Privately-held German drugmaker Boehringer Ingelheim yesterday unveiled its mid-stage oncology pipeline for the first time to journalists, who had convened at the Institute of Molecular Pathology in Vienna to hear about the group’s research and development activities.

The company first toyed with the idea of entering the oncology arena back in the 1990s, but only cemented its commitment in 2000 with the selection of a research site in Vienna. Since then, with over 200 scientists on board, eight clinical anti-cancer candidates were characterised, of which three are now showing promise in Phase II clinical trials:

BI 2536 is a first-in-class inhibitor of Polo-like kinase 1 (Plk-1), a molecule essential for cell division. The principle behind its mode of action is that, if a cancer cell wants to divide but can’t, this will induce apoptosis - programmed cell death - thereby killing the cancerous cell without harming any of the surrounding healthy ones, which often happens with other anti-proliferation drugs such as the taxanes. The agent performed very well in preclinical models, showing activity regardless of which mutation drives the cancer, and its efficacy is now being tested in Phase II trials, Wolfgang Rettig, Senior Vice President of Research at BI, told delegates at the meeting. Registration is on target for 2008.

BIBF 1120 is a triple angiogenesis blocker, designed to offer long lasting clinical benefit and better tolerability and safety than its predecessors on the market. The drug works by cutting off the oxygen and nutrient supply to cancer cells, thereby preventing the development of blood vessels to the tumour. But, unlike the first generation of angiogenesis blockers, BIBF 1120 targets VEGF, FGF and PDGF receptors in several cells essential to blood vessel formation, making it more difficult for the tumour cells to recruit other kinases to build a blood supply. “Initial results look very promising,” said Dr Rettig, “we have clear indication of efficacy in tumour shrinkage and stable disease rates.” But he added that the product would not be on the market before 2008, depending on the outcome of trials.

BIBW 2992 is a novel kinase inhibitor that blocks the activity of both EGFR and HER2. “Here we have receptor molecules that combine to form a treatment principle,” Rettig said, explaining the design behind the drug. Dual inhibition should provide added efficacy in more cancer types than older drugs on the market, which target either one or the other. In preclinical models, the efficacy of BIBW 2992 was shown to match and surpass that of Herceptin (trastuzumab), and it is known to be well-tolerated, he said. The drug’s efficacy is boosted by the fact that it targets secondary resistance: “Our inhibitor fits into the docking site and throws in an anchor, the principle being latch on…and don’t let go!” Rettig explained. BIBW 2992 is also on track for registration in 2008.

These three Phase II candidates all have innovative features and, if confirmed in Phase III development, they will “allow physicians to offer improved treatments choices to cancer patients,” claims Dr Andreas Barner, Vice Chairman of the Board of Managing Directors and responsible for the Corporate Board Division Pharmaceutical Research, Development and Medicine at BI.

And such a statement is not made lightly. Being a privately-held group, BI is not bound to publishing information about its R&D activities, and has traditionally shied away from showcasing its early-stage pipeline, preferring to report data only when there is a greater chance that the drug will make it to the patient.

And, as Dr Barner told PharmaTimes World News, not only is he very excited about the progress these mid-stage cancer compounds have made in a relatively short amount of time, he is also more than happy with the amount of candidates in the earlier stages of development, which suggests that the company is staying true to its ethos of creating “value through innovation.”