#Australia #Melbourne #CSL #Lixudebart #Alentis

CSL and Alentis Collaborate for Lixudebart

In a groundbreaking announcement, CSL and Alentis Therapeutics have entered into an exclusive global collaboration aimed at developing and commercializing lixudebart, an innovative drug targeting claudin-1 for treating various rare kidney and liver diseases.

This partnership is significant, as Alentis will receive an initial payment of $355 million and may earn up to $1.2 billion based on commercial milestones, along with a worldwide profit-sharing agreement.

Current Trials and Potential Impact

Currently, lixudebart is being studied in a Phase 2 trial named RENAL, focusing on patients suffering from ANCA-associated vasculitis and rapidly progressive glomerulonephritis (AAV-RPGN). This severe autoimmune condition can lead to irreversible kidney damage and terminal renal failure if untreated. The unique mechanism of action of lixudebart demonstrates potent anti-inflammatory and antifibrotic effects, showing promise in preventing and even reversing organ damage in ANCA-associated vasculitis and potentially numerous other renal, hepatic, and pulmonary diseases.

The ongoing Phase 2 trial aims to translate these mechanistic effects into significant clinical outcomes, marking an exciting prospect for those affected by these debilitating diseases.

Objectives of the Collaboration

By combining Alentis's deep scientific expertise as a leading clinical biopharmaceutical company focusing on claudin-1 with CSL's extensive development capabilities in nephrology, the two companies share a common goal to provide impactful, innovative therapeutic options for patients with rare renal and hepatic ailments. Beyond AAV-RPGN, they plan to advance the development of lixudebart as a potential new treatment for focal segmental glomerulosclerosis (FSGS)—a progressive and rare kidney disease—and for primary sclerosing cholangitis (PSC), an autoimmune chronic liver disease.

Dr. Mark Pruzanski, CEO of Alentis Therapeutics, emphasized that this collaboration would significantly expedite the development of lixudebart across multiple indications simultaneously. He expressed confidence in CSL's proven track record in clinical development and marketing therapies targeted at AAV and renal conditions, making them an ideal partner for bringing lixudebart to patients in need.

Challenges in Treating AAV-RPGN

Dr. Bill Mezzanotte, Executive Vice President and R&D Head at CSL, highlighted the urgency in treating patients with ANCA-associated vasculitis accompanied by rapidly progressive glomerulonephritis. These patients experience a rapid decline in kidney function, posing a risk of irreversible damage even with current treatment options. According to Mezzanotte, lixudebart presents a significant opportunity to enhance renal function and prevent progression toward end-stage renal disease and may also offer similar benefits for liver function in cases of PSC.

Financial Aspects of the Agreement

The collaboration agreement entails that CSL will fund the completion of the ongoing Phase 2 RENAL study, as well as future Phase 3 trials for AAV-RPGN. They will also finance Phase 2 trials for FSGS and PSC, along with additional development activities. Once lixudebart reaches the market, profits will be shared with CSL retaining 55% and Alentis receiving 45%.

About AAV-RPGN and Lixudebart

AAV-RPGN, a rare but severe autoimmune disease, occurs when the immune system attacks the small blood vessels within the kidneys. It is characterized by a rapid decline in renal function, often from days to weeks. Even with strong immunosuppressive therapies, many patients face significant or total loss of renal function.

Lixudebart, previously known as ALE.F02, is a monoclonal antibody in development that selectively targets exposed claudin-1, a critical player in the inflammatory and fibrotic signaling pathways of many fibrotic diseases affecting the kidneys, liver, lungs, intestines, and other solid organs. Preliminary analyses from the Phase 2 RENAL trial indicated a promising improvement in renal function, assessed via estimated glomerular filtration rate (eGFR) and proteinuria rates, after 24 weeks. In the Phase 1b FEGATO trial, involving patients with advanced liver fibrosis, lixudebart demonstrated improvements in liver function at six weeks, showcasing an encouraging safety and tolerability profile.

Lixudebart has received orphan drug designations from the FDA for treating idiopathic pulmonary fibrosis (IPF), highlighting its potential in various serious conditions.

Conclusion

Founded on pioneering research from Professor Thomas Baumert at the University of Strasbourg, Alentis is now advancing multiple clinical assets, including lixudebart. This partnership with CSL is a pivotal step forward in bringing new therapeutic options to patients suffering from rare, severe diseases, emphasizing the promise of biotechnology in modern medicine.

For more details, visit CSL's website and Alentis here.