Start Of Prolarix™ Phase 2 Study In Liver Cancer

Protherics PLC ("Protherics" or the "Company"), the international biopharmaceutical company focused on critical care and cancer, announces the initiation of a phase 2a proof-of-concept study of Prolarix™, a targeted prodrug chemotherapy being developed for the treatment of primary liver cancer (hepatocellular carcinoma or "HCC"). This follows promising data from a phase 1 study of Prolarix, presented at the American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, USA on 2 June 2008.


HCC is the sixth most common cause of cancer in the world1 and despite the recent approval of sorafenib (Nexavar®, Onyx/Bayer), a new chemotherapy which is being adopted as the standard of care for HCC, life expectancy remains less than 12 months from diagnosis. Moreover, less than 20% of patients survive beyond one year, and less than 5% survive beyond five years.


The phase 2a proof-of-concept study is designed to evaluate tumour response in addition to safety and tolerability of Prolarix in 14 patients with non-resectable HCC who have not been treated with sorafenib. The study has been initiated at a site in Belgium and additional study sites in East Asia have been identified for inclusion in the study. The results of the study are expected in the second half of 2009.


Andrew Heath, Chief Executive of Protherics commented:


"Scientifically acclaimed, Prolarix offers renewed hope for the many patients with primary liver cancer for whom there are very few treatment options. If the results from this study are positive, a licensing partner will be sought for Asia where the incidence of this type of cancer is highest."


1 Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002 CA Cancer J Clin. 2005;55;74-108



About Protherics


Protherics (LSE: PTI, NASDAQ: PTIL) is a leading international biopharmaceutical company focused on specialist products for critical care and cancer.



The Company has two critical care products, CroFab™ and DigiFab™, approved for sale in the US. The Company has the opportunity to sell these products in the US from October 2010 together with Voraxaze™, a supportive cancer care product, following anticipated approval in the US in 2010. Protherics is also developing a number of other products in the cancer arena that it can commercialise in-house.


In addition, Protherics has several potential blockbuster products that require development and commercialisation partners. These include CytoFab™ which has been partnered by AstraZeneca in a major licensing deal, and also Angiotensin Therapeutic Vaccine and Digoxin Immune Fabs for which licensing partners will be sought in 2008-2009. These products have the potential to be high value products that can provide additional funding for the Company.















Protherics reported revenues of ??26.1 million for the year ended 31 March 2008 and a strong cash balance of ??37.7 million. With headquarters in London, the Company has approximately 300 employees across its operations in the UK, US and Australia.


About Prolarix™


Prolarix is a targeted chemotherapy being developed for the treatment of primary liver cancer (hepatocellular carcinomas, HCC) and other select tumours. Prolarix is a combination therapy of two low molecular weight compounds, a prodrug* (called tretazicar; previously CB1954) and an enzyme co-substrate* (called caricotamide; previously EP-0152R). The prodrug tretazicar can be activated by an endogenous enzyme called NQO2, to a highly reactive, short-lived cytotoxic agent which causes a high degree of DNA cross-linking. The NQO2 enzyme is latent and therefore inactive in body tissue, but Protherics' scientists have discovered that the enzyme is active in the presence of a co-substrate called caricotamide. The NQO2 enzyme is absent or in low levels in many normal body tissues, including bone marrow, but its activity is increased in certain tumour types (particularly hepatocellular carcinomas). The coadministration of the prodrug tretazicar and the cosubstrate caricotamide is therefore expected to result in the enhanced activation of the prodrug in the target tumour cells, resulting in their death whilst minimising harm to healthy, non-cancerous cells.


Glossary


Prodrug* - A compound that is converted within the body into its active form and that has no therapeutic effects of its own. A prodrug is useful when the active drug may be too toxic to administer systemically, the active drug is absorbed poorly by the digestive tract, or the body breaks down the active drug before it reaches its target.


Co-substrate* - A molecule that interacts with an enzyme and is required for its activity.


Cytotoxic* - A chemical which has a direct toxic effect to cells, causing their death.


Tretazicar* is 5-(aziridin-1-yl)-2,4-dinitrobenzamide (CB1954), an antitumour prodrug

Caricotamide* is 1-carbamoylmethyl-3-carbamoyl-1,4-dihydropyridine (EP-0152R), the most stable of a series of co-substrates for NQO2 discovered by Protherics


Protherics PLC


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