ARQ-197 has two unique properties that may distinguish it from its competitors.
ARQ-197 is very selective for c-Met, in contrast to Exelixis’ compounds, which inhibit additional kinases as well. ARQ-197 and the Exelixis compounds represent two different approaches in the field of kinase inhibitors, as each approach has its merits. This issue as well as the promise of kinase inhibitor market are discussed in my previous article on Exelixis.
It is highly unlikely that one approach will be superior to the other in all cases and conditions, however, there are several reasons why a selective inhibitor might be more suitable some cases.
Based on clinical results from ongoing trials, c-MET inhibitors demonstrated signs of activity but they were not as potent as some had hoped. Coupled with the potential synergy with other drugs, this led many researchers to suggest that the way forward with c-MET inhibitors is in combination with other agents. Since anti-cancer drugs are often associated with strong side–effects, combining more than one drug increases the overall toxicity. Selective inhibitors are believed to be safer than multi-targeted inhibitors, so a benign safety profile can be a big advantage when several drugs are needed to be combined.
Another potential advantage for a compound that hits a single target is that there is a high likelihood that the clinical effect is a direct result of hitting that specific target. In the case of XL184 and XL880, there is no way of knowing which target contributes to the effect and to what extent. It is possible, for example, that the clinical effect seen with these agents has nothing to do with c-Met inhibition. Of course, when a drug leads to tumor shrinkage, it does not really matter to the patient what is the exact mechanism, but when a large pharma decides to license a compound and commit to a costly clinical program, such lack of clarity could be problematic, for example, in picking the right patients based on the targets expressed by their tumors.
2) Unique Mechanism of Action
An even more important differentiator ARQ-197 has over the rest of the compounds is its unique mechanism of action. Most kinase inhibitors in development are “ATP-competitive”, i.e. they disrupt signaling by binding to a specific region called “ATP-pocket” and prevent kinases to pass the signal. ARQ-197 disrupts c-MET signaling by binding a different region of the protein, therefore, as a non- ATP competitive kinase inhibitor, ARQ-197 is thought to be more specific and consequently safer than other agents. In addition, it may overcome common resistance mechanisms and may be used in combination with ATP-competitive c-MET inhibitors. In fact, this property can turn other c-MET kinase inhibitors from competing compounds into a combination opportunity for ARQ-197.
Second-Generation Database Companies. New companies will have a tough time pursuing the Incyte Pharmaceutical Inc. model of providing relatively raw biological or chemical information to pharma companies for significant up-front fees, milestone payments, and reach-through royalties. Now that pharma companies possess much of this information in-house, they want to buy solutions rather than information. Hence the advent of new companies like Rigel Inc., which identifies its own targets and then validates them before presenting them to pharmaceutical companies, or database companies like Genaissance Pharmaceuticals Inc. or Lexicon Genetics Inc., which provide genomic databases and accompanying services to pharma companies with focused information needs. Subscriptions to these databases are typically short-term (i.e., two to three years), and are non-exclusive. The pharma company is only interested in obtaining a lead over its competitors, not exclusive access to the tool offered by the platform company. Customized services are the unique selling proposition of these data offerings, whether it is Lexicon's mice, Genaissance's clinical cohort construction, or ArQule Inc.'s custom arrays. The economics differ from the past as well. The emphasis is on annual access fees and milestone payments, with low or very modest royalties. Downstream, the pharma company can patent freely, without having to worry about royalty stacking. As the technology advances, the trend is to digitize as much as possible, replacing the early stages of the previously high-cost wet lab experiments previously undertaken by pharmaceutical companies. READ READ READ READ READ READ READ'''''''''''''''''''' Technology Transfer, Enabling Pharma to Buy and Make for Itself. Formerly a company selling chemical libraries to multiple pharma companies, ArQule has transformed its business model; it is now training drug firms to make compounds on their own. Its first deal of this nature was with Pfizer Inc., for which it will receive well in excess of $100 million in guaranteed payments. Accompanying the transfer of ArQule's system was a "user's manual," equipment and ArQule employees loaned to Pfizer. The system is for Pfizer's internal use only; it may not sublicense it to others. The terms are non-exclusive, enabling ArQule to do the same deal with multiple pharmaceutical and biotech companies. Although $100 million is a lot to pay, Pfizer is able to use the platform to make compounds without the need to account to ArQule for royalties on downstream products. Applying these large, guaranteed payments, ArQule can now focus its attentions on internal drug development.
Top 10 Biotech Stocks 2012: ArQule Inc. (ARQL) RATED THE BEST ArQule, Inc., a clinical-stage biotechnology company, engages in the research and development of cancer therapeutics directed toward molecular targets and biological processes. Its lead product ARQ 197 is non-adenosine triphosphate competitive inhibitor of the c-Met receptor tyrosine kinase, which is being evaluated as monotherapy and in combination therapy in a Phase II clinical development program that includes trials in non-small cell lung cancer, c-Met-associated soft tissue sarcomas, pancreatic adenocarcinoma, hepatocellular carcinoma, germ cell tumors, and colorectal cancer. The company is also developing ARQ 621, a Phase I program focused on inhibition of the Eg5 kinesin spindle protein. Its clinical stage products include ARQ 501, ARQ 761, and ARQ 171, which are designed to kill cancer cells selectively while sparing normal cells through the direct activation of DNA damage response/checkpoint pathways. In addition, the company involves in pre-clinical development of B-RAF and AKIP Kinase inhibitors. The company has collaborations with Kyowa Hakko Kirin Co., Ltd. and Daiichi Sankyo Co., Ltd. ArQule, Inc. was founded in 1993 and is headquartered in Woburn, Massachusetts.