Jaguar Gene Therapy Announces FDA Clearance of IND to Study JAG201 in a Genetic Form of Autism Spectrum Disorder and Phelan-McDermid Syndrome

  • Initial study will focus on adults with disease; company plans to initiate Phase I clinical trials
    in the U.S. in 2H2024
  • Preclinical studies in rodents and NHPs demonstrated improvement in neurobehavioral, cognitive and motor functional abnormalities: JAG201 delivers a functional SHANK3 gene directly into the CNS via the AAV9 vector to treat the root cause of the disease
  • There are currently no treatments for the ~30,000 individuals in the U.S. with autism or Phelan-McDermid syndrome, where a SHANK3 mutation or deletion is present

LAKE FOREST, Illinois – January 31, 2024 – Jaguar Gene Therapy, a biotechnology company accelerating breakthroughs in gene therapy for patients suffering from severe genetic diseases, including those that affect sizeable patient populations, today announced the U.S. Food and Drug Administration (FDA) has cleared the company’s Investigational New Drug (IND) Application for JAG201, a gene therapy for a genetic form of autism spectrum disorder (ASD) and Phelan-McDermid syndrome (PMS). There are currently no treatments for the ~30,000 individuals in the U.S. with ASD or PMS where a SHANK3 mutation or deletion is present. JAG201 aims to deliver functional SHANK3 via the AAV9 vector to treat the root cause of the disease. Preclinical studies in rodents and non-human primates (NHP) demonstrated that functional SHANK3 delivery leads to improvements in neurobehavioral, cognitive and motor function abnormalities. The company plans to initiate a Phase I trial in adults with ASD or PMS where a SHANK3 mutation or deletion is present in the United States in the second half of the year.

“We are pleased to receive FDA clearance to bring our investigational SHANK3 gene therapy to the clinic. The preclinical data indicate that JAG201 may have the potential to be transformative for those suffering with the disorder,” said Joe Nolan, chief executive officer of Jaguar Gene Therapy. “This is a significant milestone for our company but more importantly for the approximately 30,000 individuals living with a genetic form of autism or Phelan-McDermid syndrome who can suffer from a range of clinical manifestations, including global developmental delay, impaired speech and communication, and worsening cognitive, social and motor function disability that ultimately requires 24-hour care and supervision. Currently, there are no treatment options to address the root cause – we hope to change that.”

“As a clinician working directly with individuals living with SHANK3 haploinsufficiency and their families, I recognize deeply the profound challenges faced every single day,” said Alexander Kolevzon, M.D., professor of Psychiatry and Pediatrics at the Icahn School of Medicine at Mount Sinai. “The interventions we offer can certainly help but, frankly, they’re inadequate. My patients and all those with SHANK3 haploinsufficiency deserve a treatment option that addresses the underlying biology.”

SHANK3 haploinsufficiency leads to synaptic dysfunction, disrupting communication between nerve cells. It causes a reduction of several key receptors and signaling proteins at excitatory synapses, resulting in impaired synaptic formation and function. Adequate synapse function is an essential prerequisite of all neuronal processing, including higher cognitive functions and learning. JAG201 delivers a functional SHANK3 minigene via an adeno-associated virus serotype 9 (AAV9) vector to target neurons in the central nervous system. The therapy is administered via a one-time unilateral intracerebroventricular (ICV) injection, targeting the entire brain and spinal cord. JAG201 is designed to transduce haploinsufficient neurons, to provide proper SHANK3 levels, and to durably restore the synaptic function required for learning and memory, which underlie appropriate neurodevelopment and maintenance of cognitive, communicative, social and motor skills. The program is exclusively licensed from Broad Institute of MIT and Harvard, and based on the groundbreaking work of Guoping Feng, Ph.D.

“My lab has focused on studying the molecular mechanisms regulating the development and function of synapses in the brain, including the role of SHANK3, because we believe the potential to address synaptic dysfunction could positively transform the lives of so many with neurodevelopmental disorders,” said Dr. Feng, Institute member of the Broad Institute and a senior scientist and director of model systems and neurobiology in the Broad’s Stanley Center for Psychiatric Research, the Poitras Professor of Brain and Cognitive Sciences at MIT, associate director of the McGovern Institute, and a member of the Yang Tan Collective at MIT. “Having directly generated promising preclinical data in rodent and non-human primate models of SHANK3 insufficiency, thereby reducing the risk of the translational potential of JAG201, I am very excited to now follow Jaguar as they progress into the clinic with JAG201.”

SHANK3 haploinsufficiency causes PMS (also known as 22q13.3 deletion syndrome), a rare genetic disorder with an estimated prevalence of 1 in 10,000.1,2 Genetic sequencing studies indicate that SHANK3 mutations may be present in approximately 1% of patients with ASD, equating to around 30,000 patients in the U.S., although this estimate is perceived as low by clinical experts given the barriers of access and low adoption of genetic testing in the diagnostic journey of ASD.3,4 In the subset of ASD patients that also have moderate to profound intellectual disability (ID), the prevalence of SHANK3 mutations increases from approximately 1% to 2.12%.3,5

An Externally Led Patient Focused Drug Development (EL-PFDD) Meeting on PMS was held with the FDA in November 2022, hosted by CureSHANK and co-planned with the Phelan-McDermid Syndrome Foundation (PMSF). Key insights from the meeting include: PMS has severe quality of life impacts on those living with the disease, as well as on parents and siblings; PMS has an overwhelming unmet medical need; and existing therapies and medical treatments are not very effective.6

“As an organization dedicated to expediting life-changing therapies for Phelan-McDermid syndrome, we are thrilled for JAG201 to be cleared for clinical trials,” said Geraldine Bliss, founder and president of CureSHANK. “I understand first-hand as the parent of a young adult with Phelan-McDermid syndrome the dearth of available therapies and the incredible potential of a treatment that addresses the root cause of this severe and pervasive disease.”

“Families deserve and are desperately waiting for treatments to address Phelan-McDermid syndrome, and we are very excited the FDA has cleared JAG201 for clinical trials,” said Ronni Blumenthal, CEO of the Phelan-McDermid Syndrome Foundation. “Members of our community are eager to have treatment options that could potentially lessen or eliminate even just one or two of the devastating symptoms of the disease, if not more, to positively improve the lives of our loved ones.”

About Jaguar Gene Therapy

Jaguar Gene Therapy, LLC is a clinical stage biotechnology company dedicated to accelerating breakthroughs in gene therapy for patients suffering from severe genetic diseases including those that impact sizeable patient populations. The company is made up of a proven team of experts who have first-hand experience in bringing novel gene therapy treatments to patients and their families. Jaguar is rapidly advancing an initial pipeline of three programs. The company’s lead IND-cleared program targets severe neurodevelopmental disorders caused by mutations or deletions in SHANK3 including a genetic form of autism spectrum disorder and Phelan-McDermid syndrome. The second pipeline program targets Type 1 galactosemia and the third targets Type 1 diabetes. Jaguar partners with Advanced Medicine Partners, soon to be spun out from Jaguar, to manufacture its therapeutics. Jaguar’s key investors include Deerfield Management Company, ARCH Venture Partners and Eli Lilly and Company. For more information, please visit and follow Jaguar Gene Therapy on LinkedIn.

Media Contact

Kate Neer


  1. Costales JL et al. Neurotherapeutics 2015; 12 (3): 620–630.
  2. What is Phelan-McDermid syndrome? Available at: Accessed January 2023.
  3. Betancur C et al. Mol Autism 2013; 4 (1): 17.
  4. Jaguar Gene Therapy market research, 2022; data on file.
  5. Leblond CS et al. PLoS Genet 2014; 10 (9): e1004580.
  6. Phelan-McDermid Voice of the Patient Report. Available at: Accessed January 2024.


Dr. Alexander Kolevzon has served as a paid consultant for Jaguar Gene Therapy.