5 Apr 2016 07:00
Atu027 update
Silence Therapeutics plc, AIM: SLN ('Silence' or 'the Company'), a leader in the development and delivery of novel RNA therapeutics, provides the final analysis of Atu027-I-02 Phase IIa study in pancreatic cancer. The primary objective of this trial was to assess safety and pharmacokinetics, and the secondary objective was to evaluate efficacy, including Progression Free Survival (PFS) and Overall Survival (OS). The presented results have been generated by an independent clinical research organisation.
This study was open label in 23 patients with incurable pancreatic cancer (metastatic and locally advanced) and included two treatment arms with Atu027 in combination with the standard of care, gemcitabine. Treatment arm 1 delivered one dose per week for three weeks, followed by one week of no treatment, giving a total of 6 administrations in 8 weeks. Treatment arm 2 delivered 2 doses per week during 4 weeks, followed by 4 weeks of no treatment, a total of 8 administrations in 8 weeks. Arm 2 therefore received 33% more Atu027 during the same treatment period. The treatment period finished when the patients had progressive disease, but following discontinuation of Atu027 treatment, patients were followed up for up to another year. Following the cessation of treatment for the last patient, Silence presented an interim analysis last year, including the PFS for the two treatment arms.
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. A post-hoc analysis of those with only metastatic pancreatic cancer showed a median PFS of 1.61 for arm 1 vs. 2.89 months for arm 2 (p=0.0247).
The current analysis includes the OS data of the study. Subjects in the higher dosed arm of the study had a median OS of 7.79 months compared to 5.62 months for the lower dose (p=0.61), with 35% of patients being censored. For the metastatic group only, the median OS in the higher dosed group was 6.74 months vs. 3.29 (p=0.6) for the lower dose group, with 26% of patients being censored. There were no changes to the safety profile of the drug.
Validation of target gene
In the period between the announcement of the preliminary Phase IIa results and this statement, an independent research group based at the Kobe University validated the key role of our target gene, PKN3, in metastatic progression. These findings were published in a Scientific Reports article entitled 'PKN3 is the major regulator of angiogenesis and tumor metastasis in mice'. The results described in the article using a knock-out model reproduce data generated in house at Silence when inhibiting endothelial PKN3 expression with Atu027 treatment. This validation of PKN3 as a causal gene in metastasis, along with our patent position covering the targeting of PKN3 in oncology with any drug modality, increases the interest of our therapeutic target for business development activities. We will now actively pursue partnering and collaboration opportunities both with Atu027 and PKN3 as a target.
Ali Mortazavi, CEO of Silence Therapeutics, said:
"The final data confirms the close relationship between PFS and OS as seen in most pancreatic cancer trials as well as the potential Atu027 has to become a new therapeutic modality in oncology. We believe the independent validation of PKN3 and its role in metastasis is potentially significant and increases the value of the patent estate we hold around the target.
We plan to do further pre-clinical work in order to ensure that PKN3 is targeted as effectively as possible. These R&D activities will include optimisation of in house technology (AtuPLEX) as well as evaluation of external delivery systems with the potential of complementing proprietary assets to strengthen our drug candidate."
Enquiries:
Silence Therapeutics plc | Tel: +44 (0)20 3457 6900 |
Ali Mortazavi, Chief Executive Officer |
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Timothy Freeborn, Chief Financial Officer |
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Canaccord Genuity Limited (Nominated Adviser and Joint Broker) | Tel: +44 (0)20 7523 8350 |
Dr Julian Feneley/Henry Fitzgerald-O'Connor/Emma Gabriel |
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Peel Hunt LLP (Joint Broker) | Tel: +44 (0)20 7418 8900 |
James Steel/Oliver Jackson |
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Media Enquiries: | Tel: +44 (0) 20 3727 1000 |
FTI Consulting |
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Simon Conway/Brett Pollard/Stephanie Cuthbert |
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Notes to Editors:
About Silence Therapeutics plc
Our technology harnesses the body's natural mechanisms to create therapeutic effects within its own cells. This technology can selectively silence or replace any gene in the genome, modulating gene expression up as well as down in a variety of organs and cell types, in vivo. We have developed proprietary modifications to improve the robustness of RNA sequences, together with advanced liposomal chemistries to enhance the delivery of therapeutics.