Roche Holding and Alnylam Pharmaceuticals Form $1 Billion Alliance on RNAi Therapeutics

Roche and the US-based biopharmaceutical company Alnylam Pharmaceuticals, Inc. announced today that they have entered into a major alliance in which Roche obtains a non-exclusive license to Alnylam's technology platform for developing RNAi (RNA interference) therapeutics. The alliance will initially cover four therapeutic areas: oncology, respiratory diseases, metabolic diseases and certain liver diseases. Alnylam and Roche also will collaborate on RNAi drug discovery for one or more disease targets in these therapeutic areas. In addition, Roche will acquire Alnylam's European research site located in Kulmbach, Germany (Bavaria), subject to regulatory approval.

This site will become Roche's Center of Excellence for RNAi therapeutics discovery.

RNAi is a potential foundation for a whole new class of human therapeutic products. RNAi is a natural mechanism that the body uses to inhibit expression of certain genes. Harnessing the activity of RNAi creates a direct opportunity to develop specific and potent drugs against diseases that are difficult to treat.

"Alnylam has made significant advances in RNAi therapeutics, one of the most promising approaches to tomorrow's healthcare technology. Working together with Alnylam provides us with new capabilities to target complex diseases within our focus areas," said Lee E. Babiss, Head of Roche Global Pharma Research. "Our mission is to find novel solutions for patients who suffer from difficult to treat diseases and we will be fully committed to this goal, together with our new colleagues located at the acquired site in Kulmbach."

"We are pleased to form this new alliance with Roche, which is widely recognized for its commitment to innovation in biotechnology. We look forward to working together to advance our transformative technology into a whole new class of drugs," said John Maraganore, Ph.D., President and Chief Executive Officer of Alnylam. "Such significant support from Roche will also strengthen Alnylam's efforts to build a leading innovation-based biopharmaceutical company. Indeed, together with our demonstrated commitment to scientific excellence, advancement of our pipeline and unparalleled intellectual property estate, we believe that this new alliance greatly extends our leadership position in the discovery and development of RNAi therapeutics."

Alnylam-Roche Collaboration

Alnylam has granted to Roche a non-exclusive license providing Roche access to broad Alnylam intellectual property (IP) and know-how, including fundamental, chemistry and delivery IP. Indications will initially include oncology, respiratory disease, metabolic disease and certain liver diseases. Alnylam maintains the right to non-exclusively license its IP to additional partners in potential future agreements. In addition, Alnylam and Roche will collaborate on one or more disease targets to be identified in the future in exchange for milestone and royalty payments.

The transaction includes Roche's acquisition of Alnylam's European research site in Kulmbach, Germany (Bavaria), with about 40 employees. The team in Kulmbach will remain dedicated to RNAi therapeutics discovery as a new Center of Excellence for RNAi therapeutics within Roche's global research organization.

The alliance could be valued at over 1 billion US dollars in consideration of upfront payments, potential product milestone payments for multiple products and field expansion payments, excluding potential royalties on future sales of commercial products. Under the terms of the agreement, Roche will pay Alnylam 331 million US dollars in upfront cash payments and equity investment, including 1.975 million shares of Alnylam common stock the Roche Venture Fund agreed to purchase at 21.50 US dollars per share, representing just less than five percent of Alnylam's outstanding common stock. Roche will also pay Alnylam milestones on products as they advance in development and commercialization as well as royalties on future sales of commercial products. Further, Roche may pay Alnylam field expansion payments to increase the number of therapeutic areas.

The close of the agreements, including Roche's purchase of Alnylam shares and purchase of Alnylam's site in Germany, is subject to certain regulatory approvals and is expected to occur within approximately 30 days.

About RNAi

RNAi (RNA interference) is a revolution in biology, representing a breakthrough in understanding how genes are turned on and off in cells, and a completely new approach to drug discovery and development. Its discovery has been heralded as "a major scientific breakthrough that happens once every decade or so," and represents one of the most promising and rapidly advancing frontiers in biology and drug discovery today which was awarded the Nobel Prize in October 2006. RNAi is a natural process of gene silencing that occurs in organisms ranging from plants to mammals. By harnessing the natural biological process of RNAi occurring in our cells, the creation of a major new class of medicines, known as RNAi therapeutics, is on the horizon. RNAi therapeutics target the cause of diseases by potently silencing specific messenger RNAs (mRNAs), thereby preventing disease-causing proteins from being made. RNAi therapeutics have the potential to treat disease and help patients in a fundamentally new way.

About Alnylam Pharmaceuticals

Alnylam is a biopharmaceutical company developing novel therapeutics based on RNA interference, or RNAi. The company is applying its therapeutic expertise in RNAi to address significant medical needs, many of which cannot effectively be addressed with small molecules or antibodies, the current major classes of drugs.

Alnylam is leading the translation of RNAi as a new class of innovative medicines with peer-reviewed research efforts published in the world's top scientific journals including Nature, Nature Medicine, and Cell. The company is leveraging these capabilities to build a broad pipeline of RNAi therapeutics; its most advanced program is in Phase II human clinical trials

for the treatment of respiratory syncytial virus (RSV) infection. In addition, the company is developing RNAi therapeutics for the treatment of influenza, hypercholesterolemia, and liver cancers, amongst other diseases. The company's leadership position in fundamental patents, technology, and know-how relating to RNAi has enabled it to form major alliances with leading companies including Merck, Medtronic, Novartis, Biogen Idec, and Roche. The company, founded in 2002, maintains global headquarters in Cambridge, Massachusetts. For more information, visit http://www.alnylam.com/.

About the Roche Venture Fund

The Roche Venture Fund makes investments in early stage biotech and diagnostics companies to support innovative technologies and medicines. Based in Basel, Switzerland, the Roche Venture Fund manages a portfolio of over 25 companies in 10 countries.

About Roche

Headquartered in Basel, Switzerland, Roche is one of the world's leading research-focused healthcare groups in the fields of pharmaceuticals and diagnostics. As a supplier of innovative products and services for the early detection, prevention, diagnosis and treatment of diseases, the Group contributes on a broad range of fronts to improving people's health and quality of life.

Roche is a world leader in diagnostics, the leading supplier of drugs for cancer and transplantation and a market leader in virology. In 2006, sales by the Pharmaceuticals Division totaled 33.3 billion Swiss francs ($26.6 billion US), and the Diagnostics Division posted sales of 8.7 billion Swiss francs ($6.96 billion US). Roche employs roughly 75,000 people in 150 countries and has R&D agreements and strategic alliances with numerous partners, including majority ownership interests in Genentech and Chugai. Additional information about the Roche Group is available on the Internet at http://www.roche.com/.

Roche and Toyama Chemical enter licensing agreement

Toyama Chemical Co., Ltd. and Roche announced today that they have entered into a licensing agreement for the worldwide research, development and commercialization of Toyama Chemical’s novel oral rheumatoid arthritis agent T-5224. By inhibiting a specific inflammatory process, T-5224 has the potential to block signs and symptoms of rheumatoid arthritis as well as the progressive destruction of joint and bone. T-5224 is currently in phase I. With this partnership, Roche is further strengthening its promising portfolio and R&D pipeline in the area of rheumatoid arthritis.

"This novel oral compound complements Roche’s developing portfolio of drug candidates in inflammation and rheumatoid arthritis. The agent T-5224 has the potential to inhibit a key trigger of rheumatoid arthritis and has already shown promising pharmacological efficacy and safety in early clinical studies," said Jean-Jacques Garaud, Head of Roche Pharma Development. "Our new collaboration is good news for all patients with rheumatoid arthritis as well as for our two companies. We are looking forward to collaborating with our new colleagues in Japan to develop T-5224."

"By entering into a research and development collaboration with Roche, one of the world’s leading research and development companies, we are able to increase Toyama’s potential for novel drug development in the anti-inflammatory field, which is a field of concentration for Toyama Chemical," said Masuji Sugata, President of Toyama Chemical.

Under the terms of the agreement, Toyama Chemical has granted Roche exclusive rights to research, develop, and sell T-5224 worldwide excluding Japan where Toyama Chemical will retain exclusive rights. The agreement also encompasses the joint research and development of back-up candidates to T-5224. Toyama Chemical will receive upfront payments and milestone payments totalling up to 370 million US dollars, based on certain development and commercial milestones. If approved for marketing, Toyama Chemical will receive royalties based on the net sales of T-5224 by Roche.

About T-5224
T-5224 is an inhibitor of the transcription factor AP-1 (Activator Protein-1) which is known to play an important role in the pathology of rheumatoid arthritis. AP-1 turns on a variety of genes in response to inflammation triggers, including many that are responsible for the proteins that are the targets of current rheumatoid arthritis products. In addition, in joint cells called osteoclasts, AP-1 stimulates the production of enzymes that are thought specifically to cause the destruction of bones and joint tissue. Therefore, by inhibiting the AP-1 process, T-5224 affects several key pathways and may prevent the progression of this disabling disease in many patients.

T-5224 was first identified as a drug candidate in rheumatoid arthritis through collaboration between Toyama Chemical Research and Professors Shunichi Shiozawa of Kobe University and Shuichi Hirono of Kitasato University. Non-clinical studies were completed through this collaboration and Phase I studies have been carried out in Japan since June of last year. Toyama Chemical is receiving, through the Contract Development Program, support from the Japan Science and Technology Agency, an independent administrative institution, for its research and development in Japan.

About rheumatoid arthritis
Rheumatoid arthritis (RA) is a progressive, systemic autoimmune disease characterized by chronic inflammation of multiple joints and fatigue as well as the possibility of osteoporosis, anaemia, and lung, skin and liver effects. This inflammation causes pain, stiffness and swelling, resulting in loss of joint function due to destruction of the bone and cartilage, often leading to progressive disability. Further, as chronic inflammation continues, there may be shortening of life expectancy as a result of effects on major organ systems. After 10 years, less than 50% of patients can continue to work or function normally on a day to day basis. RA affects more than 21 million people worldwide.

About Roche in rheumatoid arthritis
One of the most important drivers for growth at Roche over the next few years is expected to be the company’s emerging franchise in autoimmune diseases with rheumatoid arthritis as the first indication. Following the launch of MabThera (rituximab) there are a number of projects in development, potentially allowing Roche to build on further opportunities. MabThera is the first and only selective B-cell therapy for RA, providing a fundamentally different treatment approach by targeting B cells, one of the key players in the pathogenesis of RA. Actemra is Roche’s second novel medicine and is a humanised monoclonal antibody to the interleukin-6 (IL-6) receptor, inhibiting the activity of IL-6, a protein that plays a major role in the RA inflammation process. Actemra is the result of research collaboration by Chugai and is being co-developed globally with Chugai. Additional projects creating a rich pipeline include compounds in Phase I, II and III clinical trials. Notably, ocrelizumab, a fully humanised anti-CD20 antibody, is just entering phase III development for RA.

About Toyama Chemical
Toyama Chemical specializes in research and development, and strives to contribute to the further development of global health care through new drug development. Toyama concentrates its R&D in three fields: anti-infective agents, anti-inflammatory agents, and cerebral function improvers and cardiovascular drugs. Pharmaceuticals now in the pipeline include T-3811, a synthetic antibacterial agent; T-614, an oral anti-rheumatic agent; and T-817MA, a treatment for Alzheimer's disease. The company has formed strategic partnerships with domestic and overseas pharmaceutical manufacturers as well as establishing clinical research subsidiaries in the U.S. and U.K. Validation of Toyama’s success can be found in their technology exports and their royalty income which is the highest among mid-sized Japanese pharmaceutical companies. Toyama is taking an aggressive, outward-looking approach, globalizing its activities with the aim of becoming a key pharmaceutical manufacturer. Additional information about the Toyama Chemical is available on the Internet at www.toyama-chemical.co.jp/eng

About Roche
Headquartered in Basel, Switzerland, Roche is one of the world’s leading research-focused healthcare groups in the fields of pharmaceuticals and diagnostics. As the world’s biggest biotech company and an innovator of products and services for the early detection, prevention, diagnosis and treatment of diseases, the Group contributes on a broad range of fronts to improving people’s health and quality of life. Roche is the world leader in in-vitro diagnostics and drugs for cancer and transplantation, a market leader in virology and active in other major therapeutic areas such as autoimmune diseases, inflammation, metabolism and central nervous system. In 2006 sales by the Pharmaceuticals Division totalled 33.3 billion Swiss francs, and the Diagnostics Division posted sales of 8.7 billion Swiss francs. Roche employs roughly 75,000 worldwide and has R&D agreements and strategic alliances with numerous partners, including majority ownership interests in Genentech and Chugai. Additional information about the Roche Group is available on the Internet at www.roche.com

Roche's ACTEMRA Significantly Improves Symptoms of Rheumatoid Arthritis

Results of the OPTION (TOcilizumab Pivotal Trial in Methotrexate Inadequate respONders) trial, the first multinational Phase III study outside of Japan, showed that patients treated with ACTEMRA(TM) (either 4mg/kg or 8mg/kg) plus methotrexate achieved a significant and clinically important improvement in the signs and symptoms of moderate to severe rheumatoid arthritis (RA) compared to patients treated with placebo and methotrexate, a current standard of care. The data were presented today at the European Congress of Rheumatology (ECR) held by the European League Against Rheumatism (EULAR) in Barcelona, Spain.

In the 623-patient study, 58.5% of patients receiving the combination of ACTEMRA(TM) (8mg/kg) and methotrexate achieved at least a 20% improvement (ACR20) in RA symptoms compared with 26.5% of patients receiving placebo plus methotrexate after 24 weeks. The data also showed that 79.5% of patients in the ACTEMRA(TM) (8mg/kg) plus methotrexate group responded with moderate to good improvements in RA symptoms (EULAR response) compared to 34.8% for those treated with placebo and methotrexate at 24 weeks. ACTEMRA(TM) was generally well tolerated; the most common adverse events reported more frequently in the ACTEMRA(TM) arms of the OPTION trial were upper respiratory tract infection, nasopharyngitis and headache.

Other parameters measured in the study included C-reactive protein (CRP), a marker of inflammation, fatigue and hemoglobin. Patients in the ACTEMRA(TM) 8 mg/kg group showed a rapid lowering of CRP levels within two weeks, while fatigue scores showed that patients in the ACTEMRA(TM) group experienced a reduction in fatigue and a rapid improvement in hemoglobin levels. Low levels of hemoglobin are usually associated with anemia (reduction in red blood cells) that can result in tiredness and fatigue.

"There is a critical need for new therapies to treat moderate to severe RA patients, and these results suggest that IL-6 inhibition is an encouraging anti-inflammatory mechanism for reducing disease symptoms," said Mark C. Genovese, M.D., Associate Professor of Medicine at Stanford University School of Medicine.

ACTEMRA(TM) is the first humanized interleukin-6 (IL-6) receptor- inhibiting monoclonal antibody and represents a novel mechanism of action for the treatment for RA. Studies suggest that reducing the activity of IL-6, one of several key cytokines involved in the inflammatory process, may reduce inflammation of the joints, prevent long-term damage and relieve certain systemic effects of RA such as decreased hemoglobin, fatigue and osteoporosis.

"These study results underscore the potential for ACTEMRA(TM) to become a new treatment option for RA," said Lars Birgerson, M.D., Ph.D., Vice President, Global Head Medical Affairs, Roche. "We are hopeful that the ongoing Phase III trials will translate into improved clinical outcomes for patients."

About Rheumatoid Arthritis

Rheumatoid arthritis is a progressive, systemic autoimmune disease characterized by inflammation of the membrane lining in joints. This inflammation causes a loss of joint shape and function, resulting in pain, stiffness and swelling, ultimately leading to irreversible joint destruction and disability. RA affects more than 21 million people worldwide with approximately 2.5 million people affected in the United States. RA may also shorten life expectancy by affecting major organ systems and after 10 years, less than 50% of patients can continue to work or function normally on a day- to-day basis.

About the Study

The OPTION trial is a three-arm, randomized, double-blind, controlled Phase III study designed to evaluate the safety and efficacy of ACTEMRA(TM) plus methotrexate compared to placebo plus methotrexate in patients with moderate to severe RA who had an inadequate response to methotrexate alone. Patients received ACTEMRA(TM) intravenously (either 4mg/kg or 8mg/kg) every 4 weeks plus methotrexate weekly, or placebo infusions plus methotrexate weekly, for 24 weeks. The study enrolled patients at 73 trial sites in 17 countries outside the United States, and is one of five Phase III trials designed to study ACTEMRA(TM) as a potential new treatment for RA.

Data from the study were analyzed to determine patients' response to treatment by using three standard assessments: ACR score(1), developed by the American College of Rheumatology (ACR), DAS28(2), a measurement of RA disease activity, and EULAR(3), a measurement of treatment response.

In the study, 43.9% of patients treated with ACTEMRA(TM) (8mg/kg) plus methotrexate achieved at least a 50% (ACR50) reduction in symptoms compared to 10.8% of patients receiving placebo and methotrexate; ACR70 was achieved in 22% of the treatment group versus 2% in the control group. At 24 weeks, disease remission, as measured by DAS28 (5.1). DAS28

GlaxoSmithKline acquires exclusive rights to over-the-counter orlistat for markets outside the US from Roche Group

GlaxoSmithKline plc (GSK) announced today that it has acquired from Roche Group exclusive rights to the weight-loss medicine, orlistat, for over-the-counter (OTC) use in markets outside the US, excluding Japan. GSK anticipates filing orlistat for OTC approval in Europe and certain key international markets by the end of 2007.


Earlier this month, GSK received FDA approval to market OTC orlistat in the USA under the brand name alli™, and expects to launch alli during the summer.


John Clarke, President, GSK Consumer Healthcare, commented, “Today’s agreement strengthens GSK’s innovative consumer healthcare portfolio, and gives us the opportunity to globalise our efforts around OTC orlistat. This exclusive license is also testament to GSK’s ability to successfully switch prescription medicines to over-the-counter status and collaborate well with our partners. Alongside our smoking control franchise, we now have brands dedicated to addressing two of the world’s major health issues: smoking and obesity.”


In another transaction, GSK and Roche have also agreed to settle all arbitration procedures between the two companies relating to the licensing and co-marketing of carvedilol.


Financial terms of both agreements remain undisclosed. As part of the licensing agreement, Roche will receive an upfront payment from GSK; this will be offset by a payment made by Roche to GSK as a part of the settlement agreement.


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.