FNP-223 / Asceneuron, Ferrer International - LARVOL DELTA

Safety, Tolerability, Pharmacokinetics, and Brain Target Occupancy of the OGA Inhibitor ASN90 in Healthy Participants. (PubMed, Mov Disord) - P2 | "The phase 1 results of ASN90 in healthy participants provide strong support for its further development in progressive supranuclear palsy (PSP) and AD. Currently, Ferrer Internacional, S.A. is conducting a phase 2 study, known as PROSPER (ClinicalTrials.gov ID: NCT06355531), to evaluate the efficacy, safety, and pharmacokinetics of ASN90 in slowing the progression of PSP."

Clinical • Journal • PK/PD data • Alzheimer's Disease • CNS Disorders • Movement Disorders • Parkinson's Disease • Progressive Supranuclear Palsy

Ferrer Completes Recruitment of 220 Patients for the PROSPER Study, a Phase II Clinical Trial in Progressive Supranuclear Palsy (PSP), Two Months Ahead of Schedule (Businesswire)

Enrollment closed • Progressive Supranuclear Palsy

Structural Insights and Functional Dynamics of β-Lactoglobulin Fibrils. (PubMed, Nano Lett) - "Flexible domains were modeled and evaluated by MD, identifying one stable conformation (Asn90-Thr97). The ionic strength reduced the coat flexibility and promoted iron binding, suggesting environmental responsiveness. These findings link fibril flexibility to functional potential, offering mechanistic insight into engineering β-LG-based nanomaterials."

Journal • CD5

Safety, Tolerability and Pharmacokinetics of a Novel Oral OGA Inhibitor (FNP-223) First-in-Human Phase 1 Study (MDS Congress 2025) - "Objective: To evaluate the safety, tolerability, and pharmacokinetics of FNP-223 (formerly ASN90) in healthy volunteers (HV). The findings indicate that FNP-223 is safe and well-tolerated at doses ranging from 100 to 500 mg, administered twice a day in HV. Additionally, the observed dose proportionality, along with the CSF-to-plasma ratios for both Cmax and AUC, suggests that the unbound fraction of the drug can effectively diffuse across the human blood-brain barrier. This study, along with PET-based target engagement assessments, supports the continued clinical development of FNP-223 in the ongoing Phase 2 PROSPER trial involving patients with PSP."

Clinical • First-in-human • P1 data • PK/PD data • CNS Disorders • Proteinopathy

Brain Target Engagement and Pharmacokinetic-Enzyme Occupancy (PK-EO) Relationship of FNP-223: A Novel Oral OGA Inhibitor for Progressive Supranuclear Palsy – Phase 1 PET Study (MDS Congress 2025) - "Objective: To determine the brain O-GlcNAcase (OGA) occupancy, following a single oral dose of FNP-223 (formerly ASN90) and to determine PK-EO relationship... Plasma concentrations and safety data for FNP-223 align with first-time-in-human study findings. Pharmacokinetic modeling suggests that a high CNS target engagement can be achieved with a well-tolerated dose of 300 mg TID. The ongoing PROSPER Study is a randomized, double-blind, placebo-controlled Phase 2 trial assessing the efficacy, safety, and pharmacokinetics of FNP-223 in patients with progressive supranuclear palsy."

P1 data • PK/PD data • CNS Disorders • Movement Disorders • Progressive Supranuclear Palsy • OGA

Pseudouridimycin Biosynthesis: Biochemical Characterization of the Glucose-Methanol-Choline (GMC) Family Oxidoreductase, PumI. (PubMed, Biochemistry) - "Our mutational analysis identified two active site histidines (His454 and His455) and two asparagines (Asn90 and Asn499) in SrPumI as potential flavin-binding residues...Based on these experiments, a mechanism has been proposed for PumI. We believe this work will provide new insights into PUM biosynthesis, enabling pathway engineering to prepare novel PUM derivatives for prospective therapeutic applications."

Journal

Site-specific characterization of mannose-6-phosphate-containing N-glycans on recombinant idursulfase beta for lysosomal targeting in Hunter syndrome therapy. (PubMed, Int J Biol Macromol) - "Idursulfase beta (IDS, Hunterase®), a recombinant human I2S produced in CHO cells, is used clinically in enzyme replacement therapy (ERT)...Phosphorylated N-glycans exhibited site-specifically distribution: Asn221 (one P1, three P2) and Asn255 (three P1, three P2) were fully phosphorylated; Asn90 (one P1) and Asn512 (two P1) showed partial phosphorylation...Furthermore, cellular uptake studies using fluorescent-labeled IDS in human fibroblasts confirmed efficient endocytosis and lysosomal delivery. This study provides the first site-specific characterization of M6P-containing N-glycans in IDS, supporting its therapeutic efficacy in ERT for Hunter syndrome."

Journal • Hunter Syndrome • Lysosomal Storage Diseases • Metabolic Disorders • Pediatrics • Rare Diseases

Synaptic Toxicity of OGA Inhibitors and the Failure of Ceperognastat. (PubMed, bioRxiv) - "Here, we evaluated the acute synaptic effects of three structurally distinct OGAi (ceperognastat, ASN90, and MK8719) in mouse hippocampal slices. These findings indicate that OGAi produce rapid and convergent synaptotoxic effects across pre- and postsynaptic compartments, likely reflecting a class-wide mechanism. We argue that electrophysiological screening should be standard in CNS drug development and caution against targeting essential synaptic processes in chronic neurodegenerative conditions."

Journal • Alzheimer's Disease • CNS Disorders • Depression • Psychiatry • OGA • SYP

Ferrer Receives FDA Fast Track Designation for FNP-223 in Progressive Supranuclear Palsy (PSP) (Businesswire) - "Ferrer...has announced that FNP-223, a novel therapy in-licensed from Asceneuron and aimed at slowing the development of progressive supranuclear palsy (PSP), has received Fast Track designation from the US Food & Drug Administration (FDA). FNP-223, a new molecular entity in active development for PSP, is in an ongoing Phase 2 study to evaluate its safety, efficacy, and pharmacokinetics in adult patients with possible or probable PSP-Richardson syndrome (PSP-RS), the most common clinical variant of this neurodegenerative disease."

Fast track • Progressive Supranuclear Palsy

In Silico Binding of Computationally Folded Structures of Human Surfactant Protein D (hSP-D) to SARS-CoV-2 Spike Wild Type and ACE2 Show Low Likelihood of SP-D's Role in Blocking SARS-CoV-2 ACE2 Binding (ATS 2025) - "This abstract is funded by: Chester Robbins Endowment (AH) Rationale While human surfactant protein D (hSP-D) has been of immunological interest for its antiviral capabilities over at least the past two decades, there do not currently exist experimentally derived structural images that include all of hSP-D's amino acids of importance, especially the N-Acetylglucosamine (NAG) binding site at Asparagine amino acid site number 90 (ASN90). Clearly, computational folding methods can lead to dramatically different protein structure models than their X-ray or other experimentally-derived counterparts. This would make sense, considering that all three methods used here (AlphaFold, I-TASSER, ESMFold) use data from other, similar structures to be able to derive high confidence structures, but do not necessarily detail molecular conformations or even stoichiometry for effective protein structure determinations."

Surfactant • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Design, synthesis and evaluation of diphenyl ether-based kaiso inhibitors with enhanced potency. (PubMed, Bioorg Med Chem Lett) - "Notably, its inhibitory activity surpassed that of the positive control MIRA-1 (IC50 = 654.065 μM). Molecular docking and dynamic studies revealed that the binding of the compound's amino and ester moieties to the active site of kaiso protein, as well as the extension of the benzene ring towards the Asn561 position in the cavity, contributed significantly to its potency. These findings provide valuable insights for the development of new Kaiso inhibitors."

Journal • Lung Cancer • Oncology • Solid Tumor

Ferrer Advances Research into Progressive Supranuclear Palsy (PSP) with the Inclusion of the First Participant in a Phase II Clinical Trial (Businesswire) - "Ferrer...has announced the dosing of the first participant in the Phase II clinical trial, PROSPER. The study seeks to evaluate the safety and efficacy of the molecule FNP-223, a novel therapy intended to slow the progression of Progressive Supranuclear Palsy (PSP)...It is expected to include the participation of up to 220 participants and 46 clinical trial sites across the United States, the United Kingdom and 7 countries in the European Union. PROSPER is currently recruiting in the United States, with additional countries expected to begin recruitment in the fourth quarter of 2024."

Trial status • CNS Disorders • Progressive Supranuclear Palsy

N-glycosylation of Wnt3 regulates the progression of hepatocellular carcinoma by affecting Wnt/β-catenin signal pathway. (PubMed, World J Gastrointest Oncol) - "These results indicate that by inhibiting the N-glycosylation of Wnt3, the proliferation, migration, invasion and colony formation abilities of liver cancer cells can be weakened, which might provide new therapeutic strategies for clinical liver cancer in the future."

Journal • Gastrointestinal Cancer • Hepatocellular Cancer • Hepatology • Liver Cancer • Oncology • Solid Tumor • FZD7 • WNT3

Supramolecular self-assembly strategies of natural-based β-lactoglobulin modulating bitter perception of goat milk-derived bioactive peptides. (PubMed, J Dairy Sci) - "Molecular dynamic simulation and free energy calculation provided time-varying atomic trajectories of the recombinant complex, and found that peptide was stabilized in the upper region of the hydrophobic cavity with the binding free energy of -30.56 kJ mol through 4 hydrogen bonds (Glu74, Glu55, Lys69, and Ser116) and hydrophobic interactions (Asn88, Asn90 and Glu112). Current research endeavors to provide valuable physical insights into the macroscopic self-assembly behavior between protein and bitter peptide, and the meticulous design of highly acceptable taste characteristics in goat milk products."

Journal

Ferrer acquires global rights to ASN90; an O-GlcNAcase inhibitor being developed by Asceneuron specifically for the treatment of progressive superior ophthalmoplegia (PSP) [Google translation] (Businesswire) - “Spanish pharmaceutical company Ferrer and Swiss clinical-stage biotechnology company Asceneuron announce the signing of a licensing agreement. Under the agreement, Ferrer will acquire exclusive worldwide rights to develop and commercialize ASN90 for progressive superior ophthalmoplegia (PSP). PSP is a tau-related orphan disease with a largely unmet medical need. Both Ferrer and Asceneuron are delighted that the announcement of the collaboration coincides with International Rare Disease Day (February 28). The agreement underscores the commitment of both companies to improve the lives of patients with rare diseases such as PSP. Terms of the agreement include an upfront payment and various development, regulatory and commercial milestone payments. Asceneuron is eligible to receive double-digit tiered royalties on ASN90's global net sales.”

Licensing / partnership • CNS Disorders • Progressive Supranuclear Palsy

"Ferrer Acquires Worldwide Rights to ASN90, an O-GlcNAcase Inhibitor From Asceneuron, Exclusively to Treat Progressive Supranuclear Palsy (PSP) https://t.co/Xubi1cItEb" (@NewsFromBW)

CNS Disorders • Movement Disorders • Progressive Supranuclear Palsy • OGA

O-GLCNACASE INHIBITORS ASN90 AND ASN51 ARE MULTIMODAL DRUG CANDIDATE FOR AD AND PD (ADPD 2023) - "Results on ASN51-treated A53T model will be presented at the conference. Conclusions These data support the development of both ASN90 and ASN51 in tau and α-synuclein related neurodegenerative diseases, including AD and PD."

Alzheimer's Disease • CNS Disorders • Movement Disorders • Parkinson's Disease • Proteinopathy • OGA • THY1

Asceneuron Awarded Second Grant from The Michael J. Fox Foundation for Accelerated Research into Novel Parkinson's Disease Therapies (PRNewswire) - "Asceneuron SA... today announces that it has been awarded a second grant from The Michael J. Fox Foundation for Parkinson's Research (MJFF) to accelerate the study of its clinical stage O-GlcNAcase (OGA) inhibitor ASN51 as a potential new treatment for Parkinson's disease (PD)....The grant will fund a preclinical proof-of-concept study to assess the disease-modifying properties of Asceneuron's OGA inhibitor ASN51 in a preclinical model of inherited PD....The results will further interrogate the mechanism of action of OGA inhibitors with respect to a–synuclein toxicity and aggregation and provide support for the clinical exploration of ASN51 in PD patients. The project will begin immediately, with results expected in the fourth quarter of 2022."

Financing • Preclinical • CNS Disorders • Parkinson's Disease

Asceneuron Publishes Pioneering Preclinical Efficacy Data on its Novel Clinical Molecule ASN90 in Both Alzheimer's and Parkinson's Disease Models (PRNewswire) - "Asceneuron SA...today announces the publication of peer-reviewed data in the journal ACS Chemical Neuroscience regarding ASN90, an O–GlcNAcase (OGA) inhibitor, and one of its leading candidates in clinical development for treating neurodegenerative proteinopathies....In this recently published, peer-reviewed paper, Asceneuron reports the preclinical discovery and development of the novel small molecule OGA inhibitor ASN90 (formerly known as ASN120290/ASN561)....The preclinical data show that daily oral administration of ASN90 prevented the development of tau tangle pathology, as well as functional deficits in motor behavior and breathing, and increased survival. Another significant finding; novel for this class of molecules; is that ASN90 slowed the progression of motor impairment and reduced astrogliosis in a frequently utilized, preclinical model of Parkinson's disease."

Preclinical • Alzheimer's Disease • CNS Disorders • Parkinson's Disease

Asceneuron to Provide Update on O-GlcNAcase Pipeline at Upcoming Conferences (PRNewswire) - “Asceneuron SA…is pleased to announce that the Company will be presenting novel data on its O-GlcNAcase (OGA) inhibitor pipeline at the following upcoming conferences. 22nd International Conference on Alzheimer's Drug Discovery; Date: 4-5 October 2021, New York. Virtual Conference; 146th Annual Meeting of the American Neurological Association; Date: 17-19 October 2021, New Jersey. Virtual Conference. EUROTAU; Date: 25-26 October, 2021. Lille, France….Asceneuron's most clinically advanced program ASN120290, an O-GlcNAcase inhibitor, is being developed for the orphan tauopathic disease, progressive supranuclear palsy (PSP), and was granted Orphan Drug Designation by the US FDA for the treatment of Progressive Supranuclear Palsy (PSP).”

Clinical data • CNS Disorders • Progressive Supranuclear Palsy

PET Imaging Demonstrates Quantitative Enzyme Occupancy of the O-Glcnacase Inhibitor ASN120290 in Human Brain (AAIC 2019) - No abstract available.