FDA Clears Investigator-Initiated IND for SRN-101 in Recurrent High-Grade Glioma

SRN-101, an investigational adeno-associated virus (AAV) gene therapy, has received FDA clearance for an investigational new drug application to begin a phase 1 clinical trial for patients with recurrent high-grade glioma, according to a press release from Siren Biotechnology.¹

The regulatory decision follows 2 other regulatory decisions in 2026 for SRN-101: the first was the clearance of an investigational new drug application for the treatment of patients with recurrent high-grade glioma in January, and the second was the FDA’s granting of fast track designation to SRN-101 in recurrent high-grade glioma in February.^2,3

The phase 1 study will be led by Nicholas Butowski, MD, a professor of Neurological Surgery and Neuro-Oncology at University of California, San Francisco (UCSF), and will evaluate the safety and biologic activity of SRN-101 in this patient population. This regulatory milestone marks the transition of the developer’s Universal AAV Immuno-Gene Therapy platform into clinical evaluation, specifically targeting one of the most aggressive forms of primary brain cancer.

Notably, funding from the California Institute for Regenerative Medicine (CIRM) made the research possible. The CIRM is an agency out of California that funds regenerative medicine, stem cell, gene therapy research, and clinical trials.

“This [investigational new drug] clearance allows us to begin evaluating this novel investigational approach in patients with recurrent high-grade glioma,” stated Butowski, in the press release.¹ “This early-phase study will provide important safety and translational data to help inform future clinical development.”

What is SRN-101?

SRN-101 is a recombinant AAV vector expressing an engineered cytokine. When Siren Biotechnology, the developer of SRN-101 launched, they had preclinical data that showed their universal AAV immune-gene therapies “potent anti-tumor effects” in preclinical models of high-grade glioma.⁴ SRN-101 is the first agent from this collection of assets to be revealed. Reportedly, other technology innovations and solid tumor indications are in development.

“We are honored to support Dr. Butowski and the UCSF team in advancing this investigator-initiated study,” added Nicole K. Paulk, PhD, founder, chief executive officer, and president of Siren Biotechnology.¹ “UCSF has long been a leader in neuro-oncology research, and we are excited to contribute to this important effort on behalf of patients with recurrent high-grade glioma.”

Clinical Context and Unmet Need

High-grade gliomas, including glioblastoma, remain among the most lethal primary malignancies of the central nervous system. Despite a standard-of-care regimen consisting of maximal safe surgical resection followed by concurrent temozolomide and radiotherapy, median overall survival for newly diagnosed patients remains approximately 15 to 20 months.^5,6 In the recurrent setting, there is no universally accepted standard systemic therapy. Current options, such as bevacizumab (Avastin), lomustine, or re-irradiation, provide only modest gains in progression-free survival without consistently demonstrating a robust overall survival benefit.

The biological complexity of high-grade glioma, including its high degree of intra-tumoral heterogeneity and the cold immune microenvironment, has rendered most immune checkpoint inhibitors ineffective in large-scale trials. Consequently, there is significant interest in in situ immunization strategies that can actively recruit and activate immune cells within the surgical cavity or the residual tumor mass.

“People with recurrent high-grade glioma urgently need more effective treatment options,” said Ross Okamura, PhD, a research fellow in Preclinical Development at CIRM.¹ “The launch of this trial at UCSF is a major step toward identifying new options and providing hope for people with this deadly condition.”

Reference

1. Siren Biotechnology announces FDA clearance of investigator-initiated IND to advance phase 1 study in recurrent high-grade glioma. News release. Siren Biotechnology. Published March 23, 2026. Accessed March 24, 2026. https://tinyurl.com/3vyx39cd
2. Siren Biotechnology announces FDA clearance of first IND, advancing company to clinical stage. News release. Siren Biotechnology. January 28, 2026. Accessed March 24, 2026. https://tinyurl.com/2y3b3as9
3. Siren Biotechnology receives FDA Fast Track Designation for SRN-101 for the treatment of recurrent high-grade glioma. News release. Siren Biotechnology. February 24, 2026. Accessed March 24, 2026. https://tinyurl.com/mu8z7csx
4. 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 March 24, 2026. https://tinyurl.com/mwzmwu59
5. Stupp R, Mason WP, van den Bent MJ, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005;352(10):987-996. doi:10.1056/NEJMoa043330
6. Wen PY, Weller M, Lee EQ, et al. Glioblastoma in adults: a Society for Neuro-Oncology (SNO) and European Association of Neuro-Oncology (EANO) consensus review on current management and future directions. Neuro-Oncol. 2020;22(8):1073-1113. doi:10.1093/neuonc/noaa106