PharmaTher Enters into Exclusive Option Agreement with Case Western Reserve University to Develop and Commercialize Ketamine for Rett Syndrome

PharmaTher Holdings Ltd., a specialty pharmaceutical company focused on developing and commercializing novel uses and delivery forms of ketamine to treat mental health, neurological and pain disorders, is pleased to announce that the Company has entered into an evaluation and exclusive option agreement (the “Agreement”) with Case Western Reserve University (“CWRU”) in the development and commercialization for the intellectual property of ketamine in the treatment Rett Syndrome, a rare genetic neurological disorder. Ketamine has been subject to a Phase 2 clinical trial for Rett syndrome and unpublished results will be evaluated to support a defined clinical and regulatory plan for FDA feedback.

“We are pleased to have added the Rett syndrome program to our clinical stage product pipeline that focuses on novel uses and delivery forms of ketamine in the treatment of mental health,  neurological and pain disorders,” said Fabio Chianelli, CEO of PharmaTher. “In research, ketamine has shown the potential for treating Rett syndrome. We will work with CWRU and the clinical trial team in pursuing discussions with the FDA to determine all regulatory and clinical options that could expedite the pathway towards having ketamine available for Rett syndrome patients.”

Currently, there is no known cure or FDA-approved drugs for treating Rett syndrome. According to the Rett Syndrome Foundation, Rett syndrome is a rare genetic neurological disorder that occurs almost exclusively in girls. It leads to severe impairments in their ability to speak, walk, eat, and even breathe easily. Prominent features of Rett syndrome include near constant repetitive hand movements and loss of purposeful hand use. Rett syndrome is usually recognized in children between 6 to 18 months. Rett syndrome is caused by mutations on the X chromosome on a gene called MECP2. Rett syndrome occurs worldwide in 1 of every 10,000 female births, and is much rarer in boys.

Ketamine has the potential to treat Rett syndrome, which has been independently validated in two different laboratories in two different strains of Mecp2 mice and has completed a Phase 2 clinical trial with Rett syndrome, with results not published. The therapeutic potential of ketamine for treating Rett syndrome was first demonstrated by Dr. David M. Katz, Professor Emeritus, Department of Neurosciences, School of Medicine at CWRU, and colleagues, who found that treatment of heterozygous female Mecp2 mutant mice with a subanesthetic dose of ketamine (8 mg/kg) acutely reversed abnormalities in Fos expression and sensorimotor function. Chronic administration of ketamine was also found to improve symptoms and extend lifespan in null male Mecp2 mutants. The ability of low-dose ketamine to improve function across a broad range of symptoms may be related to its ability to increase cortical network activity, possibly by selective inhibition of GABAergic interneurons, as well as to decrease synaptic excitability in brainstem networks important for respiratory and autonomic control. Thus, ketamine may be ideally suited to redress the imbalance between cortical and brainstem activity that characterizes the MeCP2-deficient brain. Moreover, in addition to its acute effects on circuit function, work in other disease models has shown that ketamine also rapidly stimulates dendritic growth, BDNF levels, and expression of key synaptic proteins, at least in part through activation of mTOR signaling, which is deficient in Mecp2 mutants. These findings suggest that, in addition to acute rescue of neurological function, ketamine also has the potential to promote synaptic repair in Rett syndrome by enhancing structural and functional connectivity, as previously shown in animal models of depression and stress.

Under the terms of the Agreement, PharmaTher gained an exclusive option for up to 12 months to evaluate the regulatory, clinical development and commercialization plan for CWRU’s intellectual property portfolio, which includes, US issued patent no. 11,213,494 and US provisional patent no. 62/312,749 entitled, “Composition and method for the treatment of pervasive development disorders”, and US provisional patent no. 62/004,695 entitled, “Acute and sustained effects of low-dose ketamine treatment in mouse models of Rett Syndrome.” Consistent with industry standards, PharmaTher paid a one-time fee for entering into the Agreement, and should the Company elect to exercise its option, both the Company and CWRU will negotiate a license agreement.