CSL, Alentis partner on Rare Kidney and Liver Disease Drug

Rare Daily Staff

CSL will pay Alentis Therapeutics $355 million upfront and up to $1.2 billion in additional commercial milestones as part of a global partnership to develop lixudebart, an experimental treatment aimed at reducing inflammation and scarring in rare kidney and liver diseases.

As part of the agreement, CSL will also fund specified clinical trials and supporting development work. If the drug reaches the market, the companies will jointly promote it and share global profits, with CSL receiving 55 percent and Alentis 45 percent.

“This partnership enables us to dramatically accelerate the development of lixudebart in several indications in parallel,” said Mark Pruzanski, CEO of Alentis.

The partnership’s most advanced program targets a severe form of ANCA-associated vasculitis, an autoimmune disease in which the immune system attacks small blood vessels. When the disease affects the kidneys and causes rapidly progressive glomerulonephritis, kidney function can deteriorate within days or weeks, potentially leading to irreversible damage and kidney failure.

Lixudebart is being evaluated in these patients in the ongoing phase 2 RENAL trial. Under the agreement, CSL will fund completion of that study and a planned phase 3 trial.

The companies also plan phase 2 studies in focal segmental glomerulosclerosis, or FSGS, a rare, progressive kidney disease, and primary sclerosing cholangitis, or PSC, a chronic liver disease.

Lixudebart is a monoclonal antibody designed to target an exposed form of claudin-1, a protein the companies describe as a driver of inflammation and fibrosis in several organs.

The companies hope that blocking this target could help prevent or reverse organ damage.

For patients with severe kidney involvement from ANCA-associated vasculitis, the aim is to preserve kidney function rather than simply control inflammation.

An interim analysis of 26 patients in the phase 2 RENAL trial showed encouraging changes at 24 weeks in estimated glomerular filtration rate, a measure of how well the kidneys filter blood, and proteinuria, or protein in the urine.

The companies also reported improved liver function at six weeks in a phase 1b study involving 41 patients with advanced liver fibrosis. They described a favorable safety and tolerability profile in both studies.

The companies also reported evidence that the drug engaged its intended target in a dose-dependent manner. Target engagement supports the proposed mechanism but does not, by itself, establish a clinical benefit.