As the costs of sequencing and drug testing continue to be driven down, we’ll increasingly see technologies that take into account differences between people and even within people. The hope is that this will lead to ultra-personalized medicine. One of the most anticipated use cases is in oncology because there is even a level of heterogeneity within the same solid tumor, leading to drug ineffectiveness or even resistance. Presage Biosciences is one company that hopes to pioneer this personalized and data-driven approach, which they call ” precision oncology.” We had the opportunity to interview its founder, Dr. James Olson, who is also a pediatric oncologist at the Fred Hutchinson Cancer Research Center.
Shiv Gaglani, Medgadget: What is CIVO?
Dr. James Olson: CIVO is a technology platform, being developed by Presage Biosciences, that is designed to improve treatment decisions for cancer patients. The patented platform offers an entirely novel method for simultaneously analyzing multiple cancer drug candidates and drug combinations within a single tumor while that tumor is still in a patient. By employing this technology we can discern which drugs induce a localized anti-tumor response, which we believe will be predictive of therapeutic effect upon systemic administration of treatments.
Medgadget: How does CIVO work?
Dr. Olson: The CIVO systems allows for the precise placement of a three dimensional array of multiple microdoses of candidate treatments through the skin and directly into a solid tumor. The three dimensional aspect of the microdosing provides the ability to analyze drug effects across the span of a living tumor, capturing the heterogeneity of cancer cells and related variation in drug response.
Utilizing proprietary CIVO analysis algorithms, which incorporate complexities of tumor biology, pharmacodynamics and pharmacokinetics, multiple zones of the tumor can be evaluated for the assessment of cellular response, drug target engagement and drug penetration. The result is a quantitative, multi-dimensional portrait of drug response.
Medgadget: How would CIVO be used to help cancer patients?
Dr. Olson: We envision that oncologists will use CIVO as a tool for making treatment decisions for cancer patients. Utilizing CIVO, it is hoped that effective drugs will be chosen that provide maximal therapeutic benefit, while avoiding ineffective drugs that, for that individual patient, will provide no benefit and will only expose the patient to deleterious side effects.
Medgadget: Describe how/why CIVO was created?
Dr. Olson: The CIVO Precision Oncology platform was invented in my research lab at the Fred Hutchinson Cancer Research Center and is now being advanced at Presage Biosciences through clinical stage evaluation and research collaborations.
I treat children with cancer at Seattle Children’s, where we care for most children with cancer in the the northwestern US. In cases of recurrent cancer, all oncologists lack the technology to understand whether a patient’s cancer is resistant to the drug(s) that we prescribe. As a result, far too often we learn that the therapies we have prescribed cause adverse effects with little or no clinical benefit. Furthermore, these children cannot spend that precious time at home with their families, but instead must travel to Seattle to participate in these clinical trials.
With CIVO, we were focused on finding a method to overcome the limitations inherent in all current methods of evaluation of cancer drugs so that we could determine beforehand which drugs and drug combinations a patient’s tumor may respond to and which they will not – and to do this with far better predictive capability.
Medgadget: How does CIVO differ from traditional oncology practices in oncology drug development?
Dr. Olson: Unlike in vitro, ex vivo or conventional in vivo testing methods, CIVO provides the only evaluation method to simultaneously analyze multiple therapeutic candidates or drug combinations within the native microenvironment of a living tumor, to offer a rapid method for the selection and advancement of optimal oncology candidates. And unlike genomic methods that rely on retrospective analysis of often thousands of patients to identify markers that increase the odds response, CIVO directly measures drug response in a given patient, in their own tumor, at that point in time. We hope this elegant and empirical method will provide far better information to oncologists making difficult recommendations for treatments of cancer patients worldwide.
Medgadget: What stage of development is CIVO in?
Dr. Olson: CIVO is currently being evaluated in a Phase 1 clinical trial. This single-arm, non-therapeutic, observational study is being conducted to evaluate the feasibility of CIVO in assessing lymphoma response to multiple microinjected candidate chemotherapy agents.
Medgadget: How is the study being conducted?
Dr. Olson: The trial is enrolling patients with either newly diagnosed lymphomas who have not yet received treatment or relapsed lymphoma previously treated with one or more agents in the R-CHOP chemotherapy regimen (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone). Patients’ lymphomas are microinjected with up to four drugs comprising rituximab, vincristine, doxorubicin and prednisolone. Twenty-four hours later, the lymph node of interest is removed and analyzed for target engagement and tissue response.
Medgadget: What is the driving force behind the creation of CIVO?
Dr. Olson: When a patient learns they have cancer, they want effective drugs that cause as little toxicity as possible and oncologists, in turn, want to have methods to help determine the most appropriate treatment approach for each patient. Researchers have tried with little success to find methods of predicting cancer sensitivity to therapeutic agents using cancer cells grown in tissue culture dishes have. Patients and physicians are eager to have a reliable method to assess cancer drug sensitivity or resistance and we hope methods like CIVO may help impact the future of cancer treatment.
Medgadget: How can CIVO help other companies advance drug development efforts and which companies are currently utilizing this approach?
Dr. Olson: Using CIVO, Presage can provide oncology-focused pharmaceutical companies previously inaccessible in vivo data to validate novel targets, promote drug candidates to the right indications, and discover effective drug combinations, The majority of the work Presage does with partners is to identify novel cancer combinations. Unlike traditional mouse studies, Presage can screen dozens to hundreds of combinations in the time it would take for a single combination to be evaluated with traditional means. Presage currently has research collaborations with Celegene Corporation and Millennium: The Takeda Oncology Company.