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Short business plan

Products/Services

The product to be developed is a non-invasive urine based test that enables early detection of BC recurrence, and prognosis of future development, based on multiple BMs. BC ranks second in incidence and mortality among cancers of the genitourinary tract and accounts for more than 350,000 new cases worldwide per year. At initial diagnosis the vast majority of BC patients (70-80%) present with NMIBC, 20-30% have MIBC with approximately 5% exhibiting clinically evident distant metastases. Muscleinvasive disease results in poor prognosis with more than 50% of cases deceasing within 5 years. NMIBC is related with very high recurrence rates of 50% - 70% and a 15% overall progression. The problem of under-staging in Ta or T1 tumours range from 35% to 62%. TransBioBC will launch a prototype in-vitro diagnostic device (IVD) urinary BM test kit for early detection of BC recurrence and prediction of BC progression risk. The IVD prototype will consist of a sampling kit for urine, including urine monovettes, instructions for use, cooling units, and the necessary documents. The sampling kit will be shipped to customers on demand and analysed centrally in an ISO 13485 quality controlled laboratory environment based on multiplex assay for BM using the mirco-ELISA technology (DS) and CE-MS-based assay for urinary biomarkers (MOS). The obtained BM profiles will be classified by two separate SVM classifiers (one for relapse and one for prognosis) as cases or controls as final result report, stating assay result and clinical implications of the context of use. IVD product will have significant impact on: (a) Disease management as it would reduce the number of necessary cystoscopies, allowevidence-based guidance of therapeutic interventions, and increase patient compliance and decrease cost of care. (b) Clinical trials targeting evaluation of efficacy of new therapeutic agents, stratification ofpatients at inclusion towards theranostic and personalized medicine approaches, decrease the cost of clinical trials by reducing the number of patients to be included due to improved selection criteria, and demonstrating clinical unique selling positions for differentiation from competitors, and demonstrating clinically relevant benefits which are not detectable with current tests.

Market Analysis

Patient management. Among cancers in the US, BC has the highest per patient treatment costs, and the 5th highest overall cost, estimated at $3.4 Billions annually. Per patient BC cost from diagnosis to death range between $89,287 and $202,203 [36]. Monitoring generates ~75% of post-diagnosis costs, including post-surgical complications, tri-annual examinations and semi-annual diagnostic and laboratory testing. Progression from NMIBC to MIBC clearly increases overall treatment costs. Early detection of incident and recurrent disease plays a key role in reducing the risk of disease progression. The MIBC patient treatment costs are nearly three times those for patients with stage Tis/Ta. Given a total European population of 730 Mio citizens and the estimated prevalence of 1 in 1,450, the total number of persons in Europe under surveillance for NMIBC can be estimated to be 0.503 Mio. Considering semi-annual diagnostic laboratory testing, the total number of cystoscopies per is 1,006 Mio. Using an estimated cost of 1,000 EUR per cystoscopy, the total annual cost is about 1 Billion EUR per year. A reduction of expenses by only 15% will entail annual saving in the EU of approx. 150 Mio. EUR. Based on these calculations, it is reasonable to estimate a total of 1 million tests per year in the EU. Clinical trial in the field of BC: ClinicalTrials.gov has registered more than 600 clinical trials in the field of BC. In total 344 drug/interventions were investigated. 82 trials were sponsored by pharmaceutical industry. Fast and cost-effective evaluation of efficacy of new therapeutic agents by advanced stratification strategies for patients at inclusion are main driving forces. In the field of BC especially the development of novel monoclonal antibody based therapy approaches, e.g. Amgen’s Vectibix® (Plantinumumab), Roche’s Avastin® (Bevacizumab), and kinase inhibitors, e.g. Pfizer’s Receptor-Tyrosinkinase-Inhibitor Sutent® (Sunitinib), Bayer’s Multi-Kinase-Inhibitor Nevaxar® (Sorafenib) or GSK’s TyrosinkinaseInhibitor Tyverb® (Lapatinib) are the are state of the art. But also innovative immunosuppressors, such as Novartis’ Afinitor® (Everolimus), are applied. These data underline the importance of the BC-related drug development market with several global players involved.

Competition

The most widely used non-invasive monitoring method, i.e. urine cytology, unfortunately is associated with very high inter-observer variability and low sensitivity particularly for low-grade tumours. NMP22 is correlated with the presence of bladder cancer and was FDA approved in 1996 as NMP22 Bladder Chek Test developed by Matritech, Inc. The test could not be effectively marketed by Matritech due to its sub-optimal performance, and is currently distributed by Alere Inc. (Waltham, MA, USA). The UroVysion Bladder Cancer Kit (UroVysion Kit) is designed to detect aneuploidy for chromosomes 3, 7, 17, and loss of the 9p21 locus via fluorescence in situ hybridization (FISH) in urine specimens from persons with hematuria suspected of having bladder cancer. The test was FDA approved in 1998. The test kit is marketed by Abbott Molecular Inc., a global company engaged in molecular diagnostics However, although NMP22 Bladder Chek Test and UroVysion FISH assay received the FDA approval, none of these markers is generally applied, and their value in clinical routine is limited. Therefore, we will position our test not only as a cost-effective, non-invasive urine test for early detection of recurrent BC as the competitors, but hopefully also as a test predicting tumour progression. As such our test will be an innovator and trendsetter in the field with a unique selling position

Marketing Strategy

Clinical validation and prototype launch described in this proposal will introduce an innovative diagnostic test kit to this market. The prospective validation design will enable general acceptance by healthcare professionals and regulatory agencies, public authorities, insurances and scientific societies of clinical performance, cost-effectiveness, and safety. In market segment 1 we exploit the test kit as a "business-to-business" product for usage in clinical trials of pharmaceutical industry and scientific institutions. The test will allow to evaluate the efficacy of new therapeutic agents and to stratify patients beyond current standards to avoid undiscovered muscleinvasive disease or recurrent tumours. This will ultimately allow costumers to decrease the cost of clinical trials and therefore overall research & development cost. In parallel we will aim to obtain qualification of the validated BMs for clinical trial applications by the European Medicine Agency. MOS has already successfully initiated qualification in the field of diabetic nephropathy biomarkers and Dr. Vlahou is expert member of the EMA external qualification team. EMA qualification is considered a central cornerstone of the strategy to convince pharmaceutical companies of the BM effectiveness and robustness. Using a similar strategy, partner MOS is currently able to acquire 2 small-scale pilot studies (50-100 patients) per year as subcontractor. The aim of these projects is to perform post-hoc retrospective patient stratification for drug efficacy assessments. Based on the results of such pilot studies, SME partner MOS is currently able to acquire follow-up projects with a business volume of 1-2 Mio EUR in approximately 20% of cases. In market segment 2 we aim to launch the test kit as a "business-toconsumer" out-of–pocket product for disease management. The prospective clinical validation data provided by TransBioBC are an indispensible prerequisite to enter this segment. Product launch will start in Germany (and German speaking neighbours) as a European key market under CE label. This approach will minimize general risks associated with de-novo establishment of clinical logistic infrastructures as partner MOS has a fully ISO13485 quality controlled central laboratory with established logistic infrastructures. In a later phase additional European countries will be targeted in cooperation with locally established clinical laboratory services. Finally, TransBioBC will aim to include the test in clinical guidelines of the national and translational urological societies and will apply for reimbursement approval by public healthcare authorities and health insurances. Introduction of the test in the public health reimbursement system will initially be aimed in Germany, as partner has already initiated Health Technology Assessment (HTA) of a similar urine test kit for diabetic nephropathy. It is anticipated that such application may be submitted by end of the TransBioBC project. This submission will trigger HTA, to begin right after TransBioBC ends. According to experience, HTA of the BC test will take 2-3 years. As soon as positive assessment is achieved, the out-of-pocket market will be substituted by the public health reimbursement market. This will result in significant increase of market share strengthening the unique selling position of the test.

Business Structure and Management

Upon TransBioBC completion and product launch, SME partners MOS and DS plan a joint venture (JV) business agreement in which parties agree to develop and prospectively validate the new BM urine test kit by contributing equity. They exercise control over the enterprise and consequently share revenues, expenses and assets. The JV will establish a split-control management structure where both parent companies share decision-making responsibilities. The number of managers in controlling positions will be oriented to the areas of expertise, as this structure guaranties the functional integrity of the individual knowledge or technology. Key staff of the management structure will consist of a marketing team with a business development manager and a marketing assistant per market segment. This team will be supplemented by a web and media designer for development of corporate identity, of an attractive web page and social media presence. The laboratory and logistic staff will round up the team.

Finances

To minimize investment cost to an absolute minimum, the JV-partners will rent necessary laboratory equipment and workspace at least in the first 36 months of business. Start-up financing will be provided by JV-partners on a monthly basis as shared contributions. A major objective of the business development management in the first 6-12 months of business will be to attract private investors or business angels to additionally cushioning financial risks. The private investor of SME partner MOS has already declared is interest and a respective contractual pre-emption right was agreed. Financial plan projects break-evenpoint (BEP) around month 24 after completion of TransBioBC. This estimation is highly conservative, since neither a large-scale subcontracting project nor a national reimbursement approval was considered in the first 36 months of business. Each of these events would allow an even earlier BEP.