Vectorized Anti-Eosinophil Antibodies for Treatment of Eosinophilic Leukemias and Inflammatory Disorders

Background & Unmet Need

• Eosinophils are highly specialized, bone-marrow derived, granulocytic effector cells (white blood cells) that store and release several highly active mediators
• Eosinophils are implicated in a variety of chronic allergic disorders, including asthma and eosinophilic esophagitis (EoE), as well as certain cancers (e.g., chronic eosinophilic leukemia-not otherwise specified (CEL-NOS))
• Eosinophilic disorders have largely been treated with chronic administration of corticosteroids, which are commonly linked to numerous adverse effects
• Antibody therapeutics are effective for many patients, but must be repeatedly administered for continuous efficacy
• Unmet Need: Therapeutics for eosinophilic disorders which address eosinophil accumulation and provide sustained, long-term benefits for patients

Technology Overview

• The Technology: AAV gene therapy that provides sustained in situ expression of an anti-eosinophil monoclonal antibody for eosinophilic disorders
• Various anti-eosinophil antibodies for targets such as Siglec-8 or IL-5 may be incorporated in the vector
• AAVrh.10mAnti-Eos is an rh.10 AAV vector encoding antibody Siglec F, which induces eosinophil apoptosis
• PoC Data: A single dose of AAVrh.10mAnti-Eos resulted in high, persistent serum levels of Siglec-F
• In a mouse model of CEL-NOS, a single dose of AAVrh.10mAnti-Eos provided long-term suppression of eosinophils in blood and increased survival
• In a mouse model of EoE, AAVrh.10mAnti-Eos administration reduced blood and esophageal eosinophil numbers (P < 0.02 and P < 0.002, respectively), protected from esophageal tissue remodeling, and minimized food impaction

Technology Applications

• Treatment of CEL-NOS and other leukemias where eosinophils play a prominent role
• Treatment of EoE and related eosinophilic gastric disorders
• Treatment of other disorders in which eosinophils are elevated, including allergic and endocrine disorders

Technology Advantages

• A single dose may be sufficient for sustained therapeutic effect
• Provides a platform for expression of various anti-eosinophil antibodies, such as Siglec-8 or IL-5

Tissue remodeling, as demonstrated by increase in area of basal lamina (white bar), was decreased in mice treated with AAVrh.10mAnti-Eos in a murine model of EoE