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NTMD-Archemix Merger
[This combination may answer the question: Is there life after BiDil?]
http://www.businesswire.com/portal/site/biospace/index.jsp?ndmViewId=news_view&newsId=20081118006487&newsLang=en
>> NitroMed and Archemix Announce Merger Agreement
Merger Part of NTMD Plan to Maximize Shareholder Value
Conference Call and Webcast Scheduled for November 18, 2008 at 5:30 pm ET
LEXINGTON, Mass. & CAMBRIDGE, Mass.--(BUSINESS WIRE)--NitroMed, Inc. (NASDAQ: NTMD) and Archemix Corp., a privately-held biopharmaceutical company working to develop aptamer-based therapeutics, announced today that they have entered into a definitive merger agreement under which Archemix will merge with NitroMed in an all-stock transaction. Under the terms of the merger agreement, NitroMed will issue new shares of its common stock to Archemix stockholders based on an exchange ratio to be determined prior to the closing of the transaction. Under the exchange ratio formula defined in the merger agreement, the former Archemix stockholders are expected to own approximately 70 percent of the combined company, and the former NitroMed stockholders are expected to own approximately 30 percent of the combined company, each on a fully-diluted basis. This ratio is subject to potential adjustments as described in the merger agreement. The name of the company will be changed to Archemix Corp. and will be headquartered at Archemix’s offices in Cambridge, Massachusetts. The merger is subject to approval by Archemix’s and NitroMed’s stockholders and consummation of the previously-announced sale of NitroMed’s BiDil assets and other customary closing conditions.
Archemix is engaged in internal development of aptamer therapeutics in the area of hematologic diseases, and has out-licensed its technology to others to develop their own aptamer therapeutics in other areas. Aptamers are synthetically-derived oligonucleotides that bind to proteins with high specificity and affinity and have been shown to provide many of the advantages of oligonucleotides and monoclonal antibodies. Archemix’s most advanced proprietary candidate, ARC1779, is in Phase 2 clinical development to treat patients suffering from a family of rare blood disorders known as thrombotic microangiopathies, or TMA. A second Archemix proprietary product is scheduled to enter the clinic in mid-2009. In addition, Archemix has licensed its intellectual property to third parties to develop their own aptamer product candidates. Currently, Archemix licensees are evaluating five different aptamer product candidates in human clinical trials; two in Phase 2 and three in Phase 1. Archemix has additional partnerships with several pharmaceutical and biotechnology companies, including Merck Serono, Pfizer, Takeda, Eli Lilly and Isis Pharmaceuticals.
Assuming consummation of the previously-announced sale of NitroMed’s BiDil assets, it is estimated that cash and cash equivalents for the combined company will be approximately $50-60 million at closing.
“We view this merger as the critical second step, following the announced sale of the BiDil business, in our goal of creating value for our shareholders,” said Kenneth M. Bate, President and CEO of NitroMed. “We believe that the combination of NitroMed and Archemix will provide NitroMed’s stockholders with a company that has an exciting technology platform, proprietary products in development, business development opportunities and a solid financial foundation.”
“We believe that Archemix’s aptamer technology is a promising platform for novel drug discovery and development and it has led to a robust pipeline of potentially valuable therapeutics,” said Errol DeSouza, Ph.D., President and CEO of Archemix. “We are pursuing a strategy that enables us to develop a proprietary pipeline as well as develop a network of partnerships with leading pharmaceutical companies. We are very pleased to enter into this transaction, as we believe it will allow us to vigorously pursue this strategy and benefit shareholders of both companies.”
Details of the Proposed Transaction
The merger will take the form of a stock-for-stock merger intended to qualify as a tax-free reorganization. Under the terms of the agreement, all outstanding shares of Archemix’s common stock and preferred stock will be exchanged for shares of NitroMed’s common stock and all outstanding Archemix options and warrants will be assumed by NitroMed and become options and warrants to acquire NitroMed’s common stock.
The Boards of Directors of both companies have unanimously approved the proposed transaction. NitroMed’s and Archemix’s obligations to consummate the merger are subject to approval by the stockholders of both NitroMed and Archemix, as well as other customary conditions, such as the registration with the U. S. Securities and Exchange Commission (“SEC”) of the NitroMed shares to be issued as a result of the merger. In addition, the obligation of Archemix to complete the merger is further subject to the condition that NitroMed have completed the sale of its BiDil business.
In connection with the execution of the merger agreement, certain funds affiliated with HealthCare Ventures LLC, Rho Ventures, Invus Public Equities, L.P., and Care Capital LLC, together owning or controlling an aggregate of approximately 30% of NitroMed’s common stock, have agreed to vote their shares in favor of the transaction and refrain from selling any of the NitroMed shares they hold for three months following the closing of the transaction and 50% of the shares they hold for six months following the closing of the transaction. In addition, stockholders holding approximately 80% of Archemix capital stock have entered into similar agreements whereby they have agreed to vote their Archemix shares in favor of the merger and refrain from selling any of the NitroMed shares they receive in the merger for three months following the closing of the transaction and 50% of the shares they receive in the merger for six months following the closing of the transaction.
NitroMed expects to file a Registration Statement on Form S-4 and related joint proxy statement/prospectus with the SEC. Depending on the timing of filing and effectiveness of the Form S-4, the companies currently target the closing of the merger in the second quarter of 2009. In connection with the transaction, NitroMed intends to apply for re-listing of the combined company’s shares on NASDAQ to trade under the symbol “ARCH.” NitroMed plans to institute a reverse stock split, subject to stockholder approval, to comply with NASDAQ’s listing requirements at the time of the merger.
Cowen and Company, LLC is acting as exclusive financial advisor and Wilmer Cutler Pickering Hale and Dorr LLP is acting as legal counsel to NitroMed. Merrill Lynch & Co. is acting as exclusive financial advisor and Mintz, Levin, Cohn, Ferris, Glovsky and Popeo, P.C. is acting as legal counsel to Archemix.
Management and Board of Directors Following the Closing
Following the closing of the merger, it is expected that the management team of the combined company will be as follows: Kenneth M. Bate, President and Chief Executive Officer; Duncan Higgons, Executive Vice President, Business Operations; Gregg Beloff, Vice President and Chief Financial Officer; Page Bouchard, D.V.M., Senior Vice President, Research and Preclinical Development; and James Gilbert, M.D., Senior Vice President and Chief Medical Officer.
In addition, following the closing of the merger it is expected that the board of directors of the combined company will consist of five members of the current Archemix board of directors (Peter Barrett, Ph.D., Alex Barkas, Ph.D., Errol De Souza, Ph.D., John Maraganore, Ph.D. and Michael Ross, Ph.D.) and three members of the current NitroMed board of directors (Kenneth Bate, Mark Leschly, and Davey Scoon, C.P.A.).
Webcast/Conference Call Information
A conference call will be held today, November 18, 2008, at 5:30 p.m. Eastern Time, to discuss the planned merger between NitroMed and Archemix. The call will be led by Kenneth M. Bate, President and Chief Executive Officer of NitroMed, and Errol DeSouza, Ph.D., President and Chief Executive Officer of Archemix.
A live webcast over the Internet will be available at http://www.nitromed.com or at NitroMed-Archemix Merger Announcement Webcast and archived for two weeks.
To listen over the phone, please call
866-543-6403 (domestic/toll-free)
617-213-8896 (international).
59964532# passcode
A telephone replay will be available through December 2, 2008 at 888-286-8010 (domestic/toll-free) or 617-801-6888 (international). To access the telephone replay, please enter passcode 95097417#.
About NitroMed
NitroMed of Lexington, Massachusetts is the maker of BiDil® (isosorbide dinitrate/hydralazine hydrochloride), an orally administered medicine available in the United States for the treatment of heart failure in self-identified black patients. In this population, BiDil is indicated as an adjunct to current standard therapies such as angiotensin converting enzyme (ACE) inhibitors and beta blockers. There is little experience in patients with New York Heart Association Class IV heart failure. BiDil was approved by the U.S. Food and Drug Administration, primarily on the basis of efficacy data from the company’s landmark A-HeFT (African American Heart Failure Trial) clinical trial. For full prescribing information, visit: www.BiDil.com.
On October 22, 2008, NitroMed entered into a purchase and sale agreement with JHP Pharmaceuticals, LLC, a privately held specialty pharmaceutical company, pursuant to which NitroMed has agreed to sell to JHP Pharmaceuticals substantially all of the assets related to NitroMed’s BiDil and BiDil XR drug business. The sale of the BiDil and BiDil XR drug business is subject to NitroMed stockholder approval and other customary closing conditions.
About Archemix
Archemix is a biotechnology company focused on discovering, developing and commercializing aptamer therapeutics. Using Archemix’s processes for discovering aptamers, which are protected by its broad patent portfolio, Archemix is developing aptamer product candidates for rare hematological diseases. In addition, Archemix has licensed its intellectual property to third parties to develop their own aptamer product candidates in other areas. Currently, Archemix’s licensees are evaluating five different aptamer product candidates in human clinical trials; two in Phase 2 and three in Phase 1. Archemix has additional partnerships with several pharmaceutical and biotechnology companies, including Merck Serono, Pfizer, Takeda, Eli Lilly and Isis Pharmaceuticals.
Important Additional Information Will Be Filed with the SEC
In connection with the proposed merger, NitroMed will file with the SEC a Registration Statement on Form S-4 containing a joint proxy statement/prospectus. The joint proxy statement/prospectus will be mailed to stockholders of NitroMed and Archemix. The joint proxy statement/prospectus will contain important information about NitroMed, Archemix, the transaction and related matters. NitroMed also plans to file with the SEC and mail to its stockholders a separate proxy statement in connection with the previously-announced proposed sale of its BiDil and BiDil XR drug business. The proxy statement will contain important information about NitroMed, the proposed sale of the BiDil and BiDil XR business and related matters. Investors and security holders of NitroMed and Archemix are urged to read carefully both the joint proxy statement/prospectus relating to the merger, and the proxy statement relating to the proposed sale of the BiDil and BiDil XR drug business, when they are available.
In addition, investors and security holders of NitroMed will be able to obtain free copies of the joint proxy statement/prospectus for the proposed merger (when it is available) and the proxy statement for the proposed sale of the BiDil and BiDil XR drug business (when it is available), and other documents filed with the SEC by NitroMed through the website maintained by the SEC at www.sec.gov. In addition, investors and security holders of NitroMed will be able to obtain free copies of the joint proxy statement/prospectus for the proposed merger (when it is available) and the proxy statement for the proposed sale of the BiDil and BiDil XR drug business (when it is available), by contacting NitroMed, Inc., Attn: Secretary, 45 Hayden Avenue, Suite 3000, Lexington, MA 02421. Investors and security holders of Archemix will be able to obtain free copies of the joint proxy statement/prospectus for the merger by contacting Archemix Corp., Attn: Secretary, 300 Third Street, Cambridge, MA 02142.
NitroMed and Archemix, and their respective directors and executive officers, may be deemed to be participants in the solicitation of proxies in respect of the transactions contemplated by the merger agreement; and NitroMed, and its directors and executive officers, may be deemed to be participants in the solicitation of proxies in respect of the transactions contemplated by the purchase and sale agreement with JHP Pharmaceuticals, LLC, dated October 22, 2008, relating to the sale of the BiDil and BiDil XR drug business. Information regarding NitroMed’s directors and executive officers is contained in NitroMed’s Annual Report on Form 10-K for the fiscal year ended December 31, 2007 and its proxy statement dated April 16, 2008, which are filed with the SEC. As of October 31, 2008, NitroMed’s directors and executive officers beneficially owned approximately 33% of NitroMed’s common stock. Information regarding Archemix’s directors and officers and a more complete description of the interests of NitroMed’s directors and officers will be available in the joint proxy statement/prospectus relating to the merger. In addition, a more complete description of the interests of NitroMed’s directors and officers will be available in the proxy statement relating to the sale of the BiDil and BiDil XR drug business. <<
Cancer Drug Prospects
http://health.yahoo.com/news/reuters/us_cancer_drugs.html;_ylt=Ans2TM.2YdcQgAV2pbs01rmmxbAB
>> Modern cancer drugs more likely to get to market
By Ben Hirschler - Fri Nov 14, 7:12 AM PST
LONDON (Reuters) - Nearly one in five cancer drugs entering development now reach the market, a remarkably good success rate given the high level of failures in other disease areas, British researchers said on Friday .
A study by Cancer Research UK, based on 974 cancer drugs starting initial Phase I clinical trials since 1995, calculated there was an 18 percent probability that those in human tests would make it to commercial registration.
The last time this was measured, in 2004, the figure was estimated at 5 percent.
The sharp improvement is due to more targeted "intelligent" drug development based on a better knowledge of the biology of cancer, according to Herbie Newell, the British cancer charity's director of translational research.
"These findings highlight the fact that we are working in a really exciting time for cancer drug discovery," he said.
In the past, most cancer drugs were cytotoxic agents, designed to kill cancer cells. Such cytotoxic drugs also kill healthy cells that multiply rapidly, resulting in serious side effects such as sickness, hair loss and risk of infection.
By contrast, modern drugs are much more precise weapons because they target specific molecular switches involved in tumor growth, giving rise to fewer side effects.
The new research, published in the journal Nature Reviews Drug Discovery, found a family of molecularly targeted drugs called kinase inhibitors were almost three times more likely to reach patients than other types of anti-cancer drug.
Well-known examples of kinase inhibitors include Roche and Genentech's breast cancer drug Herceptin and Novartis's Glivec for leukemia.
Oncology is the fastest-growing section of the global pharmaceuticals market, with sales expected to increase by 15 to 16 percent in 2009, against just 4.5 to 5.5 percent for the drugs market as a whole, according to IMS Health.
Scientific advances in cancer treatment have encouraged many large drug companies to step up their investment in cancer research in recent years, resulting in a rapidly expanding line-up of targeted therapies.
Other notable products include Roche/Genentech's Avastin, Amgen's Vectibix, GlaxoSmithKline's Tykerb, ImClone's Erbitux and Pfizer's Sutent.
The arrival of such targeted treatments has extended lives for many cancer patients but their high cost -- typically running into tens of thousands of dollars -- means they can be a strain for cash-strapped healthcare budgets. <<
RE: Cook-AVII Program
I believe you are recalling the AVII collaboration with Medtronic which fizzled out in 2003. The Cook partnership began in 2006.
This link has some background on the partnership and Resten-NG (AVI-4126), which Cook has abandoned for AVI-5126:
http://www.antivirals.com/pr/pr311.php
>> AVI licensed its vascular disease program to the Cook Group Inc. (Cook) in March 2006 for device delivery of the NeuGene® antisense drug AVI–4126, while the company is focusing internal development on coronary artery bypass graft (CABG) using AVI–5126. <<
>By the way, what ever happened to Resten-NG?<
An entire chapter in the book Biotech Fiascos will be devoted to answering this. (Just kidding.) I would give the details, but I am suffering from PTASD (Post-Traumatic AVII-Shareholder Disorder.)
Global Therapeutics (Cook Medical)-AVII DES Trial
http://genengnews.com/news/bnitem.aspx?name=45202673
>> Nov 10 2008, 7:00 AM EST
Global Therapeutics Initiates Trial of Next Generation Drug-Eluting Stent Using RNA Therapeutic Agent to Treat Coronary Artery Disease
News source: Business Wire
Global Therapeutics, a leading developer of innovative solutions for the cardiology market, today announced initiation of the world’s first clinical trial of a drug eluting stent that uses an antisense RNA therapeutics agent aimed at silencing one of the genes (c-myc) responsible for causing arteries to reclose after stenting (restenosis).
“Based on our preliminary work with this class of drug, the delivery system, and the stent platform, we are extremely excited to begin what we hope will be a ground-breaking trial that advances the science of treating coronary artery disease beyond what current technologies can achieve,” explained Joseph B. Horn, president, Global Therapeutics, a Cook Group company. “With the help of our European colleagues, we eagerly anticipate a successful outcome to this landmark trial in 2009.”
Global Therapeutics’ GTX bare metal stent, which already has CE Mark approval for sale in Europe, will be coated with the latest generation antisense compound from AVI BioPharma (NASDAQ:AVII) coupled with a biodegradable excipient to release the AVI compound after stent implantation. The GTX cobalt chromium stent is designed for optimal ease of deliverability, radial strength and clinical performance. Horn added, “One of the important features is that we have rounded off the edges of our stent to minimize the potential for vessel injury. We designed this stent as a hybrid with features from coil stents (round edges) and the radial strength of a slotted tube.”
“Having our partner initiate this clinical study of a DES utilizing our RNA-based therapeutic agentis a significant milestone for AVI BioPharma and demonstrates a novel and promising application of our new generation of translation-suppressing oligomers,” said Leslie Hudson, Ph.D., President and Chief Executive Officer of AVI. “We look forward to the advancement of this program, and are excited by its potential to usher in a new generation of drug eluting stents.”
The drug used in the GTX DES device, AVI-5126, was developed by AVI BioPharma, Inc. and licensed by Cook Group. It is an enhanced antisense agent that targets a key regulatory gene involved in cardiovascular restenosis, silencing the gene before the restenosis cascade effect can be triggered. The enhanced antisense compound has increased potency compared with its predecessors, allowing for a DES system with less drug and excipient. Once implanted, the stent sheds its drug and excipient coating, leaving behind a bare metal stent after 24 hours. Importantly, the drug stays resident in the tissue for over two weeks, Horn explained.
The feasibility study is a prospective, open label, multi-center study being performed in Germany. As many as 90 patients will be enrolled in the study. All subjects will undergo clinical follow-up at 30 days and 6 months. Angiographic results will be reported at six months using quantitative coronary angioplasty (QCA) and intravascular ultrasound (IVUS).
The primary endpoint for the study is composite safety (MACE) at 30 days. Other endpoints include performance criteria such as in-stent and in-segment late loss, binary restenosis, and target lesion revascularization. Data from the study will be compared to historical controls of both bare and drug eluting stents.
About Cook Medical
Cook Medical was one of the first companies to help popularize interventional medicine, pioneering many of the devices now commonly used worldwide to perform minimally invasive medical procedures. Today, the company integrates minimally invasive medical device design, biopharma, gene and cell therapy and biotech to enhance patient safety and improve clinical outcomes in the fields of aortic intervention; interventional cardiology; critical care medicine; gastroenterology; radiology, peripheral vascular, bone access and oncology; surgery and soft tissue repair; urology; and assisted reproductive technology, gynecology and high-risk obstetrics.Founded in 1963 and operated as a family-held private corporation, Cook is a past winner of the prestigious Medical Device Manufacturer of the Year Award from Medical Device & Diagnostic Industry magazine. For more information, visit www.cookmedical.com
About AVI BioPharma
AVI BioPharma is focused on the discovery and development of RNA–based drugs utilizing proprietary derivatives of its antisense chemistry (morpholino-modified phosphorodiamidate oligomers or PMOs) that can be applied to a wide range of diseases and genetic disorders through several distinct mechanisms of action. Unlike other RNA therapeutic approaches, AVI’s antisense technology has been used to directly target both messenger RNA (mRNA) and its precursor (pre-mRNA), allowing for both up- and down-regulation of targeted genes and proteins. AVI’s RNA–based drug programs are being evaluated for the treatment of Duchenne muscular dystrophy as well as for the treatment of cardiovascular restenosis through our partner Global Therapeutics, a Cook Group Company. AVI’s antiviral programs have demonstrated promising outcomes in Ebola Zaire and Marburg Musoke virus infections and may prove applicable to other viral targets such as HCV or Dengue viruses. For more information, visit www.avibio.com. <<
HCV Results from GlobeImmune
I don't believe this was included here in the recent HCV news roundup, but GI-5005 has been mentioned here before.
http://genengnews.com/news/bnitem.aspx?name=44610403&taxid=0
Nov 1 2008, 8:00 AM EST
>> GlobeImmune Hepatitis C Therapeutic Vaccine, GI-5005, Doubles Viral Clearance and Increases RVR Rates in Phase 2 Clinical Trial
Nov 01, 2008 LOUISVILLE, CO MARKET WIRE
Four-week Phase 2 clinical trial data show that GI-5005, GlobeImmune's hepatitis C virus (HCV) targeted molecular immunogen (Tarmogen(R)), doubled viral clearance overall and in all major subgroups and doubled the rapid virologic response (RVR) rate in naive patients with high viral load. The study compared GI-5005 plus standard of care (SOC) -- pegylated-interferon plus ribavirin -- versus SOC alone in patients with chronic genotype 1 hepatitis C infection.
The study data will be presented by principal investigator John G. McHutchison, M.D., of Duke University, in a late-breaking poster next week at the 59th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD). Treatment-naive patients with high viral loads at baseline ( > 600,000 IU/mL) saw a 2.6-fold improvement in RVR, which is defined as undetectable HCV RNA levels ( < 25 IU/ml) by four weeks. Treatment-naive patients with a high viral load at baseline are particularly difficult to treat to an RVR. RVR is highly predictive of whether a patient will achieve a sustained virologic response (SVR), or "cure," which is defined as undetectable HCV RNA at six months post-treatment. A significant improvement was also noted in the rate of viral reduction in the peripheral blood using viral kinetic analysis in all patients, with a 2-fold improved slope (0.32 log10/month difference, p=0.02) for patients receiving GI-5005 in addition to SOC. Comparable magnitude of increased viral clearance in GI-5005 treated patients was noted in all patient subgroups including prior non-responders and patients with high viral load at baseline.
"These data represent early but important evidence that a patient's natural immune response can be harnessed to positively influence important virologic endpoints with the potential to impact the course of chronic HCV infection," said Dr. McHutchison. "The rational combination of novel immune approaches such as GI-5005 with IFN-based standard of care or with novel direct acting antiviral agents holds promise in terms of ultimately improving clinical outcomes, shortening the exposure to toxic therapies, or both."
David Apelian, M.D., Ph.D., GlobeImmune Chief Medical Officer, said, "These data indicate that GI-5005 can increase the rate of clearance of infected cells from the liver, something that interferon-based therapies and antivirals are not designed to do. Direct acting antivirals act primarily by inhibiting viral replication, an important step, but they have not been shown to speed the immune clearance of infected cells from the liver. Ultimately, to achieve sustained virologic response, HCV must be eradicated not just from the blood, but also the liver. GI-5005 may improve this critical part of the treatment and healing process in a way that is complementary to standard of care and the new direct acting antivirals."
An HCV-targeted cellular immune response is essential to curing a patient with hepatitis C. Twenty percent of patients infected with hepatitis C have immune responses strong enough to clear the virus on their own, without medical intervention. However, for the remaining 80 percent who go on to develop chronic infection, it takes the immune system six to twelve months to eliminate the infection, even with SOC and the best antivirals. Improving the rate of viral clearance may ultimately lead to a decrease in the time needed for therapy.
"The role of the immune response in combating hepatitis C infection is often overlooked," added Apelian. "Most of the recent development interest has been focused on new direct-acting antivirals, which inhibit viral replication. However, to improve the rate of viral clearance from the liver, it is necessary to stimulate an HCV targeted cellular immune response. We believe that the Phase 2 data to date demonstrate the potential of GI-5005 to be an important and complementary part of the treatment of hepatitis C."
The GI-5005-02 clinical trial is a randomized, multi-center, Phase 2 study evaluating 140 patients, all with genotype 1 HCV infection. In the trial, 74 percent of the patients had never received prior treatment, and the remaining 26 percent experienced prior treatment failures.
GlobeImmune's GI-5005 is a targeted molecular immunogen (Tarmogen(R)) designed to elicit an HCV-specific T-cell response. Tarmogens are whole, heat-killed recombinant S. cerevisiae yeast that express antigens from one or more disease-related proteins.
About GlobeImmune
GlobeImmune Inc. is a private company developing targeted molecular immunogens, Tarmogens(R), for the treatment of cancer and infectious diseases. The company's lead product candidate, GI-5005, is a Tarmogen for the treatment of chronic hepatitis C infection (HCV). GI-5005 is designed to complement both the current standard of care and emerging novel therapies for HCV. The company's lead oncology program, GI-4000, targets mutated versions of the Ras oncoprotein for the treatment of pancreas cancer as well as other cancers that contain mutated Ras, including non-small cell lung cancer and colorectal cancer.
For additional information, please visit the company's Web site at www.globeimmune.com. <<
Plan B
Perhaps we can give our livestock makeovers and enter them in competitions:
http://www.telegraph.co.uk/news/picturegalleries/theweekinpictures/3331785/The-week-in-pictures-31-October-2008.html?image=24
SciAm on Curing HIV
To vanquish HIV, it surely will require us
To pursue this fiend as if we're in a war.
We must commit to neutralize the virus
By eliminating every latent reservoir!
http://www.sciam.com/article.cfm?id=can-hiv-be-cured
RE: Happy Halloween,,,, ":>) JL
Dear JL,
Nobody knows coagulation factors like the vampire community!
Best Wishes (and hope we all have a festive evening),
Hob
AAT's Effect on Islet Transplantation and Beta Cells
http://www.sciencedaily.com/releases/2008/10/081030102618.htm
>> Well-known Drug (AAT) Could Overcome Obstacles To Islet Transplantation, Study Suggests
ScienceDaily (Oct. 30, 2008) — Researchers from Ben-Gurion University of the Negev (BGU) in Beer-Sheva, Israel have demonstrated that treating diabetic animals with alpha-1-antitrypsin (AAT) following an islet transplantation procedure eliminates the inflammation that causes islet transplants to fail.
Similarly significant results using the same component, human AAT, but in an alternative animal diabetes model, further indicate that inflammation reduction is key to pancreatic islet beta cell survival.
According to Dr. Eli Lewis, director of the Clinical Islet Laboratory at BGU, "We have found that by targeting multiple inflammatory molecules using a safe, non-toxic and non-steroidal drug, we can block inflammation so effectively that we literally modify the immune response, facilitating transplant acceptance to successfully treat diabetics and those at risk."
Treating diabetics with transplanted human pancreatic islet cells can restore normal glucose levels and relieve the patient from insulin injections. However, with the use of present-day immunosuppressive drugs, these transplants do not last long because of underlying inflammation that destroys the insulin producing cells, and within five years of grafting, most patients return to insulin injections.
In his study published in PNAS, Dr. Lewis reports that treating diabetic mice with serum protease inhibitor alpha-1-antitrypsin (AAT) - a naturally occurring human anti-inflammatory agent - for a short 14-day monotherapy course following an islet transplant created a protective state around the transplant and kept the islet cells alive and functioning for over 120 days after treatment was stopped.
"In fact, after grafts were removed, a second grafting session was undertaken and to our surprise, animals accepted the same strain of islets without further therapy - while foreign islets were appropriately rejected. Their immune system was, so to speak, re-formatted by human AAT to allow the graft to be recognized and accepted," said Lewis.
Dr. Lewis continues, "Apparently, by eliminating the inflammatory component during transplantation, a protective branch of immune system had been encouraged to evolve. Indeed, when the grafted islet cells were recovered and examined, we discovered increased production of anti-inflammatory molecules inside the grafts as well as a population of protective regulatory T lymphocytes. These specialized lymphocytes appear to have migrated toward the islet grafts and located at the border between the graft and the recipient, where they engage in disarming of graft-targeted immune attacks."
Islet Transplantation
Human pancreatic islet transplantation is a vital option for type-1 diabetes patients. In this procedure, globally performed in over 50 centers, islets are collected from donors soon after death in a sterile laboratory. At the same time, a diabetic transplant candidate is reached and a transplantation team is recruited. In this relatively simple surgical procedure, islets are introduced into the liver under local anesthesia, and covered by minimal immunosuppression, complete insulin independence is achieved.
Unfortunately, islet mass is rapidly reduced after engraftment by robust local inflammation. Even more unfortunate for the grafted cells, there is no anti-inflammatory coverage due to the removal of steroids from immunosuppression protocol. For this reason, the typical islet recipient will receive at least two grafts in order to restore glucose levels. But perhaps the most discouraging information is that five-year islet cell function follow-up studies reveal unacceptably high islet erosion caused in part by unrestrained ongoing inflammation. There is, therefore, great demand for an anti-inflammatory islet survival regimen that is safe, feasible and effective.
"The study comes at a critical time since the therapy that the transplant teams have been using seems to have turned its back on the patients, with more than 80 percent of recipients returning to insulin injections after five years," Dr. Lewis explains. "While many are discouraged by the method, our paper recommends a safe, well known and widely used drug to provide exactly the coverage that is currently missing to make the transplants succeed. In fact, we're almost replacing the need for steroids in this specific setup by blocking inflammation where steroids would have."
Human AAT has been used for more than 20 years in the form of weekly intravenous injections to treat a rare but serious genetic abnormality known as alpha-1 antitrypsin deficiency, the most common cause of hereditary lung emphysema. In these long-lasting treatments, AAT exhibited an impressive safety record.
The U.S. Food & Drug Administration (FDA) has already approved a human clinical trial to begin to test the impact of AAT in type-1 diabetes patients undergoing islet transplantation at the University of Colorado Health and Science Center. Other clinical trial sites around the world are currently being evaluated.
Parallel Study Conducted
The study performed by Dr. Lewis' group gains great scientific support from a parallel study performed at the Transplant Center at Beth Israel Deaconess Medical Center (BIDMC) in Boston, Massachusetts, where a different animal diabetes model has been challenged with AAT and provided yet another unexpected finding.
"We think that it will also be necessary to restore proper insulin signaling, and the way to do that is by eliminating the curious inflammatory state that exists in muscle, fat and other insulin-sensitive tissues," says the author of the companion PNAS paper Maria Koulmanda, Ph.D, director of Non-Human Primate Research at BIDMC. "We were able to demonstrate that treatment with AAT – an agent that dampens inflammation but does not directly inhibit T-cell activation – ablates invasive insulitis and restores euglycemia (normal blood glucose concentration), immune tolerance to beta cells, normal insulin signaling and insulin responsiveness in NOD (non-obese diabetic) mice with recent onset type 1 diabetes," she says.
Their experiments show that the functional mass of beta cells actually expanded in the NOD mice treated with AAT. <<
Looking Forward to an Unstrapped FDA
http://tinyurl.com/59jfwd
>> Slow and steady upends the race: Strapped FDA has delayed several new drugs, distressing revenue-hungry industry [Chicago Tribune]
Oct. 30--Stepped-up scrutiny by federal regulators is holding up the release of a string of drugs to treat such common ailments as high cholesterol and osteoporosis.
At least 10 drugs for treating a range of ailments from rheumatoid arthritis and heart disease to diabetes and acid reflux have been delayed or shelved indefinitely in the last three months, according to information compiled by the Tribune and disclosures by drug companies, including North Chicago-based Abbott Laboratories and Deerfield-based Takeda Pharmaceuticals North America Inc.
Such delays can be problematic for consumers because they may not be getting the best treatment for their ailments, drugmakers say.
Although drug companies will not say how the delays will affect sales, new revenue is needed in an industry hampered by the economic downturn and myriad expiring patents and competition from cheaper generic drugs.
A report from research firm IMS Health announced Wednesday that the U.S. market for prescription drugs is expected to grow 1 percent to 2 percent, or between $287 million and $297 million this year. That is down from a projection earlier this year of 2 percent to 3 percent.
The FDA delays come on the heels of criticism over the agency's perceived lax oversight of drugs, most notably Vioxx. The arthritis pain pill was on the market for several years before a study showed Vioxx was linked to an increased risk of stroke and heart attack, forcing Merck & Co. in 2004 to withdraw the product used by millions.
The Vioxx imbroglio and other high-profile cases contributed to changes at the FDA last year.
"The new safety responsibility is causing them to re-evaluate applications when they come in and ask further questions that might not have been asked two years ago or so because of these new safety provisions," said Alan Goldhammer, vice president for scientific and regulatory affairs for Pharmaceutical Research and Manufacturers of America, a Washington lobby for drugmakers. "It's clearly unfortunate. That does cause concern for us and ultimately patients as well."
Reviews usually take 10 months after applications are submitted. In the past, the FDA met its approval goal 90 percent of the time, the agency and the lobbying group said. Now, the FDA is getting drugs approved on time 75 percent to 80 percent of the time.
"There is a new process we are working through, but hopefully this is a blip in the system," said Dr. John Jenkins, who heads the FDA's Office of New Drugs.
The FDA blames the lag time on a still-understaffed agency's ability to deal with new duties imposed by Congress and signed into law by President George W. Bush last year.
"There have been dramatic increases in workload that have not kept pace with increases in staffing, and that is one underlying issue," Jenkins said.
Despite the delays, Abbott's cholesterol drug TriLipix and Takeda's experimental proton pump inhibitor TAK-390MR and diabetes pill alogliptin are expected to be approved in the coming months. The companies said the FDA has not requested additional information, a sign there are unlikely safety problems with the drugs.
Jenkins' office has hired 220 people in the fiscal year that ended Sept. 30. But he said those staffers have a learning curve that includes new safety requirements and risk assessments.
"We are optimistic [the additional staffers] are going to help get us back on track," Jenkins said.
bjapsen@tribune.com <<
HIV Foiled by Spreading the CCR5 delta32 Mutation Around?
Has this approach been discussed here before?
http://www.prnewswire.com/cgi-bin/stories.pl?ACCT=104&STORY=/www/story/10-28-2008/0004913439&EDATE=
>> Sangamo BioSciences Presents Data at ICAAC Demonstrating 'In Vivo' Protection Against HIV Infection by CCR5-ZFN Therapeutic
Preclinical Animal Data Demonstrates Selective Survival Advantage of
ZFN-Treated Immune Cells after HIV Infection and Reduced Viral Loads
WASHINGTON and RICHMOND, Calif., Oct. 28 /PRNewswire-FirstCall/ --
Sangamo BioSciences, Inc. (Nasdaq: SGMO) announced today the presentation
of data demonstrating that human CD4 T-cells can be made permanently
resistant to HIV infection by treatment with zinc finger DNA-binding
protein nucleases (ZFN(TM)) resulting in an increase in CD4 T-cell counts
and a reduction in viral load in an animal model of HIV infection. The
presentation, entitled, "Establishment of HIV Resistant CD4 T-cells Using
Engineered Zinc Finger Protein Nucleases (ZFNs)" is taking place today at
the joint meeting of the Interscience Conference on Antimicrobial Agents
and Chemotherapy (ICAAC) and the Infectious Diseases Society of America
(IDSA) in Washington, DC.
"We are very excited about these data and our collaboration with
Sangamo to develop an HIV/AIDS therapeutic," said Carl June, M.D., Director
of Translational Research at the Abramson Family Cancer Research Institute
at the University of Pennsylvania School of Medicine, and a co-author of
the study. "The ability to prevent immune cells from becoming infected by
HIV has the potential to provide long term control of both the
opportunistic infections characteristic of AIDS as well as the virus
itself. We look forward to bringing this program into the clinic."
Sangamo's ZFNs are designed to permanently modify the DNA sequence
encoding CCR5, a co-receptor that enables HIV to enter and infect cells of
the immune system. Individuals carrying a naturally occurring mutation of
their CCR5 gene, a variant known as CCR5-delta32, have been shown to be
resistant to HIV infection.
"These data provide good support for the evaluation of our first
ZFN-based ZFP Therapeutic in man," commented Dale Ando, M.D., Sangamo's
vice president of therapeutic development and chief medical officer. "It
was observed more than ten years ago that individuals carrying the natural
CCR5-delta32 mutation were highly resistant to infection by HIV.
Consequently, a variety of small molecule and antibody approaches have been
tested as potential therapeutics. However, a small molecule or antibody
approach requires the constant presence of a sufficiently high
concentration of drug to block therapeutically relevant numbers of the CCR5
protein, which is present in thousands of copies on the surface of each
T-cell and other tissues in the body. We believe that our ZFN technology
provides an approach that circumvents the dosing and potential toxicity
issues of a systemic therapy. By specifically modifying only CD4 T-cells,
the principal target of HIV pathology, in a one-time exposure of the cells
to ZFNs, we can generate a population of R5-tropic HIV-resistant T-cells.
We have shown that these ZFN-modified human cells are made permanently
resistant to infection by HIV. Furthermore, the cells selectively survive
and expand in an animal after HIV infection, providing a reservoir of
healthy and uninfectable immune cells. In a patient, such cells could be
available to fight both opportunistic infections characteristic of AIDS and
HIV itself. The modified cells exhibited the expected properties of normal
CD4 T-cells. These data also demonstrate that ZFN-modified human CD4
T-cells can be produced in the quantities required for the translation of
this program into the clinic. We intend to file an investigational new drug
(IND) application for this ZFP Therapeutic this year and begin a clinical
trial as soon as possible."
Data Reported in the ICAAC/IDSA Presentation
The reported results demonstrate that a one-time exposure to
CCR5-specific ZFNs resulted in the generation of an HIV-resistant
population of primary human T-cells by the permanent genetic modification
of the CCR5 gene. These ZFN-modified CD4 T-cells expanded stably in
HIV-infected cultures for several weeks and appeared to behave identically
to untreated T-cells except that they were resistant to infection by HIV.
ZFN treated primary CD4 T-cells and transformed CD4 cell lines resisted
infection with R5-tropic HIV (virus that uses the CCR5 co-receptor to enter
cells), resulting in enrichment of ZFN-generated CCR5-disrupted cells in
the population upon exposure to virus. Importantly, in the presence of HIV,
ZFN-modified CD4 T-cells also preferentially expanded in a mouse model. The
modified cells were infused into mice that lack a normal immune system and
thus do not reject human cells. After 33 days, the mice were sacrificed and
analyzed for the presence of ZFN-modified cells. Researchers determined
that ZFN-modified cells engrafted normally in the mouse and that the
proportion of modified cells present at the end of the experiment was
greater than two to three fold higher in mice in the presence of HIV
infection (p=0.008). It was also determined that 50 days after infection,
mice given the ZFN-modified cells had increased numbers of CD4 cells and a
statistically significant seven-fold reduction in viral load in their
peripheral blood (P<0.001) compared to mice given control cells. A high
level of specificity of the CCR5-ZFNs for their target site was
demonstrated by immunochemistry and direct genomic sequence analysis of
ZFN-treated human CD4 T-cells. These data suggest that, in the presence of
HIV, the ZFN-modified cells have a selective advantage allowing them to
evade infection and destruction leaving them able fight opportunistic
infections and HIV itself.
In addition, Sangamo and its collaborators have demonstrated successful
ZFN-modification of clinical-scale quantities of human CD4 T-cells and that
these modified cells exhibited the expected properties of normal T-cells.
This demonstrates that ZFN-modified human CD4 T-cells could be produced in
quantities required for the translation of this program into the clinic.
About HIV/AIDS and CCR5
HIV stands for Human Immunodeficiency Virus. HIV infection kills or
impairs cells of the immune system, progressively destroying the body's
ability to fight infections and certain cancers resulting in AIDS (Acquired
Immune Deficiency Syndrome). Individuals diagnosed with AIDS are
susceptible to life-threatening diseases called opportunistic infections,
which are caused by microbes that usually do not cause illness in healthy
individuals. According to UNAIDS/WHO, over 2.7 million people were infected
with HIV in 2007. There are now over 33 million people living with HIV and
AIDS worldwide.
CCR5 is the chemokine receptor that HIV uses as a co-receptor to gain
entry into immune cells. CCR5 is perhaps the most important of the known
co-receptors for HIV, since the most commonly transmitted strains of HIV
are strains that bind to CCR5 -- so-called "R5" strains. A small fraction
of the population carries a mutation in their CCR5 gene, called the delta32
mutation. This mutated version of the gene produces malformed CCR5
proteins, which cannot be used by HIV as a co-receptor. Individuals that
have two copies of this mutant form of CCR5 (delta32) are resistant to
infection by R5 HIV strains.
About Sangamo
Sangamo BioSciences, Inc. is focused on the research and development of
novel DNA-binding proteins for therapeutic gene regulation and
modification. The most advanced ZFP Therapeutic(TM) development program is
currently in Phase 2 clinical trials for evaluation of safety and clinical
effect in patients with diabetic neuropathy and ALS. Other therapeutic
development programs are focused on cancer, HIV/AIDS, neuropathic pain,
nerve regeneration, Parkinson's disease and monogenic diseases. Sangamo's
core competencies enable the engineering of a class of DNA-binding proteins
known as zinc finger DNA-binding proteins (ZFPs). By engineering ZFPs that
recognize a specific DNA sequence Sangamo has created ZFP transcription
factors (ZFP TF(TM)) that can control gene expression and, consequently,
cell function. Sangamo is also developing sequence-specific ZFP Nucleases
(ZFN(TM)) for gene modification. Sangamo has established strategic
partnerships with companies outside of the human therapeutic space
including Dow AgroSciences, Sigma-Aldrich Corporation and several companies
applying its ZFP technology to enhance the production of protein
pharmaceuticals. For more information about Sangamo, visit the company's
web site at http://www.sangamo.com. <<
Kamada's AAT PH III Trial Results Confirmed
http://genengnews.com/news/bnitem.aspx?name=44200884&taxid=0
>> Oct 26 2008, 6:50 AM EST
Kamada: Pivotal Phase III Data Confirms Efficacy and Safety of Intravenous Alpha-1 Antitrypsin
News source: Business Wire
Kamada (www.kamada.com), a biopharmaceutical company engaged in the development, manufacturing and marketing of specialty life-saving therapeutics, announced today that it has completed the final analysis of its US Phase III trial with intravenous Alpha-1 Antitrypsin (AAT), for hereditary AAT deficiency. In keeping with headline results announced in April, the study met its primary endpoint. The company has now officially completed the clinical stage of this product's development, high safety profile sided to meeting the primary endpoint were determined.
The company is pleased with the final outcome of this study and plans file a BLA with the FDA in 2009. Information about the study will be presented at an upcoming major medical conference.
The trial, conducted in accordance with FDA requirements, was a controlled, randomized, double-blind, partial cross-over study that compared Kamada's intravenous AAT with a comparator product. Forty-Eight AAT-deficient patients were randomized 2:1 for the first 12-weeks to weekly infusion of Kamada's AAT or weekly infusion of comparator drug; all patients then received Kamada's AAT for a further 12 weeks. The efficacy endpoints of the study were determined by serum concentration of AAT and levels of AAT and other biomarkers in epithelial lung fluid. Safety parameters were explored and determined.
Key points: The results indicate the high quality of the Kamada product and its ability to reach the required trough levels in AAT patients. With regards to safety, no safety concerns were demonstrated. The safety profile was comparable to that of the comparator product.
David Tsur, Chief Executive Officer of Kamada, commented: "This is a major achievement for Kamada and it marks another significant step in our strategy to enter the US market with this product. Our intravenous AAT is the only ready-to-use AAT product that does not require reconstitution before use, offering patients and care-givers a much more convenient treatment option. Additionally, the high purity of the product and the fact that it does not consist of any added substances increases its future acceptance in the medical community."
About Kamada
Kamada is a public biopharmaceutical company (TASE: KMDA) developing, producing and marketing a line of specialty life-saving biopharmaceuticals using its proprietary chromatographic purification technologies. Licensed and marketed worldwide, several of these specialty therapeutics are currently undergoing advanced clinical trials.
For additional information, please visit www.kamada.com or contact Sivan Shatil, Marketing Communications Manager, at sivans@kamada.com, or - 972-52-666-5762 <<
EXEL-GSK Collaboration: finis
http://genengnews.com/news/bnitem.aspx?name=44022882&taxid=0
>> Oct 23 2008, 6:15 AM EST
Exelixis Retains Rights to Develop and Commercialize XL184
News source: Business Wire
Exelixis, Inc. (Nasdaq:EXEL) today announced that GlaxoSmithKline (GSK) (LSE: GSK; NYSE: GSK) has decided not to exercise its option to license XL184. GSK also informed Exelixis that it had decided not to license the earlier compounds in the collaboration, including XL281, XL228, XL820, and XL844. As a result, Exelixis retains the rights to develop, commercialize, and/or license all of the compounds, subject to payment to GSK of a 3% royalty on net sales of any product incorporating XL184. With GSK's decision not to exercise an option to any of the compounds, the six-year collaboration between Exelixis and GSK to discover and develop oncology compounds comes to an end. GSK will continue development and commercialization of XL880, a compound developed under the collaboration and previously in-licensed by GSK, with potential additional milestone payments of up to $90 million and double-digit royalty payments to Exelixis on XL880's successful development and commercialization. Encouraging data on several of the compounds, including XL184 (MET, RET, VEGFR2), XL281 (RAF), and XL228 (BCR-ABL, IGF1R, SRC), were presented at the EORTC-NCI-AACR meeting this week, and there will be additional data presented on XL228 at the American Society of Hematology (ASH) meeting in December.
"We are pleased to retain the rights to develop and commercialize XL184," said George A. Scangos, PhD, President and Chief Executive Officer of Exelixis. "This compound is our most advanced asset with a promising mechanism of action. It has generated compelling data in patients with medullary thyroid cancer, and data emerging from the phase 2 trial being conducted in patients with glioblastoma also are encouraging. We recently initiated a phase 3 registration trial for XL184 in MTC, and we look forward to the successful progress of this and other trials for the compound. We have had a significant number of inquiries about our willingness to partner the program and we are exploring all options to advance the program and maximize its value to the company. Additionally, we believe data recently presented on XL281 and XL228, and additional data that will be presented for XL228 later this year, indicate that they also have substantial potential as anti-cancer agents."
"Exelixis now has the rights to XL184, XL281, XL228, as well as two earlier compounds, XL844 and XL820," Dr. Scangos continued. "These compounds, together with the compounds already in Exelixis' proprietary clinical pipeline, XL147, XL765, XL019, and XL888, comprise a deep pipeline of promising oncology compounds. The clarity achieved through the expiration of the collaboration will allow Exelixis to further define its clinical, commercial, and financial strategies, which will become apparent over the next few months."
Paolo Paoletti, MD, Senior Vice President of GSK Oncology R&D, commented, "GSK and Exelixis have successfully concluded this long-term collaboration which has resulted in the discovery and development of a number of promising compounds with potential benefit to cancer patients."
Additional clinical studies with XL184 are ongoing to complement the pivotal trial in patients with MTC. This is part of Exelixis' strategy to rapidly advance compounds into areas of high unmet medical need, while potentially expanding into broader commercial markets by demonstrating activity in major tumor types. A phase 1b/2 trial of XL184 as a single agent and in combination with erlotinib was recently initiated in patients with non-small cell lung cancer. In addition, a phase 2 study of XL184 in patients with glioblastoma multiforme is ongoing.
Background on Exelixis-GSK Collaboration
In October 2002, Exelixis and GSK established a broad alliance to discover, develop, and commercialize novel therapeutics in the areas of vascular biology, inflammatory disease, and oncology. Under the terms of the collaboration, Exelixis was required to deliver to GSK a number of small molecule compounds that met agreed-upon proof-of-concept criteria, and GSK had the right to select up to two of the compounds for further development and commercialization. GSK previously selected XL880, and it has now decided not to select any of the compounds remaining in the collaboration: XL184, XL281, XL228, XL820, and XL844. Exelixis and GSK will bring their six-year collaboration to a successful conclusion on October 27, 2008, as scheduled. Exelixis will have full rights to compounds not selected by GSK and may, either alone or in collaboration with partners, advance the development and commercialization, in some cases with a small royalty to GSK on sales of collaboration compounds not selected by GSK. As a result of the conclusion of the collaboration, Exelixis' exclusivity obligations will be limited to the compounds selected by GSK. Exelixis will have the right to perform additional discovery, development, and commercialization efforts against any collaboration target or compound that does not infringe upon the intellectual property associated with compounds selected by GSK for further development and commercialization.
About XL184
XL184 inhibits MET, RET, and VEGFR2, which are key drivers of tumor growth, metastasis, survival, and angiogenesis. In pharmacodynamic studies in mice, oral administration of XL184 resulted in balanced and durable inhibition of these targets. The compound has also shown activity against common mutant forms of RET and MET. XL184 has exhibited dose-dependent tumor growth inhibition and tumor regression in a variety of preclinical tumor models, including breast cancer, colon cancer, MTC, non-small cell lung cancer, and glioblastoma. In July 2008, on the basis of the encouraging phase 1 trial data, Exelixis initiated a phase 3 registration trial of XL184 for the potential treatment of MTC. Exelixis and the U.S. Food and Drug Administration had previously reached agreement on this phase 3 registration trial via the Special Protocol Assessment process.
About Medullary Thyroid Cancer
The American Cancer Society estimates that MTC accounts for 5% of all thyroid cancers. MTC occurs in sporadic and inherited forms (approximately 80% and 20% of MTC, respectively). Patients with the inherited form of MTC invariably have an activating mutation in RET in their germline DNA. Activating mutations in RET are also present in the tumor DNA of up to 50% of sporadic MTC patients with no familial history of thyroid cancer. MTC may metastasize to lymph nodes or other organs before it is ever diagnosed. Additionally, MTC does not take up radioactive iodine, which is commonly used to treat other types of thyroid cancers and to diagnose metastases. As a result, MTC is more difficult to treat than other thyroid cancers. There are no approved therapies for MTC; however, common treatments for MTC include surgery to remove malignant tissue, radiation therapy, and chemotherapy, all of which are associated with potential side effects, some of which may be long-term.
About XL228
XL228 is a protein kinase inhibitor with potent activity against wild-type and the T315I mutant forms of BCR-ABL, with additional activity against IGF1R, SRC, and Aurora A. These targets play crucial roles in cancer cell proliferation, survival, and metastasis. XL228 blocks downstream signaling from BCR-ABL T315I in cell lines and modulates phosphorylated CrkL levels in mouse xenografts consistent with inhibitory activity against BCR-ABL in vivo. XL228 has exhibited activity in a variety of solid tumor xenograft models.
About XL281
XL281 is a novel small molecule designed to selectively inhibit RAF kinases, which lie immediately downstream of RAS and are key components of the RAS/RAF/MEK/ERK kinase signaling pathway. Genetic lesions that activate this pathway are common in human tumors, with activating mutations in KRAS occurring in 30 percent of tumors and activating mutations in BRAF occurring in approximately 60 percent of melanomas. The RAS/RAF/MEK/ERK pathway also plays a key role in the transmission of growth-promoting signals downstream of receptor tyrosine kinases. This suggests that deregulation of this pathway plays a pivotal role in the progression of many human tumors, and that inhibition of the pathway may be useful in the treatment of cancer. XL281 potently inhibits BRAF, mutationally activated BRAF, and CRAF in vitro, and does not interact with kinases outside of the RAF family. XL281 displays high oral bioavailability in multiple preclinical species, and strongly inhibits RAS/RAF/MEK/ERK signaling in human xenograft tumor models. This translates into substantial inhibition of tumor growth in preclinical models of human tumors that overexpress receptor tyrosine kinases or harbor activating mutations in RAS or RAF.
About Exelixis
Exelixis, Inc. is a development-stage biotechnology company dedicated to the discovery and development of novel small molecule therapeutics for the treatment of cancer and other serious diseases. The company is leveraging its fully integrated drug discovery platform to fuel the growth of its development pipeline, which is primarily focused on cancer. Currently, Exelixis' broad product pipeline includes investigational compounds in phase 3, phase 2, and phase 1 clinical development. Exelixis has established strategic corporate alliances with major pharmaceutical and biotechnology companies, including GlaxoSmithKline, Bristol-Myers Squibb, Genentech, Wyeth Pharmaceuticals, and Daiichi-Sankyo. For more information, please visit the company's website at http://www.exelixis.com. <<
AAT May Play Key Role In Type 1 Diabetes
http://www.sciencedaily.com/releases/2008/10/081014111311.htm
>>Protein Made In Liver Restores Blood Glucose In Type 1 Diabetes Model
ScienceDaily (Oct. 15, 2008) — A protein made by the liver in response to inflammation and used to treat patients suffering from a genetic form of emphysema has been shown to restore blood glucose levels in a mouse model of Type 1 diabetes mellitus, according to a new study led by researchers at Beth Israel Deaconess Medical Center (BIDMC).
The findings, which appear in the Online Early Edition of the Proceedings of the National Academy of Sciences (PNAS) this week, provide further proof that inflammation plays a key role in the development of Type 1 diabetes and suggest that the protein – known as AAT --might be an option for clinical testing in humans.
Formerly known as juvenile-onset or insulin-dependent diabetes, Type 1 diabetes is an autoimmune disease that develops when the body's immune cells (known as T-cells) overreact and attack and destroy its own pancreatic beta cells. Without beta cells, the body is unable to produce insulin, a hormone needed to convert glucose into energy. To prevent the development of serious – and even fatal -- complications, more than 21 million individuals with Type 1 diabetes, primarily children and young adults, must receive as many as three insulin injections each day.
"To cure Type 1 diabetes, it will not be enough to halt the destructive T-cell-dependent autoimmune attack on beta cells," explains the study's lead author Maria Koulmanda, PhD, Director of Non-Human Primate Research in the Transplant Center at Beth Israel Deaconess Medical Center (BIDMC) and Associate Professor of Surgery at Harvard Medical School (HMS). "We think that it will also be necessary to restore proper insulin signaling, and the way to do that is by eliminating the curious inflammatory state that exists in muscle, fat and other insulin-sensitive tissues."
Last year, Koulmanda, together with the paper's senior author Terry Strom, MD, Director of Transplant Research at BIDMC and Professor of Medicine at HMS, established a role for insulin resistance and inflammation in the onset of Type 1 diabetes, a finding that challenged many theories regarding the autoimmune disease. Their findings demonstrated for the first time that a form of inflammation in fat and muscle was preventing insulin from "allowing" blood glucose into tissues requiring glucose. They further demonstrated that normal blood glucose levels could be successfully restored in a non-obese diabetic (NOD) mouse model by administering a triple combination therapy consisting of both tolerance-inducing and anti-inflammatory properties.
In this new paper, Koulmanda borrowed the AAT protein to achieve the same results.
"The AAT protein is made by the liver and functions to halt unchecked inflammation," she explains. "In cases of Type 1 diabetes, inflammation is the factor that determines whether T-cells exert destructive or protective forms of immunity. We, therefore, hypothesized that [in cases of Type 1 diabetes] immune tolerance could be reestablished by using the AAT protein to modify a pro-inflammatory state and turn it into an anti-inflammatory state."
Using the NOD mouse model, the authors tested the hypothesis that inflammatory mechanisms directly trigger insulitis, insulin resistance, faulty insulin signaling and the loss of immune tolerance to islets.
"We were able to demonstrate that treatment with AAT – an agent that dampens inflammation but does not directly inhibit T-cell activation – ablates invasive insulitis and restores euglycemia [normal blood glucose concentration], immune tolerance to beta cells, normal insulin signaling and insulin responsiveness in NOD mice with recent onset Type 1 diabetes," she says.
Most dramatic, adds Koulmanda, their experiments found that the functional mass of beta cells actually expanded in the NOD mice treated with AAT.
The AAT protein is already in widespread use as a replacement therapy in treating Alpha-1 antitrypsin deficiency, an inherited disorder that can cause emphysema-like lung disease in adults and liver disease in children.
"In humans, AAT has been used for more than two decades, and has maintained an impressive safety record," says Koulmanda. "We believe that treatment with AAT will prevent and delay further loss of functioning residual beta cells in patients with recent onset Type 1 diabetes.
"With this study, we've shown that modifications in inflammation indirectly – but powerfully – modify ongoing destructive-type immunity," she adds. "And most exciting, by administering AAT to the diabetic mice, we actually achieved beta cell expansion, which has never been shown with any other treatment."
This study was funded by grants from the National Institutes of Health and the Juvenile Diabetes Research Foundation.
In addition to Koulmanda and Strom, coauthors include BIDMC investigators Manoj Bhasin, Lauren Hoffman, Zhigang Fan, Andi Qipo, Hang Shi, Prabhakar Putheti, Nicolas Degauque, Towia Libermann and Jeffrey Flier; Susan Bonner-Weir of the Joslin Diabetes Center; and Hugh Auchincloss, Jr., of Harvard Medical School. <<
RE:>Ribozymes - clearly the wave of the future!<
My comment was intended ironically to demonstrate my (sorry) grasp of trends in biotechnology. Sorry if it misled you.
While the final chapter may not have been written, ribozymes have not advanced much clinically:
http://clinicaltrials.gov/ct2/results?term=ribozyme
Hob
>Are you an investor in Regado?<
No. I've followed Archemix Corp. even before they embraced aptamers. Prior to purchasing aptamer IP from Gilead Sciences in 2001, Archemix was pursuing allosteric ribozymes. Ribozymes - clearly the wave of the future!
Hob
Regado Completes PIIa Enrollment for its Anticoagulant & Reversal Agent
http://genengnews.com/news/bnitem.aspx?name=43525062&taxid=0
>> Oct 14 2008, 3:30 AM EST
Regado Biosciences Completes Patient Enrollment for Phase IIa Study of REG1 Anticoagulation System
DURHAM, N.C., Oct. 10 /PRNewswire/ -- Regado Biosciences, Inc., announced today the Company has completed enrollment in the Phase IIa clinical study of its REG1 Anticoagulation System in patients undergoing elective percutaneous coronary intervention (PCI). REG1 is a two-component system composed of an aptamer-based anticoagulant, RB006, and its matched, active reversal agent, RB007, which specifically binds to and neutralizes RB006. The Phase IIa study (REVERSAL-PCI) is designed to assess whether REG1 can replace standard heparin therapy during the performance of coronary balloon angioplasty dilatation and stenting on patients at low risk for complications associated with therapy-related bleeding or heart attack.
REVERSAL-PCI, a multi-center, open-label, randomized clinical study, has enrolled a total of 26 patients. All patients were pretreated with clopidogrel and aspirin to inhibit platelet activity and were then randomized to receive either REG1 or unfractionated heparin. In patients treated with the REG1 System, RB006 was used as the sole anticoagulant during the procedure. Following the procedure, RB007 was used to reverse the effects of RB006 with the goal of facilitating early sheath removal. Primary procedural success in the trial is defined by the absence of significant bleeding events up to hospital discharge or 48 hours post stenting, and by the absence of death, nonfatal heart attack, or need to repeat revascularization up to day 14.
David J. Mazzo, Ph.D., President and Chief Executive Officer of Regado Biosciences, stated, "The Phase IIa trial is designed to build on extensive Phase I results demonstrating, among other things, that RB006 safely and effectively inhibited the activity of factor IXa, an essential blood clotting protein, and that RB007 rapidly, safely and specifically reversed the activity of RB006. We are pleased to have reached this milestone in our clinical program and look forward to continued progress in the coming months."
About REG1 Anticoagulation System
The REG1 system consists of the first specific, direct-acting anticoagulant controllable by a matched reversal agent. Regado is developing REG1 for use in patients suffering from acute coronary syndrome who undergo coronary revascularization procedures. These procedures, which include percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG), put patients at a high risk for therapy-related bleeding complications. REG1 is being developed initially to increase safety and therapeutic flexibility as well as to improve patient outcomes in coronary revascularization procedures.
REG1 is a two-component system, consisting of an aptamer-based anticoagulant and its matched reversal agent. The anticoagulant component, RB006, is a single-stranded, nucleic acid aptamer. RB006 selectively and potently binds to and inhibits factor IXa, a protein that is critical to blood coagulation. The reversal agent, RB007, is a complementary nucleic acid that specifically binds to and neutralizes RB006. The amount of RB007 administered allows physicians to rapidly fine tune the pharmacodynamic effect of RB006, from slight reduction in anticoagulation all the way to complete reversal.[Like playing a violin?]
About Regado Biosciences
Regado Biosciences is pioneering a new therapeutic field with the discovery and development of two-component drug systems, comprising an aptamer therapeutic that can be controlled directly by a specific and matched reversal agent. Regado's technology is designed to give physicians the ability to directly control and fine tune each product's therapeutic effect. This control and flexibility allows physicians to meet the individual needs of each patient independent of the setting. Regado initially is focusing its discovery and development efforts on acute care injectable antithrombotics, a multi-billion dollar market in need of therapeutics with improved safety profiles.
Current investors in Regado include Domain (Princeton, NJ), Quaker BioVentures (Philadelphia, PA), Aurora Funds (Durham, NC) and Caxton Advantage Life Sciences Fund (New York, NY), as well as individual investors, including Robert Kierlin. <<
RE:>what have you been buying recently?<
Why are you buying HQH rather than HQL?
As of 10/10/2008, their discounts to NAV are
HQH: 14.69%
HQL: 29.14%
Cordially,
Hob("The Sun 'll Come Out Tomorrow")Globulin
Ovation PR on ATryn BLA
http://www.businesswire.com/portal/site/biospace/index.jsp?ndmViewId=news_view&newsId=20081006005930&newsLang=en
>> ATryn® (antithrombin alfa) BLA Filing Accepted by FDA
DEERFIELD, Ill.--(BUSINESS WIRE)--OVATION Pharmaceuticals, Inc. announced today that the U.S. Food and Drug Administration (FDA) has accepted for review the Biologics License Application (BLA) for ATryn® (antithrombin alfa). OVATION acquired the exclusive U.S. license to ATryn in August from GTC Biotherapeutics, allowing the company to develop and commercialize the product in this country. The acceptance of the BLA comes just one month after the FDA assigned a priority review to the product, which has also been granted orphan drug designation. An action letter is expected in February, 2009.
ATryn is under review for the treatment of a rare disorder called hereditary antithrombin deficiency, or HD, involving people who do not have sufficient antithrombin in their bloodstream. Antithrombin is a protein that helps keep blood from clotting and has anti-inflammatory properties.
“We are excited about how well ATryn is progressing through the regulatory process and are particularly pleased that FDA has accepted the filing for review,” said Jeffrey S. Aronin, OVATION President and Chief Executive Officer. “This is a key milestone that paves the way for FDA to consider its approval early next year following the Blood Products Advisory Committee meeting in January.”
ATryn is one of two product licensing agreements OVATION has completed in the last 60 days. With one of these products launching by the end of this year, and two more products – including ATryn – now under FDA review, the company is positioned to bring three new, orphan-designated products to market over the next year.
The most common adverse events listed in the approved European labeling that may occur during treatment with ATryn include dizziness, headache, bleeding, nausea, bleeding at injection site and increased bleeding during treatment.
About OVATION Pharmaceuticals
OVATION is a fast-growing biopharmaceutical company that develops, manufactures and markets medically necessary therapies to satisfy unmet medical needs for patients with severe illnesses. Headquartered in Deerfield, Ill., with products available in more than 85 countries, OVATION is committed to having a significant impact on patients’ lives through its focus on central nervous system, hematology/oncology, and hospital-based therapies. The four new launches the company expects over the next three years will be fueled by its late-stage CNS pipeline, which is one of the most robust in the industry. OVATION has been recognized for excellence in the global pharmaceutical and biotechnology industries with the 2006 and 2007 “Pharma Company of the Year” award from Scrip magazine for small to mid-sized enterprises. More information about the company, its products and full prescribing information may be found at www.ovationpharma.com. <<
Promising News for Somniloquists
http://genengnews.com/news/bnitem.aspx?name=40477637
>> Aug 15 2008, 3:41 PM EST
A therapy for baby boomers to sleep on
Contact: George Hunka
ghunka@aftau.org
212-742-9070
American Friends of Tel Aviv University
If you're over 55 and have spent more than a few sleepless nights, you're not alone -- insomnia affects about half of all people over 55 -- but you may also be at increased risk for physical and mental ailments.
Many older adults don't get enough restorative sleep, leading to serious health concerns, including cardiovascular disease, obesity, diabetes, memory problems and increased rates of depression. Unfortunately, current sleeping pills are associated with memory problems, a risk for falls, dependency, withdrawal symptoms and disturbed sleeping patterns.
Circadin, a new drug developed at Tel Aviv University by Prof. Nava Zisapel, a chemist and neurobiologist from TAU's George S. Wise Faculty of Life Sciences, may help America's aging baby boomers get the much-needed sleep they need. Recent results from Prof. Zisapel's research with Circadin appear in the Journal of Sleep Research and are reviewed in Aging Health.
How the Body Tells Time
Prof. Zisapel's research centers on the hormone melatonin, which affects the way our biological functions differentiate between day and night. "As we age, the melatonin hormone signal weakens," says Prof. Zisapel. "As a result, our bodies and brains feel less difference between day and night."
Exacerbating the effect of low melatonin levels, aging people tend to sleep in a less organized fashion than younger people, Prof. Zisapel explains. "People are sleeping in front of the TV, or nodding off during conversations, and taking long afternoon naps. This leads to less sleep at night. In a way, their sleep habits become more like babies', and less like those of healthy adults who sleep in consolidated periods during the night."
Mimicking the profile of nighttime melatonin found in our bodies, Circadin replenishes the much-needed hormone, which declines steadily with age. Clinical trials in the United States and Europe found that Circadin improves sleep quality and morning alertness, and helps those 55 and over get a better night's sleep.
Her new drug therapy "improves sleep and daytime vigilance, helping to re-organize the circadian system, the body's internal clock," Prof. Zisapel says. Added benefits include more normalized blood pressure and blood sugar levels at night. The formulation also has a profound effect on the blind, whose biological clock is disturbed because they can't see light, a trigger for synchronizing with the external day/night cycle.
Advice for Sound Sleep Hygiene
Until Circadin is available in the United States, there are some simple steps seniors can take to get a good night's sleep, Prof. Zisapel says. Spending a couple of hours outdoors every day can help. Sipping lattes on a cafe patio (away from direct sunlight) can be pleasurable, and increases the exposure to natural light from the blue-green spectrum. Experiencing a full spectrum of light during the day could also be beneficial, as is routine exercise and avoiding daytime naps and sleeping in front of the TV.
###
Prof. Zisapel is the past director of the Adams Brain Research Center at Tel Aviv University and is the Chief Scientific Officer of Neurim Pharmaceuticals, a company commercializing the technology and licensing it from Ramot, the technology transfer arm of Tel Aviv University. The new drug is currently available in Europe, and is expected to be in the United States by next year.
American Friends of Tel Aviv University (www.aftau.org) supports Israel's largest and most comprehensive center of higher learning. It is ranked among the world's top 100 universities in science, biomedical studies, and social science, and rated one of the world's top 200 universities overall. Internationally recognized for the scope and groundbreaking nature of its research programs, Tel Aviv University consistently produces work with profound implications for the future. <<
Appetite and Antioxidants: Eschew Satiety
http://www.sciencedaily.com/releases/2008/07/080730140720.htm
>> Brain Plays Key Role In Appetite By Regulating Free Radicals
ScienceDaily (Aug. 3, 2008) — Researchers at Yale School of Medicine have found the brain's appetite center uses fat for fuel by involving oxygen free radicals—molecules associated with aging and neurodegeneration. The findings, reported in the journal Nature, suggest that antioxidants could play a role in weight control.
The study's lead authors were Sabrina Diano and Tamas Horvath, who are an associate professor and professor, respectively, in the Departments of Obstetrics, Gynecology & Reproductive Sciences and Neurobiology. Horvath is also chair of the Section of Comparative Medicine.
"In contrast to the accepted view, the brain does use fat as fuel," said Horvath. "Our study shows that the minute-by-minute control of appetite is regulated by free radicals, implying that if you interfere with free radicals, you may affect eating and satiety."
The results also imply, added Horvath, "that each time a feeling of fullness or satiety is reached during a meal, you may be chipping away some time from your maximum lifespan as the most free radicals are produced when satiety-promoting brain cells are active."
Diano, Horvath and colleagues conducted the study in mice to better understand how the brain mediates neuronal activation in response to ghrelin, a hormone produced in the stomach and previously associated with growth hormone release, appetite, learning and memory.
They found that ghrelin-induced increase in appetite is driven by burning fat in hypothalamic mitochondria, which produces free radicals that are scavenged by a mitochondrial protein called uncoupling protein 2 (UCP2)
"The timing of taking antioxidants may be critical for the control of appetite," said Diano. "If taken on an empty stomach antioxidants may further increase appetite, however when taken with food, they may affect satiety. Further studies are needed to determine whether any regiment of orally taken antioxidants could be used to control appetite in animals and humans."
Other authors on the study included Zane B. Andrews, Zhong-Wu Liu, Nicholas Walllingford, Derek M Erion, Erzsebet Borok, Jeffrey M. Friedman, Matthias H. Tschöp, Marya Shanabrough, Gary Cline, Gerald I. Shulman, Anna Coppola and Xiao-Bing Gao. <<
Personalized Lymphoma Vaccines from Tobacco Plants
[Dr. Levy was a cofounder of IDEC Pharmaceuticals.]
http://genengnews.com/news/bnitem.aspx?name=39090562
>> Jul 21 2008, 5:00 PM EST
Plants Make Vaccine for Treating Type of Cancer in Stanford Study
News source: Business Wire
Plants could act as safe, speedy factories for growing antibodies for personalized treatments against a common form of cancer, according to new findings from the Stanford University School of Medicine. The findings came in the first human tests of an injectable vaccine grown in genetically engineered plants.
The treatments, which would vaccinate cancer patients against their malignant cells, could lead to earlier personalized therapy to tackle follicular B-cell lymphoma, an immune-system malignancy diagnosed in about 16,000 people each year.
Doctors regard follicular B-cell lymphoma as a chronic, incurable disease. The standard treatment, chemotherapy, has such severe side effects that patients often opt for watchful waiting in the early stages of illness. However, plant-grown vaccines, which lack side effects, could allow earlier, more aggressive management of the cancer.
"This would be a way to treat cancer without side effects," said Ronald Levy, MD, professor of oncology and the Robert K. and Helen K. Summy Professor in the School of Medicine, who is the study's senior author. "The idea is to marshal the body's own immune system to fight cancer."
The findings will appear July 21 in the advance online issue of the Proceedings of the National Academy of Science. The study was a phase-1 trial that showed plant-grown cancer vaccines were safe for patients and could be produced quickly and cheaply. Sixteen newly diagnosed lymphoma patients received the treatment; none experienced any side effects from plant-grown vaccines.
Future studies will test the vaccine's effectiveness.
The cancer vaccines rely on a biological quirk of follicular B-cell lymphoma, which is a type of non-Hodgkin's lymphoma. The cancer starts when a single immune cell multiplies uncontrollably, producing many identical clones of itself. The clones all carry the same antibody on their exterior, a marker that is unique to the cancer and is not found on any of the body's healthy cells. Levy's vaccination strategy is to inject many copies of the cancer-specific antibody into a newly diagnosed lymphoma patient, stimulating the patient's immune system to seek and destroy malignant cells.
Previous trials of this kind of vaccine, produced in animal cells and tested in mice and humans, have had mixed success, and the vaccines are not yet commercially available. Growing cancer vaccines in plants could circumvent some of the hurdles to turning the concept into a real treatment, Levy said.
Because each person's cancer antibody is unique, every patient needs a personalized vaccine. Growing personalized vaccines in animal cells takes months, costs thousands of dollars per patient and comes with the theoretical risk that a patient might inadvertently be infected with an animal virus that contaminated the cells used to grow the vaccine. Personalized vaccines could also be produced with genetically engineered bacteria, but bacteria-grown vaccines aren't ideal, either.
"The plant system has some advantages," said Levy, who is also a member of the Stanford Cancer Center and a Howard Hughes Medical Institute investigator.
The researchers chose tobacco plants that were genetically engineered to reproduce quantities of the vaccine. To make a tobacco plant churn out a human antibody, scientists isolate the antibody from the patient's tumor and put the antibody gene into a modified version of the tobacco mosaic virus. They infect a tobacco plant with the gene-carrying virus by scratching the virus on its leaves. The virus takes the gene into the plant's cells, which then churn out lots of antibody. After a few days, technicians snip off the plant's leaves, grind them up and purify the antibody. Only a few plants are needed to make enough vaccine for each patient.
"The new manufacturing system allows very rapid production of a vaccine," said Charles Arntzen, PhD, a professor of plant biology at the Arizona Biodesign Institute at Arizona State University, who was not involved in the research. "I think without the speed, it would be hard to convince a cancer patient to wait for a vaccine to be developed, rather than going on some other therapy."
"It's pretty cool technology," Levy said. "And it's really ironic that you would make a treatment for cancer out of tobacco. That appealed to me." None of the harmful chemicals found in cigarettes end up in the purified vaccines.
Not only is the technology fast, cheap and safe, but Levy said there's reason to expect that the plant-grown antibodies will generate a stronger immune response than those made in animal cells. Both plant and animal cells attach sugars to antibodies and other proteins during biochemical processing, but the plant and animal sugars are different. The difference might prompt a more robust immune response to plant-grown antibodies, Levy said.
The next research step is a phase-2 clinical trial to test the effectiveness of plant-grown vaccines in a larger group of lymphoma patients, Levy said. He's optimistic, adding, "We know that if you get the immune system revved up, it can attack and kill cancer."
The research team included scientists from Stanford, Touro University in Vallejo, Calif., and the biotechnology companies Large Scale Biology Corp., CBR International Corp., Bayer HealthCare, Integrated Biomolecule Corp., The Biologics Consulting Group Inc. and Holtz Biopharma Consulting.
The study was funded by a grant from the National Institutes of Health and by Large Scale Biology Corp.
Stanford University Medical Center integrates research, medical education and patient care at its three institutions -- Stanford University School of Medicine, Stanford Hospital & Clinics and Lucile Packard Children's Hospital at Stanford. For more information, please visit the Web site of the medical center's Office of Communication & Public Affairs at http://mednews.stanford.edu. <<
RE:Biogenerics Will Save $25 Billion on Biologics Spending in the US
http://money.cnn.com/news/newsfeeds/articles/prnewswire/200807100800PR_NEWS_USPR_____NYTH041.htm
>> Insmed Announces First Human Bioequivalence Data for a Follow-on Biologic by a U.S. Company
July 10, 2008: 08:00 AM EST
RICHMOND, Va., July 10, 2008 /PRNewswire-FirstCall/ -- Insmed Inc. (Nasdaq: INSM), a developer of follow-on biologics and biopharmaceuticals for unmet medical needs, today announced that it has demonstrated the bioequivalence of INS-19, the company’s recombinant human granulocyte colony stimulating factor (G-CSF), compared to Neupogen(R), an FDA-approved G-CSF product for the treatment of neutropenia that recorded 2007 sales of approximately $1 billion.
Human bioequivalence studies utilize well-established, FDA-recognized methodology with rigorous standards. Results of this clinical study demonstrated bioequivalence between INS-19 and Neupogen(R). G-CSF concentration profiles for the two products were identical. Absolute neutrophil count, the primary pharmacodynamic marker for G-CSF products, exhibited the same response profile to dosing with INS-19 as with Neupogen(R). These human INS-19 and Neupogen(R) data complement Insmed’s extensive analytical testing and comparative data from pre-clinical assessments.
"These results are very exciting, as they represent Insmed’s ability to replicate a protein product, to bring that product rapidly through the clinic and to demonstrate clear bioequivalence to the innovator drug," said Dr. Geoffrey Allan, President and CEO of Insmed. "To our knowledge, we are the first U.S. company to report human bioequivalence data for a follow-on biologic product, validating the idea that follow-on biologics can be a scientific reality in the U.S. and that Insmed is well positioned to be a leader in the field. Demonstration of bioequivalence is typically the sole clinical requirement to support FDA approval of generic drugs today. Thus, based on these data, Insmed intends to request a meeting with the FDA to discuss potentially initiating a Phase III clinical trial program for INS-19."
Insmed has one of the most robust follow-on biologics pipelines in the industry. Building upon the success of INS-19, the Company has also completed pre- clinical pharmacological and pharmacokinetic studies for its second follow-on biologic product, INS-20, which has demonstrated comparability to FDA-approved Neulasta(R). Based on these data, Insmed intends to initiate a Phase I bioequivalence study of INS-20 in humans in the fourth quarter of 2008. Insmed intends to seek approval of both products in the U.S. and launch the products on expiration of the relevant innovator patents.
Study Design
The study was a single-center, randomized, double-blind, two-way, crossover bioequivalence design in healthy volunteers. Thirty-two volunteers enrolled, and all completed the study as planned. Each volunteer received a single dose of either INS-19 or Neupogen(R), underwent a wash-out period, and returned to the clinic for a single dose of the alternate product. Blood samples were collected to characterize the pharmacokinetic and pharmacodynamic responses to each dose administration. Point estimates and 90% confidence intervals (CI) for the mean ratios of the products’ maximum G-CSF concentrations (Cmaxs) and areas under the G-CSF concentration curves (AUCs) were calculated, and bioequivalence was assessed.
Study Results
Results of this clinical study demonstrated bioequivalence between INS-19 and Neupogen(R). G-CSF concentration profiles for the two products were identical. The Cmaxs following INS-19 and Neupogen(R) administration were 44.7 +/- 2.1 and 45.5 +/- 1.9 ng/mL, respectively (mean +/- standard error). The AUCs for INS-19 and Neupogen(R) were 341 +/- 16 and 343 +/- 14 ng/mL*hr, respectively. In comparing INS-19 to Neupogen(R), the CI for the ratio of Cmaxs was 92-103% and the CI for the ratio of AUCs was 94-103%. These data demonstrate that the pharmacokinetic behaviour of the products was statistically indistinguishable. Absolute neutrophil count, the primary pharmacodynamic marker for G-CSF products, exhibited the same response profile to dosing with INS-19 as with Neupogen(R).
About Insmed
Insmed Inc. is a biopharmaceutical company with unique protein process development and manufacturing experience and a proprietary protein platform aimed at niche markets with unmet medical needs. For more information, please visit www.insmed.com.
The Follow-on Biologics Market
According to published reports, an estimated $10 billion worth of biologic drugs are expected to come off patent by 2010, with an additional $10 billion by 2015. Follow-on biologics would provide safe and effective therapies at a reduced cost following the expiration of the original product’s patent. A recent econometric study by economist Dr. Robert J. Shapiro, former Under Secretary of Commerce in the Clinton Administration, found that "...generic versions of the top 12 categories of biologic treatments with patent protections that have expired or that are due to expire in the near future could save Americans $67 billion to $108 billion over 10 years and $236 billion to $378 billion over 20 years."
About INS-19
Recombinant human G-CSF is a synthetic version of a human G-CSF that is produced in bacteria. G-CSF mimics the biological effects of naturally occurring G-CSF and is used to treat certain medical conditions where a person’s neutrophils are too low (neutropenia), such as in cancer patients who are receiving certain chemotherapeutic regimens, patients receiving bone marrow transplants, or in patients who have chronically low neutrophils for other reasons. Pre-clinical studies demonstrate that INS-19 and FDA-approved Neupogen(R) are comparable in both their pharmacological and toxicological profile. Detailed analytical characterisation also demonstrates that the products have a high degree of similarity. <<
Celera Sales Prediction
[Does anyone here follow the Merck drug odanacatib?
(http://clinicaltrials.gov/ct2/results?term=odanacatib)
Celera licensed it to Merck (via CRA's purchase of Axyx Pharmaceuticals).]
http://www.businessspectator.com.au/bs.nsf/Article/INTERVIEW-Newly-solo-Celera-launches-heart-risk-te-G5Q8F?OpenDocument
>> Celera launches heart-risk test in US
By Deepa Seetharaman of Reuters
NEW YORK -- Celera Corp, the newly independent maker of diagnostic tests, is betting its forthcoming heart risk test will reach $US100 million in annual sales within three years.
The company, which could soon turn a fiscal-year profit, plans to launch the test in the US broadly this month starting in the southeastern part of the country after a successful pilot program.
The test detects a gene variation, known as KIF6, present in 60 per cent of the general population that puts them at high risk for heart attacks and other cardiovascular ailments, said Kathy Ordonez, Celera president and chief executive officer, in an interview on Tuesday.
Those who test positive for the gene can head off risks by using statin drugs, a common class of medicines generally used for addressing high cholesterol.
"It's very easy for us to explain why the test is important to physicians," Ms Ordonez said on the same day the company formally separated from its parent company Applera. "The uptake has been even beyond our expectations."
"Out the gate, we'll do it through direct mail and telemarketing and using our clinical educators and then we may have a partnership as well," Ms Ordonez said.
Ms Ordonez said the partner would be a "company that operates broadly calling on general physicians in the primary market," possibly a drug maker.
The California-based company plans to launch the test in Europe within nine months to a year.
Analysts are closely watching the success of the KIF6 test, which could quickly become one of Celera's top products. Ms Ordonez said the company expects revenue from the test to be more than $US10 million in about the next year.
In three years, the company hopes annual sales of the test will reach $US100 million, or more than half its annual sales projection for the current fiscal year.
The KIF6 test is the first of several new diagnostic tests in Celera's pipeline.
Celera plans to next introduce a DNA test that will determine who benefits most from using aspirin for heart protection. In the years ahead, Celera hopes to develop a test that can detect early risk of both breast and lung cancer.
"These new genetic tools give you a much more accurate assessment of your genetic risk," Ms Ordonez said. "Knowing that you are a carrier of the risk form of these genes could be very helpful in making lifestyle decisions."
Celera was founded in 1998 by scientist J. Craig Venter to map the human genome. The company shifted its focus to diagnostic tests in 2002 after Venter left.
Celera's revenue this year has been primarily driven by its October acquisition of Berkeley HeartLab, a facility for cardiovascular testing that also performs the KIF6 tests.
It said in April it expects to be profitable, excluding one-time items, for the fiscal year which ended June 30, on revenue of $US135 million to $US140 million, compared to $US47 million in 2007 fiscal-year revenue.
"It's an important transformation," said David Speechly, Celera spokesman. "Celera of five years ago and profitability in the same sentence was just an impossibility." <<
AIDS Treatment - Is the Paradigm Shifting?
http://www.prnewswire.com/cgi-bin/stories.pl?ACCT=104&STORY=/www/story/06-30-2008/0004840885&EDATE=
>> Sangamo BioSciences Announces Nature Biotechnology Study Demonstrating the Use of Zinc Finger Nucleases to Generate HIV Resistant T Cells
Preclinical Animal Data Demonstrates Promising Therapeutic Strategy for
HIV/AIDS
RICHMOND, Calif., June 30 /PRNewswire-FirstCall/ -- Sangamo
BioSciences, Inc. (Nasdaq: SGMO) announced today the publication of data
demonstrating that human immune system cells (CD4 T-cells) can be made
resistant to HIV infection by treatment with zinc finger DNA-binding
protein nucleases (ZFN(TM)). The data suggest that the ZFN approach, which
results in the permanent modification of the CCR5 gene encoding an
important receptor for HIV infection, is a promising strategy for the
treatment of HIV/AIDS.
The work, which was carried out in the laboratory of Carl June, M.D.,
Director of Translational Research at the Abramson Family Cancer Research
Institute at the University of Pennsylvania School of Medicine, in
collaboration with Sangamo scientists, was published as an Advance Online
Publication in Nature Biotechnology
(http://www.nature.com/nbt/journal/vaop/ncurrent/abs/nbt1410.html).
"A ZFN approach represents the 'next generation' of HIV-entry blocking
agents and a potentially promising class of anti-HIV compounds," said, Dr.
June who is the senior author of the study. "These proof of principle data,
together with experience from individuals that carry a natural mutation in
their CCR5 gene suggest that permanent 'knock-out' of the of CCR5 gene is
important and clinically relevant for long-term resistance to HIV infection
and, we believe, may prove to be more effective than temporary 'knock down'
approaches based on small molecule inhibitors, antibodies, antisense or
RNAi."
Sangamo's ZFNs are designed to permanently modify the DNA sequence
encoding CCR5, a co-receptor that enables HIV to enter and infect cells of
the immune system. Individuals carrying a naturally occurring mutation of
their CCR5 gene, a variant known as CCR5-delta32, have been shown to be
resistant to HIV infection.
"The data described in this paper are an important demonstration of the
potential therapeutic properties of our product," commented Dale Ando,
M.D., Sangamo's vice president of therapeutic development and chief medical
officer. "We have demonstrated that a single treatment with our
CCR5-specific ZFNs generates a population of HIV-resistant human T-cells
similar to the situation in individuals carrying the natural CCR5-delta32
mutation. ZFN-modification of these cells is permanent and makes them
resistant to HIV. The modified cells preferentially survive and expand in
an animal after HIV infection, providing a reservoir of healthy and
uninfectable immune cells. Furthermore, we observed that animals given the
ZFN-modified cells had increased numbers of CD4 cells and substantially
lower levels of HIV in their blood compared to animals given non-modified
cells demonstrating statistically significant protection from the virus. In
an HIV-infected patient, such modified cells could be available as a
protected reservoir within the immune system to fight both opportunistic
infections and HIV itself."
Several major pharmaceutical companies have initiated programs to
develop small molecule or monoclonal antibody approaches to block the
binding of HIV to CCR5. However, a small molecule or antibody approach
requires the constant presence of a sufficiently high concentration of
these drugs or antibody to block therapeutically relevant numbers of the
CCR5 protein, which is present in thousands of copies on the surface of
each T-cell and other tissues in the body. One such drug has been approved
by the US Food and Drug Administration with a "black box" warning, the
strongest for prescription drugs, concerning the risk of liver toxicity and
the possibility of heart attacks.
Sangamo's ZFN technology represents a means of potentially
circumventing these limitations or risks by specifically modifying only CD4
T-cells, the principal target of HIV pathology, in a one-time exposure of
the cells to ZFNs. This results in permanent modification of the CCR5
protein such that HIV cannot enter and infect the cells. This approach
could potentially enable the generation of a reservoir of protected CD4
T-cells that are available to fight the opportunistic infections that are
characteristic of AIDS as well as HIV itself. Sangamo expects to initiate a
clinical trial to evaluate this approach by the end of the year.
Data Reported in the Nature Biotechnology Paper
The reported results demonstrate that a one-time exposure to
CCR5-specific ZFNs resulted in the generation of an HIV-resistant
population of human primary T-cells by the permanent genetic modification
of the CCR5 gene. These ZFN-modified CD4 T-cells expanded stably in
HIV-infected cultures for several weeks and appeared to behave identically
to untreated T-cells except that they were resistant to infection by HIV.
ZFN treated primary CD4 T-cells and transformed CD4 cell lines resisted
infection with R5-tropic HIV (virus that uses the CCR5 co-receptor to enter
cells), resulting in enrichment of ZFN- generated CCR5-disrupted cells in
the population upon long-term exposure to virus (>50 days). Importantly, in
the presence of HIV, ZFN-modified CD4 T- cells also preferentially expanded
in a mouse model. The modified cells were infused into mice that lack a
normal immune system and thus do not reject human cells. After 33 days, the
mice were sacrificed and analyzed for the presence of ZFN-modified cells.
Researchers determined that ZFN-modified cells engrafted normally in the
mouse and that the proportion of modified cells present at the end of the
experiment was greater than two to three fold higher in mice in the
presence of HIV infection (p=0.008). In a second experiment it was
determined that 50 days after infection, mice given the ZFN- modified cells
had increased numbers of CD4 cells and a statistically significant
reduction in viral load in their peripheral blood (P<0.001) compared to
mice given control cells. These data suggest that, in the presence of HIV,
the ZFN-modified cells have a selective advantage allowing them to evade
infection and destruction leaving them able fight opportunistic infections
and HIV itself.
About HIV/AIDS and CCR5
HIV stands for Human Immunodeficiency Virus. HIV infection kills or
impairs cells of the immune system, progressively destroying the body's
ability to fight infections and certain cancers resulting in AIDS (Acquired
Immune Deficiency Syndrome). Individuals diagnosed with AIDS are
susceptible to life-threatening diseases called opportunistic infections,
which are caused by microbes that usually do not cause illness in healthy
people. According to Worldaidsday.org, over 3 million people were infected
with HIV in 2005. There are now over 40 million people living with HIV and
AIDS worldwide.
CCR5 is the chemokine receptor that HIV uses as a co-receptor to gain
entry into immune cells. CCR5 is perhaps the most important of the known
co- receptors for HIV, since the most commonly transmitted strains of HIV
are strains that bind to CCR5 -- so-called "R5" strains. A small fraction
of the population carries a mutation in their CCR5 gene, called the delta32
mutation. This mutated version of the gene results in a truncated CCR5
protein which cannot be used by HIV as a co-receptor. Individuals that have
mutant delta 32 versions of both of their CCR5 genes are resistant to
infection by R5 HIV strains.
About Sangamo
Sangamo BioSciences, Inc. is focused on the research and development of
novel DNA-binding proteins for therapeutic gene regulation and
modification. The most advanced ZFP Therapeutic(TM) development program is
currently in Phase 2 clinical trials for evaluation of safety and clinical
effect in patients with diabetic neuropathy. Phase 1 clinical trials are
ongoing to evaluate a ZFP Therapeutic for peripheral artery disease. Other
therapeutic development programs are focused on ALS, cancer, HIV/AIDS,
neuropathic pain, nerve regeneration, Parkinson's disease and monogenic
diseases. Sangamo's core competencies enable the engineering of a class of
DNA-binding proteins known as zinc finger DNA-binding proteins (ZFPs). By
engineering ZFPs that recognize a specific DNA sequence Sangamo has created
ZFP transcription factors (ZFP TF(TM)) that can control gene expression
and, consequently, cell function. Sangamo is also developing
sequence-specific ZFP Nucleases (ZFN(TM)) for gene modification. Sangamo
has established strategic partnerships with companies outside of the human
therapeutic space including Dow AgroSciences, Sigma-Aldrich Corporation and
several companies applying its ZFP Technology to enhance the production of
protein pharmaceuticals. For more information about Sangamo, visit the
company's web site at http://www.sangamo.com.
This press release may contain forward-looking statements based on
Sangamo's current expectations. These forward-looking statements include,
without limitation, references to the research and development of novel ZFP
TFs and ZFNs as ZFP Therapeutics, applications of Sangamo's ZFP technology
platform, the therapeutic potential of ZFNs for the treatment of HIV/AIDS,
strategic partnerships with collaborators and clinical trials of ZFP
Therapeutics. Actual results may differ materially from these
forward-looking statements due to a number of factors, including
technological challenges, uncertainties relating to the initiation and
completion of stages of ZFP Therapeutic clinical trials, Sangamo's ability
to develop commercially viable products and technological developments by
our competitors. See the company's SEC filings, and in particular, the risk
factors described in the company's Annual Report on Form 10-K and its most
recent Quarterly Report on Form 10-Q. Sangamo BioSciences, Inc. assumes no
obligation to update the forward-looking information contained in this
press release. <<
[OT] RE:Consciousness as an inherent property of the universe
[The implicate order is presented by David Bohm as an alternative to the Copenhagen interpretation of quantum mechanics.]
http://www.fdavidpeat.com/interviews/bohm.htm
>> ...
Omni: What do you think that says about consciousness?
Bohm: Much of our experience suggests that the implicate order is natural for understanding consciousness: When you are talking to somebody, your whole intention to speak enfolds a large number of words. You don't choose them one by one. There are any number of examples of the implicate order in our experience of consciousness. Any one word has behind it a whole range of meaning enfolded in thought.
Consciousness is unfolded in each individual. Clearly, it's shared between people as they look at one object and verify that it's the same. So any high level of consciousness is a social process. There may be some level of sensorimotor perception that is purely individual, but any abstract level depends on language, which is social. The word, which is outside, evokes the meaning, which is inside each person.
Meaning is the bridge between consciousness and matter. Any given array of matter has for any particular mind a significance. The other side of this is the relationship in which meaning is immediately effective in matter. Suppose you see a shadow on a dark night. If it means "assailant," your adrenaline flows, your heart beats faster, blood pressure rises, and muscles tense. The body and all your thoughts are affected; everything about you has changed. If you see that it's only a shadow, there's an abrupt change again.
That is an example of the implicate order: Meaning enfolds the whole world into me, and vice versa-that enfolded meaning is unfolded as action, through my body and then through the world. The word hormone means "messenger," that is, a substance carrying some meaning. Neurotransmitters carry meaning, and that meaning profoundly affects the immune system. This understanding could be the beginning of a different attitude to mind-and to life.
Omni: Descartes held mind and external reality together with God. You're holding the two with meaning.
Bohm: I say meaning is being! So any transformation of society must result in a profound change of meaning. Any change of meaning for the individual would change the whole because all individuals are so similar that it can be communicated.
...<<
RE:Teva and Antisense Pharma Report Phase-2a Data in RRMS
>VLA-4 is a clinically validated target in the treatment of MS.<
This is a reference to Tysabri, Biogen Idec and Elan's drug. This trial was halted from March 2005 to Jan 2006 due to safety concerns regarding Progressive Multifocal Leucoencephalopathy.
Roche Sugarcoats Antibodies
http://health.yahoo.com/news/reuters/roche_cancer_dc.html;_ylt=Ao2b.a8F3iaXQvyerwVJF.2mxbAB
>> Roche says sugar technology has anticancer promise
By Ransdell Pierson - Tue Jun 24, 4:01 PM PDT
Provided by:
Not yet rated
NEW YORK (Reuters) - Swiss drugmaker Roche Holding AG on Tuesday said results from a preclinical study suggest that sugar related technology acquired through its purchase of GlycArt Biotechnology AG may boost effectiveness of cancer drugs.
Privately-held GlycArt, bought for $180 million in 2005, specialized in a technology called glyco-engineering. It alters the composition of sugars which naturally coat antibodies, making the antibodies better able to prod the immune system's so-called natural killer cells to attack cancer cells.
David Heimbrook, global head of oncology discovery for Roche, said the promising results were seen in mouse trials with an experimental drug called R7159, an antibody whose sugar coating was altered in the laboratory. The product is now in early-stages of human testing.
It was studied among mice with non-Hodgkins lymphoma that had become resistant to treatment with Rituxan, Roche's lymphoma medicine which is sold outside the United States as MabThera.
"The important outcome was that we saw almost complete inhibition of tumor growth" among mice given R7159, Heimbrook said in an interview following a Roche meeting with journalists in New York.
By contrast, he said tumors continued growing among mice given placebos or Rituxan in the study.
"The appeal of this platform is that it potentially could give us a whole portfolio of antibodies that work through this process," theoretically against most types of cancer, he said.
Another year of testing with R7159, now in phase 1 studies, should give a clearer picture of the technology's true potential, Heimbrook said.
Meanwhile, he said Roche is testing similar drugs in preclinical studies against a range of other types of cancer, including solid tumors. <<
Superiority of Calcium Scans
http://health.yahoo.com/news/healthday/arterialcalciumscanscanpredictdeathrisk.html;_ylt=AgNIQINYNmTXGPl79Rn7SzOmxbAB
>> MONDAY, June 23 (HealthDay News) -- Scanning the heart's arteries for calcium deposits accurately predicts the overall death risk for American adults, a new study suggests.
"So far, this is the best predictor we have of who will have a problem and who will not," said study co-researcher Dr. Matthew Budoff, associate professor of medicine at the Harbor-UCLA Medical Center.
He and his colleagues reported the finding in the July 1 issue of the Journal of the American College of Cardiology.
A calcium scan looks for calcification, a hardening of the arteries caused by high blood fats and calcium deposits that can eventually block blood vessels, causing heart attacks, strokes and other major problems.
But calcium scans can be controversial, partly because they are promoted vigorously by for-profit centers, where they often cost $300 or more.
The new study might help end that controversy, because it shows that coronary artery calcium levels are directly associated with the risk of death, Budoff said.
"I think it better validates the technique with an endpoint that people can rely on," he said. "There has been a lot of criticism of coronary calcium studies, because they have been short-term, with endpoints such as angiography or bypass surgery. Those are endpoints that are more up to the doctor to decide."
Some previous studies have been more definite. One, reported earlier this year by cardiologists at the University of California, Irvine, who looked at more than 6,700 men and women, found that the risk of a coronary event such as a heart attack was 10 times higher for people with the highest calcium deposit scores than for those with the lowest.
The newly reported study enrolled more than 35,000 people ages 40 to 80, in the cities of Torrance, Calif., and Nashville, Tenn., who were followed for an average of 5.8 years after having a coronary artery calcium scan by electron beam tomography.
"Increasing coronary artery calcium was associated with decreasing survival across all age deciles [10-year intervals]," the researchers reported.
Scanning not only indicated those at higher risk, but also could be used to indicate a better chance of survival in persons with major risk factors such as obesity, high blood pressure and diabetes, the team wrote.
"The use of coronary calcium scanning allowed us to reclassify more than 40 percent of the patients, 70 or more years old, often by excluding risk," the report said.
"It is clear that coronary artery calcium is a good predictor of cardiovascular events and cardiovascular mortality, and since cardiovascular events are a major cause of mortality, it does not surprise me that it is a good predictor of all-cause mortality," said Dr. Robert Detrano, professor of radiological sciences, who led the University of California, Irvine, study.
Calcium scanning is useful, "because you want assistance in deciding what you can do to keep the patient health," Detrano said.
The American Heart Association and the American College of Cardiology have recommended calcium scans only for persons at intermediate risk of heart disease, not for those at high or low risk. Risk is determined by considering such factors as age, family history, obesity, diabetes and cholesterol levels. Presence of one or two of those factors indicates intermediate risk, Budoff said.
"That would be a man over 45 or a women past menopause with diabetes or high blood pressure or a family history or who smokes," he said.
Budoff defended the cost of a calcium scan as "about the same as a treadmill test and cheaper than a colonoscopy." Coverage of the procedure by Medicare and medical insurers differs from region to region and company to company, he said. A calcium scan can save money in some cases by showing that someone might not need medication such as cholesterol-lowering statins, he said. "The cost is lower than the co-pay for a cholesterol pill for one year," Budoff said.
But Detrano disagreed. "That issue is still standing and still needs to be addressed, and not by a study that shows that it predicts all-cause mortality," he said.
Detrano noted that he has been working to bring better medical care to poor people in China. Americans might be able to afford calcium scanning, but "it is beyond the means of the great majority of people on this planet," he said.
Meanwhile, a study being published in the June 23 issue of Archives of Internal Medicine provided more proof of the value of calcium scanning. The study, done by a multi-institutional group and led by Dr. Aaron Folsom of the University of Minnesota, compared the prognostic value of calcium scans with measurements of the wall of the carotid artery, the major artery leading from the heart to the brain.
The study of almost 6,700 middle-aged and older Americans who were followed for up to five years found that "coronary artery calcium score is a better predictor of subsequent cardiovascular events than carotid intima-media thickness [measuring the artery's wall]," the researchers reported. But they noted that whether and how to clinically use bioimaging tests of early atherosclerosis remains a topic of debate. <<
Ovation PR
http://www.businesswire.com/portal/site/biospace/index.jsp?ndmViewId=news_view&newsId=20080623005669&newsLang=en
>> OVATION Pharmaceuticals to In-License ATryn® (antithrombin alfa) in the United States
Company Signs Definitive Agreement to Partner with GTC Biotherapeutics to Develop and Market Anti-Coagulation Product
DEERFIELD, Ill.--(BUSINESS WIRE)--OVATION Pharmaceuticals, Inc. announced today that it has signed a definitive agreement to enter into an exclusive collaboration with GTC Biotherapeutics in Framingham, Massachusetts, to develop and market ATryn® (antithrombin alfa) in the United States. OVATION will obtain the exclusive license to the U.S. rights to the product and will own certain assets, including the Biologics License Application, or BLA, following approval. The agreement calls for OVATION to make a series of potential payments to GTC for meeting regulatory, clinical, and sales milestones, with the initial payment due upon closing, which is subject to Hart-Scott-Rodino review and other conditions.
ATryn is approved in Europe but not in the U.S. for the treatment of a rare disorder called hereditary antithrombin deficiency, or HD, involving people who do not have sufficient antithrombin in their bloodstream. Antithrombin is a protein that helps keep blood from clotting and has anti-inflammatory properties. Following approval of ATryn in the U.S., which is anticipated in early 2009, OVATION will be responsible for the launch, as well as sales and marketing of the product, while GTC will continue to be responsible for manufacturing. ATryn has been granted both Orphan Drug designation and Fast-Track status for the HD indication by the U.S. Food and Drug Administration (FDA).
“Collaborating with GTC on ATryn builds on OVATION’s expertise in developing, launching and marketing specialized products,” said Jeffrey S. Aronin, OVATION President and Chief Executive Officer. “ATryn is an important addition to our hematology portfolio and represents a strong strategic fit with our overall business model of focusing on disorders where there is significant unmet medical need. We look forward to working with GTC to bring the first recombinant antithrombin product to the U.S. marketplace where we can have a meaningful impact on the lives of patients who could benefit from this innovative technology.”
ATryn has completed phase III clinical trials in the U.S. for patients with HD who are undergoing high-risk surgical procedures or childbirth. In the U.S. approximately one in 2,000 to one in 5,000 people are diagnosed with the disease each year and half of all people diagnosed suffer a thrombosis before 25 years of age.
GTC recently initiated the Biologics License Application (BLA) filing on a rolling basis. ATryn is also being developed as a potential treatment for acquired antithrombin deficiencies such as heparin resistance (HR) during coronary artery bypass graft and related surgeries and as a potential treatment for disseminated intravascular coagulation associated with severe sepsis (DIC-sepsis). DIC is the widespread formation of clots within blood vessels, which often leads to organ failure.
The most common adverse events listed in the approved European labeling that may occur during treatment with ATryn include dizziness, headache, bleeding, nausea, bleeding at injection site and increased bleeding during treatment.
About OVATION Pharmaceuticals
OVATION is a fast-growing biopharmaceutical company that develops, manufactures and markets medically necessary therapies to satisfy unmet medical needs for patients with severe illnesses. Headquartered in Deerfield, Ill., with products available in more than 85 countries, OVATION is committed to having a significant impact on patients’ lives through its focus on central nervous system, hematology/oncology, and hospital-based therapies. The four new launches the company expects over the next three years will be fueled by its late-stage CNS pipeline, which is one of the most robust in the industry. OVATION has been recognized for excellence in the global pharmaceutical and biotechnology industries with the 2006 and 2007 “Pharma Company of the Year” award from Scrip magazine for small to mid-sized enterprises. More information about the company, its products and full prescribing information may be found at www.ovationpharma.com.
This press release is intended for business journalists and investors. <<
Medical Brokering To Forestall the System's Breaking
http://genengnews.com/news/bnitem.aspx?name=37491385
>> Jun 19 2008, 4:45 PM EST
System constraints forcing Canadian physicians to become medical brokers in prioritizing
Contact: Jim Gilden
media.relations@sagepub.com
805-410-7335
SAGE Publications
Hip/knee replacement candidates
Los Angeles, London, New Delhi, Singapore (June 19, 2008) Health-care system constraints combined with a lack of a uniform referral process are leaving Ontario physicians brokering which patients are in greatest need of hip and knee replacement, a study led by a St. Michael's Hospital researcher funded by the Canadian Institutes of Health Research has revealed. The variability in this process means not everyone who needs this surgery will actually get surgery.
"Findings from our study suggest several system factors are shifting the onus to physicians and surgeons to prioritize which candidates will receive hip and knee replacement," said lead author Pamela Hudak, a researcher in the Keenan Research Centre in the Li Ka Shing Knowledge Institute of St. Michael's Hospital. [What is the SOC for a shifted onus?] "Physicians appear to adjust their criteria, often on a case-by-case basis, to identify which patients will be referred for or, in the case of surgeons, offered surgery. Ultimately this results in a varied approach in determining the best candidates, leaving many eligible and suitable candidates on waiting lists or to manage their problems as best they can with conservative approaches like medications."
The study, conducted by a team of researchers from across the University of Toronto and published last week in the journal Medical Decision Making, published by SAGE, examined the impact of patient characteristics, including age, weight/obesity, comorbidity and perioperative risk, and gender and caretaker roles in the decision-making process of 18 family physicians, 15 rheumatologists and 17 orthopedic surgeons from across Ontario.
"Although we expected these characteristics to affect candidates chosen for surgery, we did not expect the significant impact system constraints, such as lack of home care and postoperative support, waiting lists and access to operating rooms, would have on the decision-making process," Hudak explained. "Waiting lists prompted some physicians to refer patients earlier than normal while the lack of available home care and postoperative support, crucial for hip and knee replacement patients, prevented other physicians from referring patients. Beyond these limitations, surgeons also said they would take on more cases if more operating room time was available. These limiting factors can then affect how surgeons and physicians prioritize their patients, especially without common guidelines."
Based on these restrictions, researchers found that not only are physicians required to identify candidates for surgery but have become medical brokers whereby they are prioritizing and negotiating which candidates are the best candidates for the procedures.
"A lack of shared understanding among physician groups in our study about whom and when to refer patients suggests that they are currently operating with less than optimal tools for appropriate brokering," said the study authors. "More explicit information is required about whom to prioritize and how to ensure that prioritized candidates make their way through the system in a timely fashion."
###
The article "Not Everyone Who Needs One Is Going to Get One: The Influence of Medical Brokering on Patient Candidacy for Total Joint Arthroplasty" by Pamela L. Hudak, Pamela Grassau, Richard H. Glazier, Gillian Hawker, Hans Kreder, Peter Coyte, Nizar Mahomed, and James G. Wright is published Online First and is available FREE for a limited time at http://mdm.sagepub.com/cgi/rapidpdf/0272989X08318468v1. <<
RE:Can someone please post the full article?
>> Genentech to Focus Research
On Neuroscience, Infectious Disease
By KATHY SHWIFF
June 11, 2008 3:41 p.m.
Genentech Inc. will focus on developing drugs in the neuroscience and infectious disease categories as well as finding new uses for current best-sellers, said Susan Desmond-Hellmann, president of product development.
The company's flagship product Avastin -- already marketed to treat colon, lung and breast cancer -- is being studied on patients with renal cancer and some types of brain tumors. Data on Avastin's effects on ovarian cancer patients are expected in 2010 and on prostate cancer patients in 2010 or 2011. The company also is developing 14 new molecules to treat various cancers.
Speaking at a Goldman Sachs health-care conference in California, Ms. Desmond-Hellmann said Genentech was disappointed by results of a recent study of Rituxan in lupus patients, following the failure of the drug in treating an aggressive form of multiple sclerosis. Rituxan is already on the market for non-Hodgkin's lymphoma and rheumatoid arthritis, with 2007 sales of $2.29 billion. More information on how Rituxan affects lupus is due in the first quarter, she said.
Looking at the future of drug research, Ms. Desmond-Hellmann expects future drugs to target smaller numbers of patients, saying, "The days of big cholesterol-lowering drugs for millions of people may be behind us."
Write to Kathy Shwiff at kathy.shwiff@dowjones.com <<
Request For NovoSeven Study
With the drug losing patent protection in 2011, would there be economic incentive to fund a study?
http://genengnews.com/news/bnitem.aspx?name=37020324
>> Jun 11 2008, 10:45 AM EST
Pharmaceutical study: Less hemorrhaging after stroke, but not fewer deaths
Contact: Dr. Annette Tuffs
annette.tuffs@med.uni-heidelberg.de
49-622-156-4536
University Hospital Heidelberg
Published in the New England Journal of Medicine; the Department of Neurology at the University of Heidelberg Hospital coordinated the study in Europe
An international study published in May 2008 in the New England Journal of Medicine has shown that the coagulation factor VIIa can limit the extent of a cerebral hemorrhage. However, in the long term it does not prevent death or severe impairment.
Further studies must clarify whether the new treatment with the genetically engineered substance is suitable for a special group of patients who as the study suggests could profit from therapy in spite of this. These are patients with a limited hemorrhage size (delta 60ml), with limited amounts of blood in the cerebrospinal fluid space (delta 5ml), who are not over an age 70 years and who will be treated within 2.5 hours or less.
Some 841 patients in 73 centers in 20 countries took part in the study. Member of the steering committee, study coordinator for Europe, and co-author of the published article is Professor Dr. Thorsten Steiner, Senior Physician at the Department of Neurology, University of Heidelberg Hospital (Medical Director: Professor Dr. Werner Hacke).
Cerebral hemorrhages account for 15 percent of all strokes. They are often fatal; some 80 percent of the surviving patients are severely disabled. Especially problematic is further increase of the hematoma, which occurs in one third of patients in the first four hours. Thus far there is no way of treating.
An earlier study proved reduction of outcome and mortality
Three years ago, a phase-2 study with recombinant coagulation factor VIIa with the trade name NovoSeven, which is not yet approved for clinical use, showed that the compound could lower the death rate after a hemorrhage and limit impairment. This study was also published in the "New England Journal".
The new study compares the effectiveness of factor VIIa in two dosages (20 and 80 micrograms) with a placebo. The extent of the hemorrhage visible on a CT scan was noticeably larger (26%) in the placebo group than in the patients treated with 80 micrograms (11%) and 20 micrograms (18%). But there was still no difference in the number of patients who died after a stroke or were severely disabled by it. However, patients who were treated with the higher dosage of factor VIIa suffered more frequently from thromboses and embolisms.
Fewer high-risk patients in the placebo group / New study on a certain patient group?
"A decisive reason for the negative result is the fact that there were more high-risk patients in the patient groups treated with factor VIIa than in the placebo group," stated Professor Steiner. These patients more frequently had intraventricular hemorrhages (bleeding in the spaces of the brain containing cerebral spinal fluid) and high blood pressure. "Intraventricular bleeding increases the mortality by a factor of 4 to 5 and high blood pressure increases the risk of a secondary hemorrhage," said Professor Steiner. The age of the patients and timing of treatment were also factors.
"We have also determined that after a cerebral hemorrhage reaches a certain size, clinical improvement is very unlikely, irrespective of treatment," continued Professor Steiner. It is possible that the medication is effective mainly in patients whose hemorrhages have not yet exceeded a certain size, who have no or only a limited amount of blood in the ventricle, and do not exceed a certain age. This should be examined in another study.
"We would welcome a decision of the manufacturer of this medication decide to conduct a study on this special group of patients," said Professor Steiner. To what extent high blood pressure increases the risk of secondary hemorrhaging in the acute phase of a hemorrhagic stroke is currently being examined in another study.
... <<
NVS Licenses ADCC Technology
http://genengnews.com/news/bnitem.aspx?name=37018457&taxid=0
>> Jun 11 2008, 2:00 AM EST
BioWa Licenses POTELLIGENT(R) Technology to Major Pharmaceutical Company for Use in Antibody Research and Development
PRNEWSWIRE
PRINCETON, N.J., June 11 /PRNewswire/ -- BioWa, Inc. announced today that it has licensed its POTELLIGENT(R) Technology to Novartis for the development of antibody therapeutics with enhanced antibody-dependent cellular cytotoxicity (ADCC).
The license provides Novartis with access to BioWa's POTELLIGENT(R) Technology platform to research, develop, manufacture, and commercialize ADCC-enhanced antibodies for an undisclosed number of targets. In return, BioWa will receive license fees, development milestone payments and royalties on products developed by Novartis. Additional terms were not disclosed.
"POTELLIGENT(R) Technology has shown its clinical benefits in various clinical trials for oncology and inflammatory diseases," said Dr. Masamichi Koike, President and CEO of BioWa. "We are pleased to make this technology available to a world-wide, industry leader like Novartis. We believe that this agreement significantly helps us to maximize the value of POTELLIGENT(R) Technology and to fulfill our mission to bring the benefit of the technology to patients in need as quickly as possible."
About POTELLIGENT(R) Technology
POTELLIGENT(R) Technology improves potency and efficacy of antibody therapeutics by enhancing ADCC, one of the major mechanisms of action for antibody therapeutics. POTELLIGENT(R) Technology involves the reduction of the amount of fucose in the carbohydrate structure of an antibody using a proprietary fucosyltransferase-knockout CHO cell line as a production cell. Research shows that POTELLIGENT(R) Technology dramatically enhances ADCC activity of an antibody in vitro, and significantly increases potency and efficacy of the antibody in vivo. A number of POTELLIGENT(R) antibodies are being investigated in human clinical trials.
About BioWa, Inc.
BioWa is a wholly owned subsidiary of Kyowa Hakko Kogyo Co., Ltd. (TSE: 4151), Japan's leading pharmaceutical and largest biotech company, and is the exclusive worldwide licensor of AccretaMab(TM) platform. AccretaMab(TM) platform consists of POTELLIGENT(R) and COMPLEGENT(TM) Technologies, creating a superior antibody molecule with enhanced ADCC and CDC activities. BioWa is offering POTELLIGENT(R) and COMPLEGENT(TM) Technologies to partners under a license to maximize the value of these technologies. In addition, BioWa is focused on development of ADCC/CDC enhanced monoclonal antibody-based therapeutics to fight cancer and other life-threatening and debilitating diseases. Both BioWa and Kyowa have POTELLIGENT(R) antibody products at various clinical stages. For more information about BioWa, visit its web site at http://www.biowa.com.
POTELLIGENT(R), COMPLEGENT(TM), and AccretaMab(TM) are the trademarks of Kyowa Hakko Kogyo Co., Ltd. All rights are reserved.
SOURCE BioWa, Inc. <<
RE: HIF-1 Inhibition
>>The Duke team has completed a phase I trial with a HIF1 inhibitor. "We are actively pursuing this clinically and will be moving this study into Phase 2," Dewhirst said. "We are interested in other applications of HIF-1 inhibition in combination with radiation and chemotherapy for different diseases."<<
Could this be the trial being referred to? (though it doesn't seem to be completed.)
http://clinicaltrials.gov/ct2/results?term=nct00466583
RE: IGF-1 Pathway
[With cancer, there's always another wrinkle.]
http://genengnews.com/news/bnitem.aspx?name=34741901&taxid=0
>> May 1 2008, 12:50 AM EST
Study raises questions about prostate cancer therapies targeting IGF-1
Contact: Dean Forbes
dforbes@fhcrc.org
206-667-2896
Fred Hutchinson Cancer Research Center
SEATTLE
Therapies under development to treat prostate cancer by inhibiting the ability of insulin-like growth factor (IGF-1) to activate its target receptor could have unexpected results especially if a major tumor suppressor gene p53 is already compromised, according to new research by investigators at Fred Hutchinson Cancer Research Center.
IGF-1 is a polypeptide hormone that can influence growth, differentiation and survival of cells expressing the type 1 receptor (IGF-1R). Past clinical, epidemiological and experimental studies have strongly implicated IGF-1 as a contributing factor in the natural history of prostate cancer. However, very little has been done to prove absolutely that the expression or activation of the IGF-1 signaling pathway at physiologically relevant levels is sufficient to cause a healthy prostate cell to become a cancer cell.
Norman Greenberg, Ph.D., and colleagues conducted a pair of experiments by manipulating gene expression directly in the epithelial compartment of the mouse prostate gland to better understand the role of IGF-1R. In contrast to studies that correlated elevated levels of IGF-1 with the risk of developing prostate cancer, Greenbergs research showed that eliminating IGF-1R expression in an otherwise normal mouse prostate caused the cells to proliferate and become hyperplastic. Although persistent loss of IGF-1R expression ultimately induced cell stasis and death, both of these processes are regulated by the tumor suppressor gene p53 that is commonly mutated in human prostate cancers. Hence the researchers hypothesized that tumors with compromised p53 might not respond predictably to therapies targeting IGF1 signaling.
To test their reasoning they conducted a second experiment by crossing mice carrying the prostate-specific IGF-1R knockout alleles with transgenic mice that develop spontaneous prostate cancer when p53 and select other genes are compromised. The results were as predicted: Prostate epithelial-specific deletion of IGF-1R facilitated the emergence of aggressive prostate cancer in the genetically-engineered tumor prone mice.
Published in the May 1 edition of Cancer Research, the study supports a critical role for IGF-1R signaling in prostate tumor development and identifies an important IGF-1R-dependent growth control mechanism, according to the authors. Title of the paper is Conditional deletion of insulin-like growth factor-1 receptor in prostate epithelium.
If our predictions hold true, tumor cells with intact p53 may show the best response to therapy targeting the IGF-1R signal, however when p53 is not functioning normally, response to this therapy may not be as expected, said Greenberg, the studys corresponding author and a member of the Hutchinson Centers Clinical Research Division.
Greenbergs message to clinicians who administer IGF-R1 therapy: Were all hoping for good results but lets proceed with caution.
A search of the database for clinical trials registered with the National Cancer Institute found 18 trials in process that use therapies to inhibit IGF-R1. None of them include a tumors p53 status as a criterion for recruiting research participants, said Greenberg.
###
In addition to lead author Brent Sutherland, Ph. D., of the Hutchinson Center, contributing research also came from scientists at Baylor College of Medicine in Houston, Texas, the Center for Cancer and Stem Cell Biology at Texas A&M University and the Institut National de la Sante et de la Recherche Medicale in Paris, France.
The study was funded by the National Cancer Institute, the Prostate Cancer Foundation and Phi Beta Psi.
Note to reporters/editors: To obtain a copy of the study, please contact Dean Forbes, 206-667-2896 or dforbes@fhcrc.org
At Fred Hutchinson Cancer Research Center, our interdisciplinary teams of world-renowned scientists and humanitarians work together to prevent, diagnose and treat cancer, HIV/AIDS and other diseases. Our researchers, including three Nobel laureates, bring a relentless pursuit and passion for health, knowledge and hope to their work and to the world. For more information, please visit fhcrc.org. <<
Stem Cell Treatment after Diskectomy
http://www.businesswire.com/portal/site/biospace/template.PAGE/menuitem.ab520ce17e34ab71ff00d635c0908a0c/index.jsp?ndmViewId=news_view&newsId=20080603006211&newsLang=en
June 3, 2008
>> First Spine Surgery Using Adult Stem Cells Performed at The Medical Center of Aurora
AURORA, Colo.--(BUSINESS WIRE)--Dr. Jeffrey Kleiner, spinal surgeon, performed the first diskectomy in the United States using adult stem cells to help repair the lower back. This milestone marks the beginning of how some types of back surgery will be performed in the future.
“By injecting stem cells into the disk we hope to allow cellular recovery of the damaged tissue,” said Dr. Kleiner. “The stem cells should take on the properties of the cells within the disk and ultimately improve the hydration of the disk and prevent the progression of degeneration.”
The stem cells used in this surgery were harvested from the adult patient and were cultured and grown to larger numbers using a proprietary technique by a local Colorado company, Regenerative Sciences. They were injected back into the same patient during the surgery this morning. This autologous process has been used for percutaneous injections to the back and joints before, but never during a spine surgery.
“Stem cells have shown great promise over the past three years for treating back pain,” said Dr. Kleiner. “In combination with the diskectomy, we hope to offer patients long-term relief from their back pain and to decrease their risk of needing additional surgeries.”
A diskectomy is a surgery to remove a herniated or bulging intervertebral disk. Dr. Kleiner has been performing this surgery using a minimally invasive technique for the past 18 years. <<
Information about Regenerative Sciences can be found here:
http://www.regenexx.com
Synthetic molecules hold promise for new family of anti-cancer drugs
http://genengnews.com/news/bnitem.aspx?name=36772789
>> Synthetic molecules hold promise for new family of anti-cancer drugs
Contact: Jerry Barach
jerryb@savion.huji.ac.il
972-258-82904
The Hebrew University of Jerusalem
Prof. Shimon Gatt (left) and Dr. Arie Dagan in their laboratory at the Hebrew UniversityHadassah Medical School.
Jerusalem, June 4, 2008 -- Synthetic molecules designed by two Hebrew University of Jerusalem researchers have succeeded in reducing and even eliminating the growth of human malignant tissues in mice, while having no toxic effects on normal tissue.
For their work in developing these harbingers of a possible new generation of anti-cancer drugs, Dr. Arie Dagan and Prof. Shimon Gatt of the Department of Biochemistry of the Hebrew University-Hadassah Medical School were among those receiving the Kaye Award for Innovation today during the 71st meeting of the Hebrew University of Jerusalem Board of Governors.
The molecules developed by Dagan and Gatt affected the metabolism of various sphingolipids and consequently those of cancer cells. Sphingolipids are a family of complex lipid molecules that are involved in signaling pathways that mediate cell growth, differentiation and death.
Several of the most active molecules developed by Dagan and Gatt are derivatives of ceramide (a member of the sphingolipid family). Ceramide induces programmed cell death (apoptosis) in a variety of cancer cells.
The natural levels of ceramide in cancer cells are generally too low to induce a therapeutic effect. In preclinical studies to date, various treatments with the synthetic molecules resulted in an elevation of ceramide levels in cancer cells, thereby leading to their death by apoptosis. In addition, these synthetic molecules appear to be synergistic with chemotherapeutic drugs.
Dagan and Gatt state that their studies demonstrated that their synthetic compounds reduced considerably the sizes of pancreatic, prostate and breast tumors with little or no effects on normal cells and tissues. The researchers see this as a precursor to the development of a new generation of anti-cancer drugs that induce, selectively, apoptosis only to tumorous cells. These drugs are expected to be highly effective while inducing fewer side effects than current anti-cancer drugs.
###
Prof. Shimon Gatt and Dr. Arie Dagan's development of synthetic sphingolipid analogs as anti-cancer drugs is patented by Yissum, the technology transfer company of the Hebrew University of Jerusalem. Yissum licensed the technology to BioLineRx, a clinical stage drug development company traded on the Tel Aviv Stock Exchange,, for the development of these synthetic molecules as anti-cancer drugs.
The Kaye Innovation Awards have been given annually since 1994. Isaac Kaye of England, a prominent industrialist in the pharmaceutical industry, established the awards to encourage faculty, staff and students of the Hebrew University to develop innovative methods and inventions with good commercial potential which will benefit the university and society. <<
KRAS Mutation Testing - Enter Roche
http://genengnews.com/news/bnitem.aspx?name=36643236&taxid=0
>> Jun 2 2008, 2:00 AM EST
Roche Signs Exclusive Distribution Deal with DxS for K-RAS and EGFR Cancer Mutation Tests
PLEASANTON, Calif., June 2 /PRNewswire/ -- Roche and DxS Ltd. have signed an exclusive distribution agreement for the DxS TheraScreen K-RAS Mutation Test and TheraScreen EGFR 29 Mutation Test. The tests are intended, when considered with other clinically relevant factors, to aid doctors in identifying suitable patients likely to benefit from a specific cancer therapy based on their mutation status.
"There is a growing demand for tests to indicate disease prognosis and identify patient groups more likely to benefit from a particular drug," said Daniel O'Day, President and CEO of Roche Molecular Diagnostics. "Through our partnership with DxS, we can leverage our extensive global infrastructure and commercial reach to provide these tests, which have the potential to improve treatment outcome in some patients."
Under the terms of the agreement, Roche is granted exclusive world-wide distribution rights for the K-RAS Test, which has CE Mark certification in Europe. For the EGFR test, which also has CE Mark certification, Roche is granted exclusive distribution rights for all global markets except the United States, Canada, Mexico, and Hong Kong.
"We are extremely pleased to have concluded this distribution agreement with Roche," said Dr. Stephen Little, CEO of DxS Ltd. "Not only does it enable us to meet the growing demand for these tests, but also gives doctors and patients access to standardized test results that provide further information to enhance treatment decisions."
The TheraScreen K-RAS Mutation Test was the first clinically validated, CE-Mark certified companion diagnostic for tumor-specific mutations in patients with colorectal cancer. In addition, some drugs used to treat colorectal and other cancers are only indicated for patients who have a non- mutated (or "wild-type") K-RAS gene. The test detects seven mutations in codons 12 and 13 of the K-RAS oncogene, which are frequently found in many cancer types. These mutations are common in colorectal cancer, pancreatic cancer, lung adenocarcinoma, gall bladder cancer, bile duct cancer and thyroid cancer.
The TheraScreen EGFR 29 Test is designed to enable detection of 29 of the most common somatic mutations in the EGFR gene and detects mutations with greater sensitivity than sequencing. Recent studies in non-small cell lung cancer have shown that some patients carry somatic mutations in the epidermal growth factor receptor (EGFR) gene. These mutations may correlate with responsiveness to the EGFR tyrosine kinase inhibitors, with some mutations having a sensitizing effect and others being linked to resistance. Ongoing trials in metastatic NSCLC are investigating whether such a test could aid doctors in selecting lung cancer patients suitable for first line treatment
with EGFR tyrosine kinase inhibitors, such as Tarceva, in the future.
About DxS
DxS is a UK-based personalized medicine company providing molecular diagnostics to aid doctors and drug companies in selecting therapies for patients. DxS offers products, technology and services to the healthcare industry to enable the delivery of safe and effective medicines. Working predominantly in the field of cancer, DxS has a range of companion diagnostic and research kits that detect mutations in oncogenes associated with cancer drug response. The TheraScreen(R) range of CE Mark certified diagnostic products includes kits that detect mutations in the EGFR and K-RAS genes. Tumor mutation products are available for research use for EGFR, RAS, RAF, BCR-ABL and other genes that show a correlation between patient mutation status and drug response. DxS also provides a genetic analysis service to support clinical development. For more information, visit www.dxsdiagnostics.com.
About Roche
Headquartered in Basel, Switzerland, Roche is one of the world's leading research-focused healthcare groups in the fields of pharmaceuticals and diagnostics. As the world's biggest biotech company and an innovator of products and services for the early detection, prevention, diagnosis and treatment of diseases, the Group contributes on a broad range of fronts to improving people's health and quality of life. Roche is the world leader in in-vitro diagnostics and drugs for cancer and transplantation, and is a market leader in virology. It is also active in other major therapeutic areas such as autoimmune diseases, inflammatory and metabolic disorders and diseases of the central nervous system. In 2007 sales by the Pharmaceuticals Division totaled 36.8 billion Swiss francs, and the Diagnostics Division posted sales of 9.3 billion francs. Roche has R&D agreements and strategic alliances with numerous partners, including majority ownership interests in Genentech and Chugai, and invested over 8 billion Swiss francs in R&D in 2007. Worldwide, the Group employs about 79,000 people. Additional information is available on the Internet at www.roche.com. <<
RE:SNUS merges with private firm, OncoGenex Technologies:
OncoGenex is pursuing cancer treatments using antisense licensed from Isis Pharmaceuticals. LLY is also developing antisense cancer treatments based on Isis IP.
First generation antisense had a lugubrious track record with regard to cancer (and virtually everything else.) It seems noteworthy that LLY is still aboard after the Affinitak debacle.