April 15, 2008 (Vol. 28, No. 8)

Company Strives to Merge Biology and Chemistry to Expedite Development Process
Drug development generally starts with the discovery of a biological target and ends in clinical trials. In between these biological starting and ending points, biotechnology companies must find ways to synthesize, modify, and manufacture a drug candidate. All of these processes require the skills of chemists like those at Anthill Technologies. “We are flexible and experienced in merging biology and chemistry,” says Joseph Hogan Jr., Ph.D., an organic chemist who founded Anthill in 2005.

Throughout his career as a chemist at Polaroid and Waters and as founder of ArQule, Dr. Hogan observed that biologists and chemists often have difficulty communicating with each other. Chemistry is a logic-driven, reductionist science, where a premise is tested, and the response leads to the adjustment of the premise for further testing. On the other hand, biology is an emergence science controlled by feedback loops.

“Nature did not logically develop biology,” says Dr. Hogan, president and CEO of Anthill. Instead, Nature solves problems through trial and error, often resulting in suboptimal chemical solutions. For instance, the synthesis of three major polymers involved in biology—proteins, oligonucleotides, and carbohydrates—is based on chemical reactions that run uphill under unfavorable mass action conditions. “Nature did this three times with exquisite control using three different chemical approaches,” says Dr. Hogan, “so I think of biology as a special kind of chemistry.”

Dr. Hogan also studied how ants optimize combinatorial situations such as finding and transporting food. “Ants are a tremendous example of emergence biology,” he adds.

In fact, mathematicians have developed algorithms and so-called emergence software based on anthill strategies, which businesses use to optimize operations like the delivery of overnight packages nationwide. The chemical experts at Anthill also use a type of internally developed emergence software to probe new building blocks to create novel chemical compositions and processes.

The company’s high-speed chemical discovery engine, the applied chemistry operating system, or ACOS™, reduces the time, cost, and risk associated with evaluating targeted drug leads. The capabilities of ACOS include the rapid design and synthesis of focused libraries (5–50 mg) for lead discovery and optimization, accelerated medicinal chemistry (50 mg–10 g), process R&D for rapidly evaluating multiple synthetic routes, and fast scale-up of drug quantities for preclinical and clinical testing.

In addition to its Massachusetts-based operations, Anthill offers a full spectrum of R&D programs such as GMP synthesis of preclinical and clinical candidates and experimental ADMET profiling, performed by partners in India, Europe, and China.

Perfecting Lead Compounds

Often customers come to Anthill with a lead compound that they want to quickly perfect in order to satisfy investors or garner a milestone payment from a pharmaceutical partner. “For example, they may need 50 mg of a molecule with a particular substituent arrangement, but it’s difficult to synthesize. Or, a customer wants to move a substituent on a ring to a different site to see if it will cause a certain therapeutic outcome, but they cannot find the chemical reagents to do the job. We make all of that happen,” says Dr. Hogan. “We construct what’s necessary to attack the applied chemistry problems, and we do it fast and flexibly.”

As a fast-order chemistry synthesis operation, Anthill can solve short-term chemical problems that tend to slow or halt progress. “We’re like the Wizard of Oz behind the curtain,” Dr. Hogan says. “Customers want their product fast and we find the best route to a finished product. The goal is to quickly make enough of a compound to ascertain its properties and potential commercial value.”

Anthill’s methods also extend to rapid scale-up processes. While synthesizing molecules, ACOS software can be configured to obtain information about how temperature, solvents, and other factors affect process development. Not only does Anthill merge biology and chemistry, but it also combines organic chemistry, analytical chemistry, separation science, and automation engineering by running synthesis, extraction, filtration, and separation steps in parallel. In some cases, a less than optimal chemical synthesis still yields a pure product because of elegant separation methods. “There’s a lot of cross-discipline hybridization going on,” says Dr. Hogan. “It’s a different way of thinking.”

Anthill also creates libraries of compounds based on certain chemical criteria, which are delivered to clients on a set schedule. “Today’s researchers want focused libraries of 50 to 100 molecules with specific characteristics built around a theme,” notes Hogan. “That’s different from a few years ago when people wanted large combinatorial libraries to test.”

Although many compositions are synthesized in-house, others are outsourced by Anthill to achieve an optimal combination of speed and cost for customers, Dr. Hogan notes. Anthill is a high-speed chemistry company and has no intention of becoming a drug discovery company itself. “It’s important to our customers that we are not competing with them,” says Dr. Hogan.

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