PTIL Protherics (MM)

SIGNATURES

Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned, thereunto duly authorized.

PROTHERICS ANNOUNCES INTERIM RESULTS

FOR SIX MONTHS ENDED 30 SEPTEMBER 2007
 

Strong progress in broad late-stage pipeline
 

Sharp rise in revenues, gross profits and cash position

London, UK, Brentwood, TN, 20 November 2007 - Protherics PLC (“Protherics” or the “Company”), the biopharmaceutical company focused on critical care and cancer, today announces its unaudited interim results for the six months ended 30 September 2007.

Operational Highlights

Financial Highlights
 

Commenting on the results, Stuart Wallis, Chairman, said:
 

“Protherics delivered good progress in the first half with its broad clinical pipeline and has today announced that the phase 2 DEEP study in pre-eclampsia has completed recruitment. We have also generated a significant increase in revenues and gross profits due to the strong market performance of CroFab and DigiFab. With CytoFab, the scaled up manufacturing process has produced a highly potent product, allowing us to defer much of our investment in manufacturing until the start of phase 3 with no anticipated impact on product launch. AstraZeneca is expected to start its CytoFab phase 2 programme imminently.
 

“The rest of our development pipeline continues to advance as planned, with six phase 2 programmes expected to be on-going in 2008, including the phase 2b severe pre-eclampsia study which is on track to deliver results in the second quarter of 2008. With a diverse and developing portfolio, strong trading and a robust cash position, we are confident in Protherics’ prospects.”

| Ends |
 
 

There will be an analyst meeting at 9.30am UK time on Tuesday 20 November 2007 in London at the offices of Financial Dynamics at Holborn Gate, 26 Southampton Buildings, WC2A 1PB. There will be a simultaneous conference call and webcast. For further details, please contact Mo Noonan on +44 (0)20 7269 7116. To access the webcast please visit www.protherics.com
 
 

For further information contact:

Notes for Editors:
 

About Protherics

Protherics (LSE: PTI, NASDAQ: PTIL) is a leading biopharmaceutical company focused on the development, manufacture and marketing of specialised products for critical care and cancer.
 

Protherics has developed and manufactures two biologics for critical care which are FDA approved and currently sold in the US: CroFab™, a pit viper antivenom and DigiFab™, a digoxin antidote. The Company’s strategy is to use the revenues generated from its marketed and out-licensed products to help fund the advancement of its broad, late stage pipeline.
 

Protherics has two major development opportunities in its critical care portfolio. CytoFab™ is being developed by AstraZeneca, for the treatment of severe sepsis, after a major £195 million licensing deal with AstraZeneca in December 2005. An additional, expanded phase 2 programme is due to start shortly. In addition, Protherics is currently undertaking a phase 2b study with Digoxin Immune Fab for the treatment of pre-eclampsia. This study is expected to report in the first half of 2008.
 

Protherics has a pipeline of four novel cancer products in clinical development, and intends to undertake the sales and marketing of these products in the US and or the EU. Protherics is preparing to resubmit a BLA for Voraxaze™, an adjunct to high dose methotrexate therapy, under a rolling submission in the US starting in H1 2008.

Protherics has a strong cash position, with cash balances at 30 September 2007 of £46.9 million, having completed a £38 million equity fundraising in January 2007 and received a £10 million milestone payment from AstraZeneca in April 2007.
 

With headquarters in London, the Company has approximately 290 employees across its operations in the UK, US and Australia.
 

For further information visit: www.protherics.com

Disclaimer

This document contains forward-looking statements that involve risks and uncertainties including with respect to future growth, technology acquisitions, product sales and manufacturing, and regulatory approval of Protherics’ products for marketing and distribution. Although we believe that the expectations reflected in such forward-looking statements are reasonable at this time, we can give no assurance that such expectations will prove to be correct. Given these uncertainties, readers are cautioned not to place undue reliance on such forward-looking statements. Actual results could differ materially from those anticipated in these forward-looking statements due to many important factors, including the market for the Company’s products, the timing and receipt of regulatory approvals, the successful integration of acquired businesses and intellectual property, and other factors discussed in Protherics’ Annual Report on Form 20-F and other reports filed from time to time with the U.S. Securities and Exchange Commission. We do not undertake to update any oral or written forward-looking statements that may be made by, or on behalf of, Protherics.

INTERIM STATEMENT

Corporate Overview

Protherics’ strategy is to build a leading biopharmaceutical company, focused on the development, manufacture and marketing of specialist products in critical care and cancer. The performance of our marketed critical care products, CroFab™ and DigiFab™, over the six month period has been strong, with excellent underlying and reported growth. With increased investment in R&D, substantial progress has been made in our development pipeline over the period: we continued to focus on the work required to support our regulatory submissions for Voraxaze™, provided CytoFab™ clinical trial material to our partner AstraZeneca and moved several of our development programmes into phase 2 development.
 

Progress has also been made in realising value from our non-core assets gained through our acquisitions of MacroMed Inc. and CoVaccine B.V. A licensing agreement was signed with Nobilon B.V., the human vaccine development unit of Organon BioSciences which was recently acquired by Schering Plough. Nobilon will use our CoVaccine HT adjuvant in the development of a seasonal elderly flu vaccine and a pandemic flu vaccine. An agreement was also signed with MyungMoon Pharm. Co. Ltd. for the use of our ReGel™ injectable, thermosensitive sustained release polymer delivery system for the development of anti-inflammatory products for the treatment of arthritis. We also have interest from a number of other parties in our non-core assets.

R & D pipeline update

CytoFab™ - for sepsis resulting from uncontrolled infection

CytoFab™ is an anti-TNF-alpha polyclonal antibody fragment (Fab) product for the treatment of sepsis, which was out-licensed to our partner, AstraZeneca, in December 2005. Protherics has completed the manufacturing process scale up at its approved facility in Wales, and large scale batches of CytoFab™ have been produced using the new commercial process. The results of this work have been extremely pleasing on several fronts. Firstly, preclinical models have revealed good comparability of the scaled up, revised process with the clinical trial material used in our previous phase 2b study. Secondly, the product yields and batch consistency of the manufactured material are in line with expectations.
 

Thirdly, and importantly, the potency of the new material is considerably ahead of our expectations, reducing our requirement for serum and consequently the number of batches that need to be processed to meet demand on launch. This means that Protherics can use its existing manufacturing facility in Wales to supply product for market launch without the need for a larger standalone production facility. As a result, the majority of the manufacturing investment to build a second facility will be deferred until the end of the phase 2 study, with no anticipated impact on the timing of product launch. With the next milestone payments largely allocated to manufacturing investment, it has been agreed with AstraZeneca that the schedule of the milestone payments to Protherics will remain as per the original licensing agreement in 2005. As a result, Protherics expects to receive its next milestone payment in 2010.
 

AstraZeneca is poised to start its expanded 480 patient phase 2 programme having recently held a clinical investigators meeting and initiated several of the trial sites. We all look forward to CytoFab™ again being administered to patients with this life-threatening condition.
 

CytoFab™ revenues of £1.1 million were recognised in the six months ended 30 September 2007 compared to £1.1 million in the corresponding six months period to 30 September 2006.
 

Digoxin Immune Fab – treatment of pre-eclampsia
 

Protherics has the rights to use Digoxin Immune Fabs (DigiFab™ and GlaxoSmithKline’s Digibind®) as potential treatments for pre-eclampsia, a potentially life-threatening condition of pregnancy occurring in approximately 7-9% of pregnancies. With no products currently available to treat this condition, and very few in development, Digoxin Immune Fabs have the opportunity to meet a considerable unmet need in the treatment of pre-eclampsia.
 

Recruitment in the phase 2b DEEP study to investigate the use of Digibind® in 50 patients with severe pre-eclampsia has been completed and the last patient dosed. The study is on track to report in the second quarter of 2008. 
 

Voraxaze - for the control of high dose methotrexate therapy in cancer

Voraxaze™ (glucarpidase) contains an enzyme that rapidly breaks down the cancer drug methotrexate (MTX). Voraxaze™ has been developed to prevent or reduce the serious and potentially life threatening toxicity that can result when patients receiving high doses of MTX (HDMTX) for the treatment of cancer have difficulty eliminating MTX from the body.
 

Protherics has commenced the additional manufacturing work requested by the FDA to support a Voraxaze™ marketing application in the US.  We have agreed the design of a small study to address the interaction of Voraxaze™ with leucovorin with FDA and the protocol has been filed to our IND. The study is expected to commence at the start of 2008. Protherics has requested a meeting with the EMEA to discuss the suitability of this study to support a potential re-submission of a Marketing Authorisation Application in the EU.
 

Voraxaze™ continues to be available in Europe and elsewhere outside the US on a named patient basis. In the US it is being supplied under a Treatment Protocol with recovery of development costs. In Europe, revenues for the six months ended 30 September 2007 amounted to £0.8 million (£0.6 million in 2006), while revenues from Treatment Protocol in the US were £0.4 million, ahead of our expectations.
 

OncoGel™ – locoregional control of solid tumours
 

OncoGel™ is a novel locally-administered sustained-release formulation of paclitaxel, an established chemotherapeutic for the treatment of solid tumours.
 

Following the successful phase 2a oesophogeal cancer study which was reported in May 2007, we recently initiated a randomized multinational phase 2b study to evaluate OncoGel™ administered in combination with pre-operative chemoradiotherapy versus pre-operative chemoradiotherapy alone in 124 patients. The primary endpoint of the study is a blinded assessment of tumour response with overall survival a secondary endpoint. Protherics expects to have preliminary data available from the phase 2b study in 2010.
 

In March, we initiated a phase 1/2 study of OncoGel™ in primary brain cancer and we have completed recruitment of patients into the first dose cohort. The Data Safety Monitoring Board has considered data from the first cohort of three patients, which includes serious adverse events that may be related to treatment with OncoGel, and has recommended continuing the study with a modified protocol; further recruitment into the study is pending agreement with FDA.
 

Prolarix ^TM – targeted therapy for liver cancer and certain other solid tumours
 

Prolarix™ is comprised of a small molecule prodrug, tretazicar, which is converted to a highly cytotoxic agent when administered with its cosubstrate, caricotamide, by an endogenous enzyme, NQ02. This enzyme has elevated activity in certain tumours, in particular hepatocellular carcinoma (HCC) offering a potentially selective therapeutic effect.
 

A phase 1 study of Prolarix™ is being run under the auspices of Cancer Research UK (CRUK). The maximum tolerated dose (“MTD”) for Prolarix™ has been determined, and an additional cohort of six patients is being recruited to evaluate the effects of repeated cycles of Prolarix™ on various tumour types. The study is expected to complete in the first half of 2008. Having reached the MTD, Protherics plans to start a phase 2 programme in the first half of 2008 to investigate tumour responses in primary liver cancer (HCC) patients treated with up to six cycles of Prolarix™. This phase 2 programme will comprise an open-label run-in to a larger controlled study in which Prolarix™ will be added to sorafenib and compared with sorafenib alone. The open-label run-in should provide an early indication of potential efficacy in HCC patients.
 

Acadra™ (acadesine) – selective therapy for B-cell Chronic Lymphocytic Leukemia (B-CLL)
 

Most drugs used to treat B-CLL by killing B-cells also kill T-cells, increasing the risk of serious infection, a common cause of death in patients with B-CLL. Acadra™ is a potentially selective treatment for B-CLL: it has been shown to cause the death of B-cells whilst sparing T-cells when administered to blood samples taken from patients with B-CLL. It has also been shown to cause the death of B-cells when administered to the blood of patients who are refractory to fludarabine, one of the most commonly used treatments for B-CLL.
 

Protherics and its co-development partner, Advancell, have initiated a phase 1/2 study with Acadra™ in patients with recurrent or refractory B-CLL. The study is being undertaken in Belgium, France and Spain and will enroll up to 30 B-CLL patients. Part I of the study is an open-label assessment of the safety and tolerability of escalating single doses of Acadra™ followed, in Part II, by an assessment of repeated doses for up to 5 cycles of treatment. In addition to safety and tolerability, the pharmacokinetics of acadesine and its active metabolite, ZMP, will be determined and its effects on B-cell and T-cell counts will be assessed. Part I of the study is expected to be completed around mid-2008, with the intention of providing initial evidence of a potential selective effect, with the final study results expected in H1 2009.
 

Angiotensin Therapeutic Vaccine – management of high blood pressure
 

Protherics’ Angiotensin Therapeutic Vaccine is designed to induce endogenous antibodies to angiotensin, one of the key hormones involved in the regulation of blood pressure. Encouraging clinical and preclinical results suggest that effective neutralisation of angiotensin may cause a clinically significant reduction in blood pressure in hypertensive patients.
 

Protherics intends to start a phase 2a study with the new formulation which incorporates our novel adjuvant, CoVaccine HT, in the first half of 2008. The goal of this study will be to confirm that the new formulation increases levels of anti-angiotensin antibodies in hypertensive patients and to establish whether this results in a reduction in blood pressure. On successful completion of this study we intend to out-license the vaccine.
 

Marketed Products, Business Environment and Financial Update
 

CroFab™ [Crotalidae Polyvalent Immune Fab (Ovine)] – pit viper antivenom
 

CroFab™ is a polyclonal antibody fragment for the management of minimal or moderate North American crotalid (pit viper) envenomation. It is currently the only product marketed for these bites in the US, where there are around 8,000 pit viper bites reported each year. We believe that CroFab™ continues to increase its market penetration and has now captured over half of a potential $70-80 million per annum market opportunity.
 

CroFab™ sales were £10.3 million in the half year compared to £7.2 million in the corresponding six months to 30 September 2006. The improvement in sales was driven by higher shipments of product to Fougera during the biting season and an increase in product sales.
 

DigiFab™ [Digoxin Immune Fab (Ovine)] – treatment for life-threatening digoxin toxicity
 

It is estimated that 16 million digoxin prescriptions were written in the US in 2006 (IMS data). Digoxin has a narrow therapeutic range, and toxicity is estimated to occur in 26% to 29% of all patients. Moreover, reported digoxin toxicities in the US were 10.5% higher in 2005 than in 1995 (AAPCC data).
 

DigiFab™ is now the market leader in the US digoxin toxicity market, estimated to be worth approximately $25 million per annum. Sales by our distributor, Fougera, to the wholesale market increased by 24% over the prior period.
 

The Company’s focus on delivering CroFab™ during the snake bite season has necessarily led to timing the manufacture of DigiFab™ into the second half of the year, thereby leading to a reduction in shipments of DigiFab™ in the first half of 2007. As a result, total DigiFab™ revenues remained steady at £1.9 million but with a strong order backlog, the Company anticipates that shipments in the second half and over the full year will exceed that of the prior year.
 

The regulatory review process to gain marketing approval in Europe via an initial approval in the UK has been very slow and we have now been requested to supply more data to support the application made by Beacon Pharmaceuticals, our licensee in most mainland European countries. Named patient sales of DigiFab™ outside of the US continue to increase.
 

ViperaTAb ™ – European viper antivenom
 

ViperaTAb ™ sales at £0.2 million were marginally down on the prior year (2006: £0.3 million).
 

Impact of US $ exchange rate
 

US derived revenues show the underlying sales performance in US dollars increased by 41% year on year. The weakening of the US $ to the £ resulted in an average exchange rate of $2.01 (2006: $1.85)
 

Named patient sales of Voraxaze ™ outside of the US increased by 33% to £0.8 million in the half year ended 30 September 2007 from £0.6 million in the corresponding six month period, as awareness of the product in the medical community continues to build. In addition, the FDA allowed Protherics to supply Voraxaze in the US under a Treatment IND with cost recovery resulting in an additional £0.4 million of revenues in the period.
 

CytoFab ™ revenues of £1.1 million for the six months represent a portion of the initial upfront payment of £16.3 million received under the licensing agreement with AstraZeneca, which is being recognised under IFRS over the estimated period to product approval. Revenues from BSE testing remain constant at £0.1 million.