Quark Pharma extends pact with Pfizer to develop compounds containing … – pharmabiz.com

Silence Therapeutics Plc, a leading international RNAi therapeutics company, announced that its partner, Quark Pharmaceuticals, has extended its existing exclusive Licensing Agreement with Pfizer.

This amendment will enable Quark to perform a phase II a clinical study to assess the effect of PF-655 in a new indication, looking at visual function in patients with moderate and advanced Open-Angle Glaucoma (OAG). PF-655 incorporates Silence’s AtuRNAi technology and was sub-licensed to Pfizer by Quark in 2006, and on which Silence is entitled to receive a share of milestones and royalties that may be earned by Quark in the future on this compound.

The OAG study will be conducted in parallel with a Phase 2b study of PF-655 in diabetic macular oedema.

Silence has previously announced that it stood to receive up to $95m from Quark in relation to its licensing agreement with Pfizer. As a result of this amendment to the Quark/Pfizer license, Silence anticipates its share of these payments could now reach $120m. Silence has previously announced the receipt of $6m from Quark in relation to this licence.

Commenting on the announcement, Tony Sedgwick, Chief Executive Officer of Silence, said: “This is an exciting development for Silence. This will create a fifth external clinical programme using Silence’s IP and AtuRNAi, which is funded and managed by one of our partners. This will increase the potential share of milestones and royalties that Silence can earn under its agreement with Quark and is a further validation of the Silence technology.”

Quark and Pfizer have amended their existing exclusive Licensing Agreement on May 1 in order to enable Quark to perform a phase II a clinical study to assess the effect of PF-655 on visual function in patients with moderate and advanced Open-Angle Glaucoma (OAG). This study will be conducted in parallel with an ongoing phase II b study (QRK202) in diabetic macular edema (DME). The OAG study will evaluate the potential of PF-655 to enhance visual function in glaucoma. Under the amended agreement, should Pfizer assume development and potential commercialization of PF-655 in either or both indications following review of the Phase 2a PF-655 data, Quark will receive option exercise payments and be will eligible to receive development and regulatory milestones specific to each indication, as well as sales milestones and royalties. Quark may be eligible to receive additional total payments of up to approximately $165 million associated with development and approval of PF-655 for OAG.

Preclinical studies of PF-655 conducted by Quark suggest the potential of the compound as a neuroprotective and potentially neuroenhancing agent in diseases such as OAG, by preventing optic neural cell apoptosis and stimulating optic neural cell regeneration. In addition, in a Phase 2a study in patients with DME (Pfizer DEGAS study #B0451004), repeated injections of PF-655 showed a dose-dependent increase in visual acuity independent of changes in retinal thickness. The beneficial effects of PF-655 on visual function may potentially be due to effects on retinal cells themselves, rather than on vascular permeability.

The OAG study will be a Phase 2a, multi-center, double-masked, randomized, repeat dose, safety, tolerability and efficacy study in up to 108 patients with moderate and advanced OAG. In addition, Quark is currently conducting a Phase 2b study (QRK202) in DME patients testing higher doses of PF-655 alone and in combination with Lucentis(R) to further evaluate the safety and efficacy of PF- 655 in DME and to determine the optimal dose for pivotal Phase 3 studies.

Daniel Zurr, Ph.D. President and Chief Executive Officer of Quark stated: “We are very excited to evaluate the effect of PF-655 on visual loss in glaucoma in future clinical studies. The mechanism of action and biological activity of PF-655 are novel and its axon regenerating effects may provide a long awaited breakthrough in the treatment of glaucoma. We are pleased and grateful to our partner, Pfizer, for their support in pursuing this new indication.”

Quark Pharmaceuticals, Inc. is a clinical-stage pharmaceutical company engaged in discovering and developing novel RNA interference (RNAi)-based therapeutics.

Silence Therapeutics plc is a leading biotechnology company dedicated to the discovery, development and delivery of targeted, systemic RNA interference (RNAi) therapeutics for the treatment of serious diseases.

View the original article here

Scripps Research Institute Scientists Create Compounds that Dramatically Alter Biological Clock and Lead to Weight Loss

The New Molecules Could Lead to Unique Treatments for Obesity, Diabetes, High Cholesterol, and Sleep Disorders

JUPITER, Fla., March 29, 2012 /PRNewswire-USNewswire/ — Scientists from the Florida campus of The Scripps Research Institute have synthesized a pair of small molecules that dramatically alter the core biological clock in animal models, highlighting the compounds’ potential effectiveness in treating a remarkable range of disorders—including obesity, diabetes, high cholesterol, and serious sleep disorders.

The study was published on March 29, 2012, in an advance, online edition of the journal Nature.

The study showed that when administered in animal models the synthetic small molecules altered circadian rhythm and the pattern of core clock gene expression in the brain’s hypothalamus, the site of the master cellular clock that synchronizes daily rhythms in mammals; circadian rhythms are the physiological processes that respond to a 24-hour cycle of light and dark and are present in most living things.

When given to diet-induced obese mice, these same small molecules decreased obesity by reducing fat mass and markedly improving cholesterol levels and hyperglycemia—chronically high blood sugar levels that frequently lead to diabetes.

“The idea behind this research is that our circadian rhythms are coupled with metabolic processes and that you can modulate them pharmacologically,” said Thomas Burris, a professor at Scripps Florida who led the study. “As it turns out, the effect of that modulation is surprisingly positive—everything has been beneficial so far.”

Burris stressed that these compounds were first generation—the first to hit their targets in vivo with room for improvement as potential treatments. “In terms of therapeutics, this is really the first step,” he said.

In the new study, the team identified and tested a pair of potent synthetic compounds that activate proteins called REV-ERB alpha and REV-ERB beta, which play an integral role in regulating the expression of core clock proteins that drive biological rhythms in activity and metabolism.

In the study, the scientists observed clear metabolic effects when the synthetic compounds were administered twice a day for 12 days. Animals displayed weight loss due to decreased fat mass with no changes in the amount of food they ate. The animals followed the human model of obesity closely, eating a standard Western diet of high fat, high sugar foods, yet still lost weight when given the compounds.

In one of the study’s more striking findings, both synthetic compounds were shown to reduce cholesterol production. Cholesterol in the blood of treated animal models decreased 47 percent; triglycerides in the blood decreased 12 percent.

The circadian pattern of expression of a number of metabolic genes in the liver, skeletal muscle, and in fat tissue was also altered, resulting in increased energy expenditure, something of a surprise. In the study, the scientists observed a five percent increase in oxygen consumption, suggesting increased energy expenditure during the day and at night. However, these increases were not due to increased activity—the animals displayed an overall 15 percent decrease in movement during those same time periods.

In addition to its impact on metabolism, the two compounds also affected the animals’ activity during periods of light and darkness, suggesting that this class of compound may be useful for the treatment of sleep disorders, including the common problem of jet lag.

The first authors of the study, “Regulation of Circadian Behavior and Metabolism by Synthetic REV?ERB Agonists,” are Laura A. Solt and Yongjun Wang of Scripps Research. Other authors include Subhashis Banerjee, Travis Hughes, Douglas J. Kojetin, Thomas Lundasen, Youseung Shin, Jin Liu, Michael D. Cameron, Romain Noel, Andrew A. Butler, and Theodore M. Kamenecka of Scripps Research; and Seung?Hee Yoo and Joseph S. Takahashi of the Howard Hughes Medical Institute and University of Texas Southwestern Medical Center.

The study was supported by the National Institutes of Health and the Howard Hughes Medical Institute.

About The Scripps Research Institute
The Scripps Research Institute is one of the world’s largest independent, not-for-profit organizations focusing on research in the biomedical sciences. Over the past decades, Scripps Research has developed a lengthy track record of major contributions to science and health, including laying the foundation for new treatments for cancer, rheumatoid arthritis, hemophilia, and other diseases. The institute employs about 3,000 people on its campuses in La Jolla, CA, and Jupiter, FL, where its renowned scientists—including three Nobel laureates—work toward their next discoveries. The institute’s graduate program, which awards Ph.D. degrees in biology and chemistry, ranks among the top ten of its kind in the nation. For more information, see http://www.scripps.edu.

SOURCE The Scripps Research Institute

Posted: March 2012

View the original article here