CSL joins forces with Alentis on claudin candidate

CSL has licensed rights to a potentially first-in-class anti-claudin-1 antibody developed by Alentis Therapeutics in a deal that could be worth up to $1.55 billion.

Melbourne, Australia-based biotech CSL is paying the Swiss biotech $355 million in an initial payment, with another $1.2 billion in potential milestones, for rights to lixudebart, which is currently in the phase 2 RENAL trial in a rare and potentially life-threatening autoimmune disease.

Lixudebart (formerly ALE.F02) has potential across a range of kidney, liver, and other diseases, according to CSL, which includes rare diseases among its core therapeutic categories.

Claudin-1 is a tight junction protein that plays a role in maintaining the integrity of neighbouring cells and regulates transport and communication between them. In some diseases, such as cancers, fibrotic diseases, and chronic inflammatory conditions, it can be under- or over-expressed or start behaving abnormally.

As a cell-surface protein, it has drawn attention as an actionable target for drug development, and Alentis is considered the frontrunner in the category. Lixudebart is designed to bind exposed claudin-1 on cell surfaces to shut down pro-inflammatory and pro-fibrotic signalling cascades.

In RENAL, it is being tested in ANCA-associated vasculitis with rapidly progressive glomerulonephritis (AAV-RPGN), a destructive inflammatory illness that targets blood vessels and can cause irreversible kidney damage and end-stage renal disease.

"Patients diagnosed with ANCA-associated vasculitis with rapidly progressive glomerulonephritis face rapid kidney function decline, leaving them at risk of irreversible damage even with currently available treatments," said Dr Bill Mezzanotte, CSL's head of R&D.

"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 [FSGS], while potentially showing similar benefit on liver function in primary sclerosing cholangitis [PSC]," he added.

If it reaches the market, profits on lixudebart sales will be shared 55% to CSL and 45% to Alentis. Under the terms of the deal, CSL will fully fund the completion of the RENAL trial, a planned phase 3 trial in AAV-RPGN, phase 2 trials in FSGS and PSC, and other development activities.

CSL has an established position in rare diseases through its development of products like Filspari (sparsentan) for IgA nephropathy (IgAN) and focal segmental glomerulosclerosis (FSGS), Zemaira/Respreeeza (alpha-1 proteinase inhibitor) for alpha-1 antitrypsin deficiency, and haemophilia B gene therapy Hemgenix (etranacogene dezaparvovec).

The deal comes amid a challenging period for CSL, punctuated by the company's first operating loss since the mid-1990s, with its $11.7 billion acquisition of Swiss biotech Vifor in 2022 not delivering on expectations, pipeline disappointments, and Hemgenix held back by supply constraints.

In February, chief executive Paul McKenzie abruptly departed the company after only a brief tenure, and CSL is being run on an interim basis by Gordon Naylor as the search for a permanent replacement goes on.