Rationale and Trial Design for an AK-antiVEGF Gene Therapy Trial for Vestibular Schwannoma

Monday, October 13, 2025

9:48 AM - 9:54 AM EDT

Location: 244

Disclosure(s):

Brian M. Lin, MD:

faculty for this accredited education activity has no relationship(s) with ineligible companies to disclose.

Aaron D. Tward, MD, PhD:

faculty for this accredited education activity has no relationship(s) with ineligible companies to disclose.

Introduction: Current treatment options for vestibular schwannoma (VS) include surgical resection and/or radiation therapy, which can cause significant morbidity (e.g., facial paralysis and hearing loss). Systemic administration of bevacizumab can decrease VS tumor size and improve hearing in some patients with VS associated with neurofibromatosis type 2; however, long-term systemic use of vascular endothelial growth factor (VEGF) inhibitors is associated with toxicity. AK-antiVEGF (AAVAnc80-antiVEGF) is a gene therapy candidate in clinical development for potential treatment of VS. Intracochlear administration of AK-antiVEGF is intended to enable exposure of the tumor to anti-VEGF protein, while limiting systemic exposure and potentially minimizing adverse effects.

Methods: Non-human primate (NHP) studies informed clinical trial design. Four different intracochlear doses of AK-antiVEGF were delivered bilaterally, and safety and exposure were evaluated following 1 – 6 months. Computational modeling estimated the change in anti-VEGF protein concentration as it diffuses from perilymph into the internal auditory canal where VS tumors originate. The open-label, Phase 1/2 dose escalation trial will monitor for safety and tolerability of AAVAnc80-antiVEGF in adults with unilateral VS and Profound hearing loss, defined by pure-tone thresholds or word recognition scores. Evaluation of bioactivity / preliminary efficacy will be based on MRIs and audiologic assessments.

Results: Across all doses, local and systemic tolerability were demonstrated in NHPs and, based on computational modelling, biologically active levels of anti-VEGF protein are expected in the tumor environment after diffusion from perilymph, supporting selection of clinical doses that are expected to achieve a therapeutically relevant concentration at the typical VS tumor site of origin.

Conclusions: A one-time local administration of AK-antiVEGF in NHPs results in durable expression of anti-VEGF protein that is well tolerated. Taken together, these data support clinical development of AK-antiVEGF for the treatment of VS.

Presenting Author(s)

Brian M. Lin, MD

Neurotologist
Atrius Health
Boston, MA, United States

Disclosure(s):
faculty for this accredited education activity has no relationship(s) with ineligible companies to disclose.

Co-Author(s)

RC

Robyn Hao Chiang, PhD

Akouos, Inc. (a wholly owned subsidiary of Eli Lilly and Company), United States

Disclosure information not submitted.
AH

Ann E. Hickox, PhD

Executive Director, Regulatory & Clinical Development Advisor
Eli Lilly and Company
Boston, MA, United States

Disclosure information not submitted.
KL

Kathleen E. Lennon, RN

Sr.Lead-Medical Affairs
Akouos, Inc. (a wholly owned subsidiary of Eli Lilly and Company)
Boston, MA, United States

Disclosure information not submitted.
JP

Jeananne Phillips, ST

Lead - Clinical Surgery
Eli Lilly and Company
Boston, MA, United States

Disclosure information not submitted.
YG

Yuan Gao, PhD

Akouos, Inc. (a wholly owned subsidiary of Eli Lilly and Company), United States

Disclosure information not submitted.
JS

Junaid I. Syed

Sr Scientist
Eli Lilly and Company Eli Lilly and Company Eli Lilly and Company
Boston, MA, United States

Disclosure information not submitted.
YF

Yi Feng, PhD

Akouos, Inc. (a wholly owned subsidiary of Eli Lilly and Company), United States

Disclosure information not submitted.
RN

Robert Ng, PhD

Akouos, Inc. (a wholly owned subsidiary of Eli Lilly and Company), United States

Disclosure information not submitted.
SD

Samantha Davis, PhD

Akouos, Inc. (a wholly owned subsidiary of Eli Lilly and Company), United States

Disclosure information not submitted.
YA

Yukako Asai, PhD

Director, Early Preclinical Development - Gene Therapy
Eli Lilly and Company
Boston, MA, United States

Disclosure information not submitted.
KG

Katherine D. Gribble, PhD

Director, Target Discovery
Eli Lilly and Company
Newton, MA, United States

Disclosure information not submitted.
MV

Michelle D. Valero, PhD

Executive Director and Head- Early Preclinical Development
Akouos, Inc. (a wholly owned subsidiary of Eli Lilly and Company)
Boston, PA, United States

Disclosure information not submitted.
AT

Aaron D. Tward, MD, PhD

Associate Professor
University of California, San Francisco/ Eli Lilly and Co.
San Francisco, CA, United States

Disclosure(s):
faculty for this accredited education activity has no relationship(s) with ineligible companies to disclose.
ES

Emmanuel J. Simons, PhD

Akouos, Inc. (a wholly owned subsidiary of Eli Lilly and Company), United States

Disclosure information not submitted.
EA

Eva Andres-Mateos, PhD

Assoc. Vice President, Translational and Bioanalytical
Eli Lilly and Company
Boston, MA, United States

Disclosure information not submitted.
KR

Kathleen Z. Reape, MD

Akouos, Inc. (a wholly owned subsidiary of Eli Lilly and Company), United States

Disclosure information not submitted.

Senior Author(s)

Michael J. McKenna, MD

Disclosure information not submitted.