Investor Update

Basel, 29 September  2013

Roche presents updated data on investigational cancer immunotherapy MPDL3280A (anti-PDL1) in lung cancer at ECC 2013

  • Rapid and durable responses observed in difficult-to-treat patients
  • Data suggest tumor PD-L1 biomarker status predictive of treatment efficacy

Roche (SIX: RO, ROG; OTCQX: RHHBY) today announced that the company has presented important new data on MPDL3280A (RG7446, also known as anti-PDL1) at the 2013 European Cancer Congress (ECC), September 27 to October 1, 2013, in Amsterdam, The Netherlands. These data were highlighted as part of ECC 2013’s official press program.

The data from an updated analysis of a Phase 1 study assessing MPDL3280A monotherapy in patients with advanced or metastatic non-small cell lung cancer (NSCLC) showed that MPDL3280A was generally well tolerated and yielded often rapid, durable responses. Response rates were particularly high in patients who had greater expression of PD-L1 in their tumors as measured by a Roche Tissue Diagnostics immunohistochemistry (IHC) assay.

“These results in patients with limited treatment options for their lung cancer are encouraging, and PD-L1 expression could help determine which patients derive the most benefit,” said Hal Barron, MD, Chief Medical Officer and Head of Global Product Development at Roche. “Based on these data, we are moving quickly into late-stage clinical studies that will also include a Roche companion diagnostic to potentially identify those who are more likely to respond to treatment.”

MPDL3280A is an investigational medicine designed to make cancer cells more vulnerable to the body’s immune system, referred to more broadly as cancer immunotherapy, by interfering with a protein called PD-L1 (Programmed Death-Ligand 1). PD-L1 is expressed in tumors and is believed to function as a key part of the cancer-immunity cycle by acting as a ‘stop sign’, preventing the immune system from destroying cancer cells. MPDL3280A is being studied in clinical trials to understand whether its unique approach of blocking PD-L1 (i.e. removing the stop sign) could help the immune system to respond to and destroy tumor cells.

Results from the MPDL3280A study in NSCLC presented at ECC 2013

  • The MPDL3280A Phase 1 study included 85 heavily-pretreated, locally-advanced or metastatic NSCLC patients; 55% of patients had received at least three prior systemic therapies. The safety analysis presented included all 85 patients; the efficacy analysis included 53 patients who had received their first dose of MPDL3280A by 1 October 2012.
  • MPDL3280A was generally well tolerated; the majority of adverse events were Grade 1 or 2 and did not require intervention. A total of 12.6 percent of patients experienced a treatment-related Grade 3 or 4 adverse event, including fatigue (2%), dyspnea (shortness of breath; 0.7%), nausea (0.4%) and vomiting (0.4%). No grade 3 or 4 pneumonitis (lung inflammation) was observed.
  • Twenty-three percent of the 53 NSCLC patients who were dosed with MPDL3280A as a single agent by 1 Oct 2012 achieved a best objective response as measured by RECIST 1.1 critera. Eleven of twelve responding patients continued to respond as of the data cutoff date, and the 24 week PFS rate was 44.7% (95% CI: 31.2%-58.3%).
  • The association between PD-L1 expression and treatment benefit was analysed; objective response was particularly pronounced in the population with the highest level of PD-L1 expression (IHC 3; defined as tumors containing ≥10% PD-L1-positive tumor-infiltrating immune cells) at 83% (5 of 6 patients, 95% CI: 40.2%-99.1%).
  • When considering disease control rate (DCR), a measure which combines best objective response of complete response, partial response and stable disease, patients with high levels of PD-L1 expression (IHC 2/3; defined as tumors containing ≥5% PD-L1-positive tumor-infiltrating immune cells) achieved a DCR of 69% compared to a DCR of 48% in the low-PD-L1 expression (IHC 0/1; defined as tumors containing <5% PD-L1-positive tumor-infiltrating immune cells) population.

MPDL3280A Phase Ia: Best Response by PD-L1 immunohistochemistry (IHC Status) – NSCLC

Diagnostic Population a)(n = 53)ORR b)% (n/n)PD Rate% (n/n)
IHC 383% (5/6)17% (1/6)
IHC 2 and 346% (6/13)23% (3/13)
IHC 1/2/331% (8/26)38% (10/26)
All Patients c)23% (12/53)40% (21/53)

a) IHC 3: ≥ 10% tumor immune cells positive for PD-L1 (IC+); IHC 2 and 3: ≥ 5% tumor immune cells positive for PD-L1 (IC+); IHC 1/2/3: ≥ 1% tumor immune cells positive for PD-L1 (IC+); IHC 0/1/2/3: all patients with evaluable PD-L1 tumor IC status.
b) ORR (overall response rate) includes investigator-assessed unconfirmed and confirmed partial response.
PD=progressive disease
c) All patients includes patients with IHC 0/1/2/3 and 7 patients have an unknown diagnostic status.
Patients first dosed at 1-20 mg/kg by Oct 1, 2012; data cutoff Apr 30, 2013.

Based on the results of this Phase 1 study and others, Roche has initiated two Phase 2 studies of MPDL3280A in patients with NSCLC, and pivotal studies are planned. In addition, a Phase 1 melanoma study is assessing the potential utility of the combination of Zelboraf® (vemurafenib) and MPDL3280A in patients with previously untreated, BRAFV600-mutation positive metastatic disease. The potential of MPDL3280A is also being explored in combination with Avastin® (bevacizumab) in a Phase 1 study enrolling patients with advanced solid tumours. Further studies in other tumor types are planned.

Presentation details for MPDL3280A (Anti-PDL1)

Abstract #3408: Clinical activity, safety and biomarkers of PD-L1 blockade in non-small cell lung cancer (NSCLC): Additional analyses from a clinical study of the engineered antibody MPDL3280A (anti-PDL1). Proffered Papers Session, Sunday, September 29, 09:14 – 09:26 in Elicium 2.

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, infectious diseases, inflammation, metabolism and neuroscience. Roche is also the world leader in in vitro diagnostics and tissue-based cancer diagnostics, and a frontrunner 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 2012 Roche had over 82,000 employees worldwide and invested over 8 billion Swiss francs in R&D. The Group posted sales of 45.5 billion Swiss francs. Genentech, in the United States, is a wholly owned member of the Roche Group. Roche is the majority shareholder in Chugai Pharmaceutical, Japan. For more information, please visit www.roche.com.

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