GlaxoSmithKline and Synta announce elesclomol granted US orphan drug designation by the FDA

GlaxoSmithKline (GSK) and Synta Pharmaceuticals Corp. (NASDAQ: SNTA) today announced that the US Food and Drug Administration (FDA) has granted orphan drug designation to elesclomol (formerly STA-4783) for the treatment of patients with metastatic melanoma. Elesclomol is being developed under a global collaboration agreement between Synta and GSK. Elesclomol is an investigational drug that is not approved for any indication in any market at this time.


Orphan drug status is designed to encourage biotechnology and pharmaceutical companies to develop drugs for rare diseases which affect fewer than 200,000 people in the United States. In November 2006 elesclomol received Fast Track designation from the FDA for development in metastatic melanoma.


“We are pleased that the FDA granted elesclomol orphan drug status for the treatment of metastatic melanoma,” said Eric Jacobson, M.D., Senior Vice President and Chief Medical Officer, Synta Pharmaceuticals. “With the incidence of melanoma increasing more rapidly than any other cancer during the past ten years, there is a significant need for innovative therapies such as elesclomol.”


“Orphan drug status is an acknowledgment of the significant need to develop new therapies for patients with metastatic melanoma, a disease for which there are few treatment options,” said Paolo Paoletti, Senior Vice President of the OncologyMedicineDevelopmentCenterat GSK. “Through the development of products like elesclomol, GSK Oncology is reaffirming its commitment to address clinical needs in cancer treatment and improve the lives of patients.”


About elesclomol (formerly STA-4783)

Elesclomol is a novel, injectable, investigational drug candidate that is believed to kill cancer cells by elevating oxidative stress levels beyond a breaking point, triggering programmed cell death. This mechanism of action, called oxidative stress induction, represents a novel way of selectively killing cancer cells.


A pivotal Phase 3 clinical trial of elesclomol in combination with paclitaxel in metastatic melanoma (the SYMMETRYSM trial) was initiated in October 2007 and Phase 2 trials in other indications, and in combination with other agents, are planned. Information about the SYMMETRY trial can be found at www.clinicaltrials.gov.


In a double-blind, randomised, controlled Phase 2b clinical trial in 81 patients with metastatic melanoma, elesclomol in combination with paclitaxel met the primary endpoint, doubling the median time patients survived without their disease progressing, compared to paclitaxel alone (p = 0.035). The most common adverse events in the elesclomol plus paclitaxel group included fatigue, alopecia, constipation, nausea, hypoaesthesia, arthralgia, insomnia, diarrhoea, and anaemia.


About US orphan drug status

The Orphan Drug Act (ODA) provides economic incentives to encourage biotechnology and pharmaceutical companies to develop drugs for rare diseases which affect fewer than 200,000 people in the United States. Orphan drug designation entitles GSK and Synta to seven years of market exclusivity for elesclomol for the treatment of patients with metastatic melanoma. Additional incentives for orphan drug development include tax credits related to development expenses, reduction in FDA user fees and FDA assistance in clinical trial design.


About metastatic melanoma

The incidence of melanoma has increased more rapidly than any other cancer during the past ten years. According to the American Cancer Society, melanoma accounts for approximately five percent of all skin cancers but causes about 75% of all skin cancer-related deaths. An estimated 60,000 people will be diagnosed and nearly 8,200 people will die from melanoma this year in the USalone. If diagnosed and surgically removed while localised in the outermost skin layer, melanoma is potentially curable; however, for patients with metastatic disease, the prognosis is poor. Treatments are limited and the expected survival for patients with metastatic melanoma is only six to nine months.


About GlaxoSmithKline

GlaxoSmithKline – one of the world's leading research-based pharmaceutical and healthcare companies – is committed to improving the quality of human life by enabling people to do more, feel better and live longer. For company information, visit GlaxoSmithKline at www.gsk.com.


GSK Oncology is dedicated to producing innovations in cancer that will make profound differences in the lives of patients. Through GSK’s “bench to bedside” approach, we are transforming the way treatments are discovered and developed, resulting in one of the most robust pipelines in the oncology sector. Our worldwide research in oncology includes collaborations with more than 160 cancer centers. GSK is developing a new generation of patient-focused cancer treatments in prevention, supportive care, chemotherapy and targeted therapies.




About Synta Pharmaceuticals

Synta Pharmaceuticals Corp. is a biopharmaceutical company focused on discovering, developing, and commercialising small molecule drugs to extend and enhance the lives of patients with severe medical conditions, including cancer and chronic inflammatory diseases. Synta has a unique chemical compound library, an integrated discovery engine, and a diverse pipeline of clinical- and preclinical-stage drug candidates with distinct mechanisms of action and novel chemical structures. AllSynta drug candidates were invented by Synta scientists using our compound library and discovery capabilities. Synta has a partnership with GlaxoSmithKline for the joint development and commercialisation of elesclomol. For more information, please visit www.syntapharma.com.

US Food and Drug Administration Approves RECOTHROM

Bayer HealthCare announced today that its partner, ZymoGenetics Inc., received US Food and Drug Administration (FDA) approval of RECOTHROM™ Thrombin, topical (recombinant) for use as a topical hemostatic product. Bayer acquired the product rights for all markets outside the US in 2007 and will provide US sales support for a three-year period as part of a co-promotion agreement.
“The first regulatory approval of RECOTHROM is a significant signal of the product’s strong clinical data,” said Hans Bishop, Head of Bayer’s global Hematology/Cardiology Business Unit. “RECOTHROM is an attractive addition to our specialty pharmaceutical portfolio. Our partnership with ZymoGenetics demonstrates Bayer’s continued focus on working collaboratively with innovative biotechnology companies to develop and commercialize novel protein therapeutics.”

RECOTHROM, previously referred to as rThrombin, is the first and only recombinant, plasma-free thrombin approved for use as a topical hemostatic product. The FDA has approved RECOTHROM as an aid to hemostasis whenever oozing blood and minor bleeding from capillaries and small venules is accessible and control of bleeding by standard surgical techniques is ineffective or impractical.

The FDA approval of RECOTHROM triggers a US-Dollar 40 million milestone payment from Bayer to ZymoGenetics. ZymoGenetics will compensate Bayer HealthCare for its US sales efforts by paying a tiered commission of up to 20% on US sales and up to US-Dollar 20 million in sales bonus payments upon achievement of certain US sales levels during a three-year co-promotion period.

About RECOTHROM™
RECOTHROM is a recombinant form of human thrombin that is structurally and functionally similar to human thrombin. It is not derived from animal or human blood. With thrombin being used in more than 1 million surgeries each year in the United States, RECOTHROM gives surgeons the opportunity to provide their patients with a plasma-free thrombin alternative for surgical hemostasis. The production of recombinant proteins is not dependent on the availability of blood from animals or human donors and can be scaled-up to meet market demand.

About Bayer HealthCare
The Bayer Group is a global enterprise with core competencies in the fields of healthcare, nutrition and high-tech materials. Bayer HealthCare, a subsidiary of Bayer AG, is one of the world’s leading, innovative companies in the healthcare and medical products industry and is based in Leverkusen, Germany. The company combines the global activities of the Animal Health, Consumer Care, Diabetes Care and Pharmaceuticals divisions. The pharmaceuticals business operates under the name Bayer Schering Pharma AG. Bayer HealthCare’s aim is to discover and manufacture products that will improve human and animal health worldwide. Find more information at www.bayerhealthcare.com.

Bayer Schering Pharma is a worldwide leading specialty pharmaceutical company. Its research and business activities are focused on the following areas: Diagnostic Imaging, Hematology/Cardiology, Oncology, Primary Care, Specialized Therapeutics and Women's Healthcare. With innovative products, Bayer Schering Pharma aims for leading positions in specialized markets worldwide. Using new ideas, Bayer Schering Pharma aims to make a contribution to medical progress and strives to improve the quality of life. Find more information at www.bayerscheringpharma.de.

GSK via its Centre Of Excellence for External Drug Discovery, exercises its options to further develop Exelixis’ anti-cancer C-Met inhibitior XL880

Exelixis, Inc. (Nasdaq: EXEL) today announced that GlaxoSmithKline (GSK) has exercised its option to exclusively license XL880 for further development and commercialisation. XL880 is a small molecule compound currently being evaluated in phase 2 trials in patients with papillary renal cell carcinoma (PRC), gastric cancer and head and neck cancer. Under the terms of the collaboration between Exelixis and GSK initiated in October 2002 and amended in January 2005, GSK’s selection of XL880 entitles Exelixis to a selection milestone of $35 million and additional payments upon the attainment of specific development and commercialisation milestones. The $35 million selection milestone will be applied to repayment of an advance that GSK paid to Exelixis in 2005. Exelixis is also entitled to receive double-digit royalties on product sales if the compound is approved for marketing and commercialised. Exelixis will have certain co-promotion rights to XL880 in North America.


“XL880 is the first MET inhibitor to be evaluated in phase 2 trials, and the clinical data generated to date for this compound has been very compelling,” said George A. Scangos, Ph.D., President and Chief Executive Officer of Exelixis. “We believe that XL880 has substantial potential as a first-in-class therapy, and GSK and Exelixis look forward to the completion of the ongoing XL880 phase 2 trials and evaluation of pivotal trial options. We are pleased that GSK shares our belief in the significant clinical and commercial potential of this compound. Additionally, we believe that GSK’s selection of XL880 validates our strategy of building a franchise in the area of MET inhibition to exploit the potential of this promising target.”


“The exercise of the XL880 option confirms GSK’s growing status as a world leader in the development of new oncology medicines for use in thetreatment, prevention and supportive care of cancer patients,” commented Paolo Paoletti, MD, Senior Vice President of the Oncology Medicines Development Centre at GSK. “It further strengthens our oncology pipeline and demonstrates our commitment to identifying compounds that have the potential to deliver real benefit to patients. The data we have seen from trials conducted by Exelixis have given us confidence in the potential of XL880 for treating diseases for which there is high unmet medical need.”


The collaboration between Exelixis and GSK, which is managed by GSK’s Centre of Excellence for External Drug Discovery (CEEDD), covers seven compounds and their back-up and follow-up compounds currently in the Exelixis development pipeline. Under the terms of the collaboration, Exelixis submits the covered compounds to GSK as they achieve clinical proof-of-concept, which is a pre-determined measure of efficacy, generally based on phase 2 trial data, and GSK has the option to select two compounds, and potentially a third compound, for further clinical development and commercialisation. However, in the case of XL880, GSK requested in August 2007 to review the compound’s data prior to achievement of proof-of-concept. Exelixis agreed to the request and submitted the XL880 data package to GSK in September 2007.


Interim data from an ongoing phase 2 trial of XL880 in patients with PRC were presented in October 2007 at the 2007 AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics. Investigators reported at the conference that 15 of 19 patients (79%) with measurable disease evaluable for tumor response at the time of the data presentation had a decrease in tumour size (4-33%), including one patient with a partial response per RECIST criteria. All 19 evaluable patients with at least one post-baseline tumour assessment were reported to have had stable disease for at least three months, including 12 patients with stable disease for 6 to 15+ months. In 16 patients evaluable for safety at the time of the data presentation, the majority (72%) of adverse events (AEs) related to XL880 were Grade 1, 21% were Grade 2, and 5% were Grade 3 or higher. The Grade 3 AEs were hypertension in three patients. No Grade 4 or 5 AEs related to XL880 treatment were reported by investigators. A total of 15 serious adverse events (SAEs) in seven patients were reported, of which three were considered related to XL880 (two events of vomiting in one patient and hypertension in another patient).


Data from a phase 1 study of XL880 in patients with advanced solid tumours also were presented at the AACR-NCI-EORTC International Conference. Consistent with data previously reported from the phase 1 study, XL880 was reported to be generally well tolerated when given once daily over a 28-day cycle. Ten of 22 patients showed stable disease for at least three months. In a preliminary analysis of plasma samples from 21 patients, statistically significant changes in pharmacodynamic biomarkers were detected in the phase 1 clinical trial consistent with effects reported with other anti-angiogenic agents. This finding is also consistent with the hypertension that has been observed in patients receiving XL880.


Dr. Scangos noted, “We believe the selection of XL880 is a significant event that reflects the maturation of our pipeline and our discovery and development capabilities. XL880 represents one of many potentially significant compounds in our pipeline that we hope will help people with cancer. We believe that GSK’s selection of this novel compound will expedite the development of XL880 and may provide us with additional resources to advance our other compounds into and through clinical development.”


The effectiveness of GSK’s election to develop and commercialise XL880 and the associated technology transfer by Exelixis to GSK are subject to antitrust clearance, which is expected to occur in the first quarter of 2008.


About XL880

XL880 has attractive pharmaceutical properties, with high solubility and oral bioavailability. In preclinical studies, XL880 potently inhibited both MET and VEGFR with nanomolar potency, and retained potent activity against mutationally activated forms of MET found in hereditary papillary renal cell carcinomas. The compound also demonstrated dose-dependent tumor growth inhibition in models of breast cancer, colorectal cancer, non-small cell lung cancer, and glioblastoma, and has been shown to cause substantial tumor regression in all models tested. Significantly, a single dose of XL880 completely inhibited tumor growth for 21 days in a glioblastoma model. Three phase 2 trials of XL880 are ongoing in patients with PRC, gastric cancer and head and neck cancer.


About GlaxoSmithKline

GlaxoSmithKline - one of the world's leading research-based pharmaceutical and healthcare companies - is committed to improving the quality of human life by enabling people to do more, feel better, and live longer. For company information, visit GlaxoSmithKline at www.gsk.com.


GSK Oncology is dedicated to producing innovations in cancer that will make profound differences in the lives of patients. Through GSK’s “bench to bedside” approach, we are transforming the way treatments are discovered and developed, resulting in one of the most robust pipelines in the oncology sector. Our worldwide research in oncology includes partnerships with more than 160 cancer centres. GSK is developing a new generation of patient focused cancer treatments in prevention, supportive care, chemotherapy and targeted therapies.


About the GSK CEEDD

GlaxoSmithKline is enhancing the way it discovers and develops drugs by creating a small, dedicated team that will feed the GSK pipeline solely through the efforts of its external alliances. The CEEDD (Centre of Excellence for External Drug Discovery) was formed as further validation of GSK’s strategy to create small, independent and accountable R&D teams (known as Centres of Excellence for Drug Discovery or CEDDs). In essence, the CEEDD is virtualising a portion of the GSK pipeline; namely from target to clinical proof-of-concept, by forming multiple risk-sharing/reward sharing alliances. Capitalising on the speed and efficiency of its collaborators will allow GSK to deliver pharmaceutical products faster to patients. For more information, visit the CEEDD at www.ceedd.com.


About Exelixis

Exelixis, Inc. is a development-stage biotechnology company dedicated to the discovery and development of novel small molecule therapeutics for the treatment of cancer and other serious diseases. The company is leveraging its fully integrated drug discovery platform to fuel the growth of its development pipeline, which is primarily focused on cancer. Currently, Exelixis' broad product pipeline includes investigational compounds in phase 2 and phase 1 clinical development for cancer and renal disease. Exelixis has established strategic corporate alliances with major pharmaceutical and biotechnology companies, including GlaxoSmithKline, Bristol-Myers Squibb Company, Genentech, Wyeth Pharmaceuticals and Daiichi-Sankyo. For more information, please visit the company's web site at http://www.exelixis.com.

Sciele Pharma Signs Agreement with Addrenex Pharmaceuticals to Market CLONICEL

Sciele Pharma, Inc. (NASDAQ: SCRX) today announced that it has signed an exclusive agreement with Addrenex Pharmaceuticals, Inc. to market, upon approval by the U.S. Food & Drug Administration (FDA), CLONICEL(R), a patented, sustained-release formulation of clonidine hydrochloride for the treatment of hypertension and attention deficit and hyperactivity disorder in North America. Sciele will also have the right of first refusal for other Addrenex products focused on pediatrics, women's health, and cardiovascular/metabolic diseases. Under the terms of the agreement, Sciele has purchased a $6 million equity stake in Addrenex and will have the right to increase its equity stake in Addrenex by an additional 10%. Sciele will also make regulatory milestone payments of up to $11 million and royalty payments to Addrenex on product sales.

Clonidine hydrochloride is an alpha-2 agonist approved for the treatment of hypertension. During the past year, approximately 11.7 million prescriptions were dispensed for clonidine hydrochloride tablets and approximately 1.8 million prescriptions were dispensed for clonidine patches, according to IMS Health's National Prescription Audit Plus data. CLONICEL(R) is a 12-hour, sustained-release formulation of clonidine hydrochloride, which currently is in pivotal clinical trials for hypertension. A 505(b)(2) NDA filing with the FDA is expected in the second half of 2007. A Phase III clinical trial utilizing CLONICEL(R) for ADHD is expected to begin in the second half of 2007.

Patrick Fourteau, Chief Executive Officer of Sciele Pharma, said, "This agreement with Addrenex provides us with the opportunity to further expand both our cardiovascular and pediatric product lines. We continue to execute on our strategy to diversify our product portfolio and expand our late-stage product pipeline through the licensing and acquisition of products."

Moise Khayrallah, Ph.D., Chief Executive Officer of Addrenex, said, "We are very happy that a successful company such as Sciele sees the potential of our lead compound CLONICEL(R). We look forward to a rewarding partnership that will allow Addrenex to develop and commercialize this product as well as future compounds in our adrenergic regulation portfolio."

About Sciele Pharma, Inc.

Sciele Pharma, Inc. is a pharmaceutical company specializing in sales, marketing and development of branded prescription products focused on Cardiovascular/Diabetes, Women's Health and Pediatrics. The Company's Cardiovascular/Diabetes products treat patients with high cholesterol, hypertension, high triglycerides, unstable angina and Type 2 diabetes; its Women's Health products are designed to improve the health and well-being of women and mothers and their babies; and its Pediatrics products treat allergies, asthma, coughs and colds, and attention deficit and hyperactivity disorder (ADHD). Founded in 1992 and headquartered in Atlanta, Georgia, Sciele Pharma employs more than 900 people. The Company's success is based on placing the needs of patients first, improving health and quality of life, and implementing its business platform - an Entrepreneurial Spirit, Innovation, Speed of Execution, Simplicity, and Teamwork.

About Addrenex Pharmaceuticals, Inc.

Addrenex Pharmaceuticals is a focused, specialty pharmaceutical company that develops and commercializes drugs to treat adrenergic dysregulation. Addrenex Pharmaceuticals is based in Morrisville, North Carolina, on the edge of Research Triangle Park. The company was formed in 2006 by a practicing physician and a drug development expert with the mission to explore the impact that neurotransmitter regulation has on a variety of diseases and disorders. Addrenex identified adrenergic regulation as its initial research focus. Adrenergic dysregulation is implicated in medical conditions such as hypertension, ADHD, migraine, and post-menopausal symptoms. Addrenex will use the knowledge and experience gained from developing CLONICEL(R) as the foundation for additional discovery and development in the area of adrenergic regulation.