NEWS RELEASE


Innovative ICR-discovered drug to enter first clinical trial, targeting HSF1 pathway

2021-08-26 00:00:00

Cancer patients are set to receive, for the first time, a highly innovative investigational drug called NXP800 – which was discovered at The Institute of Cancer Research, London – in a phase I clinical trial sponsored by an oncology-focused biopharmaceutical company, Nuvectis Pharma.

The investigational oral drug inhibits the so-called Heat Shock Factor-1 (HSF1) pathway, and was discovered by scientists at the Cancer Research UK Cancer Therapeutics Unit at The Institute of Cancer Research (ICR).

The first-in-human study is due to begin later this year.

The phase I trial will be led by Professor Udai Banerji, Deputy Director of Drug Development at the ICR and The Royal Marsden NHS Foundation Trust, in patients with advanced cancers from The Royal Marsden.

The ICR’s expert teams in pharmacodynamics and pharmacokinetics will lead on gathering data on the body’s handling of NXP800 and its biological effects – providing biomarkers that form a ‘Pharmacological Audit Trail’ of the drug’s behaviour.

As a ‘transcription factor’, HSF1 is a master switch that controls the activity of genes in the cell. In healthy cells HSF1 activates a specific gene programme in response to certain types of cellular stress.

But in cancers, HSF1 is hijacked and its gene activation programme is modified in a way that is needed by the tumour cells to survive, grow and spread. Cancer cells are subject to a range of stresses and the modified HSF1 gene activation programme helps them to overcome these. Patients with high levels of HSF1 gene activation in their cancers have poorer overall survival.  

While transcription factors are traditionally known to be very difficult to target with drugs, scientists at the ICR identified a small molecule that inhibits HSF1’s gene activation programme.

They did this by using cellular ‘phenotypic screening’ – involving testing hundreds of thousands of chemical compounds for their ability to switch off the HSF1 gene activation programme in live cancer cells in culture. This was followed by medicinal chemistry to optimise the handling of the drug in the body.

In pre-clinical studies, NXP800 was shown to potently block human cancer cell growth in culture and cause regression of tumours in mice – with hard-to-treat ovarian clear cell carcinoma (OCCC) and endometrioid ovarian cancers being the most sensitive to treatment.

Nuvectis has licensed worldwide development and commercialization rights to the HSF1 drug candidate NXP800 from its previous commercial investor, the CRT Pioneer Fund (CPF) managed by Sixth Element Capital.

Professor Paul Workman, Chief Executive of The Institute of Cancer Research, London, and the originator and leader of its HSF1 programme, said:

“We’re enormously excited to see our new first-in-class HSF1 pathway inhibitor is on the cusp of reaching clinical trials, thanks to this new partnership with the highly experienced team at Nuvectis. This is following a long-running and highly innovative team science project at ICR to discover an oral clinical candidate in partnership with the CPF.

“This is a prime example of the original and creative drug discovery and development that is possible through synergistic partnerships between academics, clinicians and private enterprise and that could lead to a totally new type of treatment for patients with hard-to treat cancers.”

Professor Udai Banerji, Deputy Director of Drug Development at The Institute of Cancer Research, London, and The Royal Marsden NHS Foundation Trust, said:

“NXP800 is an innovative first-in-class drug and we are excited to be nearing the stage of the drug development pathway when patients will start receiving it. This phase I trial will aim to establish a safe dose and dosing schedule for NXP800, as well as provide initial evidence of its clinical activity in a range of cancer types – and we hope that it will lead on to late-stage clinical development.”

Ron Bentsur, Chairman and Chief Executive Officer of Nuvectis, said:

"We are excited to have partnered with the ICR and CPF on this important project.  We believe that NXP800 has the potential to become a first-in-class HSF-1 pathway inhibitor and benefit patients suffering from OCCC, late-stage endometroid ovarian as well as other types of cancers. We look forward to the pending commencement of the phase I study in the capable hands of the ICR and The Royal Marsden."

Dr Robert James, Managing Partner at Sixth Element Capital, said: 

“We are delighted to have partnered NXP800 with Nuvectis and that this very novel agent will now march forward into clinical evaluation for the benefit of the cancer patients. This is a further exemplification of the CRT Pioneer Fund’s successful investment strategy to develop and commercialise early stage and highly innovative cancer therapies.”

Tony Hickson, Chief Business Officer at Cancer Research UK, said:

“Projects like this demonstrate exactly what we wanted to achieve when setting up the CRT Pioneer Fund – seamlessly bridging the gap between drug discovery and clinical trials so we can bring innovative treatments to people with cancer in the safest and quickest time possible.

“We are looking forward to seeing the results of the upcoming phase 1 clinical trial and hope to one day see it benefit patients with a range of hard-to-treat cancer types.”

-- ENDS --

Notes to editors

For more information please contact Henry French in the ICR press office on 020 7153 5153 or henry.french@icr.ac.uk. For enquiries out of hours, please call 07595 963 613.

 

The Institute of Cancer Research, London, is one of the world's most influential cancer research organisations. 

Scientists and clinicians at The Institute of Cancer Research (ICR) are working every day to make a real impact on cancer patients' lives. Through its unique partnership with The Royal Marsden NHS Foundation Trust and 'bench-to-bedside' approach, the ICR is able to create and deliver results in a way that other institutions cannot. Together the two organisations are rated in the top four centres for cancer research and treatment globally.

The ICR has an outstanding record of achievement dating back more than 100 years. It provided the first convincing evidence that DNA damage is the basic cause of cancer, laying the foundation for the now universally accepted idea that cancer is a genetic disease. Today it is a world leader at identifying cancer-related genes and discovering new targeted drugs for personalised cancer treatment.

The ICR is a charity and relies on support from partner organisations, funders and the general public. A college of the University of London, it is the UK’s top-ranked academic institution for research quality and provides postgraduate higher education of international distinction.

The ICR's mission is to make the discoveries that defeat cancer.

For more information visit ICR.ac.uk

 

About Nuvectis Pharma

Nuvectis Pharma, Inc. is a biopharmaceutical company focused on the development of innovative precision medicines for serious conditions of unmet medical need in oncology. Nuvectis was founded in 2020 and is led by a team of industry veterans with broad and extensive drug development experience, and a proven track record of clinical and regulatory success. NXP800, our lead drug candidate, has the potential to become a first-in-class HSF1-pathway inhibitor and a Phase 1 trial of NXP800 in patients with advanced solid tumors is set to begin in 4Q2021. For more information, please visit www.nuvectis.com

 

About Sixth Element Capital LLP and the CRT Pioneer Fund

Sixth Element Capital LLP (6EC) is a UK based fund manager, which manages the CRT Pioneer Fund. 6EC’s experienced partners focus on creative and collaborative novel financing solutions designed to fund and manage innovative science in order to bring new therapeutic products and technologies to market, creating long term value and benefit to stakeholders. The CRT Pioneer Fund is a specialist oncology investment fund established by 6EC in 2012. The £70 million fund is dedicated to investments in oncology development programs in Europe. The fund was established to bridge the investment gap between cancer drug discovery and early clinical development.

For more information, please see www.sixthelementcapital.com

 

About Cancer Research UK’s Commercial Partnerships Team  

Cancer Research UK is the world’s leading cancer charity dedicated to saving lives through research. Cancer Research UK’s specialist Commercial Partnerships Team works closely with leading international cancer scientists and their institutes to protect intellectual property arising from their research and to establish links with commercial partners. Cancer Research UK’s commercial activity operates through Cancer Research Technology Ltd., a wholly owned subsidiary of Cancer Research UK. It is the legal entity which pursues drug discovery research in themed alliance partnerships and delivers varied commercial partnering arrangements.  http://commercial.cancerresearchuk.org/