Interview conducted by April Cashin-Garbutt, BA Hons (Cantab)
Please can you give a brief introduction to Crown Bioscience and the oncology drug discovery services you provide?
Crown serves pharmaceutical companies and biotech companies. We have two areas of focus: oncology and metabolic diseases.
In the oncology space we focus on pre-clinical services. Essentially, we have all the tools to help our customers move from target discovery, target validation, to a clinical candidate.
Crown is a U.S. company. We have two research sites in China: one in Beijing, one in Taicang, close to Shanghai. We have another research site in the U.S., in North Carolina, and of course now, with the acquisition of Precos, we have also research capabilities in Europe.
Translational science is one of the main focuses of the company. We have been working on special animal models often called "PDX," or Patient-Derived Xenograft models. These have made a significant difference in the way people develop compounds and take oncology compounds to the clinic.
Crown has been an early developer of these technologies and today we are the company with the largest and best characterized PDX collection in the world. We started to build these technologies in 2007. Originally people were interested but it has only been in this last year that it has become recognized and accepted as a critical tool for oncology drug discovery and development.
CrownBio have recently acquired the shares of PRECOS. What were the reasons behind this acquisition and what technologies will CrownBio’s clients now be able to access?
There are multiple reasons. Precos was initially incubated as a business unit at the University of Nottingham. The University of Nottingham was one of the pioneers in the development of the Patient-Derived Xenograft models, and has remained very active in this research field.
Precos has developed quite a number of models that are very interesting. All the Precos models are Caucasian models. Crown, because of our operations in China, mostly has Asian models, that is models representing Asian patients. We do have some Caucasian models in the U.S., but we're quite interested to get access to more Caucasian models. That's one of the reasons we acquired Precos.
The other reason is, besides those models, Precos has always been a very research oriented company. They have been developing other translational tools and cancer biology tools which are very relevant if you try to develop new compounds for cancer indications. So, there's a very good technical complementarity between the two companies. We focus on similar technologies. We're both very interested in the translational space in oncology.
Precos is obviously also in Europe. For Crown, so far the largest part of our revenues are coming from the US and Asian markets. We have some presence in Europe and by acquiring Precos, we show our strong desire to increase our impact in European markets and serve more European customers.
How do CrownBio’s and PRECOS’ technologies complement each other?
Both companies had a very early interest in translational science and how it applies to oncology. Based on that, we have both been working to develop better animal models and try to make them more predictive.
The problem with the early models is that by and large they are not very predictive of how a compound might behave when you take it into patients. There's always been a strong interest in developing models that would be much more predictive, and that will allow drug developers to better understand what will happen when they take a drug candidate into patients and into the clinic.
I think to a great extent, PDX models achieve that. Both Crown and Precos have been thinking along these lines for quite a while.
As I mentioned, the models Precos have developed are Caucasian, thus they are complimentary to the large Asian collection we have. Also, Precos has been working on specialized models like models for drug resistance, which are very important. Precos also started working on models aimed at understanding the impact of combining both drugs and irradiation, which is a very common practice in treating cancer patients, but has not been explored very much in animal models. Again, that's of very high interest to us.
There's a great synergy in continuing to develop better translational tools and to improve the way we discover and develop drugs.
What impact will this acquisition have on CrownBio’s position in the market?
We want to have more presence in Europe. Again, if you look at the fields of cancer biology and cancer translational science, I think that in the i U.S. we are the dominant player. I think in Asia we are a dominant player. I think we have some presence in Europe, and I believe this will expand significantly with our acquisition of Precos.
What excites you most about the current drug discovery solutions you offer?
I think that for the first time we have tools which are very much predictive of clinical activity. There's been a lot of talk about the fact that pharmaceutical companies have not been very efficient. There are a lot of failures. There are not as many compounds being approved.
If you look at the whole process of discovering and developing new drugs, the step which is the most critical in driving the cost and efficiency is the probability of success of Phase 2 clinical trial. So, if you have a very predictive translational tool, such as Crown’s PDX models, which can teach you what is the most likely successful indication for your new drug candidate, and what is the most likely patient population who will benefit from your drug candidate, and how you can select these patients, such a tool can have a profound impact on how you discover and develop new oncology drug candidates.
It has been shown many times now that tumors growing in these PDX models very closely resemble the tumors growing in patients. So, each PDX model very closely mimics a cancer patients. If you have enough of these models, then you can start to mimic human clinical trials in the animal models. When you take a new compound into these models you can often see that the drug will work on certain models, but will not work on other models. Then you can ask the question "why is it working in this model, but it's not working in those models?" Since we have developed extensive “profiling” information (such as Genomics information) for these models, we can start to make correlation between the response (or lack of response) and our profiling data. So, we realized the drug candidate works in these models because certain genes are amplified or modified in these models. And they don’t work in these other models because those genes are not modified to the same extent.
More and more data are showing that these correlations are quite translatable to human situations. So when you know this information, you can go into the human population and say "Ok, now I know which patient is most likely to benefit from the drug," and you can apply that knowledge to better design your Phase 2 clinical trial and increase your probability of success. And that will make a huge difference in our ability to bring more promising drugs, drugs which are more “personalized” for specific cancer types,and for specific patients to the market.
What are CrownBio’s plans for the future?
We're always interested in technologies that can make a difference in discovering and developing important drugs. We will continue to focus on oncology because we believe there are still a lot of unmet medical needs in this field. We will be looking for technology that can make the process of bringing new drugs to the patient more efficient and more successful. Certainly, within translational science there's still a lot of work to do. I think we can improve upon those models. As I mentioned before, we can look for models that help us to better understand drug resistance or cancer recurrence. In many cases patients get into remission so the cancer is initially treated, but often after a few years the cancer comes back and often, that cancer is more aggressive.
We want to build models that allow us understand resistance and recurrence. We are going to build models that help us better understand the combination of drugs with radiation. Also we want to work and see if we can build in-vitro biology tools (which are easier to engage and cheaper to engage), that would have the same predictive power of these PDX models. There will be cheaper tools, faster tools to better understand how to take a compound forward to patients.
Where can readers find more information?
About Jean-Pierre Wery
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.