itanapraced (CHF-5074) / Chiesi, CereSpir - LARVOL DELTA

Selective Gamma-Secretase Inhibition by CHF5074 Attenuates Inflammation and Neovascularization in a Murine Model of Choroidal Neovascularization. (PubMed, Curr Eye Res) - "CHF5074 inhibited the tube formation of HUVECs co-cultured with LPS and ATP-treated BV2 cells. CHF5074 significantly suppresses angiogenesis in laser-induced choroidal neovascularization models, suggesting its potential as a novel agent for preventing and treating CNV."

Journal • Preclinical • Inflammation • CD31 • IL10 • IL1B • PECAM1 • TNFA

DEVELOPING NOVEL THERAPEUTIC TREATMENT FOR PARKINSON'S DISEASE (ADPD 2023) - "Our findings reveal a therapeutically targetable, fe ed-forward mechanism through which AICD promotes LRRK2 -mediated neurotoxicity in PD."

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

The APP intracellular domain promotes LRRK2 expression to enable feed-forward neurodegenerative mechanisms in Parkinson's disease. (PubMed, Sci Signal) - "Itanapraced showed similar effects in a neurotoxin-induced PD mouse model, suggesting that inhibiting the AICD may also have therapeutic benefits in idiopathic PD. Our findings reveal a therapeutically targetable, feed-forward mechanism through which AICD promotes LRRK2-mediated neurotoxicity in PD."

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

Structure-activity relationships of flurbiprofen analogues as stabilizers of the amyloidogenic protein transthyretin. (PubMed, J Struct Biol) - "Overall, considering together binding selectivity and protective effects on TTR native structure by flurbiprofen analogues in the presence of plasma proteins, as determined by Western Blot,the aforementioned properties of analyzed compounds appear to be better (CHF5075 and CHF4802) or similar (CHF4795) or worse (CHF5074, also known as CSP-1103) as compared to those of diflunisal, used as a reference TTR stabilizer...Distinct interactions with TTR appear to characterize flurbiprofen analogues and the NSAID diflunisal and its analogues as TTR stabilizers. Relationships between stabilizing effect on TTR by flurbiprofen analogues determined experimentally and molecular details of their interactions with TTR have been established, providing the rationale for their protective effects on the native protein structure."

Journal • Amyloidosis

Flurbiprofen as a biphenyl scaffold for the design of small molecules binding to PD-L1 protein dimer. (PubMed, Biochem Pharmacol) - "Then, we identified three FLB analogues (diflunisal, CHF-5074 and HCT1026) forming stable complexes with PD-L1...Our approach proposes a new strategy to discover PD-L1-binding small molecules and raises the intriguing possibility that FLB can bind transiently to PD-L1, thus possibly explaining some of its biological effects. Our study opens new perspectives for the use of FLB (and analogs) as an immune modulator in oncology and other therapeutic domains."

Journal • Review • Immune Modulation • Inflammation • Oncology • PD-L1

Evaluation of effects of multiple dose regimens of CHF 5074 on potential biomarkers of neurodegeneration in subjects with mild cognitive impairment (CT05) (clinicaltrials.gov) - P2, N=261; Not yet recruiting; Sponsor: Chiesi; New P2 trial

New P2 trial • Alzheimer's Disease

Cerespir Incorporated is pleased with positive interim phase 2 results for CHF 5074 in patients with mild cognitive impairment, presented by Chiesi at the AAIC 2013 meeting in Boston (Cerespir Press Release) - P2, N=96; CT04 (NCT01303744); Sponsor: Chiesi; "ApoE4 carriers (n=12) performed significantly better (p<0.05) than ApoE4 non-carriers on Immediate Word Recall and Trail Making Test-A with improvements representing 25-38%...CHF 5074 resulted in a dose-depended reduction in inflammatory biomarkers (TNF-alpha and sCD40L) in cerebrospinal fluid collected after 12 weeks of dosing. CereSpir™ Incorporated and Chiesi Farmaceutici...have entered into a Letter of Intent and are negotiating a licensing agreement, whereby CereSpir will acquire the exclusive global development and commercialization rights to CHF 5074."

Anticipated licensing / partnership • Biomarker • P2 data • Alzheimer's Disease

Evaluation of safety & tolerability of multiple dose regimens of CHF 5074 and exploration of effects on potential markers of clinical efficacy in patients with mild cognitive impairment (CT04) (clinicaltrials.gov) - P2, N=96; Active, not recruiting -> Completed; Completion date: May 2012 -> Apr 2012

Completion date • Trial completion • Alzheimer's Disease

Cerespir Incorporated assembles world class Clinical Advisory Board chaired by professor Robert A. Hauser to support Cerespir's Parkinson's disease development program for itanapraced (PRNewswire) - "'Itanapraced has a novel mechanism of action with the potential to slow or stop progression of PD,' said Professor Robert A. Hauser...J. Timothy Greenamyre...studies mechanisms of neurodegeneration in Parkinson's disease, with a focus on gene-environment interactions. Translational studies use pharmacological and 'gene therapy' approaches....Rajesh Pahwa...He has conducted more than 75 clinical trials related to Parkinson's disease and other movement disorders."

Media quote