By Jennifer Boggs, BioWorld Today

“When one door closes, another opens” could easily be the motto for the biotech industry; even as companies tighten their belts in response to economic challenges, those restructuring moves have created new opportunities in the space.

One such venture is Zenobia Therapeutics Inc., which emerged last summer after ActiveSight, the San Diegobased division of Rigaku Americas Corp., ended some of its research work in a cost-cutting move. But only weeks before the doors closed on that research, Vicki Nienaber, chief scientific officer at ActiveSight, was awarded a grant from the Michael J. Fox Foundation for Parkinson’s Research to work on a new target in collaboration with Johns Hopkins University.

In order to receive the grant money, Nienaber needed a company. So she and a handful of other former ActiveSight scientists founded Zenobia. “The doors closed on ActiveSight on the last day of May,” Nienaber told BioWorld Today. “And on the first day of July, we moved into our lab” in the La Jolla Cove Research Center, home of the original site of the Scripps Research Institute.

Zenobia’s focus is on central nervous system diseases, particularly areas that are “not really addressed by big pharma but have large market potential,” she said. Drug discovery at Zenobia is based on the fragmentbased screening approach, a process that Nienaber helped invent while at Abbott – specifically the crystallographic fragment-based screening method – and later worked on while at San Diego-based SGX Pharmaceuticals Inc. and then at ActiveSight. In fact, Zenobia’s eight-member team is made up of alumni from either ActiveSight or SGX, she said. Prior to fragment-based screening methods, most drug discovery work involved high-throughput screening, which involved the creation of a large library of compounds screened for particular activity. But the process requires running a considerable number of compounds before finding one that covers a specific target, and researchers would “spend a lot of money and end up with a certain level of disappointment,” Nienaber said.

With the fragment-based approach, “you screen pieces of molecule,” rather than the whole compound, to find pieces one at a time, she said. “Though some were skeptical, because the compounds you start with don’t bind that tightly, with other tools like X-ray crystallography, you’re able to optimize them fairly rapidly and even tailor compounds to the target.”

Fragment-based screening also is particularly effective at creating molecules with low molecular weight, which are needed to be able to cross the tricky blood-brain barrier to treat neurological diseases, like Parkinson’s. And Zenobia is tackling that disease via a new target, LRRK2, which gained national attention last year after Google co-founder Sergey Brin revealed he had the LRRK2 mutation that raised his risk for developing Parkinson’s. Brin’s announcement was a “fortuitous event” for Zenobia, and “a lot of people gained interest in the target,” Nienaber said.

Thanks to the grant from the Michael J. Fox Foundation, the company is able to advance discovery work with Johns Hopkins, aiming to develop compounds that blocks the activity of the LRRK2 protein and preserves brain function. Zenobia will use its screening technology to find compounds for further testing in pre-clinical models. Nienaber called the MJF Foundation an “incredibly savvy group. They understand the gap in funding between the NIH [National Institutes of Health] grants for early research” and the venture capitalists, who tend to shy away from early research-stage firms. 

To date, Zenobia’s funding has come from grants, as well as from contract work involving its fragment-based screening services. “I think the model is changing out of necessity, and you have to get creative now,” she said. “You can’t just start a company, go to VCs and get $10 million, especially if you’re early stage.”

Another source of income for the start-up firm, surprisingly, has been fragment-based screening kits for people who want to learn how to fragment screen, Nienaber said. “We’ve sold 10 so far, primarily to academic labs, which are feeling more pressure than ever to move into translational medicine.” 

Zenobia, whose name comes from a 3rd-century female Syrian warrior who conquered Egypt – an apt moniker given that the company’s executive team comprises mostly women – with a slogan of “fighting to cure disease, also has plans to move into other CNS diseases beyond Parkinson’s, such as Huntington’s disease and pediatric neuroblastoma.