Mahzi Therapeutics Doses First Patient in Gene Therapy Trial for Pitt Hopkins Syndrome

Mahzi Therapeutics Inc. has dosed the first patient in its Phase 1/2 UNITE clinical study evaluating MZ-1866, an investigational gene therapy for Pitt Hopkins syndrome. This marks a key transition for Mahzi—from development to active clinical execution.

Why This Moment Matters?

Pitt Hopkins syndrome is rare, severe, and underserved.

Key facts:

• Caused by mutations in the TCF4 gene
• Affects roughly 1 in 34,000–41,000 individuals
• Around 8,000 people are estimated to live with the condition in the US
• No disease-modifying therapies currently exist

The UNITE study represents the first investigational gene therapy trial ever launched for this condition.

Inside the Phase 1/2 UNITE Study

The UNITE trial is a global, multicenter, open-label study.

Core design elements:

• Single administration of MZ-1866
• Approximately 12 participants
• Sites across the US, Israel, and Spain
• Delivery via intracerebroventricular administration

Primary focus is safety and tolerability. Exploratory endpoints assess development, communication, cognition, and motor function.

How MZ-1866 Works?

MZ-1866 is an AAV9-based gene replacement therapy.

It is designed to:

• Deliver a functional copy of TCF4 isoform B
• Target the underlying disease biology
• Restore gene function rather than manage symptoms

Isoform B is the longest known and one of the most abundant TCF4 isoforms in the brain.

Voices from the Community

Mahzi CEO Yael Weiss, MD, PhD, called the dosing milestone a defining achievement for the company and the program.

From the patient community, Pitt Hopkins Research Foundation described the trial as a historic moment—one built on years of advocacy, collaboration, and persistence.

Academic and Public Funding Support

The program was developed in collaboration with the University of California San Diego Muotri Lab.

Trial funding was supported by the California Institute for Regenerative Medicine (CIRM), a state agency backing stem cell and gene therapy research.

About Mahzi Therapeutics

Mahzi Therapeutics is a clinical-stage biotech focused on precision therapies for neurogenetic disorders. Its model emphasizes:

• Deep partnerships with patient foundations
• Collaboration with academic labs
• Translational science aimed at rare, high-need populations

Bottom line: First-patient dosing in the UNITE study is more than a clinical milestone.
It is the first concrete step toward a disease-modifying therapy for Pitt Hopkins syndrome—and a signal that gene therapy is finally reaching this long-overlooked community.

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