("Sareum" or the "Company")

Research & Co-Development Collaborations Update

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

Dr Tim Mitchell, CEO of Sareum, said: "We are extremely pleased with the progress that has been made in the last six months across all our programmes, and CHK1 in particular which is reaching a crucial phase of development as it nears its first in-human trials."

Checkpoint Kinase 1 (CHK1) - Targeting Lung, Pancreatic and Other Cancers

CHK1 is a key element of an important biochemical network that controls the repair of DNA damage, including the cancer cell DNA damage triggered by chemotherapy or radiotherapy. Studies have shown that oral dosing of the CHK1 inhibitor being funded by the Sareum / CRT Pioneer Fund co-development partnership, and other lead series compounds can enhance the activity of a relevant chemotherapy in in vivo models of lung, pancreatic and colon cancers. Furthermore, strong efficacy has been demonstrated by these inhibitors in several in vivo models, including AML (Acute Myeloid Leukaemia), lymphoma and paediatric neuroblastoma, when dosed as single agents.

Initial chemistry, formulation and toxicology studies have made good progress as the programme moves through preclinical development and towards Phase I clinical trials.

Ongoing toxicology studies will determine the initial doses to be used in the planned Phase I first-in-human clinical trials. The remaining steps will be to produce and verify a GMP (Good Manufacturing Practice) batch of suitably formulated candidate drug for administration to patients in these trials.

As noted in our October 2014 Final Results statement, this stage of the programme is on-track to complete in Q4 of this year. If successful, a clinical trial application will be made to the UK regulator, MHRA.  If this is approved, human trials in cancer patients would then be initiated.

In parallel, the intellectual property estate that underpins the CHK1 programme continues to be developed. This includes the granting of a patent for one of the inventions associated with the CHK1 cancer programme by the European Patent Office in September 2014. 

Aurora+FLT3 - Targeting AML and Other Blood Cancers

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, 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.

This is our second programme to formally enter preclinical development. As with CHK1, the first task is to demonstrate control of production and to assess its safety profile. Current studies, being conducted by contract research organisations in China and funded by our co-development partners, Hebei Medical University Biomedical Engineering Center, are concentrated on producing larger scale batches of compound for initial safety assessments.

Once these have been successfully completed, the next steps will be to produce further batches of the compound and undertake the pivotal toxicology studies. We expect to substantially complete these studies during 2015 and, if successful, file clinical trials applications early in 2016.

Alongside this preclinical development of the compound intended for intravenous dosing, good progress is being made in developing a new formulation that can be used to administer the candidate molecule via the oral route.

The intellectual property protecting this programme has also continued to strengthen, with patents being granted in Japan (July 2014), China (December 2014) and the USA (January 2015).

TYK2 - Targeting Psoriasis, Inflammatory Bowel Disease and Other Autoimmune Disorders

TYK2 is a member of the JAK kinase family that plays 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, inflammatory bowel disease (IBD) and multiple sclerosis.

In October 2014 we and our collaborators at SRI International reported, in the peer-reviewed Journal of Immunology, the discovery of the TYK2/JAK1 inhibitor, SAR-20347. This molecule, when dosed via the oral route, was shown to reduce the levels of inflammatory cytokines and resulted in a striking decrease in psoriasis disease severity in a standard preclinical disease model.

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

TYK2 has also been associated with the blood cancer T-ALL. T-ALL is a type of leukaemia that predominantly affects children as well as adults. It is thought that inhibition of TYK2 may be effective as a treatment for T-ALL. Accordingly, we have begun to investigate the potential for our TYK2 inhibitors to selectively destroy T-ALL cells.

As with our other programmes, we continue to develop the patents that protect the intellectual property embodied in this programme. In November 2014, the European Patent Office notified us of their intention to grant our patent application that describes some of the molecules developed to date and their use in treating autoimmune diseases.

Sareum Holdings plc
Tim Mitchell 01223 497 700
Sanlam  Securities UK Limited (Nomad)
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Hybridan LLP (Broker)  
Claire Noyce / William Lynne 020 3713 4581 / 4582
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, headquartered in Cambridge UK, that produces targeted small molecule therapeutics, focusing on cancer and autoimmune disease. Sareum aims to successfully deliver drug candidates 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 two programmes undergoing pre-clinical 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