Tacere Therapeutics Inc. stands at the crossroads of two of the more lucrative partnering opportunities in the biotech space: RNAi and HCV.
Founded in July 2006, the San Jose, Calif.-based company is preparing to start clinical trials late next year with lead product TT-033, a combination of three short-hairpin RNAs (shRNAs) delivered within an adeno-associated virus (AAV) protein coat to three separate regions of the hepatitis C virus.
Tacere's work with shRNA, also known as "expressed RNA," differentiates the company from others in the field, said co-founder and Chief Financial Officer Mike Catelani. Most RNAi companies are pursuing "delivered" RNA, which uses a small-molecule type of approach to deliver short-interfering RNA (siRNA), he explained.
TT-033's AAV delivery has "a very good safety profile" and has been shown in preclinical studies to provide "very good delivery to hepatocytes," Catelani said. In a mouse study, a single administration of TT-033 provided more than 60 percent inhibition of the three targeted regions of the HCV genome for two months.
The opportunity is significant for HCV therapies that can improve on the standard of care, pegylated alpha interferon and ribavirin, which can cause serious side effects and only works in about 55 percent of patients. Leading the pack are small-molecule protease and polymerase inhibitors such as Vertex Pharmaceuticals Inc.'s telaprevir, Schering-Plough Corp.'s SCH 503034 and ViroPharma Inc.'s HCV-796.
Yet Tacere predicts that many of the new HCV drugs still will have side effects due to co-administration with interferon, not to mention resistance issues over time. TT-033 is designed to be administered in a single dose given via peripheral IV, and its ability to target three separate regions of the HCV genome is anticipated to prevent resistance. Additionally, its three shRNAs were selected to be effective against all HCV genotypes.
Although Tacere is new, TT-033 is not. The product emerged from Avocel Inc., an RNAi start-up acquired by Benitec Ltd. in 2004. After two years of early stage development, Benitec decided to divest TT-033 and return its focus to intellectual property acquisitions. Sara Hall, current CEO of Tacere, previous CEO of Benitec and founder of Avocel, teamed up with Catelani to license TT-033 along with Benitec's broad patent on expressed RNA.
Hall and Catelani named Tacere after the Italian word for silence. As of now, they are the only full-time employees, but they plan to begin building up the team in the fall as they work on expanding their RNAi pipeline and preparing for clinical trials.
Hall said a recent pre-IND meeting with CBER went "very well" and the company should have "no trouble with IND approval" unless the IND-enabling studies turn up something "completely unexpected."
Thus far, Tacere's funding has come from a seed round provided by Hokkaido Venture Capital Inc., of Tokyo. Hall said Hokkaido had been interested in investing in the Series A round for Avocel, but the financing was never completed due to the Benitec acquisition. She added that Asian investors are a good fit for RNAi because they have smaller funds and can invest in earlier-stage, riskier prospects.
Additional financing came by way of an equity investment from Oncolys BioPharma Inc., also of Tokyo. In exchange, Oncolys got an option to acquire Asian rights to TT-033.
While Tacere plans to eventually raise a Series A, Hall said she'd like to postpone the round until the company is near or in the clinic, so the "Series A has the value proposition of a Series B." In the mean time, Tacere is "in discussions" with a potential partner regarding a nonequity-based deal.
If precedent serves, Tacere should have no problem generating partnering interest. Earlier this month, Alnylam Pharmaceuticals Inc. signed a potential $1 billion nonexclusive RNAi deal with Roche Holding AG, and Silence Therapeutics plc inked a potential $403 million RNAi deal with AstraZeneca plc. Last year, Merck & Co. Inc. purchased then RNAi-leader Sirna Therapeutics Inc. for $1.1 billion. (See BioWorld Today, Nov. 1, 2006, July 9, 2007, and July 10, 2007.)
HCV drugs have commanded significant big pharma interest as well, including a potential $545 million ex-U.S. rights deal between Vertex and Janssen Pharmaceutica NV, a potential $530 million preclinical co-development deal between InterMune Inc. and F. Hoffmann-La Roche Ltd. and a potential $307 million preclinical deal between Enanta Pharmaceuticals Inc. and Abbott Laboratories Inc. Novartis AG has been particularly active in HCV, signing a deal worth up to $552 million with Human Genome Sciences Inc., a deal worth up to $570 million with Anadys Pharmaceuticals Inc., and deals worth well over a billion dollars with Idenix Pharmaceuticals Inc. (See BioWorld Today, March 27, 2003; June 3, 2005; March 30, 2006; June 7, 2006; July 5, 2006; Oct. 18, 2006; and Dec. 13, 2006.)