Combining the power of nature and genomics to create new medicines

DemurisTM has a large portfolio of drug projects and state-of-the-art platform technologies in natural product discovery, design and production

The rise in drug resistant pathogens is causing serious health concerns and an increasing economic burden. There is a growing demand for new agents to treat these evolving diseases. Demuris is developing a suite of new antibiotic compounds active in key areas of unmet medical need.

The starting points for Demuris’ portfolio of new drug project portfolio lies in a unique collection of Actinomycete bacteria. These organisms specialise in making natural product (NP) compounds with powerful biological activities that kill or manipulate the behaviour of surrounding organisms, including bacteria, fungi, plants and animals.

Demuris is also developing advanced molecular biology and synthetic biology methods to identify new NPs, and manipulate them to make better drug-like molecules and at much higher yields.

Demuris can also offer its technology platform as a service for academics and companies wishing to discover and develop new drugs.

... only a fraction of the natural products that these bacteria are capable of making has been screened

LATEST NEWS

Demuris and collaborators identify antibiotic with potential to treat Multi-Drug-Resistant Tuberculosis

In the journal Molecular Cell (DOI: https://doi.org/10.1016/j.molcel.2018.08.028) we report the screening and identification of this compound along with its mechanism of action.

Through screening a relatively small number of extracts (only 2,000) from the Demuris Actinomycete Collection we identified the natural product antibiotic kanglemycin A. This compound is produced by an actinomycete bacterium and is similar to rifampicin but has several additional features which give it superior activity.

Biochemical and X-ray crystallography methods enabled us to understand how this compound works. It binds to the essential bacterial enzyme RNA polymerase, but crucially not the human version. It bypasses the normal rifampicin resistance mechanisms by making additional interactions with the RNA polymerase not seen before. It is these interactions that allow it to be active against the mutated and usually resistant version of the RNA polymerase in MDR-TB.

The work at Demuris was funded by Innovate UK and without this support from the UK government this project could not have gone ahead.

We have patented this compound and we are now looking to develop new versions which we expect to be even more active against MDR-TB.

The research project involved a large multidisciplinary team involving Newcastle and Penn State University scientists, Public Health England, Newcastle upon Tyne Hospitals NHS Foundation Trust and Demuris Ltd.

Professor Jeff Errington, CEO at Demuris, said: “This exciting project validates our company strategy of using state of the art genetic and biochemical assays and a uniquely diverse and well dereplicated collection of actinobacteria to discover new antibiotics. We have also benefitted by having access to a world class group of academic scientists covering the microbiology, biochemistry and structural biology methods needed for the project. This is the first of a string of new drug starting points coming from the Demuris portfolio”.

Dr Nick Allenby, Principal Scientist at Demuris, said: “There is an urgent need for new antibiotics to combat drug resistant Mycobacterium tuberculosis.

“We have shown that our compound discovered through a collaboration with Newcastle University is effective against these drug resistant strains.

“However, before we can start to think about using the compound much more work and development is needed. The next step for our compound is to prove that it is safe and effective for use in the clinic.”

Professor Nikolay Zenkin, from Newcastle University’s Institute for Cell and Molecular Biosciences said: “Treatment of TB involves a cocktail of antibiotics administered over many months, and resistance to several key antibiotics is becoming a major public health problem around the world.

“Our findings are very exciting and the first step towards developing a new, effective drug treatment for patients with rifampicin resistant TB to prevent fatalities in the future.”

Dr Michael Hall, from Newcastle University, who led chemical characterization of kanglemycin A, added: “This is an exciting development for the future treatment of rifampicin resistant TB and shows what can be achieved when local businesses and universities work together.”

Demuris Limited
Newcastle Biomedicine Bio-Incubators,
Faculty of Medical Sciences, Framlington Place,
Newcastle upon Tyne, NE2 4HH, UK

Tel: +44 (0)191 223 5608
Fax: +44 (0)191 223 5609
Email: enquiries@demuris.co.uk

Demuris Limited is registered in England, company number: 06255507

Demuris Limited 2015