Although cancer’s status as the leading therapeutic area for drug candidates looks set to remain unrivaled for the foreseeable future, the emphasis on each stage of drug discovery and development tends to fluctuate according to each drug maker’s pipeline. However, preclinical cancer drug development has experienced a renewed surge on the heels of the dramatic success of immunomodulatory therapies in the clinic. As the annual American Society of Clinical Oncology meeting, held in Chicago, recently highlighted, there is no sign of this wave subsiding as further successes are reported on a weekly basis. Charles River Laboratories (CRL), a preclinical contract research organization (CRO), has a unique front-row view on how the industry is unfolding.
The recent wave is driven by a number of factors, including a need to characterize how drugs in the market can enhance or benefit from interactions with the immune system that have been galvanized by immunomodulators. Alternatively, some companies are seeking a new lease on life for drugs that were shelved during clinical trials or even earlier due to a lack of efficacy. Finally, there is a large number of agents yet to reach the market that have the potential to either broaden the limited subset of patients who benefit from the spectacular effects of immunotherapies, or to mitigate undesirable and sometimes life-threatening side effects.
Despite having a proven track record in developing new drugs in collaboration with drug makers, intellectual property is not at the forefront of the CRO agenda. CRL contributes to the fight against cancer by providing expertise in testing that makes drug development speedier, more efficient and more translational, ultimately boosting the chances of a drug’s success in the clinic substantially.
A focus on in vitro and in vivo pharmacology studies leads to the development of know-how in interpretation of data and exposure to a wide range of therapies acquired with a large and diverse client base. As a result, CRL operates as a hub for leading companies and academic institutions and advises them on strategies for selecting their best candidates. CROs often guide clients away from paths that have proven to be dead ends for similar therapies and instead, lead them toward models that have yielded better quality data. Benefits include shorter development times and quicker go/no-go decisions. CROs frequently guide drug makers who have had little success in showing efficacy for a therapy to select models that present an easy medium and high challenge based on extensive historical data using the same class of therapy in those models. The inclusion of different levels of difficulty allows differentiation between moderate, exceptional or low performance and helps candidate selection. Examples include choosing syngeneic murine models with appropriate levels of T-cell recruitment or other immune cell characteristics according to the mechanism of a given therapy, or suitable models for assessing antibody drug conjugates (ADC) based on the target profile.
CRL experiences the early wave of novel therapeutic approaches and partners with a number of global companies who have new ways of modeling human disease conditions or strive to get more translational data from ever smaller sample sizes. This enables the science to advance and allows for more efficient use of animals in studies where they are necessary, preventing wastage.
A substantial portion of the work carried out by CRL is third-party validation of results first seen in the labs of smaller drug makers and academic laboratories. As these innovators seek a larger partner or investment, it is crucial to obtain unimpeachable data which can easily be provided by a CRO of good reputation for quality.
Finally, CRL is actively engaged in a number of not-for-profit research partnerships with academia and drug makers. Both the flagship oncology site in North Carolina and the newer CRL family member Oncotest headquartered in Germany have collaborated over the years to yield peer-reviewed publications with a wide number of partners in the US, Europe and Asia including the Mayo Clinic and the Max Planck Institute. CRL looks to engage in public-interest consortia such as PREDECT, a five-year Innovative Medicines Initiative (IMI) partnership between pharmaceutical companies and academia in Europe focused on comparing the pathological and molecular profiles of novel in vitro platforms with those of human tumors. The consortium recently wound down after highlighting more appropriate in vitro platforms both for target validation and subsequent preclinical studies.
Regrettably cancer is a serious and highly personal disease which will continue to afflict the population as a leading cause of death and decline in quality of life for the foreseeable future. The industry seems to be recognizing that and there are noticeable trends towards working more closely together. We see this with rival pharmaceutical companies who collaborate on clinical trial designs in order to accelerate timelines, and the proliferation of consortia such as Vice President Biden’s Genomic Data Commons launch. In the past, CROs were not a part of these initiatives, but as they become more sophisticated and develop unique skill sets, they have become vital partners in the struggle to overcome a disease whose complexity of origination and pathology only becomes more complex with each new data set published. The closer the collaboration between government, academia, commercial drug makers and CROs becomes, the quicker the terrifying impact of cancer will be reduced and contained.
About the author
Aidan Synnott is Site Director and Global Business Operations Lead at Charles River Laboratories, where he oversees the company’s oncology discovery services sites.
Filed Under: Drug Discovery