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Nerve-Blocking Drugs And Cancer
https://news.cuanschutz.edu/news-stories/sensory-nerves-appear-to-drive-head-and-neck-cancer-growth
Nature Biotechnology on NASH Therapies
https://www.nature.com/articles/s41587-023-01787-8
Pharmacyclics bought ibrutinib from Celera Genomics.
From Wikipedia:
>>
History[edit]
Ibrutinib was created by scientists at Celera Genomics as a tool compound for studying BTK function; it covalently binds its target which is ideal for a reagent but generally not considered ideal for drugs.[19]
In 2006, in the course of acquiring an HDAC-focused program from Celera after its own initial discovery program had failed, Pharmacyclics also picked up Celera's small molecule BTK inhibitor discovery program for $2M in cash and $1M in stock and named the tool compound PCI-32765.[19][20] In 2011 after the drug had completed Phase II trials, Johnson & Johnson and Pharmacyclics agreed to co-develop the drug, and J&J paid Pharmacyclics $150 million upfront and $825 million in milestones.[21] Pharmacyclics was acquired by AbbVie in May 2015, and Abbvie projected global sales of US$1 billion in 2016 and $5 billion in 2020.[22]
<<
I was invested in Celera, but decided not to buy PCYC for about 2 or 3 dollars a share at the time.
Bepirovirsen
https://www.gsk.com/media/9855/fy-2022-results-slides.pdf
See slide 12.
A placebo recommended by nine out of ten homeopaths who are members in good standing of Homeopaths Without Borders,
Sanofi terminates RGLS Ph II for Alport syndrome
https://app.quotemedia.com/data/downloadFiling?type=HTML&webmasterId=501&ref=116826219&CK=1505512
GSK 2005 Buyout of ID Biomedical
IDBE was developing FluInsure, a non-live intranasally delivered flu vaccine. Proteosomes ("a licensed or proprietary adjuvant/delivery technology") were a component of FluINsure. Hey, an intranasally delivered flu vaccine seems like a good idea!
Posters on the message board were also excited about StreptAvax, a vaccine to prevent disease caused by Streptococcus pneumonia bacteria. Multiple shots on goal!
You contended that IDBE shareholders were lucky to be rescued and that GSK sought the buyout for IDBE's research and manufacturing facilities. Time proved you right.
vinmantoo ---
Am I correct in remembering you as a poster on the Yahoo ID Biomedical (IDBE) message board?
GSK really saved our bacon on that investment!
(No offense to anyone Jewish or Muslim.)
(GSK)- Is it surprising (i.e., to knowledgeable people) that GSK plans a Phase III trial of bepirovirsen as a monotherapy?
Bepirovirsen PR
https://www.gsk.com/en-gb/media/press-releases/gsk-presents-promising-new-data-for-bepirovirsen-an-investigational-treatment-for-chronic-hepatitis-b/
>>
25 June 2022
GSK presents promising new data for bepirovirsen, an investigational treatment for chronic hepatitis B
For media and investors only
Issued: 25 June 2022, London UK
* Interim analysis from the B-Clear phase IIb trial shows bepirovirsen’s potential to suppress both the surface antigen and the virus of hepatitis B, leading to the possibility of functional cure
* Phase III trial evaluating bepirovirsen as a monotherapy is anticipated to start in the first half of 2023
* Exploring potential combination treatments to further reduce the global burden of chronic hepatitis B
*
GSK plc today announced promising interim results from the B-Clear phase IIb trial showing that bepirovirsen, an investigational antisense oligonucleotide treatment for hepatitis B, reduced levels of hepatitis B surface antigen (HBsAg) and hepatitis B virus (HBV) DNA after 24 weeks’ treatment in people with chronic hepatitis B (CHB).
These interim analysis data were presented today in an oral late-breaker session at the European Association for the Study of the Liver’s International Liver Congress 2022 in London, UK. The final results from the study will be submitted for presentation at a scientific congress later this year, and for publication in a peer-reviewed journal.
Chris Corsico, SVP, Development, GSK, said: “Chronic hepatitis B affects nearly 300 million people with approximately 900,000 patients dying each year from its associated complications.[1],[2] These encouraging data support further investigation of bepirovirsen, both as monotherapy and in combination, as a potentially transformative new treatment option for patients with chronic hepatitis B.”
Current treatment options have limited success in leading to functional cure, where the virus is not eliminated from the body but is at low levels that are undetectable in blood and can be controlled by the immune system without medication. The mainstay of therapy includes nucleoside/nucleotide analogues (NA) which are often taken for life because they suppress but rarely clear the virus. Bepirovirsen’s unique mechanism of action works to reduce HBV replication, suppress HBsAg and stimulate the immune system. Bepirovirsen has the potential to lead to functional cure in patients with CHB.
Professor Man-Fung Yuen, Principal Investigator and Chief of Division of Gastroenterology and Hepatology, Queen Mary Hospital, The University of Hong Kong, said: “The data presented today are a promising step forward for the millions of people living with chronic hepatitis B worldwide. Specifically, the reduction in hepatitis B surface antigen and HBV DNA to below the lower limit of quantification has the potential to be clinically meaningful and lead to functional cure. This could help people living with CHB and healthcare providers manage the long-term consequences of CHB which include the social burden as well as the risk of developing life-threatening liver complications.”
GSK is also exploring combinations of bepirovirsen and other therapeutic modalities in the following trials. Combination treatments could increase functional cure rates in more patients, thereby further reducing the global disease burden of CHB. Trials include:
* Phase IIb trial of bepirovirsen in sequential combination with pegylated interferon (PegIFN) treatment
*
* Phase II trial of bepirovirsen in combination with GSK’s chronic hepatitis B targeted immunotherapy
*
About the B-Clear phase IIb trial
The B-Clear phase IIb study is investigating the efficacy and safety of 12 or 24 weeks treatment with bepirovirsen in people with CHB on stable NA treatment or not on NA treatment at study start. The primary endpoints are the proportion of patients achieving HBsAg levels below the Lower Limit of Quantification (LLOQ), and HBV DNA levels below LLOQ sustained for 24 weeks without rescue medication after end of treatment with bepirovirsen.
The study consists of two parallel cohorts, one for patients receiving NA treatment and the other for patients who were not on NA. Patients from each arm were randomised to 1 of 4 treatment arms within each cohort, with treatment administered weekly with or without loading doses (LD) on days 4 and 11:
* Bepirovirsen 300 mg with LD for 24 weeks;
* Bepirovirsen 300 mg with LD for 12 weeks then 150 mg for 12 weeks;
* Bepirovirsen 300 mg with LD for 12 weeks then placebo for 12 weeks;
* Placebo with LD for 12 weeks then bepirovirsen 300 mg without LD for 12 weeks.
In both cohorts, virologic responses were observed at the end of treatment:
* For those patients receiving NA treatment (n=227), 24 weeks treatment of 300 mg bepirovirsen resulted in HBsAg < LLOQ and HBV DNA < LLOQ in 28% of patients at end of treatment.
* For patients not on NA (n=230), 24 weeks treatment of 300 mg bepirovirsen resulted in HBsAg < LLOQ and HBV DNA < LLOQ in 29% of patients at end of treatment.
* The durability of these responses is being assessed.
*
Treatment-related serious adverse events (SAEs) were observed in <1% of patients receiving NA treatment and 1% of patients who were not on NA. SAEs were reported in 3% and 4% of patients receiving NA treatment and those who were not on NA, respectively. There were no clinically meaningful differences in adverse events across treatment arms in either trial.
About chronic hepatitis B
Hepatitis B is a viral infection of the liver, caused by the hepatitis B virus, that can cause both acute and chronic liver disease.[1] Chronic hepatitis B (CHB) is a long-lasting infection and occurs when the body’s immune system is unable to fight off the virus and it persists in the blood and liver.[2] It is estimated that there are 296 million people globally with CHB.[1] As of 2019, 30.4 million people were aware of their infection, while 6.6 million of the people diagnosed were on treatment.[1] Even when treated, CHB can progress to liver complications including cirrhosis and liver cancer, which results in nearly 900,000 deaths per year.[2]
Viral suppression is the current goal for treatment of CHB. However, viral replicative activity may return upon cessation of treatment, requiring lifelong therapy to prevent viral rebound. The concept of functional cure of CHB aims to eliminate the virus from circulating in the blood and prevent any disease activity in the liver. As only a limited number of patients currently treated for CHB achieve HBsAg loss, considered the hallmark for achieving functional cure, development of therapeutic approaches to reach functional cure are needed.
About bepirovirsen (GSK3228836)
Bepirovirsen is an investigational antisense oligonucleotide (ASO) designed to specifically recognise the RNA that the hepatitis B virus uses to replicate itself in the infected liver cells (hepatocytes) and make the viral antigens (proteins) which facilitate chronicity of the disease by helping to avoid clearance by the immune system. The ASO recruits the liver’s own enzymes to eliminate the RNA by digesting it to an inactive form. The subsequent reduction in the levels of the RNA results in a decrease in both the virus and the production of viral antigen (HBsAg) by the hepatocytes, which can be measured by a drop in the HBV DNA and antigen levels in the circulating blood. Bepirovirsen has an additional property of stimulating immune responses via Toll-like receptor 8 (TLR8) which may help the immune system to achieve durable clearance of the virus from circulating blood.
Bepirovirsen (previously known as ‘ISIS 505358 or IONIS-HBVRX’) was discovered by and jointly developed with Ionis Pharmaceuticals. Bepirovirsen is one of the ASO HBV programme assets in-licensed by GSK from Ionis Pharmaceuticals in August 2019.
About GSK
GSK is a science-led global healthcare company. For further information please visit www.gsk.com/
about-us.
Cautionary statement regarding forward-looking statements
GSK cautions investors that any forward-looking statements or projections made by GSK, including those made in this announcement, are subject to risks and uncertainties that may cause actual results to differ materially from those projected. Such factors include, but are not limited to, those described in the Company's Annual Report on Form 20-F for 2021, GSK’s Q1 Results for 2022 and any impacts of the COVID-19 pandemic.
References
[1] World Health Organisation, Hepatitis B Key Facts, June 2022
[2] World Health Organization. Global Hepatitis Report, 2017
<<
Abbott's pioneering infectious disease-testing platform, IRIDICA, now available in Europe
(Actually, the technology was pioneered by Isis Pharmaceuticals and sold to Abbott in 2009.)
http://www.multivu.com/players/English/7380751-abbott-pioneering-infectious-disease-testing-platform-iridica/
How did ISIS become a party to this litigation?
I don’t know the details.
In 1998 Isis began a collaboration with Merck on HCV:
http://www.wikinvest.com/stock/Isis_Pharmaceuticals_(ISIS)/Merck_Inc
In 2002 Isis’s GeneTrove division did work for Merck (pardon the rhyme):
http://ir.isispharm.com/phoenix.zhtml?c=222170&p=irol-newsArticle&ID=1290295&highlight=
Hob
RE: GILD is also defending against a patent-infringement lawsuit by MRK
Isis Pharmaceuticals is a party to this. From the 2013 Isis Annual Report (page 54):
Gilead Litigation In August 2013, Gilead Sciences Inc. filed a suit in the United States District Court of the Northern District of California related to United States Patent Nos. 7,105,499 and 8,481,712 that are jointly owned by Merck Sharp & Dohme Corp. and Isis Pharmaceuticals, Inc. In the suit Gilead is asking the court to determine that Gilead’s activities do not infringe any valid claim of the named patents and that the patents are not valid. Isis and Merck Sharp & Dohme Corp. filed their answer denying Gilead’s noninfringement and invalidity contentions, contending that Gilead’s commercial sale and offer for sale of sofosbuvir prior to the expiration of the ‘499 and ‘712 patents will infringe those patents, and requesting monetary damages to compensate for such infringement. Under Isis’ agreement with Merck, Merck is responsible for the costs of this suit.
ISIS has targeted TDP-43:
http://www.sciencecodex.com/common_rna_pathway_found_in_als_and_dementia-99292
A Bloomberg news story from today has BIIB declaring that they have done preclinical work on TDP-43.
Here's a PR announcing the 12-10-2012 BIIB-ISIS collaboration:
http://ir.isispharm.com/phoenix.zhtml?c=222170&p=irol-newsArticle&ID=1765705&highlight=
>>Press Release
Biogen Idec and Isis Pharmaceuticals Announce Collaboration For Antisense Programs To Treat Neurological Disorders
--Biogen Idec has Option to Develop and Commercialize Promising Compounds from Three Research Programs to Treat Neurological or Neuromuscular Disorders--
--Isis Expands its Severe and Rare/Neuro Franchise with Three Promising New Targets--
WESTON, Mass. and CARLSBAD, Calif., Dec. 10, 2012 /PRNewswire/ -- Biogen Idec (NASDAQ: BIIB) and Isis Pharmaceuticals, Inc. (NASDAQ: ISIS) today announced that they have entered into a global collaboration agreement under which the companies will discover and develop antisense drugs against three undisclosed targets to treat neurological or neuromuscular disorders. Biogen Idec and Isis are also developing antisense drugs to treat spinal muscular atrophy and myotonic dystrophy type 1 under previously established collaborations.
"Our latest collaboration with Isis to discover and develop novel targets for the treatment of neurological disorders is a perfect fit within our early-stage research strategy," said Richard Brudnick, vice president and co-head of business development at Biogen Idec. "This will be our third collaboration with Isis, which is reflective of our respect for them as a partner and as a leader in antisense technology. By combining Isis' knowledge with Biogen Idec's expertise as a leader in neurology, we believe this latest discovery collaboration holds great potential for finding novel approaches to treating neurologic diseases."
Under the terms of the agreement, Isis will receive an upfront payment of $30 million and is responsible for the discovery of a lead antisense drug for each of the three undisclosed targets. Isis is eligible to receive substantial development milestone payments to support research and development of each program prior to the exercise by Biogen Idec of its option to license each program. Biogen Idec has the option to license a drug from each of the three programs through the completion of Phase 2 trials. Isis could receive up to another $200 million in a license fee and regulatory milestone payments per program. In addition, Isis will receive double-digit royalties on sales of drugs. Isis will be responsible for development of the drugs through the completion of the initial Phase 2 clinical trial, with Biogen Idec providing advice and assistance on research and the clinical trial design and conduct and regulatory strategy for each program. IfBiogen Idec exercises its option, it will assume global development, regulatory and commercialization responsibilities.
"We look forward to broadening our drug discovery and development efforts to include new neurological disease targets with Biogen Idec, a world leader in neurological diseases. Combining our antisense drug discovery with Biogen Idec's expertise in severe neurological diseases has significantly enhanced the development of our spinal muscular atrophy and myotonic dystrophy programs. For example, Biogen Idec's contributions have added significant value across multiple areas, such as government affairs, biomarker development, clinical trial design and regulatory expertise, bolstering our development activities for these programs," said B. Lynne Parshall, chief operating officer and chief financial officer at Isis. "We have been very successful in our partnering efforts this year, driven primarily by the advancement of the drugs in our pipeline. The high level of interest in our drug discovery technologies allows us to select the optimal partner for each program, while commanding significant value for our assets."
This collaboration follows two worldwide option and collaboration agreements between Biogen Idec and Isis, which were announced earlier in 2012, to develop and commercialize antisense drugs for the treatment of spinal muscular atrophy and myotonic dystrophy type 1.
About Biogen Idec
Through cutting-edge science and medicine, Biogen Idec discovers, develops and delivers to patients worldwide innovative therapies for the treatment of neurodegenerative diseases, hemophilia and autoimmune disorders. Founded in 1978, Biogen Idec is the world's oldest independent biotechnology company. Patients worldwide benefit from its leading multiple sclerosis therapies, and the company generates more than $5 billion in annual revenues. For product labeling, press releases and additional information about the company, please visit www.biogenidec.com.
About Isis Pharmaceuticals, Inc.
Isis is exploiting its leadership position in antisense technology to discover and develop novel drugs for its product pipeline and for its partners. Isis' broad pipeline consists of 25 drugs to treat a wide variety of diseases with an emphasis on cardiovascular, metabolic, severe and rare diseases, and cancer. Isis' partner, Genzyme, plans to commercialize Isis' lead product, KYNAMRO™, inthe United States and Europe following regulatory approval. Isis' patents provide strong and extensive protection for its drugs and technology. Additional information about Isis is available at http://www.isispharm.com/.
<<
ARRY Collaborator Obtains Funding
http://home.businesswire.com/portal/site/biospace/index.jsp?ndmViewId=news_view&newsId=20131003005222&newsLang=en
>>
October 03, 2013 08:00 AM Eastern Daylight Time
Loxo Oncology Raises $33 Million in Series A Financing to Fund Development of Small Molecule Oncology Drugs
Loxo Oncology Names Board of Directors and Scientific Advisory Board
NEW YORK--(BUSINESS WIRE)--Loxo Oncology, Inc., a biopharmaceutical company focused on targeted cancer therapies for genetically-defined populations, announced today that it has completed a $33 million Series A financing round. The round included founding investor Aisling Capital and new investors OrbiMed Advisors LLC and an undisclosed investor.
“Specifically, we expect to advance our lead product candidate through clinical proof of concept and a second program into the clinic.”
“This funding allows us to advance our pipeline on multiple fronts,” said Josh Bilenker, M.D., chief executive officer of Loxo Oncology. “Specifically, we expect to advance our lead product candidate through clinical proof of concept and a second program into the clinic.”
In conjunction with the financing, Loxo Oncology announced the formation of its Board of Directors, which includes Steven Elms and Dov Goldstein, M.D., managing partner and partner at Aisling Capital, respectively; David Bonita, M.D., private equity partner at OrbiMed Advisors; and Keith Flaherty, M.D., director of the Henri and Belinda Termeer Center for Targeted Therapies at Massachusetts General Hospital.
Additionally, Loxo Oncology appointed four new members to its Scientific Advisory Board. These nationally-recognized physician/scientists are providing critical advice and expertise to the company around rational target selection, product profile definition and clinical development strategy. Loxo Oncology was founded to translate these insights into drugs through the world-class research and discovery capabilities of Array BioPharma Inc., with which it entered into a multi-year license and collaboration agreement in July 2013.
In addition to Dr. Flaherty, who is chair of the Scientific Advisory Board, the new members include:
Jeffrey A. Engelman, M.D., Ph.D., director, Center for Thoracic Cancers, Massachusetts General Hospital Cancer Center; associate professor of Medicine, Harvard Medical School
Ross L. Levine, M.D., associate member, Human Oncology and Pathogenesis Program, and associate attending physician, Leukemia Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center; associate professor of Medicine, Weill Cornell Medical College
Ben Ho Park, M.D., Ph.D., associate professor of Oncology, Breast Cancer Research Program, and Joint Appointment, Whiting School of Engineering, Department of Chemical and Biomolecular Engineering, Johns Hopkins University; attending physician, Johns Hopkins Hospital, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
David Solit, M.D., Ph.D., director, Developmental Therapeutics, and associate professor of Medicine, Cell and Developmental Biology, Memorial Sloan-Kettering Cancer Center
About Loxo Oncology
Loxo Oncology was incorporated in Delaware in May 2013 and was founded by Josh Bilenker, M.D., a partner at Aisling Capital. Loxo Oncology is committed to bringing targeted cancer therapies rapidly into the clinic that have an opportunity for outsized clinical effects in genetically defined patient populations. Loxo Oncology derives its company name from an attendant of the Greek goddess Artemis, who represented the concept of trajectory in the sport of archery.
About Aisling Capital
Aisling Capital is a life sciences-dedicated venture capital firm with over $1.6 billion under management. The firm invests in companies developing pharmaceutical and medical products, as well as in businesses that provide drug development, manufacturing and other important services to the healthcare industry. Headquartered in New York, Aisling invests in both private and public companies utilizing a wide variety of investment structures. The Aisling Capital team's combination of clinical, operational, transactional and capital markets experience allows the firm to identify, execute and realize investments across the life sciences industry. For more information, visit www.aislingcapital.com.
About OrbiMed Advisors
OrbiMed is a leading investment firm dedicated exclusively to the healthcare sector with approximately $7 billion in assets under management. OrbiMed invests globally across the spectrum of healthcare companies on a worldwide basis, from venture capital start-ups to large multinational companies. OrbiMed's team includes over 60 experienced professionals with offices in New York, San Francisco, Shanghai, Mumbai and Herzliya. OrbiMed manages a series of private equity funds, public equity funds, royalty and debt funds, and other investment vehicles.
Contacts
For Loxo Oncology
Julie Normart, 415-946-1087
jnormart@wcgworld.com
<<
ISIS—Factor XI is an unusual place to intervene in the coagulation cascade.
Here's a company using an antibody to target upstream of Factor XI:
http://aronorabio.com/site/inhibition-of-factor-xii-mediated-activation-of-factor-xi-provides-protection-against-experimental-acute-ischemic-stroke-in-mice/
Aronora LLC had a monoclonal antibody called Aximab that targeted FXI directly. Aronora reported findings about its possible use in treating sepsis. Apparently Aximab is no longer in development.
Hob
Phase II Study of ISIS FXI Rx in Total Knee Arthroplasty
"To propel a stock price that's abruptly fallen,
Isis tests its anticoagulant in the Lands of Stalin
(and Canada)."
http://clinicaltrials.gov/ct2/show/NCT01713361
Cancer stem cell definitions and terminology: the devil is in the details
http://www.nature.com/nrc/journal/v12/n11/abs/nrc3368.html?lang=en?WT.ec_id=NRC-201211
>> Perspectives
Nature Reviews Cancer 12, 767-775 (November 2012) | doi:10.1038/nrc3368
OPINION:
Cancer stem cell definitions and terminology: the devil is in the details
Peter Valent1, Dominique Bonnet2, Ruggero De Maria3, Tsvee Lapidot4, Mhairi Copland5, Junia V. Melo6, Christine Chomienne7, Fumihiko Ishikawa8, Jan Jacob Schuringa9, Giorgio Stassi10, Brian Huntly11, Harald Herrmann1, Jean Soulier12, Alexander Roesch13, Gerrit Jan Schuurhuis14, Stefan Wöhrer15, Michel Arock16, Johannes Zuber17, Sabine Cerny-Reiterer1, Hans E. Johnsen18, Michael Andreeff19 & Connie Eaves20 About the authors
Abstract
The cancer stem cell (CSC) concept has important therapeutic implications, but its investigation has been hampered both by a lack of consistency in the terms used for these cells and by how they are defined. Evidence of their heterogeneous origins, frequencies and their genomic, as well as their phenotypic and functional, properties has added to the confusion and has fuelled new ideas and controversies. Participants in The Year 2011 Working Conference on CSCs met to review these issues and to propose a conceptual and practical framework for CSC terminology. More precise reporting of the parameters that are used to identify CSCs and to attribute responses to them is also recommended as key to accelerating an understanding of their biology and developing more effective methods for their eradication in patients.<<
STAT3 inhibition has been reported to target CSCs:
http://www.sciencedaily.com/releases/2009/08/090810104925.htm
Star-crossed Isis Pharmaceuticals is testing an antisense inhibitor of Stat3.
Hob
Teva has experience with Isis antisense
Teva is evaluating ATL/TV 1102 for development in MS and other indications.
http://www.antisense.com.au/!upload_files/attachment/AGM%202009%20presentation_final(1).pdf
>ATL/TV1102 for Multiple Sclerosis
Product
• 2nd generation antisense inhibitor of VLA-4 protein
• VLA-4 is a clinically validated target in MS
• MS drug Tysabri®on market‚ monoclonal antibody (mAb) to VLA-4; Most effective MS drug to date for treatment of relapsing-remitting MS
• Antisense inhibition of VLA-4 has demonstrated positive effects in work undertaken to date
• Positive animal data in MS animal studies comparable to VLA-4 mAb
• Data published in peer reviewed scientific journal
• Phase I study confirmed ATL1102 to be safe and well tolerated
• Successful Phase IIa trial confirming drug activity and safety in MS patients Successful Phase IIa trial confirming drug activity and safety in MS patients
• Patents granted in US, Europe, Australia and Japan; pending in Canada
• Teva are currently undertaking chronic toxicology studies which are expected
to be completed by the end of 2009<
Isis Gets $10 Million
http://www.prnewswire.com/news-releases/isis-pharmaceuticals-to-receive-10-million-from-oncogenex-license-of-ogx-011-to-teva-79793227.html
>> Isis Pharmaceuticals to Receive $10 Million From OncoGenex' License of OGX-011 to Teva
OGX-011 Phase 3 Studies in First- and Second-Line Advanced Prostate Cancer and Non-Small Cell Lung Cancer Expected to Begin in 2010 and Early 2011
CARLSBAD, Calif., Dec. 21 /PRNewswire-FirstCall/ -- Isis Pharmaceuticals, Inc. (Nasdaq: ISIS) today announced that it will receive a $10 million payment from OncoGenex Pharmaceuticals, Inc. (Nasdaq: OGXI) as a result of OncoGenex' license of OGX-011 to Teva Pharmaceutical Industries Ltd. ( TEVA). OGX-011 is a second-generation antisense drug co-discovered by Isis and OncoGenex that has completed a successful Phase 2 program in patients with advanced prostate cancer and advanced non-small cell lung cancer. Teva and OncoGenex will collaborate on a global Phase 3 clinical program for OGX-011 in patients with prostate and non-small cell lung cancer.
"We are pleased with OncoGenex' selection of Teva Pharmaceuticals, a leading pharmaceutical company, as a partner to complete the development and commercialization of OGX-011. OGX-011 will be the second antisense drug to enter Phase 3 development from our second-generation antisense technology. We are encouraged by the Phase 2 results of OGX-011 presented earlier this year in patients with advanced prostate cancer and look forward to the drug progressing into a broad Phase 3 program," said B. Lynne Parshall, COO and CFO of Isis Pharmaceuticals. "2009 has been an eventful year for Isis' satellite companies, continuing to affirm our strategy of maximizing the value of our antisense drug discovery platform with both traditional and unique partnerships. Not only do these relationships provide continuing short-term benefit, but, as drugs move forward in the hands of capable partners, they promise significant benefit to patients and more significant financial rewards to Isis in the future."
Under the terms of OncoGenex' agreements with Teva, Isis will receive $10 million of the upfront monies paid. This constitutes 30% of the $20 million license fee and 30% of the premium on Teva's equity investment in OncoGenex as well as a portion of the $30 million prepaid development costs that OncoGenex will subsequently contribute to the development of OGX-011. Isis will also receive 30% of the up to $370 million in milestone payments OncoGenex is eligible to receive in addition to 5.5 - 7% royalties on all sales of OGX-011.
ABOUT ISIS PHARMACEUTICALS, INC.
Isis is exploiting its expertise in RNA to discover and develop novel drugs for its product pipeline and for its partners. The Company has successfully commercialized the world's first antisense drug and has 21 drugs in development. Isis' drug development programs are focused on treating cardiovascular, metabolic and severe neurodegenerative diseases and cancer. Isis' partners are developing antisense drugs invented by Isis to treat a wide variety of diseases. Isis and Alnylam Pharmaceuticals are joint owners of Regulus Therapeutics Inc., a company focused on the discovery, development and commercialization of microRNA therapeutics. Isis also has made significant innovations beyond human therapeutics resulting in products that other companies, including Abbott, are commercializing. As an innovator in RNA-based drug discovery and development, Isis is the owner or exclusive licensee of over 1,600 issued patents worldwide. Additional information about Isis is available at www.isispharm.com. <<
Harlan Resurfaces
http://biz.yahoo.com/prnews/090218/ny71900.html?.v=1
>> Senesco Technologies Reports Second Quarter Fiscal 2009 Financial Results
Wednesday February 18, 8:00 am ET
NEW BRUNSWICK, N.J., Feb. 18 /PRNewswire-FirstCall/ -- Senesco Technologies, Inc. ("Senesco" or the "Company") (NYSE Alternext US: SNT) today reported financial results for the three months ended December 31, 2008.
Net loss for the three month period ended December 31, 2008 was $1,624,341, or $0.09 per share, compared with a net loss of $1,049,838 or $0.06 per share, for the three month period ended December 31, 2007. This increase in net loss was primarily the result of an increase in non-cash expenses associated with the outstanding convertible notes that were issued during the year ended June 30, 2008, and an increase in operating expenses.
Quarterly and Recent Highlights
Senesco announced results of maximum tolerated dose, preclinical toxicology, and efficacy / dose-range finding studies in mice for SNS-01, the Company's multiple myeloma drug candidate.
Senesco's data was presented at the 2008 Annual Meeting of the American Society of Hematology in a presentation entitled "Preclinical Studies Using Polyethylenimine (PEI) Nanoparticles Complexed with Eukaryotic Translation Initiation Factor 5A (eIF5A) siRNA and eIF5A Plasmid DNA Demonstrates Significant Anti-Myeloma Activity in Vitro and in Vivo".
Senesco's preclinical multiple myeloma data was presented at the 20th EORTC-NCI-AACR Symposium on "Molecular Targets and Cancer Therapeutics".
Senesco appointed Harlan W. Waksal, M.D., co-founder of ImClone Systems Incorporated, to the Company's Board of Directors. Dr. Waksal was instrumental in moving forward the clinical development program for ERBITUX® (cetuximab), an oncology drug now approved in colorectal and head & neck cancers.
Management delivered the Company's corporate presentation at the 10th Annual Rodman & Renshaw Healthcare Conference, and the 11th Annual BIO CEO & Investor Conference.
"We remain focused on our goal of filing an Investigational New Drug Application for SNS-01 before the end of calendar year 2009," said Bruce Galton, President and CEO of Senesco. "The recently announced results of the maximum tolerated dose, preclinical toxicology, and efficacy / dose range finding studies for SNS-01 was an important step toward accomplishing this goal."
The Company did not record any revenue for the three month period ended December 31, 2008. Total revenues of $6,250 for the three month period ended December 31, 2007 consisted of the amortized portion of previous milestone payments received in connection with certain agricultural license agreements.
Research and development expenses during the three month period ended December 31, 2008 were $579,286, compared with $392,254 during the three month period ended December 31, 2007, an increase of 47.7%. This increase was primarily a result of an expansion of Senesco's human health programs, specifically the Company's multiple myeloma research program, which was partially offset by a decrease in agricultural research expenses as a result of a decrease in the allocation of resources from agriculture to human health at the University of Waterloo.
General and administrative expenses were $649,056 for the three month period ended December 31, 2008, compared with $585,851 during the three month period ended December 31, 2007, an increase of 10.8%. This increase was primarily due to a $64,000 increase in stock based compensation, an approximately $21,000 increase in professional fees, which were the result of an increase in legal fees, and an approximately $16,000 increase in director fees, which were due to the Company implementing a cash compensation plan for non-employee directors beginning July 1, 2008.
At December 31, 2008, Senesco had cash, cash equivalents and investments of $3,615,788, and working capital of $3,562,743, which the Company estimates will fund its operations for approximately the next seven months, as of December 31, 2008.
About Senesco Technologies, Inc.
Senesco Technologies, Inc. is a U.S. biotechnology company, headquartered in New Brunswick, NJ. Senesco has initiated preclinical research to trigger or delay cell death in mammals (apoptosis) to determine if the technology is applicable in human medicine. Accelerating apoptosis may have applications to development of cancer treatments. Delaying apoptosis may have applications to certain diseases such as glaucoma, ischemia and arthritis, among others. Senesco takes its name from the scientific term for the aging of plant cells: senescence. Delaying cell breakdown in plants extends freshness after harvesting, while increasing crop yields, plant size and resistance to environmental stress. The Company believes that its technology can be used to develop superior strains of crops without any modification other than delaying natural plant senescence. [Will this technology translate to the field of human cosmetics?] Senesco has partnered with leading-edge companies engaged in agricultural biotechnology and earns research and development fees for applying its gene-regulating platform technology to enhance its partners' products. <<
Aldehyde Tags Customize Proteins
http://genengnews.com/news/bnitem.aspx?name=49366422
>> Tailor-made recombinant proteins in mammals
Contact: Paul Preuss
paul_preuss@lbl.gov
510-486-6249
DOE/Lawrence Berkeley National Laboratory
Aldehyde tags put chemical modifications where theyre needed
BERKELEY, CA A new way to direct chemical modifications to specific sites on recombinant proteins including the monoclonal antibodies so important in the pharmaceutical industry has been developed by Carolyn Bertozzi and her colleagues at the U.S. Department of Energy's Lawrence Berkeley National Laboratory and the University of California at Berkeley.
Many therapeutic proteins, including insulin for diabetes, can be made in bacterial systems like Escherichia coli, but most protein pharmaceuticals must be expressed in cultured mammalian cells. The researchers have now found a way to extend the use of "aldehyde tags," which they previous developed for recombinant proteins expressed in bacteria, to label proteins that can only be expressed by mammalian systems.
"Proteins made with recombinant DNA are a major weapon in the armory against disease," says Bertozzi, who is a member of Berkeley Lab's Materials Sciences and Physical Biosciences Divisions and director of the Molecular Foundry, a Department of Energy (DOE) nanoscience user research facility. "But protein therapeutics are far from perfect. Many have short half-lives, so the patient must inject them repeatedly. And it is often difficult to introduce novel features into a recombinant protein."
While a specific chemical change can extend a protein's lifetime or turn it into a target for diagnostic imaging, for example, or convert an antibody into a drug that seeks out and attacks cancer cells, directing a chemical modification to the right place in the protein can be a challenge.
"Some protein modification methods have been around for a long time; typically they make use of the amino acid residue lysine. But there are lots of kinds of proteins in a cell, and any of them may include dozens or even hundreds of lysines, so it's hard to modify just one and not all of them," says Bertozzi, who is also a professor in the Departments of Chemistry and Molecular and Cell Biology and a Howard Hughes Medical Institute Investigator at UC Berkeley.
Says Bertozzi, "Ways to get around nonspecificity have been found in the laboratory, but these lab methods usually aren't very practical for drug manufacture because they can't be generalized or scaled up."
Enter Bertozzi's aldehyde tag: the tag is an aldehyde group displayed as part of an amino acid side chain with chemical reactivity completely unlike the 20 standard amino acids that normally make up a protein. When the aldehyde tag appears at a specific site on a given protein, a chemical equipped to react with an aldehyde group which is not an ordinary event, but instead is what Bertozzi calls "orthogonal to nature" will target that location and none other.
"To do this we actually borrowed a machinery from nature, which is out there in pretty much all organisms and was just waiting for us to take advantage of," Bertozzi says. "It's called the formylglycine generating enzyme, or FGE, and it resides in the endoplasmic reticulum, a part of the eukaryotic cell that participates in protein secretion."
In nature, FGE is part of the cell's machinery for regulating the catalytic functions of enzymes called sulfatases. FGE does this by converting a cysteine residue, one in a sequence of six core amino acids in a particular sulfatase, into the nonstandard amino acid residue formylglycine. "Formyl" is another name for a simple aldehyde group.
"So all we had to do was clone the nucleotides encoding those six residues from the sulfatase sequence into the DNA of the target protein we want to produce, at the site corresponding to where we wanted the chemical modification to occur." Bertozzi calls that six-residue sequence the aldehyde tag. "You just sit back and allow the cell to express the protein. When it does, the FGE system is already in place to convert the cysteine to formylglycine" the nonstandard amino acid bears the aldehyde.
Having developed this technique for pinpointing chemical reactions to sites on recombinant proteins from E. coli, Bertozzi and her colleagues showed that it works equally well in the most common mammalian system, CHO cells (Chinese hamster ovary cells), as well as in the HEK cell system (human embryonic kidney cells).
"You can put anything you want on the tagged protein," she says, "You attach small molecule drugs, or polymers that change the pharmacokinetics such as polyethylene glycol polymers, or another protein molecule, or anything you're interested in attaching to a protein."
Because of their obvious therapeutic importance, the researchers used antibodies in their first tests. Immunoglobulin G (IgG) is the most widely used, clinically important type of antibody. For example, it can be rendered anti-inflammatory by chemically modifying part of its structure known as the Fc fragment. Conventionally this is done by targeting lysines, but there are many of these, and some lie near sites that, if modified, would cripple the antibody instead of making it therapeutic.
Bertozzi's group proved they could precisely tag the Fc fragment of the IgG molecule so that it would selectively bind with chemicals engineered to react with the aldehyde. The Fc fragments were the only proteins in the mix with which the experimental labels reacted.
"From the biotech perspective, secreted antibody-like proteins like these are the most interesting," Bertozzi says, "but the aldehyde tag technique is versatile and easy to apply, with a wide range of applications in the biotech industry." Her team showed that aldehyde tags could successfully label mammalian membrane-associated proteins and proteins occurring in the intracellular fluid as well.
"What's so appealing about the method is that it's really simple," Bertozzi says. She's sufficiently confident of the value of the aldehyde tag method for pharmaceutical manufacture to have licensed the technology through the University of California and, with former graduate student David Rabuka, cofounded a startup named Redwood Biosciences. "You don't need any high-tech genetic engineering or any fancy chemistry it's really as simple as cloning a little six-residue tag into the gene of your target protein. That's why we call it 'low-tech, high-concept.'" <<
Superior Trader Indicator
http://news.yahoo.com/s/ap/20090113/ap_on_sc/sci_financial_finger
>> Finger length may predict financial success
By RANDOLPH E. SCHMID, AP Science Writer – 7 mins ago
WASHINGTON – The length of a man's ring finger may predict his success as a financial trader. Researchers at the University of Cambridge in England report that men with longer ring fingers, compared to their index fingers, tended to be more successful in the frantic high-frequency trading in the London financial district.
Indeed, the impact of biology on success was about equal to years of experience at the job, the team led by physiologist John M. Coates reports in Monday's edition of Proceedings of the National Academy of Sciences.
The same ring-to-index finger ratio has previously been associated with success in competitive sports such as soccer and basketball, the researchers noted.
The length ratio between those two fingers is determined during the development of the fetus and the relatively longer ring finger indicates greater exposure to the male hormone androgen, the researchers noted.
Previous studies have found that such exposure can lead to increased confidence, risk preferences, search persistence, heightened vigilance and quickened reaction times.
In a separate study last year, Coates and colleagues reported that the hormone that drives male aggression and sexual interest also seemed able to boost short term success at finance.
They studied male financial traders in London, taking saliva samples in the morning and evening. They found that those with higher levels of testosterone in the morning were more likely to make an unusually big profit that day. Testosterone, best known as the male sex hormone, affects aggression, confidence and risk-taking.
In the new study, the researchers measured the right hands of 44 male stock traders who were engaged in a type of trade that involved rapid decision-making and quick physical reactions.
Over 20 months those with longer ring fingers compared to their index fingers made 11 times more money than those with the shortest ring fingers. Over the same time the most experienced traders made about 9 times more than the least experienced ones.
Looking only at experienced traders, the long-ring-finger folks earned 5 times more than those with short ring fingers.
While the finger ratio, showing fetal exposure to male hormones, appears to signal likely success in high-actively trading that calls for risk-taking and quick reactions, it may not indicate people who would do well at other sorts of financial activities, the researchers said.
Some traders require additional skills on dealing with clients and sales workers.
And the advantage may even reverse for some, Coates team said, such as traders taking a more analytical and long-term approach to the markets.
One study, which looked at average finger ratios in university departments found that faculty from math, science and engineering exhibited longer index finger ratio, rather than ring finger, they noted. <<
Re: New small-cap Survey
You've not included the once and future winner:
http://finance.google.com/finance?q=AMEX:ADH
>> Adherex Technologies Inc. (USA) (Public, AMEX:ADH) - Add to Portfolio
26.27
+26.24 (75,172.21%)
Jan 10 - Close <<
Prozac and Cancer
http://www.aftau.org/site/News2?page=NewsArticle&id=8323
>> Not Just for Depression Anymore
Thursday, December 18, 2008
TAU research shows Prozac can fight cancer drug resistance
Dr. Dan Peer
Prozac is regularly prescribed to ease the emotional pain of patients who are being treated for cancer. But can this common anti-depressant help to fight cancer itself?
Dr. Dan Peer of the Department of Cell Research and Immunology at Tel Aviv University is proving that it can. A study he and his colleagues recently completed validates that Prozac (chemical name fluoxetine) dramatically enhances the effectiveness of a widely used anti-cancer drug.
“The good news is that the medical community won't have to wait — Prozac can be used for this purpose right away,” says Dr. Peer, noting that doctors in the U.S. already prescribe it to treat depression in chemotherapy patients.
Fighting Drug Resistance in Colon Cancer Patients
“Prozac is a very interesting non-specific blocker of cancer resistance,” says Dr. Peer, whose study focused on colon cancer and the anti-cancer drug doxorubicin.
In their laboratory experiments, the Tel Aviv University scientists led by graduate student Mirit Argov together with Prof. Rimona Margalit, found that Prozac enhanced doxorubicin's efficacy more than 1,000%. Prozac, in effect, worked to block the cancer drug from leaving the interior of the cancer cell and poisoning the healthy non-cancerous cells that surrounded it.
In animal models, a mild doxorubicin-fluoxetine treatment combination slowed down tumor progression significantly. These results suggest that pairing Prozac with chemotherapeutic drugs to curb drug resistance warrants further clinical study, says Dr. Peer.
His research was just published in Cancer Letters, and his suggestions are now listed as recommendations in the latest version of Cancer Encyclopedia.
Working Backward to Make Great Advances
“Working with a major drug developer, we have validated Prozac's potential, and now Tel Aviv University can lead a humanitarian effort to save lives around the globe,” he says.
Since it is very hard to protect this patent because any clinician can prescribe Prozac, it is impossible for Tel Aviv University to commercialize its research, says Dr. Peer. Instead, he suggests that researchers join forces internationally to implement retrospective studies of all the types of cancer treatment in which Prozac was prescribed. And further clinical experiments to validate the use of Prozac with chemotherapy is also needed, he stresses.
“The next step is to take the files of chemo patients and determine whether they received Prozac for their depression,” says Dr. Peer. “This will streamline the understanding in the scientific community of whether, how and for which cancer-fighting drugs Prozac can be an effective partner. It will also give us invaluable information on how to design new drugs."
Dr. Peer's Tel Aviv University lab is also developing several new drug delivery nanotechnologies to bring novel therapeutics into breast, blood, pancreatic and brain cancers. A recent technological breakthrough to reprogram immune cells involved in ulcerative colitis and Crohn’s disease was reported in Science earlier this year and it is the basis of a new platform technology developed in his group. <<
Abbot Buys Isis Subsidiary (Ibis Biosciences, Inc.)
[Isis developed the T5000 Biosensor System with government money and various government agencies were its first customers. The 2001 "anthrax mailings" case was rumored to have been solved using the biosensor.
( http://pubs.acs.org/cen/news/86/i32/8632notw8.html ) ]
http://ir.isispharm.com/releasedetail.cfm?ReleaseID=354715
>> Abbott Exercises Its Option to Acquire Ibis Biosciences, a Subsidiary of Isis
CARLSBAD, Calif. and ABBOTT PARK, Ill., Dec 17, 2008 /PRNewswire-FirstCall via COMTEX News Network/ --
Total acquisition price will be $215 million
Acquisition will expand Abbott's position in molecular diagnostics for infectious disease
Isis Pharmaceuticals, Inc. (Nasdaq: ISIS) and Abbott (NYSE: ABT) announced today that Abbott has exercised its option to purchase the remaining equity ownership in Ibis Biosciences, Inc., an Isis subsidiary, for a closing purchase price of $175 million. In addition to the closing purchase price, Isis will receive earn out payments from Abbott tied to post-closing sales of Ibis systems, including instruments and assay kits.
Earlier this year, Abbott invested $40 million in Ibis in exchange for approximately 18.6% of Ibis' outstanding equity. This investment, along with the $175 million that would be due at closing, would result in a total acquisition price of $215 million plus earn out payments.
The closing of the acquisition of the remaining equity ownership in Ibis is subject to the satisfaction of the terms and conditions of a stock purchase agreement that has been executed by the parties, including obtaining clearance under the Hart-Scott-Rodino Antitrust Improvements Act of 1976, and is expected to occur in January, 2009.
"Abbott's confidence in Ibis is reflected in its decision to invest in Ibis' technology and to exercise its option to purchase Ibis. We have already presented development plans for the next-generation instrument that will facilitate our rapid growth into clinical diagnostics," said Michael Treble, President of Ibis. "This year we have made substantial progress by advancing our broad pathogen detection and characterization capabilities and establishing a foundation for our commercial clinical diagnostic products. We look forward to continuing this progress."
"The broad applicability of Ibis' technology has been demonstrated in biodefense applications, microbial forensics and infectious disease detection and surveillance, and we believe that it has the potential to be a powerful tool in the detection and surveillance of infectious diseases in the hospital and clinical settings," added Stafford O'Kelly, Vice President, Molecular Diagnostics, Abbott.
"Ibis is an example of Isis' broad innovation, and will provide substantial benefit to our shareholders, both now as well as in the future, as Isis receives earn out payments associated with sales of Ibis products," said Stanley Crooke, M.D., Ph.D., Chairman and CEO of Isis. "Ibis has refined its approach toward larger commercial markets, and we believe its relationship with Abbott will allow Ibis to continue to move quickly forward along this path."
About Ibis T5000 Biosensor System and Ibis Biosciences, Inc.
Ibis Biosciences, Inc., a majority-owned subsidiary of Isis Pharmaceuticals, has developed and is commercializing the Ibis T5000(TM) Biosensor System for rapid identification and characterization of infectious agents. The Ibis T5000 is currently intended for research use only and not for use in diagnostic procedures. It is capable of identifying virtually all bacteria, viruses and fungi, and can provide information about drug resistance, virulence and strain type of these pathogens. Commercial applications for the Ibis T5000 Biosensor System include epidemiologic surveillance, monitoring of pandemic diseases, identification of emerging or previously unknown pathogens, forensic characterization of human samples, identification of sources of hospital-associated infections, and, in the future, human infectious disease diagnostics. Ibis develops, manufactures and markets Ibis T5000 instruments and assay kits. Additional information about Ibis can be found by selecting the Ibis link from Isis' homepage at www.isispharm.com.
About Abbott Molecular
Abbott's molecular diagnostics business, headquartered in Des Plaines, Ill., provides physicians with critical information based on the early detection of pathogens and key changes in patients' genes and chromosomes, allowing for earlier diagnosis, selection of appropriate therapies and monitoring of disease progression. The business includes instruments and reagents used to conduct sophisticated analysis of patient DNA and RNA.
About Abbott
Abbott is a global, broad-based health care company devoted to the discovery, development, manufacture and marketing of pharmaceuticals and medical products, including nutritionals, devices and diagnostics. The company employs more than 68,000 people and markets its products in more than 130 countries.
Abbott's news releases and other information are available on the company's Web site at www.abbott.com.
About Isis Pharmaceuticals, Inc.
Isis is exploiting its expertise in RNA to discover and develop novel drugs for its product pipeline and for its partners. The Company has successfully commercialized the world's first antisense drug and has 19 drugs in development. Isis' drug development programs are focused on treating cardiovascular and metabolic diseases. Isis' partners are developing antisense drugs invented by Isis to treat a wide variety of diseases. Isis is a joint owner of Regulus Therapeutics LLC, a joint venture focused on the discovery, development and commercialization of microRNA therapeutics. As an innovator in RNA-based drug discovery and development, Isis is the owner or exclusive licensee of over 1,500 issued patents worldwide. Additional information about Isis is available at www.isispharm.com. <<
Rand Corp. Examines Trade-Offs of Drug Price Controls
[If I understand correctly, $40,000-$60,000 is the value of an additional year of life expectancy, but this ignores the time value of money.]
http://www.reuters.com/article/healthNews/idUSTRE4BF0WX20081216
>> Drug price controls may shorten lives:
Tue Dec 16, 2008 12:40am EST By Julie Steenhuysen
CHICAGO (Reuters) - Imposing European-style price controls on prescription drugs in the United States would result in modest cost savings that would be more than offset by shortened life spans as the pace of drug innovation slows, U.S. researchers said on Tuesday.
They said lowering insurance co-payments would be a better way of attacking the problem of rising prescription drug prices in the United States, which pays more per capita for pharmaceuticals than any other nation.
"We found policies that regulate the prices of drugs could result in modest savings for consumers, in the best cases on the order of $5,000 to $10,000 per person over a lifetime," said Darius Lakdawalla of the nonprofit Rand Corporation, who worked on two studies appearing in a special report on drug pricing in the journal Health Affairs.
"But in many other cases, those policies resulted in very substantial losses to consumers in the form of reduced life expectancy and those would be worth tens of thousands of dollars," Lakdawalla said in a telephone interview.
Some policymakers have suggested the United States adopt some form of price regulation as a way to curb rising prescription drug costs. Most European countries regulate drug costs, which is one reason European nations spend less than two-thirds as much per person on drugs each year than the United States.
Lakdawalla and colleagues used computer models of price regulation in 19 countries to simulate the impact of price controls that cut drug company revenues by 20 percent.
They said introducing price regulations into a largely unregulated market like the United States would result in less investment in developing life-saving drugs, which in the long run would reduce the life expectancy of Americans.
"We found longevity declines on the order of about a half of year for people at the age of 55 when you look out to people who are alive in 2050 and 2060," he said.
Lakdawalla said a better approach would be to cut drug insurance co-payments by 20 percent, which would increase life expectancy in the United States by a half year by 2060 as more people take needed drugs and higher drug profits stimulate innovation.
"In the best cases it would lead to a benefit on the order of $20,000 to $30,000 per person," Lakdawalla said.
All five papers in the section were funded by a grant from the pharmaceutical company Pfizer Inc. Lakdawalla also got funding from the National Institute on Aging.
F.M. Scherer of Harvard questioned some of the assumptions made by Lakdawalla in a commentary in the journal, including the assumptions about the rate at which lost drug company profits would translate into less innovation.
A team of researchers that included Harvard economist David Cutler, a health policy adviser for President-elect Barack Obama, suggested in the same journal that drug prices had reached a "turning point."
They noted that while drug prices tripled from 1997 through 2007, spending in 2007 grew just 1.6 percent, the slowest rate since 1974, as many brand-name drugs lose patent protection.
Cutler and colleagues noted that prescription drug spending trends have changed dramatically in the past five years, and assumptions based on older trends no longer apply. <<
Ovation Raises Its Standing
http://www.businesswire.com/portal/site/biospace/index.jsp?ndmViewId=news_view&newsId=20081212005083&newsLang=en
>> OVATION Pharmaceuticals Donates More than $2.8 Million in 2008 Global Humanitarian Programs
Product Reaches Severely Ill Patients in Tajikistan, Africa and Guatemala
DEERFIELD, Ill.--(BUSINESS WIRE)--In a continued effort to address the unmet medical needs of people suffering from severe illnesses, OVATION Pharmaceuticals donated more than $2.8 million in specialty medications to global humanitarian missions serving developing nations and countries in crisis. Product donations were distributed in Tajikistan, Africa and Guatemala through two international humanitarian assistance organizations – AmeriCares and Project HOPE.
“As a pharmaceutical company focused on treatments where there is significant unmet medical need, we believe making a positive impact on the health of underserved global communities is an important goal,” said Jeffrey S. Aronin, President and Chief Executive Officer of OVATION. “Enabling patients to have access to potentially life saving medications they need, even in countries where treatment options are limited, is part of our higher purpose as a company.”
AmeriCares, an international relief organization, arranged for a U.S.-based pediatric heart surgery team to travel to Guatemala to provide charitable medical care. OVATION supported the “Guatemala Heart Mission” by donating vials of medication to treat infants with patent ductus arteriosus, a congenital heart defect where a blood vessel (ductus arteriosus) in the heart fails to close after birth.
The majority of the company’s product donations were distributed through Project HOPE, a not-for-profit international health education and humanitarian assistance organization. OVATION’s partnership with Project HOPE helped deliver needed medications to hospitals and clinics in Dushanbe, Tajikistan, as well as to the Congo and Lesotho, Africa, through the Ministry of Health and Social Services and the Sentebale Trust, founded by Prince Harry of the British Royal Family and Prince Seeioso of the Lesotho Royal Family.
The Sentebale Trust and the Minister of Health work together to improve the lives of Basotho children. OVATION’s donation helped treat children with rare cancers.
“The medicines donated by OVATION allowed Project HOPE to reach a group of patients with hard-to-treat illnesses who otherwise may not have access to treatment.” said Pat Bacuros, Director, In-Kind Giving, Project HOPE.
About OVATION Pharmaceuticals
OVATION is a fast-growing biopharmaceutical company that develops, manufactures and markets medically necessary therapies to satisfy unmet medical needs for patients with severe illnesses. Headquartered in Deerfield, Ill., with products available in more than 85 countries, OVATION is committed to having a significant impact on patients' lives through its focus on CNS, hematology/oncology, and hospital-based therapies. The three new launches the company expects over the next three years will be fueled largely by its late-stage CNS pipeline, which is one of the most robust in the industry. OVATION has been recognized for excellence in the global pharmaceutical and biotechnology industries with the 2006 and 2007 "Pharma Company of the Year" award from Scrip magazine for small to mid-sized enterprises. More information about the company, its products and full prescribing information may be found at http://www.ovationpharma.com/ <<
Re: LLY
[I was so ensorcelled by the spelling error in the 2nd paragraph of this article that I failed to post it in its entirety. Readers would have missed LLY's plan to jump into bio-similars.]
http://www.forbes.com/markets/2008/12/11/lilly-byetta-updates-markets-equity-cx_lal_1211markets27.html?partner=relatedstoriesbox
>>Lilly Blossoms
Lisa LaMotta, 12.11.08, 02:40 PM EST
The drugmaker beats expectations on guidance due to a good handle on the forex market.
Eli Lilly is like a rare flower flourishing during a drought. The company seems well-prepared for the recessionary climate and the upcoming patent expirations as its competitors continue to whither, [sic] largely due to its ability to gauge the currency markets.
On Thursday, Eli Lilly (nyse: LLY - news - people ) held its annual investors meeting where it forecast guidance for 2009 that was above Wall Street's consensus estimate of $4.26, excluding special items. On that basis, Lilly now expects to earn $4.35 to $4.55 per share. The special item, of course, is the dilution shareholders will experience due to the acquisition of Carl Icahn'sImClone (nasdaq: IMCL - news - people ), approximately 30 cents to 35 cents per share.
Yet Lilly looks stronger in the long run due to the ImClone acquisition, which strengthens the company's cancer-drug pipeline. Lilly said at its investors meeting that 40.0% of its pipeline is now biotech-based.
The company was better prepared than most competitors to weather foreign exchange expense, despite almost 50.0% of its revenues coming from overseas. "The biggest thing they demonstrated is that they have developed a good strategy to hedge against currency," Leerink Swann analyst Seamus Fernandez said to Reuters. "There's virtually no impact from forex." Meanwhile, Merck surprised analysts and investors last week with a higher-than-expected impact from foreign currency.
Shares of Lilly jumped 4.1%, or $1.41, to trade at $36.41, on Thursday afternoon.
"The pharmaceutical industry, however, continues to face major challenges, and we must act quickly and decisively to address them," said John C. Lechleiter, Lilly's chief executive. "We must respond to the demand for greater value among payers, providers and patients. We must also prepare for the wave of patent expirations that will come in the early part of the next decade."
Lilly affirmed its earnings guidance for 2008, saying it expects to earn $3.97 to $4.02 per share, excluding the ImClone acquisition, which will bring the company to a loss of $1.56 to $2.06 per share for the year.
The company is trying to reduce research and development costs for bringing new drugs to market from the $1.2 billion it spent in 2007 to just $800.0 million by 2010. The company said it had reduced costs enough that it now brings a new drug to market for about $1.0 billion.
We are fundamentally transforming our business, and are doing so from a position of strength," Lechleiter added.
Following in competitor Merck's footsteps, Lilly told investors that it would eventually jump into the realm of biogenerics, a class of drugs that is expensive to make, but has a high return on investment. These drugs would likely not be considered generic versions of existing drugs, but bio-similars due to the amount of research and slight variations that would go into them.
Lilly announced, in conjunction with its partners Amylin Pharmaceuticals (nasdaq: AMLN - news - people ) and Alkermes (nasdaq: ALKS - news - people ), that it was still in talks with the U.S. Food and Drug Administration about once-weekly Byetta, an injectible diabetes treatment. The daily-use Byetta came under fire earlier this year when it became associated with pancreatitis, a condition that is common in diabetes patients. The companies said Byetta LAR was on track to be submitted to the FDA for approval in the first half of 2009. Robert W. Baird analyst Thomas Russo called Byetta LAR "the most eagerly awaited product in diabetes." Shares of Amylin shot up 21.1%, or $1.80, to $10.36, on the news.
Lilly also announced that it has been in talks with regulators about prasugrel, a blood clot-prevention treatment that is partnered with Daiichi Sanko. The drug has been delayed by the FDA twice so far. <<
LLY's Competitors: Directionless?
http://www.forbes.com/markets/2008/12/11/lilly-byetta-updates-markets-equity-cx_lal_1211markets27.html?partner=relatedstoriesbox
>>Lilly Blossoms
Lisa LaMotta, 12.11.08, 02:40 PM EST
The drugmaker beats expectations on guidance due to a good handle on the forex market.
Eli Lilly is like a rare flower flourishing during a drought. The company seems well-prepared for the recessionary climate and the upcoming patent expirations as its competitors continue to whither, [sic] largely due to its ability to gauge the currency markets.
On Thursday, Eli Lilly (nyse: LLY - news - people ) held its annual investors meeting where it forecast guidance for 2009 that was above Wall Street's consensus estimate of $4.26, excluding special items. On that basis, Lilly now expects to earn $4.35 to $4.55 per share. The special item, of course, is the dilution shareholders will experience due to the acquisition of Carl Icahn'sImClone (nasdaq: IMCL - news - people ), approximately 30 cents to 35 cents per share.
Yet Lilly looks stronger in the long run due to the ImClone acquisition, which strengthens the company's cancer-drug pipeline. Lilly said at its investors meeting that 40.0% of its pipeline is now biotech-based.
The company was better prepared than most competitors to weather foreign exchange expense, despite almost 50.0% of its revenues coming from overseas. "The biggest thing they demonstrated is that they have developed a good strategy to hedge against currency," Leerink Swann analyst Seamus Fernandez said to Reuters. "There's virtually no impact from forex." Meanwhile, Merck surprised analysts and investors last week with a higher-than-expected impact from foreign currency.
Shares of Lilly jumped 4.1%, or $1.41, to trade at $36.41, on Thursday afternoon.
"The pharmaceutical industry, however, continues to face major challenges, and we must act quickly and decisively to address them," said John C. Lechleiter, Lilly's chief executive. "We must respond to the demand for greater value among payers, providers and patients. We must also prepare for the wave of patent expirations that will come in the early part of the next decade."
Lilly affirmed its earnings guidance for 2008, saying it expects to earn $3.97 to $4.02 per share, excluding the ImClone acquisition, which will bring the company to a loss of $1.56 to $2.06 per share for the year. <<
Achaogen: Next Generation Antibacterials
Heretofore flying under the radar working on government projects, Achaogen has revealed its plans on its enhanced website. The company intends to file an IND for an aminoglycoside antibacterial in early 2009:
http://72.167.254.30/pipeline/neoglycosides
>> NEOGLYCOSIDES: OUR NEXT-GENERATION AMINOGLYCOSIDES
Aminoglycosides are a well-known, established and highly effective class of antibacterials, widely used in the treatment of difficult, hospital-based infections. In particular, the class is known for its rapid bactericidal activity against Gram-negative pathogens, as well as for its predictable pharmacokinetic profile, and its excellent stability and solubility, and compounds like gentamicin and amikacin have been widely prescribed in hospitals and critical care settings for decades.
As with other antibacterial agents, however, currently marketed aminoglycoside agents are encountering increasing rates of resistance among common infectious bacteria. As a result, there is a clear need for a new member of this class to supplant generic aminoglycosides and provide an effective therapy for multi-drug resistant (MDR) bacterial infections, including both Gram-negative pathogens (e.g., Klebsiella pneumoniae) and Gram-positive pathogens (e.g., Staphylococcus aureus, or MRSA).
Achaogen’s novel aminoglycoside agents—which we call neoglycosides—overcome all known aminoglycoside resistance mechanisms. Leveraging modern chemistry and biology, as well as the extensive scientific and clinical knowledge gained from decades of aminoglycoside usage, Achaogen is poised to restore this important class of antibacterials to prominence and utility against 21st-century pathogens.
ACHN-490: An antibacterial agent for the 21st Century
Achaogen’s lead compound, ACHN-490, is effective against systemic infections caused by multi-drug resistant (MDR) Gram-negative bacteria (e.g., E. coli and K. pneumoniae) and MRSA. We intend to file an IND with the FDA in early 2009. <<
Achaogen is a private company, but I believe Isis Pharmaceuticals has an interest:
(Isis once investigated targeting bacterial RNA with small molecule drugs: RNA - it's a shape, not just a tape!)
http://ir.isispharm.com/releasedetail.cfm?ReleaseID=220242
>> Isis Pharmaceuticals Licenses Proprietary Antibiotic Program to Achaogen
Jan 31, 2006 /PRNewswire-FirstCall via COMTEX News Network/ -- Isis Pharmaceuticals, Inc. (Nasdaq: ISIS) has announced today that it has licensed its proprietary aminoglycosides program to Achaogen, a biotechnology company pursuing unique strategies to combat drug-resistant pathogens. Aminoglycosides are a group of antibiotics that inhibit bacterial protein synthesis and are used to treat serious bacterial infections. The Isis program that has been licensed to Achaogen resulted from research conducted in Isis' Ibis division to identify drugs to treat antibiotic-resistant infections.
"This licensing agreement will allow us to benefit from Achaogen's expertise and highly focused research efforts in developing therapies against drug-resistant bacteria, while Achaogen will benefit from our aminoglycoside research and access to our intellectual property," said C. Frank Bennett, Ph.D., Senior Vice President, Antisense Research at Isis Pharmaceuticals. "This transaction with Achaogen is another example of our successful satellite company partnering program. Through these relationships, we are expanding the reach and potential of our research programs and participating in the success of multiple companies and products."
In exchange for the exclusive, worldwide license to Isis' aminoglycoside program, Achaogen will issue $1.5 million of Achaogen stock to Isis and make milestone payments for key clinical and regulatory achievements and royalties on product sales. Achaogen will be solely responsible for the continued development of the aminoglycoside program and products. <<
An Achilles heel in cancer cells
[Oxidative stress induction is the rationale behind Synta Pharmaceutical's small-molecule drug elesclomol (partnered with GSK). Elesclomol is in a Phase III trial for metastatic melanoma, an indication that has not been friendly to companies trying to bring a drug to market.]
http://genengnews.com/news/bnitem.aspx?name=46775100
>> Dec 8 2008, 12:27 PM EST
An Achilles heel in cancer cells
Contact: Jeanne Galatzer-Levy
jgala@uic.edu
312-996-1583
University of Illinois at Chicago
A protein that shields tumor cells from cell death and exerts resistance to chemotherapy has an Achilles heel, a vulnerability that can be exploited to target and kill the very tumor cells it usually protects, researchers from the University of Illinois at Chicago show in a new study published in the Dec. 9 issue of Cancer Cell.
Akt is a signaling protein, called a kinase, that is hyperactive in the majority of human cancers.
"Akt is perhaps the most frequently activated oncoprotein (cancer-promoting protein) in human cancer," says Nissim Hay, professor of biochemistry and molecular genetics at the UIC College of Medicine. Pharmaceutical companies have been trying to find ways to inhibit Akt to improve cancer therapy, he said, but most candidate drugs have acted too broadly and proved toxic.
"One of Akt's major functions in tumor cells is promoting cell survival," Hay said. "Tumor cells with hyperactive Akt are not only resistant to the external stresses that can induce cell death but also to chemotherapy."
But Akt is also required for metabolism and the proliferation of cancer cells, and it was as a byproduct of its role in metabolism that the researchers were able to exploit Akt hyperactivity against the tumor cell.
"We found that cells with hyperactive Akt have increased intracellular levels of reactive oxygen species (ROS) and at the same time impaired ability to scavenge ROS," Hay said. These ROS are highly reactive byproducts of metabolism that can damage the cell. Cells usually respond to high levels of ROS by undergoing cell suicide, or apoptosis.
"And, to our surprise, we found that although Akt can protect cancer cells from many of the external signals that would ordinarily induce cell death, including many chemotherapy drugs, it cannot protect from ROS inducers," said Hay.
The researchers found that if they treated cancer cells with chemicals that raise ROS levels, the cells die. Akt could not protect cells from this form of apoptosis and, indeed, because Akt impaired the normal ROS scavenging in the cell, hyperactive Akt actually had the effect of making the cells more vulnerable to these ROS inducers. This enabled selective killing of cancer cells, expressing hyperactive Akt, and not normal cells.
The researchers also devised another strategy to exploit Akt's Achilles heel to successfully target and kill cancer cells.
An FDA-approved chemotherapy drug called rapamycin can be used to arrest cell tumor growth. A drawback of this drug is that it doesn't kill the cells, it just arrests the growth of the tumor. When the drug is removed the tumor may grow again.
"Rapamycin's other drawback is complicated feedback regulation that we turn to our advantage," Hay said. "It turns out rapamycin's target and Akt talk to each other in the cell." If the rapamycin target is hyperactive, Akt is inhibited, and if Akt is active, the rapamycin target is activated.
"So even though cancer cells treated with rapamycin stop dividing, they activate Akt, which makes the cells more resistant to other chemotherapy drugs," said Hay. "But we use that to our advantage. Because overactivation of Akt sensitizes the cells to ROS mediated cell death, if we treat the cells with ROS inducers and rapamycin together we can now kill the cells, not just arrest their growth."
The new study "provides a proof of the principle that Akt's Achilles heel -- a consequence of its role in metabolism -- can be exploited in at least these two ways to selectively target and kill cancer cells," Hay said. <<
Men in Danger: Crisis or Opportunity?
[Strictly from an investment standpoint, this should expand the demand for cosmetic procedures.]
http://www.independent.co.uk/news/science/its-official-men-really-are-the-weaker-sex-1055688.html
>> It's official: Men really are the weaker sex
Evolution is being distorted by pollution, which damages genitals and the ability to father offspring, says new study. Geoffrey Lean reports
Sunday, 7 December 2008
The male gender is in danger, with incalculable consequences for both humans and wildlife, startling scientific research from around the world reveals.
The research – to be detailed tomorrow in the most comprehensive report yet published – shows that a host of common chemicals is feminising males of every class of vertebrate animals, from fish to mammals, including people.
Backed by some of the world's leading scientists, who say that it "waves a red flag" for humanity and shows that evolution itself is being disrupted, the report comes out at a particularly sensitive time for ministers. On Wednesday, Britain will lead opposition to proposed new European controls on pesticides, many of which have been found to have "gender-bending" effects.
It also follows hard on the heels of new American research which shows that baby boys born to women exposed to widespread chemicals in pregnancy are born with smaller penises and feminised genitals.
"This research shows that the basic male tool kit is under threat," says Gwynne Lyons, a former government adviser on the health effects of chemicals, who wrote the report.
Wildlife and people have been exposed to more than 100,000 new chemicals in recent years, and the European Commission has admitted that 99 per cent of them are not adequately regulated. There is not even proper safety information on 85 per cent of them.
Many have been identified as "endocrine disrupters" – or gender-benders – because they interfere with hormones. These include phthalates, used in food wrapping, cosmetics and baby powders among other applications; flame retardants in furniture and electrical goods; PCBs, a now banned group of substances still widespread in food and the environment; and many pesticides.
The report – published by the charity CHEMTrust and drawing on more than 250 scientific studies from around the world – concentrates mainly on wildlife, identifying effects in species ranging from the polar bears of the Arctic to the eland of the South African plains, and from whales in the depths of the oceans to high-flying falcons and eagles.
It concludes: "Males of species from each of the main classes of vertebrate animals (including bony fish, amphibians, reptiles, birds and mammals) have been affected by chemicals in the environment.
"Feminisation of the males of numerous vertebrate species is now a widespread occurrence. All vertebrates have similar sex hormone receptors, which have been conserved in evolution. Therefore, observations in one species may serve to highlight pollution issues of concern for other vertebrates, including humans."
Fish, it says, are particularly affected by pollutants as they are immersed in them when they swim in contaminated water, taking them in not just in their food but through their gills and skin. They were among the first to show widespread gender-bending effects.
Half the male fish in British lowland rivers have been found to be developing eggs in their testes; in some stretches all male roaches have been found to be changing sex in this way. Female hormones – largely from the contraceptive pills which pass unaltered through sewage treatment – are partly responsible, while more than three-quarters of sewage works have been found also to be discharging demasculinising man-made chemicals. Feminising effects have now been discovered in a host of freshwater fish species as far away as Japan and Benin, in Africa, and in sea fish in the North Sea, the Mediterranean, Osaka Bay in Japan and Puget Sound on the US west coast.
Research at the University of Florida earlier this year found that 40 per cent of the male cane toads – a species so indestructible that it has become a plague in Australia – had become hermaphrodites in a heavily farmed part of the state, with another 20 per cent undergoing lesser feminisation. A similar link between farming and sex changes in northern leopard frogs has been revealed by Canadian research, adding to suspicions that pesticides may be to blame.
Male alligators exposed to pesticides in Florida have suffered from lower testosterone and higher oestrogen levels, abnormal testes, smaller penises and reproductive failures. Male snapping turtles have been found with female characteristics in the same state and around the Great Lakes, where wildlife has been found to be contaminated with more than 400 different chemicals. Male herring gulls and peregrine falcons have produced the female protein used to make egg yolks, while bald eagles have had difficulty reproducing in areas highly contaminated with chemicals.
Scientists at Cardiff University have found that the brains of male starlings who ate worms contaminated by female hormones at a sewage works in south-west England were subtly changed so that they sang at greater length and with increased virtuosity.
Even more ominously for humanity, mammals have also been found to be widely affected.
Two-thirds of male Sitka black-tailed deer in Alaska have been found to have undescended testes and deformed antler growth, and roughly the same proportion of white-tailed deer in Montana were discovered to have genital abnormalities.
In South Africa, eland have been revealed to have damaged testicles while being contaminated by high levels of gender-bender chemicals, and striped mice from one polluted nature reserved were discovered to be producing no sperm at all.
At the other end of the world, hermaphrodite polar bears – with penises and vaginas – have been discovered and gender-benders have been found to reduce sperm counts and penis lengths in those that remained male. Many of the small, endangered populations of Florida panthers have been found to have abnormal sperm.
Other research has revealed otters from polluted areas with smaller testicles and mink exposed to PCBs with shorter penises. Beluga whales in Canada's St Lawrence estuary and killer whales off its north-west coast – two of the wildlife populations most contaminated by PCBs – are reproducing poorly, as are exposed porpoises, seals and dolphins.
Scientists warned yesterday that the mass of evidence added up to a grave warning for both wildlife and humans. Professor Charles Tyler, an expert on endocrine disrupters at the University of Exeter, says that the evidence in the report "set off alarm bells". Whole wildlife populations could be at risk, he said, because their gene pool would be reduced, making them less able to withstand disease and putting them at risk from hazards such as global warming.
Dr Pete Myers, chief scientist at Environmental Health Sciences, one of the world's foremost authorities on gender-bender chemicals, added: "We have thrown 100, 000 chemicals against a finely balanced hormone system, so it's not surprising that we are seeing some serious results. It is leading to the most rapid pace of evolution in the history of the world.
Professor Lou Gillette of Florida University, one of the most respected academics in the field, warned that the report waved "a large red flag" at humanity. He said: "If we are seeing problems in wildlife, we can be concerned that something similar is happening to a proportion of human males"
Indeed, new research at the University of Rochester in New York state shows that boys born to mothers with raised levels of phthalates were more likely to have smaller penises and undescended testicles. They also had a shorter distance between their anus and genitalia, a classic sign of feminisation. And a study at Rotterdam's Erasmus University showed that boys whose mothers had been exposed to PCBs grew up wanting to play with dolls and tea sets rather than with traditionally male toys.
Communities heavily polluted with gender-benders in Canada, Russia and Italy have given birth to twice as many girls than boys, which may offer a clue to the reason for a mysterious shift in sex ratios worldwide. Normally 106 boys are born for every 100 girls, but the ratio is slipping. It is calculated that 250,000 babies who would have been boys have been born as girls instead in the US and Japan alone.
And sperm counts are dropping precipitously. Studies in more than 20 countries have shown that they have dropped from 150 million per millilitre of sperm fluid to 60 million over 50 years. (Hamsters produce nearly three times as much, at 160 million.) Professor Nil Basu of Michigan University says that this adds up to "pretty compelling evidence for effects in humans".
But Britain has long sought to water down EU attempts to control gender-bender chemicals and has been leading opposition to a new regulation that would ban pesticides shown to have endocrine-disrupting effects. Almost all the other European countries back it, but ministers – backed by their counterparts from Ireland and Romania – are intent on continuing their resistance at a crucial meeting on Wednesday. They say the regulation would cause a collapse of agriculture in the UK, but environmentalists retort that this is nonsense because the regulation has get-out clauses that could be used by British farmers. <<
More rivaroxaban Success
[The link has additional news about Factor Xa inhibitors.]
http://genengnews.com/news/bnitem.aspx?name=46696016
>> Once-Daily Oral Rivaroxaban Compared With Subcutaneous Enoxaparin Every 12 Hours for Thromboprophylaxis After Total Knee Replacement: RECORD4 [Abstract #35]
Alexander G.G. Turpie, MD, McMaster University, Hamilton, Ontario, Canada
This study concluded that investigational rivaroxaban, an oral Factor Xa inhibitor, is more efficacious than a current standard of therapy, enoxaparin, for the prevention of venous thromboembolism following total knee replacement surgery without significantly increasing the risk of bleeding. Coupled with previous research that demonstrated that post-operative rivaroxaban was more effective than pre-operative enoxaparin in preventing deep-vein clotting, along with an easier method of administration (oral versus subcutaneous injection), this study may change the way physicians prevent serious blood clots in patients undergoing major orthopedic surgery.
In this study, a total of 3,148 patients were randomized to receive either once-daily oral rivaroxaban (10 mg) starting six to eight hours after surgery or twice-daily subcutaneous injections of enoxaparin beginning 12 to 24 hours after surgery for 10 to 14 days. Patients underwent mandatory, bilateral venography (X-ray of the vein) between days 11 and 15.
The primary endpoint of the study was the combined occurrences of deep-vein thrombosis, non-fatal pulmonary embolism, and all-cause mortality up to day 17. The main safety endpoint was major bleeding observed after one dose of the drug until two days after the end of treatment. Efficacy was determined first by a test for non-inferiority in the per-protocol population of 1,702 patients, followed by a test for superiority in the intention-to-treat population of 1,924 patients.
The results indicated that rivaroxaban significantly reduced the incidence of adverse events (the combination of blood clots and death) by 31 percent as compared with enoxaparin, with no significant increase in the rate of major bleeding events. Rivaroxaban and enoxaparin appeared equally effective at preventing major venous blood clots and pulmonary embolism. <<
RE:Exploring Gene Therapy To Fight AIDS
Sangamo Bioscience is targeting CCR5 receptors in order to produce such a mutation.
#msg-33184801
Sangamo has reaffirmed its intent to file an IND this year:
http://investor.sangamo.com/releasedetail.cfm?ReleaseID=352220
...
>We have also advanced our preclinical pipeline and expect to file Investigational New Drug (IND) application for the first of our ZFN-based therapeutic programs for HIV/AIDS before the end of 2008.<
...
Isis at ASH
[Interestingly, last year Isis licensed IP to Archemix for the development of aptamers. Archemix, via partnerships, has a history of targeting clotting factors.]
http://www.isispharm.com/featured_research_ASH-2008_12.html
>> Isis will present exciting research evaluating the therapeutic opportunity for antisense drugs to treat thromboembolic disorders at the 50th American Society of Hematology (ASH) Annual Meeting and Exposition, held at the Moscone Center in San Francisco, CA, on December 6-9, 2008
Isis' strategy is to expand its pipeline of 19 drugs in development into new therapeutic areas, and the broad applicability and efficiency of Isis' antisense technology enables the successful execution of this strategy. In thrombosis, there are many different clotting factors related to both bleeding and clotting disorders that could offer selective and effective antisense therapeutic targets. In earlier work, Isis demonstrated that antisense compounds can selectively inhibit all clotting factors made in the liver. At ASH, Isis scientists will present research updates on two clotting factors, Factor XI and Factor VII. <<
Unraveling the Placebo Effect
[at least in regard to anxiety]
http://genengnews.com/news/bnitem.aspx?name=46514805
>> Dec 3 2008, 11:44 AM EST
Genes determine whether sugar pills work
Contact: Tomas Furmark
tomas.furmark@psyk.uu.se
46-073-683-3487
Uppsala University
It is a well-known fact in drug trials that individuals can respond just as well to placebos, sugar pills, as to the active drug. On the other hand, it is difficult to explain why only certain people get better from placebos. A team of researchers from Uppsala University and Gothenburg University have now found gene variants that can impact the placebo effect and a mechanism in the brain that characterizes those who respond to placebos.
The study, published in Journal of Neuroscience, examined 108 individuals suffering from social phobia using a brain camera (PET, positron emission tomography). The individuals were participating in a treatment study looking into how anxiety-moderating drugs affect brain activity. Just under one fourth of the subjects were given a placebo instead of a drug. This was a double-blind study, meaning that neither the subjects nor the research team know who was taking the drug or the sugar pill.
Before and after an eight-week period of treatment, the participants were asked to give a stressful oral presentation while their brain activity was monitored. When all the metering was finished and the study was decoded, it turned out that 40 percent of the placebo group had received the same degree of anxiety relief from the sugar pill as other groups got from a drug.
Those who responded well to the placebo had a significant reduction in activity in the amygdala in the temporal lobe, while this reduction was not found in the others. In previous research the amygdala has stood out as a key structure for emotional reactions. Both serotonin-active drugs (SSRI preparations) and cognitive behavioral therapy moderate activity in this area.
"Thus, successful placebo treatment works through the same mechanism in the brain," says Tomas Furmark at the Uppsala University Department of Psychology, who directed the study.
The study also analyzed two genes that influence the reabsorption and synthesis of serotonin in the brain (the serotonin transporter gene and the tryptophan hydroxylase-2 gene). The findings showed that only individuals who had certain variants, alleles, of these genes had a moderation of activity in the amygdala. Above all, the tryptophan hydroxylase-2 genes variants could predict the degree of relief from anxiety achieved by the placebo pill as well as the moderation of the amygdala.
Statistical analyses showed that it is a genetic effect on the activity in the amygdala that influences the propensity to respond to a placebo, that is, a path from the gene, via the brain, to behavior.
The study shows for the first time that genes influence the placebo effect by regulating the propensity to react in an area of the brain that is important for our feelings.
This could have significant consequences for all drug testing and other treatment studies that use a placebo.
"The findings show that the possibilities of demonstrating that an active treatment functions better than a placebo can be affected by the gene variants in the trial subjects. It is also possible that genes can explain why certain people respond well or poorly to anxiety-moderating drugs and psychotherapy respectively," says Tomas Furmark. <<
Sirtuins Forestall Aging in Mice
[This PR suggests that excessive deregulation is bad for longevity and the economy. Maybe we can give resveratrol to the Obama economic team.]
http://genengnews.com/news/bnitem.aspx?name=46260336
>> Nov 26 2008, 12:24 PM EST
Researchers identify a potentially universal mechanism of aging
Contact: David Cameron
david_cameron@hms.harvard.edu
617-432-0441
Harvard Medical School
BOSTON, Mass. (Nov. 26, 2008) Like our current financial crisis, the aging process might also be a product excessive deregulation.
Researchers have discovered that DNA damage decreases a cell's ability to regulate which genes are turned on and off in particular settings. This mechanism, which applies both to fungus and to us, might represent a universal culprit for aging.
"This is the first potentially fundamental, root cause of aging that we've found," says Harvard Medical School professor of pathology David Sinclair. "There may very well be others, but our finding that aging in a simple yeast cell is directly relevant to aging in mammals comes as a surprise."[Why is this a surprise? This is the kind of claim the supplement industry has promoted for years.]
These findings appear in the November 28 issue of the journal Cell.
For some time, scientists have know that a group of genes called sirtuins are involved in the aging process. These genes, when stimulated by either the red-wine chemical resveratrol (http://web.med.harvard.edu/sites/RELEASES/html/11_1Sinclair.html) or caloric restriction (http://web.med.harvard.edu/sites/RELEASES/html/sinclair.html), appear to have a positive effect on both aging and health.
Nearly a decade ago, Sinclair and colleagues in the Massachusetts Institute of Technology lab of Leonard Guarente found that a particular sirtuin in yeast affected the aging process in two specific waysit helped regulate gene activity in cells and repair breaks in DNA. As DNA damage accumulated over time, however, the sirtuin became too distracted to properly regulate gene activity, and as a result, characteristics of aging set in.
"For ten years, this entire phenomenon in yeast was considered to be relevant only to yeast," says Sinclair. "But we decided to test of this same process occurs in mammals."
Philipp Oberdoerffer, a postdoctoral scientist in Sinclair's Harvard Medical School lab, used a sophisticated microarray platform to probe the mammalian version of the yeast sirtuin gene in mouse cells. The results in mice corroborated what Sinclair, Guarente, and colleagues had found in yeast ten years earlier.
Oberdoerffer found that a primary function of sirtuin in the mammalian system was to oversee patterns of gene expression (which genes are switch on and which are switch off). While all genes are present in all cells, only a select few need to be active at any given time. If the wrong genes are switched on, this can harm the cell. (In a kidney cell, for example, all liver genes are present, but switched off. If these genes were to become active, that could damage the kidney.) As a protective measure, sirtuins guard genes that should be off and ensure that they remain silent. To do this, they help preserve the molecular packaging called chromatin that shrink-wraps these genes tight and keeps them idle.
The problem for the cell, however, is that the sirtuin has another important job. When DNA is damaged by UV light or free radicals, sirtuins act as volunteer emergency responders. They leave their genomic guardian posts and aid the DNA repair mechanism at the site of damage.
During this unguarded interval, the chromatin wrapping may start to unravel, and the genes that are meant to stay silent may in fact come to life.
For the most part, sirtuins are able to return to their post and wrap the genes back in their packaging, before they cause permanent damage. As mice age, however, rates of DNA damage (typically caused by degrading mitochondria) increase. The authors found that this damage pulls sirtuins away from their posts more frequently. As a result, deregulation of gene expression becomes chronic. Chromatin unwraps in places where it shouldn't, as sirtuin guardians work overtime putting out fires around the genome, and the unwrapped genes never return to their silent state.
In fact, many of these haplessly activated genes are directly linked with aging phenotypes. The researchers found that a number of such unregulated mouse genes were persistently active in older mice.
"We then began wondering what would happen if we put more of the sirtuin back into the mice," says Oberdoerffer. "Our hypothesis was that with more sirtuins, DNA repair would be more efficient, and the mouse would maintain a youthful pattern gene expression into old age."
That's precisely what happened. Using a mouse genetically altered to model lymphoma, Oberdoerffer administered extra copies of the sirtuin gene, or fed them the sirtuin activator resveratrol, which in turn extended their mean lifespan by 24 to 46 percent.
"It is remarkable that an aging mechanism found in yeast a decade ago, in which sirtuins redistribute with damage or aging, is also applicable to mammals," says Leonard Guarente, Novartis Professor of Biology at MIT, who is not an author on the paper. "This should lead to new approaches to protect cells against the ravages of aging by finding drugs that can stabilize this redistribution of sirtuins over time."
Both Sinclair and Oberdoerffer agree with Guarente's sentiment that these findings may have therapeutic relevance.
"According to this specific mechanism, while DNA damage exacerbates aging, the actual cause is not the DNA damage itself but the lack of gene regulation that results," says Oberdoerffer. "Lots of research has shown that this particular process of regulating gene activity, otherwise known as epigenetics, can be reversedunlike actual mutations in DNA. We see here, through a proof-of-principal demonstration, that elements of aging can be reversed."
Recent findings by Chu-Xia Deng of the National Institute of Diabetes, Digestive and Kidney Diseases, has also found that mice that lack sirtuin are susceptible to DNA damage and cancer, reinforcing Sinclair's and Oberdoerffer's data.
###
This research was funded by the National Institutes of Health, and the Glenn Foundation for Medical Research. David Sinclair is a consultant to Genocea, Shaklee and Sirtris, a GSK company developing sirtuin based drugs. <<