Another hepatitis C candidate knocked the socks off investors Tuesday as Jerusalem's BioLineRx Ltd. added a new prong to its pipeline, inking a worldwide, exclusive license agreement with the French firm Genoscience to develop and commercialize the orally available protease inhibitor (PI) BL-8020.

Terms of the deal were not disclosed, but that didn't stop investors from swarming to BioLineRx's stock like a honey pot. Shares (NASDAQ:BLRX) more than doubled during midday, hitting a 52-week high of $6.87 before settling back to close at $5.55, for a 68.7 percent gain on the day. More than 6 million shares changed hands compared to an average trading volume of just a few thousand.

Privately held Genoscience, based in Marseille, France, has been developing BL-8020 an an antiviral therapy for more than a decade. The company's co-founder and president, Philippe Halfon, who also serves as CEO of Alphabio Laboratory in Marseille, is a specialist in molecular virology and a former consultant to Roche Diagnostics and Schering Plough (now part of Merck & Co. Inc.). Halfon's research focuses on HIV, human papillomavirus and hepatitis.

Still in preclinical development, BL-8020 inhibits HCV-induced autophagy, a cellular remodeling process typically associated with cancer, neurodegenerative and other diseases. Although Genoscience has disclosed few details about the compound, the PI targets the NS3/4A antigens with a new mechanism of action, according to the companies, which did not respond to interview requests.

Preclinical studies of BL-8020 have suggested that the candidate, in combination with other HCV agents, has a synergistic effect that may enable the development of lower dosages, resulting in greater potency with fewer side effects while reducing the duration of therapy.

Genoscience also has modified the HCV compound to avoid mutations involved in HCV protease drug resistance. The potential to combine two drugs that act by different mechanisms may benefit patients who have developed resistance to existing treatments and may serve as an effective strategy against other viruses, including HIV, according to the companies. They did not disclose whether the compound also could be developed as a monotherapy in HCV.

The core of Genoscience's technology development is a software platform known as GenMol that was developed by Gérard Pepe, the company's co-founder, chief technology officer and director of research at the Centre National de la Recherche Scientifique. Pepe specializes in molecular modeling – docking simulation experiments centered on macromolecular systems such as polypeptides and nucleic acids.

Genoscience has wielded the technology to conduct "structure-based drug design," modifying target structures in a completely interactive manner. The software allows for the rotation and elongation of the target structure to obtain in vitro results "in silico" and to account for the aqueous environment of the ligand and the enzyme when calculating the energy of association. The company's goal has been to engineer a lead compound with an IC50 of less than 100m in the cellular replicon assay and to move the compound through preclinical studies – presumably, to partner for human trials.

Genoscience also has developed a drug screening HCV platform that includes an NS3/NS4A enzymatic screening assay, a fluorescence resonance energy transfer assay and a cellular replicon system.

BioLineRx is a small company with big ambitions. The biotech, which completed its U.S. initial public offering last July following a 2007 IPO for its listing on the Tel Aviv market, has built a portfolio of five clinical-stage candidates in a variety of indications. (See BioWorld Today, Feb. 8, 2007, and Sept. 28, 2010.)

Its Phase II/III CLARITY trial of BL-1020, an oral GABA-enhanced antipsychotic for schizophrenia, is under way in India. The company regained rights to the drug last year after a partnership with Cypress Bioscience Inc. came apart in the wake of the San Diego biotech's buyout. (See BioWorld Today, June 22, 2010, and May 13, 2011.)

BL-1040, a resorbable polymer solution for heart attack treatment, completed a Phase I/II study and was out-licensed to Ikaria Inc., of Hampton, N.J., for $282.5 million. (See BioWorld Today, July 7, 2009.)

BL-5010 has completed a Phase I/II study in nonsurgical removal of skin lesions. Small molecule BL-1021 is in Phase I development for neuropathic pain, and BL-7040 has completed Phase I development in inflammatory bowel disease. BioLineRx has 12 additional products in various stages of preclinical development for central nervous system diseases, oncology, infectious diseases, cardiovascular and autoimmune diseases.

The company's business model is based on acquiring molecules – mainly from biotech incubators and academic research institutions – then conducting feasibility studies and early stage development. BioLineRx seeks to partner promising compounds for pivotal studies and commercialization.

The Israeli company isn't well known in the U.S., so investor enthusiasm seemed almost entirely focused on the deal du jour in the red-hot HCV space. A half-dozen firms are jockeying to be first to supplant existing PIs Incivek (telaprevir, Vertex Pharmaceuticals Inc.) and Victrelis (boceprevir, Merck & Co. Inc.) as the next-generation of HCV drugs. In a blockbuster buy that closed earlier this month, Gilead Sciences Inc. ponied up $11 billion for Pharmasset Inc. and its nucleotide analogue, PSI-7977. (See BioWorld Today, Nov. 22, 2011.)

Bristol-Myers Squibb Co. also has a portfolio of HCV therapies, including Phase III NS5A inhibitor daclatasvir, Phase II NS3 protease inhibitor TMC435, NS5A inhibitor BMS-790052 and PEG-interferon lambda. Its pending $2.5 billion acquisition of Inhibitex Inc. adds a nuc with INX-189. (See BioWorld Today, Jan. 10, 2012.)

In October 2011, Roche AG bagged Anadys Pharmaceuticals Inc., which is developing HCV candidate setrobuvir (ANA598), for $230 million. (See BioWorld Today, Oct. 18, 2011.)

Johnson & Johnson subsidiary Tibotec Pharmaceuticals and Boehringer Ingelheim GmbH are in late-stage trials testing protease inhibitor combos without interferon, while Achillion Pharmaceuticals has a portfolio of PIs ranging from preclinical to Phase II development. (See BioWorld Today, June 23, 2011.)

Abbott and partner Enanta Pharmaceuticals Inc. are in Phase II studies with oral PI ABT-450/r (ABT-450 and ritonavir). (See BioWorld Today, Dec. 13, 2006, and Oct. 14, 2011.)

And Idenix Pharmaceuticals Inc. is awaiting the FDA's decision to lift a partial clinical hold on the oral nuc IDX184 after the company reported interim Phase IIb data earlier this month showing the compound was well tolerated and no serious adverse events were associated with therapy. (See BioWorld Today, Nov. 17, 2011.)