Irish cancer biotech reaches a vital inflection point

29 Sep 2017

From left: Inflection Biosciences co-founders Darren Cunningham and Dr Michael O’Neill. Image: Inflection Biosciences

Inflection Biosciences is on the cusp of delivering groundbreaking treatments for the global battle against cancer.

“A successful drug for the treatment of cancer could generate several billions of dollars in revenue every year,” explained Darren Cunningham, CEO of biotech start-up Inflection Biosciences.

Cunningham, a former Elan and Amarin executive, is explaining the size of the prize when it comes to turning molecules into actual FDA-approved drugs. He is illustrating the potential his young company could have if it succeeds in turning research and trials into lifesaving products in the next 18 months.

‘Many would say that the PI3K inhibitors have yet to deliver on their great promise’

Emboldened by successful trials of treatments that it has licensed and hopes to bring to commercialisation, Inflection Biosciences has raised €2.5m in venture capital to date from private investors and Enterprise Ireland.

The Dublin company, which was established in 2012, is currently in the pre-clinical stage of development for its biotechnology that could play a decisive role in defeating breast cancer.

According to Cunningham, the technology is 18 months from getting to the first patients but will first have to go through a battery of tests and trials by the FDA as well as the European Medicines Agency.

“Our molecules – when they are approved for sale we get to call them drugs, but until then they are molecules or compounds – are first-in-class dual mechanism PIM/PI3K inhibitors. Our programmes are unique and we are not aware of any other company taking precisely the same approach.”

World-class research

Irish cancer biotech reaches an inflection point

Inflection Biosciences CEO Darren Cunningham. Image: Inflection Biosciences

Cunningham explained that the PI3K pathways in our cells mutate for various reasons and, when mutated, this drives cancer.

He said that PI3K is one of the most frequently mutated pathways among all cancers. As such, the industry has invested heavily in developing molecules to inhibit or shut down this pathway.

He explained that there are more than 30 molecules in clinical trials trying to inhibit the PI3K pathway, across more than 100 trials.

“To date, two PI3K inhibitors have been approved and many would say that the PI3K inhibitors have yet to deliver on their great promise. One of the reasons PI3K inhibitors have failed is that patients relapse, the treatment stops working. In effect, resistance is encountered, and this resistance is due to alternative cancer pathways being activated so as to bypass the PI3K pathway, thus allowing the cancer to grow again.

“Over the past three or so years, it has become more evident from third-party research published, and our own internal research, that one of the major alternative pathways which gets activated is PIM kinase. This would call for targeting both the PI3K pathway and the PIM kinase pathway at once to overcome or delay the onset of resistance, and this is exactly what Inflection Biosciences molecules can do – they are dual mechanism PIM/PI3K inhibitors.”

For example, the PI3K pathway is mutated in 33pc of all breast cancers, with 1m women per annum diagnosed globally.

“As such, there was particular interest within the industry to target the PI3K pathway with treatments in breast cancer. So far, no PI3K inhibitors have been approved in breast cancer.”

He pointed to research published from Dana-Farber – one of the world’s leading cancer research institutions based in Boston – in the past year, which aimed to understand why PI3K inhibitors were encountering resistance in breast cancer, identified PIM kinase as a major player in causing that resistance, and proposed co-targeting of PIM and PI3K in these subsets of breast cancer patients.

Following up on this world-class research, Inflection Biosciences carried out its own pre-clinical research this year with its dual mechanism inhibitor.

“We have demonstrated efficacy in a PI3K mutation-driven breast cancer model. We believe this could be a very significant opportunity for the company and have teamed up with Dr Bryan Hennessy and his team at RCSI to progress this treatment, with the hope of getting it to patients here in Ireland, and internationally in the coming few years.”

The prize: saving potentially millions of lives

Cunningham credits his time at Elan for challenging him and giving him the wherewithal to consider starting his own biotech company. After eight years as head of business development and investor relations at Amarin, he decided it was time to start up.

He teamed up with Dr Michael O’Neill who had a background in big pharma companies, and Inflection Biosciences was born.

The key to biotech entrepreneurship, Cunningham explained, is discovering the right research. In June 2013, the company secured a pipeline of potential treatments from the Spanish National Cancer Research Centre in Madrid.

“That was our big breakthrough in terms of getting the company going, and we have been fortunate enough to attract investors who have stayed with us and who gave us the time and space that is critical when it comes to fundraising for biotech.”

Inflection Biosciences has also teamed up with some of the world’s most pre-eminent cancer institutes, including Royal College of Surgeons in Ireland (RCSI), Thomas Jefferson University of North Carolina, the University of Sydney and University of Munich.

Cunningham said that the reality is, Inflection Biosciences will need to join forces with a larger biotech or pharma player to get through the larger approval trials and bring the product to manufacture. At the same time, he agreed it would be good for the indigenous Irish biotech sector to have a company with longevity and success.

“Ultimately, it makes commercial sense to join up with a biotech or a large pharma company to get to the marketplace.

“But our priority right now is to get to the next phases of the cancer trials and, out of a population of 50 patients, we hope to see a number of those patients responding to the product and living longer.”

Cunningham said that the company is currently working with more than 30 research partners in China, India, the UK, France, the US and Sydney to bring its molecules to trial.

“Ireland is actually a good breeding ground for this kind of activity. The US is certainly a target market for the company. It helps that Irish research is very well-received worldwide. And, while we are a small economy, we consistently participate at a global level.”

John Kennedy is a journalist who served as editor of Silicon Republic for 17 years