14th Mar 2006 07:01
Oxford Biomedica PLC14 March 2006 For Immediate Release 14 MARCH 2006 OXFORD BIOMEDICA PLC PRELIMINARY RESULTS FOR THE YEAR ENDED 31 DECEMBER 2005 Oxford, UK - 14 March 2006: Oxford BioMedica (LSE: OXB), the leading genetherapy company, today announces its preliminary results for the year ended 31December 2005. Operational highlights: TroVax(R) (cancer) • Initial analyses of results from Phase II trials in metastatic colorectal cancer with chemotherapy suggest that TroVax improves survival as well as tumour response rate • Initial results from Phase II trials in renal cell carcinoma with interleukin-2 showed good safety and strong immune responses (initial tumour response data from the first few patients will be published at the time of ASCO, June 2006) • Phase III pivotal study protocol for renal cell carcinoma submitted to FDA • Entered discussions with QUASAR on proposed Phase III trial in Stage II/III colorectal cancer MetXia(R) (cancer) • Results from stage one of the Phase II trial in pancreatic cancer confirmed the product's safety and tolerability and showed dose-related gene transfer at the tumour site • Stage two dose escalation of cyclophosphamide progressing according to plan Targeted Antibody Therapy (cancer) • Wyeth presented preclinical data showing encouraging efficacy, including improved survival in a lung cancer model ProSavin(R) (Parkinson's disease) • Preclinical studies confirmed previous conclusions on safety and showed that the product induces almost full recovery to the most recent time point of 20 weeks RetinoStat(R) (retinopathy) • Preclinical results from studies conducted with the Institute of Ophthalmology and Johns Hopkins University showed statistically significant efficacy Technology licensing • Strategic alliance with Sigma-Aldrich to develop and commercialise LentiVector(R)-RNAi reagents • Licensing agreements for the LentiVector technology for research applications with Pfizer and two undisclosed global biopharmaceutical companies Financial highlights: • Revenue £0.8 million: increased £0.3 million (64%) over 2004• Operating expenses £12.2 million: £1.2 million (9%) less than 2004• Loss for the year £9.1 million: £1.4 million (13%) less than 2004• Cash burn £7.7 million: £2.0 million (21%) less than 2004• Total of £29.0 million raised from issue of shares in 2005• Year end cash, cash equivalents and current asset investments £43.8 million (2004: £22.4 million) Board changes: • Dr Mike McDonald, Chief Medical Officer appointed on 2 February 2006 • Raj Uppal, Non-Executive Director, resigned from the Board on 13 March 2006 Professor Bob Hawkins, Clinical Director of Medical Oncology at the ChristieHospital in Manchester and Principal Investigator for several TroVax trialscommented on the data from the Phase II studies of TroVax with chemotherapy,saying: "The data using TroVax in combination with chemotherapy in colorectalcancer look very encouraging particularly considering the size of the study. Ifthese data were reproduced in a suitably powered pivotal study then they wouldlikely support an efficacy claim in a license application." Commenting on the annual results, Oxford BioMedica's Chief Executive, ProfessorAlan Kingsman said: "We are very pleased to report strong progress across theentire development portfolio and in our licensing and business developmentactivities during 2005. Our lead candidate, TroVax, continues to reportpromising results in clinical trials and we look forward to reporting more dataat ASCO in June 2006. The preliminary analysis of patient survival in the PhaseII colorectal cancer trials is encouraging and these data add further value aswe progress our deal discussions. We remain focussed on achieving our keyobjectives of securing a commercial partner for TroVax and commencing Phase IIItrials. The fund raising in 2005 provides us with the financial strength to addvalue to our programmes while pursuing licensing deals and productcollaborations." Analyst meeting and web cast: An analyst briefing will be held at 10:00 am today at the offices of BuchananCommunications, 45 Moorfields, London EC2. Simultaneously to the analystbriefing at 10.00 am, there will be a live audio web cast of the resultspresentation. To connect to the web cast facility, please go to the Company'swebsite: http://www.oxfordbiomedica.co.uk/ approximately 10 minutes (09:50 am)before the start of the briefing. This will also be available for replay shortlyafter the presentation. -Ends- For further information, please contact:Oxford BioMedica plc: Professor Alan Kingsman, Chief Executive Tel: +44 (0)1865 783 000City/Financial Enquiries: Lisa Baderoon/ Mark Court/ Mary-Jane Johnson Buchanan Tel: +44 (0)20 7466 5000Communications Scientific/Trade Press Enquiries:Katja Stout/ Gemma Bradley Tel: +44 (0)20 7886 8150Northbank Communications Notes to editors: 1. Oxford BioMedica Oxford BioMedica (LSE: OXB) is a biopharmaceutical company specialising in thedevelopment of novel gene-based therapeutics with a focus on the areas ofoncology and neurotherapy. The Company was established in 1995 as a spin outfrom Oxford University, and is listed on the London Stock Exchange. Oxford BioMedica has core expertise in gene delivery, as well as in-houseclinical, regulatory and manufacturing know-how. In oncology, the pipelineincludes an immunotherapy and a gene therapy in multiple Phase II trials, and apreclinical targeted antibody therapy in collaboration with Wyeth. Inneurotherapy, the Company's lead product is a gene therapy for Parkinson'sdisease, which is expected to enter clinical trials in 2006, and four furtherpreclinical candidates. The Company is underpinned by over 80 patent families,which represent one of the broadest patent estates in the field. The Company has a staff of approximately 70 split between its main facilities inOxford and its wholly owned subsidiary, BioMedica Inc, in San Diego, California.Oxford BioMedica has corporate collaborations with Wyeth, Intervet,Sigma-Aldrich, Viragen, MolMed, Virxsys and Kiadis; and has licensed technologyto a number of companies including Merck & Co, Biogen Idec and Pfizer. Furtherinformation is available at www.oxfordbiomedica.co.uk CHAIRMAN'S REPORT The year 2005 was a breakthrough for Oxford BioMedica. The Company achieved anumber of "firsts". These included: first Phase II results with TroVax(R) inrenal cell carcinoma; first Phase II results of TroVax in the adjuvant settingof colorectal cancer; first discussions with the FDA regarding Phase IIIdevelopment of TroVax; first Phase II results of MetXia(R) in pancreatic cancer;first preclinical efficacy data from the Company's partner Wyeth for thetargeted antibody cancer therapy; and first strategic alliance to develop andcommercialise LentiVector(R)-based systems. During 2005, the Company also reported further encouraging results from thePhase II trials of TroVax in colorectal cancer, more preclinical proof ofprinciple data from the neurotherapy portfolio and licensing agreements for theLentiVector technology with Pfizer and two leading biopharmaceutical companies. I am pleased to announce that we have achieved this development progress whilealso maintaining firm financial control. Total operating expenses were £1.2million lower than 2004. As a result of higher tax credit receipts, the cashburn (total of net cash used in operating activities and capital expenditure)for 2005 was £2.0 million less than 2004 at £7.7 million (2004: £9.7 million).In December 2005, we were delighted that new and existing investors supported asuccessful share offering, which raised £30.1 million before expenses includingan investment of £2.9 million by Sigma-Aldrich. The Directors believe that theCompany's cash and bank deposits at the end of 2005 of £43.8 million provide thefinancial strength to deliver on our objectives to add further value to thepipeline and to secure the anticipated commercial collaborations for our leadproducts. The financial report for 2005 is the Company's first report to beprepared in accordance with International Financial Reporting Standards (IFRS). I am grateful to all those that have supported and contributed to OxfordBioMedica during the year. We welcome our eight new staff who joined during theyear, in particular, Dr Mike McDonald, who was appointed in September 2005 tothe new position of Chief Medical Officer. Mike brings considerable experiencein clinical development and regulatory affairs from 20 years in thepharmaceutical and biotechnology industry and has already made a significantcontribution to the progress of TroVax. In February 2006, Mike joined the Boardas an Executive Director. I would also like to thank Raj Uppal, one of ourNon-Executive Directors, who resigned from the Board on 13 March 2006. Raj hasmade a valuable contribution to the Board and has been an excellent source ofadvice over the years, having joined the Board in February 2001. I would also like to recognise the support and commitment shown to OxfordBioMedica by our partners. In particular during 2005, I would like to thank ournew strategic alliance partner, Sigma-Aldrich, and our three new technologylicensees, Pfizer and two leading biopharmaceutical companies, and I would liketo congratulate Wyeth on its progress with the targeted antibody therapy. Also,as ever, I want to thank our dedicated staff for their efforts during the year,without whom we would not be able to report such significant achievements. Dr Peter JohnsonCHAIRMAN OPERATING REVIEW The Company's core development pipeline is focused on treatments for cancer andneurobiological diseases. Two products are in clinical trials and a furtherthree candidates are expected to enter clinical development in 2006-07. Theinternal pipeline of seven product candidates has attracted considerable supportfrom research and clinical funding agencies as well as charitable organisations,which have provided grants or services in kind. A further two products are indevelopment with commercial partners. Oxford BioMedica established an active licensing programme for its suite ofgene-delivery technologies in early 2004. This initiative has secured ninelicensees or partners to date, including Pfizer and Sigma-Aldrich during 2005. ONCOLOGY The oncology pipeline exploits the expertise of the Company and its partners intumour biology, immunology and product development. It comprises three majorproduct candidates as well as a product for treating cancer in companionanimals. These novel cancer therapies are designed to deliver a combination ofimproved efficacy and safety over existing treatments. The in-house cancer pipeline is focussed on TroVax and MetXia, which have bothgenerated encouraging clinical results in 2005. The Company has two main goalswithin the TroVax programme. The first is to secure a commercial partner and thesecond is to maintain the planned product registration date of 2009. For MetXia,the Company expects to report further clinical data in 2006 and to opendiscussions with regulatory authorities and potential partners. The Company'spartners, Wyeth and Intervet, made progress with their respective cancerprogrammes during 2005. Product optimisation and preparations for clinical/fieldtrials are expected to be completed during 2006 for both candidates. TroVax(R) TroVax is Oxford BioMedica's lead cancer immunotherapy product candidate. It isdesigned to stimulate a specific anti-cancer immune response and has potentialapplication in many tumour types. The product induces an immune response againstthe tumour antigen 5T4, which is broadly distributed throughout a wide range ofsolid tumours. The product consists of a pox virus (MVA) gene-transfer system,which delivers the gene for 5T4. MVA is known to induce the breaking of immunetolerance to self antigens, such as 5T4, that are expressed from thisgene-delivery system. Over 100 patients have now been treated with TroVax in sixclinical trials (collectively over 400 doses). TroVax has attracted externalsupport from Cancer Research UK and the US National Cancer Institute. Theseorganisations are conducting or plan to conduct clinical trials with TroVax,which would otherwise cost Oxford BioMedica the equivalent of approximatelyUS$5.5 million. There are five Phase II trials of TroVax ongoing, three in colorectal cancer andtwo in renal cell carcinoma. In 2004, recruitment was completed in Phase IItrials of TroVax in first-line treatment of metastatic colorectal canceralongside irinotecan-based (IFL) and oxaliplatin-based (FOLFOX) chemotherapy.The complete safety and immunology data from 23 'per protocol' patients fromthese two trials were presented at the International Colorectal Cancer Congressin Aventura, Florida, USA, in October 2005. These data showed that the primary endpoints of safety and anti-tumourimmunological responses were achieved, and confirmed the excellent safetyprofile of TroVax with no serious adverse events being attributed to theproduct. All 23 patients mounted an anti-tumour immune response following TroVaxtreatment and these responses were, on average, of higher magnitude and longerduration than those seen in later stage patients in the Company's previouslycompleted Phase I/II trial in colorectal cancer. This suggests that thechemotherapy regimens do not impair the ability of TroVax to elicit ananti-tumour response and, in fact, may enhance some aspects of the response. TheCompany is particularly encouraged by the high frequency and level of anti-5T4cytotoxic (killer) T-cells (CD8) induced by TroVax. Over 70% of the patientsshowed identifiable CD8 responses. In some patients, the CD8 levels werecomparable with the high levels that are generally only seen in response toviral infections. This was the first comprehensive demonstration by the Companythat TroVax induces the production of these cells, which are generally regardedby the industry as being the key anti-tumour effectors. This observation alonehas increased the interest of potential partners in TroVax. In the two Phase II trials of TroVax with chemotherapy, the secondary endpointof clinical benefit exceeded the Directors' expectation from their assessment ofpreviously reported data for chemotherapy alone. Based on unaudited data acrossboth trials, 91% of per protocol patients, who received TroVax withchemotherapy, showed disease control: 17% had complete responses; 49% hadpartial responses; and 25% had stable disease. These figures are based on CTscan data according to industry-standard criteria for measuring tumour response,known as Response Evaluation Criteria in Solid Tumours (RECIST). There were differences between the results for the two chemotherapy regimens. Inthe TroVax plus IFL trial, 58% of patients showed complete or partial responsesaccording to RECIST. In the TroVax plus FOLFOX trial, 73% showed complete orpartial responses. Although these trials were small in terms of patient numbersand were not designed with control arms, the Directors believe that these levelsof clinical benefit are encouraging when compared to published trial data forchemotherapy alone in similar settings. Interestingly, like the earlier Phase I/II study, there was a trend showing a relationship between clinical benefit andimmune response. In the TroVax plus FOLFOX trial, an independent statisticianidentified a statistically significant (p < 0.02) correlation between the5T4-specific immune response and tumour responses. For both trials, finalaudited tumour response rates, statistical analyses and patient survival dataare anticipated in 2006. The Company is currently accumulating survival information for these two studiesand preliminary analysis of patients who had received at least two injections ofTroVax suggests that the product may provide a survival benefit when comparedwith the published data for the chemotherapies alone. However, it should benoted that patient numbers are too small to provide a rigorous conclusion andcomparisons with historical data can be unreliable. In order to improve thestatistical value of the analysis the combined published survival curves for thetwo chemotherapies were compared with the combined survival of patientsreceiving TroVax in addition to the chemotherapies. This showed that TroVaxextended median survival from 72 weeks to 88 weeks and improved survival attwelve months from 70% to 90%. At the time of writing, 13 of the 30 patients inthis survival analysis remained alive with follow-up times exceeding 75 weeksthrough to 128 weeks. The Directors regard these data as encouraging and believethat, if these observations were reproduced in a pivotal study, they would besufficient to support a Biologics License Application (BLA). The Company expectsto report further data from these trials at the American Society of ClinicalOncology (ASCO) annual meeting in Atlanta, Georgia, USA, on 2-6 June 2006. A third Phase II trial, initiated by an investigator with sponsorship fromCancer Research UK, completed enrolment in October 2005. The trial is evaluatingTroVax in colorectal cancer patients who have operable liver metastases.Patients receive TroVax immunisations before surgery (neoadjuvant) and aftersurgery (adjuvant). Preliminary data were presented at the National CancerResearch Institute conference in Birmingham, UK, in October 2005. The datashowed that TroVax was well tolerated in patients undergoing resection ofcolorectal cancer liver metastases and that the liver metastases expressed 5T4on the tumour cells and/or tumour stroma. Encouragingly, all patients in thetrial mounted an anti-tumour immune response to 5T4. The clinical outcomes oftrial participants will be followed up and presented by Cancer Research UK indue course. In addition to colorectal cancer, the Company is targeting metastatic renal cellcarcinoma (RCC) as a lead indication for the development of TroVax. TheDirectors believe that RCC is an indication where TroVax might achieve a rapidroute to product registration. In 2004, a Phase II trial in this setting wasinitiated at the New York-Presbyterian Hospital, New York, USA, under anapproved Investigational New Drug protocol. The principal investigator for thetrial is Dr Howard Kaufmann, a leading expert in clinical immunotherapy and anadvisor on TroVax. The trial is designed to gather information on the safety ofTroVax in this setting and also on the ability of TroVax to elicit immuneresponses to the tumour antigen 5T4. Dr Kaufmann gave a presentation in October 2005 at the World Vaccine Congress inLyon, France, highlighting the potential of TroVax as a treatment for RCC. ThePhase II trial is an open-label study of TroVax in combination with high doseinterleukin-2 (IL-2) therapy, which is a treatment for RCC approved by the USFood and Drug Administration (FDA). In his presentation, Dr Kaufmann reportedthat there had been no serious adverse events related to TroVax, which isconsistent with the safety profile of the product across all trials, and TroVaxtreatment was well tolerated. Five patients were 'immune response evaluable',having received at least two TroVax immunisations. All five patients showed highanti-tumour antibody responses to 5T4. The antibody levels were at the top endof the range reported from the Phase II trials with TroVax in patients withcolorectal cancer undergoing chemotherapy. This trial is intended to recruit up to 25 patients. To date, 14 patients havebeen recruited. Further data, including more detailed immunological analyses andefficacy as measured by objective tumour responses, are expected to be presentedat ASCO in June 2006. The Company initiated a second Phase II trial in RCC at the Methodist Hospitalin Houston, Texas, USA, in November 2005. The principal investigator for thistrial is Dr Robert Amato, who is Associate Professor of Urology at the MethodistHospital and a renowned expert on the treatment of RCC. This trial is designedto evaluate the safety and immunogenicity of TroVax in conjunction with low doseIL-2, which is commonly used as standard of care treatment for RCC. To date,there are 13 patients in the study, out of a target enrolment of 25 patients.The Company plans to report safety, immunology and preliminary clinical outcomesfrom the trial at ASCO in June 2006. The Company is adding to its Phase II programme in RCC with a third trial thatis expected to commence at the Christie Hospital in Manchester, UK, in the nextfew weeks. The principal investigator is Professor Robert Hawkins who is aleading expert in the treatment of RCC and who has been involved in severalstudies of TroVax. This new trial is designed to evaluate TroVax in combinationwith interferon-alpha, which is widely used as standard of care for treatment ofRCC in the UK. The trial is open-label, with a target to recruit about tenpatients, in order to assess safety and immunological responses following thecombination treatment. In addition to the Phase II studies described above, the US clinical trialsconsortium, Southwest Oncology Group (SWOG), is finalising the design of a PhaseII trial with TroVax in breast cancer, which will be sponsored by the USNational Cancer Institute (NCI). These organisations provide valuable fundingand endorsement of TroVax and plan to conduct a trial that is expected to enrol120 patients with late stage breast cancer. The NCI and SWOG are responsible forall aspects of the trial, including the date of commencement. Although theanticipated timetable for initiating this trial has been extended, OxfordBioMedica remains encouraged by the level of commitment towards TroVax and thisPhase II trial shown by the NCI and SWOG. The current expectation is for thetrial to start in the second half of 2006. In considering the future development of TroVax and its commercial launch, theCompany has taken account of several factors. The broad distribution of 5T4 onmany tumours and the fact that, as expected, the immune response appears similarin patients with different tumour types and in different clinical settingsprovide a wide choice of indications for further development. The Company isfocusing initially on the two cancer types where it has clinical experience,colorectal cancer and RCC. Metastatic RCC tends to be an aggressive cancer with median survival ofapproximately one year from diagnosis. The relatively rapid progress of thedisease in the majority of patients creates an opportunity for a definitivestudy to demonstrate the impact of TroVax on prolonging survival within arelatively short time frame. Studies in tumour types with slower progressionwould take longer to complete pivotal trials. Therefore, the Directors believethat RCC provides the fastest route to registration. Colorectal cancer represents a very large market opportunity but the Directorsbelieve that trials in this setting would take longer to generate data forproduct registration. A number of new combination therapies for metastaticcolorectal cancer have extended median survival from approximately 16 months to20 months. The Company intends to pursue both colorectal cancer and RCC but itwill give RCC initial priority because of the Directors' focus on bringing theproduct to market as quickly as possible. However, it is important to note thatthe Directors believe that product approval for the treatment of RCC willfacilitate rapid regulatory review of subsequent registration applications forcolorectal and other cancer types. Furthermore, the Company expects that anyprospective partner for the TroVax programme would pursue several indications,including colorectal cancer. The Company has two near-term goals within the TroVax programme. The first is tosecure a commercial partner and the second is to maintain the plannedregistration date of 2009. In order to achieve the latter the Company plans toinitiate a Phase III trial of TroVax in RCC in 2006. Based on its proposed trialdesign, the Directors believe that registration in 2009 is possible. This planwill be implemented in parallel with negotiations with potential partners forTroVax. In preparation for Phase III trials and product registration, themanufacturing process for TroVax has been scaled for commercial production. Another objective is to broaden the clinical experience with TroVax to othercancer types where the 5T4 antigen is evident. The NCI Phase II trial in breastcancer is part of this strategy but the Company may initiate Phase II trials inother cancer types during 2006. The Company is discussing trial plans withclinicians, and is seeking to offset some of the trial costs through externalfunding. The Company reported its provisional Phase III trial design in RCC in November2005, based on a combination treatment of TroVax with IL-2. Followingconsultation with clinical advisors and the FDA, the Company has broadened thescope of the trial such that TroVax would be used in combination with eitherIL-2, interferon-alpha or Sutent(R) (sunitinib). The revised trial designbroadens the utility of TroVax, and hence, increases its commercial potential inRCC. The planned Phase III trial, referred to as TRIST (TroVax Renal ImmunotherapySurvival Trial), is a randomised, placebo controlled, two-arm study of TroVax incombination with standard of care, versus placebo and standard of care. Thecurrent plan is to recruit about 700 patients and will involve about 120 centresin the USA, European Union and Eastern Europe. The proposed primary endpoint issurvival improvement. The protocol includes the appointment of a Safety andEfficacy Monitoring Board (SEMB) to assess the safety and potential efficacy ofthe drug combinations at various time points during the trial. The Company has requested a Special Protocol Assessment (SPA) from the FDA forTRIST. The SPA is a process for official FDA evaluation and guidance on PhaseIII trial design. At the conclusion of the SPA process, Oxford BioMedica expectsto receive a written agreement that if the study achieves its proposed endpointthen it may be used to support an efficacy claim in a submission to the FDA forproduct registration. The Company expects to complete the SPA process and othertrial preparations for the start of patient recruitment in the second half of2006. However, the SPA process could take longer than expected and the FDA maydemand significant changes to the trial design, which could change the Company'stimelines. The Company plans to seek 'orphan drug' designation for TroVax in both the USAand Europe for the RCC indication. The granting of orphan drug status isintended to encourage the development of new treatments for life-threatening orchronically debilitating diseases where patient numbers are below certainthresholds. It would provide Oxford BioMedica and any prospective commercialpartner with various benefits in terms of regulatory exclusivity, assistancewith clinical development and a waiver of filing fees. In addition to the Phase III programme in RCC described above, the Companydisclosed in November 2005 that it is in discussion with QUASAR, a UK-basedclinical trial network funded from a variety of sources including the UKgovernment's Department of Health. QUASAR has expressed interest in conducting aPhase III trial in Stage II/III colorectal cancer patients. TroVax would be usedat or around the time of surgery with the endpoint being an increase indisease-free survival at three years. The study would be configured to achieveregistration in Europe and the USA and could involve several thousand patients. The Company's financial contribution to this trial would be in the order of £4million. If the Company were to run such a trial without QUASAR, the Directorsestimate that it would cost approximately £70 million. The proposal is subjectto a number of further review processes and QUASAR may conclude not to conductits proposed Phase III trial for reasons that may be unrelated to the product. The clinical data that have been generated so far place TroVax amongst theleading candidate cancer immunotherapy products in development worldwide. Assuch, it has attracted interest from companies and research organisationsthroughout the world. The Company has made good progress with prospectivecommercial partners for TroVax, and securing a commercial partner for TroVax inat least one major territory remains a key objective for the Company during2006. MetXia(R) MetXia is Oxford BioMedica's gene-based cancer therapeutic developmentcandidate. The product is based on a highly-engineered retrovirus gene deliverysystem expressing a specific human cytochrome P450 gene. Cytochrome P450,delivered in this way, activates the chemotherapeutic prodrug cyclophosphamideat the tumour site, thereby increasing the effective concentration of theanti-tumour, cytotoxic derivative in the tumour mass. MetXia is potentially useful in the treatment of a number of solid tumours andtheir metastases, particularly those where cyclophosphamide is commonly used asa treatment. The Company is targeting its development efforts for MetXia on thetreatment of pancreatic cancer through direct administration of both MetXia andcyclophosphamide to the tumour. A two-stage Phase II trial was initiated in2004. In August 2005, the Company announced that the first stage wassuccessfully completed. The objectives of the first stage were to assess the safety of administeringMetXia locally to the pancreatic tumour, to confirm gene transfer at the tumoursite following local delivery and to identify an optimal dose of MetXia for thesecond stage of the trial. In the first stage of the trial, two dose levels ofMetXia were assessed in six patients, in combination with a low dose ofcyclophosphamide. Each patient had two administrations of MetXia, prior to andsubsequent to surgery, followed by administration of cyclophosphamide. Both doselevels of MetXia were safe and well tolerated. Importantly, dose-dependentexpression of the P450 gene delivered by MetXia was observed in tumour biopsiestaken at surgery. Patient recruitment is ongoing for the second stage of the trial using a fixed,optimal dose of MetXia and increasing doses of cyclophosphamide, in up to 25patients, at two centres in the UK: the Royal Liverpool University Hospital,Liverpool, and the Sir John McMichael Centre for Clinical Investigation andResearch at the Hammersmith Hospital, London. The objective of this stage is todetermine the optimal dose of cyclophosphamide and to evaluate clinical benefitas well as safety. To date, three patients have been treated in the second stageof the Phase II trial. Patient recruitment has been slower than expected owingto the restrictive criteria for patient selection and poor tolerability ofsurgery, although the Company still expects to report initial efficacy and toidentify the optimal dose of cyclophosphamide during 2006. The Company plans to open discussions with the regulatory authorities todetermine the most expeditious route to obtain approval of MetXia in pancreaticcancer. A pivotal trial in pancreatic cancer could start in 2007, although theregulatory authorities may recommend more extensive Phase II development. MetXia's mechanism may be relevant in a number of malignant tumours, includingbreast cancer, prostate cancer and glioma (brain cancer). The Directors believethat the commercial opportunity for MetXia may be considerable and the Companyplans to seek commercial partners for the product following successfulcompletion of the current Phase II trial. 5T4 Targeted Antibody Therapy (Wyeth) Wyeth has licensed rights to Oxford BioMedica's proprietary antibody against the5T4 tumour antigen for the treatment of cancer. Wyeth is using the antibody todevelop an antibody-toxin conjugate based on its expertise with the anti-canceragent calicheamicin. The collaboration with Wyeth has the potential to generateUS$24 million in upfront and milestone payments, plus royalties on productsales. The collaboration was signed in 2001 as an option to license and, in2003, Wyeth exercised its option to develop the product. In 2005, Wyeth continued its preparations for clinical development, includingmanufacturing scale-up and pivotal non-clinical safety studies. The product isdescribed as a 'development candidate' in Wyeth's R&D pipeline. During the year,for the first time, Wyeth reported some of its preclinical data at a scientificmeeting. Preclinical efficacy data were presented at the World Congress on Advances inOncology and International Symposium on Molecular Medicine in Crete, Greece inOctober 2005. The presentation included preclinical data showing that theantibody-toxin is cytotoxic against tumour cells expressing the 5T4 antigen, andthat the product inhibited tumour growth in in vitro models of various human5T4-expressing cancers. In a preclinical model of lung cancer, 100% of micetreated with the antibody-toxin survived through an observation period of 150days, whereas those treated with a control had a median survival of 40 to 60days. Like TroVax, the product could, in principle, be used to treat a range ofcancers. Thus, the Directors believe that the antibody-toxin may havesubstantial commercial potential. Wyeth has full responsibility and control overthe development of the product. In 2006, Wyeth is expected to submit itsInvestigational New Drug (IND) application for the start of clinical trials withthe antibody-toxin, disclose the initial patient group and commence clinicaldevelopment. The start of clinical trials triggers a further milestone paymentto Oxford BioMedica under the terms of the collaboration. TroVax-Vet(R) (Intervet) TroVax-Vet is Oxford BioMedica's veterinary 5T4 tumour antigen-targetedimmunotherapy programme for the treatment of cancer in companion animals,focusing on dogs and cats. The development and commercialisation collaborationwith Intervet, the veterinary unit of Akzo Nobel, was signed in 2003. Intervetis one of the world's top veterinary companies. Under the Intervetcollaboration, Intervet funds the programme and Oxford BioMedica receivesdevelopment milestones and royalties on product sales. Intervet completed a relevant preclinical efficacy study with canine TroVax-Vetin 2005. The data demonstrate that the product stimulates a strong immuneresponse against the canine version of the 5T4 antigen. In 2005, Intervetinitiated further product optimisation studies, evaluating different vaccineconfigurations, dosages and routes of administration. Intervet anticipates thestart of field trials in dogs with naturally occurring cancer towards the end of2006 or in early 2007. NEUROTHERAPY Oxford BioMedica's neurotherapy development portfolio addresses Parkinson'sdisease, vision loss, nerve injury and acquired and inherited motor neurondisease. The pipeline comprises five therapeutic candidates based on theCompany's proprietary LentiVector(R) technology. All five programmes continue tomeet expectations in their ongoing preclinical development. The Company ispreparing regulatory submissions for the start of clinical trials with the mostadvanced product, ProSavin for Parkinson's disease. Given the commonality of theLentiVector system to all the neurotherapy products, the infrastructure forProSavin that relates to manufacturing scale-up and safety testing can beapplied to the entire portfolio. Hence, the time invested in the preclinicaldevelopment of ProSavin should accelerate the programmes for the otherdevelopment candidates. The Company anticipates entering clinical developmentwith at least one neurotherapy product each year from 2006, starting withProSavin. ProSavin(R) The Company's lead neurobiology candidate product, ProSavin, is a novel approachto the treatment of Parkinson's disease. ProSavin uses a LentiVector system todeliver the genes for three enzymes that are required for the synthesis ofdopamine. The product is administered locally to the striatum, converting cellsinto a replacement dopamine factory within the brain. The Company first presented preclinical efficacy data with ProSavin in anindustry standard in vivo model of Parkinson's disease in 2004. In thesestudies, treatment with ProSavin resulted in almost complete recovery ofmovement behaviour, which is seldom achieved in this model according to theliterature. During the past year, the Company has confirmed these results byconducting long-term efficacy and safety studies and dose ranging studies, whichhave established the parameters for setting the human dose. The expanded body ofdata suggests that a single treatment with ProSavin has a statisticallysignificant (pRelated Shares:
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