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Industry Insight

Overcoming the Challenges of Oncology Drug Discovery

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Industry Insight

Overcoming the Challenges of Oncology Drug Discovery

Oncology drug discovery can be a long and costly process, presenting drug developers with a number of challenges. 
We spoke to Dr Jean-Pierre Wery, President of Crown Bioscience, to find out how patient-derived xenografts (PDX) can help in this process, and learn more about the recent acquisition of Molecular Response’s PDX business.

AM: Can you tell us a little about Crown Bioscience Inc.?

JW: Crown Bioscience Inc., founded in 2006, is a platform technology company with expertise in the discovery and development of drug treatments for Oncology and Metabolic Disease. We are headquartered in Santa Clara, California and we also have operations in China, the United Kingdom and the USA. Our proprietary HuPrime®, HuKemia®, HuBase™, HuMark™, HuTrial™ and HuSignature™ platforms enable unique lead optimization and translational strategies to deliver superior clinical candidates. 

Since acquiring the assets and facilities of Molecular Response, we now have the world’s largest and most comprehensive collection of patient derived models; both clinically and ethnically diverse, deriving tumor models from Asia, the USA and Europe. Through our extensive in vitro and in vivo platforms, we offer clients assistance in quantifying the efficacy of their potential drug candidates and selecting the correct patient populations to treat before entering clinical trials.

With mounting pressure on drug developers to test potential therapeutics at an early stage, there is a considerable demand for patient-relevant disease models with which to determine stability, efficacy and the safety of each new drug candidate. Our unique collection of in-passage models, have been well-validated and developed to provide a comprehensive drug discovery platform with global capacity, enabling us to deliver results within a matter of months rather than the years taken to complete clinical trials.

We not only provide drug developers with the facility to test the performance of their drugs against specific tumor types, through parallel studies we can also give indications as to which additional cancers may benefit from new treatments. In this way we can identify the most relevant cancers for novel treatments, ensuring that the potential of promising candidates is fully realized.

Crown is committed to developing new screening platforms and patient models for the identification of new drug targets and treatment compounds in oncology. In conjunction with leading research institutions and pharmaceutical drug developers we hope to improve patient outcomes across the globe, downgrading cancer from a mortal disease to a manageable chronic disease.

AM: What are the main challenges faced by oncology drug developers?

JW: The main challenges for any emerging therapeutic compound concern the efficacy and safety of the drug when administered in the clinic. Before a drug can be approved for use in the treatment of human disease, it must first demonstrate that it does not cause lasting damage to the patient and is equally if not more effective than existing treatments for the same condition. In order to validate a candidate and establish these two factors, the drug must undergo extensive clinical trials to ensure compliance with stringent regulations that ensure the safety of the patient. However, sponsoring a candidate through to approval is an extremely long and costly process and the failure of a candidate can lead to irretrievable financial losses for drug developers. High clinical attrition rates (which reach 95% in oncology) have only increased the uncertainty felt amongst investors and executives and this has led to the abandonment of many promising candidates before their true potential is realized.

Whilst safety is always the primary consideration, attrition in the clinic is increasingly being attributed to the lack of efficacy of new compounds during trials. Many researchers believe this is a direct result of a lack of validated biomarkers and drug targets which are essential in the development of novel targeted treatments. Without the ability to identify relevant drug targets, and a relevant clinical population to treat, the possibility of success in the clinic is considerably reduced and the likelihood of abandonment is increased.

AM: How can improved pre-clinical models such as patient-derived xenografts help the oncology drug discovery process?

JW: Patient-derived xenografts (PDX) provide a patient-relevant platform on which to test therapeutics and accurately assess the effects of administering drug agents to patients with specific tumor types. Drug developers can use PDX models to screen the safety and efficacy of their compounds before investing in lengthy and extremely costly clinical trials. In this way pharmaceuticals can promote only their most promising candidates, thereby maximizing their chances of achieving success in the clinic. 

PDX studies also allow developers to run parallel trials of their compounds to identify relevant biomarkers that indicate which cancer sub-types and patient populations would benefit most from their therapeutic. Having identified a relevant drug target, a developer can advance into the clinic, confident that their compound will prove effective in combating the specified cancer type. This ability to screen therapeutics across a wide range of tumor types also has significant implications for previously abandoned candidates, as their potential can now be measured in a pre-clinical environment at a greatly reduced cost to the developer. In this way PDX provides a platform which can ensure the potential of all novel therapeutics is realized and developed into effective drug treatments.

AM: Crown Bioscience recently acquired Molecular Response’s PDX business. Can you tell us some more about this acquisition, and some of the benefits it will bring about?

JW: As part of the deal, Crown has acquired all of Molecular Response’s existing PDX models as well as 8,000 viable human tumors for model development from Molecular Response’s viable tumor bank of over 140,000 unique cryopreserved 100% US tumor samples. In addition, we will have the option to select and develop models from the wider collection if required. 

We have also assumed control of the Molecular Response facilities and personnel in San Diego, which has now been designated as a global center of excellence for Translational Oncology. It will serve to complement our existing operations in Beijing; Shanghai; Kannapolis, North Carolina and the UK, providing local expertise and support to Crown’s global clients.

The addition of Molecular Response’s PDX model bank firmly establishes our collection as the world’s largest and most comprehensive collection of patient derived models both clinically and ethnically diverse, deriving tumor models from Asia, the USA and Europe. The majority of the newly acquired tissues come from patients who have received prior treatment, many from metastatic tumors, at multiple stages of cancer development. Each tumor is supported by a companion molecular biobank and a suite of curated patient and sample data with the full collection representing over 76 clinical diagnoses. 

Our unique, clinically relevant models reflect the patient situation for each aspect of cancer progression across a wide range of cancer types and patient-relevant populations. Following the acquisition, our clients now have access to an even larger resource of relevant models containing clinically proven molecular markers present in global populations for the development of effective therapeutics. The additional tissue samples will also allow us to rapidly generate new models to cater to clients requiring specific cancer types in order to test their potential candidates.

Jean-Pierre Wery was speaking to Anna-Marie MacDonald, Editor for Technology Networks.

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Prior to joining CrownBio, Dr. Wery was Chief Scientific Officer at Monarch Life Sciences, a company dedicated to the discovery and development of protein biomarkers. Prior to joining Monarch, Dr. Wery spent three years at Vitae Pharmaceuticals, Inc. where he was VP of Computational Drug Discovery. Before joining Vitae he worked for 12 years at Eli Lilly and Company in various scientific and management positions. Dr. Wery received his B.S. and Ph.D. in Physics from the U. of Liege, Belgium. Following his Ph.D., he did postdoctoral studies at Purdue University with Prof. Jack Johnson. Dr. Wery has authored more than 50 abstracts and publications.
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