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The initial screening will focus on adults with the disease; The company expects to start Phase I clinical trials in the United States 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, Ill. , Jan. 31, 2024–(BUSINESS WIRE)–Jaguar Gene Therapy, a biotechnology company accelerating advances in genetic cures for patients suffering from serious genetic diseases, adding those affecting patient populations today announced that the U. S. Food and Drug Administration (FDA) has legalized the company’s investigational new drug (IND) application for JAG201, a genetic cure for a genetic form of autism spectrum disorder (ASD). ) and Phelan-McDermid syndrome (PMS). There is currently no treatment for the approximately 30,000 people in the United States with ASD or PMS when a SHANK3 mutation or deletion occurs. 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 (NHPs) have shown that functional management of SHANK3 influences innovations in abnormalities in neurobehavioral, cognitive, and motor functions. The company plans to initiate a Phase I trial in adults with ASD or PMS offering a SHANK3 mutation or deletion in the United States in the second part of the year.
“We are pleased to receive FDA clearance to bring our investigational SHANK3 gene therapy to the clinic. The pre-clinical 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 physician who works directly with others living with SHANK3 haploinsufficiency and their families, I deeply recognize the profoundly demanding situations we face every day,” said Alexander Kolevzon, M. D. , professor of psychiatry and pediatrics at the Icahn School of Medicine at Mount Sinai. The interventions we are proposing may help, but, frankly, they are inadequate. My patients and all those suffering from SHANK3 haploinsufficiency deserve a remedy 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 reading the molecular mechanisms that regulate progression and serve as synapses in the brain, adding the role of SHANK3, as we believe that the potential for synaptic dysfunction can definitively reshape the lives of many other people with neuroprogression. disorders,” said Dr. Feng, a Broad Institute fellow, senior scientist and director of Model Systems and Neuroprogression. He is a neurobiologist at the Stanley Center for Psychiatric Research at Broad, 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 knowledge in rodent and non-human primate models with SHANK3 deficiency, thereby reducing the threat of the translational perspective of JAG201, I am excited to continue with Jaguar as it moves into the clinic with JAG201. “
SHANK3 haploinsufficiency causes premenstrual syndrome (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 imply that SHANK3 mutations may occur in approximately 1% of ASD patients, which is equivalent to approximately 30,000 patients in the United States. this estimate is perceived as low among clinical experts given barriers to access and low acceptance of genetic testing in the ASD diagnostic pathway. 3,4 In the subset of ASD patients who also have moderate disease up to profound intellectual disability (ID), the prevalence of SHANK3 mutations increases from approximately 1% to 2. 12%. 3,5
An external assembly on Patient-Oriented Drug Progression (EL-PFDD) in PMS, organized through CureSHANK and jointly planned with the Phelan-McDermid Syndrome Foundation (PMSF), was held with the FDA in November 2022. The main conclusions of the assembly are as follows: PMS has a serious effect on the quality of life of other people living with the disease, as well as on parents and siblings; PMS has a huge unmet medical need; and existing medical remedies and remedies are not very effective. 6
“As an organization committed to accelerating life-changing treatments for Phelan-McDermid syndrome, we are thrilled that JAG201 has been approved for clinical trials,” said Geraldine Bliss, founder and president of CureSHANK. “As the mother of a young adult with Phelan McDermid Syndrome, I personally sense the lack of available treatments and the incredible prospect of a remedy that addresses the root cause of this serious and widespread 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 committed to accelerating advances in genetic treatment for patients with serious genetic diseases, including those affecting large patient populations. The company is comprised of a proven team of experts with first-hand experience in bringing new genetic treatment treatments to patients and their families. Jaguar is moving forward through an initial portfolio of three programs. The company’s core program, approved by the IND, targets severe neurodevelopmental disorders caused by SHANK3 mutations or deletions, adding a genetic form of autism. spectrum disorder and Phelan-McDermid syndrome. The ongoing program currently targets type 1 galactosemia and the third targets type 1 diabetes. Jaguar partners with Advanced Medicine Partners, soon to be a spin-off of Jaguar, to manufacture its therapeutic products. Jaguar’s major investors come with Deerfield Management Company, ARCH Venture Partners, and Eli Lilly and Company. To learn more, visit www. jaguargenetreatment. com and follow Jaguar Gene Therapy on LinkedIn.
References
1. Costales JL et al. Neurotherapies 2015; 12(3):620-630. 2. What is Phelan-McDermid syndrome?Available in: https://pmsf. org/about-pms/. Consultado January 2023. 3. Betancur C et al. Mol Autism 2013; four (1): 17. four. Jaguar Gene Therapy Market Study, 2022; archived knowledge. 5. Leblond CS et al. PLoS Genet 2014; 10(9): e100four580. 6. Phelan-McDermid Voice of Patient Report. Available at: https://www. cureshank. org/s/CureSHANK_VoicePatientReport_2022. pdf. Retrieved January 2024.
Disclosure
Dr. Alexander Kolevzon has been paid for Jaguar Gene Therapy.
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Contacts
Kate Neermedia@jaguargenetherapy. com (815) 978-3891