Bio-IT World | COMPANY TO WATCH | Ambrx tinkers with the building blocks of life 

By Pauline Parry 

QUATERNARY CODE: Ambrx brain trust includes (left to right) Troy Wilson, Tom Daniel, Peter Schultz, and Richard DiMarchi. They aim to take research "from the institute benchtop to the commercial bioreactor."

January 12, 2004 | IT TAKES A brave person to start a new company in today's economic climate. But Peter Schultz is not one to shrink in the face of a challenge. Schultz's latest venture, Ambrx, was launched in the spring of 2003. Despite numerous significant commitments — director of the Genomics Institute of the Novartis Research Foundation, overseeing about 400 research scientists, and head of a large research lab at The Scripps Research Institute — Schultz is an entrepreneur at heart. "You have to allow the science to drive you," he says. "When you have an idea with a large application and want to exploit it, you have to be willing to go beyond conventional funding sources and go to the private sector to get money to allow you to get great people to do good science."

San Diego-based Ambrx — the name is derived from the amber "stop" codon, or signal, used in the genetic code — follows in the footsteps of other Schultz-inspired companies, including Affymax Research Institute, Symyx Technologies, Phenomix, Kalypsys, and Syrrx. Schultz's goal, together with co-founders Richard DiMarchi (CEO) and Troy Wilson (chief business officer), is to create an organization that, in Wilson's words, would take the academic research "from the institute benchtop to the commercial bioreactor."

One of Schultz's long-standing interests lies in expanding the genetic code to create new proteins in vivo by designing methods to usurp normal cellular systems. His group has created biological systems in which the genetic code is expanded from a triplet (three-base) code to a quaternary code, as well as modifying transfer RNA (tRNA) adaptors to allow non-natural amino acids to be incorporated into proteins. This "chemical biotechnology," as DiMarchi calls it, builds new proteins in vivo via genetic engineering, incorporating novel amino-acid building blocks beyond the 20 commonly found in nature — creating proteins with new physical, chemical, and pharmacological properties. Currently, bacteria and yeast have been modified allowing up to 15 novel amino acids to be incorporated into proteins.

Ambrx Essentials  Focus: Protein therapeutics incorporating non-natural amino acids Scientific founder: Peter Schultz (Scripps) Current funding: $12.5M Investors: 5AM Ventures, Tavistock Life Sciences Current staff: 10 Location: San Diego

"The introduction of defined chemical modifications into proteins will enable the creation of new and better medicines," says chief scientific officer Tom Daniel. The goal is to create pharmaceutically preferred entities based on natural proteins. "There is significant room for improvement in the area of therapeutic proteins," DiMarchi adds. The company aims to increase the performance of protein-based drugs by improving both efficacy and safety. Also, it hopes to introduce molecular changes to allow easier routes of administration and to decrease required doses. Finally, the company believes that its technology will reduce the high cost of producing protein therapeutics.

At this early stage, Ambrx will not commit to an interest in any specific therapeutic area or set of biological targets. But senior management's expertise in cancer, endocrinology, infectious disease, and inflammation indicates likely prospects.


The Business Model and Plan 
Ambrx expects to partner its research efforts with big pharmaceutical and biotechnology companies, and does not anticipate taking a compound to the marketplace without partnering with a pharmaceutical entity. It also expects to have a significant number of academic research collaborations, including an ongoing relationship with Schultz. "We work very closely with Peter and expect that to continue," Daniel says.

While Schultz brings the technology to the company, the executive team has the experience to exploit it. DiMarchi, formerly head of product development at Lilly Research Laboratories, was involved in the development of several Lilly drugs and is a co-inventor of Humalog, the first biosynthetic protein approved for human use. Wilson joined Ambrx from the Genomics Institute of the Novartis Research Foundation, where he was vice president of business development and general counsel. Daniel was previously at Amgen, where he was a vice president and therapeutic area head of inflammation.

In September 2003, the company announced the completion of a successful Series A round of $12.5 million, led by 5AM Ventures and Tavistock Life Sciences. "We now have enough money," DiMarchi says, "to do the experiments to provide substantive proof of concept and to initiate three to four research programs." Management anticipates generating compounds with superior pharmacological profiles in one of these programs within two years.

With money, technology, and a seasoned executive team in place, Schultz believes the future is bright for Ambrx. "This company could become one of, if not the, leader in the protein space," he says.

Pauline Parry is an experienced biotech executive and a contributing editor for Bio·IT World. E-mail: pparry@pobox.com.


PHOTO OF WILSON, SCHULTZ, DIMARCHI BY: SANDY HUFFAKER JR.