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Roche presents early data on the next generation of therapeutic antibodies and other targeted therapies at ASCO


Five new oncology medicines may be submitted for regulatory approval within 3 years

Roche (SIX: RO, ROG; OTCQX: RHHBY), today provided an overview of the new medicines in early-stage studies that will be presented at the 46th Annual Meeting of the American Society of Clinical Oncology (ASCO) taking place June 4-8 in Chicago. The combined Roche and Genentech oncology pipeline includes 22 new investigational medicines in clinical development of which five are expected to be submitted for regulatory approval by 2013. These include the therapeutic armed-antibody T-DM1, the new therapeutic antibodies pertuzumab and GA101, and novel molecules designed to target different mutations within cancer signaling pathways: RG7204 (mutated BRAF inhibitor) and GDC-0449 (Hedgehog Pathway Inhibitor).

“The molecules in Roche’s oncology portfolio result from our research philosophy of identifying the underlying causes of disease and following the science to deliver effective treatment options for people with cancer,” said Hal Barron, M.D., Head of Global Development and Chief Medical Officer for Roche. “Data from our oncology pipeline molecules presented at ASCO demonstrate the strength of our approach, from novel therapeutic antibodies including T-DM1 and GA101, to a range of investigational medicines against the mutated pathways that cause cancer, such as inhibitors of mutated Raf and PI3 kinase.”
Roche’s next generation of antibodies

* Antibody-drug conjugates: Featured at ASCO 2010 is phase Ib/II data on the combination of T-DM1 and pertuzumab for advanced HER2-positive breast cancer. T-DM1 is a ground-breaking ‘armed antibody’ combining the therapeutic antibody, trastuzumab, with a cell-killing agent (DM1) delivered directly to the tumor. Roche and Genentech have 50 promising new armed antibodies in various stages of early research and development.
* Glycoengineered antibodies: Roche and Genentech have also pioneered a technology (glycoengineering) that enhances the ability of a monoclonal antibody to induce an immune response against cancer cells. Roche currently has several glycoengineered antibodies in development including RG7159 (GA101) for the treatment of B-cell malignancies (chronic lymphocytic leukemia and non-Hodgkin’s lymphoma) and RG7160 (GA201) that binds to Epidermal Growth Factor Receptor (EGFR) and has shown promising early results in treating colorectal cancer. Data on both of these compounds are being presented at ASCO.

Roche at the forefront of novel cancer-cell targets

Mutations within pathways that normally control the growth, spread and survival of cells are common causes of cancer. Roche is investigating many targets within these mutated signaling networks, including Ras, Raf, MEK, Akt, PI3 kinase and the Hedgehog Signaling Pathway. Data on many of Roche’s compounds in this area are being presented at ASCO, in particular Raf, PI3 kinase and Hedgehog Signaling Pathway inhibitors.
Key abstracts on Roche’s early-stage oncology pipeline at ASCO:

Antibody-Drug Conjugates and HER Dimerization Inhibitors

A Phase Ib/II Trial of Trastuzumab-DM1 (T-DM1) With Pertuzumab for Women With HER2-Positive Locally Advanced or Metastatic Breast Cancer Who Were Previously Treated With Trastuzumab (Abstract #1012) – Saturday, June 5, 2010, 8:00 a.m. – 12:00 p.m. CST, Room E450b; 12:00 – 1:00 p.m. CST in East Hall D1

This early-phase trial evaluated a novel combination of an antibody-drug conjugate, T-DM1, with a HER dimerization inhibitor, pertuzumab, in previously treated women with advanced HER2-positive breast cancer.

T-DM1 attaches trastuzumab (Herceptin) and the highly potent chemotherapy DM1 together using a stable linker, which keeps T-DM1 in one piece until it reaches the cancer cells. To fight cancer, T-DM1 retains trastuzumab effects, such as locating and binding to cancer cells, allowing it to block out-of-control signals that make the cancer grow, and also calling on the body’s immune system to attack the cancer. Then, once T-DM1 is internalized by cancer cells, it destroys them by releasing the DM1.
Glycoengineered Fully Human Antibodies

Activity of the CD20-Directed Monoclonal Antibody GA101 Relative to Rituximab in Waldenstrom’s Macroglobulinemia, and Applicability to Patients Expressing Fc Gamma RIIIA-158 F/F (Abstract #8112) – Saturday, June 5, 2010, 8:00 a.m – 12:00 p.m. CST, South Hall A2

Phase I PK/PD Study of RO5083945 (GA201), the First Glycoengineered Anti-EGFR Monoclonal Antibody With Optimized Antibody Dependent Cellular Cytotoxicity (Abstract #2522) – Saturday, June 5, 2010, 8:00 a.m – 12:00 p.m. CST, Room E450a

These early stage studies evaluated GA101 and GA201, glycoengineered antibodies that target the CD20 and EGFR proteins, respectively. GA101 is currently in Phase II/III trials for CD20-positive B-cell blood cancers, such as non-Hodgkin’s lymphoma and chronic lymphocytic leukemia. GA201 is currently in Phase I clinical studies for various solid tumors including, advanced head and neck cancer.

Roche, Genentech and GlycArt (a wholly owned member of the Roche Group) are collaborating to develop these new types of monoclonal antibodies.
Hedgehog Pathway Inhibitor (GDC-0449/RG3616)

Safety Analysis of a Randomized Phase II Trial of Hedgehog Pathway Inhibitor GDC-0449 Versus Placebo With FOLFOX or FOLFIRI and Bevacizumab in Patients With Previously Untreated Metastatic Colorectal Cancer (Abstract #3530) – Tuesday, June 8, 2010, 8:00 a.m – 12:00 p.m. CST, Room S403

A Phase I Pharmacokinetic Trial of Sonic Hedgehog Antagonist GDC-0449 in Pediatric Patients With Recurrent or Refractory Medulloblastoma: A Pediatric Brain Tumor Consortium Study (PBTC 25) (Abstract #CRA9501) – Saturday, June 5, 2010, 4:45 – 5:00 p.m. CST, Room S504.

These studies feature results about GDC-0449 (RG3616), an orally-administered small molecule inhibitor of the Hedgehog signaling pathway. Hedgehog signaling is abnormally activated in certain types of cancers including colorectal, medulloblastoma (a type of brain cancer) and basal cell carcinoma (a type of skin cancer). It is thought that GDC-0449 may inhibit two types of overactive Hedgehog signaling: either within the cancer cell itself (caused by mutations in the pathway) or in surrounding cells (caused by over-expression of Hedgehog).

Genentech and Roche, under a collaboration agreement with Curis, Inc., are currently studying GDC-0449 in Phase II trials across multiple tumor types and in combination with approved treatments.
Mutant BRAF Inhibitor (RG7204/PLX4032)

Early FDG-PET Responses to PLX4032 in BRAF-Mutant Advanced Melanoma (Abstract #8529) – Monday, June 7, 2010, 8:00 a.m – 12:00 p.m. CST, Room S403

PLX4032 (RG7204), a Selective Mutant RAF Inhibitor: Clinical and Histologic Characteristics of Therapy-Associated Cutaneous Neoplasms in a Phase I Trial (Abstract #8592) – Sunday, June 6, 2010, 8:00 a.m – 12:00 p.m. CST, South Hall A2

PLX4032 in Metastatic Colorectal Cancer Patients With Mutant BRAF Tumors (Abstract #3534) – Sunday, June 6, 2010, 2:00 – 6:00 p.m. CST, South Hall A2

Mutations in the BRAF gene are found in about half of advanced melanomas, as well as other tumors types including colorectal cancer (~10 percent). RG7204 (PLX4032) is a potential first-in-class inhibitor of the cancer-causing BRAF mutations. Two studies presented at ASCO further confirm the safety and efficacy profile observed in a prior Phase I study of RG7204 in people with advanced melanoma that have a mutation in the BRAF gene.

Genentech and Roche are sponsoring Phase II (BRIM2) and Phase III (BRIM3) studies of RG7204 in people with previously treated and untreated advanced BRAF mutation-positive melanoma, respectively. Genentech, Roche and Plexxikon, Inc. are collaborating to develop RG7204 along with a companion diagnostic to test for the BRAF mutation.
PI3 Kinase Inhibitors (GDC-0941/RG7321, GDC-0980/RG7422)

A First-in-Human Phase I Study to Evaluate the Pan-PI3K Inhibitor GDC-0941 Administered QD or BID in Patients With Advanced Solid Tumors (Abstract #2541) – Monday, June 7, 2010, 8:00 a.m – 12:00 p.m. CST, South Hall A2

A First-in-Human, Phase l Study to Evaluate the Dual PI3K/mTOR inhibitor GDC-0980 Administered QD in Patients With Advanced Solid Tumors or Non-Hodgkin’s Lymphoma (Abstract #3079) – Monday, June 7, 2010, 8:00 a.m – 12:00 p.m. CST, South Hall A2

The PI3K signaling pathway controls different aspects of cell growth and is frequently overactive and mutated across a wide range of cancers.

Roche and Genentech have begun enrolling patients in a Phase I trial of the PI3K inhibitor (GDC-0941/RG7321) combined with a MEK inhibitor (GDC-0973/RG7420) in solid tumors. MEK is part of the RAS-RAF signaling pathway that is also involved in tumor growth. This approach of simultaneously testing two investigational medicines represents a new targeted approach to cancer treatment. Inhibiting two parallel cancer growth pathways at the same time may be more effective in treating cancer patients who have multiple mutations driving their tumor growth.
About Roche

Headquartered in Basel, Switzerland, Roche is a leader in research-focused healthcare with combined strengths in pharmaceuticals and diagnostics. Roche is the world’s largest biotech company with truly differentiated medicines in oncology, virology, inflammation, metabolism and CNS. Roche is also the world leader in in-vitro diagnostics, tissue-based cancer diagnostics and a pioneer in diabetes management. Roche’s personalised healthcare strategy aims at providing medicines and diagnostic tools that enable tangible improvements in the health, quality of life and survival of patients. In 2009, Roche had over 80’000 employees worldwide and invested almost 10 billion Swiss francs in R&D. The Group posted sales of 49.1 billion Swiss francs. Genentech, United States, is a wholly owned member of the Roche Group. Roche has a majority stake in Chugai Pharmaceutical, Japan. For more information:

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