Freeline publishes further data for FLT180a

Freeline publishes further data for FLT180a at ISTH 2020

Updated FLT180a data in the B-AMAZE study in severe Haemophilia B patients demonstrated the potential for sustained normal FIX activity levels

Syncona Ltd, a leading healthcare company focused on founding, building and funding a portfolio of global leaders in life science, announces that its portfolio company, Freeline, is presenting further data from the ongoing B-AMAZE Phase 1/2 clinical trial investigating its gene therapy product candidate, FLT180a, for the treatment of Haemophilia B, at the International Society on Thrombosis and Haemostasis (ISTH) 2020 Congress. The presentation is part of a late-breaking abstract session and is in addition to five other posters from Freeline featuring throughout the virtual event, from 12-14 July 2020.

The presentation entitled: "A novel adeno associated virus (AAV) gene therapy (FLT180a) achieves normal FIX activity levels in severe Haemophilia B (HB) patients (B-AMAZE study)" is taking place today, Monday 13 July 2020, at 11.45-13.00 ET.

Chris Hollowood, Chief Investment Officer of Syncona, said: "We are pleased to see additional encouraging data generated from this Haemophilia B trial. Patients in the first cohort have now shown durable expression of FIX activity for two years after dosing and the latest cohort, which has been expanded, is showing promising levels of expression in the normal range. We look forward to seeing Freeline progressing its lead programme in Haemophilia B to a pivotal study."

Trial background

FLT180a is Freeline's AAV gene therapy for the treatment of Haemophilia B. A novel capsid is used to deliver this gene therapy and has the potential to drive higher protein expression than other programs have demonstrated in the clinic to date. Freeline is seeking to identify the optimal dosing regimen for FLT180a with the goal of consistently delivering to patients Factor IX (FIX) activity levels in the normal range of between 50 to 150 per cent, which no other treatment has been able to achieve to date.

The normal range of FIX activity in the general population's blood is between 50 per cent and 150 per cent and patients diagnosed with severe and moderate Haemophilia B have FIX activity below five per cent.

Update on data

Reportable data[1] is available for 10 patients who have been treated across four dose cohorts with FLT180a. The first dose cohort (two patients) has follow-up over 104 weeks, the next two dose cohorts (two patients in each) have data available over 26 and 52 weeks respectively. The most recent dose cohort (four patients) has FIX activity level readings available at 3 weeks, with two of those patients also having data available at 26 weeks.

All patients had severe or moderate Haemophilia B with baseline FIX activity levels prior to gene therapy of 2 per cent or less.

·      In the first, low dose cohort (4.5 x10¹¹) durable expression of FIX activity has now been seen for two years post dose with an average FIX level activity at 52 and 104 weeks of 38% and 38% FIX activity respectively, which are FIX levels commonly associated with mild haemophilia B.

·      Durable FIX activity levels in the normal range were seen at doses of 7.5 x10¹¹ and 9.75x10¹¹. The latest cohort, at dose level four (9.75x10¹¹), has been expanded to four patients, all of whom are showing encouraging FIX expression greater than 50 per cent as of 15 June 2020.

·      To date no bleeds have required supplemental FIX in any of the patients studied.

Further data is in the table below.

Freeline believes that a dose above 7.5x10¹¹ up to and including 9.75x10¹¹ has the potential to create sustained FIX activity levels in the normal range in patients with severe Haemophilia B. The data supports the development of a phase 3 pivotal study.

Three patients (in the upper three dose cohorts) saw reductions in FIX expression following a rise in ALTs[2] as set out in the table below. Freeline has continued to optimise its prophylactic immune management regimen throughout the trial, working to identify a regimen that consistently controls ALTs to prevent loss of FIX expression. The business has implemented a regimen for the last three patients in the latest expanded dose cohort (9.75x10¹¹) involving prophylactic corticosteroids and tacrolimus[3], which appears effective in preventing rises in ALTs during the highest risk period.

Data table

^a Arithmetic means, per dose level for FIX activity levels (%) at corresponding study visits

^b FIX activity levels (%) measured by local assay (results for minimum of 2 patients).

^c Includes one patient with reduction in FIX expression following elevated ALTs

^d Data from one patient with reduction in FIX expression following elevated ALTs

^e Includes one patient with reduction in FIX expression following elevated ALTs

^f Data from two patients and includes one patient with reduction in FIX expression following elevated ALTs

 [ENDS]

Enquiries

Syncona Ltd

Annabel Clay / Siobhan Weaver

Tel: +44 (0) 20 3981 7940

FTI Consulting

Ben Atwell / Natalie Garland-Collins / Tim Stamper

Tel: +44 (0) 20 3727 1000

Copies of this press release and other corporate information can be found on the company website at: www.synconaltd.com  

Forward-looking statements - this announcement contains certain forward-looking statements with respect to the portfolio of investments of Syncona Limited. These statements and forecasts involve risk and uncertainty because they relate to events and depend upon circumstances that may or may not occur in the future. There are a number of factors that could cause actual results or developments to differ materially from those expressed or implied by these forward-looking statements. In particular, many companies in the Syncona Limited portfolio are conducting scientific research and clinical trials where the outcome is inherently uncertain and there is significant risk of negative results or adverse events arising. In addition, many companies in the Syncona Limited portfolio have yet to commercialise a product and their ability to do so may be affected by operational, commercial and other risks.

About Syncona

Syncona is a leading FTSE250 healthcare company focused on founding, building and funding a portfolio of global leaders in life science. Our vision is to build a sustainable, diverse portfolio of 15 - 20 companies focused on delivering transformational treatments to patients in truly innovative areas of healthcare, through which we are seeking to deliver strong risk-adjusted returns for shareholders.

We seek to partner with the best, brightest and most ambitious minds in science to build globally competitive businesses. We take a long-term view, underpinned by a strategic capital base which provides us with control and flexibility over the management of our portfolio. We focus on delivering dramatic efficacy for patients in areas of high unmet need.

About Freeline

Freeline is a privately held clinical-stage biotechnology company focused on AAV based gene therapy targeting the liver. Our vision is to create better lives for people suffering from chronic systemic diseases using the potential of gene therapy as a one-time curative treatment. Freeline is headquartered in the UK and has operations in Germany and the US.