Register for free to join our community of investors and share your ideas. You will also get access to streaming quotes, interactive charts, trades, portfolio, live options flow and more tools.
Register for free to join our community of investors and share your ideas. You will also get access to streaming quotes, interactive charts, trades, portfolio, live options flow and more tools.
Meridian Bioscience (2-07) Receives FDA Clearance for New E. coli Test
Tuesday February 20, 9:47 am ET
CINCINNATI--(BUSINESS WIRE)--Meridian Bioscience, Inc., Cincinnati, Ohio (NASDAQ:VIVO - News) today announced that it has received clearance from the U.S. Food and Drug Administration (FDA) to market ImmunoCard STAT!® EHEC, a revolutionary new test for the diagnosis of E. coli infection. The new product detects all Shiga-toxin producing E. coli and is the first rapid (20 minute) E. coli diagnostic that differentiates between Toxin 1 & Toxin 2.
With the recent national E. coli outbreaks (spinach in September 2006 and lettuce in December 2006), there has been an increased need in the hospital market for a highly accurate, quick, easy-to-use E. coli test. New CDC recommendations published in September 2006 recommend that laboratories use a test that detects all Shiga-toxin producing E. coli, not just a test that detects the O157 E. coli strain. ImmunoCard STAT!® EHEC, with its easy-to-perform procedure, provides a practical solution that will enable laboratories to adopt those new CDC recommendations.
ImmunoCard STAT!® EHEC is the first product resulting from a strategic partnership that was announced in August 2006 with the Performance & Life Science Chemicals Division of Merck KGaA, Darmstadt, Germany and its American company EMD. This new-to-the-world product introduction demonstrates the value of the long-term strategic partnership that has been formed.
John A. Kraeutler, President and Chief Operating Officer, stated, "Disease caused by E. coli can be devastating, particularly with children, and Meridian is proud to introduce an advanced method for rapid E. coli testing that will significantly improve patient care. The launch of ImmunoCard STAT!® EHEC further solidifies Meridian's position as a leader in the field of E. coli testing."
Meridian is a fully integrated life science company that manufactures, markets and distributes a broad range of innovative diagnostic test kits, purified reagents and related products and offers biopharmaceutical enabling technologies. Utilizing a variety of methods, these products and diagnostic tests provide accuracy, simplicity and speed in the early diagnosis and treatment of common medical conditions, such as gastrointestinal, viral and respiratory infections. Meridian's diagnostic products are used outside of the human body and require little or no special equipment. The Company's products are designed to enhance patient well-being while reducing the total outcome costs of healthcare. Meridian has strong market positions in the areas of gastrointestinal and upper respiratory infections, serology, parasitology and fungal disease diagnosis. In addition, Meridian is a supplier of rare reagents, specialty biologicals and related technologies used by biopharmaceutical companies engaged in research for new drugs and vaccines. The Company markets its products and technologies to hospitals, reference laboratories, research centers, veterinary testing centers, physician offices, diagnostics manufacturers and biotech companies in more than 60 countries around the world. The Company's shares are traded through NASDAQ's Global Select Market, symbol VIVO. Meridian's website address is www.meridianbioscience.com.
BioMarin (2-07) Announces Results From Phase 2 Clinical Study of 6R-BH4 in Poorly Controlled Hypertension
Tuesday February 20, 9:00 am ET
No Significant Difference Observed Between 6R-BH4 and Placebo
NOVATO, Calif., Feb. 20 /PRNewswire-FirstCall/ -- BioMarin Pharmaceutical Inc. (Nasdaq and SWX: BMRN - News News) today announced results from its Phase 2a placebo-controlled double-blind study of 6R-BH4 in patients with poorly controlled hypertension. Results demonstrate that there was no statistically significant or clinically meaningful effect of 6R-BH4 on any efficacy or safety parameter measured, relative to placebo.
Jean-Jacques Bienaime, Chief Executive Officer of BioMarin stated, "We are surprised and disappointed by these results, especially considering the numerous encouraging pre-clinical and clinical studies of 6R-BH4 in diseases with endothelial dysfunction. We plan to analyze the data in detail to better understand the background therapy and other characteristics of patients in the study. We have no immediate plans to change the course of ongoing or planned clinical studies of 6R-BH4."
Mr. Bienaime continued, "We remain on track to file our new drug application for Phenoptin in PKU next quarter. While 6R-BH4 is the active ingredient in Phenoptin, this development has no effect on our program for Phenoptin in PKU. 6R-BH4 works by an entirely different mechanism of action and metabolic pathway in PKU, and the safety data in the hypertension study did not change the safety profile of the drug."
Study Design
The 8-week multi-center, randomized, double-blind, placebo-controlled study enrolled 116 patients with poorly controlled systemic hypertension, approximately half with type 2 diabetes. Among other eligibility criteria, to participate in the study, patients had elevated blood pressure while on at least two different medications for hypertension. Study patients received oral doses of 5 mg/kg of 6R-BH4 or placebo twice daily for an eight-week period.
Primary Efficacy Endpoint Results
Patients receiving placebo experienced a 6.4 mm Hg drop in systolic blood pressure compared to a drop of 4.8 mm Hg for patients receiving 6R-BH4. The difference was not statistically significant.
Conference Call Information
BioMarin will hold a conference call today, February 20, 2007, at 11:00 a.m. ET to discuss the results of the Phase 2 study of 6R-BH4 in poorly controlled hypertension and fourth quarter and year-end 2006 financial results. This event can be accessed on the investor section of the BioMarin website at http://www.BMRN.com.
Date: February 20, 2007
Time: 11:00 a.m. ET
U.S. and Canada Toll-Free Dial in #: 800.901.5217
International Dial in #: 617.786.2964
Participant Code: 35915200
Replay Toll-Free Dial in #: 888.286.8010
Replay International Dial in #: 617.801.6888
Replay Code: 94899251
About 6R-BH4
6R-BH4, commonly known as BH4 or tetrahydrobiopterin, is a naturally occurring enzyme cofactor that is required for numerous biochemical and physiologic processes, including the synthesis of nitric oxide (NO). NO has been shown to play a key protective role throughout the cardiovascular system and produces multiple positive effects, such as relaxing smooth muscle, reducing blood pressure, controlling inflammation and reducing platelet aggregation. Researchers have demonstrated that a deficiency of BH4 can disrupt NO synthesis, resulting in a loss of normal endothelial NO production. This loss of endothelial NO production, commonly referred to as endothelial dysfunction, has been associated with many cardiovascular diseases, including hypertension, diabetic vascular disease, peripheral arterial disease, coronary arterial disease and pulmonary hypertension, and has been shown to be a strong predictor of cardiovascular adverse events in a number of clinical studies.
6R-BH4 is the same enzyme cofactor currently being evaluated in BioMarin's Phenoptin(TM) (sapropterin dihydrochloride) for phenylketonuria (PKU). In March 2006, BioMarin and Merck Serono (a division of Merck KGaA, Darmstadt, Germany), BioMarin's corporate partner for the Phenoptin and 6R-BH4 programs, announced positive results from the Phase 3 clinical study of Phenoptin for PKU. All primary and secondary endpoints of the study were met. The type and incidence of adverse events was similar in the Phenoptin and placebo groups. Phenoptin was well tolerated and investigators reported that no serious adverse event occurred.
About BioMarin
BioMarin develops and commercializes innovative biopharmaceuticals for serious diseases and medical conditions. The company's product portfolio is comprised of two approved products and multiple clinical and preclinical product candidates. Approved products include Naglazyme® (galsulfase) for mucopolysaccharidosis VI (MPS VI), a product wholly developed and commercialized by BioMarin, and Aldurazyme® (laronidase) for mucopolysaccharidosis I (MPS I), a product which BioMarin developed through a 50/50 joint venture with Genzyme Corporation. Investigational product candidates include Phenoptin(TM) (sapropterin dihydrochloride), a Phase 3 product candidate for the treatment of phenylketonuria (PKU), and 6R-BH4 for cardiovascular indications, which is currently in Phase 2 clinical development for the treatment of peripheral arterial disease. For additional information, please visit http://www.BMRN.com. Information on BioMarin's website is not incorporated by reference into this press release.<<<
Acorda (2-07) - Eye on Acorda Therapeutics
Tuesday February 20, 8:30 am ET
>>> Anthony Payne submits: Acorda Therapeutics (NasdaqGM: ACOR) today announced its financial results for the fourth quarter and full year ended December 31, 2006. A number of positives for the year 2006 were also mentioned in the press release. The company will be holding a conference call at 8:30AM ET to discuss the results.
The major achievement during the year was the positive result from a Fampridine-SR Phase III trial for patients with Multiple Sclerosis. Fampridine-SR is a slow acting version of the potassium channel blocker 4-aminopyridine which appears, in laboratory tests, to improve impulse conduction in nerve fibers in which the insulating layer of the spinal cord, called myelin, has been damaged. It is not a cure and is not being tested as such. 4-aminopyridene, in much higher doses, is also used as an effective bird poison!
The company also mentioned a number of other corporate events during the year, addition of two new members to the Board and an additional payment from Paul of $5 million to fund an increase in sales force for its Zanaflex product. Zanaflex is a short-acting marketed drug for the management of spasticity, or pain and weakness associated with MS and other diseases. Its total sales were $18.1 million in 2006. On Friday February 16, 2006 the stock rose an impressive 9% on no news and now is close to a 52 week high.
Fampridine-SR was initially being developed for Spinal Cord Injury [SCI] and was the lead development product in December 2003 when the company originally filed its S1 to go public. The company at that time was conducting two Phase 3 clinical trials in people with SCI for the reduction of muscle stiffness, or spasticity. Their stated goal at that time was to submit an NDA for Fampridine-SR for the treatment of spasticity in SCI in 2004.
In 2004 it was later revealed by the company that data from one of the two SCI trials although showing a strong positive trend in a primary endpoint of reducing muscle spasticity, neither SCI trial achieved statistical significance in its primary endpoints. The development for this indication was subsequently dropped. The company in its withdrawn 2003 S1 indicated that it would be filing an FDA for the MS indication in 2005. In fact that filing will not actually take place until late 2008 or 2009 based on the need for an additional Phase III trial.
The Company’s other products are all in pre-clinical trials and cannot be used in support of its current valuation. In addition, we believe there is sufficient doubt over final approval of Fampridine-SR for the MS indication, notwithstanding the positive Phase III results, based on its history and the requirement for another trial to significantly discount its value. Zanaflex, though an interesting and increasingly successful product will never be a large revenue drug. Therefore our initial view of ACOR is that the value to date over $500 million (excluding cash and short-term investments) is not supportable by the current pipeline and marketed product. <<<
BioMarin (2-07) Announces Fourth Quarter and Full Year 2006 Financial Results
Tuesday February 20, 8:00 am ET
Positive Outlook for 2007 Driven by Increasing Revenue and Advancing Product Pipeline
Conference Call and Webcast to Be Held Today at 11:00 a.m. ET (17:00 CET)
NOVATO, Calif., Feb. 20 /PRNewswire-FirstCall/ -- BioMarin Pharmaceutical Inc. (Nasdaq and SWX: BMRN - News News) today announced financial results for its fourth quarter and year ended December 31, 2006. The net loss was $10.4 million ($0.11 per share) for the fourth quarter of 2006, compared to a net loss of $15.0 million ($0.20 per share) for the fourth quarter of 2005. The net loss for the year ended December 31, 2006 was $28.5 million ($0.34 per share), compared to a net loss of $74.3 million ($1.08 per share) for the year ended December 31, 2005, representing a reduction of $45.8 million, or approximately 61.6 percent.
As of December 31, 2006, BioMarin had cash, cash equivalents, and short-term investments totaling $288.8 million.
Jean-Jacques Bienaime, Chief Executive Officer of BioMarin commented, "In 2006, we continued to improve our financial profile by increasing product revenue, reducing the net loss, and strengthening the balance sheet. We also advanced our product pipeline by completing the Phenoptin Phase 3 clinical trials with very positive results and making significant progress in the pre-clinical development of Phenylase for PKU. Looking ahead in 2007, we expect continuing growth of Naglazyme and Aldurazyme sales to substantially offset research and development spending for ongoing clinical programs. In addition, we are hopeful that Phenoptin will be approved by the FDA as the first treatment option for PKU patients by the end of the year."
Product Sales
Net sales of Naglazyme® (galsulfase), an enzyme replacement therapy for mucopolysaccharidosis VI (MPS VI), were $16.3 million for the fourth quarter of 2006, compared to $12.9 million for the third quarter of 2006, representing a sequential increase of approximately 26.4 percent. Naglazyme net sales were $46.5 million for the year ended December 31, 2006. Naglazyme was approved by the U.S. Food and Drug Administration (FDA) in late May 2005, and by the European Commission in late January 2006. Naglazyme net sales for the three months and year ended December 31, 2005 were $3.7 million and $6.1 million, respectively. BioMarin is commercializing Naglazyme in the United States, Europe, and Latin America, and through distributors in other international markets.
Net sales of Aldurazyme® (laronidase), an enzyme replacement therapy for mucopolysaccharidosis I, (MPS I) by BioMarin/Genzyme LLC increased by approximately 25.0 percent to $26.5 million for the fourth quarter of 2006, compared to $21.2 million in the fourth quarter of 2005. Net sales for the year ended December 31, 2006 increased by approximately 26.0 percent to $96.3 million, compared to $76.4 million for the year ended December 31, 2005. BioMarin's share of the profit of BioMarin/Genzyme LLC was $5.7 million for the fourth quarter of 2006, compared to a profit of $3.1 million for the fourth quarter of 2005. BioMarin's share of the profit from BioMarin/Genzyme LLC for the year ended December 31, 2006 was $19.3 million, compared to $11.8 million for the year ended December 31, 2005.
Royalty and License Revenues
Royalty and license revenues for the fourth quarter and full year 2006 were $0.8 million and $15.9 million, respectively, and include royalties on net product sales of the Orapred product line, including Orapred® (prednisolone sodium phosphate oral solution) and Orapred ODT(TM) (prednisolone sodium phosphate orally disintegrating tablets). BioMarin expects to receive an additional milestone payment of $4.0 million on the first anniversary of FDA approval of Orapred ODT in June 2007.
Financial Guidance
2007 Projected Net Product Sales
BioMarin estimates 2007 net sales of Naglazyme to be in the range of $74 million to $78 million and sales of Aldurazyme by the joint venture for 2007 to be in a range of $115 million to $125 million.
2007 Projected Net Loss
BioMarin estimates its GAAP net loss for the fiscal year ending December 31, 2007 to be in the range of $20 million to $25 million, which includes approximately $16 million to $18 million in non-cash stock compensation expense.
Recent Events and Fourth Quarter 2006 Highlights
-- On January 29, BioMarin announced that the remaining $51.4 million of
convertible notes due 2008 was converted into common stock.
-- On January 16, BioMarin announced positive results from the Phase 3
diet study of Phenoptin for PKU.
-- On January 4, BioMarin announced the initiation of the Phase 2
clinical study of 6R-BH4 in peripheral arterial disease.
-- On December 18, BioMarin announced positive results from the Phase 3
extension study of Phenoptin for PKU.
BioMarin will host a conference call and webcast to discuss fourth quarter and full year 2006 financial results today, Tuesday, February 20, at 11:00 a.m. ET (17:00 CET). This event can be accessed on the investor section of the BioMarin website at http://www.BMRN.com.
Date: February 20, 2007
Time: 11:00 a.m. ET (17:00 CET)
U.S. & Canada Toll-free Dial in #: 800.901.5217
International Dial in #: 617.786.2964
Participant Code: 35915200
Replay Toll-free Dial in #: 888.286.8010
Replay International Dial in #: 617.801.6888
Replay Code: 94899251
About BioMarin
BioMarin develops and commercializes innovative biopharmaceuticals for serious diseases and medical conditions. The company's product portfolio is comprised of two approved products and multiple clinical and preclinical product candidates. Approved products include Naglazyme® (galsulfase) for mucopolysaccharidosis VI (MPS VI), a product wholly developed and commercialized by BioMarin, and Aldurazyme® (laronidase) for mucopolysaccharidosis I (MPS I), a product which BioMarin developed through a 50/50 joint venture with Genzyme Corporation. Investigational product candidates include Phenoptin(TM) (sapropterin dihydrochloride), a Phase 3 product candidate for the treatment of phenylketonuria (PKU), and 6R-BH4 for cardiovascular indications, which is currently in Phase 2 clinical development for the treatment of poorly controlled hypertension and peripheral arterial disease. For additional information, please visit http://www.BMRN.com. Information on BioMarin's website is not incorporated by reference into this press release. <<<
Amedisys (2-07) Reports Record Fourth Quarter And Full Year Revenues And Earnings
Tuesday February 20, 7:00 am ET
Company Also Announces Appointment of New CFO
Company To Host Conference Call Today at 10:00 am ET
BATON ROUGE, La., Feb. 20 /PRNewswire-FirstCall/ -- Amedisys, Inc. (Nasdaq: AMED; "Amedisys" or "the Company"), one of the nation's largest providers of home health nursing services, today reported its financial results for the fourth quarter and year ended December 31, 2006.
For the year ended December 31, 2006, the Company reported record net income of $38.3 million, or $1.72 per diluted share, on record net service revenue of $541.1 million. Net income includes a charge of $0.03 per diluted share for the write off of deferred financing fees related to early retirement of the Company's senior credit facility. For the same period in the previous year, Amedisys reported net income of $30.1 million, or $1.41 per diluted share, on net service revenue of $381.6 million. The diluted weighted average number of shares outstanding approximated 22.3 million in the year ended December 31, 2006 and 21.3 million in the comparable period of 2005.
For the quarter ended December 31, 2006, the Company reported record quarterly net income of $11.4 million, or $0.48 per diluted share, on record quarterly net service revenue of $144.0 million. Amedisys reported net income of $7.3 million, or $0.34 per diluted share for the quarter ended December 31, 2005 on net service revenue of $118.9 million. The diluted weighted average number of shares outstanding approximated 23.8 million for the quarter ended December 31, 2006 and 21.3 million for the comparable period of 2005.
All earnings per share data have been adjusted for Amedisys' four-for-three stock split.
The Company generated $43.1 million and $43.5 million in cash flow from operations in 2006 and 2005, respectively. Included in cash flow from operations is $18.8 million in 2005 payroll taxes that were deferred and paid in 2006 rather than 2005 under the Hurricane Katrina Relief Act extended deadlines. Had the Company paid the $18.8 million of payroll taxes in 2005, cash flow from operations would have been $24.7 million in 2005 and $61.9 million in 2006. In the quarter ended December 31, 2006, the Company raised $118.0 million in net proceeds by selling 3.0 million shares of its common stock. In conjunction with the offering, the Company repaid the outstanding balance of $43.1 million and terminated its senior credit facility.
"We have enjoyed yet another year of record revenues and record net income," said William F. Borne, Chief Executive Officer of Amedisys. "Our earnings per share have grown over 20 percent in each of the past four years. Further, we have worked diligently to position our balance sheet in a manner that allows us to aggressively pursue organic growth via start-ups and potential attractive acquisition candidates."
For 2007, Amedisys expects that net revenues will be in the range of $625 million to $650 million and diluted earnings per share, based on the Company's estimate of 26.5 million shares outstanding and including stock option expense, will be in the range of $2.05 to $2.15. This guidance includes approximately 40 home health and 4 to 5 hospice start-ups but does not include any acquisitions. Capital expenditures are expected to be about two percent of revenue, plus approximately $6.0 million related to the deployment of our Point of Care system.
Separately, Amedisys also announced today the resignation of its Chief Financial Officer, John Giblin, for personal reasons. "I have enjoyed my brief time at Amedisys and believe the Company is poised to continue its impressive trend of growth and profitability," said Mr. Giblin.
"We wish John well and would like to thank him for his contributions to Amedisys during his short tenure with us," said Mr. Borne. "However, we understand that, in the best interests of his family, it was important for him to be closer to Atlanta at this time."
In conjunction with Mr. Giblin's departure, Amedisys has appointed Dale E. Redman, 59, the Company's interim Chief Financial Officer. However, it is the Company's intent that Mr. Redman will be appointed permanent Chief Financial Officer in the near future.
"We are quite fortunate to so quickly fill the CFO position with an individual that possesses such a wealth of experience in interacting with the capital markets and financial reporting," said Mr. Borne. "Dale has spent nearly his entire 34 year career in senior level finance positions, and we are pleased to have someone of his caliber join the Amedisys management team. On behalf of the Board of Directors and other management team members, I would like to welcome Dale to the Amedisys family."
Most recently, Mr. Redman served as a Managing Director at Windward Capital Consulting, LLC, where he assisted businesses with capital issues and provided management consulting services in support of companies' growth strategies. Prior to this, Mr. Redman served for 10 years as Executive Vice President and Chief Financial Officer of the United Companies Financial Corporation, which was a publicly traded home mortgage and home equity lender based in Baton Rouge, La. In addition, Mr. Redman is an Adjunct Instructor in Finance at Louisiana State University, where he graduated with a Masters Degree in Accounting.
To participate in the conference call, please dial 800-632-2975 (Domestic) or 973-935-8755 (International) a few minutes before 10:00 a.m. ET on Tuesday, February 20, 2007. A replay of the conference call will be available from 12:00 p.m. ET on February 20, 2007 until 12:00 p.m. ET on February 27, 2007. The replay dial in number is 877-519-4471 (Domestic) or 973-341-3080 (International). The replay pin number is 8425791.
The call will also be available on the Internet live and for seven days thereafter at the following:
http://www.videonewswire.com/event.asp?id=37884
Amedisys, Inc., a leading provider of home health nursing services, is headquartered in Baton Rouge, Louisiana. Its common stock trades on The Nasdaq Global Select Market under the symbol "AMED".
This press release includes statements that may constitute "forward-looking" statements, usually containing the words "believe", "estimate," "project," "expect" or similar expressions. Forward-looking statements inherently involve risks and uncertainties that could cause actual results to differ materially from the forward-looking statements. Factors that would cause or contribute to such differences include, but are not limited to, continued acceptance of the Company's services in the marketplace, competitive factors, changes in government reimbursement procedures, dependence upon third-party vendors, and other risks discussed in the Company's periodic filings with the Securities and Exchange Commission. By making these forward-looking statements, the Company undertakes no obligation to update these statements for revisions or changes after the date of this release.
Additional information on the Company can be found at:
http://www.amedisys.com
Contact: Amedisys, Inc.
Larry Graham
President/Chief Operating Officer
(225) 292-2031
lgraham@amedisys.com
AMEDISYS, INC. AND SUBSIDIARIES
CONSOLIDATED BALANCE SHEETS
(Amounts in thousands, except share data)
As of December 31,
2006 2005
ASSETS
Current assets:
Cash and cash equivalents $84,221 $17,231
Restricted cash 4,797 -
Patient accounts receivable, net of allowance for
doubtful accounts of $9,870 and $12,387 at
December 31, 2006 and 2005, respectively 74,929 68,139
Prepaid expenses 4,133 2,693
Other current assets 11,125 4,277
Total current assets 179,205 92,340
Property and equipment, net 52,960 27,389
Goodwill 213,032 197,002
Intangible assets, net of accumulated amortization
of $4,899 and $3,108 at December 31, 2006
and 2005, respectively 12,733 11,447
Other assets, net 5,826 11,819
Total assets $463,756 $339,997
LIABILITIES AND STOCKHOLDERS' EQUITY
Current liabilities:
Accounts payable $14,339 $29,922
Accrued expenses 46,587 41,948
Obligations due Medicare 6,139 10,551
Current portion of long-term obligations 3,223 10,144
Current portion of deferred income taxes 11,630 4,173
Total current liabilities 81,918 96,738
Long-term obligations, less current portions 2,114 43,063
Deferred income taxes 10,781 3,556
Other long-term obligations 4,936 4,041
Total liabilities 99,749 147,398
Stockholders' equity:
Preferred stock, $.001 par value, 5,000,000 shares
authorized; none issued or outstanding - -
Common stock, $.001 par value, 30,000,000 shares
authorized; 25,902,210 and 15,881,691
issued and 25,798,723 and 15,877,524 shares
outstanding at December 31, 2006 and 2005,
respectively 26 16
Additional paid-in capital 279,553 146,684
Treasury stock at cost, 103,487 and 4,167 shares of
common stock held at December 31, 2006
and 2005, respectively (379) (25)
Unearned compensation - (628)
Retained earnings 84,807 46,552
Total stockholders' equity 364,007 192,599
Total liabilities and stockholders' equity $463,756 $339,997
AMEDISYS, INC. AND SUBSIDIARIES
CONSOLIDATED INCOME STATEMENTS
(Amounts in thousands, except per share data)
For the Year Ended Dec. 31,
2006 2005 2004
Net service revenue $541,148 $381,558 $227,089
Cost of service, excluding depreciation and
amortization 235,458 163,032 96,078
General and administrative expenses:
Salaries and benefits 133,315 93,116 56,885
Non-cash compensation 2,560 369 31
Other 94,053 67,966 36,591
Depreciation and amortization 10,106 6,973 4,126
Operating expense 475,492 331,456 193,711
Operating income 65,656 50,102 33,378
Other income (expense):
Interest income 1,197 1,464 550
Interest expense (4,907) (2,932) (510)
Miscellaneous, net (49) 106 (59)
Total other (expense) (3,759) (1,362) (19)
Income before income taxes 61,897 48,740 33,359
Income tax expense (23,642) (18,638) (12,855)
Net income $38,255 $30,102 $20,504
Net income per common share (1):
Basic $1.75 $1.45 $1.18
Diluted $1.72 $1.41 $1.14
Weighted average shares outstanding (1):
Basic 21,809 20,808 17,409
Diluted 22,289 21,293 18,057
(1) The share and net income per share information presented above for
the years ended December 31, 2005 and 2004 have been adjusted to
reflect the four-for-three stock split effected in the form of a
33-1/3% stock dividend for holders of record as of November 27, 2006.
--------------------------------------------------------------------------------
Source: Amedisys, Inc. <<<
Medarex (2-07) Announces Sale of Shares in Genmab A/S
Tuesday February 20, 7:00 am ET
>>> PRINCETON, N.J., Feb. 20 /PRNewswire-FirstCall/ -- Medarex, Inc. (Nasdaq: MEDX - News) announced today that it has sold approximately 2.5 million shares of Genmab A/S which stock is traded on the Copenhagen Stock Exchange. The trade is expected to settle on February 21, 2007. Medarex expects to receive approximately $150 million (USD) in net proceeds from the sale. The sale of Genmab shares is expected to reduce Medarex's equity ownership in Genmab to approximately 11 percent.
About Medarex
Medarex is a biopharmaceutical company focused on the discovery, development and potential commercialization of fully human antibody-based therapeutics to treat life-threatening and debilitating diseases, including cancer, inflammation, autoimmune disorders and infectious diseases. Medarex applies its UltiMAb® technology and product development and clinical manufacturing experience to generate, support and potentially commercialize a broad range of fully human antibody product candidates for itself and its partners. Over thirty of these therapeutic product candidates derived from Medarex technology are in human clinical testing or have had INDs submitted for such trials, with six of the most advanced product candidates currently in Phase III clinical trials. Medarex is committed to building value by developing a diverse pipeline of antibody products to address the world's unmet healthcare needs. For more information about Medarex, visit its website at www.medarex.com. <<<
Acorda Therapeutics (2-07) Reports Fourth Quarter and Full Year 2006 Financial Results
Tuesday February 20, 6:00 am ET
>>> HAWTHORNE, N.Y.--(BUSINESS WIRE)--Acorda Therapeutics, Inc. (Nasdaq:ACOR - News) today announced its financial results for the fourth quarter and full year ended December 31, 2006. The Company also reviewed its recent highlights.
"2006 was a transforming year for Acorda," commented Ron Cohen, M.D., the company's President and Chief Executive Officer. "In September we announced positive Phase 3 clinical trial results for Fampridine-SR, showing a significant increase in walking ability in people with multiple sclerosis. In addition, sales of Zanaflex Capsules grew strongly in 2006, and we completed our second expansion of our sales force to 65 professionals. We plan to build on these accomplishments in 2007, with another Phase 3 trial for Fampridine-SR, a strategic alliance to commercialize Fampridine-SR outside of the U.S. and continued growth in Zanaflex sales."
Fourth Quarter and Recent Highlights
Fampridine-SR
The Company's MS-F203 Phase 3 data has been accepted for a platform presentation at the American Academy of Neurology (AAN) meeting on May 2, 2007 at 4:15 pm (ET).
On December 8, 2006, Acorda announced that, based on feedback from its meeting with the U.S. Food and Drug Administration (FDA), it would design and conduct an additional Phase 3 trial of Fampridine-SR in people with MS. Acorda expects this study to be of shorter duration than its MS-F203 study with a single primary outcome, a consistent response on the Timed 25 Foot Walk. A protocol was submitted to the FDA for a Special Protocol Assessment (SPA). In response, the Agency has requested small amendments to the protocol that Acorda plans to implement. These do not involve significant changes to the overall design or the size of the trial.
As of February 15, 2007, over 1,300 people had been exposed to Fampridine-SR in clinical trials. This number includes more than 300 people treated for more than 6 months, approximately 150 people treated for more than one year and over 120 for greater than two years.
Zanaflex Capsules
On Jan. 8, 2007, the Company announced it had completed the expansion of its sales force for Zanaflex Capsules to 65 people, 52 of whom are area business managers in field, calling on specialist and primary care physicians who are high-volume prescribers. This new sales force is expected to reach approximately 7,400 specialists and primary care physicians and will lay the foundation for the potential Fampridine-SR launch.
Corporate
On February 7, 2007, the Company announced that it received a second $5 million payment as part of its amended agreement with an affiliate of Paul Capital Healthcare (formerly Paul Royalty Fund) to receive a total of $10 million to fund the expansion of its Zanaflex Capsules(TM) (tizanidine hydrochloride) sales force from 32 to 65 professionals and other Zanaflex Capsules operations. The second payment was made upon the achievement of specified sales goals for 2006.
The Company reported the addition of two new board members. Barry Greene, Chief Operating Officer of Alnylam Pharmaceuticals, joined the Board on January 9, 2007 and Ian Smith, Chief Financial Officer of Vertex Pharmaceuticals, Incorporated, joined the Board on February 1, 2007.
On December 1, 2006, Saints Capital converted its $2.5 million full-recourse convertible promissory note into 210,863 shares of common stock.
On November 15, 2006, the Company announced that it had been selected for addition to the Nasdaq Biotechnology Index.
On October 4, 2006, Acorda announced the completion of a $31.5 million private placement of approximately 3.2 million shares of its common stock.
Financial Results
Zanaflex Gross Sales - For the fourth quarter ended December 31, 2006, the Company reported gross sales of Zanaflex Capsules of $6.9 million and gross sales of Zanaflex® tablets of $1.3 million providing combined gross sales of $8.2 million, compared to $2.7 million in combined gross sales for the same quarter in 2005. For the full year ended December 31, 2006, the Company reported gross sales of Zanaflex Capsules of $18.1 million and gross sales of Zanaflex tablets of $8.4 million providing combined gross sales of $26.5 million, compared to $5.9 million in combined gross sales for the same period in 2005. Gross sales are recognized using a deferred revenue recognition model, meaning Zanaflex product shipments to wholesalers are recorded as deferred revenue and only recognized as revenue when end-user prescriptions of Zanaflex Capsules and tablets are reported.
Zanaflex Shipments - Zanaflex Capsules shipments for the quarter ended December 31, 2006 were $10.6 million and Zanaflex tablet shipments were $2.0 million providing total shipments of $12.6 million compared to $1.7 million of Zanaflex Capsules shipments and $2.3 million of tablet shipments for total shipments of $4.0 million for the same quarter in 2005. For the year ended December 31, 2006, Zanaflex Capsules shipments were $24.2 million and Zanaflex tablets shipments were $6.7 million providing total shipments of $30.9 million compared to $7.8 million of Zanaflex Capsules shipments and $10.3 million of tablet shipments for total shipments of $18.1 million for the prior year.
The Company reported net loss of $7.0 million for the quarter ended December 31, 2006, or $0.30 per share, compared to a net loss of $15.8 million, or $75.59 per share, for the same period in 2005. The Company reported a net loss of $60.0 million for the full year ended December 31, 2006, or $3.27 per share, compared to a net loss of $60.4 million, or $295.27 per share, in 2005.
As of December 31, 2006, Acorda held cash, cash equivalents, and short-term investments of $53.8 million, compared to $13.8 million at December 31, 2005.
Conference Call and Webcast
Ron Cohen, President and Chief Executive Officer and David Lawrence, Chief Financial Officer will host a conference call today at 8:30 am ET to review the Company's fourth quarter and year end 2006 results. To access the call, please dial 866-356-3093 (domestic) or 617-597-5381 (international) and provide the access code 62235705 five minutes prior to the start time. A replay of the call will be available from 10:30 a.m. Eastern Time on February 20, 2007 until 11:59 p.m. Eastern Time on March 20, 2007. To access the replay, please dial 888-286-8010 (domestic) or 617-801-6888 (international), and provide the access code 70560177. A live audio webcast of the call can also be accessed from the Company's website, at http://www.acorda.com, for the next 30 days. <<<
Neuro, Sorry to be so snippy, but no I haven't gone off my medication. Perhaps I need to go on some however.. :o) I've had a couple rough months lately, sorry to take it out on you.
Striaterminalis, Concerning structures, we don't know the exact structure of CX-717. We do know that both CX-717 and Org-24448 (CX-691) are benzofurazans. We know the exact structure of Org-24448 (it's been published by Organon and named "Farampator"), but not of CX-717. CX-701 is possibly also a benzofurazan.
There are numerous possible reasons why the histo finding occurs with CX-717 but apparently not with the other compounds -
1) They haven't done the exact same animal tox testing under the exact same conditions with the other compounds. While Dr. Stoll sounded confident that the other compounds weren't associated with the finding, I still wonder if all 3 compounds have been tested under absolutely identical conditions - same lab, same protocol, same everything.
2) CX-717 or one of its metabolites is doing something unique that the other compounds aren't, either in the tissue before death, after death, or in conjunction with the fixative.
Until we get an answer to this question, it's really impossible to gauge the odds here, which is why assigning a 70% positive odds estimate to this situation seems pretty ridiculous IMO.
Let's ask the expert, Neuro -
And the reason this "artifact" doesn't occur with CX-701 or Org-24448 is ......... ?
The FDA is going to want an answer.
Striaterminalis, And the reason this "artifact" doesn't occur with CX-701 or Org-24448 is ......... ?
Network Appliance (2-07) Stock Climbs
Thursday February 15, 12:21 pm ET
Network Appliance Shares Up After 3Q Results, Outlook
>>> NEW YORK (AP) -- Shares of Network Appliance Inc. gained on Thursday, after the provider of network-attached storage systems posted its fiscal third-quarter results and issued an outlook that impressed investors.
Late Wednesday, the company said that its revenue for the quarter, which ended in January, came in well above Wall Street's expectations. Earnings per share beat average analyst estimates by a penny, according to a Thomson Financial poll.
Shares of the Sunnyvale, Calif.-based company rose $1.58, or 4.1 percent, to $39.99 in Thursday afternoon trading on the Nasdaq Stock Market. Earlier in the day, shares traded as high as $40.42. The stock has changed hands between $25.85 and $41.56 in the past 52 weeks.
Friedman Billings Ramsey analyst Clay Sumner upgraded the company to "Outperform" from "Market Perform," and set a target price of $46.
Sumner said Network Appliance posted a strong quarter, with free cash flow of 55 cents per share "once again far outstripping" adjusted earnings of 29 cents a share. He said that the company's growth is accelerating, adding that the market is now significantly undervaluing NetApp on a cash flow basis.
Investors, Sumner wrote, may have become too focused on earnings leverage, "while possibly missing the extraordinary cash flows being produced by Network Appliance's operations, efficient tax planning, and strong deferred revenue growth." <<<
Alright, I'll leave all the sheep to the shepherd, smiling as he leads you over the cliff again. Good luck at the track Horseguy, you'll need it :o)
Daviddal, I actually did create several conservative boards on I-Hub, one bio stock related and another non-bio. No CD board though, man talk about boring :o)
Well, we all have to make our own investment decisions in the end. I still follow Cortex mostly out of curiosity over how it will turn out, and as a hobby brought on I guess by boredom. In the back of my mind I suppose I still think about taking that one last shot at the gold ring, but I just don't see the odds with this FDA decision as favorable at all. This board does need a semi-informed gadfly though, since the rest of you guys seem off the deep end of optimism.
Neuro, I lambasted Gaddy & Co numerous times, and their lack of integrity, their lack of a credible post-meldown pipeline, but I was astounded that you seemed to continue supporting them and their pipeline prospects. I didn't follow PARS for very long, but I subsequently heard that you had been a long time supporter, so I guess it's difficult to do a 180 degree reversal, even if it is warranted. There were a lot of folks criticizing you on various boards at that time, and that's how I started putting the larger picture together. I realize that you have the NI franchise reputation to protect, but your credibility wasn't enhanced by your continued support of PARS during that post-meltdown period. You should have just come clean and denounced Gaddy & Co as the crooks they were. But I digress..
One suggestion I would make, as a neutral observer, is to refrain from making NI stock picks/portfolios, and stick to
reporting/collating the various activities and programs in the neuro sector. That's what your corporate subscribers want primarily. The stock picking recommendations I assume were aimed more at small investors, but having that aspect of the NI publication opens you up to all kinds of potential problems, disgruntled subscribers, the perception of financial self interest due to your own personal investments, etc.
Neuro, I realize you've had a bad couple years with various stock predictions, but sometimes one just needs to suck it up and admit when they've miscalculated. What really jaded me was when you continued to avidly support PARS after their meltdown, the merits of their remaining "pipeline", company management, etc. The PARS meltdown didn't shock me, but your continued support for the company did bigtime. I don't know what the reason for that continued loyalty was (ego, reputation, financial, whatever), but for me it put into question your objectivity, and I see a similar pattern here with Cortex.
Daviddal, Yes I do miss the action, and I could certainly use the money from a "big score" wager. I've considered it, but just can't pull the trigger on this particular binary event. I'm going to stick to the slow boring road to riches (btw, the CDs are 5.76% and 5.3%, and I do plan to have 50% allocated to equities).
Tyco (2-07) Posts Broad Based Q1 Profit Gains
Tuesday February 6, 8:44 am ET
>>> Tyco International, the world's #1 maker of electronic connectors and security systems, said its Q1 2007 earnings from continuing operations was $0.37/share ($742 million), down from $0.39 ($803m) in Q1 2006. Excluding breakup and other one-time costs, its $0.45/share was slightly higher than consensus estimates of $0.44. Revenues were up 7.6% to $10.3b. All the company's four main segments -- electronics, fire and safety, healthcare and engineered products -- posted higher profits and revenues. In January Tyco formally filed to split the company into three. Today it said it would spin off its electronics and health-care units early in the second quarter; the dismantling should cost it $1.2-1.6 billion. Tyco said it bought back 22 million shares (1%) in the quarter, for about $659 million. It gave revenue growth guidance of 6% to 7% in Q2. Shares are trading up $0.29 (0.9%) at $33.50 this morning in the pre-market.<<<
Takeovers (2-07) Off to Good Start in 2007
Friday February 16, 4:58 pm ET
By Joe Bel Bruno, AP Business Writer
Takeovers Off to Good Start in 2007, Seen Smashing $4 Trillion Record
>>> NEW YORK (AP) -- The rumors about a potential takeover of aluminum producer Alcoa Inc. this past week created an enthusiastic buzz on Wall Street that acquisitions this year will smash the $4 trillion record set in 2006.
Seven weeks into 2007, the amount of money for takeovers brokered by investment banks and private equity firms is trending above last year. In the U.S., market researcher Dealogic said volume has soared 86 percent to $228.6 billion from last year, while global volume rose 36 percent to $477.4 billion.
The statistics indicate that while the dollar amounts of these deals are growing, the number of them isn't. There have been 519 deals in the U.S. so far this year, down 38 percent from 2006, while global transactions declined 25 percent to 2,392.
Analysts believe this shows a shift in M&A trends. Wall Street might see the number of deals edge lower. But, those still in the mix will fetch increasingly higher takeover bids, such as a potential Alcoa deal that would easily top $30 billion.
"How big can it go? That's not the focus," said Gregg Slager, a senior partner with accounting firm Ernst & Young's private equity practice. "This is still all about value creation regardless of the size. The economy is strong, capital is readily available, and this creates opportunity."
While it might be about value creation, the competition among private equity firms and investment banks is increasing. Big deals such as the bidding war between Vornado Realty Trust and Blackstone Group over real estate investment trust Equity Office Properties are escalating deal volume.
In fact, it has become an intense Wall Street mating dance. In trying to gauge one of his suitor's interest, Equity Office Properties founder Samuel Zell sent an e-mail to Vornado Chairman Steven Roth that read "Roses are red, violets are blue; I hear a rumor, is it true?"
The e-mail, obtained by The New York Times, sought to determine if Roth might be interested in raising his bid to trump buyout giant Blackstone's offer of $48.50 per share. Roth responded: "Roses are red, violets are blue. I love you Sam, our bid is 52." And the deal was secured to buy the largest U.S. commercial real estate company.
If anything, the wooing that goes on in these big deals shows the willingness to raise the stakes. The exception so far this year has been Nasdaq Stock Market Inc.'s unwillingness to raise its offer price for the London Stock Market; the takeover attempt collapsed earlier this month.
One thing is for certain, that U.S. companies are sitting on record cash stockpiles -- at last count $605 billion racked up by members of the Standard & Poor's 500 index -- that can be used to expand through mergers and acquisitions.
"This amount of money is looking to be deployed, that has really made a difference in tactics and in attitude," said Bob Profusek, co-head of global M&A for law firm Jones Day. "There's this huge amount of money that needs to be invested."
That only means good things for investors, where the-sky's-the-limit offers can send share prices flying high. For example, rumors this week that Anheuser-Busch Cos. might be taken over caused its shares to hit a 52-week high. Speculation that Alcoa might be on the block helped send the entire Dow Jones industrial average higher on hope that acquisition activity will remain on a breakneck pace.
It also means Wall Street investment banks could be set up for another record-breaking year of profits. Investors have cheered results from the top five U.S. securities firms and sent their shares to new highs. Morgan Stanley, Merrill Lynch & Co., Lehman Brothers Holdings Inc., Bear Stearns Cos. and Goldman Sachs Group Inc. might all see appreciation in their shares as they garner more investment banking business.
This isn't lost on smaller firms. JMP Group, a boutique investment banking firm and asset manager based in San Francisco, has filed to raise some $100 million in an initial public offering on the New York Stock Exchange. The firm, founded in 1999 by executives from the old Montgomery Securities that was later bought by Bank of America Corp., last year posted a profit of almost $2.4 million on revenue of $63.6 million.
JMP joins others that have scrambled to go public in the past year to take advantage of robust M&A activity. Last year several boutique firms decided to go public to take advantage of the escalating capital markets environment. Shareholders that got in on their IPOs are now sitting on some pretty big returns.
Keefe, Bruyette & Woods Inc. has seen its shares advance 18 percent since it became a public company in November. Cowen Group Inc., founded in 1918 and most recently a division of French bank Societe Generale, has realized a 35 percent jump in its shares since going public in July. <<<
Fiserv (2-07) Credit Union Businesses Continue Strong Track Record of New Contract Signings, Renewals, and Product Launches in 2006
Monday February 19, 9:00 am ET
>>> BROOKFIELD, Wis.--(BUSINESS WIRE)--Fiserv, Inc. (NASDAQ: FISV - News) announced year-end 2006 achievements for its Credit Union Group, which includes AFTECH, CUSA Technologies, GalaxyPlus, IntegraSys®, Summit Information Systems, USERS Inc. and XP Systems. The group continued to sign new clients at a healthy pace, while launching the new technologies today's credit unions depend on to succeed in a competitive and complex environment.
In 2006, the Fiserv credit union companies converted 33 new credit union clients to their core systems, representing $2.8 billion in assets and more than 460,000 members. During the same period, the Fiserv credit union businesses signed core processing agreements with 49 credit unions, representing more than $6 billion in assets and more than 660,000 members. The group now provides core processing for 2,715 credit unions nationally.
Equally important, the Fiserv Credit Union Group maintained long-standing relationships with current clients by renewing contracts with 973 credit unions in 2006. Those contract renewals represent credit unions with combined assets of more than $37.5 billion, serving more than 5.7 million member accounts.
"Fiserv's ability to attract new credit unions and retain the business of our current clients is a direct result of our focus on client satisfaction and product innovation," said Tom Neill, Fiserv's Group President of Depository Institution Processing.
Fiserv now provides core processing services to more than one-third of all credit unions with $1 billion or more in assets. "Partnering with many of the industry's largest credit unions and leading technology innovators enables Fiserv to stay ahead of our competition on new product development and services. Our mission is to help our clients gain market leadership by better serving their members. Our Fiserv 2.0 companywide strategy is to continue to provide value, opportunity and growth for our clients," Neill said.
In 2006, the Fiserv credit union companies delivered numerous new technology solutions that help credit unions meet member expectations and respond to timely issues. Key product launches included solutions in the areas of fraud monitoring and detection, member ID verification, multifactor authentication (MFA), online bill payment, data warehousing, online account enrollment, call center and audio response integration, member relationship management (MRM), health savings accounts and financial management. "The Fiserv Wisdom(TM) Financial Management Suite is a prime example of our approach to rolling out common products across our core processors," Neill said, noting that Wisdom is now used by more than 500 credit unions.
In keeping with their philosophy of nurturing strong client relationships, the Fiserv credit union companies together hosted nearly 4,000 credit union representatives and vendors at their client conferences. "Events such as these enable the Fiserv companies to develop more intimate client relationships, gain a better understanding of our clients' business and technology needs, and stay in sync with the credit union market," Neill said.
About Fiserv, Inc.
Fiserv, Inc. (NASDAQ: FISV - News), a Fortune 500 company, provides information management systems and services to the financial and insurance industries. Leading services include transaction processing, outsourcing, business process outsourcing (BPO), software and systems solutions. The company serves more than 17,000 clients worldwide and is the leading provider of core processing solutions for U.S. banks, credit unions and thrifts. Fiserv was ranked the largest provider of information technology services to the financial services industry worldwide in the 2004, 2005 and 2006 FinTech 100 surveys. Headquartered in Brookfield, Wis., Fiserv reported more than $4.5 billion in total revenue for 2006. For more information, please visit www.fiserv.com.<<<
Bio Generics (2-07) - Are Generic Bio Drugs on the Way?
Thursday February 15, 5:40 am ET
>>> AP reports that according to the results of a study to be released today, patients and insurance providers could save at least $71 billion over ten years if legislation (introduced yesterday) is passed allowing FDA approval of generic biotech drugs. The study was conducted by pharmacy benefit manager Express Scripts Inc. The average biotech drug costs $71,600/year, vs. $1,200 for a traditional drug, and biotech inflation is rising three times faster. Generic drugs typically cost 60% less than brand name, but some experts say stricter FDA requirements on biodrugs, and higher manufacturing expenses, won't allow for the same level of discounting by generic drug makers. Kathleen Jaeger, CEO of the Generic Pharmaceutical Association said even if generic biologics were just 25% cheaper the cost savings for consumers would be huge. But Jim Greenwood, CEO of the Biotechnology Industry Organization, says that true bio-generics are impossible, because derivatives from a living source can not be exactly copied.
Sources: Press Release of Study, AP/New York Times
Commentary: Senators Reintroduce 'Fair' Bill to Ban Authorized Generics • Generic vs. Generic • Teva: Aiming for the Lead in Generic Pharmaceuticals
Stocks/ETFs to watch -- Top generic drug makers: Teva Pharmaceutical Industries (NasdaqGS: TEVA), Barr Pharmaceuticals Inc. (NYSE: BRL - News), Mylan Laboratories Inc. (NYSE: MYL - News), Watson Pharmaceuticals Inc. (NYSE: WPI - News). Top biotech companies: Genentech Inc. (NYSE: DNA - News), Amgen Inc. (NasdaqGS: AMGN), Gilead Sciences Inc. (NasdaqGS: GILD)<<<
Biotech Generics (2-07): Who Stands Where? - Barron's
Sunday February 18, 3:52 pm ET
>>> Eli Hoffmann submits: Annotated article summary from this weekend's Barron's; For Biotech, Here Come the Clones by Bill Alpert
Summary: On Wednesday a bipartisan group introduced a bill in Congress that would have the FDA give approval to generic biologic drugs, something traditional drugs have already had for 20 years. The lack of competition allows biotech companies to charge hefty prices for their treatments, to the pleasure of shareholders but not patients. Biotech's biggest customer is the government's Medicare program, which spent $3 billion on just three anemia drugs from Amgen Inc. (NasdaqGS: AMGN) in F2005, causing one analyst to remark "Amgen is obviously the big target here." Amgen counters that reproducing biological products is complex, and should be heavily tested. Backers of the bill include General Motors Corp. (NYSE: GM - News) (it has the #1 private medical bill in the U.S.), health insurer Aetna Inc. (NYSE: AET - News), generic giant Teva Pharmaceutical Industries (NasdaqGS: TEVA) and pharmacy benefit manager Express Scripts Inc. (NasdaqGS: ESRX). Some bio-drugs are easier to reproduce, such as: human insulin made by Novo Nordisk (NYSE: NVO - News) [the company has thus moved into modifieds that improve treatments], Amgen's two red blood cell boosters, and enzymes that treat metabolic disorders made by Genzyme Corp. (NasdaqGS: GENZ). On the harder to copy side: Monoclonal antibodies made by Genentech Inc. (NYSE: DNA - News), interferons sold by Biogen (NasdaqGS: BIIB), and Amgen's anemia drugs. Other companies who have shown an interest in the bill: Novartis AG (NYSE: NVS - News), Pfizer Inc. (NYSE: PFE - News), Barr Pharmaceuticals Inc. (NYSE: BRL - News), and Medco Health Solutions Inc. (NYSE: MHS - News). <<<
Neuro, "Maybe so, but the conclusions you have drawn do not logically follow from the information thus far made available".
IMO, it's your more "rosy" conclusions that don't follow from the info/data available. Would you have arrived at the same rosy conclusions if you didn't have such a large financial stake in the outcome? I realize it's difficult to face reality when one is sitting on massive losses, but one's own situation has no bearing on the outcome of a binary event. Just because one desperately needs a good outcome doesn't mean the "bio gods" will be listening to their prayers.
It may actually be time to bring out some of the remaining bio goats for sacrifice, if there are any left after my own "slam dunk" pronouncements last year. To get a good outcome here, it seems we're going to need some type of divine intervention :o)
Neuro, Daviddal, You both seem to be letting your large financial stakes in this company affect your objectivity. Something just ain't right with this compound, and no amount of rationalizing or wishful thinking is going to make it right. I'm not saying that the FDA won't possibly raise the dosing limits, or that such an event won't help the stock, but I just don't see a BP choosing to move CX-717 through the long road toward an NDA filing when a better, untainted compound like CX-701 is available. It might be different if CX-717 was well into Phase 3 and there were no alternative compounds available.
Striaterminalis, When it comes to this "phenomenon", to me nothing seems very obvious. The most puzzling thing is the quick freezing vrs slow fixation difference, which suggests -
1) There may be no cellular change until after death.
2) There may be no cellular changes immediately after death, but only several hours after death (the quick vrs slow variable).
3) The cellular changes may be related in some way to the use of the fixative (the fixative vrs freezing variable).
But then one has to ask, why does this phenomenon ONLY occur with CX-717 and not with CX-701 or Org-24448? The phenomenon is not only compound specific to CX-717, it is also dose dependent and duration dependent. So CX-717 has to be doing something unique (uniquely bad) that the other Ampakines don't do. With this baggage, I just don't see a BP ultimately advancing this compound if there is a better Ampakine compound like CX-701 available, regardless of the FDA dosing decision.
That's a good point about BDNF and neurogenesis. Even though CX-717 is a low impact, at high enough doses for longer periods, there should be at least modest BDNF upregulation. This modest upregulation, in the ~30% range as I recall, was previously demonstrated using CX-727, also a low impact, and an analog of CX-717. Perhaps the "structural cellular changes" being seen could conceivably be related to new neurons forming. Of course then we get back to the same old questions - why not with other compounds, why not with freezing vrs fixation, why would they disappear after 2 weeks of dosing cessation, etc. Who knows ..
From that BDNF article -
>>> They detected newly generated neurons in several forebrain structures, including in the parenchyma (gray matter) of the striatum, septum, thalamus and hypothalamus — areas that serve a multitude of cognitive and vital neurological functions. The newborn cells were identified by infusing the brain with the cell proliferation marker BrdU, which serves as a permanent label for newborn cells, in conjunction with the BDNF. Until this study was done, neurogenesis (the production of neurons) had not been demonstrated in the thalamus and hypothalamus during postnatal life, and in only very limited numbers in the septum and striatum.<<<
Striaterminalis, Dr. Stoll said the "structural cellular changes" were not visible microscopically when the tissue is quickly frozen and examined without use of the fixative. They've done electron microscopic examination to try to verify this, with those results soon. And hopefully the last data set results will also be given soon for the period beyond 2 weeks post-cessation of drug to see if the cellular changes resolved completely beyond 2 weeks.
Trying to summarize what we know / think we know -
We know we have some structural cellular changes occurring, though not in what target organ. There were no apparent clinical manifestations seen in the animals in the time frame of the longest studies (3 months). The cellular changes only occur after 2 weeks of very high level dosing with CX-717. At low dosing levels there are no cellular changes, and with other Ampakine compounds there are no cellular changes. So the phenomenon is specific to CX-717, and it is dose level dependent, as well as dose duration dependent. Most but not all of the cellular changes disappear by 2 weeks after dosing is stopped (beyond that, results are pending). When the tissue is frozen right after death without fixative there are no cellular changes seen (pending confirmation from the electron microscopic study). When the tissue is processed in the normal slower manner, and with the use of fixatives, the cellular changes are seen. Also, the extent/magnitude of the cellular changes does not appear to increase/worsen between 2 weeks and 3 months of continued dosing.
Wells Fargo, Bank of America (2-07) Betting On Brokers
>>> Jocelynn Drake, Option Advisor 02.16.07, 5:00 PM ET
One sector that continues to skip higher is the broker/dealer sector. The Amex Securities Broker/Dealer Index (XBD) has gained roughly 5.3% since the start of 2007, outpacing the S&P 500 Index's (SPX) return, during the same period, of only 2.7%. The XBD is in the process of bouncing off support at its ascending 10-week moving average, which has boosted the index since mid-September.
Wells Fargo put the sector back in the spotlight when it announced that it will offer 100 free stock trades a year to customers holding balances of $25,000. This announcement comes after rival Bank of America unveiled in October that it plans to give away up to 360 free online stock trades annually to customers with at least $25,000 in deposits. The company has been gradually introducing its free online trading offer, with plans to complete the rollout during the spring.
Wells Fargo said its offer differs from its rival's because its $25,000 threshold includes loan balances and money in brokerage accounts toward the minimum requirement.
Until the release of Bank of America's plan in October, the price-cutting war among online brokerage rivals Charles Schwab Corp., TD Ameritrade Holdings and E*Trade Financial had grown quiet.
Meanwhile, the company reported earnings in January of 64 cents per share, matching the consensus estimate. In fact, Zacks reports that the company has matched or surpassed the Street's estimate in each of the past four quarters. Wells Fargo isn't due to report earnings again until April. The consensus estimate currently stands at 65 cents per share, a nickel higher than its year-ago profit. <<<
Haysaw, Thanks for that info. So most but not all of the histo changes disappear after 2 weeks of cessation of the drug, and they were waiting for the last data set to see about further resolution after periods longer than 2 weeks.
Well, at the very least that should rule out dead/apoptotic cells. I don't know, something tells me we're going to get screwed again by the FDA, call it a premonition/sixth sense, whatever. This is completely non-scientific, but looking at Cortex's 10 year chart, one sees a calamitous drop in the stock every 4 years that lasts about a year, it's uncanny, and gives the chart a perfect saw tooth pattern. I know that type of analysis is baloney, but at this point it seems like to get any read on this stocks's future probably requires a visit to a psychic.
Teva (2-07) article -
>>> Why Teva Pharmaceutical Makes Me Mad
Friday February 16, 12:45 pm ET
Shlomo Greenberg submits: The stock, not the company - and I blame the media.
I have an ax to grind with Teva Pharmaceutical Industries Ltd. (NasdaqGS: TEVA) - sorry, not the company itself, but the stock. It takes note of the media more than any other leading stock, and if one panders to the media’s whims, it serves him right if people are mad at him. As a longstanding shareholder in this company, and one who has been a follower of Teva since 1969, I have long since arrived at the conclusion that this stock has a life of its own, and that it adamantly refuses to act like its mother, the company.
What has happened in practice is that over the years it has become apparent that the disobedience of the daughter, the stock, has an effect over the short-term, but with the passage of time, the stock has begun to act like the company. Note that it is the stock, not the company, which has become an obsession in Israel. Americans ask, “how’s Teva doing?” while, on the other hand the good folk in Israel ask, “what’s happening with the stock?” Are the stock and company two different things? Not over the long-term, but in the short-term they definitely are, and I’ll try and prove this below.
If you look back, you will find that 2006 was not a unique year for the stock. It has experienced numerous falls and then rallies in the past, but what they all have in common is that they never had anything to do with the business side of Teva. They always happened because of the media and commentators. There have been brief crises in the past, and there were also longer ones too, as in 2006, and each of them had nothing whatsoever to do with the company’s business situation.
One of the major crises in the last 20 years was the one concerning Copaxone. The analysts, commentators and experts decided that Teva had made a terrible error in allocating resources to an ethical drug. When they learned that the ethical drug in question was a multiple sclerosis drug based on pharmacological ingredients, there was an outcry. “Everyone is opting for proteins, and you’re opting for chemicals?” they railed. But professors Ruth Arnon and Menahem Sela managed, with the relentless backing by Teva chairman Eli Hurvitz and his board, to develop, produce and, most important of all, to convince the medical world that this was something unique.
Teva’s stock, on the other hand, which listened to the commentators day after day, took a beating. It fell by more during that period than it did during the previous year. At that time, I learned a thing or two about long-term investments from a group of American pensioners at an old age home in Boca Raton in Florida, who had formed an “investors club” for investments in Israel. I got a call from one from them asking what had caused the falls. “We can’t understand why the stock has gone down” they said. So I sent them a review written by a New York analyst, which explained the risks in Copaxone. They read it and replied, “Pick up Teva when it’s coming down, the man can’t tell the difference between dark and light. Does the fact that Teva has tried to develop an ethical drug mean that the generic industry is past its prime? Teva got an idea from two geniuses, one from the Weizmann Institute, and the other from Ness Ziona. So should Hurvitz have turned down their idea, given the cost involved? “Remember this, son,” the old folk from Boca Raton said back then. “If the stock falls because of commentaries that have nothing to with the company’s core business, buy!” I have regularly used that maxim in this column ever since.
Another occasion on which Teva collapsed was when the UK billionaire Robert Maxwell vanished at sea. He was a major shareholder and it was feared that the company that held his asset portfolio would offload two million shares onto the market, as all the experts and market makers predicted. I was reminded then of the investment club at Boca Raton; the stock listened to the experts and fell 22%.
Teva climbed to an all-time high of almost $46 in mid-December 2005. By July 2006 it had fallen 35% to $29.50. It hovered between $30 and $32 for the rest of the year, with slight gains either way. Since the beginning of 2007, it has climbed 20%. What happened to the company from mid-December to the end of 2006? Nothing. Quite the contrary, 2006 was the most successful year in Teva’s history. What is interesting here is that 2006 was also perhaps the worst year in the stock’s history.
What does this prove? That there’s no connection between company and stock? Perish the thought. It proves that the stock (the investors) listen to commentaries in the media, not the company. That’s all there is to it. And here is some proof to support this claim. Why did Teva rise to an all-time high at the end of 2005 (- and perhaps the stock gained a bit too much back then)? Because the prevailing opinion at that time was that both 2006 and 2007 would be record years for the company. In addition, there were also the highly positive developments in the generics sector, as well as, of course, Copaxone (that pitiful idea, remember?). To this one must also add the growth generated by the ongoing mergers and acquisitions policy.
Teva more than met all the expectations for 2005. But what about the stock? It collapsed. It started with the merger with Ivax Diagnostics (AMEX: IVD - News), which created a merger-based loss in the first quarter of 2006; it continued with the renewed fears over Copaxone, thanks to Elan Corp. (NYSE: ELN - News) and its Tysabri, and it ended with the announcement of the departure of president and CEO Israel Makov, the man who took Teva from $3 billion sales when he joined to $8 billion when he stepped down. It was from Makov that I learned that Teva is one of the most well-oiled business machines in the world. True, I imagine that the company would not have made the same rate of progress had he not joined it, and I have not a shred of doubt that relations between him and Hurvitz were strained, but it would be far fetched to attribute such a severe crisis in the stock to this.
What actually happened last week? The company continued as usual, but the stock sailed upwards, not because of the facts heaven forbid, but because of the songs of praise from all corners for the forecasts. In other words, those people who bolted because of one theoretical crisis or another, returned again and pounced on Teva stock, since those people who predicted the crisis are now marveling at the forecasts. The truth is that the fourth-quarter results did not meet the forecasts, and the stock, which would have probably fallen were it not for Teva’s strong guidance, rose. Great.
Save for a few professional players, Teva is a long-term investment for the simple reason that it is the leader in a business-medical niche that is only growing in size all the time. As one whose opinions on Teva have been common knowledge ever since this column began, I would say that the problems that led the analysts to lower their ratings for Teva in 2006 - i.e. the fears that it would be unable to repeat the phenomenal growth of 2006, Copaxone’s decline and the fear that incoming CEO Shlomo Yanai will be unable to step into Makov’s shoes, fears which I feel never had any justification, still exist today. The only difference is that the analysts don’t mention them any more. <<<
Myriad Genetics (2-07) article by Feuerstein -
In this article he makes some good points about the Flurizan Phase 2 study. My main interest in Myriad is in their genetics testing business, which cranked out over $120 mil in revenues last year and is growing. Flurizan is in Phase 3 for AD, so there's reason to be wary since the trial could bomb out (results in 2008). AD has been a bio graveyard for the most part. At least Myriad has a reliable source of revenues to fund their drug development, and over $200 mil in cash -
>>> Myriad Genetics Doesn't Make The Grade
By Adam Feuerstein
Senior Writer
2/8/2007 8:26 AM EST
URL: http://www.thestreet.com/newsanalysis/biotech/10337586.html
Myriad Genetics (MYGN) is one of several companies trying to hit the Alzheimer's disease jackpot by developing a drug that blocks the formation of toxic beta-amyloid protein deposits in the brain.
At the risk of sounding too much like a nattering nabob of negativism, I believe the odds for success here are low. (I know, first I take a bearish stance on Neurochem (NRMX) and its Alzheimer's drug, and now I do the same with Myriad.)
What's my beef with experimental Alzheimer's drugs? There's no beef, I promise -- I simply believe these first two Alzheimer's drugs with disease-modifying potential are lacking.
Flurizan is Myriad's beta-amyloid-lowering drug now being evaluated in two phase III trials. On Tuesday, Myriad announced that it was punting on a planned 12-month interim analysis this fall of the first of these studies. Instead, the company will let the trial run through to completion in the first half of 2008.
So, with data from the Flurizan study not coming until next year, isn't it a bit early to worry about this as a stock-moving event? Agreed, but at the same time, I view the canceled interim analysis as a crack in Myriad's confidence in its Alzheimer's drug candidate.
Myriad's stock has been on a tear because the company's base genetics-testing business is profitable and growing. But my general feeling is that Myriad's valuation is overinflated because of Flurizan.
As a stand-alone business, genetic testing (or diagnostics) tends to have lower profit margins than selling drugs. So, subtract Flurizan from Myriad's plate and the company wouldn't (shouldn't) deserve the premium multiple it gets today.
Myriad shares closed Wednesday up 3.5% to $37.11.
All right, let's focus on Flurizan. Like with my analysis on Neurochem, my skepticism is grounded in poor phase II data, which suggests the phase III trials are high-risk.
Last July, Myriad announced results of a 24-month, follow-up analysis of its phase II study that found patients with mild Alzheimer's disease receiving high-dose Flurizan (800 milligrams dosed twice a day) "demonstrated a substantial benefit over other dose groups in the study and that this benefit continued to increase over 24 months, for each of the evaluated areas of cognition, memory loss, global function and activities of daily living."
These data were presented at the 10th International Conference on Alzheimer's Disease and Related Disorders, in Madrid, Spain, by Dr. Gordon Wilcock of the University of Oxford. Wilcock was the lead investigator for the phase II trial.
Note that patients in both Flurizan dose groups, as well as the placebo patients, all seem to do equally well for the first nine months of the study. (The error bars for each three-month time point either overlap or almost touch each other, suggesting that the point differences shown on the graph are a bit suspect.)
From months 9 to 12, however, the 800-mg dose group and placebo patients decline dramatically. The steep slope declines of the graphs represent a loss of cognition, as measured by a mean change in the ADAS-cog test.
The primary endpoint of the phase II study was measured at 12 months, and it's at this point that the study failed to show a statistically significant difference between Flurizan and placebo using ADAS-cog and other tests.
But Myriad wants you to forget about the results at 12 months and instead focus on what happens to patients who continue taking Flurizan through 24 months. Here, in this voluntary continuation of the phase II study, Myriad claims that the cognitive ability of high-dose Flurizan patients stabilizes -- and even improves at some time points -- from 12 to 24 months, as illustrated by the flattening of the slope of the curve.
What might explain this dramatic improvement? Myriad says, simply, that the drug takes longer than 12 months to show full effects. The longer a patient takes Flurizan, the greater the benefit.
But I have an alternative -- and more skeptical -- explanation: Notice that the size of the high-dose Flurizan patient group decreased by 52% from 48 patients at the start of the study to 23 patients after 12 months -- when the dramatic improvements began to be recorded. (Look at the yellow "N's" on the chart.)
This is a classic example of selection bias, where patients who are doing better remain in the study and artificially skew longer-term results. Patients doing badly at 12 months dropped out and ceased being tracked.
When Myriad announced the initial results from the Flurizan phase II study in May 2005, it also announced an amendment to the ongoing phase III studies to extend the study period to 18 months from 12 months, claiming the longer time period boosted chances for the study's success. (Yes, Myriad actually started its phase III studies before having data from the phase II study, yet another red flag ...)
As I mentioned above, the Flurizan phase II study failed at 12 months to meet its primary endpoint, which was to show a statistically significant treatment effect between Flurizan 800 mg taken twice a day compared with placebo on three different measures of Alzheimer's disease severity. (Those tests were the Alzheimer's Disease Cooperative Study -- Activities of Daily Living inventory (ADCS-ADL), Clinical Dementia Rating -- Sum of Boxes (CDR-sb), and the Alzheimer's Disease Assessment Scale -- Cognitive function subscale (ADAS-cog).)
Myriad describes Flurizan as a Selective Amyloid Beta-42 Lowering Agent. As a reminder, the "beta-amyloid" theory of Alzheimer's believes damaging beta-amyloid plaques form when certain enzymes cut amyloid precursor protein (APP) into fragments. Instead of being cleared from the body, some of these fragments clump together into plaques, which damage nerve cells in the brain.
Flurizan is supposed to work by attaching itself to gamma secretase, one of the enzymes responsible for cutting up APP. Once attached, Flurizan forces gamma secretase to modulate its behavior, cutting APP into smaller -- and less sticky -- fragments that can't form into brain-damaging plaques.
Researchers I've consulted say that Myriad's approach to lowering beta-amyloid plaques -- in this case, by working upstream where enzymes cut APP into the sticky fragments -- is feasible.
But the hurdles inherent in this approach are high. It's difficult to get enough drug into the brain to have a therapeutic effect on gamma secretase (as opposed to just getting sufficient drug levels in plasma).
Myriad has presented retrospective analyses from the phase II study showing patients that were able to achieve higher blood levels of Flurizan performed better. But the problem is that it's difficult -- maybe impossible -- to know in advance which patients will be able to achieve those higher concentrations of Flurizan in their system.
The U.S.-based phase III trial of Flurizan has enrolled 1,600 patients with mild Alzheimer's (randomized to drug or placebo) and uses the same clinical endpoints from the phase II study. These clinical measures, however, will be assessed after 18 months of treatment.
Expect to see that data in the first half of 2008. We'll wait a while for the final data to determine the ultimate outcome, but I'm skeptical that Flurizan will be able to achieve a statistically significant benefit for patients of Alzheimer's. <<<
Aiming, Looks like my new OT board got the ax and disappeared down an Orwellian memory hole. Oh well, no great loss. Kind of weird though, I wonder what happened.
Aiming, Well, the good thing is that it doesn't sound like dead cells, since those wouldn't revert back to normal after dosing is stopped for a couple weeks. Likewise for mutagenic changes. And it doesn't sound like calpain/spectrin since those changes probably wouldn't resolve either (assuming those changes would be something like axonal breakage).
The metabolite angle might make sense, though it has to be more than just a metabolite interacting with the fixative. It's more because of the cellular changes. A metabolite interacting with fixative might show up looking weird under a microscope, but it shouldn't cause structural cellular changes. But then again, I'm not a histopathologist, so who knows.
As for the target organ - if the cellular change is due to a metabolite of CX-717, then trying to figure out in what organ the effect is occurring would depend on when CX-717 starts to break down - while it's still in the brain, or after it's in the bloodstream on the way to the liver, or in the liver. If it starts to be broken down while still in the brain, then the histo phenomenon could be found there as opposed to the liver.
I don't know, there's just too much uncertainty here, and I don't know enough about any of this stuff to make an educated guess. There's the histo phenomenon itself of which we investors know very little. Then there's the FDA imposed dosing restriction level, of which we know very little. And then the biggest variable is the FDA itself and what in the world they might do. I'd have to conclude that there is insufficient data to make anything but the wildest of guesses on the outcome here.
Thanks Neuro. Well, that changes things considerably. Dead neurons from excitotoxicity, or snapped axons from beta spectrin breakdown, aren't the kind of cellular changes that would be easily reversible.
I'm starting to wonder if this may be something outside of the CNS, like a metabolite of CX-717 affecting cells in the liver. CX-717 has structural differences from other compounds like CX-701 and Org-24448, so when it is broken down into its metabolites, one or more of the metabolites
will be different from those other compounds, and perhaps that metabolite that is unique to CX-717 interacts with a component found in the fixative. That could explain - 1) why there is nothing seen with the other compounds, 2) why quick freezing without fixative shows nothing abnormal, 3) why the cellular changes resolve after dosing is stopped (the organ, say liver, eventually clears out all of the metabolite, and the histo changes in the organ's cells, presumably of a transient nature, revert back to normal), and 4) would also jive with the phenomenon of being dose dependent.
As for why the cellular change doesn't continue to worsen between week 2 and 3 months, perhaps the organ clears the metabolite at a rate sufficiently fast to prevent a cumulative effect from occurring, or perhaps there is an upper threshold to the cellular change, beyond which no additional changes are possible (saturation), so beyond 2 weeks no additional cellular effect is possible.
Neuro, one additional question -
While the metabolism of a small molecule drug like an Ampakine would ultimately occur in the liver, do you know when it first begins to break down into its metabolites - a) in the CNS, b) in the bloodstream, or c) in the liver? Thanks Neuro!
Jerry, board, I just created a new board for off topic postings called the Anything / Everything board. On that board anything goes - politics, religion, sports, music, Angelina's boobs, whatever :o)
http://www.investorshub.com/boards/board.asp?board_id=8393
Neuro, By any chance do you remember Dr. Stoll saying that the cellular changes disappear if dosing is stopped for a period of time prior to the sacrificing of the animals? I vaguely remember something like that, but if you don't recall I can go back and check the last several presentations since I have them recorded. Thanks Neuro.
If that is indeed the case, and the cellular changes revert back to normal following cessation of dosing, I'm going to have to do a major reevaluation. All I remember for sure is him saying that the cellular changes don't seem to get any worse between 2 weeks and 3 months.
Gilead's (2-07) New Drug Application for Ambrisentan Receives Priority Review Status
Friday February 16, 4:00 pm ET
PDUFA Date Set for June 18, 2007
>>> FOSTER CITY, Calif.--(BUSINESS WIRE)--Gilead Sciences, Inc. (Nasdaq:GILD - News) today announced that the U.S. Food and Drug Administration (FDA) has accepted for filing and granted a Priority Review for the company's New Drug Application (NDA) for marketing approval of ambrisentan (5 mg and 10 mg) for the once-daily treatment of pulmonary arterial hypertension (PAH).
Priority Review status is assigned to drug products that, if approved, would be a significant improvement compared to marketed products in the treatment, diagnosis or prevention of a disease. A Priority Review means that the time it takes FDA to review a new drug application is reduced. The FDA goal for reviewing a drug with Priority Review is six months. Gilead submitted its NDA for ambrisentan on December 18, 2006. The FDA has established a target review date, under the Prescription Drug User Fee Act (PDUFA), of June 18, 2007.
About Ambrisentan
Ambrisentan is a non-sulfonamide, propanoic acid-class, endothelin receptor antagonist that is selective for the endothelin type-A (ETA) receptor. Activation of the ETA receptor by endothelin, a small peptide hormone, leads to vasoconstriction and cell proliferation. PAH is associated with elevated endothelin blood levels. Ambrisentan has been granted orphan drug designation for the treatment of PAH in both the United States and European Union.
As an investigational compound, ambrisentan has not yet been determined safe or efficacious in humans.
GlaxoSmithKline holds rights to commercialize ambrisentan in territories outside of the United States.
About Pulmonary Arterial Hypertension
PAH is a debilitating disease characterized by constriction of the blood vessels in the lungs leading to high pulmonary arterial pressures. These high pressures make it difficult for the heart to pump blood through the lungs to be oxygenated. Patients with PAH suffer from shortness of breath as the heart struggles to pump against these high pressures causing such patients to ultimately die of heart failure. PAH can occur with no known underlying cause, or it can occur secondary to diseases such as connective tissue disease, congenital heart defects, cirrhosis of the liver and HIV infection. PAH afflicts approximately 200,000 patients worldwide.
About Gilead Sciences
Gilead Sciences is a biopharmaceutical company that discovers, develops and commercializes innovative therapeutics in areas of unmet medical need. The company's mission is to advance the care of patients suffering from life-threatening diseases worldwide. Headquartered in Foster City, California, Gilead has operations in North America, Europe and Australia. For more information on Gilead Sciences, please visit the company's website at www.gilead.com or call Gilead Public Affairs at 1-800-GILEAD-5 or 1-650-574-3000. <<<
Daviddal, Well, if it's an artifact, it's a dose dependent, compound specific artifact. We can't dismiss this as a mere artifact of the fixation process that is independent of the drug. The presence of the drug is a prerequisite for the cellular "phenomenon", it only occurs at higher doses, and it doesn't occur with other compounds. And after the dosing is stopped for a while, the "phenomenon" disappears. CX-717 (and only CX-717) is clearly doing something to bring about the phenomenon.
Ombow, Thanks. He sounded a little pissed, so I guess I won't make any more requests :o) Based on Baudry's paper, it looks like the calpain/spectrin phenomenon may not be associated with high impact vrs low impact per se, and the binding site of the compound may not matter either. Both high impacts CX-614 and cyclothiazide bind at the same site (though in a different orientation within that site), and one induces calpain activity while the other doesn't. CX-717 binds at a completely separate site, but that may not matter if the key to calpain activation is in the deactivation mechanism of action vrs desensitization. Oh well, it still would be nice to know if CX-614 produces the same type histo changes as CX-717.
I'm also starting to wonder if perhaps the cellular change might be somewhere other than the CNS. If Dr. Stoll would just drop a few small hints at the next presentation that would be much appreciated, and I don't see how a little more info would hurt Cortex or help competitors. I wouldn't expect him to say "the cells of the hippocampus are dying" or anything like that.
Neuro, It still doesn't make sense why the phenomenon, whether it occurs before or after death, is only associated with CX-717. Dr. Stoll indicated pretty clearly that they had run CX-701 through the same regime as CX-717 went through and saw no finding. He also clearly said that Org-24448 wasn't associated with the cellular phenomenon either.
That's one reason why I figure the calpain/spectrin hypothesis might be a possibility, since we know it occurs with some Ampakines but not others, and the breakdown of spectrin protein should theoretically produce structural changes visible under a microscope.
I was initially under the impression that the calpain/spectrin process was a high impact-only phenomenon (we know it occurs with CX-614), but the Baudry paper instead suggests a link to the deactivation mechanism of Ampakine action vrs the desensitization mechanism. He found that high impacts like cyclothiazide, which act almost exclusively by inhibiting receptor desensitization, don't induce calpain mediated spectrin degradation. Cortex's compounds (even the high impact CX-614) act more via inhibiting receptor deactivation, although there is a wide range, with some acting by varying degress of both deactivation and desensitization mechanisms. The differing mechanisms between the various Cortex compounds could conceivably explain why CX-717 would be associated with the histo phenomenon while its analog CX-701 isn't.
Anyway, the mystery continues. After this is all over, I hope Cortex tells us the details of this mystery, or I'm going to be mightily pissed :o)
Neuro, Yes, but as you said, they are still doing further examination of the frozen sections to verify that there were no cellular changes present, and we'll see what the electron microsope finds. Wouldn't it be ironic if all along the changes were in the liver? We investors are really groping in the dark here, but absent any additional info from Cortex, that's about all we can do. Or we could talk more about our drug experiences back in college :o) I noticed you didn't come clean yet Neuro, so let's hear about it - mescaline, peyote :o) Just kidding, but inquiring minds want to know :o)
BTW, from Wikipedia, here's some info on Oligodendrocytes. They are the mature version of Oligodendroglial cells, and are involved in myelination in the CNS -
>>> Oligodendrocyte
From Wikipedia, the free encyclopedia
Oligodendrocytes (from Greek literally meaning few tree cells), or oligodendroglia (Greek, few tree glue),[1] are a variety of neuroglia. Their main function is the myelination of axons exclusively in the central nervous system of the higher vertebrates, a function performed by Schwann cells in the peripheral nervous system. A single oligodendrocyte can extend to up to 50 axons, wrapping around approximately 1 mm of each and forming the myelin sheath.
Contents [hide]
1 Origin
2 Function
3 Pathology
4 Notes
5 References
Origin
Oligodendroglia arise during development from an oligodendrocyte precursor cell which can be identified by its expression of a number of antigens, including the ganglioside GD3 (Curtis et al., 1988; LeVine and Goldman, 1988; Hardy and Reynolds, 1991; Levine et al., 1993), the NG2 chondroitin sulfate proteoglycan (Levine et al., 1993), and the platelet derived growth factor-alpha receptor subunit (PDGF-alphaR) (Pringle et al., 1992). In the rat forebrain the majority of oligodendroglial progenitors arise during late embryogenesis and early postnatal development from cells of the subventricular zones (SVZ) of the lateral ventricles. SVZ cells migrate away from these germinal zones to populate both developing white and gray matter, where they differentiate and mature into myelin-forming oligodendroglia (Hardy and Reynolds, 1991; Levison and Goldman, 1993). However, it is not clear whether all oligodendroglial progenitors undergo this sequence of events. It has been suggested that some undergo apoptosis (Barres et al., 1992) and that some fail to differentiate into oligodendroglia but persist into maturity as adult oligodendroglial progenitors (Wren et al., 1992).
[edit] Function
The nervous system of mammals depends crucially on this sheath for insulation as it results in decreased ion leakage and lower capacitance of the cell membrane. There is also an overall increase in impulse speed as saltatory propagation of action potentials occurs at the nodes of Ranvier in between Schwann cells (of the PNS) and oligodendrocytes (of the CNS); furthermore miniaturization occurs, whereby impulse speed of myelinated axons increases linearly with the axon diameter, whereas the impulse speed of unmyelinated cells increases only with the square root of the diameter.
As part of the nervous system they are closely related to nerve cells and like all other glial cells the oligodendrocytes have a supporting role towards neurons. They are intimately involved in signal propagation, providing the same functionality as the insulation on a household electrical wire.
[edit] Pathology
Diseases that result in injury to the oligodendroglial cells include demyelinating diseases such as multiple sclerosis and leukodystrophies. Oligodendroglia are also susceptible to infection by the JC virus, which causes progressive multifocal leukoencephalopathy (PML), a condition which specifically affects white matter, typically in immunocompromised patients. Tumors of oligodendroglia are called oligodendrogliomas.
[edit] Notes
^ (Ragheb 1999, p. 14).
[edit] References
Ragheb, Fadi (1999), The M3 Muscarinic Acetylcholine Receptor Mediates p42mapk Activation and c-fos mRNA Expression in Oligodendrocyte Progenitors, Ottawa: National Library of Canada [link accessed 2006-03-07]
Raine, C.S. (1991). Oligodendrocytes and central nervous system myelin. In Textbook of Neuropathology, second edition, R.L. Davis and D.M. Robertson, eds. (Baltimore, Maryland: Williams and Wilkins), pp. 115–141. <<<