R&D Banner

Research & Development


Three New Projects Progress to Phase I Clinical Trials

CSL has extensive experience producing large scale polyclonal immunoglobulins isolated from human plasma with successful therapies including PRIVIGEN® and HIZENTRA®. Polyclonal antibodies are made by several different plasma cells and bind to multiple targets. We are now developing a portfolio of monoclonal antibodies (MAbs) using recombinant technology to treat important areas of unmet medical need. MAbs are made by identical cells that are all clones of a unique parent cell (monoclonal) and bind to the same target.

Our portfolio of MAbs includes three new therapies developed by innovative research and manufactured in our world-class biotechnology manufacturing facilities. Two therapies, CSL324 and CSL312, progressed to first-in-human studies over the past year and the third, CSL346 will enter in late 2017. All three MAbs have novel mechanisms of action and the potential to treat multiple indications in patients.

CSL324

CSL324 targets the granulocyte colonystimulating factor receptor (G-CSFR), a major regulator of neutrophils (white blood cells). By controlling the mobilisation of neutrophils from the bone marrow into the blood and reducing their recruitment to inflamed tissue sites, CSL324 could prevent the destruction of healthy tissue in autoimmune disease. The therapy may present a new treatment option for inflammatory diseases of the skin, joints and lungs that can be debilitating and have serious quality-of-life consequences for the patients affected. The Phase I trial started in July 2016 and is exploring proof of biological concept with a particular focus on identifying effective therapeutic dosing.

CSL312

CSL312 binds to and inhibits the activity of Factor XIIa, a plasma protein which plays a role in inflammation and thrombosis. CSL312 is being studied for use in multiple indications, including Hereditary Angioedema (HAE) – a disorder characterised by recurrent and attacks of swelling that can affect the face, extremities, gastrointestinal tract and upper airways. HAE attacks involving the face or throat can result in airway closure, asphyxiation and, if untreated, death. CSL312 provides the possibility of subcutaneous administration once every two to three weeks instead of bi-weekly dosing using current treatments, improving the quality of life for patients. CSL has marketed its plasma derived replacement therapy for HAE (Berinert®) for over 30 years and in June 2017 we received US approval for HAEGARDA® – the first and only subcutaneous prophylactic therapy to treat HAE. With the recent approval of HAEGARDA® and the initiation of clinical trials in October 2016 using CSL312, we remain committed to innovative research and to developing advanced treatment options for people living with HAE.

Another potential application under investigation for CSL312 is the prevention of thrombosis – the process of blood clot formation - particularly on artificial surfaces such as cardiac implants. The inhibition of Factor XIIa can prevent clotting without increasing the risk of bleeding, and may prevent thrombosis in acute indications such as bypass surgery.

CSL346

CSL346 is an anti-VEGF-B monoclonal antibody that may be used to control glucose absorption in insulin-resistant patients with Type 2 diabetes by targeting fatty acid metabolism. Type 2 diabetes is one of the fastest growing chronic diseases, affecting more than 420 million people globally. CSL346 may also be beneficial for diabetic nephropathy; one of the most common kidney complications associated with Type 2 diabetes. Data published in February 2017 showed a reduction in the accumulation of lipid deposits within the kidney and moderation of the progression of kidney disease in mice treated with CSL346. These findings challenge the hypothesis that kidney diabetic disease is simply the result of chronic elevated blood glucose. The Phase I clinical trial due to start later this year will focus on proof of biological concept with a view to unlocking the full therapeutic potential of the molecule.

CSL’s three new MAbs represent an exciting new generation of high-tech protein-based therapies in our Breakthrough Medicines pipeline and their development exemplifies our patient-centric commitment to work every day like a patient’s life depends on it, because it does.

 

strategy

Immunoglobulins

Products such as HIZENTRA® and PRIVIGEN®.

Direction: Maintain leadership position through focus on improved patient convenience, yield improvements, expanded labels, new formulation science and specialty Igs.

Breakthrough Medicines

Protein-based therapies such as anti IL-3R antibody (CSL362) and reconstituted High Density Lipoprotein (CSL112).

Direction: Develop new protein-based therapies for significant unmet medical needs and multiple indications.

Haemophilia Products

Plasma-derived products such as HAEMATE P® and recombinant coagulation factors such as IDELVION® and AFSTYLA®.

Direction: Support and enhance plasma products and develop a novel recombinant portfolio with a focus on scientific and product innovation and patient benefit.

Specialty Products

For acquired and perioperative bleeding such as BERIPLEX® and RIASTAP®, and BERINERT®, CORIFACT® and ZEMAIRA®, for certain types of deficiencies.

Direction: Leverage our high quality, broad specialty plasma products portfolio through new markets, novel indications and new modes of administration.