Cell therapy weekly: first IND cleared for AAV-based cancer therapy
This week: The US Food and Drug Administration (FDA; MD, USA) placed a clinical hold on two of REGENXBIO‘s (MD, USA) Mucopolysaccharidosis gene therapies, Cellares (CA, USA) secured US$257 million in a Series D funding round, and Siren Biotechnology (CA, USA) received Investigational New Drug (IND) application clearance for it’s AAV-based gene therapy for high-grade glioma.
The news highlights:
- Clinical hold for two Mucopolysaccharidosis gene therapies
- Series D funding for automated “Smart Factories”
- First IND clearance for an oncology gene therapy
Clinical hold for two Mucopolysaccharidosis gene therapies
The FDA has placed a clinical hold on RGX-111 and RGX-121 after a patient in REGENXBIO’s Phase I/II trial of RGX-111 developed an intraventricular CNS tumor. An investigation into whether this serious adverse event is related to the therapeutic is said to be ongoing.
RGX-111 is a gene therapy designed to treat Mucopolysaccharidosis Type I by delivering the α-l-iduronidase (IDUA) gene to the CNS via an AAV9 vector. It has received orphan drug product, rare pediatric disease and Fast Track designations from the FDA.
RGX-121 — which the FDA has also put on hold, citing similarities in products, study populations, and shared risk between the clinical studies — is a gene therapy for Mucopolysaccharidosis Type II, and also utilizes an AAV9 vector to deliver a functional copy of a different gene (the iduronate-2-sulfatase (IDS) gene) to the CNS.
“We are surprised by FDA’s decision to place our RGX-121 program on hold while the investigation of this single, inconclusive incident in RGX-111 continues,” said Curran Simpson, President and CEO of REGENXBIO. “These are separate therapies, and the positive safety profile of RGX-121 in more than 30 patients treated, including those dosed nearly seven years ago, remains unchanged. Patient safety is our top priority, and we, our investigators, and the patient community remain confident in the benefit-risk ratio of RGX-121 and are highly encouraged by the meaningful efficacy profile demonstrated in the pivotal trial. RGX-121 presents an opportunity to address the urgent, significant unmet medical need in this ultra-rare disease community, and continued delay means continued neurodevelopmental decline in boys with MPS II.”
Series D funding for automated “Smart Factories”
Cellares has raised US$257 million in a Series D funding round, which will support the global expansion of automated Integrated Development and Manufacturing Organization (IDMO) Smart Factories in California, New Jersey, the Netherlands and Japan. These facilities aim to enable large-scale manufacturing of cell therapies for hundreds of thousands of patients annually.
“The barrier to curing more patients is no longer scientific — it is industrial,” said Fabian Gerlinghaus, Co-Founder and CEO of Cellares. “With FDA validation, global commercial demand, and the capital to scale, we are building the high-tech infrastructure required to deliver cures and life-changing treatments worldwide. This financing puts Cellares on a clear, disciplined path toward becoming a public company.”
This funding round, which brings the company’s total capital raised to $612 million, was co-led by BlackRock and Eclipse, and includes new investors such as T. Rowe Price, Baillie Gifford, Duquesne Family Office, Intuitive Ventures, EDBI, and Gates Frontier, alongside existing backers like DC Global Ventures, DFJ Growth, and Willett Advisors.
First IND clearance for an oncology gene therapy
The FDA has cleared an IND application for Siren Biotechnology’s lead investigational program in adult patients with recurrent high-grade glioma. This clearance enables the company’s first first-in-human clinical trial, marking its transition to a clinical-stage biotechnology company.
According to Siren Biotechnology, this is the first time an IND application has been cleared for an adeno-associated virus (AAV)-based therapy in an oncology indication.
“This IND clearance represents a defining moment for Siren as we transition from a preclinical-stage company into the clinic,” said Nicole K. Paulk, Founder CEO, and President of Siren Biotechnology. “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.”