AGM statement and clinical trial interim analysis

1 June 2015

Silence Therapeutics plc

AGM statement and pancreatic cancer trial interim analysis

Silence Therapeutics plc, AIM: SLN, ("Silence" or "the Company"), a leader in the development and delivery of novel RNA therapeutics, is holding its Annual General Meeting today. At the meeting, Chairman Dr Alastair Riddell, will make the following statement.

"Following the draft interim analysis of our Atu027-I-02 Phase 2a trial in pancreatic cancer, as announced on 23 March 2015, we have now completed a full interim analysis of the patient data.

The study was open label in 23 patients with incurable pancreatic cancer and included two treatment arms. Both arms received the standard of care, gemcitabine, in combination with Atu027.

No safety issues were detected for the combination of Atu027 with gemcitabine. Silence previously announced that a dose-dependent effect in Progression Free Survival (PFS) was observed between the two arms, for the whole patient safety population (both metastatic and locally advanced pancreatic cancer). Those exposed to the higher dose of Atu027 presented a longer median duration of PFS; 5.33 months compared to 1.81 months for those on the lower exposure regimen. One patient from each arm is still participating in the study and will continue to be monitored.

In addition, a post-hoc analysis of those patients with metastatic cancer, a sub group of 19 patients within the two arms, revealed statistically significant differences in PFS between arms (p=0.0247). This analysis showed a median PFS period of 2.89 months for metastatic patients within treatment arm two, which received a 33% more total dose of Atu027 over an eight week period, while the metastatic patients within arm one saw a median PFS period of 1.61 months.

We are encouraged by these results and will now work on optimising the dosing schedule in pre-clinical models before planning a larger Phase 2 study in the next 18 months, in which efficacy will be a primary endpoint.

There is a high unmet medical need in pancreatic cancer, which is the fifth most common cause of death by cancer within the EU. Average five year survival rates are currently only 3% and this has improved little since the 1970s*. The poor results with the current standard of care in pancreatic cancer means that there are opportunities for breakthrough designation and accelerated approval.

The anti-metastatic mode of action of Atu027 implies that the applications of our drug candidate are not limited to pancreatic cancer and there is potential to address other solid tumours with poor prognosis. We look forward to building on this opportunity to develop a drug with real benefits for patients."

A conference call for analysts and investors will be held at 9am UK time today. For dial-in details, please contact Rozi Morris at [email protected]

* Cancer Research UK, May 2015, http://www.cancerresearchuk.org/cancer-info/cancerstats/keyfacts/pancreatic-cancer/

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About Silence Therapeutics (www.silence-therapeutics.com)

Silence Therapeutics is a leading RNA therapeutics company. It has developed proprietary modifications to improve the robustness of RNA sequences together with advanced liposomal chemistries to enhance the delivery of its therapeutics. Its technology can selectively silence or replace the expression of any gene in the genome, modulating expression up as well as down in a variety of organs and cell types, in vivo. This allows the development of therapeutics for diseases with high unmet clinical need.

About Atu027

Atu027 is Silence's most advanced RNA interference (RNAi) drug. Its gene silencing mechanism is engineered to target production of the protein PKN3 and is combined with the Company's proprietary lipoplex delivery system. PKN3 was discovered in-house to be a key factor in cancer metastasis and Silence has an extremely robust patent position in the role of PKN3 in cancer. Atu027 has been shown in extensive preclinical studies to have an anti-metastatic effect by targeting the systemic vasculature, this complements therapies targeting primary tumours.

A Phase 1 safety study in patients with advanced solid tumours was completed in 2013, with a good safety and tolerability profile. This progressed to a Phase 2a open-label safety study in 23 patients with incurable pancreatic cancer, which completed recruitment in July 2014. Atu027 has now been tested in 60 patients in oncology.