Ambition and More

NGP. What are you focusing on at ArQule?
TC. We are very much a molecularly targeted drug discovery company, and while you hear that a lot of companies are in that space, in fact, they really don’t have such specific targets – the claim versus the reality is often different. In our case, we’re happy to report that what we thought was a molecular target specific inhibitor, actually inhibits specifically only the target. We may well be an industry-leading company that has a true c-met-kinase inhibitor in contrast to some of the multi-kinase inhibitors that are being developed by our fellow competitors.

1. NGP. You are responsible for all the research activities and new oncology drug candidate selection. What does this mean?
   TC. Basically, in the previous business model, large multi-national pharmaceutical companies such as Pfizer, Merck and Novartis, will come in and say we want a library of a particular group of chemotypes. In some cases they just sent us their library requirements and we simply synthesized the molecules for them.. In other cases, they gave us the targets that they wanted us to format our assays and to screen our libraries against them as well. So it all depends on what they needed from us.
   
   We are moving away from the chemistry service mode into cancer drug discovery and development mode. So what that means is we will format assays for various novel and validated targets. We will screen ArQule’s proprietary compounds against those targets, and hopefully, we will be smart enough, and we think we are, to pick the right molecules so we can start moving them into the clinic.
2. NGP. You’re also responsible for human clinical pharmacokinetics. Do you face particular challenges in this?
   TC. Clinical testing of drugs has always been a challenge. Competing for patients is tough. Data management and scrubbing is difficult, and some of our current staff really don’t have that kind of skill set, so a lot of retraining and a lot of really rapid recruiting has been happening. But overall we’re making that transition, although it’s hasn’t been smooth sailing some times.
3. NGP. What were your thoughts on transparency in clinical trials?
   TC. Clinical trials by definition can never be completely transparent as patients are involved and personal medical information needs to be protected. However, given that, I would say once one can achieve anonymity on the patient’s part, everybody should have the right to know what a sponsor is seeing and doing. Because that helps the whole field – from the FDA, to other pharma companies, and to the patients themselves. So, I believe that once the patient’s identity and rights are protected we should try to strive for transparency.
4. NGP.  And how long do you think it will be before that happens?
   TC. I’m hoping with support from different quarters including my colleagues at ArQule and colleagues from other pharma companies – especially the big multi-national pharmaceutical companies – and with the regulatory agencies working on it, this may be achieved within the next five years or so.
5. NGP. You’ve built competitive advantage to drug discovery and development platforms, and can you explain how your preclinical and clinical development platforms work?
   TC. Within the last 10 years we have learned from the best in our industry. We have picked up a lot of things, like what to do and what not to do. Through that proprietary know-how, we’ve learnt and built our own custom-made platform chemistry and implemented smart screening strategy, which will allow us to generate hundreds of high quality drug-like leads within a couple of months. If you go to a big pharma company and ask the chemists to generate that number of optimized hits, it will take about a year, so we have speed on our side, which is what makes a difference in our business.
6. NGP. What are the main challenges that you come across as a small biotechnology company?
   TC. As we are a small company, when we decided to exit the chemistry services business and move into full-time discovery and development, finding the staff that had that kind of experience and knowledge was a challenge.  We had to restructure corporate activities normally carried out by 300 chemists toward how to deal with clinical trials. That was a huge transition – to trade in one skill set for another to allow us to do what was needed was hard on everyone.
   
   But, it’s beginning to work out for us. Recruiting has always been a challenge, especially in the Boston area. So many biotech and pharmaceutical companies are there, but I believe that we bring in the right people, and hopefully with some of the newer technologies coming into play, that will help in the process of recruiting too.
7. NGP. And what’s in the pipeline for ArQule in the next 10 years?
   TC. Hopefully our productivity will go up. If you look at our industry as a whole, 15 years ago, for every 100 compounds that were put into Phase I development, 14 of them made it into a new drug. Now we put 100 compounds into the clinic, 8 of them become a new drug. I would like to see us in the 14 to 20 successful-drugs-per 100 IND range, and with the right tools and the right decision makers in place, we may be able to do just that.
8. NGP. So, what do you think we should be on the lookout for in the future?
   TC. In my mind the next generation technologies are not going to be more high throughput screening, more unknown genomics, proteomics, metabolonomics. Rather, I believe it’s maybe more going after specific targets and specific cellular changes because we’ve been with these -omics for five to 10 years now, and if you ask most of my colleagues, they would agree with me that very little has ever come out of these –omics effort. More specificity is required, and when we do that, we will improve our so-called hit ratios in drug discovery and development.

About ArQule

ArQule is a clinical-stage biotechnology company engaged in the research, development and commercialization of targeted cancer therapeutics. ArQule’s expertise in molecular biology enables them to understand certain biological processes that are responsible for different types of human cancers and to discover novel drug candidates to treat these diseases. The chemistry capabilities enable them to generate product candidates possessing pre-selected, drug-like properties and a high degree of specificity for cancer cells.

About the contributor

Prior to ArQule, Dr. Thomas C. K. Chan was VP of R&D and Chief Technology Officer of MacroChem Corporation, a specialty pharmaceutical company, from 2000 to 2005. From 1997 to 2000, he served as Senior Director of Pharmacology and Toxicology at EPIX Medical, Inc. From 1992 to 1997, he was Director of Therapeutic Development at Creative BioMolecules, Inc. From 1990 to 1992, he was Associate Director of the Purdue Cancer Center, and held an appointment as a tenured professor at Purdue/Indiana Universities from 1985 to 1992.