25th Oct 2005 15:02
Major Technical Innovation in Drug And Tumour Modelling Results in Partial Vesting of Share Options Oxford, UK 25th October 2005 Physiomics (AIM: PYC), a European systems biologysimulation company, has developed a sophisticated addition to its core cellgrowth model showing why different cancer cells respond in different ways to aninnovative new class of anti-cancer drugs. The simulation work also shows howsome time-consuming laboratory work to grow cancer cells could now be modelledquickly in a computer rather than taking significantly longer in a laboratory.The utility of Physiomics' computer simulation approach was discussed1.2 at theInternational Conference on Systems Biology meeting in Boston, USA, 19th-21stOctober 2005.The technical innovation shows, using Physiomics' SystemCell‚® software, complexvirtual cells "growing" in the computer to mimic the experimental behaviour ofmany cancer cells and their responses to drugs. This important developmentpaves the way for realistic and predictive models of tumours' drug responses.It also meets the criteria laid down by Physiomics' Remuneration Committee onkey technical criteria such that 25% of the unapproved options granted on 26June 2005 are now available for exercise.A better predictive system for testing cancer therapeutics is expected to beenormously valuable to pharmaceutical companies and could confer significantpatient benefit through better treatment. Currently, only 5% of all cancerdrugs that are tested in clinical trials are approved for patient use, half theindustry norm 3. The new work on cell growth examines why small geneticdifferences between cancer cells mean that some die when treated whereas otherssurvive and grow. This is not obvious from standard cell biology work, and itopens up the possibility of optimising treatment using appropriate drugcombinations depending on patient profiles.The data used to develop this model is from the scientific literature andfocuses specifically on an aurora kinase inhibitor drug candidate, VX-680,developed by Vertex Pharmaceuticals Inc. and licensed to Merck & Co. Inc4.Published data on an aurora kinase inhibitor being developed by AstraZeneca hasalso been used. Aurora kinase inhibitors are a new type of therapeutic that hasshown excellent cancer killing ability in preclinical studies. Some 16 aurorakinase inhibitors are under development by companies such as Astex TherapeuticsLtd, Chroma Therapeutics, Cyclacel Ltd, Millennium Pharmaceuticals Inc, RigelPharmaceuticals Inc and Serenex, in addition to Merck & Co and Vertex.Physiomics believes that computer simulations could help to optimise thetransition from preclinical to clinical development and help in theoptimisation of dose scheduling, one of the major problems in clinical trials.Studies5 have shown that improving the drug development success rate by 10%overall could save $242m per drug. Physiomics and Bayer Technology Servicescollaborate on Clinical Response Prediction in the area of cancer."For the pharmaceutical industry the virtual approach could represent hugesavings in time and money by predicting the effective drug dose and schedulefor different cell types. This currently is done step by step in thelaboratory, or in inflexible clinical trials." said Dr John Savin, CEO ofPhysiomics. "Our technology is also very relevant for working out how best touse the new generation of targeted therapeutics and for reducing their clinicaldevelopment risks." --ENDS- 1) Cell Cycle Simulations for Examining the Effects of Drugs inhibiting AuroraKinase According to Cancer Cell Phenotype, Chassagnole et al, Poster at ICSB20052) Cell Cycle Lab: Using SystemCell‚® Technology for Multiple-Cell Simulations,Finney et al, Poster at ICSB 20053) Can the pharmaceutical industry reduce attrition rates? Kola, I. and Landis,J. Nature Reviews Drug Discovery, 3 (2004) 711-7154) VX-680, a small molecule inhibitor of Aurora Kinases induces endoreplicationand apoptosis preferentially in p53 and p21 deficient cells, Gizatullin, F,, etal, Poster LB-238 AACR Meeting 2004.5) Tufts Center Impact Report 2002For further information please contact:Physiomics plcDr John Savin (CEO) Tel: + 44 1865 784 980Mr David Evans (Chairman) Northbank Communications Tel: + 44 207 886 8150Emma Palmer (financial enquiries)Fiona Brown/Rowan Minnion (media)Notes to EditorsAbout aurora kinasesAurora kinases are key enzymes involved in the later stages of cell division,particularly the formation and control of the machinery that enables cells todivide. When applied to cancer cells, inhibitors of these enzymes prevent thecells from dividing properly. This can lead in some tumour types to cell growthbeing halted quickly. In other types of cancer cells, growth continues for morecycles before the cells start to die. Understanding the differences betweenthese aspects has been problematic.A key part of Physiomics' work in this area has been reproducing two biomarkersof drug action. These are the extent of aurora kinase modification of a proteinused to package DNA (histone H3), and a measure of the number of gene copiesthat a cell has (polyploidy). In addition, the model starts to explain why somecell types respond well to the drug and others do not. In the next stage of thedevelopment, different drug doses and schedules plus combinations with existingtherapeutics could be explored.About treatment of virtual tumoursUsing the Physiomics advanced cell cycle model and SystemCell software,populations of virtual cells have been "grown" in a computer and a virtual drugthat targets aurora kinase administered. The virtual cell populationquantitatively reproduced the observed experimental behaviour published in theliterature (4).One type of responsive cell stopped growing after drug administration due tothe action of the drug on the individual cells in the population model. Anothercell type with a common cancer-causing alteration (reduction of p53 levels)kept on growing with two, four and eight times the normal amount of DNA. Cellswith higher levels of DNA then started to experience cell death.In both cases, the virtual experiment reproduced results acquired over fivedays of actual experimental time in under an hour of computational time. Thisindicates that the model should have potential in predicting the effect ofhuman drug doses, as well as the activity of new drugs and drug combinations.About Physiomics plcPhysiomics plc (AIM:PYC) is a computational systems biology services companyapplying simulations of cell behaviour to drug development to reduce the highattrition rates of clinical trials. As 80-90 per cent of all clinical drugcandidates fail to reach the market, estimates show that an overall ten percent improvement in success rates could reduce the cost of one drug'sdevelopment by as much as $242 million, from the current estimate of around$800 million.Physiomics is currently focused on optimising the design of cancer clinicaltrials as a service to major pharmaceutical companies. In addition, it hassecured an option to in-license two innovative molecules in the cancer areafrom Cronos Therapeutics. Physiomics has a major collaboration with BayerTechnology Services GmbH to develop globally clinical response predictionservices using both companies' proprietary technologies and mathematical cellmodels, including the SystemCell‚® technology developed by Physiomics. In June2005, Physiomics became a distributor of Bayer's PK-Sim‚® product forunderstanding the way pharmaceuticals are distributed round the body.Physiomics, based in Oxford, UK, was founded in 2001, and floated on AIM in2004.For further information, please visit www.physiomics-plc.comSystemCell is a registered trademark of Physiomics plcAbout Bayer Technology ServciesBayer Technology Services GmbH is the center for technological competence ofthe Bayer Group worldwide. The Bayer company employs more than 2,100 expertsworldwide at its headquarters in Leverkusen and other German locations, as wellas in regional offices in Baytown (Texas, USA), Antwerp (Belgium), Mexico City(Mexico) and Shanghai (Peoples Republic of China). Bayer Technology Servicesposted sales of EUR 520 million in 2004, including utilities procurement forall Bayer sites in Germany (first six month only). In addition tofully-integrated solutions along the life cycle of pharmaceutical and chemicalplants - from development through engineering and construction to processoptimization, Bayer Technology Services offers a broad range of products andservices for all stages of diagnostics and drug research and development.Examples include nano-phosphors, the pharmacokinetic simulation software PK-Sim‚® as well as sophisticated data mining and modeling techniques. Additionalinformation about Bayer Technology Services is available at www.bayertechnology.com Physiomics plc Registered in England and Wales Number 4225086 Registered Office: The Magdalen Centre, Oxford Science Park, Oxford OX4 4GA, UKENDPHYSIOMICS PLCRelated Shares:
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