R&D programmes overview

Our development programmes focus on the potential of autologous ex-vivo gene therapy to restore normal gene function in primary immune deficiencies, metabolic diseases and haematological disorders

Ex-vivo lentiviral gene therapy programme Preclinical phase Clinical phase Approval
 
In vitro Laboratory studies Pre-IND
P1/2 P2/3
 
ADA-SCID
 
 
MPS IIIA (Sanfilippo A)
 
 
Preclinical Programmes
 
 
Programmes in primary immune deficiencies
Programmes in metabolic disorders

ADA-SCID (adenosine deaminase severe combined immunodeficiency)

A rare, life-threatening primary immune deficiency

Severe combined immunodeficiencies (SCIDs) are rare and life-threatening inherited disorders of the immune system. Affected children are vulnerable to severe recurrent infections and have a high risk of death within the first year of life if not treated

ADA-SCID is characterized by a deficiency in the enzyme adenosine deaminase (ADA). It is caused by mutations in the ADA gene and accounts for 10–15% of all cases of SCID.

ADA is normally expressed throughout the body, so in addition to a severely compromised immune system patients may also present with neurodevelopmental, behavioural, skeletal and hepatic abnormalities

Treatment options include allogenic haematopoietic stem cell transplant (HSCT), chronic enzyme replacement therapy or autologous ex-vivo  gene therapy. When a HLA-matched sibling or family donor is not available, allogeneic transplants are associated with a high risk of mortality.1 Enzyme replacement with pegylated-ADA can be highly effective in the short term, but chronic use involves lifelong weekly injections and long-term survival rate (78% at 20 years) is less promising2

Autologous ex-vivo lentiviral gene therapy

Orchard is developing ex-vivo lentiviral gene therapy to restore normal gene function in patients with ADA-SCID

Summary of clinical data to date*

  • >30 patients treated at UCL and UCLA as of March 2016
  • 100% survival with a follow-up of 2–49 months
  • Evidence of immune reconstitution
  • No evidence of insertional mutagenesis
For more information please contact:

info@orchard-tx.com

*As of March 2016
  1. Hassan et al. shows 1-year survival of 43-67% for transplants from haploidentical and HLA-matched donors. Hassan A et al. Blood 2012;120:3615–24
  2. Gaspar HB et al. Blood 2009;114:3524–32

MPS IIIA (mucopolysaccharidosis type IIIA)

A rare, life-threatening metabolic disease

Mucopolysaccharidosis type III (MPS III, Sanfilippo syndrome) consists of four clinically similar neurodegenerative, lysosomal storage diseases that affect ~1–2 in 100,000 births1

The relative prevalence of each form of MPS III varies by geography
  • Type A is the most common form in Northwestern Europe (~75% of patients in the UK)2
  • Type B is the most common form in Southeast Europe1
  • Other forms (types C and D) are rare everywhere1

MPS IIIA is characterized by deficiency of the enzyme heparan sulfamidase. The disease is caused by mutations in the SGSH gene, which is inherited in an autosomal recessive pattern

MPS IIIA affects children in early life, with a progressive decline in cognitive and behavioural functions and subsequent motor function decline. The disease ultimately results in severe dementia and early death, usually in late teens or early twenties

Currently treatment options are limited to palliative care only.1 As yet, no treatment has been shown to correct or relieve the neurological manifestations of the disease

Autologous ex-vivo lentiviral gene therapy

Orchard is developing ex-vivo lentiviral gene therapy to restore normal gene function in patients with MPS IIIA

Summary of preclinical data to date*

  • An increase in heparan sulfamidase expression in the periphery and the brain of pre-clinical models of MPS IIIA, leading to clearance of lysosomal material in neurons
  • Evidence of normalization of hyperactive behaviour in pre-clinical models of MPS IIIA
  • The next steps are to complete the ongoing pre-clinical programmes and open a first-in-man clinical study
  • Through its academic collaborations, Orchard has access to more than 10 research programmes
For more information please contact:

info@orchard-tx.com

*As of March 2016
  1. Valstar MJ et al. J Inherit Metab Dis 2008;31:240–52
  2. University of Manchester / Central Manchester Foundation Trust

Follow-on ex-vivo lentiviral gene therapy programmes

  • Orchard has a pipeline of potentially transformative autologous ex-vivo gene therapies
  • Through its academic collaborations, Orchard has access to more than 10 programmes
  • We are actively seeking additional candidates in disease areas of high unmet need
  • Our mission is to accelerate promising pre-clinical and early clinical results into commercially approved and reimbursed medicines, globally