Royal College of Surgeons in Ireland Coláiste Ríoga na Máinleá in Éirinn

RCSI and Inflection Biosciences enter research collaboration to target therapy-resistant breast cancer

23 November 2017

RCSI and Inflection Biosciences Ltd, a private company developing innovative therapeutics for cancer, today announced a research collaboration that aims to understand why there can be resistance to major breast cancer therapies and examine potential new treatments by Inflection Biosciences for patients with a cancer that does not respond effectively to existing therapies.

The potential new treatments (dual mechanism PIM/PI3K inhibitors) are novel molecules that work by blocking two abnormal proteins that occur in breast cancer, known as PIM and PI3K. One in nine Irish women will get breast cancer at some point in their lives. Recent improvements in treatment and diagnosis mean that many more women now survive the disease. Unfortunately, current treatments have no effect in up to 20 per cent of patients and where treatment does work, many patients relapse as treatment resistance emerges.

The research team at RCSI is led by Professor Bryan Hennessy, Senior Clinical Lecturer at RCSI, Consultant Medical Oncologist in Beaumont Hospital, Dublin, and Our Lady of Lourdes Hospital, Drogheda, and Adjunct Professor in the Division of Cancer Medicine at MD Anderson Cancer Centre (MDACC). Prof. Hennessy is also Clinical Lead at Cancer Trials Ireland.

Speaking at today’s announcement, Prof. Hennessy said: “I am excited about exploring the potential use of these novel molecules in the treatment of cancer, especially breast cancer, given that they will target the abnormal proteins, PIM and PI3K, which play an important role in therapy-resistant forms of this disease. The early results have shown this treatment approach to be effective in breast cancer cells that have become resistant to standard of care treatments.”

Dr Michael O’Neill, Director of Research and Development at Inflection Biosciences added: “Our dual acting molecules are able to treat cancer cells by targeting both PIM and PI3K pathways. This makes our compound more effective than compounds which attack either cancer pathway alone. We are delighted to have Professor Hennessy and the team at RCSI involved in this important research and their expertise will be of great benefit as we continue to develop these important treatments.”

Director of Research and Innovation at RCSI, Professor Ray Stallings, welcomed the announcement saying: "RCSI is delighted to announce this collaboration with Inflection Biosciences. RCSI's research strategy has a strong focus on excellence in translational research for the benefit of patients and healthcare systems. This partnership exemplifies how collaboration between academia and industry can help improve human health through high quality, impactful scientific research."

The collaboration has been supported by an Enterprise Ireland Innovation Voucher.

Inflection Biosciences news 

Pictured (L-R): Professor Bryan Hennessy, Senior Clinical Lecturer at RCSI, Consultant Medical Oncologist in Beaumont Hospital, Dublin and Our Lady of Lourdes Hospital, Drogheda and Adjunct Professor in the Division of Cancer Medicine at MD Anderson Cancer Centre (MDACC); Darren Cunningham, Chief Executive Officer at Inflection Biosciences Ltd; and Dr Michael O’Neill, Director of Research and Development at Inflection Biosciences. 

About PIM and PI3K in breast cancer

PIK3CA (which encodes the PI3K alpha isoform) is the most frequently mutated oncogene in breast cancer. The high prevalence of cancer-associated PI3K pathway alterations underpins the large number of treatments in development targeting this pathway. However, PI3K inhibitors have only shown clinical efficacy in a limited subset of breast cancer patients with intrinsic and acquired resistance posing a significant challenge. PIM kinase is elevated in triple negative breast cancer and mediates resistance to HER-2 therapies. Recent studies have shown that PIM kinase overexpression confers resistance to PI3K inhibitors in breast cancer cells. Whereas PI3K inhibitors primarily induce cell cycle arrest, leaving a reserve of tumour cells that may acquire or exhibit resistance, PIM suppression drives the cell cycle arrest induced by PI3K inhibition into apoptosis. Therefore, combined PI3K and PIM kinase inhibition represents a synergistic combination with therapeutic potential in breast cancer.

About RCSI

RCSI is ranked among the top 250 (top 2%) of universities worldwide in the Times Higher Education World University Rankings (2018) and its research is ranked first in Ireland for citations. It is an international not-for-profit health sciences institution, with its headquarters in Dublin, focused on education and research to drive improvements in human health worldwide. RCSI is a signatory of the Athena SWAN Charter.

About Inflection Biosciences

Inflection Biosciences Ltd, based in Dublin and London, is developing small molecule therapeutics for the treatment of cancer. The company's pipeline of highly innovative cancer treatments was licensed from the Spanish National Cancer Research Centre (CNIO). The pipeline comprises the IBL-300 series (PIM/PI3K/mTOR inhibitors) and IBL-202 (PIM/PI3K inhibitor) selected from a series of unique dual mechanism kinase inhibitors and the IBL-100 series (selective pan-PIM kinase inhibitors), currently in pre-clinical stages of development. Data generated to date suggests potential application in a range of treatment resistant solid tumours and haematological malignancies. Inflection Biosciences was named ‘Start-up Company of the Year’ at the 2014 Irish Pharma Awards. For more information please visit