Boehringer Ingelheim (Canada) Ltd./Ltée19 April 2014
22. October 2008

Boehringer Ingelheim broadens oncology pipeline with promising new data for potentially first in class Plk1 inhibitor

BI 6727, a highly potent and selective Plk1 inhibitor, represents latest advance in company's Plk1 programme

Ingelheim, Germany. 22 October 2008 - Boehringer Ingelheim's most promising new cell cycle kinase inhibitor and potentially first-in-class compound, BI 6727, has shown encouraging results in a phase I clinical trial in patients with advanced tumours who have failed to respond to other treatments.1 The data, presented today at a prestigious plenary session and included in the official press conference of the 20th EORTC-NCI-AACR Symposium in Geneva, Switzerland, is testament to the company’s ongoing commitment to research and development of innovative cancer treatments in areas of significant unmet medical need. Boehringer Ingelheim's research efforts are focused on three main areas: angiokinase inhibition, signal transduction inhibition and cell cycle kinase inhibition, under which BI 6727 falls.

Unlike established anti-cancer agents, BI 6727 works by selectively blocking a part of the cell's make-up that is crucial for cell division. BI 6727 is one in a series of compounds being developed by Boehringer Ingelheim in this field. By inhibiting the activity of Polo-like kinase 1 (Plk1), which is highly expressed in proliferating cells and most tumours, BI 6727 effectively disrupts the cell division and induces cell death, thereby inhibiting cancer growth. Due to its unique mode of action, typical side effects induced by established anti-mitotic agents such as neuropathy have not occurred.

According to Professor Patrick Schöffski, Head of the Department of Medical Oncology at the University Hospitals Leuven, Belgium, Chairman of the scientific committee for the congress, secretary general of the EORTC and lead investigator in the trial, the results indicate an exciting scientific advance.

"Compelling new science in fields such as cell cycle kinase inhibition brings us a step closer to better understanding the multiple pathways involved in the growth and spread of tumours and will hopefully provide us with better treatments to add to the armoury against this deadly disease," said Professor Schöffski.

"Results to date for BI 6727 have indicated that the drug can be safely administered to patients with advanced solid tumours and that it has potential anti-tumour activity. This agent certainly warrants further investigation," he added.

In the study, which assessed the maximum tolerated dose, overall safety, pharmacokinetics and preliminary efficacy of BI 6727, a total of 50 patients were treated at doses of 12 to 450 mg. Results were encouraging; 32% of patients had stable disease and two patients with advanced bladder and ovarian cancers showed confirmed responses, both of whom had previously failed other standard and experimental treatments. The clear anti-tumour activity demonstrated, not typically seen in a phase I trial, illustrates the significance of these findings. Furthermore, BI 6727 was shown to be well-tolerated with no serious side effects detected.

Preclinical data2 were also presented at the meeting which showed highly selective target inhibition, cellular activity at very low levels and long-lasting tumour exposure for BI 6727. This, combined with the phase I data presented suggests a promising future for BI 6727, supporting Plk1 as a therapeutic target and warranting further investigation.

The new results presented today complement Boehringer Ingelheim's additional progress in the fields of signal transduction inhibition and angiokinase inhibition. Boehringer Ingelheim recently announced the commencement of pivotal phase III trials for its most advanced compound, signal transduction inhibitor Tovok™ (BIBW 2992) and its novel triple angiokinase inhibitor3 Vargatef™ (BIBF 1120) is planned to enter phase III in the near future.

Commenting on the growth of the Boehringer Ingelheim oncology portfolio, Dr Manfred Haehl, Corporate Senior Vice President Medicine at Boehringer Ingelheim said, "The latest data for our Plk1 inhibitor BI 6727, including initial safety and efficacy results, further reinforce our continued growth in oncology research and are evidence of our sustained leadership in Plk1 inhibition. As a company, we are really excited by the potential these impressive first results hold and look forward to ongoing growth within our oncology pipeline."

Based on the encouraging results presented at the EORTC-NCI-AACR Symposium, BI 6727 will advance further in clinical development. The Phase II programme will assess the efficacy and safety of BI 6727 in several tumour types.

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.

Boehringer Ingelheim is committed to discovering and developing novel cancer treatments that have the potential to provide significant clinical and quality of life benefits for patients. This commitment is underpinned by using advances in science to develop a range of targeted therapies in areas of medical need, including 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.

Boehringer Ingelheim is working in close collaboration with the international scientific community and a number of the world’s leading cancer centres to research and develop these potential new treatments for cancer.

Boehringer Ingelheim
The Boehringer Ingelheim group is one of the world’s 20 leading pharmaceutical companies. Headquartered in Ingelheim, Germany, it operates globally with 135 affiliates in 47 countries and 39,800 employees. Since it was founded in 1885, the family-owned company has been committed to researching, developing, manufacturing and marketing novel products of high therapeutic value for human and veterinary medicine.

In 2007, Boehringer Ingelheim posted net sales of 10.9 billion euro while spending one fifth of net sales in its largest business segment Prescription Medicines on research and development.

For more information please visit www.boehringer-ingelheim.com.

References

1. Schöffski, P et al. A phase I single dose escalation study of the novel polo-like kinase I inhibitor BI 6727 in patients with advanced solid tumours. Presented Thursday 23 October 2008 at the 20th EORTC-NCI-AACR. Plenary session 5. Molecular targets-state of the science 10:15-12:00. Abstract Number: 36. 
2. Rudolph, D et al. Characterisation of BI 6727, a novel polo-like kinase inhibitor with a distinct pharmacokinetic profile and efficacy in a model of taxane-resistant colon cancer. Presented Thursday 23 October 2008 at the 20th EORTC-NCI-AACR. Poster Display Period: 12:00PM –15:00PM; Abstract Number: 430.
3. Hilberg F et al. Eur J Cancer Suppl. 2004;2:50.