅血球內必有祂的道理!


 


Human Polymerized Hemoglobin for the Treatment of Hemorrhagic Shock when Blood Is Unavailable: The USA Multicenter Trial
Journal of the American College of Surgeons, Volume 208, Issue 1, January 2009, Pages 1-13

Abstract: BackgroundHuman polymerized hemoglobin (PolyHeme, Northfield Laboratories) is a universally compatible oxygen carrier developed to treat life-threatening anemia. This multicenter phase III trial was the first US study to assess survival of patients resuscitated with a hemoglobin-based oxygen carrier starting at the scene of injury.


Study Design: Injured patients with a systolic blood pressure≤90 mmHg were randomized to receive field resuscitation with PolyHeme or crystalloid. Study patients continued to receive up to 6 U of PolyHeme during the first 12 hours postinjury before receiving blood. Control patients received blood on arrival in the trauma center. This trial was conducted as a dual superiority/noninferiority primary end point.


Results: Seven hundred fourteen patients were enrolled at 29 urban Level I trauma centers (79% men; mean age 37.1 years). Injury mechanism was blunt trauma in 48%, and median transport time was 26 minutes. There was no significant difference between day 30 mortality in the as-randomized (13.4% PolyHeme versus 9.6% control) or per-protocol (11.1% PolyHeme versus 9.3% control) cohorts. Allogeneic blood use was lower in the PolyHeme group (68% versus 50% in the first 12 hours). The incidence of multiple organ failure was similar (7.4% PolyHeme versus 5.5% control). Adverse events (93% versus 88%; p=0.04) and serious adverse events (40% versus 35%; p=0.12), as anticipated, were frequent in the PolyHeme and control groups, respectively. Although myocardial infarction was reported by the investigators more frequently in the PolyHeme group (3% PolyHeme versus 1% control), a blinded committee of experts reviewed records of all enrolled patients and found no discernable difference between groups.


Conclusions: Patients resuscitated with PolyHeme, without stored blood for up to 6 U in 12 hours postinjury, had outcomes comparable with those for the standard of care. Although there were more adverse events in the PolyHeme group, the benefit-to-risk ratio of PolyHeme is favorable when blood is needed but not available.


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後記:


Northfield Laboratories Inc.在FDA拒絕核准其PolyHeme之後不久,於2009-05-09宣佈結束營運,將裁撤所有人員,位於伊利諾州Evanston的總部與原本準備量產PolyHeme的工廠都將關閉。在此為Northfield Laboratories Inc.的從1994到2009的股價曲線圖留下紀錄...............畢竟,那美好的一仗已經打過。