Mahzi Pharmaceuticals Clinical Trial

Phase 1/ 2 Study of MZ-1866, an AAV-9 Gene Therapy Delivered by Intracerebroventricular Injection to Participants With Pitt Hopkins Syndrome

Gene therapy is no longer a distant dream—it is becoming a reality for the Pitt Hopkins community. Building on years of foundational research from the Muotri Lab at UC San Diego, Mahzi Therapeutics has launched the first-ever gene therapy clinical trial for Pitt Hopkins syndrome.

Enrollment is now beginning at U.S. trial sites in California, Illinois & Colorado (see details below), with recruitment starting in the older age cohort (ages 12–25). A second cohort, ages 2–11, is expected to follow later in 2026. Additional trial sites in Israel and Spain will be announced as they open.

This historic trial represents a major milestone for Pitt Hopkins research, and we will continue to share updates as enrollment expands and additional sites come online.

Currently available information about this clinical trial can be found at:
https://clinicaltrials.gov/study/NCT07135050

Update Feb. 25, 2026: The first patient has now been dosed, read more here.

If you have questions, please reach out to us at information@pitthopkins.org.

LETTER TO THE COMMUNITYCOMMUNITY MEETING RECORDINGTYPICAL TRIAL FLOWFREQUENTLY ASKED QUESTIONSSOCIAL MEDIA FIRST PATIENT DOSED - PRESS RELEASESITE LOCATIONS
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LETTER TO THE COMMUNITY

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COMMUNITY MEETING

Mahzi Therapeutics and the Pitt Hopkins Research Foundation hosted two Community Meetings on November 18 and 19, 2025, to share an overview of the upcoming gene therapy clinical trial for Pitt Hopkins syndrome. During these sessions, the Mahzi team presented key information about trial design, eligibility and what participation will look like for families. The meetings also included a live Q&A, giving parents and caregivers the opportunity to speak directly with experts and learn more about what this milestone means for our community.

We extend our sincere thanks to all families who were able to attend either session. Your engagement, questions, and partnership continue to play a critical role as we move forward together.

For those who were unable to join, or for anyone who would like to rewatch the information, the full meeting recording is available below.

Typical Flow of a Clinical Trial:

FREQUENTLY ASKED QUESTIONS

MZ-1866 is an investigational gene therapy treatment. An investigational drug is one that has not been approved for safety or effectiveness in humans by government agencies (e.g., US FDA) and is being studied to see if the condition improves with use. A gene therapy is a treatment that adds a functional copy of a gene to individuals that may either lack the gene or have a copy that is not functioning properly.

Individuals with Pitt Hopkins Syndrome have one copy of the TCF4 gene that is working properly and one that is not. MZ-1866 provides additional copies of the properly functioning gene, with the aim of restoring normal function of the target cells. A copy of TCF4 gene is delivered inside a modified version of a virus called adeno-associated virus 9 (AAV9). AAV9 is a virus that is used as a carrier (envelope) for the copy of the TCF4 gene to reach the targeted cells. To use AAV9 as carrier, the viral DNA is first removed and then replaced with the TCF4 gene. AAV9 is nonpathogenic, which means that it is not likely to cause infection or illness in the body.

The AAV9 virus carrier was specifically selected due to its low likelihood for altering the patient’s DNA. AAV viruses will deliver their cargo to the nucleus of the cell (the control center for genetic information). In most cases, the gene therapy does not insert itself in the cell DNA and it will make TCF4 independently. However, there have been some reports of cases where the gene delivered by AAV combines with patient DNA. To date, there is no evidence that this has led to development of any disease.

MZ-1866 is intended address the root cause of Pitt Hopkins Syndrome by providing additional copies of properly functioning TCF4 genes. While it is not known what aspects of Pitt Hopkins Syndrome may be improved by MZ-1866, the Phase 1-2 trial will measure MZ-1866 impact on cognitive, functional, motor, and behavioral aspects of the condition.

MZ-1866 has been tested in patient cells (outside of the body), mice, and nonhuman primates. These studies are part of a complete package that will be reviewed by regulators in each country to assess the potential benefits and risks associated with initiating a first-in-human trial with MZ-1866.

A clinical trial is a structured and regulated research trial that tests whether a new medical treatment, like a drug or therapy, works. Each trial tries to answer a specific set of scientific questions. Ultimately, the goal is to find better ways to treat or cure a condition.

An open-label trial is one where both the researcher and the participant in a research trial know the treatment the participant is receiving. The MZ1866-CL101 trial is planned to be an open label trial. All enrolled participants will receive a single dose of MZ-1866.

Mahzi is planning a Phase 1/2 trial of MZ-1866, Study MZ1866-CL101. The purpose of this clinical trial is to assess whether MZ-1866 is a safe and tolerable treatment for children and adults aged 2-25 years with Pitt Hopkins syndrome. This trial is a first-in-human trial. That means that MZ-1866 has not been tested in people before. Study MZ1866-CL101 is an open label trial where each participant will receive a single dose of MZ-1866.

Participants will be enrolled in the trial for approximately 2 years. During this time, participants will have multiple trial visits (either at the trial site or at home) where assessments will be performed to evaluate each participants’ health and developmental status.

MZ-1866 is delivered by an intracerebroventricular (ICV) injection. An ICV injection is a medical procedure in which a treatment is delivered directly into the fluid-filled spaces (ventricles) inside the brain. The procedure involves creating a hole in the skull and inserting a small tube (catheter) into the ventricle. The treatment is then slowly injected into the ventricle. This surgical method is routinely used by neurosurgeons when a treatment needs to reach the brain quickly or when other ways of delivering medicine might not work as well. The procedure will take less than an hour, although the overall time in the surgical suite may be longer than this as general anesthesia is required. In addition, participants must stay in the hospital for monitoring before and after the procedure.

No, MZ-1866 is being investigated as a single administration treatment.

Approximately 12 children and adults aged 2-25 years old will be enrolled in this trial.

Mahzi has published Inclusion/Exclusion Criteria on www.clinicaltrials.gov. These do not include all the criteria required for eligibility and parents/caregivers should speak with their treating physician to determine whether a patient may be eligible for the trial. Patients won’t be able to take part if they are currently in another clinical trial for an investigational product for Pitt Hopkins Syndrome (drug/treatment/medication) or have taken part in one in the past. If patients are currently enrolled in a trial that is not for the treatment of Pitt Hopkins Syndrome, they should discuss this with their treating physician to see if they may be eligible for this trial.

Mahzi Therapeutics is not involved in the selection of participants for enrollment in the trial. Enrollment in the trial is the responsibility of the investigator at each trial site.

A specific list of genetic mutations or clinical comorbidities that would exclude a potential participant from enrollment does not exist. Clinical comorbidities and other genetic mutations will be assessed on a case-by-case basis and eligibility will be determined by the investigator at each trial site.

There are risks of participating in a clinical trial. A participant may experience side effects from an investigational drug or with procedures in the trial. A side effect is an undesirable symptom, which may be related to the treatment, to other medications taken while on the trial, or to any of the procedures or tests performed in the trial. Trial participants will be monitored closely throughout the trial. The trial investigator may prescribe or recommend medicines if a side effect is experienced.

Study MZ1866-CL101 is the first time MZ-1866 will be tested in humans. Not all the side effects are known. However, there are some known risks of AAV capsid (the envelope used to deliver the functional TCF4 gene). Immune system reactions have been seen in both animal and human studies of investigational AAV gene therapies. Medication to reduce the response of the immune system will be given to participants in the planned MZ-1866 clinical trial. For more information on understanding the immune responses for AAV-9 gene therapies, please visit this helpful link from the American Society of Cell and Gene Therapy (ASGCT):  https://patienteducation.asgct.org/research-clinical-trials/community-quick-takes/aav-immune-response

The full explanation of risks associated with participation in the planned clinical trial will be shared during the informed consent process for each participant screened for the trial. These risks will be shared and discussed in depth so that participants/caregivers are fully informed before deciding whether to participate in the trial. For more information on understanding the informed consent process in a clinical trial, please visit this link from ASGCT:  https://patienteducation.asgct.org/research-clinical-trials/community-quick-takes/informed-consent

Yes. Short term immune suppression is required to prevent potential immune reactions to the gene therapy. More details about immune suppression will be provided by the trial investigator during the informed consent process.

Mahzi’s goal is to open sites in the United States, Israel, and Spain. Details will be released as clinic sites open. The following are currently open for enrollment.

  • Site Name: UCSF Benioff Children’s Hospital Oakland (Oakland, California)
    • Investigator: Alex Fay, MD, Ph.D.
    • Site Contact: Matt Thura, matt.thura@ucsf.edu
  • Site Name: Rush University Medical Center (Chicago, Illinois)
    • Investigator: Elizabeth Berry-Kravis, M.D., Ph.D.
    • Site Contact: Milana Milic, milana_milic@rush.edu
  • Site Name: Children’s Hospital Colorado (Aurora, Colorado)
    • Investigator: Diana Walleigh, MD
    • Site Contact: Sky Gould, sky.gould@childrenscolorado.org; 750-777-1583

Participants from locations outside the designated trial sites are not automatically excluded from participation. However, eligibility will be assessed on a case-by-case basis by the investigator at each site. Families should be aware of the trial’s duration and the requirement to attend multiple trial visits at the trial center throughout their participation. Therefore, a participant’s location in relation to the trial site may be considered when determining eligibility for the trial.

No compensation will be provided for participation; however, travel and lodging will be arranged and covered by a vendor selected by Mahzi. Additionally, reimbursement for reasonable expenses will be provided. Further details about which expenses can be reimbursed will be provided to participants during the informed consent process.

Mahzi has hired a travel and reimbursement vendor who will support families by arranging and pre-paying travel and lodging expenses. Additionally, the vendor will reimburse for specific out-of-pocket expenses incurred because of travel. Further details about which expenses can be reimbursed, and reimbursement limits will be provided to participants during the informed consent process.

Mahzi Therapeutics is not involved in the selection of participants for enrollment in the trial. Enrollment in the trial is the responsibility of the investigator at each trial site. Once clinical trial sites are open, parents/caregivers will be able to contact sites directly to discuss whether the patient may be eligible to participate. Contact information for each site will be shared closer to each site’s activation date and will be posted on www.clinicaltrials.gov. Mahzi will also be providing information through the Pitt Hopkins Research Foundation (https://pitthopkins.org/).

SOCIAL MEDIA POLICY FOR THIS CLINICAL TRIAL

As participants prepare for the Mahzi open-label gene therapy clinical trial, please know that it will be a required part of the study that families do not share any trial-related experiences—positive, negative, or clinical in nature—on social media or in public forums. This expectation is not meant to limit connection or support; rather, it is essential for protecting the scientific integrity of the trial and ensuring the fastest possible path to FDA review and approval.

Even in an open-label design where everyone knows who receives the therapy, the FDA still demands clean, unbiased data to determine safety and efficacy. Public posts can unintentionally influence how other families notice symptoms, interpret changes, or report side effects. Because this trial includes caregiver-reported outcomes, even small shifts in perception caused by seeing others’ posts can introduce bias. The FDA monitors the total data landscape—including publicly shared content—and if they believe results may have been influenced by social media, they may require additional studies, delay progress to the next phase, or request that data be repeated.

Our entire community shares the same goal: safe, effective therapies for individuals with Pitt Hopkins syndrome. Following these guidelines is one of the most powerful ways each family can help prevent unnecessary FDA delays and keep our path to treatment as fast and as successful as possible.

First Patient Dosed – February 25 Press Release

It feels almost surreal to be able to share what is without a doubt the most remarkable milestone in the history of the Pitt Hopkins research. Today we are announcing that the first patient has been dosed with Mahzi’s gene-replacement therapy, MZ-1866, and is doing well. Eight years in the making, this extraordinary achievement reflects countless hours of dedication and an unwavering belief in hope.

This win belongs to so many, and our gratitude for all of them is beyond words.

Our first patient and their family are quiet heroes. Their courage and determination to pursue a better life for their child will help open the door to a better future for so many others.

The Muotri Lab, led by Dr. Alysson Muotri at UCSD, whose visionary research not only demonstrated that gene therapy could work in cellular models, but also reminded us that hope was real.

Yael Weiss and her devoted team at Mahzi Therapeutics, who took this drug out of academia and made it a top-tier product ready for human trials.

Our incredible donors who have stuck with us through thick and thin.

The Pitt Hopkins community, who believed in us even when the road to treatment felt impossibly long.

And above all, our Pitt Hopkins children—you are the true heroes. Your remarkable courage, resilience, and heart inspire us every day to keep moving forward, not only to hope for miracles, but to fight for them. Always.

Read the Full Press Release here.

SITE LOCATIONS

The two sites that are currently open for enrollment are listed below. To get more information, please contact them via their emails listed. Please note that the age cohort 12-25 is enrolling first. Those within that age group will begin enrollment first and the younger age group will not enroll until later in 2026.
  • UCSF Benioff Children’s Hospital Oakland (Oakland, California)
    • Contact: Matt Thura – matt.thura@ucsf.edu
    • Principal Investigator: Alex Fay, M.D., Ph.D.
  • Rush University Medical Center (Chicago, Illinois)
    • Contact: Milana Milic – milana_milic@rush.edu
    • Principal Investigator: Elizabeth Berry-Kravis, M.D., Ph.D.
  • Children’s Hospital Colorado (Aurora, Colorado)
Additional sites will open in the coming months in
• Israel
• Spain
Contact information for these sites will be shared when available.

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