Silence Therapeutics’ Atu027 Demonstrates Promising Antitumor Activity in Phase I Study Presented at ASCO

Silence Therapeutics plc has announced positive updated data from its ongoing Phase I study of Atu027, one of the most clinically advanced RNAi therapeutics in the area of oncology, in patients with advanced solid tumors.

Study results show that nine of the 24 patients treated with Atu027 to date achieved stable disease after repeated treatment with six of these cases confirmed at study end (three months after treatment initiation) and three other patients continuing to receive treatment with Atu027 under compassionate use.

Among the patients who achieved stable disease, one individual with neuroendocrine cancer achieved disease stabilization for nine months with a second neuroendocrine cancer patient showing partial regression of pulmonary metastases. An additional patient with breast cancer experienced a slight regression in liver metastases.

Interim study data, which include results for the 24 patients who have received the study’s first eight escalating doses of Atu027, are being presented today in a poster presentation at the 2011 American Society of Clinical Oncology (“ASCO”) Annual Meeting in Chicago.

In addition to the encouraging antitumor activity, study results show Atu027 to be well tolerated with no observed dose-limited toxicities or evidence of cytokine activation. Favorable pharmacokinetic (PK) data showed dose-dependent increases in siRNA and lipid levels, suggesting no evidence of drug accumulation during repeat treatment.

Additionally, the maximum tolerated dose for Atu027 has not been reached yet, further supporting the tolerability of the treatment and providing the opportunity to examine the possibility of enhanced efficacy at higher doses.

Dose escalation and patient enrollment is continuing in the study with the goal of evaluating a total of 11 escalating doses of Atu027 in approximately 33 patients. Silence expects to complete the ongoing open label, single-center, dose-finding Phase I trial in the second half of 2011.

“The next step in translating the promising science of RNA interference into meaningful therapeutics with the potential to help patients is the gathering and presentation of positive clinical study data. We believe that the combination of antitumor activity, impressive PK results and the clean safety profile that has been demonstrated by Atu027 in this study so far, represents significant clinical progress not just for Silence but for the entire field of RNAi therapeutics,” said Philip Haworth, Ph.D., chief executive officer of Silence Therapeutics.

Haworth continued, “The Atu027 data presented today provide valuable validation for Silence’s foundational RNAi technology platform, as well as our AtuPlex delivery technology, which is the only systemic lipid-based siRNA delivery technology in clinical trials that does not require suppression of the immune system prior to treatment. We look forward to completing this ongoing study and reporting final data once available.”

“We are clearly optimistic by the results that indicate activity in this study so far, particularly the impressive tolerability and safety being displayed by Atu027,” stated the study’s principal investigator, Dirk Strumberg, M.D., Professor of Medicine and Director, Department of Hematology and Medical Oncology, University of Bochum, Marienhospital Herne. "For an early-stage study, it is pleasantly surprising to see some patients who are suffering with difficult-to-treat tumours experience prolonged disease stabilization."

Data from Silence’s ongoing Phase I study of Atu027 were presented today at the ASCO meeting in a poster titled “First-in-human phase I study of Atu027, a liposomal small interfering RNA formulation, targeting protein kinase N3 (PKN3) in patients with advanced solid tumors.”