Benitec Limited stakes claim for HCV RNA interference patent...

From the PharmaLive.com News Archive - Jun. 18, 2010

Melbourne, June 18, 2010 - (ABN Newswire<http://www.abnnewswire.net/index.asp?lang=>) - Benitec Limited (ASX:BLT) (PINK:BNIKF) are pleased to announce that US Patent 7727970 "Multiple promoter expression cassettes for simultaneous delivery of RNAi agents targeted to Hepatitis C virus" has been granted by the United States Patent and Trademark Office (USPTO). The granted claims cover the use of an RNA interference construct (with multiple promoters) to inhibit the level of Hepatitis C virus in animal cells, tissues and organs. Moreover, the USPTO has granted Benitec an additional 805 days patent term in recognition of the delays in examining the patent application. Additional related applications remain pending to extend the scope of protection.

Benitec has licensed the rights to use this patent for Hepatitis C exclusively to Tacere Therapeutics, Inc., who recently announced that Pfizer has exercised its option to further develop and commercialise Tacere's Hepatitis C Virus (HCV) compounds.

Benitec's Chief Scientific Officer, Dr Peter French said, "The grant of this patent is an important further recognition of our dominant global position in the transformational DNA-directed RNA interference field and provides increased depth and breadth to our patent portfolio. Benitec's ddRNAi-related patent estate (solely owned or licensed exclusively for humans from CSIRO) currently comprises over 100 patents and patent applications covering 20 jurisdictions, of which more than 30 are granted, accepted or allowed."

Link: http://www.abnnewswire.net/media/en/docs/63116-ASX-BLT-596073.pdf

Idenix Pharmaceuticals Initiates Proof-of-Concept Study for Protease Inhibitor IDX320 in Hepatitis C Patients

Idenix Pharmaceuticals Initiates Proof-of-Concept Study for Protease Inhibitor IDX320 in Hepatitis C Patients

PR Newswire US - Jun. 10, 2010

CAMBRIDGE, Mass., June 10 /PRNewswire-FirstCall/ -- Idenix Pharmaceuticals, Inc. (Nasdaq: IDIX), a biopharmaceutical company engaged in the discovery and development of drugs for the treatment of human viral diseases, today announced that it has initiated a 3-day proof-of-concept study of IDX320, a protease inhibitor for the treatment of hepatitis C virus (HCV) infection, under a Clinical Trial Application (CTA). The study is evaluating IDX320 in treatment-naive hepatitis C genotype 1-infected patients.

"The potent and multi-genotypic activity demonstrated in vitro, as well as the favorable pharmacokinetics observed in healthy volunteers, suggests a promising profile for further development of IDX320," said Jean-Pierre Sommadossi, Ph.D., chief executive officer of Idenix. "The landscape for combination development in HCV is evolving quickly. Assuming favorable results from the IDX320 proof-of-concept study, we plan to discuss with regulatory agencies a direct-acting antiviral combination strategy with IDX320 and IDX184, our HCV nucleotide polymerase inhibitor."

Douglas Mayers, M.D., Idenix's chief medical officer commented, "We are encouraged by the results seen to date with IDX320 and are hopeful that future clinical studies will allow us to continue advancing this program with the ultimate goal of treating a wide range of patients infected with HCV."

The proof-of-concept trial in HCV-infected patients is a Phase I/II randomized, parallel-arm, double-blind, placebo-controlled study evaluating the safety and antiviral activity of IDX320 in treatment-naive adult patients infected with chronic hepatitis C. The study will evaluate four doses of IDX320, ranging from 50 to 400 mg once-per-day, administered for three days. Each cohort of the study will evaluate eight patients randomized six to IDX320 and two to placebo. 

About IDX320

IDX320, a macrocyclic HCV protease inhibitor, is an inhibitor of NS3/4A proteases from genotypes 1a, 1b, 2a and 4a (IC50 values from 0.8 to 1.9 nM), as well as from genotype 3a (IC50=23 nM). IDX320 did not inhibit nine tested cellular proteases (IC50 > 10 uM) in vitro, suggesting high selectivity. IDX320 bound tightly to the HCV protease enzyme with a long dissociation half-life (> 9 hours). After single 2 mg/kg oral doses of IDX320 in two animal species, favorable bioavailability and a long plasma half-life were observed, with substantial plasma concentrations 24 hours post dose. Comparable drug exposure was confirmed in healthy volunteers (n=6) receiving a single 200 mg oral dose. Further, no significant in vitro inhibition of human drug metabolizing enzymes, CYP450s and UGT1A1, by IDX320 suggests low potential for drug-drug interactions in patients.

About IDX184

IDX184 is a novel, liver-targeted nucleotide prodrug of 2'-methyl guanosine monophosphate, which includes Idenix's proprietary liver-targeting technology. This technology enables the delivery of nucleoside monophosphate to the liver, leading to the formation of high levels of nucleoside triphosphate, potentially maximizing drug efficacy and limiting systemic side effects with low, once-daily dosing. IDX184 in combination with pegylated interferon and ribavirin has demonstrated a generally favorable safety profile and potent antiviral activity in an ongoing Phase IIa study.

RetroVirox Inc seeking funding to advance it's HCV & HIV proprietary discovery programs...

RetroVirox Inc. is seeking to raise funds to support the company's hepatitis C virus (HCV) and other antiviral programs, including one aimed at Dengue virus. But the San Diego-based firm, which began operating in May 2009, wants to advance its antiviral programs only so far, through the investigational new drug (IND) application process or Phase I.

"We don't plan to be a clinical stage company," Juan Lama, president, CEO and director of RetroVirox, told BioWorld Today.

Instead, he said the company is focused on the early stages of discovery and preclinical development of lead compounds. RetroVirox could go in a few different directions based on that model.

It would work to identify new compounds that could lead to first-in-class antivirals and out-license those compounds, approach potential partners to continue clinical development, or possibly put all of its assets up for sale, Lama indicated.

The company is interested in partnerships, venture capital and also non-dilutive opportunities such as small business innovation research (SBIR) funding, he said.

Founded by a group of scientists and entrepreneurs in the fields of virology and drug discovery, the company's expertise is in utilizing cell-based assays to discover new small-molecule compounds with antiviral activity. To do this, RetroVirox has developed proprietary assays to identify compounds that block viral entry by targeting host factors rather than viral proteins.

RetroVirox employs four to six scientists with expertise in virology, assay development, high-throughout screening and medicinal chemistry.

The company offers its services to other biotech companies, providing antiviral assays and screening of libraries for antiviral compounds. In that regard, RetroVirox would work similar to a contract research organization, providing assays in the virology area and identifying potential new compounds to offset its research and development expenses.

Still, the company's major focus is on advancing its own discovery programs, explained Lama, who has governed the firm since its inception.

The company's platform technology has achieved proof-of-concept in the area of HIV, and based on that technology, RetroVirox is developing proprietary assays to create a platform to discover drugs against other major human viruses, including HCV. The technology potentially could be used to inhibit viral entry for almost any virus containing a lipid membrane, Lama said.

Ideally, RetroVirox would like to advance its HCV and HIV programs first, to an IND or Phase I. "We are actually working in both [programs] at the same time, although given the burden of HCV infection we intend to put more effort in the HCV program," Lama said.

In the U.S. alone, more than 3 million are infected with HCV.

So far, RetroVirox has received a little over $1.1 million in financing, with much of that coming from three National Institutes of Health Small Business Innovation Research (SBIR) awards, and the remaining from early stage investors.

The current SBIR Phase I funds would last for the next 18 months. A Phase II SBIR grant could cover another two to three-year period, Lama said.

Under the grants awarded in the last 12 months RetroVirox received $872,000 to fund development of novel HIV entry drugs that could potentially overcome limitations of current therapies. The company received its last award in May to finance the discovery of anti-HIV drugs that block removal of the virus receptor, the CD4 protein.

RetroVirox believes that the mode of action used in its antiviral programs has never been targeted before and holds some key advantages over other antivirals. The company takes aim at human proteins that are needed by the virus to become infectious and enter other cells.

While conventional viral entry inhibitors block binding between the viral envelope and receptor proteins, RetroVirox's approach targets intracellular intracellular proteins, which may not bind directly to viral factors. The company believes that those intracellular host factors could display higher barriers to the emergence of resistant virus, one of the major hurdles in antiviral therapy.

Unlike other entry inhibitors such as the FDA-approved CCR5 blocker maraviroc (Pfizer Inc.'s Selzentry), which act on one of the HIV receptors, RetroVirox's molecules are efficient at blocking entry of all HIV strains, regardless of the co-receptor used by the virus, Lama said.

University of Edinburgh scientists develop new test to determine best treatment for HCV

New customised treatment for hep C

(UKPA) – 3 days ago

Customised treatments for hepatitis C patients are being developed by scientists at a leading university.

A new test is said to rule out the trial and error of patients being prescribed different courses of drugs to treat the infectious disease.

Scientists at the University of Edinburgh say they can test how effective drugs will be for the patient before they are prescribed.

Only one antiviral treatment for hepatitis C is currently available but new drugs are likely to be approved next year, which will be screened using the new method developed in Edinburgh.

The scientists also said the disease can be monitored to check when it is becoming resistant to drugs and the effectiveness of switching to other treatments can be evaluated.

Researcher Ingrid Imhof, of the university's centre for infectious diseases, said: "This new system will make it easier to select in advance the best treatment option for each individual patient, saving them from ineffective treatments with potentially serious side-effects."

All six strains of hepatitis C were use to infect liver cells. The cells were then tested using a range of drugs.
The team, led by Professor Peter Simmonds, analysed each strain of the disease to check the effectiveness of the drugs and any resistance to them. The study findings were published in the Journal of Virology. An estimated 250,000 people in the UK and around 170 million people around the world have hepatitis C.

The disease, which often has no symptoms, can cause swelling and scarring of the liver. Carriers can have the disease for years without knowing.

Symptoms, when apparent, are fatigue, alcohol intolerance and weight loss. Long-term carriers are more at risk of developing liver disease and liver cancer.