Investor Update

Basel, 11 December 2012

Promising data presented at ASH support continued development of multiple investigational medicines and demonstrate breadth of Roche’s robust hematology pipeline

Data from studies of four investigational medicines for hematological cancers presented at ASH

Roche (SIX: RO, ROG; OTCQX: RHHBY) announced encouraging data from four investigational medicines at the 2012 American Society of Hematology (ASH) Annual Meeting in Atlanta where over 500 abstracts related to Roche compounds will be included in this year’s scientific program. Presentations included early-stage data across a range of hematological cancers from several of Roche’s investigational medicines, including two antibody-drug conjugates (anti-CD79b [RG7596] and anti-CD22 [RG7593]), a small molecule BCL-2 inhibitor (RG7601) and a small molecule antagonist of MDM2 (RG7112). Data from these phase I studies have indicated that each candidate has promising anti-tumor activity and an acceptable tolerability profile in heavily pre-treated patients thereby supporting continued devolvement of these medicines.

“The data from these investigational medicines highlight our long-term commitment to develop even better treatments for people with hematological cancers,” said Hal Barron, M.D., Chief Medical Officer and Head, Global Product Development. “We are excited about the promise of our hematology pipeline, which includes obinutuzumab (GA101), a glycoengineered anti-CD20 in phase III studies, as well as our early stage molecules.”

Key study results presented include:

  • anti-CD79b antibody-drug conjugate, RG7596, anti-CD79b-MMAE is an ADC composed of the cytotoxic agent MMAE linked to an anti-CD79b monoclonal antibody and is designed to target MMAE to B-cells via CD79b. Based on data from the dose-escalation portion of an ongoing phase I study, RG7596 demonstrated anti-tumor activity in heavily pre-treated patients with relapsed/refractory B-cell non-Hodgkin lymphoma (NHL) including follicular lymphoma, diffuse large B-cell lymphoma (DLBCL) and mantle cell lymphoma (MCL). Among 17 patients treated at clinically relevant doses, 8 had an objective response to RG7596 monotherapy with encouraging evidence of durable responses. RG7596 was generally well tolerated. Observed toxicities of neutropenia and peripheral sensory neuropathy were consistent with the known mechanism of action of the study drug and were manageable. Enrollment and analysis of RG7596 clinical activity in indication-specific expansion cohorts is ongoing. Currently, RG7596 and RG7593 are also being investigated in a head-to-head efficacy and safety comparison as combination treatments with rituximab in a phase II study in NHL.
  • anti-CD22 antibody-drug conjugate, RG7593, anti-CD22-MMAE is an ADC composed of the highly cytotoxic microtubule inhibitor MMAE linked to an anti-CD22 monoclonal antibody and is designed to target MMAE to B-cells via CD22. Based on data from the dose-escalation portion of an ongoing phase I study, RG7593 demonstrated anti-tumor activity in heavily pre-treated patients with relapsed/refractory B-cell NHL including follicular lymphoma and DLBCL. Among 17 patients treated at clinically relevant doses, 7 had an objective response to RG7593 monotherapy with encouraging evidence of durable responses. RG7593 was generally well tolerated. Observed toxicities of neutropenia and peripheral sensory neuropathy were consistent with the known mechanism of action of the study drug and were manageable. Enrollment and analysis of RG7593 clinical activity in indication-specific expansion cohorts is ongoing. Currently, RG7593 and RG7596 are also being investigated in a head-to-head efficacy and safety comparison as combination treatments with rituximab in a phase II study in NHL.
  • BCL-2 inhibitor, RG7601 (ABT-199/GDC-0199), designed to facilitate apoptosis, also known as programmed cell death, and thereby to reduce tumor masses and to prevent tumor growth and resistance to therapy. In a phase I study, RG7601 monotherapy shows anti-tumor activity in patients with MCL, DLBCL, follicular lymphoma and Waldenström macroglobulinemia (WM). To date, no dose limiting toxicities have been identified and dose escalation is continuing to identify the optimal dosing regimen and maximum tolerated dose (MTD) of RG7601 in NHL. The most common adverse events (AEs) experienced by more than 15% patients were nausea (30%), diarrhea (20%), dyspepsia (17%), fatigue (17%) and cough (17%). Grade 3/4 AEs occurring in more than 2 patients were neutropenia (10%) and anemia (13%). RG7601 is being co-developed with Abbott. Data from the CLL portion of the study have been previously reported and will be updated at a future medical meeting.
  • MDM2 antagonist, RG7112, designed to stabilize tumor suppressor protein p53, activate p53-mediated cell death and inhibit cancer cell growth. Phase I results provide proof of mechanism and evidence for single-agent clinical activity of MDM2 antagonism in leukemia by demonstrating complete remission (5 of 31 (16%) at the MTD), lysis of leukemic blasts and activation of p53 pathway targets in leukemic cells from patients treated with RG7112. Major AEs occurring in more than 20% of patients included nausea, diarrhea and vomiting and other major (>10% of patients) AEs were complications of leukemia (e.g. neutropenic fever).

Key abstract information:

  • RG7596 (DCDS4501A)
    A Phase I Study of the Anti-CD79b Antibody-Drug Conjugate (ADC) DCDS4501A Targeting CD79b in Relapsed or Refractory B-Cell Non-Hodgkin’s Lymphoma (NHL)
    Session 624. 12.15 Sunday December 9. Sidney Marcus Auditorium, Level 4, Building A.
  • RG7593 (DCDT2980S)
    A Phase I Study of DCDT2980S, an Antibody-Drug Conjugate (ADC) Targeting CD22, in Relapsed or Refractory B-Cell Non-Hodgkin’s Lymphoma (NHL)
    Session 624. 13.00 Sunday December 9. Sidney Marcus Auditorium, Level 4, Building A.
  • RG7601 (ABT-199)
    The BCL-2- Specific BH3-Mimetic ABT-199 (GDC-0199) is Active and Well-Tolerated in Patents with Relapsed Non-Hodgkin Lymphoma: Interim Results of a Phase I Study.
    Session 623. 07:45 Monday December 10. A411-A412, Level 4, Building A.
  • RG7112
    Results of the Phase 1 Trial of RG7112, a Small-Molecule MDM2 Antagonist, in Acute Leukemia
    Session 615. 17.00 Monday December 10. A101, Level 1, Building A.

In addition to the data presented at ASH, first patient in has been achieved for a multi-center, open-label, dose-finding study that will evaluate the safety and pharmacokinetics of RG7601 (ABT-199/GDC-0199) administered in combination with obinutuzumab (GA101) to patients with relapsed/refractory or previously untreated chronic lymphocytic leukemia. The combination has the potential to change the outlook for patients with relapsed CLL by shifting the treatment paradigm from aggressive chemotherapy-based regimens to the use of targeted therapy.

About RG7596 and RG7593

RG7596 and RG7593 are antibody-drug conjugates (ADC) consisting of an anti-CD79b or anti-CD22 monoclonal antibody respectively which is linked to a microtubule-disrupting agent. Both are being developed utilizing Seattle Genetics ADC technology. Additionally, a phase II clinical trial evaluating anti-CD22 ADC (RG7593) or anti-CD79b ADC (RG7596) in combination with rituximab for relapsed or refractory follicular non-Hodgkin lymphoma and relapsed or refractory diffuse large B-cell lymphoma is ongoing.

About RG7601 (ABT-199/GDC-0199)

RG7601 is a potent BH3-mimetic selectively targeting and binding to the anti-apoptotic BCL-2 protein, which is highly expressed in CLL, indolent non-Hodgkin lymphoma and some aggressive lymphomas as well as other B-cell neoplasms. RG7601 is being developed in collaboration with Abbott.

About RG7112

RG7112 is an oral, selective, small molecule MDM2 antagonist that inhibits binding of MDM2 to p53. MDM2 plays an important role in regulating the degradation of p53. Blocking the MDM2-p53 interaction stabilizes p53 and activates p53-mediated cell death and inhibition of cell growth. Clinical studies of RG7112 in combination are also underway.

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 personalized healthcare strategy aims at providing medicines and diagnostic tools that enable tangible improvements in the health, quality of life and survival of patients. In 2011, Roche had over 80,000 employees worldwide and invested over 8 billion Swiss francs in R&D. The Group posted sales of 42.5 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: www.roche.com.

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