24 February 2016


(“Sareum” or “the Company”)

Research & Co-Development Collaborations Update

Sareum (AIM: SAR), the specialist cancer drug discovery and development business, reports positive progress with its cancer and autoimmune disease research programmes and announces the following updates on each of these programmes.

Dr Tim Mitchell, CEO of Sareum, said: “Good progress has been made in all our lead programmes.  This year will focus on the start of CHK1 clinical trials, progressing toxicology studies for Aurora+FLT3, and evaluating lead compounds from our TYK2 programme in relevant autoimmune and cancer disease models.”

Checkpoint Kinase 1 (CHK1)

Targeting lung, pancreatic and other cancers, in partnership with the CRT Pioneer Fund

Preclinical toxicology studies to determine initial doses to be used in Phase I clinical trials were completed during 2015, as was the production of a GMP (Good Manufacturing Practice) batch of the drug candidate, CCT245737, for administration to patients in these trials.

Applications for two clinical trials in cancer patients were made to MHRA, the UK regulator, in January 2016 and trials are expected to commence shortly after approvals are obtained.  One trial plans to examine CCT245737 in combination with other standard-of-care chemotherapies, ultimately targeting lung and pancreatic cancers. The second trial plans to assess CCT245737 as a single anti-cancer agent in patients with various cancer types.

The evaluation of CCT245737 in the two planned trials will be facilitated by the use of biochemical tests, known as biomarkers. These biomarkers can demonstrate that the candidate drug is performing as expected, by quantitatively measuring the degree of CHK1 inhibition in cancer patients.  A novel biomarker strategy has been developed by scientists at the Institute of Cancer Research, funded by the Sareum and CRT Pioneer Fund co-development partnership, which is intended for use in these trials.


Targeting AML and other blood cancers, in partnership with HMUBEC

The work is being performed at two Chinese CROs with strong experience of preclinical development to the standards required by the China FDA and US FDA. This preclinical development is being funded entirely by HMUBEC.

The drug candidate has been assessed in a wide range of disease models which confirmed AML, and particularly FLT3 mutant AML, as the initial therapeutic target. Development of a biomarker strategy to support future Phase 1 clinical trials has commenced and is making good progress.

There were significant challenges to overcome in order to convert the synthetic route used during the discovery phase, where only small quantities of compound are required, into a route capable of delivering kilogram quantities of GMP grade material for toxicology testing and clinical trials. These challenges have been addressed, such that large quantities of material are now available to support toxicology and safety pharmacology studies which should be completed in 2016.  

Toxicology studies, which will determine the initial doses to be used in the planned Phase 1 trial, have started.

The intellectual property protecting this programme has been strengthened further, with patents being granted in Europe and the USA (September 2015).



Targeting psoriasis, rheumatoid arthritis and other autoimmune disorders, in partnership with SRI International


Following its success in a psoriasis model, the programme lead compound, SAR-20347, has also been shown to reduce joint inflammation in a dose-dependent manner in a rheumatoid arthritis model, being more effective than a commonly-used steroid treatment. Additional model studies indicate that this disease model efficacy is due to specific TYK2-dependent pathway inhibition, rather than general immunosuppression. Importantly, we were also able to demonstrate this TYK2-dependent pathway inhibition in human blood-derived immune cells.

The next steps are to evaluate SAR-20347 in disease models of IBD, multiple sclerosis and lupus. New analogues have recently been synthesised and initial analysis indicates improved activity and selectivity over SAR-20347. These molecules will be evaluated in relevant disease models in due course.

Targeting T-ALL and other cancers

Initial studies, assisted by funding of £140k from the Innovate UK Biomedical Catalyst Fund, to investigate the potential of our lead molecules to inhibit TYK2 signalling to treat T-ALL have shown sufficient validation to warrant further investigation. The next steps will be to scale up the synthesis of example lead compounds to study their effects in disease models and these studies will continue through to August 2016.


Background on Sareum’s cancer and autoimmune disease research programmes


CHK1: Most chemotherapies work by damaging the DNA of rapidly dividing cells. In response, cancer cells can activate an enzyme, known as CHK1, which delays cell division and gives cancer cells an opportunity to repair their damaged DNA. This enables the cancer cells to survive the DNA damage and become resistant to the cell-killing effects of chemotherapeutic agents.


Studies have shown that oral dosing of CCT245737, the CHK1 clinical development candidate being funded by the Sareum / CRT Pioneer Fund co-development partnership, and other lead series compounds can boost the activity of relevant chemotherapies in in vivo models of lung, pancreatic and colon cancers. Furthermore, strong efficacy has been demonstrated by these inhibitors when dosed as a single anti-cancer agent in several in vivo models, including those of AML (Acute Myeloid Leukaemia) lymphoma and paediatric neuroblastoma.

A detailed description of CCT245737 was published in the high-impact journal, Oncotarget, in July 2015.

Aurora+FLT3: Mutations to FLT3 kinase, including ITD (Internal Tandem Duplication) are the most common genetic defects associated with AML. Patients with AML that carry these mutations have significantly poorer outcomes. Aurora kinase activity is required for cell division and is often found to be over-activated in cancer cells. It is thought that a combination of FLT3 and Aurora kinase inhibition will be able to target AML whilst being less susceptible to the drug resistance observed in the clinic with FLT3 specific inhibitor molecules such as Quizartinib.

In in vivo disease models of AML, the candidate molecule demonstrates greater than 98% tumour inhibition. The molecule also has potent cell-killing activity against other cancers, particularly Acute Lymphoblastic Leukaemia (ALL), neuroblastoma and Anaplastic Large-Cell Lymphoma.

TYK2 is a member of the JAK kinase family. These play a key role in many autoimmune and inflammatory diseases. Their over stimulation results in the excess production of cytokines (signalling molecules) that lead to diseases such as psoriasis, rheumatoid arthritis, inflammatory bowel disease (IBD) and multiple sclerosis.

Reports in the scientific literature have also identified TYK2 inhibition as a potential strategy to directly target the growth of certain cancers, or to overcome resistance to targeted drugs in the treatment of certain cancers.  Cancers potentially requiring TYK2 signalling to spread or to develop resistance include small cell lung cancer, bone cancers and T-ALL, a type of leukaemia that predominantly affects children and adolescents.





Sareum Holdings plc


Tim Mitchell

01223 497 700

WH Ireland Limited (Nominated Adviser and Co-Broker)

Chris Fielding / Nick Prowting

020 7220 1650

Hybridan LLP (Co-Broker)


Claire Noyce / William Lynne

 020 3764 2341 / 2342

The Communications Portfolio (Media enquiries)


Ariane Comstive

07785 922 354




Notes for editors:

About Sareum Holdings plc

Sareum is a drug discovery and development company delivering targeted small molecule therapeutics, focusing on cancer and autoimmune disease, for licensing to pharmaceutical and biotechnology companies at the pre-clinical or early clinical trials stage.

Sareum operates an outsourced research model, working with collaborators (SRI International, the CRT Pioneer Fund and Hebei Medical University Biomedical Engineering Center) and a world-wide network of research providers.  Its research pipeline includes a programme awaiting approval to start clinical trials and another undergoing preclinical IND-enabling studies.

SKIL® (Sareum Kinase Inhibitor Library) is Sareum's drug discovery technology platform that has so far produced the Company's Aurora+FLT3, Aurora+ALK, VEGFR-3, FLT3 & TYK2 kinase cancer and auto-immune disease research programmes. SKIL® can also generate drug research programmes against other kinase targets.

Sareum Holdings plc is listed on the AIM market of the London Stock Exchange, trading under the symbol SAR. For further information, please visit www.sareum.co.uk


- Ends -