Minerva Neurosciences (NERV) Stifel 2026 Virtual CNS Forum summary

Overview of schizophrenia and unmet needs

• Negative symptoms in schizophrenia are highly disabling and lack approved treatments in the U.S., with current antipsychotics failing to address them and sometimes worsening these symptoms.

• Negative symptoms, especially avolition, significantly impair quality of life and functioning, and are often underdiagnosed.

• Improving negative symptoms may also enhance cognitive function and overall patient functioning.

• Traditional trial designs for positive symptoms are inadequate for negative symptoms, requiring new approaches.

• Differentiating primary from secondary negative symptoms is crucial, as antipsychotics can induce secondary symptoms.

Clinical development and trial design

• Roluperidone, a non-dopamine-blocking drug, targets negative symptoms and is being tested as monotherapy in patients with stable positive symptoms.

• Over 800 patients have participated in trials, showing low relapse rates and significant improvements in negative symptoms and functioning.

• The primary endpoint is the Marder negative score at week 12, with functioning assessed by the PSP scale as a key secondary endpoint.

• The current pivotal study tests 64 mg roluperidone versus placebo, with a subsequent descriptive comparison of relapse rates against antipsychotics.

• The study uses a double-dummy design to maintain blinding due to differing side effect profiles.

Efficacy, safety, and regulatory engagement

• Both registrational studies showed significant improvements in negative symptoms, with the higher dose (64 mg) consistently effective.

• Functional improvements were observed, with some patients regaining the ability to work.

• Roluperidone demonstrated a favorable safety profile, lacking common antipsychotic side effects such as sedation and movement disorders.

• The FDA agreed that a statistically significant p-value is sufficient for clinical meaningfulness, supported by responder and anchor analyses.

• Relapse will be assessed using psychometric endpoints (e.g., PANSS score increase) and hard clinical outcomes like hospitalization and suicidality.