HAMBURG, Germany—Evotec AG has entered into a research collaboration, called TargetDBR (DNA Break Repair), with the laboratories of Prof. Peter Glazer and Prof. Ranjit Bindra at the Yale University School of Medicine. The objective of the collaboration is to identify novel mechanisms, targets and compounds that have the potential to interfere with DNA repair and thus have potential applications in many cancer indications.
DNA repair mechanisms allow cancer cells to cope with extensive genome rearrangements, as well as to escape conventional radiotherapy and chemotherapy. This is the first collaboration to be announced as part of Evotec's open innovation alliance with Yale University. Financial details were not disclosed.
Yale and Evotec will collaborate in a highly integrated fashion and share potential commercial rewards. Explaining the process, Dr. Cord Dohrmann, chief scientific officer at Evotec, says, “Evotec aims to establish true partnerships in which each partner focuses on its core expertise. Usually, this means that Evotec covers primarily drug discovery aspects whereas our partners at Yale focus more on basic biological questions associated with the mechanism or target we are pursuing. That is to say, we strive to create plug-and-play situations in which there is no time or effort wasted in transferring or acquiring technologies, but rather we progress the project from day one.”
At least at the beginning, key components of Evotec’s drug discovery infrastructure will be high-content screening, medicinal chemistry and proteomics, he adds.
TargetDBR is based on systematic cell screens designed to identify DNA repair inhibitors and their mechanisms of action. The application of Evotec's high-content cellular screening platforms allied to chemoproteomics-based target deconvolution reportedly will enable the identification not only of novel DNA repair inhibitors but also of novel tractable targets in DNA repair pathways. The initial focus will be on increasing the effectiveness of glioblastoma brain tumor treatments, but it is expected that the DNA repair inhibitors will also find application in many other cancer types.
“Glioblastoma is one area of glaring unmet medical need where we urgently need new treatment options,” Dohrmann observes. “The potential to combine conventional treatment options with drugs that block DNA repair mechanisms is very compelling in this area. We are very excited about the opportunity to collaborate with Peter and Ranjit to identify and develop novel classes of DNA repair inhibitors that have the potential to become highly effective therapeutics against difficult-to-treat cancers such as glioblastoma.”
The most common primary malignant brain tumors are malignant gliomas and glioblastomas. While the incidence is relatively low at about two to three cases per 100,000 people, glioblastoma tumors are aggressive, resulting in a dismal prognosis for patients and an associated poor quality of life. Standard-of-care therapy involves radiation and chemotherapy with temozolomide and provides a median survival of 15 months.
“Deficiencies in DNA repair mechanisms constitute not only initiating events leading to cancer but also provide potential therapeutic targets on the basis of the concept of synthetic lethality,” Dohrmann states. “Synthetic lethality requires the impairment of two genes in combination to lead to a lethal phenotype. Impairment of each gene should be viable. Synthetic lethal approaches to cancer therapy are being explored to improve effectiveness while reducing potential side effects.”
“Through this collaboration with Evotec, novel biological discoveries and medical insights made at Yale are being effectively translated into a state-of-the-art drug discovery project. The collaboration is already demonstrating the benefit of the Yale-Evotec open innovation alliance in accelerating drug discovery projects,” said Dr. Jon Soderstrom, managing director of Yale's Office of Cooperative Research, in a news release about the joint effort.
In January 2013, Evotec AG and Yale University entered into a strategic agreement to leverage first-rate science performed at Yale University together with Evotec's drug discovery infrastructure and expertise into highly innovative discovery approaches in diseases of high unmet medical need. Evotec and Yale have defined a wide range of scientific fields—including metabolic diseases, central nervous system problems, immunological diseases and cancer—where they will jointly assess and potentially pursue novel assays, screens and models but in particular exploratory drug targets and compounds.