If you have an ACS member number, please enter it here so we can link this account to your membership. (optional)

ACS values your privacy. By submitting your information, you are gaining access to C&EN and subscribing to our weekly newsletter. We use the information you provide to make your reading experience better, and we will never sell your data to third party members.



No Place Like Home

Retooled ComInnex rejoins a chemistry network that is the brainchild of a Hungarian entrepreneur

by Ann M. Thayer
July 22, 2013 | A version of this story appeared in Volume 91, Issue 29

Credit: ComInnex
ComInnex scientist optimizes a high-temperature cyclization with ThalesNano’s Phoenix reactor.
This is a photo of a ComInnex scientist optimizing a high temperature cyclization with ThalesNano's Phoenix flow reactor system.
Credit: ComInnex
ComInnex scientist optimizes a high-temperature cyclization with ThalesNano’s Phoenix reactor.

For 30 years, Ferenc Darvas has been a globe-hopping academic, inventor, and serial entrepreneur. The seemingly indefatigable 71-year-old Hungarian is still on the go—editing journals, organizing conferences, and serving as an associate professor in the College of Medicine at Florida International University. His most recent business venture is to help create the Budapest-based firm ComInnex.

Although ComInnex has been working for the past year to establish itself as a chemistry services firm, the people behind it have a long history with Darvas’ network of companies, and reconnecting is central to its growth strategy. Ideas flow as Darvas and managers from ComInnex and his other businesses envision innovative links. At the same time, they know they are treading where another, larger company failed.

The ComInnex management and scientific team is primarily from the former Hungarian operation of Albany Molecular Research Inc., a U.S.-based contract research and manufacturing firm. AMRI purchased the Budapest operation in 2006 to be its European drug discovery center. It expanded the location in 2009, only to close it early last year as part of a cutback in its drug discovery services business.

This was when Darvas stepped in. AMRI had bought the business from him in 2006 when it was known as ComGenex. He founded ComGenex in 1992 based on his own solution-phase synthesis technology, which he claims became the first industrialized combinatorial chemistry technique.

For 14 years before it caught AMRI’s eye, ComGenex grew rapidly, accumulating more than 200 customers, according to past company reports. In 2002, it spun off a microscale flow chemistry instrument firm called ThalesNano. After selling ComGenex to AMRI for about $12 million, Darvas continued to invest in ThalesNano while setting up Darholding, a largely family-run management corporation.

After AMRI closed the 100-person operation, Darvas saw an opportunity to help his displaced former colleagues and create a business together again. “Of course the market had changed a lot,” he says, “but we had some money left over from the ComGenex sale, and if we could be shown the opportunity, we were willing to restart the business.”

The Com­Innex start-up team thought hard about how a new company could succeed, says Gergely Makara, former director of chemistry at AMRI Hungary and now ComInnex’ chief executive officer. “We don’t want to become just a contract research organization focused on chemistry,” he says. “We want to be innovators in technology and, through collaborations with our sister companies, provide services that aren’t available elsewhere.”

Those sister companies are located around the world. Darvas’ first private venture was CompuDrug, which was created in 1983 in then-communist Hungary and is now based in Florida. He formed Ireland-based Druggability Technologies Group, which includes NanGenex and NanoForm Therapeutics, in 2011. And ComCix provides human resources and information technology services for Darvas’ network.

“The best-performing systems are distributed systems,” he believes. “The multiple centers play with each other intelligently, sometimes compete with each other intelligently, and if you freeze a complex network into a less flexible, pyramidal hierarchy, you slow down spontaneous development.”

Like the network, the ownership system is complex, Darvas acknowledges. Darholding, friends, other private investors, and employees own stakes in the firms.

“Some of our former colleagues got substantial shares in the new corporation,” Darvas says about ComInnex. In return, many agreed to work initially for no or reduced pay. They did so, he adds, “in an absolutely positive spirit and very enthusiastically worked long hours to make the company successful.” ComInnex returned the undisclosed investment within six months and broke even last year.

Although they operate separately, many Darholding companies share a building in a Budapest business park. This infrastructure helped ComInnex get started, Makara says. “We could get down to the science right away.” From about 15 people initially, the staff grew to 40 within several months and should reach at least 50 by year-end, he says.

Makara’s near-term goal is to solidify the contract research business and integrate innovative chemistries into its offerings, including ones developed with ThalesNano.

For example, ComInnex drew on Thales­Nano’s experience with flow hydrogenation reactors to access new chemical space. “A lot of the molecules in corporate collections are built around flat mono- or bicyclic cores,” Makara explains. “And pharma especially would like to get away from flat molecules that can often have toxicity and solubility problems.”

Exploiting the reactors’ short residence time and high-pressure capabilities, Com­Innex scientists can selectively reduce an aromatic ring to either a partially or fully saturated ring. “We can generate these three-dimensional shapes in a high-throughput fashion to make very different new molecules and, in most cases, new intellectual property,” Makara says. Com­Innex intends to use the method to create its own libraries or provide the method to customers seeking to amend their compound collections.

Ideas flow the other direction too. “We utilize ComInnex as a chemistry resource,” seeking feedback on existing flow chemistry systems and ideas for new ones, ThalesNano CEO Richard Jones says. “There is definitely a mutual benefit for both firms in how we draw on each other’s expertise and how we advance ourselves in the market.

“While we are both very careful to avoid specifics about customers’ chemistry, we can get an indication of which way the market is moving to help adapt and focus our technology,” Jones adds.

The connection is very much like the one ThalesNano had with ComGenex. In 2004, they worked together on a prototype of Darvas’ first continuous-flow hydrogenation reactor. ComGenex used it to make combinatorial compound libraries, and ThalesNano launched it as the first H-Cube reactor in 2005. Last October, ThalesNano sold its 700th system.

In late 2012, ThalesNano launched its latest flow reactor, the Phoenix, which can operate at up to 450 °C and 1,450 psi. These are parameters a chemist wouldn’t normally access but that can make otherwise intractable reactions run, Jones says. “All of the initial testing on a functional level and then on real chemistry examples was done with ComInnex.”

This means ComInnex enjoys early access to new tools or ones tweaked to its specific needs. Having unique chemistry tools to solve customers’ problems means that “we can distinguish ourselves, which is a major advantage for a young company in a very competitive market,” Makara says. For ThalesNano, the work puts its instruments on display with potential customers.

Both new instrumentation and new chemistry are the focus of a grant ComInnex received from Hungary’s National Development Agency. It has developed a pyrolysis unit for carrying out batch reactions under a range of conditions and a companion high-pressure flow instrument. The work also involves novel nanoformulations for pharma and fine chemicals applications. “We are generating novel heterocycles that are not necessarily available without these technologies,” Makara says.

Darvas is proud of creating a network that ranks high among small and medium-sized enterprises in Hungary. Getting there required grit. The Hungarian business climate has been “a good school in which to learn flexibility,” he says. “The economic climate changes so suddenly and so inconsistently that the situation creates an incalculable business environment and presents real challenges.”

Former American Chemical Society president Attila E. Pavlath can attest to Darvas’ determination, having come to know him through working together in the Hungarian chapter of ACS. “Darvas is a very efficient and talented combination of scientist and entrepreneur,” Pavlath says.

Entrepreneurism was not possible during the Communist regime, but when change came, Darvas “quickly grabbed the opportunity to use his scientific background and business talent to start commercial activities,” Pavlath adds. Had an anticapitalist system not held Darvas back for many years, “he would have created a large international industrial complex,” Pavlath muses.

Although Darholding is not quite that yet, the many companies it encompasses have customers throughout the U.S., Europe, and Japan. “Earlier ComGenex clients have been very happy to learn that ComInnex returned to the business with the same team and with a similar theme as ComGenex,” Darvas says.

Continuity is important, but “the main factor is a high-quality, energetic, and young management and technical team,” Darvas says. “For me, being over 70, I focus on areas where I can contribute actively to the benefit of the network.” ◾


This article has been sent to the following recipient:

Chemistry matters. Join us to get the news you need.