Intra-Cellular highlights data presentations at ACNP annual meeting

Intra-Cellular Therapies announced data presentations at the American College of Neuropsychopharmacology, ACNP, 62nd Annual Meeting. Poster M91: “Lumateperone in the Treatment of Patients With Major Depressive Disorder and Bipolar Disorder with Anxious Distress and Mixed Features.” The poster presented at ACNP reports on an important post-hoc analysis from Study 403 evaluating the antidepressant effects of lumateperone in a pre-specified subgroup of patients with mixed features exhibiting anxious distress. Lumateperone improved change from baseline for MADRS total score at Day 43 compared with placebo in all three populations with anxious distress: combined major depressive disorder/bipolar depression population, MDD individual population, and bipolar depression individual population. Greater improvements vs placebo in MADRS Total score occurred by Day 15 and persisted throughout the study. Similarly, in the Clinical Global Impression Scale-Severity lumateperone was superior versus placebo in all three patient populations. Cohen-D effect sizes on the CGI-s ranged from 0.48 to 0.66. The data presented in this poster represent further analyses from Study 403. Study 403 evaluated lumateperone 42mg as monotherapy in the treatment of major depressive episodes in patients with MDD with mixed features and in patients with bipolar depression with mixed features. Topline results for Study 403 are shown in Poster M88 and described below. Poster M131: “Discovery and Characterization of ITI-1549, a Novel Non-hallucinogenic Psychedelic For the Treatment of Neuropsychiatric Disorders.” The company is developing novel non-hallucinogenic psychedelics that allow exploration of this psychoactive drug class in neuropsychiatric conditions including mood disorders without the liabilities of known psychedelics, such as induction of hallucinations and risks for cardiac valvular pathologies. The lead molecule in this program, ITI-1549, is advancing through IND enabling studies and is expected to enter human testing in late 2024 or early 2025. This poster describes the in-vitro and in-vivo preclinical characterization of ITI-1549. In vitro, similar to known hallucinogenic psychedelics, ITI-1549 exhibits high affinity binding to 5-HT2a receptors. Functionally, ITI-1549 acts as an agonist at 5-HT2A receptors favoring postsynaptic signaling within the beta-arrestin pathway over G-protein coupled pathways. In conclusion, ITI-1549 may be a safe, non-hallucinogenic psychedelic without the liability to induce hallucinations and cardiac pathologies while retaining the potential as an acute or chronic treatment of mood, anxiety and other neuropsychiatric disorders. Poster M88: “Lumateperone Treatment for Major Depressive Episodes with Mixed Features in Major Depressive Disorder and Bipolar I or Bipolar II Disorder.” This poster describes further data analyses from Study 403 in mixed features. In this study, lumateperone 42mg was statistically significant on the primary endpoint of symptom reduction on the MADRS for the combined mixed features patient population of MDD and bipolar depression and the individual patient populations of MDD with mixed features and bipolar depression with mixed features. Lumateperone 42mg also met the key secondary endpoint by demonstrating a statistically significant and clinically meaningful reduction in the Clinician’s Global Impression scale or CGI compared to placebo at Week 6 in all three patient populations. Lumateperone was generally safe and well tolerated, with a side effect profile consistent with prior lumateperone trials. The most common adverse events in the study were somnolence, dizziness and nausea.