Automation of MicroC as a CDx for myeloma therapies

Multiple myeloma MM is a debilitating and currently incurable hematological malignancy While the median survival has increased to years MM patients ultimately relapse and become resistant to therapy Once they reach this stage it is often a trial and error process until an effective therapy can be found Furthermore the MM bone marrow tumor microenvironment plays a significant role in disease progression and resistance to therapy There is a critical need for a clinical tool able to predict therapeutic response to drugs for specific patients We have developed an ex vivo microfluidic platform MicroC that can rapidly analyze the therapeutic response of a patient s MM cells to various drugs in coculture with their own microenvironmental cell components When MicroC was initially tested by measuring the ex vivo toxicity responses of patient MM cells to bortezomib a drug commonly used in MM therapy MicroC responses could be segregated into two groups which retrospectively correctly identified all patients as either clinically responsive or non responsive to bortezomib containing therapies We propose to develop and automate MicroC as a companion diagnostic for bortezomib and other MM therapies To achieve this project Lynx Biosciences is uniquely positioned through four key collaborations Dr Natalie Callander as a collaborator and Director of the University of Wisconsin Myeloma Clinical Program Professor David Beebe as an expert consultant and pioneer of simple microfluidic devices Salus Discovery as a collaborator to develop an automated sample processing workflow and Microfluidic ChipShop a manufacturing partner with years of experience in development and fabrication of microscale medical device platforms The proposal consists of two aims To develop a GMP process for fabrication of injection molded MicroC devices To automate cell isolation seeding and treatment within MicroC At the conclusion of Phase I we will have developed a large portion of the framework for the clinical rollout of the technology We will have a reliable and robust process for both the fabrication and operation of the MicroC ready to handle the larger scale required for Phase II Phase II will include a prospective clinical trial to test the predictive capabilities of MicroC by using the automated assay platform to segregate patients for therapy containing bortezomib and potentially other therapies Ultimately MicroC may be applied for use in reviving drugs which were not successful in late stage clinical trials identifying potentially successful preclinical drugs prior to initiation of clinical trials and hematological malignancies other than MM Project Narrative Currently many cancer patients including multiple myeloma MM patients are treated empirically or with drug combinations based on their physician s experience and clinical trial data it is impossible to predict which cancer therapies will be successful for individual patients Cancer therapies including MM therapies are also very costly andgt $ per month with potentially significant side effects In this proposal we aim to develop and automate an assay technology which enables clinicians to make more informed decisions regarding therapy course utilize precious time more effectively and reduce the cost associated with ineffective therapies