BladMetrix: a novel urine test for early detection and monitoring of bladder cancer

Bladder cancer is reported to be the most expensive cancer per patient, due to a high risk of recurrence, necessitating frequent testing for monitoring of disease after surgery. Patients presenting with symptoms are typically examined by a costly and uncomfortable procedure called cystoscopy in order to provide a definite diagnosis. Currently, a large proportion of symptomatic patients undergoing cystoscopies have a negative test result and could with better non-invasive tests have been spared the discomfort of the procedure. Such a test would also be of great benefit in the monitoring of pasients after surgery, reducing the need for monitoring cystoscopies. We are developing a urine based test for bladder cancer for which we aim to demonstrate clinical utility for both early diagnosis and monitoring. We are currently in the process of optimizing a first-generation version of the test, by qualifying novel promising bladder-specific DNA biomarkers. Data from analysis of urine samples collected at Aker hospital indicate that we can define a test based on our markers that displays very high diagnostic accuracy. We are currently verifying these data on urine samples collected from a larger independent cohort of symptomatic patients before diagnosis. Results from this analysis will allow us to define the optimal marker composition of the test, as well as verify its diagnostic accuracy for early detection of bladder cancer We have included 50 patients in ongoing clinical study monitoring bladder cancer patients that have received surgery and have agreed to provide urine samples during scheduled follow-ups. Preliminary results are highly encouraging, and indicate that the marker can detect disease recurrence at high accuracy, which could contribute to reduce the need (frequency) for monitoring cystoscopies. We will continue to monitor included patient and update the analyses until the last included patient has completed the 2-yr follow-up, end of 2020 or early 2021. The project has developed new patentable inventions which have been subject to 3 independent patent applications expected to support commercialization of the test. During the project we have also worked on securing granted patents for a previously filed biomarker patent, which has now been granted in US and Europe. We are in an active dialogue with various potential industrial partners, and aim to have identified a preferred partner for further commercial development by end of the year.

The BIOTEK project has been successful in providing the basis for commercialization of the technology. The R&D data support the utility of the test as a primary monitoring tool. The IPR appear very good, with both granted patents and positive patentability reviews of more recent applications. On the business side, we have received positive feedback from KOLs on our TPP. Health benefit analysis and the expected pricing support the business case. Feedback from industry is encouraging, and we remain confident that the results of the ongoing two-year clinical study with 50 patients and the results from a recently 20 mNOK funded nation-wide study on 500 patients will strengthen the interest from industrial parties. In summary, the BIOTEK project has been successful. The results validate the business case and merit further commercial development. We plan to submit an application for a FORNY grant, the successful completion of which we expect to lead to a commercial exit.

Bladder cancer affects 430 000 new patients each year and is reported to be the most expensive cancer per patient. Patients presenting with symptoms are typically evaluated by urine cytology, before referral to cystoscopy for a definite diagnosis. Cystoscopy in combination with cytology does well in identifying high grade cancer, but exhibits poor sensitivity for detecting low-grade cancer. Currently, a large proportion of symptomatic patients undergoing invasive cystoscopies have a negative test result and could with better non-invasive tests have been spared the discomfort of the procedure. Due to a high risk of recurrence after organ-preserving surgical resection of the cancer, patients are currently monitored by cystoscopy at regular intervals after treatment, in order to detect recurrence as early as possible. The large number of monitoring cystoscopies performed per patient represents a significant strain on both patient quality of life and healthcare costs. We have identified a panel of methylated DNA biomarkers which exhibits a high sensitivity and specificity for detecting bladder cancer. Importantly, the panel discriminates efficiently between bladder cancer and other urological cancers (94% sensitivity, 90% specificity), and displays unmatched sensitivity for detection of early grade lesions. We aim to develop a urine-based qPCR test based on these markers to improve early detection and monitor of bladder cancer, reducing the number of unnecessary invasive cystoscopies performed today, with benefits to both the patient and society. The project involves optimization and definition of a prototype test and demonstration of its clinical utility in prospective clinical trials. Successful completion of the project is expected to lead to a licensing agreement with an international molecular diagnostics company or to the establishment of a new company to commercialize the product, towards a prospective market introduction in the US and EU.