Partner research update

Vectura Group plc

Ablynx reports positive top line results for its anti-RSV Nanobody® (ALX-0171) inhaled using Vectura's FOX® device in a Phase I/IIa study in infants hospitalised with RSV infection

·      Primary endpoint of safety and tolerability met

·      Anti-viral effect demonstrated and encouraging initial indication of therapeutic effect

·      Results support advancing the programme into a Phase II efficacy study in infants

·      Potential general proof-of-principle for the administration of Nanobodies^® by inhalation

Chippenham, UK - 3 May 2016: Vectura Group plc (LSE: VEC; "Vectura" or "the Company"), announce the results of their partner, Ablynx, positive top line results from the first-in-infant Phase I/IIa study of its wholly-owned, inhaled, anti-RSV Nanobody, ALX-0171, in 53 infants, aged 1-24 months, hospitalised as a result of a respiratory syncytial virus (RSV) infection. The study met its primary endpoint, demonstrating the favourable safety and tolerability profile of ALX-0171 when administered daily by inhalation in the target infant population, with no treatment-related serious adverse events reported.ALX-0171 was detected in the serum of subjects after treatment, consistent with lung exposure. Anti-drug antibodies had no effect on the pharmacokinetics and no relation with adverse events was seen. Treatment with inhaled ALX-0171 had an immediate impact on viral replication and also reduced viral load, as compared to placebo. Analysis of a composite of clinical efficacy endpoints, the Global Severity Score1, led to an encouraging initial indication of a therapeutic effect for infants treated with ALX-0171.

VR465 - Global

ALX-0171 is a Nanobody drug candidate, administered through inhalation, for the treatment of respiratory syncytial virus (RSV) infection in infants. VR465 is being developed by our partner Ablynx and utilises Vectura's smart nebuliser technology device, the FOX^®, to deliver the Nanobody to patients. The FOX^® device used in this programme has been adapted for use with neonates and infants.

FOX^®

The FOX^® device is a hand-held, self-contained, battery powered inhalation system that delivers nebulised liquid drugs with high performance using a vibrating mesh technology.  The mesh-based aerosolisation engine is proprietary to Vectura.  As with all of Vectura's smart nebuliser delivery systems, the FOX^® provides targeted inhalation therapy for applications where precise and targeted delivery to the lungs is needed.  To achieve this, the device creates a liquid aerosol and co-ordinates delivery after the patient has inhaled using the FAVORITE (Flow And Volume Regulated Inhalation TEchnology) principle for precise delivery to the lungs. The FOX^® inhalation system also makes use of a flow sensing/controlling value system, is rechargeable and can be Bluetooth^®-enabled. FOX^® is CE marked and 510(k) approved and in April 2014, gained a Red Dot Award for product design.

James Ward-Lilley CEO, commented:

"These results and the additional marked antiviral effect in RSV-infected infants is a positive step which Ablynx believes support advancement into a Phase II efficacy study in infants. This announcement continues to demonstrate a validation of the Vectura smart nebuliser technology underpinned by a strong partnering relationship, combining the device capabilities of Vectura and the powerful Nanobody technology and development expertise of Ablynx. This progress is a further example of how Vectura continues to a partner of choice for the application of novel formulation and device technologies in the development of medicines."

-Ends-

Enquiries

About the first-in-infant Phase I/IIa study

The first-in-infant Phase I/IIa study recruited 53 hospitalised RSV-infected infants, aged 1-24 months, in multiple clinical centres in Europe and the Asia-Pacific region. The study consisted of an open-label lead-in phase with 5 infants, aged 5-24 months, who received ALX-0171 and a double-blind, placebo-controlled phase with 48 infants, aged 1-24 months, who were randomised to ALX-0171 or placebo. 

The primary endpoint of the study was the assessment of safety and tolerability for once daily inhalation of ALX-0171 for three consecutive days. Secondary endpoints included assessments of clinical effect (including effect on feeding, oxygen saturation, respiratory rate, wheezing, coughing and general appearance), immunogenicity, pharmacokinetics (PK) and pharmacodynamics (PD) of inhaled ALX-0171.

Serum samples were collected for PK analysis on the last day of treatment (day 3) post-dose. Anti-viral activity (viral load and time to undetectable virus) was measured in nasal swabs (plaque assay and qRTPCR2), prior to dosing and then 6 hours post-dose on each day of treatment. An analysis of the clinical effect used the Global Severity Score, a clinical score that categorises infants with respiratory infections based on 7 parameters: feeding intolerance, medical intervention, respiratory difficulty, respiratory frequency, apnoea, general condition and fever. The data collected in the study were matched to corresponding parameters in the Global Severity Score to assess the time course of disease severity in the treated group versus placebo. 

About RSV and ALX-0171

Respiratory syncytial virus (RSV) is the most common cause of lower respiratory tract infections and the leading viral cause of severe lower respiratory tract disease in infants and young children worldwide. It is the primary cause of infant hospitalisation and virus associated deaths in infants, with estimated global annual infection and hospitalisation rates of 34 million and 3-4 million respectively3. It is associated with an estimated 3,000-8,500 deaths in infants <2 years globally per year4. In addition, RSV infections have been linked to an increased risk of asthma development later in life5. Current treatment of RSV infections is primarily focussed on symptomatic relief, hence the need for an effective and specific anti-RSV therapeutic.  

Ablynx's ALX-0171 has been developed to address this unmet medical need and is a potential breakthrough for the treatment of RSV infection in infants. This wholly-owned trivalent Nanobody binds to the F-protein of RSV, thereby inhibiting viral replication and neutralising RSV activity by blocking virus uptake into cells. The physical robustness of the Nanobody allows administration via inhalation directly to the site of infection, i.e. the respiratory tract including the lungs. ALX-0171 has shown a potent anti-viral effect against a broad range of RSV strains in vitro and it has demonstrated a marked therapeutic effect following administration via nebulisation in a neonatal animal model for infant RSV infection6. Repeated daily inhalation of ALX-0171 was proven to be well-tolerated in multiple Phase I clinical studies, including a study in subjects with hyper-reactive airways.

About Vectura

Vectura is an independent pharmaceutical product development company that focuses on the development of inhaled pharmaceutical therapies for the treatment of diseases that  affect or can be treated with drugs that act on the airways (airways diseases), incorporating inhaled device formulation and clinical development. This segment of the pharmaceutical market includes significant indications such as asthma and COPD, in addition to a wide range of other indications including cystic fibrosis, pulmonary fibrosis and other diseases of the lung.

Vectura has eight⁽¹⁾ products marketed by partners with growing global royalty streams and a portfolio of drugs in clinical development, a number of which have been licensed to major pharmaceutical companies. Vectura has development collaborations and licence agreements with several global pharmaceutical and biotechnology companies, including Hikma (through its wholly-owned subsidiary, West-Ward Pharmaceuticals), Novartis, Sandoz, Baxter, GSK, UCB, Ablynx, Grifols, Janssen and Tianjin KingYork Group Company.

Vectura has established a pipeline focused on airways diseases, where all programmes are justified on the basis of technical feasibility and commercial attractiveness. The focus of Vectura's internal resource allocation is on Vectura's wholly-owned assets, in particular VR475 and VR647.

 (1) Advate®  came off patent at the end of January 2016. Vectura does not expect to receive any material royalties from that product during its financial year ending 31 March 2017, or thereafter.

For further information, please visit Vectura's website at www.vectura.com.

Forward-looking statements

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