CSL and Alentis Therapeutics have entered an exclusive global agreement to co-develop and co-promote lixudebart, the companies said, describing the therapy as a potential first-in-class treatment that targets claudin-1 in a range of kidney, liver and other diseases.
Lixudebart is being evaluated in the ongoing Phase 2 RENAL trial in patients with ANCA-associated vasculitis with rapidly progressive glomerulonephritis, or AAV-RPGN, which the companies said is a rare and potentially life-threatening autoimmune disease that can cause irreversible kidney damage and end-stage renal disease. Alongside AAV-RPGN, the partners will advance the treatment for focal segmental glomerulosclerosis, a rare progressive kidney disease, and for primary sclerosing cholangitis, an autoimmune chronic liver disease.
Under the agreement, CSL will make an initial payment of US$355 million to Alentis, which is eligible for up to US$1.2 billion more in commercial milestone payments. CSL will fully fund completion of the ongoing Phase 2 RENAL trial, a planned Phase 3 trial in AAV-RPGN, Phase 2 trials in FSGS and PSC, and other supporting development activities. Once the therapy is commercialised, global profits are to be shared 55 per cent to CSL and 45 per cent to Alentis.
In an interim analysis of 26 patients with AAV-RPGN in the Phase 2 RENAL trial, the companies said lixudebart showed improvement in kidney function as assessed by eGFR and proteinuria at 24 weeks. In the Phase 1b FEGATO trial in 41 patients with advanced F3/F4 liver fibrosis, they said it demonstrated improved liver function at six weeks. Both studies showed dose-dependent claudin-1 target engagement, and the companies said the safety and tolerability profile was favourable. The FDA has granted lixudebart Orphan Drug designation for idiopathic pulmonary fibrosis.
Dr Mark Pruzanski, chief executive of Alentis Therapeutics, said the partnership would allow development of lixudebart in several indications in parallel and that CSL's clinical development and commercialisation work in AAV and kidney diseases made it the right partner. Dr Bill Mezzanotte, CSL's executive vice president and head of R&D, said patients with AAV-RPGN face rapid kidney function decline and that CSL believes lixudebart could become an important therapeutic option, first in AAV-RPGN and hopefully also in FSGS, with potentially similar benefit for liver function in PSC.