Pharnext SA announced that the first patient has been enrolled in the PREMIER Open Label Extension (PREMIER-OLE) study of PXT3003 for the treatment of Charcot-Marie-Tooth disease type 1A (‘CMT1A') in the United States. This patient, who has completed the double-blind, placebo-controlled PREMIER trial, was enrolled in May 2021. All patients who complete the PREMIER trial will be eligible to join the PREMIER-OLE study and will receive the high dose (‘HD') of PXT3003 until the treatment is commercially available, should PXT3003 be approved in the US and Europe, respectively by the FDA and the EMA.

PXT3003 is the Company's lead program to treat CMT1A, a debilitating disease with currently no existing approved therapies. The PREMIER trial, which recently completed enrollment with a total of 387 patients, is an international, randomized, double-blind, two-arm placebo-controlled, pivotal Phase III study, where the primary objective is to evaluate the efficacy and safety of PXT3003 versus placebo in mild-to-moderate CMT1A patients, over a 15-month period. The dose of PXT3003 tested in the PREMIER trial corresponds to the HD tested in the prior Phase III clinical study, the PLEO-CMT trial, and the ongoing open-label extension Phase III study, the PLEOCMT-FU trial.

As agreed with regulatory agencies, the primary efficacy endpoint will be the Overall Neuropathy Limitations Scale (‘ONLS') which measures functional motor disability. Recent data from the ongoing PLEOCMT-FU trial (open-label follow-up extension study of the first phase III study, the PLEO-CMT trial) announced in May 2022has shown a good safety profile and continuous treatment effect of PXT3003 measured on the ONLS after 5 years of total treatment time. 123 Patients with mild-to-moderate CMT1A are still on treatment with PXT3003 High Dose in the PLEOCMT-FU trial.

Charcot-Marie-Tooth (‘CMT') disease encompasses a heterogeneous group of inherited, severe, debilitating, progressive and chronic peripheral neuropathies. CMT1A, the most common type of CMT, is an orphan disease with a prevalence of 1/5000 people affecting about 150,000 people in Europe and the U.S. and about 1,500,000 people worldwide. The genetic mutation responsible for CMT1A is a duplication of the PMP22 gene coding for a peripheral myelin protein.

The duplication of this gene results in overexpression of the PMP22 protein and failure of Schwann cells to produce normal myelin (neuronal sheath). The lack of a normal myelin structure and function leads to abnormal peripheral nerve conduction and axonal loss. As a result of peripheral nerve degradation, patients suffer from progressive muscle atrophy in both the legs and arms causing problems with walking, running and balance as well as abnormal hand functioning.

They might also suffer from mild to moderate sensory disorders. First symptoms usually appear during adolescence and will progressively evolve throughout life. Patients with the most severe form of CMT1A end up in wheelchairs, representing at least 5% of cases.

To date, no curative or symptomatic medications have been approved and treatment consists of supportive care such as orthotics, leg braces, physical and occupational therapy or surgery.