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.