With its lead product partnered to Genentech Inc., Inotek Pharmaceuticals Corp. raised $19.3 million in a Series C financing to support clinical trials with the next few compounds in its pipeline.

New investors in the round included Hercules Technology Growth Capital Inc., Meditor Capital Management and Mitsubishi UFJ Capital. Inotek's Chief Business Officer Jeffrey Walsh noted that while Hercules is well known for providing venture debt, in this case, the firm made an equity investment.

All of Inotek's existing investors also participated in the insider-led round, including Care Capital LLC, La Caisse de dépôt et placement du Québec, MedImmune Ventures, Pitango Venture Capital and Rho Ventures.

Beverly, Mass.-based Inotek has raised $74.3 million in equity financing to date, counting the current round, a $35 million Series B in October 2005 and a $20 million Series A in February 2004. The firm also has proven adept at raising nondilutive financing. Prior to its Series A, Inotek secured more than $50 million in grants and contracts, and last year, the company garnered a $20 million up-front payment as part of a potential $600 million deal with Genentech.

The Genentech deal centered on Inotek's lead candidate INO-1001, a small-molecule, poly-ADP polymerase (PARP) inhibitor. Genentech, of South San Francisco, licensed rights in cancer and is funding that program's clinical development as well as research focused on identifying next-generation compounds. Genentech also has an option to INO-1001 in cardiovascular disease, where a recently completed Phase IIa trial indicated the compound suppressed PARP in patients with acute ST-elevated myocardial infarction undergoing primary percutaneous coronary intervention. (See BioWorld Today, July 25, 2006.)

Walsh said the Series C financing, along with existing cash, will be used to achieve "first proof-of-efficacy data" with the next three compounds in Inotek's pipeline. Among those are INO-8875, an adenosine-1 agonist in Phase I for cardiac arrhythmias; INO-4885, an antioxidant in Phase I for an undisclosed critical care indication; and an unnamed adenosine-1 agonist in preclinical development for an ophthalmic indication.

Walsh predicted that efficacy data with all three compounds will be available in 2008 or 2009. For INO-8875, the current Phase I trial involves atrial fibrillation patients, so Walsh said Phase Ia or Phase Ib data due in 2008 may show the compound's effect on rate control. Phase Ia data for INO-4885, a peroxynitrite decomposition catalyst that may be applicable in a variety of oxidant-mediated diseases, are expected later this year or early next year. And the ophthalmic program is slated to begin clinical trials early next year.

Inotek has an assortment of other programs in preclinical development as well. The research with Genentech on next-generation PARP inhibitors has churned out candidates with potential applicability outside cancer and cardiovascular disease, which Inotek still holds all rights to. One such compound, INO-1188, is in investigational new drug application-enabling studies for ulcerative colitis and Crohn's disease, while potential compounds for stroke and post-prostatectomy erectile dysfunction are in earlier preclinical development.

Inotek also has a preclinical monoclonal antibody program targeting flagellin, but Walsh said the company intends to partner it out and stay focused on small molecules. Even some of Inotek's small molecules may be up for grabs. Walsh said that the company is "in discussions with several firms around several programs" and that the PARP inhibitors in particular have generated a lot of interest.

Inhibitors of PARP, an enzyme involved in cell repair, proliferation and signaling that may contribute to chemotherapy resistance and may block necrosis and inflammation, have garnered interest across the board over the past few years. In addition to Inotek's deal with Genentech, KuDOS Pharmaceuticals Ltd. was acquired by AstraZeneca plc thanks in part to its Phase I PARP inhibitor. And Guilford Pharmaceuticals Inc., which was acquired by MGI Pharmaceuticals Inc., had among its many other assets a preclinical PARP program. (See BioWorld Today, Jul. 22, 2005.)

Another company in the PARP space is BiPar Sciences Inc., which raised $35 million in a Series B financing earlier this year to drive its PARP inhibitor for cancer through Phase I and into Phase II trials. (See BioWorld Today, Feb. 27, 2007.)

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