Australian biopharma company CSL and Switzerland-based Alentis Therapeutics have entered into an exclusive global collaboration agreement to co-develop and co-promote lixudebart, an investigational therapy targeting claudin-1 that has the potential to become a first-in-class treatment for a range of kidney, liver and other diseases.
Alentis’ lead antibody for fibrosis, lixudebart is currently being evaluated in the ongoing Phase 2 RENAL trial in patients with ANCA (antineutrophil cytoplasmic antibody)-associated vasculitis with rapidly progressive glomerulonephritis (AAV-RPGN). AAV-RPGN is a rare and potentially life-threatening autoimmune disease that can cause irreversible kidney damage and progression to end-stage renal disease.
According to the companies, lixudebart has a novel mechanism of action designed to exert anti-inflammatory and anti-fibrotic effects that may help prevent or reverse organ damage in ANCA-associated vasculitis (AAV) and other kidney, liver and lung diseases. The ongoing Phase 2 trial is evaluating whether these mechanistic effects translate into meaningful clinical benefits.
The collaboration combines Alentis’ expertise in developing claudin-1-targeted therapies with CSL’s global clinical development and commercialisation capabilities in nephrology.
In addition to AAV-RPGN, CSL and Alentis plan to develop lixudebart as a potential treatment for focal segmental glomerulosclerosis (FSGS), a rare progressive kidney disease, and primary sclerosing cholangitis (PSC), a chronic autoimmune liver disease.
“This partnership enables us to dramatically accelerate the development of lixudebart in several indications in parallel,” said Dr Mark Pruzanski, CEO of Alentis Therapeutics.
He added that CSL’s clinical development and commercialisation capabilities in AAV and kidney diseases make it a suitable partner to help bring lixudebart to patients.
Dr Bill Mezzanotte, EVP and Head of R&D at CSL, said patients with AAV-RPGN can experience rapid declines in kidney function and remain at risk of irreversible kidney damage despite currently available treatments.
“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, first in AAV-RPGN and hopefully also in focal segmental glomerulosclerosis, while potentially showing similar benefit on liver function in primary sclerosing cholangitis,” he said.
Mezzanotte added that the partnership with Alentis reflects CSL’s commitment to building a global nephrology franchise and its strategy of establishing external partnerships to develop potentially high-value therapies.
Under the agreement, CSL will make an upfront payment of USD 355 million to Alentis, while Alentis is eligible to receive up to an additional USD 1.2 billion in commercial milestone payments.
CSL will also fully fund completion of the ongoing Phase 2 RENAL trial and the planned Phase 3 trial in AAV-RPGN, as well as Phase 2 trials in FSGS and PSC and other supporting development activities.
Upon commercialisation, global profits from lixudebart will be shared, with CSL receiving 55% and Alentis 45%.
Lixudebart: Clinical Trial Results
Lixudebart, formerly known as ALE.F02, is an investigational monoclonal antibody that selectively targets exposed claudin-1, a protein implicated in inflammatory and fibrotic signalling pathways in numerous fibrotic diseases of the kidney, liver, lung, intestine and other solid organs.
In an interim analysis of 26 patients with AAV-RPGN enrolled in the ongoing Phase 2 RENAL trial, lixudebart showed improvements in kidney function, as measured by estimated glomerular filtration rate (eGFR), and proteinuria at 24 weeks.
In the Phase 1b FEGATO trial involving 41 patients with advanced F3/F4 liver fibrosis, lixudebart demonstrated improvements in liver function at six weeks.
In both studies, lixudebart demonstrated dose-dependent claudin-1 target engagement and a favourable safety and tolerability profile.
The US Food and Drug Administration (FDA) has granted lixudebart Orphan Drug designation for the treatment of idiopathic pulmonary fibrosis (IPF).
