Passage Bio Advances Gene Therapy for Frontotemporal Dementia, Expanding Trial & Extending Runway

By Patrick Walker

PHILADELPHIA, PA – Passage Bio, Inc. (NASDAQ: PASG) is making strides in the fight against frontotemporal dementia (FTD), a devastating neurodegenerative disorder, with positive developments surrounding its lead gene therapy candidate, PBFT02. The company recently announced advancements in its ongoing Phase 1/2 clinical trial, alongside financial maneuvers extending its cash runway, positioning it as a key player in a rapidly evolving and competitive field.

PBFT02 utilizes an adeno-associated virus (AAV1) vector to deliver a functional GRN gene directly to the brains of patients with FTD caused by mutations in the GRN gene. Early data from the trial show consistent increases in progranulin levels, a protein deficient in many FTD patients, alongside early indications of reduced neurofilament light chain (NfL) levels – a biomarker often correlated with neuronal damage. Crucially, the company has received positive feedback from the Food and Drug Administration (FDA) to expand the trial to include patients with FTD caused by mutations in the C9orf72 gene, significantly broadening the potential patient population.

“The FDA’s alignment with our plan to expand the trial is a significant milestone,” said a source close to the company. “It validates our approach and brings hope to a far larger number of individuals affected by this cruel disease.”

Expanding the Reach: Addressing a Wider FTD Population

FTD encompasses a range of disorders characterized by progressive changes in personality, behavior, and language. Genetic mutations, including those in the GRN and C9orf72 genes, account for a significant proportion of cases. Currently, there are no FDA-approved disease-modifying therapies for FTD, leaving patients and their families with limited treatment options.

The expansion of the upliFT-D trial to include C9orf72-related FTD is particularly noteworthy. While GRN-related FTD accounts for a sizable portion of cases, C9orf72 mutations are also a frequent cause. Addressing both genetic subtypes with a single therapy represents a significant step forward.

Navigating a Competitive Landscape

Passage Bio isn’t alone in its pursuit of FTD treatments. The field is attracting increasing attention from pharmaceutical companies and biotech firms alike. Several competitors are developing novel therapies, including antibody treatments and other gene therapies.

Key players include Alector and GSK, whose Latozinemab is in Phase 3 trials; Prevail Therapeutics (owned by Eli Lilly) with its PR006 gene therapy; and Denali Therapeutics/Takeda, working on DNL593 to restore PGRN levels. Other companies like AviadoBio and Vesper Bio are also advancing innovative approaches.

“The competition is intense, but that’s ultimately a good thing for patients,” a leading FTD researcher commented. “It drives innovation and accelerates the development of potentially life-changing therapies.”

Passage Bio differentiates itself through its focus on the AAV1 vector and its observed ability to achieve higher levels of human progranulin expression compared to other AAV serotypes. The company’s commitment to a targeted approach – specifically addressing genetic subtypes of FTD – also sets it apart.

Securing Financial Stability for Long-Term Growth

Alongside clinical progress, Passage Bio has been proactive in managing its finances. The company recently implemented a series of cost-reduction measures, including a workforce reorganization and a transition to outsourced analytical testing. These efforts have extended the company’s cash runway into the first quarter of 2027, providing a solid foundation for continued research and development.

As of September 30, 2025, Passage Bio reported cash, cash equivalents, and marketable securities of $52.8 million. While the company still faces financial challenges, the extended runway provides breathing room to navigate the complex regulatory landscape and advance its pipeline.

Patient Advocacy and the Hope for a Future

The advancements at Passage Bio are being closely watched by patient advocacy groups, including the Association for Frontotemporal Degeneration (AFTD). The AFTD actively reports on clinical trials and highlights the urgent need for effective FTD treatments.

“The expansion of the upliFT-D trial and the positive data observed so far are encouraging,” a spokesperson for the AFTD stated. “Patients and families are desperate for new options, and we are hopeful that this research will ultimately lead to a breakthrough.”

The lack of approved therapies for FTD underscores the significant unmet medical need. For patients and caregivers, every step forward in clinical development offers a glimmer of hope. The combination of promising clinical data, a strategic focus on genetic subtypes, and a commitment to financial sustainability positions Passage Bio as a key player in the ongoing fight against this devastating disease.

While challenges remain, the company’s progress offers a beacon of hope for individuals and families affected by frontotemporal dementia, and the broader FTD community eagerly awaits future updates on the development of PBFT02 and other innovative therapies.