Development of an immune-armed therapeutic adenoviral platform for pediatric brain tumors

Introduction

Diffuse Midline Gliomas (DMGs) are the most aggressive pediatric brain tumors in desperate need of curative treatment. The median life expectancy of these children remains below 14 months after diagnosis, and nearly none survive beyond the second year.

Challenges in Treatment

Similarly, for other high-risk pediatric brain tumors, there is hardly any option after recurrence, and long-term survivors are faced with life-long sequelae that impact their quality of life. In this scenario, there is an urgent need for innovative, efficacious, and safe therapies for these patients.

Oncolytic Viruses as a Solution

Oncolytic viruses are promising anticancer biotherapeutic agents that offer a unique combination of safety profile, direct antineoplastic activity, and the induction of anti-tumor immune responses. Recently, a Phase I clinical trial showed that combining the oncolytic adenovirus Delta-24-RGD and radiotherapy is non-toxic and results in anti-tumor responses and prolonged median overall survival (17.8 months) in patients.

Limitations of Current Approaches

However, results are still insufficient to be curative due to counteracting mechanisms intrinsic to the tumor microenvironment and also triggered by the virus that eventually exceeds its immunostimulatory properties.

Proposed Technology: POPCORN

The proposed technology, termed “POPCORN,” is an oncolytic-based platform capable of expressing immunomodulatory single-domain antibodies directed to intrinsic targets in these tumors.

Development Plan

We will develop the POPCORN Proof of Concept using a state-of-the-art experimental approach and validate its safety and efficacy in vitro and relevant in vivo DMG models.

1. Perform IND-enabling studies.
2. Apply for PUMA/PRIME designation.
3. Work on the IPR strategy.
4. Generate a value proposition to develop and commercialize the POPCORN platform.

Vision for the Future

We envision the POPCORN platform becoming a game changer in treating DMGs, providing a one-of-a-kind tool for eliminating these aggressive tumors that could be extended to other difficult-to-treat pediatric brain tumors.