Proteome Regulatory News (PRM)

Proteome Sciences plc ("Proteome Sciences" or the "Company")

Preliminary results for the year ended31st December, 2013

29th May, 2014

§ Revenue increased 86% to £2.14m (2012: £1.15m)

§ Licences / Sales / Services revenue up 137% to £1.92m (2012: £0.81m)

§ TMT® reagent sales rose 63% in 2013

§ Loss after tax reduced 26% to £3.15m (2012: £4.25m)

§ Cash at year-end £0.60m (2012: £0.86m). Placing of 3.57m shares in February 2014 raised £5m

§ Significant benefits from the launch of TMT® 10-plex

§ Strategic $2.1m licence and research agreement with Thermo Fisher Scientific

§ Sharp growth in biomarker assays assisted by SysQuant® workflows

§ 17 patents granted , further 32 applications filed

§ Our Alzheimer's disease research endorsed by David Cameron in Keynote G8 Summit speech

Outlook

§ Strong licences / sales / services growth

§ Increased pipeline and interest in biomarker services

§ Expansion of SysQuant® coverage in cancer and CNS

§ Customer shift from pilot studies to large scale projects

§ TMT® growth running close to double 2013 levels

§ New biological data showing wider mode of action for Ck1d outlicensing

§ SysQuant® trial in liver cancer planned for 2014

Commenting on these results, Christopher Pearce, Chief Executive of Proteome Sciences, said:

"Strong progress has been made in 2014 across our three core activities: PS Biomarker Services™, Proprietary Biomarkers and TMT® reagents. TMT® reagents have become the market leader and growth is running at close to double 2013 levels.

Our pipeline and interest in biomarker services is expanding quickly as customers shift from pilot studies to large contracts with more expected to follow. SysQuant® and TMT® calibrator significantly differentiate Proteome Sciences in the marketplace. We believe that these will make a considerable contribution to our assay portfolio and underpin our position in Personalised Medicine.

We are very encouraged by the results of our blood biomarkers for the diagnosis of early stage Alzheimer's disease which show positive predictive accuracy of 94% in Alzheimer's and 88% in mild cognitive impairment. Furthermore, we are delighted that we have received confirmation that the related 1000 sample study undertaken with King's College Hospital is to be published in a major peer review journal. These important developments bring the prospect of a blood test for the early stage diagnosis and prognosis of Alzheimer's Disease considerably closer.

Against this background, we are confident that we should see fast growth in revenues across the business for the foreseeable future."

Attached: summary Chairman's message and operational review, consolidated income statement, consolidated balance sheet, consolidated statement of changes in equity, consolidated cashflow statement and notes to the financial statements.

ENDS

Cautionary statement on forward-looking statements

This document contains certain forward-looking statements relating to the Group. The Group considers any statements that are not historical facts as "forward-looking statements". They relate to events and trends that are subject to risk and uncertainty that may cause actual results and the financial performance of the Group to differ materially from those contained in any forward-looking statement. These statements are made by the directors in good faith based on information available to them and such statements should be treated with caution due to the inherent uncertainties, including both economic and business risk factors, underlying any such forward-looking information.

For further information please contact

Proteome Sciences plc:

www.proteomics.com 

Tel: +44 (0)1932 865065

Christopher Pearce, Chief Executive

Email: christopher.pearce@proteomics.com

James Malthouse, Finance Director

Email: james.malthouse@proteomics.com

Ian Pike, Chief Operating Officer

Email: ian.pike@proteomics.com

Advisers:

Nominated Adviser:

Cenkos Securities plc

Stephen Keys / Camilla Hume

Tel: +44 (0)7397 8900

Notes to Editors:

About Proteome Sciences:

Proteome Sciences, Cobham, UK is a global leader in applied proteomics and peptidomics offering high sensitivity, proprietary technologies for protein and peptide biomarker discovery, validation and assay development. PS Biomarker Services™ uses isobaric and isotopic Tandem Mass Tag® (TMT®) workflows developed on the latest Orbitrap® Fusion Tribrid, Orbitrap® Velos and TSQ Vantage mass spectrometers to deliver rapid, robust and reproducible biomarker assay development outsourcing solutions for customers in the pharmaceutical, diagnostic and biotechnology sectors. Services are provided from its ISO 9001: 2008 accredited facilities in Frankfurt, Germany. By combining Selected Reaction Monitoring (SRM) and TMT® workflows, highly multiplexed assays can be developed rapidly and are suitable for screening hundreds of candidate biomarkers in larger validation studies and transferred for immunoassay development. The Company's own research has discovered a large number of novel protein biomarkers in key human diseases primarily in neurological, neurodegenerative conditions and cancer and for chemical sensitizers. Patented blood biomarkers, including Alzheimer's disease, stroke, brain damage, cancers and chemical sensitizers are available to license for diagnosis, monitoring and treatment.

Preliminary results for the year ended

31st December 2013

Considerable progress was made in each of the three main business divisions - proprietary biomarkers, biomarker services and reagents and these were reflected in the 86% growth in 2013 revenue.

The number of biomarkers covered by our assays grew sharply assisted by further developments from our SysQuant® global phosphorylation workflow. New tests launched included the Breast Cancer Triplex Assay, CSF 16-plex TMT®-SRM assay and assays in Alzheimer's Disease (AD) for Amyloid Beta, Tau and Phospho Tau. This trend is expected to continue.

We concluded a strategically important $2.1m licence and research agreement with Thermo Fisher Scientific for MS3 TMT® where Proteome Sciences was provided with cash and state-of-the-art equipment. Our SensiDerm™ multiplex assay was selected by Cosmetics Europe in the first set of in vitro priority tests for development and optimisation as replacement for animal testing following the EU ban in 2013.

Results presented at the Alzheimer's Association International Conference and at HUPO on CK1d confirmed that our two lead compounds caused a dramatic drop in the amount of phosphorylated tau protein in the brain, an effect increasingly recognised as key to the development of effective Alzheimer's treatments.

The general introduction of TMT® 10-plex and the MS3 three stage fragmentation methodology following favourable critical exposure at the ASMS meeting from the key opinion leaders, created a buoyant background which is expected to grow further as the products start to be used in wider applications in systems biology.

All of these elements are key contributors to the development and implementation of Personalised Medicine.

Revenue

The Group's operations are organised into three geographic regions: United Kingdom, Germany and US. Internal reporting on performance is allocated accordingly. The Group also manages the performance of the business according to its major products and services, as set out below:

Licences / Sales / Services

Strong performance in 2013

Revenue increased by 86% during the year to £2.14m (2012: £1.15m). In the breakdown, Licences/Sales/Services rose 137% to £1.92m (2012: £0.81m) of which TMT® Reagent sales increased by 63%. Grant Services were £0.22m (2012 £0.35m). The drive to increase sales of our products and services through expanded business development activities was strongly reflected with an 86% increase in 2013 revenue.

With a growing pipeline of contracts, as we continue to raise our corporate and research profile, further strong performance is expected from licences, products and services that should result in a significant increase in revenue again in 2014.

PS Biomarker Services™

We delivered a 137% increase in licences, sales and contracts to £1.92m (2012: £0.81m) through the addition of a number of new tests and workflows and the pace of growth and development continues to move rapidly ahead in 2014.

In 2013 we announced the licence/research contract with Thermo Fisher Scientific using MS3 TMT®. This represents a significant breakthrough in the application of mass spectrometry over existing LC-MS/MS and one which unlocks a much wider range of proteomic applications for basic research, drug discovery and diagnostics. The new workflows provide considerably improved quantitative performance and results and MS3 TMT® services can only be accessed from Proteome Sciences.

Through TMT® Calibrator, we have developed antibody-free methods for relative or absolute quantitation of multiple biomarkers by mass spectrometry achieving sensitivity, accuracy and reproducibility similar to ELISA. This is powered by MS3-TMT® 10-plex and uses an internal 4-point calibration curve.

After the launch of the triplex breast cancer tests (BTSA), a first contract was successfully completed for a pharmaceutical company with further contracts expected to follow on. The test measures changes in three key proteins: oestrogen, progesterone and HER2 for regular monitoring of the changes taking place in the patient's tumours and resistance to select the best therapy for the patient at that time. This will help the way clinicians manage breast cancer and should significantly improve patient outcome.

As pharmaceutical companies increasingly switch their programmes in AD to address tau in combination with beta amyloid for the next generation of drugs and patient management, our efforts have been focused on the development of a comprehensive range of biomarker tools and services. We have released novel plasma and CSF based targeted assays for the detection of known and potential Alzheimer's disease biomarkers:-

- Abeta (Amyloid beta) isoforms assay

- CSF 16-plex assay

- Plasma 9-plex assay

The expansion of our assays and workflows places PS Biomarker Services™ in a pre-eminent position, in particular in AD, to provide a comprehensive range of tools and services to the pharmaceutical and diagnostics industries.

The pipeline and level of interest in biomarker services continues to grow in 2014, reflecting the shift from pilot studies to large scale programmes and this is delivering fast rates of revenue growth.

TMT® revenue -

Fast growth rate is expected to continue

TMT® product sales increased by 63% in 2013. This growth has continued and should be extended in 2014 as TMT® 10-plex reagents become widely available and the planned arrival of TMT® 20-plex and TMT® 30-plex later this year will further expand the coverage and size of the market. The strong endorsement of the key opinion leaders should further increase the visibility and penetration of TMT® into mainstream biology and medical research groups and the pace of growth has accelerated where it is running at close to double 2013 levels.

SensiDerm™

We were delighted the SensiDerm™ 10 protein multiplex TMT®-SRM assay was selected by Cosmetics Europe in April in the first set of priority tests for further development and optimisation. Since that time, we have been actively engaged with Cosmetics Europe and a number of industrial partners in the process. The priority is to introduce fast, accurate and cost effective in vitro assays not only for cosmetics but for other products manufactured with sensitizers/allergens including chemical ingredients and household products all affected by the EU ban on animal testing in March 2013. Similar policies and pressures relating to animal testing are following close behind in the US and Asia. With a novel in vitro SRM testing method and the patents filed over 100 skin and 100 respiratory markers for each, Proteome Sciences now has the prospect of substantial additional revenue streams as animal testing replacements are introduced for a broad range of in vitro applications in industrial testing. Although the timing and amount of funding available from Cosmetics Europe has been delayed, further development of SensiDerm™ is expected in 2014.

Alzheimer's Disease

During his key note address to the G8 Dementia Summit, UK Prime Minister David Cameron drew attention to the ground-breaking work Proteome Sciences is doing discovering and validating blood biomarkers for early stage diagnosis of Alzheimer's disease (AD). The research is at an advanced stage following the announcement of excellent results in the summer showing positive predictive accuracy of 94% in AD and 88% in mild cognitive impairment (MCI) and that brings the prospect of a blood test considerably closer.

In parallel, we were strongly encouraged by the news from our collaborators at King's College, London that they have made a significant step forward to develop a test which could allow doctors to detect AD at an early stage before any noticeable warning signs. Out of thousands of proteins in blood, the group have identified a group of 10, based on results from over 1,000 individuals, that they believe could be used to identify Alzheimer's. Further details are awaited with great interest and are expected to be in the form of a high profile detailed scientific paper that is likely to command considerable media attention.

The KCL research has followed a complementary immunoassay approach to the mass spectrometry workflow developed by Proteome Sciences and this should provide considerable cross validation to our novel biomarkers and workflows.

Proteome Sciences controls the commercial rights relating to both sets of discoveries.

The biomarkers from these two programmes will provide content for three major applications: for patient stratification, for drug testing and for clinical diagnosis in AD. We are actively marketing the results and content to pharmaceutical and diagnostics companies to commercialise these through licences, assays and biomarker services contracts. Each of these application is in a major area of unmet need and will command substantial commercial values.

GAME CHANGERS

SysQuant® - Looking for ways to treat the un-treatable

During the last 12 months we have continued to develop SysQuant®, the proprietary phosphoproteomics workflow, for the analysis of tumour biopsy samples to identify key proteins that can be targeted with existing cancer drugs. The current system for the approval of drugs is based on demonstrating utility in a tumour found in a particular organ or tissue and extending this to other sites. This currently requires separate drug trials. Tumours that are particularly aggressive, such as pancreatic cancer are rarely used to trial new drugs and as such the treatment choices remain limited.

Recent understanding of the causes of cancer suggest that rather than focus on the site of a tumour to select the most appropriate drugs we need to look at the signalling pathways operating in each individual. Targeting two or three of these pathways simultaneously can then provide better treatment outcomes, even in advanced cases. To be able to deliver this highly personalised approach to cancer medicine requires a tool for comprehensive pathway profiling - SysQuant®.

Working with the Department of Hepatobiliary Cancer at King's College Hospital we analysed the tumours of 12 patients with pancreatic cancer using SysQuant®. In total, 6,284 unique phosphorylation sites were quantified along with 2,101 proteins, representing the largest single data set in pancreatic cancer. Significantly, we were able to identify multiple cancer-generating pathways that were activated in the patients with some pathways highly active in all 12 patients whilst others were only found in a subset of the patients. In each case we were able to identify unique combinations of targets for existing anti-cancer drugs that could potentially have provided a superior treatment outcome.

We have made further improvements to the SysQuant® workflow since this study was published in the journal PLOS ONE in March 2014, and we intend to start a prospective trial of SysQuant® to predict outcome in liver cancer this year.

CK1d - rapid progress in biological validation

Strong progress continues to be made with CK1d. Further results and data for the small molecule inhibitors of CK1d in the tau pathway were presented at the 2013 Alzheimer's Association International Conference (AAIC) in Boston and most recent data at the HUPO meeting in Yokohama. These results show that the two lead compounds are orally available, achieve therapeutic levels in the brain of experimental AD models and improve cognitive behaviour. When the tau protein of treated animals was analysed, a dramatic drop was seen in both total levels of tau protein as well as tau phosphorylation. The reduction of tau is recognised as a key goal in the development of effective treatments for Alzheimer's.

To advance the outlicensing process, we have continued to extend the amount of biological data and results supporting our two compounds, PS110 and PS27805. In addition to the normal research methods we applied SysQuant® for the first time in a CNS study to analyse different regions of the brain of treated and control animals. Outstanding results were obtained with over 20,000 unique phosphorylation sites and 8,000 proteins mapped and these provided the most comprehensive analysis to date seen in tau and many other signalling pathways relevant to AD. This confirmed again that our compounds for CK1d reduced tau phosphorylation and identified key pathways relating to energy production, amyloid processing and oxidation changes.

The signalling pathway changes seen using SysQuant® endorse and establish a much wider mode of action for our two lead compounds to prevent tau damage in the brain of mice. This extends their value and utility as important clinical candidates in AD.

The timing of the SysQuant® results is highly opportune ahead of the 2014 AAIC in Copenhagen in July where we will be presenting the data and this will be used as the platform to invigorate licensing discussions.

TMT® - central to improved quantitation

Scientists working to discover protein-based biomedical breakthroughs with the goal of accelerating discovery of effective therapies are constrained by the time and cost required to identify and quantify large numbers of proteins.

TMT® was developed by Proteome Sciences to advance multiplexing technology - the ability to analyse multiple protein samples in a single mass spectrometer run - to gain new insight into complex disease mechanisms. The launch of TMT® 10-plex in 2013, multiplexing 10 protein samples from cells, tissues or fluids "Represented a landmark increase. Combining new isobaric reagents with purpose-driven instrumentation allows for proteome-wide measurements of protein expression differences simultaneously across 10 samples in about 24 hours. It is simply fantastic." according to key opinion leader Dr. Steven Gygi at Harvard Medical School.

Demonstrating the importance of TMT®, an industry-academic collaboration has been set up between Harvard Medical School and Thermo Fisher Scientific to develop new ways of protein quantitation on a much larger scale than currently possible using TMT® and to develop improved methods and training to make this expertise available to the greater scientific community. The combination of TMT® with new generation mass spectrometry technology provides the route to increase the amount of quantitation by orders of magnitude, but importantly without sacrificing data quality.

Thermo Fisher Scientific, the global leader in mass spectrometry, has reiterated that these advances will usher in a new era in functional proteomics, increasing understanding of mechanisms of disease and evaluation of potential new therapies.

TMT® is central to these programmes and this will be reflected through increased usage and sales globally in mainstream systems biology. The planned launch of TMT® 20- and 30-plex in 2014 should increase and accelerate that process.

Acceleration in Biomarker Services

The main focus continues to be the expansion of PS Biomarker Services™ and the amount of assays and services that we provide principally using our own proprietary content. This has been considerably extended through the rapid development and availability of SysQuant® and TMT® calibrator workflows.

The Orbitrap Fusion mass spectrometer provided as part of the licensing deal with Thermo Fisher Scientific last June was installed at the end of 2013 and this is delivering most impressive results with increases of over 100% in the number of proteins quantified using TMT®. Through this, considerable additional capacity is available to process and expand customer contracts at PS Biomarker Services™.

The pipeline and level of interest in biomarker services continues to grow in 2014, reflecting the shift from pilot studies to large scale programmes. We signed the term sheet for a large biomarker services contract to process a cohort of patient samples from which we aim to develop a companion diagnostic. A pilot study, the prelude to a potential major contract in cancer, has been signed and we are actively finalising a number of new biomarker services contracts with existing and new customers. By way of update we are pleased that the pilot study report just submitted has provided stunning results and should put Proteome Sciences in a strong position to secure the major contract on offer. The process will be further assisted by the appointment of Dr. Chee Gee See as Director of Personalised Medicine who has made a considerable impact in opening new opportunities and applications with the major pharmaceutical companies.

Proteome Sciences has an intense sequence of high profile presentations from April to August at the major global meetings to showcase its leading technology development and applications assays, its assays and services in particular its SysQuant® and TMT® calibrator workflows in cancer and CNS and the expanding multiplex capabilities and growing range of users for TMT® mass tags. These include:

April American Association for Cancer Research (AACR)

May American Society of Clinical Oncology (ASCO)

June American Society for Mass Spectrometry (ASMS)

July Alzheimer's Association International Conference (AAIC)

August 10th Siena Meeting - From Genome to Proteome

The increased exposure and endorsement from key opinion leaders has created the buoyant background to our business and services and this is expected to expand with the increased use of our products and services in mainstream systems biology.

IP portfolio

Our 600 plus patent IP portfolio of key biomarkers across a broad range of diseases, applications and technologies that supports our extensive asset base has been further extended. Another 17 patents were granted in 2013 with a further 32 applications filed over the period. Our IP estate underpins the value that has been created through our research and this will be reflected by licence fees, milestones and royalties.

Financial review

Financial performance

Revenue for the twelve month period ended 31st December, 2013 increased 86% of £2.14m (2012: £1.15m). In the breakdown of revenue, Licences/Sales/Services rose 137% to £1.92m (2012: £0.81m) of which TMT® Reagent sales increased 63%. Grant services were lower at £0.22m (2012: £0.35m) and TMT® Reagent sales increased 63%. The loss before tax was £3.28m (2012: £5.20m) including other gains and losses of £nil (2012: losses of £0.76m).

Costs and available cash

Administrative expenses in 2013 showed a slight fall to £4.92m and are likely to remain relatively constant in 2014. After the R&D tax credit of £0.50m, the loss after taxation for the period was £2.78m (2012: £4.25m). Excluding other gains and losses, the loss after taxation was £2.78m (2012: £3.49m). There was a further reduction (£0.59m) in the level of net decrease in cash and cash equivalents to (£2.77m) (2012: £3.34m). The net cash outflow from operating activities fell to (£2.77m) (2012: £3.34m).

Cash at the year-end was £0.60m (2012: £0.86m). A placing of 3.57m ordinary shares was completed in February 2014 which added £5.00m pre-expenses to the cash total.

Outlook for 2014

Strong progress has been made from three core activities: PS Biomarker Services™, Proprietary Biomarkers and TMT® chemical reagents. The number of assays/products in 2013 increased at a fast pace and was reflected by the significant rise in revenue. This trend is expected to continue during 2014.

The profile of TMT® continues to rise, becoming the market leader and with growth running at close to double 2013 levels.

Our pipeline and interest in biomarker services is expanding quickly as customers shift from pilot studies to large-scale projects with this reflected by the contracts announced to date in the current year and with many more to follow. Strong growth is anticipated from Licences, Sales and Services.

SysQuant® and TMT® calibrator significantly differentiate Proteome Sciences in the marketplace. We believe that these will make a considerable contribution to our assay portfolio and revenues and firmly underpin our position in Personalised Medicine as lead providers of biomarker content and workflows for drug development and early diagnosis. 

Proteome Sciences is exceptionally placed to capitalise on the development of Personalised Medicine through its technology and the biomarkers, assays and services that it has established and these should better reflect the long term value of our business.

Against this background, we are confident that we should see continued fast growth in revenues from our main activities for the foreseeable future.

Steve Harris

Chairman

Unaudited consolidated income statement

For the year ended 31st December 2013

Unaudited consolidated statement of comprehensive income

For the year ended 31st December 2013

Unaudited consolidated balance sheet

As at 31st December 2013

Unaudited consolidated statement of changes in equity

For the year ended 31st December 2013

Unaudited consolidated cash flow statement

For the year ended 31st December 2013

Notes to the unaudited consolidated cash flow statement

Notes to the financial information

1. The financial information set out in the announcement does not constitute the Group's statutory accounts for the years ended 31st December 2013 or 2012. The financial information for the year ended 31st December 2012 is derived from the statutory accounts for that year which have been delivered to the Registrar of Companies. The auditor reported on those accounts; their report was not modified, but contained an Emphasis of Matter - Going Concern statement. It did not contain a statement under s498(2) or (3) Companies Act 2006.

The audit of the statutory accounts for the year ended 31st December 2013 is not yet complete. These accounts will be finalised on the basis of the financial information approved by the directors as set out in this preliminary announcement and will be posted to shareholders next week. After that time, the statutory accounts will be available at the Company's registered office: Coveham House, Downside Bridge Road, Cobham, Surrey KT11 3EP.

While the financial information included in this preliminary announcement has been computed in accordance with International Financial Reporting Standards ("IFRS"), as adopted by the EU, this announcement does not itself contain sufficient information to comply with IFRS. The Group intends to publish full financial statements that comply with IFRS.

2. Basis of preparation - going concern

These financial statements have been prepared on the going concern basis. The Directors have reviewed the going concern principle in the light of the guidance provided by the FRC. The Group's business activities, and the factors likely to affect its future development, are set out in the Annual Report, and include the Group's objectives, policies and processes for managing its capital, its financial risk management objectives and its exposure to credit and liquidity risks.

As at 31 December 2013 the Group had cash resources of £600,262 and realized a loss for the year of £3,149,159. Subsequent to the year end the Group raised a further £5,000,000 (before expenses) through a placing to raise further funds for the development of the Group's activities. As explained in the Strategic Report in the Annual report some of the Group's products are still in the research and development phase and as such the Directors consider that costs could exceed income in the short term. The Group's projections indicate that the Group should have sufficient resources to meet its current obligations as they fall due for at least the 12 months from the date of signing these financial statements, using its available cash resources together with anticipated income from sales, services, outlicensing, grant income and R&D tax credits. The Directors have reviewed the progress and status of the various commercial discussions which are underway in relation to the elements of forecast income, and consider that they represent a reasonable basis for the revenue as forecast, but recognise that there is some risk surrounding the timing and quantum of such revenue, associated with the ongoing research and development and the nature of the business.

The Group is dependent on the unsecured loan facility provided by the Chief Executive of the Group, which is repayable on demand. The Directors are not aware of any reason to conclude that the facility will not continue to be made available to the Group, on the existing terms, for at least 12 months from the date of approval of the financial statements.

Accordingly, having reviewed each of the factors that could impact on the going concern of the Group, the Directors have concluded that no material uncertainties exist that cast significant doubt about the ability of the Group to continue as a going concern for at least the next 12 months and the financial statements have therefore been prepared on the going concern basis.

3. Revenue

During the year a licence and research collaboration agreement was concluded with Thermo Fisher Scientific, with a total value of $2.1m. Revenue recognised in 2013 under this agreement relates to the transfer of the licence to a three-stage mas spectrometry (MS3) fragmentation methodology. This was represented by consideration comprising cash and the loan of equipment by Thermo Fisher Scientific for a period of at least three years. The Directors have concluded that the fair value of the MS3 licence transferred at the commencement of the agreement is represented by the cash and loan of the machine elements of the consideration, and have therefore valued this element of the revenue at the agreed total contract value less the element relating to the ongoing research collaboration agreement.

4. Loss per share from continuing operations

The calculations of basic and diluted loss per ordinary share are based on the followinglosses and numbers of shares.

In 2013 and 2012 the loss attributable to ordinary shareholders and weighted average number of ordinary shares for the purpose of calculating the diluted earnings per ordinary share are identical to those used for basic earnings per ordinary share. This is because the exercise of share options that are out of the money would have the effect of reducing the loss per ordinary share and is therefore not dilutive under the terms of the International Financial Reporting Standard 33.