lenrispodun (ITI-214) / J&J - LARVOL DELTA

Intra-Cellular Therapies Reports Third Quarter 2024 Financial Results, Provides Corporate Update… (GlobeNewswire) - "Our lenrispodun Phase 2 clinical trial is evaluating improvements in motor symptoms, changes in cognition and inflammatory biomarkers in patients with PD. We anticipate completion of this study by the end of 2025."

P2 data • CNS Disorders • Parkinson's Disease

Lenrispodun as Adjunctive Therapy in the Treatment of Patients With Motor Fluctuations Due to Parkinson's Disease (clinicaltrials.gov) - P2 | N=132 | Recruiting | Sponsor: Intra-Cellular Therapies, Inc. | Trial completion date: Feb 2025 ➔ Oct 2025 | Trial primary completion date: Feb 2025 ➔ Sep 2025

Trial completion date • Trial primary completion date • CNS Disorders • Movement Disorders • Parkinson's Disease • COMT

Intra-Cellular Therapies Reports Fourth Quarter And Full-Year 2023 Financial Results And Provides Corporate Update (Yahoo Finance) - "Lenrispodun (ITI-214) Parkinson’s disease (PD) program: Patient enrollment in our Phase 2 clinical trial is ongoing. The objective of this study is to evaluate improvements in motor symptoms in patients with PD. Changes in cognition and inflammatory biomarkers are also being assessed. We expect to complete patient enrollment in late 2024 with topline results anticipated in the first half of 2025."

Enrollment status • P2 data • CNS Disorders • Parkinson's Disease

Levodopa-induced dyskinesia: do current clinical trials hold hope for future treatment? (PubMed, Expert Opin Pharmacother) - No abstract available

Journal • CNS Disorders • Movement Disorders • Parkinson's Disease

Lenrispodun as Adjunctive Therapy in the Treatment of Patients With Motor Fluctuations Due to Parkinson's Disease (clinicaltrials.gov) - P2 | N=132 | Recruiting | Sponsor: Intra-Cellular Therapies, Inc. | Trial completion date: Nov 2024 ➔ Feb 2025 | Trial primary completion date: Nov 2024 ➔ Feb 2025

Trial completion date • Trial primary completion date • CNS Disorders • Movement Disorders • Parkinson's Disease • COMT

Lenrispodun as Adjunctive Therapy in the Treatment of Patients With Motor Fluctuations Due to Parkinson's Disease (clinicaltrials.gov) - P2 | N=132 | Recruiting | Sponsor: Intra-Cellular Therapies, Inc.

New P2 trial • CNS Disorders • Movement Disorders • Parkinson's Disease

Intra-Cellular Therapies Reports Fourth Quarter and Full-Year 2022 Financial Results and Provides Corporate Update (GlobeNewswire) - “ITI-1284-ODT-SL program: In 2023, we plan to begin Phase 2 programs in agitation in patients with Alzheimer’s disease (AD), generalized anxiety disorder, and psychosis in patients with AD….Lenrispodun (ITI-214) is our lead PDE1 inhibitor compound….We expect to commence clinical conduct in a Phase 2 trial in Parkinson’s disease later this month….ITI-333 program: ITI-333, a 5-HT2A receptor antagonist and μ-opioid receptor partial agonist, provides potential utility in the treatment of opioid use disorder, pain and mood disorders. A multiple ascending dose study in healthy volunteers evaluating pharmacokinetics (PK), safety and tolerability commenced clinical conduct in the first quarter of 2023. ”

New P1 trial • New P2 trial • Alzheimer's Disease • CNS Disorders • Pain • Parkinson's Disease

Intra-Cellular Therapies Reports Fourth Quarter and Full-Year 2022 Financial Results and Provides Corporate Update (GlobeNewswire) - “Net product sales of CAPLYTA were $87.4 million for the fourth quarter of 2022, compared to $25.5 million for the same period in 2021, representing a year-over-year increase of 243% and a 22% increase over the third quarter of 2022….Research and development (R&D) expenses for the fourth quarter of 2022 were $33.9 million, compared to $29.5 million for the fourth quarter of 2021. This increase is primarily due to higher lumateperone and non-lumateperone project costs, including the ITI-1284, ITI-214, and ITI-333 programs.”

Commercial • Sales • Alzheimer's Disease • Bipolar Disorder • CNS Disorders • Depression • Major Depressive Disorder • Pain • Parkinson's Disease

Intra-Cellular Therapies Reports Third Quarter 2022 Financial Results and Provides Corporate Update (GlobeNewswire) - "In our PDE 1 inhibitor program, for lenrispodun, we have recently completed or have ongoing Phase 1 trials including drug-drug interaction, bioavailability from scale up batches and food effect studies."

Trial completion • CNS Disorders • Parkinson's Disease

Intra-Cellular Therapies Reports Second Quarter 2022 Financial Results and Provides Corporate Update (GlobeNewswire) - "Intra-Cellular Therapies, Inc...announced its financial results for the second quarter ended June 30, 2022 and provided a corporate update....We have initiated our Phase 2 clinical program with lenrispodun for Parkinson’s disease and expect to commence patient enrollment in the second half of 2022."

New P2 trial • Trial initiation date • CNS Disorders • Parkinson's Disease

Single doses of a highly selective inhibitor of phosphodiesterase 1 (lenrispodun) in healthy volunteers: a randomized pharmaco-fMRI clinical trial. (PubMed, Neuropsychopharmacology) - P1 | "Future investigations should determine whether lenrispodun improves inhibitory control in target populations such as individuals with attention deficit hyperactivity disorder. Trial registration: ClinicalTrials.gov identifier: NCT03489772."

Journal • ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • CNS Disorders • Psychiatry

ITI-214, a potent and selective PDE1 inhibitor, inhibits tumor growth when combined with a checkpoint inhibitor in a mouse model of breast cancer (AACR 2022) - "In conclusion, this study demonstrates a synergistic ability of ITI-214 and anti-PD-1 to alter the tumor microenvironment and control tumor growth in mice. Translating these findings to the clinic suggests that ITI-214 may provide a means to expand the utility of immune checkpoint inhibitors to treatment-refractory tumors."

Checkpoint inhibition • Preclinical • Breast Cancer • Oncology • Solid Tumor • CCL2 • TNFA

ITI-214: Expiry of patent related to composition-of-matter in 2029 with term extension until 2034 (Intra-Cellular Therapies) - Annual Report 2021: Expiry of patent related to treatment of cardiovascular disorders in 2034; Expiry of patent related to compounds beyond 2030

Patent • CNS Disorders • Parkinson's Disease

The Effects of Acute and Chronic Selective Phosphodiesterase 1 Inhibition on Smooth Muscle Cell-Associated Aging Features. (PubMed, Front Pharmacol) - "Yet, after chronic treatment, the effects of PDE1 inhibition might be counteracted by the interplay between differential PDE1A and C expression. These results warrant further pharmacodynamic profiling of PDE enzyme regulation during chronic PDE1 inhibitor treatment."

Journal • Cardiovascular • Immunology • Inflammation • CDKN1A • IL10 • IL6 • TNFA

Single Doses of a Highly Selective Inhibitor of Phosphodiesterase 1 (Lenrispodun) in Healthy Volunteers: A Randomized Pharmaco-fMRI Clinical Trial (ACNP 2021) - "A low dose (1.0 mg) of lenrispodun increased BOLD fMRI signals in the IFG during the stop signal task consistent with improved neural inhibitory control. However, lenrispodun did not induce an attenuating effect on BOLD fMRI signals in the dAI during the extinction phase of a fear conditioning task. Collectively, these results support the hypothesis that PDE 1 inhibition affects neural inhibitory control."

Clinical • ADHD (Impulsive Aggression) • Alzheimer's Disease • Attention Deficit Hyperactivity Disorder • CNS Disorders • Psychiatry

[VIRTUAL] The Effects of Acute and Chronic Selective Phosphodiesterase 1 Inhibition in Associated Smooth Muscle Cell-Specific Aging Features (AHA 2021) - "We here tested the effects of PDE1 inhibition in SMC-specific Ercc1 DNA repair mutant mice, a model of isolated, accelerated SMC aging.Design and SM22αCre+ Ercc1fl/- (SMC-KO) and SM22αCre+ Ercc1fl/+ littermate (SMC-LM) mice receive either vehicle or the PDE1 inhibitor lenrispodun (dose 40mg/kg/day) in drinking water for 8 weeks... PDE1 inhibition may therapeutically be useful in restoring age-related vascular dysfunction by preserving microvascular function and potentiating NO-cGMP signaling. Yet, its chronic effects might be counteracted by the upregulation of PDE1a in vasculature. These results warrant further pharmacodynamic profiling of PDE enzyme regulation during chronic PDE1 inhibitor treatment."

Cardiovascular • ERCC1

Intra-Cellular Therapies Reports Third Quarter 2021 Financial Results and Provides Corporate Update (GlobeNewswire) - “Lumateperone: Study 403 is ongoing and is evaluating lumateperone 42mg in patients with MDD and in patients with bipolar depression...We expect to complete this study in the second half of 2022; Study ITI-007-025, a Phase 1 single ascending dose study of LLAI, is ongoing. We expect to complete this study later this year….ITI-1284 program: We have initiated our program for the development of ITI-1284-ODT-SL for the treatment of agitation in patients with probable Alzheimer’s disease. Clinical conduct in this program is expected to commence early in 2022. Studies in dementia-related psychosis and certain depressive disorders in the elderly are planned for the first half of 2022. Phosphodiesterase type I inhibitor (PDE1) program: Our Phase 2 clinical program evaluating lenrispodun (ITI-214) in Parkinson’s disease has been initiated, and we expect to commence patient enrollment in the first half of 2022.”

New P2 trial • New trial • Trial completion date • Alzheimer's Disease • Bipolar Disorder • CNS Disorders • Depression • Major Depressive Disorder • Parkinson's Disease • Schizophrenia

Intra-Cellular Therapies Announces Publications Highlighting Beneficial Effects of Phosphodiesterase Type I Inhibition with Lenrispodun (ITI-214) on Cardiovascular Function in Patients with Heart Failure and in Models of Accelerated Aging (GlobeNewswire) - "...findings further define the mechanism of action and potential therapeutic utility of PDE1 inhibitors for several conditions, including diseases where inflammation plays a role, such as Parkinson’s disease and indications where the cardiovascular system may be affected. Intra-Cellular Therapies, Inc...today highlights the publication of four manuscripts that report on the mechanism of action of lenrispodun (ITI-214) and the potential cardiovascular therapeutic effects of Phosphodiesterase Type I (PDE1) inhibition."

Preclinical • CNS Disorders • Parkinson's Disease

Acute Hemodynamic Effects and Tolerability of Phosphodiesterase-1 Inhibition With ITI-214 in Human Systolic Heart Failure. (PubMed, Circ Heart Fail) - P1/2 | "Single-dose ITI-214 is well-tolerated and confers inodilator effects in humans with heart failure with reduced ejection fraction. Further investigations of its therapeutic utility are warranted."

Journal • Atrial Fibrillation • Cardiovascular • Congestive Heart Failure • Heart Failure • Hypotension

Intra-Cellular Therapies Reports Second Quarter 2021 Financial Results and Provides Corporate Update (GlobeNewswire) - "A Phase 2 study evaluating lenrispodun (ITI-214) in Parkinson’s disease is expected to commence in the second half of 2021."

New P2 trial • CNS Disorders • Parkinson's Disease

Selective PDE1 inhibition ameliorates vascular function, reduces inflammatory response, and lowers blood pressure in ageing animals. (PubMed, J Pharmacol Exp Ther) - "In the present study, we studied the effect of acute and chronic treatment with ITI-214, a selective phosphodiesterase 1 inhibitor on vascular ageing features in Ercc1 mice...These findings suggest PDE1 inhibition would provide a powerful tool for nitric oxide - cGMP augmentation and have significant therapeutic potential to battle arteriopathy related to ageing. Significance Statement The findings implicate the key role of PDE1 in vascular function and might be of clinical importance for prevention of mortalities and morbidities related to vascular complications during ageing, as well as for progeria patients that show a high risk of cardiovascular disease."

Journal • Cardiovascular • Hypertension • Inflammation • ERCC1

[VIRTUAL] Effects of ITI-214, a potent and selective phosphodiesterase type 1 inhibitor, on tumor myeloid cellular composition, tumor volume and survival in mouse models of colorectal cancer when combined with an anti-PD-1 checkpoint inhibitor (AACR 2021) - "Together, these studies demonstrate a synergistic ability of ITI-214 and anti-PD-1 to alter the tumor environment and control tumor growth. Translating these findings to humans suggests that ITI-214 may provide a means to expand the utility of immune checkpoint inhibitors in immunogenic tumors."

Checkpoint inhibition • Preclinical • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • CCL2 • CD4 • TNFA

Intra-Cellular Therapies Presents Data on Antitumor Effects of Phosphodiesterase I Inhibition in a Preclinical Colorectal Cancer Model at the 2021 American Association for Cancer Research (AACR) Annual Meeting (GlobeNewswire) - “The poster describes results from preclinical studies demonstrating that the Company’s selective PDE1 inhibitor, lenrispodun (ITI-214), alters the tumor microenvironment and exhibits compelling anti-tumor activity when combined with a programmed cell death-1 (PD-1) immune checkpoint inhibitor in an animal model of colorectal cancer…Importantly, the effect of combining an anti-PD-1 immune checkpoint inhibitor and lenrispodun treatment produced a complete response in about 50% (7/15) of treated mice as compared to 10% (1/10) in anti-PD-1 alone treated mice, 20% (1/5) in the lenrispodun alone group and 0% (0/9) in the control group. This translated into a statistically significant effect on survival for the combination treatment group as compared to control (p=0.001).”

Preclinical • Colorectal Cancer • Gastrointestinal Cancer • Oncology

ITI-214: Expiry of patent related to composition-of-matter in 2029 with term extension until 2034 (Intra-Cellular Therapies) - Annual Report 2020: Expiry of patent related to treatment of cardiovascular disorders in 2034; Expiry of patent related to compounds beyond 2030

Patent • CNS Disorders • Parkinson's Disease

Intra-Cellular Therapies Reports Fourth Quarter and Full-Year 2020 Financial Results And Provides Corporate Update (GlobeNewswire) - "We plan to advance lenrispodun into a Phase 2 clinical study in Parkinson’s disease in 2021."

New P2 trial • CNS Disorders • Parkinson's Disease