Avalo Therapeutics (AVTX) TD Cowen 45th Annual Healthcare Conference summary

Key insights and market overview

• HS market is expected to expand significantly, with novel targets like IL-1β gaining attention for their role in disease pathogenesis.

• AVTX-009, an anti-IL-1β monoclonal antibody, is positioned for a best-in-disease profile in HS, with a 15-fold higher affinity and longer half-life than lutikizumab.

• Phase II LOTUS trial for AVTX-009 began in late 2023, with top-line data expected in 2026 and a cash runway extending into 2027.

• The HS market is projected to exceed $10 billion by 2035, driven by increased diagnosis, earlier referrals, and more effective therapies.

• AVTX-009 has potential applications in other immune-mediated diseases, including osteoarthritis, gout, and inflammatory bowel disease.

Scientific rationale and clinical evidence

• IL-1β is a dominant immunoregulator in HS, with gene expression over 100-fold higher in lesions compared to normal skin.

• Clinical validation for IL-1β targeting comes from AbbVie's lutikizumab, which showed efficacy in refractory HS patients.

• AVTX-009 offers higher affinity, longer half-life, and greater bioavailability than lutikizumab, supporting less frequent dosing and potentially superior efficacy.

• IL-1α is not elevated in HS lesions and neutralization has shown no clinical benefit, supporting a focus on IL-1β.

• High affinity is critical due to limited drug penetration in inflamed skin lesions, making AVTX-009's properties advantageous.

Clinical development and trial design

• LOTUS phase II trial is a three-arm, placebo-controlled study with two AVTX-009 dosing regimens, targeting HiSCR 75 at 16 weeks as the primary endpoint.

• Patient population includes both TNF-experienced failures (60%) and biologic-naive patients (40%), with a focus on moderate to severe disease.

• HiSCR 75 was chosen as a stringent, clinically relevant endpoint to improve signal-to-noise ratio and align with evolving regulatory standards.

• Sites are open in the US, Canada, Australia, Europe, and Turkey, with phase III planned for 2027.