FDA Clears IND for Investigational Program in Recurrent High-Grade Glioma

The FDA has cleared an investigational new drug (IND) application for SRN-101, an adeno-associated virus (AAV)–based immuno-gene therapy, for the treatment of adult patients with recurrent high-grade glioma, according to a press release from the developer, Siren Biotechnology.¹

The company now plans to initiate a first-in-human clinical trial in patients with recurrent high-grade glioma. The developer stated that this is the first FDA-cleared IND for an AAV-based therapy in an oncology indication.

SRN-101 utilizes a recombinant AAV vector designed to deliver an engineered cytokine payload directly to the tumor microenvironment.² According to preclinical data released by the company, this universal AAV immuno-gene therapy exhibited potent anti-tumor effects in models of brain cancer. The therapy is designed to combine the precision and durability of AAV gene therapy with the immune-modulating potential of cytokine-based approaches.

By delivering the cytokine payload locally, the treatment aims to stimulate a sustained immune response within the solid tumor.

“This IND clearance represents a defining moment for Siren as we transition from a preclinical-stage company into the clinic,” stated Nicole K. Paulk, PhD, founder, chief executive officer, and president of Siren Biotechnology, in the announcement.¹ “Reaching this milestone reflects years of focused platform development, rigorous translational work, and close engagement with regulators, and it positions us to begin evaluating our approach in patients.”

The upcoming first-in-human clinical study will evaluate SRN-101 in a population of adult patients with recurrent high-grade glioma. High-grade gliomas, including glioblastoma, are characterized by their aggressive nature and limited therapeutic options, often offering poor prognoses despite standard-of-care surgery, radiation, and chemotherapy. While specific dosing schedules for the initial trial have not been disclosed, the study will focus on the localized and durable delivery of the AAV-based payload.

“We are excited to announce SRN-101 as the lead universal AAV immuno-gene therapy asset in our platform’s pipeline. Our team has worked tirelessly to develop an approach that demonstrates remarkable promise for the treatment of high-grade gliomas but also has transformative potential for use in additional indications,” Paulk stated in another press release regarding the development of SRN-101.²

The IND application was supported by the successful completion of nonclinical as well as Chemistry, Manufacturing, and Controls (CMC) activities required for clinical evaluation. Research focused on SRN-101 was supported by funding from the California Institute for Regenerative Medicine (CIRM), an agency dedicated to funding investigations in regenerative medicine, stem cell, and gene therapy. CIRM aims to create infrastructure expanding the accessibility of clinical trials for people throughout California.

SRN-101 holds both orphan drug and rare pediatric disease designations from the FDA, the latter of which applies specifically to its development for pediatric-type diffuse high-grade gliomas. These designations underscored the high unmet medical need in both adult and pediatric populations. Developers plan to leverage their universal AAV platform to expand into additional solid tumor indications following the initial clinical results in glioma.

“SRN-101 has the potential to address a critical gap in effective high-grade glioma therapies by leveraging the body’s immune response in a targeted, innovative way. This approach could represent a major breakthrough in how we treat one of the most devastating brain cancers and offers a new path of hope for patients,” Nicholas Butowski, MD, neuro-oncologist and director of Translational Research in Neuro-Oncology at the University of California, San Francisco, stated in a press release at the time of the orphan drug and rare pediatric disease designations.²

References

1. Siren Biotechnology announces FDA clearance of first IND, advancing company to clinical stage. News release. Siren Biotechnology. January 28, 2026. Accessed January 29, 2026. https://tinyurl.com/2y3b3as9
2. Siren Biotechnology reveals SRN-101 as lead asset for high-grade gliomas with both orphan drug and rare pediatric disease designations from the FDA. News release. Siren Biotechnology. November 18, 2024. Accessed January 29, 2026. https://tinyurl.com/mwzmwu59