Staff Writer

CeNeRx BioPharma Inc. raised $15 million in a Series B financing to support its recently initiated Phase II trial of lead drug Tyrima for major depressive disorder.

Existing investor Aisling Capital led the Series B round, which also included existing investors L Capital Partners and Pappas Ventures. The financing was CeNeRx's first since closing an $18.5 million Series A round back in 2005. (See BioWorld Today, Nov. 30, 2005.)

In the interim, the Research Triangle Park, N.C.-based company accessed a small amount of debt financing. But CEO Barry Brand said CeNeRx has been "very efficient in our use of capital - our investors love us."

Brand plans to continue that efficiency: He expects the Series B to carry CeNeRx through the completion of its Phase II trial of Tyrima, with money left over to advance the company's preclinical cannabinoid pipeline and in-license another program for central nervous system disorders.

The Tyrima study is a randomized, double-blind, placebo-controlled Phase II trial of about 272 patients with moderate to severe major depressive disorder. The primary endpoint of relieving depression will be assessed using the Montgomery-Asberg Depression Rating Scale, while secondary endpoints will look at safety, tolerability and pharmacokinetics. Data are expected by the end of next year.

In previous Phase I studies, Tyrima was well tolerated and showed a good pharmacokinetic profile. But CeNeRx has other reasons to think the drug will work, Brand said.

He explained that Tyrima is a reversible inhibitor of monoamine oxidase A (RIMA) - the same mechanism used by the antidepressant moclobemide, which is not approved in the U.S. but is a top-selling product in Europe and Canada, where it is marketed by F. Hoffmann-La Roche Ltd.

RIMAs improve on the old monoamine oxidase inhibitors (MAOIs) in several ways, Brand continued. Once popular antidepressants, MAOIs lost favor in part because they can cause hypertension when combined with foods rich in tyramine, such as cheeses and wines. Brand said RIMAs avoid that problem with more selective enzyme targeting. He noted that Tyrima also is reversible, so if tyramine levels begin to get too high, the drug will unbind from the target enzyme until levels return to normal.

MAOIs also are contraindicated with many drugs, which can cause problems for physicians seeking to maximize efficacy by combining antidepressants. Brand said many patients are treated with selective serotonin reuptake inhibitors (SSRIs) such as Prozac (fluoxetine, Eli Lilly and Co.), Paxil (paroxetine, GlaxoSmithKline plc) or Zoloft (sertraline, Pfizer Inc.). Yet the benefits of targeting multiple neurotransmitters have led to the success of dual serotonin and noradrenaline reuptake inhibitors (SNRIs) like Effexor (venlafaxine, Wyeth Pharmaceuticals Inc.), and many doctors prescribe the SSRIs or SNRIs in combination with Wellbutrin XL (bupropion, GlaxoSmithKline plc), which inhibits reuptake of norepinephrine and dopamine.

RIMAs, Brand said, targets all three neurotransmitters - serotonin, norepinephrine and dopamine - in a single drug, eliminating the need for combinations. He added that while moclobemide is an older drug, Tyrima is a "next-generation" RIMA and has patent protection, giving it the potential to be the first triple-action antidepressant in the U.S.

Brand said he does not envision Tyrima replacing SSRIs in first-line treatment, but he noted that two-thirds of patients on antidepressants do not achieve a full response to existing therapies, which is where Tyrima may prove beneficial.

Additionally, Tyrima's ability to restore energy may make it applicable in treating atypical depression, for which no drugs are approved. Brand said CeNeRx will look at patients with atypical depression as a subset analysis within the Phase II trial and may start a separate program to focus on them after reviewing the data.

CeNeRx licensed rights to Tyrima from Krenitsky Pharmaceuticals Inc., of Durham, N.C. If the Phase II trial goes well, the biotech may consider teaming up with a big pharma partner for further development.

In the nearer term, CeNeRx is looking to partner its preclinical portfolio of cannabinoid compounds, which it licensed from PharmaNess Neurosciences Scarl of Pula, Italy. Preclinical proof-of-concept studies have been completed in pain, obesity, glaucoma and spasticity, but Brand said the portfolio contains 18 compounds and is "more than we can develop" internally.

Yet CeNeRx continues to in-license new compounds for central nervous system disorders. The company is looking for drugs with a precedent, like Tyrima, and is evaluating a "steady stream" of interesting prospects, Brand said.

In other financing news:

• Advanced Cell Technology Inc., of Worcester, Mass., received the initial $250,000 in funding from Transition Holdings Ltd. The company previously announced that it would sell $500,000 of one-year 7 percent convertible debentures over the next 90 days. The proceeds will be used for working capital and general corporate purposes and will support operations while the company seeks partners for its advanced clinical programs.