Syncona Regulatory News (SYNC)

Syncona Limited

Freeline publishes further data for FLT180a

7 February 2020

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 a novel gene therapy, FLT180a for Haemophilia B, at The European Association for Haemophilia and Allied Disorders (EAHAD) conference.

The presentation is entitled: "Phase 1/2 preliminary data from B-AMAZE study of adeno associated virus (AAV) gene therapy (FLT180a) confirms progress towards achieving Factor IX levels in the normal range for patients with severe or moderately severe Haemophilia B."

Chris Hollowood, Chief Investment Officer of Syncona and Executive Chairman of Freeline, said: "We are highly encouraged by the data being generated in our lead programme in Haemophilia B. We believe that Freeline has developed a product that could be best-in-class for patients living with Haemophilia B. A functional cure was an aspiration of Freeline's when the business was founded just under five years ago and this data takes an important step towards that goal. We look forward to identifying the optimal dose in the coming months and subsequently moving the product into a pivotal trial.

The data also demonstrates the power of our next generation capsid. The step change in performance delivered by the capsid will allow Freeline to lead the systemic gene therapy space beyond Haemophilia to diseases, such as Fabry Disease and Gaucher Disease, where high expression levels will be needed for meaningful clinical impact."

Trial background

Freeline is a systemic gene therapy company focused on liver expression of proteins for a range of chronic diseases. Freeline uses a novel capsid which is capable of driving high protein expression. FLT180a is a next-generation AAV gene therapy for people with Haemophilia B that leverages this next-generation capsid. Freeline is seeking to identify the optimal dosing regimen for FLT180a with the goal of delivering to patients Factor IX (FIX) activity levels between 70 to 150 per cent, in the upper part of the normal range, 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 eight patients who have been treated across four dose cohorts with FLT180a. The first dose cohort (two patients) has follow-up over 78 weeks, the next two dose cohorts (two patients in each) have data available over 26 weeks and the most recent dose cohort (two patients) have FIX activity level readings available after three weeks:

·; Dose Level One: Two patients treated with the lowest dose, 4.5x1011 vector genomes/kg body weight and had average FIX level activity at 78 weeks of 43.5%

·; Dose Level Two: Two patients received a single dose at 1.5x1012 vector genomes/kg body weight and had average FIX level activity at 26 weeks of 160%

o One patient within the cohort experienced a rise in ALT (see below) that was followed by a decline in expression at 26 weeks

·; Dose Level Three: Two patients received a single dose at 7.5x1011 vector genomes/kg body weight and had average FIX activity at 26 weeks of 32%

o One patient within the cohort experienced a rise in ALT that was followed by a decline in expression at 26 weeks

·; Dose Level Four: Two patients received a single dose at 9.75x1011 vector genomes/kg body weight and had average FIX activity at three weeks of 109%

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 low dose cohort, stable expression of FIX activity has now been seen for over 18 months. Six patients have completed follow-up for six months, and amongst those, three have FIX activity levels over 50%. The two patients in dose level four (9.75x1011) have shown encouraging early expression and the current focus is to expand this dose cohort to establish safety and efficacy.

No patients in the trial have had any bleeding episodes requiring treatment or required any FIX supplementation post gene therapy.

Alanine aminotransferase (ALT) is an enzyme that is predominantly found in the liver. Damage to liver cells can lead to release of more ALT in the bloodstream and therefore ALT levels in the blood can be used as a marker of liver damage or toxicity, and risk of loss of FIX expression. Systemic gene therapy programmes often show rises in ALTs between months one and six. Freeline has been developing its immunosuppression regimen throughout the trial, to seek to identify a regimen that consistently controls ALTs and therefore provides patients receiving therapy with the maximum confidence of normal activity. The business continues to evolve this and has implemented a regimen for dose level four involving prophylactic corticosteroids and tacrolimus[2]. Immunosuppression appears to be effective in controlling ALTs and there were no clinical symptoms associated with ALT rises. No ALT rises were observed in the low dose cohort (4.5x1011).

Further data is in the table below.

Next steps

Freeline continues to enrol Haemophilia B patients as part of its Phase 1/2 dose-ranging trial in order to identify the optimal dose to achieve normal FIX activity levels and will provide a further update in H2 CY2020.

Valuation

In line with Syncona's valuation policy, we continue to hold our investment in Freeline at fair value based on cost until material clinical data is generated, or a third-party financing or other factor occurs, that indicates that cost is no longer the appropriate measure of fair value. Syncona anticipates that the point at which Freeline selects the optimal dosing regimen for FLT180a and indicates that it will move to a pivotal trial, it will constitute material clinical data.

Syncona remains the sole institutional investor in Freeline alongside UCL Technology Fund. Syncona has a 79 per cent fully diluted stake in Freeline which as at 31 December 2019 is valued at £148.6 million.

Data table

*Patients received steroids after week 3

**One patient within this cohort experienced a rise in ALT that led to a decline in expression at 26 weeks

 [ENDS]

Enquiries

Syncona Ltd

Siobhan Weaver / Annabel Clay

Tel: +44 (0) 20 3981 7940

FTI Consulting

Ben Atwell / Natalie Garland-Collins

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.