Two studies investigating afatinib* in patients with locally advanced or recurrent/metastatic head and neck cancer are open for recruitment.

FOR NON-US MEDIA ONLY

Ingelheim, Germany, 26 January 2012 – Boehringer Ingelheim announced today the initiation of two phase III clinical trials, LUX-Head & Neck 1 and LUX-Head & Neck 2. These trials evaluate afatinib* in patients with metastatic and recurrent head and neck cancer, and in patients with locally advanced disease, respectively.

Afatinib* is an irreversible ErbB Family Blocker which inhibits signal transduction of all kinase receptors from the ErbB Family, and is known to play a critical role in the growth and spread of the most pervasive cancers and cancers associated with high mortality (lung, breast, and head & neck cancers). Over-expression of the Epidermal Growth Factor Receptor (EGFR, also referred to as ErbB1) 1 is found in at least 90% of head and neck cancers and strongly correlates with poor prognosis and overall survival. 2

Positive results from a recently presented phase II study show that afatinib* is the first targeted therapy with at least comparable anti-tumour activity to cetuximab in patients with metastatic head and neck cancer whose cancer has returned (recurrent disease) after treatment with platinum-based chemotherapy. 3
Each year, approximately 560,000 cases of head and neck cancer are diagnosed worldwide, and 300,000 patients die annually. 4

For patients with recurrent/metastatic disease, treatment options include systemic chemotherapy. Despite the introduction of chemotherapy in this setting approximately 30 years ago, patients with recurrent/metastatic head and neck cancer still have a poor prognosis, with a median survival of only 6-10 months. 5 In locally advanced head and neck cancer, chemoradiotherapy is an important option. However, due to high recurrence rates, patients with locally advanced disease tend to also have a poor prognosis.

“Currently, approximately 50% of patients with locally advanced head and neck cancer will have a recurrence and there is an urgent need for more treatment options” said Dr Ezra Cohen, Associate Professor of Medicine at the University of Chicago Medical Center “We hope potential new treatments such as afatinib will increase the effective options for patients with head and neck cancer.”
LUX-Head & Neck 1 will evaluate, if afatinib* can prolong progression-free survival (primary endpoint) and improve overall survival in patients with recurrent/metastatic head and neck cancer who progress after platinum-based treatment.

LUX-Head & Neck 2 will evaluate, if afatinib* can prevent the recurrence of the disease and improve overall survival in patients with locally advanced disease after chemoradiotherapy.

The initiation of these phase III clinical trials represents yet another important milestone for Boehringer Ingelheim to broaden and further develop its oncology pipeline across a range of different cancers.

This expands the phase III clinical trial programme for Boehringer Ingelheim Oncology which currently includes trials with afatinib* in NSCLC and breast cancer and nintedanib* (BIBF 1120) in NSCLC and ovarian cancer.
If investigators are interested in becoming involved in the study and have potentially eligible patients, they should contact Boehringer Ingelheim at:
clintriage.rdg@boehringer-ingelheim.com
Notes to editors
About Trial Nr. 1200.43 (LUX- Head & Neck 1) and Trial Nr 1200.131 (LUX -Head & Neck 2)
LUX- Head & Neck 1 (1200.43

http://clinicaltrials.gov/ct2/show/study/NCT01345682
A randomised, open-label, phase III study to evaluate the efficacy and safety of oral afatinib* versus intravenous methotrexate in patients with recurrent and/or metastatic head and neck squamous cell carcinoma who have progressed after platinum-based therapy
LUX-Head & Neck 2 (1200.131)

http://clinicaltrials.gov/ct2/show/NCT01345669
A randomised, double-blind, placebo-controlled, phase III study to evaluate the efficacy and safety of afatinib* as adjuvant therapy after chemoradiotherapy in primary unresected HPV (Human Papilloma Virus) negative patients with stage III, IVa, or IVb loco-regionally advanced head and neck squamous cell carcinoma
About Head and Neck Cancer
Head and neck cancer is the term used to describe malignant tumours originating in the upper aerodigestive tract (UADT), including the oral cavity, larynx, pharynx and nasopharynx. The vast majority (90%) of head and neck cancers are squamous cell carcinomas (HNSCC) arising from the epithelial membranes (mucus linings) of these regions, 6 and as such they have many common features relating to their aetiology and classification. Additionally, the Epidermal Growth Factor Receptor (EGFR/ErbB1), which is critical for tumour growth, 7 is over-expressed in at least 90% of head and neck cancers. 2

Radiotherapy in combination with platinum-based chemotherapy (most often cisplatin) - administered either as a definitive treatment or after surgery - plays a role in the management of locally advanced and/or inoperable head and neck cancers; this is known as ‘chemoradiotherapy’. Chemoradiotherapy, however, is associated with significant side effects and toxicities. In addition, locally advanced head and neck cancer is associated with a poor prognosis due to high recurrence rates. 8
About Boehringer Ingelheim in Oncology
Building on scientific expertise and excellence in the fields of pulmonary and cardiovascular medicine, metabolic disease, neurology, virology and immunology, Boehringer Ingelheim has embarked on a major research programme to develop innovative cancer drugs. Working in close collaboration with the international scientific community and a number of the world’s leading cancer centres, Boehringer Ingelheim’s commitment to oncology is underpinned by using advances in science to develop a range of targeted therapies for various solid tumours and haematological cancers.

The current focus of research includes compounds in three areas: angiogenesis inhibition, signal transduction inhibition and cell-cycle kinase inhibition. Nintedanib* (BIBF 1120) is currently in phase III clinical development in NSCLC and Ovarian cancer. Afatinib* is currently in phase III clinical development in NSCLC and breast cancer. In the area of cell-cycle kinase inhibition, Boehringer Ingelheim is developing an inhibitor of polo-like kinase 1 (Plk1), volasertib*, a protein that is involved in the processes of cell division.

Boehringer Ingelheim’s oncology pipeline is evolving and demonstrates the company’s continued commitment to the disease area.
Boehringer Ingelheim

26 January 2012
Boehringer Ingelheim launches ‘Lean-to-Clinic’ program for fast drug product supply
Ingelheim/Germany, 26 January 2012 – Boehringer Ingelheim has expanded its biopharmaceutical cell line development services and provides drug substance as fast as 13 months at competitive prices. The novel program is called ‘Lean-to-Clinic’ and leverages Boehringer Ingelheim’s established platforms and processes for the production of monoclonal antibodies using the proprietary BI-HEX® high expression system.
The improved approach combines Boehringer Ingelheim’s automated high throughput technologies in process science with a lean drug development approach to offer cost-effective services with shorter timelines. Within the Boehringer Ingelheim "one-stop-shop" service drug substances for toxicological and clinical studies may be delivered after only 13 months and drug products for clinical studies already after 16 months.
“‘Lean to Clinic’ is another milestone of our winning offers strategy to secure technology leadership, flexibility and customer orientation”, commented Simon Sturge, Corporate Senior Vice President Biopharmaceuticals at Boehringer Ingelheim. “‘Lean to Clinic’ consists of streamlined work packages and significantly speeds up cell line development, phase I process development and preclinical and clinical supplies from mammalian cell cultures.”
About Boehringer Ingelheim
The Boehringer Ingelheim group is one of the world’s 20 leading pharmaceutical companies. Headquartered in Ingelheim, Germany, it operates globally with 145 affiliates in 50 countries and more than 42,000 employees. Since its foundation in 1885, the family-owned company has been committed for more than 125 years to researching, developing, manufacturing and marketing novel products of high therapeutic value for human and veterinary medicine.Today, Boehringer Ingelheim is one of the world’s leading companies for contract development and manufacture of biopharmaceuticals. All types of services from mammalian cell line or microbial strain development to final drug production can be delivered within a one-stop-shop concept. Boehringer Ingelheim delivers services for pre-clinical development up to global market supply with a strong commitment to its customers at its global manufacturing facilities for mammalian cell culture and microbial fermentation. Boehringer Ingelheim has brought 19 molecules to market and has many years of experience in multiple molecule classes such as monoclonal antibodies, recombinant proteins, interferons, enzymes, fusion molecules and plasmid DNA. Furthermore, high-titer platform technologies for new antibody mimetic formats such as scaffold proteins and antibody fragments are available for the manufacture of customer products.