CSL has agreed to pay Alentis Therapeutics US$355 million up front in an exclusive deal to jointly develop and promote lixudebart, an experimental antibody that could become the first of a new class of treatments for people with rare kidney and liver disease.
Under the agreement, Alentis can receive up to a further US$1.2 billion in commercial milestone payments. CSL will also pay the full cost of finishing the Phase 2 RENAL trial and running the planned Phase 3 trial in the drug's lead kidney indication. It will also fund Phase 2 trials in two further diseases and other supporting development work. Once commercialised, CSL will take 55 per cent of global earnings, and Alentis will take 45 per cent.
Lixudebart is in an ongoing Phase 2 trial in patients with vasculitis associated with antineutrophil cytoplasmic antibodies (ANCA) and rapidly progressive glomerulonephritis. In this rare and potentially fatal autoimmune disease, the immune system attacks small blood vessels in the kidney. Patients can lose kidney function within days or weeks. CSL said most patients suffer significant or total loss of kidney function despite strong immunosuppressive treatment, and the disease can cause permanent kidney damage and kidney failure.
The Alentis antibody selectively targets exposed claudin-1, which drives the inflammatory and fibrotic signalling found in many fibrotic diseases of the kidney, liver, lung, intestine and other solid organs. By acting on both inflammation and fibrosis, it aims to address two of the main causes of lasting organ injury.
"We believe lixudebart has the potential to become an important new therapeutic option to help improve kidney function and prevent progression to end-stage kidney disease," said Dr Bill Mezzanotte, CSL's executive vice president and head of research and development.
"Our collaboration with Alentis reflects CSL's commitment to building a leading global nephrology franchise, and our strategic intent to create high-value external partnerships," he said.
An interim analysis of 26 patients in the RENAL trial found lixudebart produced promising improvements in kidney function at 24 weeks, measured by eGFR and proteinuria. In the Phase 1b FEGATO trial, 41 patients with advanced F3/F4 liver fibrosis showed improved liver function after six weeks of treatment. In both studies, the candidate's engagement with its target increased with dose, and safety and tolerability were favourable.
The companies also plan to test lixudebart in focal segmental glomerulosclerosis, a chronic kidney disease, and in primary sclerosing cholangitis, a chronic liver disease that currently has no available therapy. The US Food and Drug Administration has already granted lixudebart Orphan Drug designation for idiopathic pulmonary fibrosis.
