Could you give an overview of Newron Pharmaceuticals?

This year, Newron has drawn important medical and market attention for its breakthrough schizophrenia therapy, evenamide. For more than 20 years we have been known as a biopharmaceutical company focused on the development of novel therapies for patients with diseases of the central nervous system (CNS) and pain. We have a long-standing commitment to delivering innovative treatments to improve the quality of life for patients with CNS disorders. Our team has a proven track record of drug development and commercialization.

We successfully took our first drug to market, Xadago (safinamide), for the treatment of Parkinson's disease – approved in the European Union in 2015 and the US in 2017. Significantly, that drug originated from the same class of compounds as evenamide, our lead drug for the treatment of patients with schizophrenia. Both compounds have a glutamatergic mechanism, which was important in Xadago for treating dyskinesia in Parkinson's disease, and which has shown remarkable results in evenamide for schizophrenia patients who are not benefitting from their current antipsychotic medication, or who are resistant to treatment. There are currently no other drugs on the market for chronic or Treatment Resistant Schizophrenia (TRS) that provide this unique glutamatergic mechanism of action, making evenamide a potentially market-shaping therapeutic. What is the existing treatment paradigm for patients with schizophrenia and how can evenamide potentially change this landscape?

The current treatment landscape for patients with schizophrenia typically involves the use of first-generation or second-generation antipsychotics. These primarily target dopamine and serotonin receptors in the brain to help manage the symptoms of psychosis, such as hallucinations, delusions, and thought disorders. However, not all patients with schizophrenia respond adequately to these medications, and many experience side effects or have difficulty adhering to their treatment regimen.

This is where evenamide could be a potential game-changer for this patient population. Evenamide’s mechanism of action involves modulating the excessive release of glutamate by blocking voltage-gated sodium channels. It is through this control of the excessive release of glutamate that evenamide has shown promise in repairing neural connectivity in patients with schizophrenia.

Furthermore, evenamide can be added to a patient's existing antipsychotic treatment without requiring them to discontinue and change their current medication, which would be a unique benefit. This could provide an effective option for patients and physicians and could help minimize the risk of patient relapse, often a concern when changing medications.

If approved, evenamide would be the first add-on therapy for schizophrenia patients, potentially offering a brand new and much-needed treatment option for the majority of schizophrenia patients who are poor responders or treatment-resistant. There have not been any transformational new schizophrenia drugs for this group of patients in more than 30 years! Can you provide an overview of the clinical progress made with evenamide over the past year?

2024 was marked by significant milestones for our evenamide program, and we reported two sets of exceptional data on its use as an add-on treatment for patients with treatment resistant schizophrenia, as well as for patients with chronic schizophrenia.

At the start of the year, in January, we were excited to share the one-year results from study 014/015, a Phase II open label trial evaluating evenamide as an add-on therapy to a single antipsychotic in TRS patients.

Then in April, we announced data from study 008A, a potentially pivotal four-week randomized, double-blind and placebo-controlled Phase III study of evenamide as an add-on therapy in patients with chronic schizophrenia demonstrating inadequate benefit from their current second-generation antipsychotic. What is the clinical significance of these results to date?

The data from our 014/015 study demonstrated that evenamide as an add-on treatment for patients with TRS was associated with sustained, clinically significant benefits that increased throughout the one-year course of treatment, with more than 70% of patients experiencing a clinically important reduction in disease severity.

Remarkably, 25% of patients achieved “remission,” the highest level of improvement that can be obtained in a patient with schizophrenia and one that has never been described before in TRS patients.

Furthermore, approximately 50% of patients that completed one-year of treatment with evenamide no longer met the criteria used to diagnose treatment resistance and there were no patient relapses during the one-year treatment period.

The data from study 008A for chronic schizophrenia patients met its key safety and efficacy endpoints: the primary endpoint (improvement of the Positive and Negative Syndrome Scale (PANSS) Total Score) and key secondary endpoint (improvement of the Clinical Global Impression of Severity (CGI-S)), with a 96% rate of study completion.

A further detailed analysis of this data announced in May 2024 revealed significant multi-domain benefits in PANSS and Clinical Global Impression of Change (CGI-C) ratings, confirming a highly statistically significant improvement for evenamide irrespective of the population analyzed or the statistical methods used. In addition, the benefits noted on efficacy measures increased up to day 29, indicating potentially greater and more enduring effects during long-term treatment with evenamide. How will this help advance schizophrenia treatment?

The vast majority of patients with schizophrenia are poor responders or suffer from treatment resistance (TRS) and do not, or insufficiently respond to the current medicines available on the market, highlighting the urgent patient need for new medicines within this therapeutic area.

Taken together, the data from our two groundbreaking studies has reaffirmed evenamide’s favorable safety and tolerability profile and demonstrated its efficacy on multiple measures of psychopathology in both TRS and chronic schizophrenia. The data also add to the growing evidence that the glutamatergic inhibition mechanism of action offers an innovative therapeutic option to schizophrenia patients who do not benefit from current antipsychotic treatments. What will make 2025 a transformative year for Newron Pharmaceuticals?

Newron has made tremendous progress over the past year. Looking at the rest of 2025, we believe we are headed for a transformational year based on the results of our work.

Following a very diligent and focused partnering process, at the end of 2024, we announced a major licensing agreement with EA Pharma, a subsidiary of Eisai Co., Ltd., to develop, manufacture and commercialize evenamide in Japan and other Asian territories. Newron will receive up to a maximum total of €117 million from EA Pharma, including an upfront payment of €44 million, financial contributions to our upcoming, pivotal Phase III one-year study to be performed outside of the licensed territories, regulatory and commercialization milestones, and tiered royalties up to a double-digit percentage of net sales for evenamide.

This was followed closely in January 2025 by a second major licensing agreement, this time with South Korea’s leading CNS specialist, Myung In Pharm, to commercialize evenamide in South Korea as an add-on therapy for TRS and poorly responding patients with schizophrenia. Importantly, Myung In Pharm will contribute 10% of the total patient population to be enrolled into our upcoming pivotal Phase III trial and cover the costs related to this population.

But perhaps the most important upcoming milestone in 2025 for Newron will be the initiation of our pivotal Phase III randomized, double-blind, one-year trial evaluating evenamide as add-on treatment in at least 600 patients with TRS. As a result of our strong partnering momentum and clinical data generated to date, the planning for this trial is already well advanced and is due to start in the first half of 2025.

We are enormously gratified with both the promise and progress of evenamide and we want to particularly thank the patients, their physicians, and the trial investigators for their participation in the very significant studies we have conducted to date.

We are all excited about the clear benefits evenamide can bring to the community of schizophrenia patients who are currently underserved by the therapies on the market and who are in great need of innovative and potentially transformative treatments.