Emactuzumab designated as an Orphan Medicinal Product in Europe

• TGCT is a debilitating disease that often impacts patients in the prime of their life
• Designation to include both localized and diffuse forms of the disease

DUBLIN, Aug. 31, 2022 /PRNewswire/ -- SynOx Therapeutics Limited ("SynOx" or the "Company"), the late-stage clinical biopharmaceutical company, announces a regulatory update on emactuzumab, in development for the treatment of Tenosynovial Giant Cell Tumour (TGCT) and other diseases. The European Medicines Agency (EMA) has designated emactuzumab as an orphan medicinal product in the indication of TGCT for both localized and diffuse types of the disease.

TGCT is a rare, chronically debilitating disease affecting the synovium, tendon sheaths and bursa membranes, primarily of knee, hip and ankle joints. It causes loss of function of the affected joints, pain, stiffness and limited range of motion. TGCT has an incidence of 43 cases per million patient years, of which 4 per million patient years relate to diffuse TGCT¹. No systemic treatments have been approved for TGCT in the EU. Most patients receive surgical intervention, with a post-surgery recurrence rate of up to 50%.²

Emactuzumab is a novel monoclonal antibody inhibiting CSF-1R that offers a short course of treatment. Phase I/II studies indicated good tolerability and a manageable safety profile and substantial preliminary efficacy in TGCT patients with rapid, robust tumour reduction and durable response.

Synox is planning a phase III trial (TANGENT) to assess the efficacy and safety of emactuzumab in patients with localized or diffuse TGCT where surgical removal of the tumour is not viewed as an option. More details can be found on www.clinicaltrials.gov (with trial identifier NCT05417789) and at www.tangentstudy.com. 

Ray Barlow, Chief Executive Officer of SynOx, said: "We have made significant progress in the development of emactuzamab in TGCT in the last 12 months. The positive opinion regarding the orphan drug designation marks an important step in SynOx's continuing journey to provide a potential therapeutic option for patients with this debilitating disease. We are now recruiting patients on to our phase III registrational trial (TANGENT) and look forward to providing an update on progress in the near future."

¹ (Mastboom MJL et. al. Acta Orthopaedica 2017 2017; 88 (6): 688-694)
² (Lin F, et. al. JHEOR, 2022).

About SynOx Therapeutics

SynOx Therapeutics Limited is a Dublin, Ireland-based, late-stage clinical biopharmaceutical company developing emactuzumab, a best-in-class monoclonal antibody against CSF-1R, for the treatment of tenosynovial giant cell tumour (TGCT) and other macrophage related disorders. SynOx is led by an experienced team of industry professionals with a successful track record of developing and bringing products to commercialisation. It is backed by a strong syndicate of premier life science investors including HealthCap, Medicxi, Forbion and Gimv. Other shareholders include Celleron Therapeutics and Roche Ventures.

About Tenosynovial Giant Cell Tumour (TGCT)

Tenosynovial Giant Cell Tumour (TGCT), previously termed pigmented villonodular synovitis (PVNS), is a type of tumour that affects the soft tissue lining of joints and tendons. 

TGCTs are categorised as fibrohistiocytic tumours by the WHO classification and are subclassified based on growth patterns (localised- and diffuse types) and location (tendon sheath, and intra- and extra-articular forms). TGCTs are locally destructive and aggressive tumours.

TGCT is a rare disease, with an incidence of 39 per million persons for localized TGCT and 4 per million persons for diffuse TGCT (Mastboom et al. 2017). While TGCT is not in itself a life-threatening disease, it does result in important functional impairments, significant joint damage, and decline in quality of life, which carries a high healthcare burden and loss of work productivity.

In diffuse TGCT, the tumour is multinodular, infiltrative of soft tissue mass with villous projections, largely composed of immune cells and transformed, osteoclast-like cells drawn to the joint by the over-expression of CSF-1. This creates an inflammatory milieu, where diseased tissue diffusely borders healthy tissue, which has implications for the unsatisfactory success rate of surgical excision. 

TGCT is clinically characterised by pain, swelling, and range of movement limitations with significant impact on quality of life as a result. It is predominantly a mono-articular disease, typically affecting the lower limbs (knee, hip, ankle), although shoulder, elbow and smaller joints may also be altered. Unique instances of poly-articular disease have been documented.

Symptoms typically progress slowly but can be aggressive and destructive. If left untreated complications include moderate to severe joint deformity, degenerative articular changes, and osteoarthritis, which if severe enough, have led to cortical bone destruction and occasionally the need for arthrodesis or amputation.

About CSF-1 and Emactuzumab

CSF-1 (or macrophage colony-stimulating factor) is a cytokine that binds to the CSF-1 receptor (CSF-1R), expressed on macrophages and certain other cells, with effects on production, differentiation, and function of these cells.

Emactuzumab is a humanised IgG1 CSF-1R targeted antibody that inhibits and depletes macrophages in the tumour tissue. Emactuzumab was originally discovered and developed by Roche and has been tested in several phase 1/b studies as a monotherapy and in combination with other agents, including chemotherapeutics and immunotherapies. In clinical studies as a monotherapy in 63 patients with TGCT, emactuzumab has shown a substantial effect on tumour response (ORR ~71%) and was well tolerated [see "Long-term clinical activity, safety and patient-reported quality of life for emactuzumab-treated patients with diffuse-type tenosynovial giant-cell tumour." (Cassier et al)]

Emactuzumab may also have utility in other macrophage driven diseases and the company is actively considering potential options in these areas.