Assistant Managing Editor

With the first Phase I data and the first patents relating to deuterium-modified compounds firmly in hand, Concert Pharmaceuticals Inc. set out looking for a partner and ended up scoring big by signing GlaxoSmithKline plc to a multiproduct collaboration that could be worth more than $1 billion in up-front and milestone payments.

Lexington, Mass.-based Concert gets $35 million up front, including a $16.7 million equity investment. Specific future payments were not disclosed, but President and CEO Roger Tung said the "majority will come from development and regulatory milestones," with the smaller portion from commercial-stage milestones.

That's an impressive deal, particularly considering that the three Concert compounds involved have yet to enter clinical development. The closest is CTP-518, an HIV protease inhibitor, which is set to start human testing in the second half of this year.

The agreement also includes the application of Concert's deuterium chemistry platform to three undisclosed GSK compounds, but most of the dollar-figures in the deal relate to the small biotech's compounds. "We view this really as a way to enable the advancement of our pipeline," Tung told BioWorld Today.

Even so, the deal definitely "gives us Phase II economics at the Phase I stage," he added, attributing it to Concert's de-risked approach to drug development. The firm's technology relies on existing drugs but uses a chemistry platform that replaces certain hydrogen atoms with deuterium, an isotope of hydrogen that lends itself to a stronger chemical bond and improvement in metabolic properties.

CTC-518, for instance, is a deuterium-modified version of atazanavir, a protease inhibitor marketed as Reyataz by Bristol-Myers Squibb Co. But "as with all HIV protease drugs, it's co-dosed with ritonavir" to boost blood levels of the drug, which is effective "but at some expense," with side effects including elevated blood lipids and gastrointestinal side effects, not to mention the fact that it increases the complexity of the dosing regimen, Tung said.

The addition of ritonavir also essentially precludes an HIV protease inhibitor from being formulated as part of a fixed-dose regimen in the way that Gilead Sciences Inc. and BMS combined three antiretroviral medications - one non-nucleoside reverse transcriptase inhibitor and two nucleoside/nucleotide reverse transcriptase inhibitors - into the three-in-one fixed-dose therapy Atripla.

Concert's CTP-518 is aimed at eliminating the need for a boosting agent, which would make it safer and also "enable its inclusion in fixed-dose regimens," Tung said. Preclinical data to date have shown that by replacing certain hydrogen atoms of atazanavir with deuterium, the drug retains its antiviral activity but with improved plasma trough levels.

If successful, CTP-518 also could end up becoming part of London-based GSK's recent deal with Pfizer Inc., which pooled the HIV portfolios of both firms into one specialty firm. As structured, the arrangement allows for both big pharma firms to bring in new additions to the pipeline. (See BioWorld Today, April 17, 2009.)

"It's a specialty newco focusing only on HIV, so [CTP-518] would get their undivided attention," Tung said. It also helps that Tung has a bit of history with GSK. As co-founder of Vertex Pharmaceuticals Inc., he helped invent the HIV protease inhibitors Agenerase (amprenavir) and Lexiva (fosamprenavir calcium), both of which have been marketed by GSK and now are part of the newly formed specialty HIV firm.

Concert is being more reticent about the other two compounds to be included in the GSK deal. One is a drug aimed at chronic kidney disease. Its identity has not been disclosed, "but we will say that we've seen extremely good evidence" that it might have effect as both a single agent and in combination with angiotensin modulators, such as ACE inhibitors, to reduce the rate of kidney decline, Tung said.

That same compound also might end up showing efficacy in other indications, which could extend the GSK agreement beyond the initial $1 billion potential since that figure "assumes one indication per compound," he said. If other indications are pursued, Concert would be eligible for additional milestones.

The third compound in the deal has not been chosen, and Tung said he expects the two firms to reach agreement on that program within one year. That decision must be made jointly, he added, preserving Concert's "ability to independently create our own pipeline."

Concert's early stage pipeline includes antiviral compounds against HIV and hepatitis C virus, as well as research in pulmonary hypertension, chronic pain and other areas. "It's pretty broad," Tung said, which is why it attracted GSK: "It covers a lot of the areas they're interested in."

Prior to the GSK deal, Concert had relied solely on venture capital to sustain operations. Since April 2006, the firm has raised about $110 million, the last financing coming in late April 2008 with a $37 million Series C round. (See BioWorld Today, May 1, 2008.)

Published  June 3, 2009