First clinical trial of innovative drug targeting HSF1 pathway begins

The first cancer patients are to receive doses of an innovative new drug that targets a master regulatory pathway in cells, as part of a new clinical trial.

The drug, called NXP800, was discovered at The Institute of Cancer Research, London, and targets the pathway regulated by the HSF1 transcription factor.

Targeting a master switch

HSFI is a ‘master switch’ in cells that controls the activity of a variety of genes – and its signalling is hijacked by a variety of cancers to support their growth and spread.

The phase I clinical trial is sponsored by oncology-focused biopharmaceutical company Nuvectis Pharma, which is now leading the drug’s development.

The trial is being 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.

The trial will have two parts: dose escalation, to evaluate the safety and tolerability of NXP800, and dose expansion, which will also evaluate its anti-tumour activity.

Ovarian cancer hope

The dose-expansion phase will focus on evaluating NXP800 in patients selected using biomarker analysis, initially in clear cell ovarian and endometrioid ovarian cancers.

Preclinical studies in cancer cells and in mice have suggested the drug could be particularly effective in women with ovarian clear cell and endometrioid ovarian cancers with defects in the ARID1A gene.

During the trial, expert teams in pharmacodynamics and pharmacokinetics from the ICR will lead on gathering data on the molecular effects of NXP800 and how it is processed by the body. Biomarkers will be measured to form a ‘pharmacological audit trail' of the drug’s behaviour.

ICR-discovered drug

The trial follows the discovery of NXP800 in a multi-year project carried out by an ICR team led by Professor Paul Workman, Harrap Professor of Pharmacology and Therapeutics at ICR, with earlier work supported by the ICR and funding organisations including Cancer Research UK, the Battle Against Cancer Investment Trust (BACIT) and the CRT Pioneer Fund LP – a specialist oncology investment fund managed by Sixth Element Capital. 

The medicinal chemistry component of the multidisciplinary research project was led by Professor Keith Jones at the ICR.

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

“We’re very pleased to begin the first trial of this innovative new drug, NXP800, in partnership with Nuvectis. We look forward to assessing the drug’s safety and pharmacokinetics, checking it is acting on cancer signalling as expected, and optimising its dose and schedule. We hope to unlock its therapeutic potential in specific hard-to-treat cancers where new treatments are urgently needed.”

Taking discoveries to patients

Professor Kristian Helin, Chief Executive of The Institute of Cancer Research, London, said:

“We’re delighted to see this innovative inhibitor of HSF1 signalling enter its first clinical trial. I hope the results of clinical trials will show that this new drug can make a real difference in the treatment of cancers patients, including those with clear cell and endometrioid ovarian cancers. NXP800 is the 12th ICR-discovered drug we’ve taken into clinical trials for cancer patients since 2005, in collaboration with industrial partners like Nuvectis. That track record is unrivalled in the academic world.”

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

“We are pleased to have achieved this important milestone in the NXP800 development programme. NXP800 has demonstrated great promise in preclinical studies, and we’re excited to advance it into clinical trials.”

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.”