Cerebral dopamine neurotrophic factor (CDNF) / Herantis - LARVOL DELTA

High-capacity microfluidic compartmentalized cell cultures for studying axonal regrowth in sporadic ALS iPSC-derived motor neurons (Neuroscience 2025) - "In addition, the cell compatibility of the plate has been tested with several primary and iPSC-derived neuronal cultures.As an example of the utility of the co-culture plate, it was used to evaluate the effects of HER-096, a peptide drug developed based on the active site of cerebral dopamine neurotrophic factor (CDNF), on axonal regrowth post-axotomy in motor neuron cultures derived from sporadic ALS iPSCs. doi: 10.1021/acschemneuro.3c00409. PMID: 38150531; PMCID: PMC10797611."

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

GRP78 INTERACTION MEDIATES THE NEUROPROTECTIVE EFFECTS OF CDNF AND HER -096 (ADPD 2025) - "HER-096 is a brain -penetrating peptidomimetic derived from the active site of human CDNF protein and is developed as a disease -modifying treatment for Parkinson's disease. UPR pathway is a key mediator of the neuroprotective activity of C -CDNF where interaction with GRP78 plays a central role. HER -096 is designed based on the GRP78 -binding interface and mimics the cytoprotective effects of CDNF."

CNS Disorders • Movement Disorders • Parkinson's Disease • HSPA5

Neurotrophic factors for Parkinson's disease: Current status, progress, and remaining questions. Conclusions from a 2023 workshop. (PubMed, J Parkinsons Dis) - "This was a follow up to a previous meeting held in 2019.1 This 2023 workshop reviewed new relevant data that has emerged in the intervening 4 years around the development of new GFs and better models for studying them including the merit of combining treatments as well as therapies that can be modulated. We also discussed new insights into GF delivery and trial design that have emerged from the analyses of completed GDNF trials, including the patient voice, as well as the recently completed CDNF trial.2 We then concluded with our recommendations on how GF studies in PD should develop going forward."

Journal • Review • CNS Disorders • Gene Therapies • Movement Disorders • Parkinson's Disease

Structural basis of CDNF interaction with the UPR regulator GRP78. (PubMed, Nat Commun) - "Finally, mutating the key residues of CDNF mediating its interaction with GRP78 not only results in impaired binding of CDNF but also abolishes the neuroprotective activity of CDNF-derived peptides in mesencephalic neuron cultures. These results suggest that the molecular interaction with GRP78 mediates the neuroprotective actions of CDNF and provide a structural basis for development of next generation CDNF-based therapeutic compounds against neurodegenerative diseases."

Journal • CNS Disorders • Movement Disorders • Parkinson's Disease • HSPA5

EXPLORING THE MULTIPLE MECHANISMS UNDERLYING HER-096 NEUROPROTECTION AND REGENERATION (ADPD 2024) - "Aims: HER-096 is a brain-penetrating peptidomimetic derived from the active site of human CDNF protein and is developed as a disease-modifying treatment for Parkinson's disease. A multi-omics approach was employed to uncover the multimodal mechanism underlying the effects of HER-096 on functional recovery in chronic and acute degeneration. Our results suggest that HER-096 promotes functional recovery and regeneration of stressed neurons via multiple complementary ways."

CNS Disorders • Movement Disorders • Parkinson's Disease

A PHASE 1A FIRST-IN-HUMAN CLINICAL TRIAL OF HER-096, A SUBCUTANEOUSLY ADMINISTERED CDNF-DERIVED PEPTIDOMIMETIC (ADPD 2024) - "Preliminary assessments suggest a good safety profile for single ascending subcutaneous doses of HER-096. Full data analysis will be completed after database lock by November 2023 and the results will be reported in the AD/PD 2024 conference presentation."

Clinical • P1 data

HER-096 is a CDNF-derived brain-penetrating peptidomimetic that protects dopaminergic neurons in a mouse synucleinopathy model of Parkinson's disease. (PubMed, Cell Chem Biol) - "Subcutaneously administered HER-096 modulated UPR pathway activity, protected dopamine neurons, and reduced α-synuclein aggregates and neuroinflammation in substantia nigra of aged mice with synucleinopathy. Peptidomimetic HER-096 is a candidate for development of a disease-modifying therapy for Parkinson's disease with a patient-friendly route of administration."

Journal • Preclinical • CNS Disorders • Developmental Disorders • Inflammation • Movement Disorders • Parkinson's Disease

Inside information: Herantis Pharma received a waive-off for approximately EUR 4.5 million of the principal amount of the CDNF development loans granted by Business Finland (Herantis Pharma Press Release) - "Herantis Pharma Plc...announces today that Business Finland has reached the positive decision of waiving off EUR 4,495,649 of the principal amount of the loans granted by it to Herantis for the development of CDNF (Cerebral Dopamine Neurotrophic Factor)....The waive-off is subject to the fulfillment of one remaining payment by Herantis towards Business Finland by 31 October 2023 in the amount of approximately EUR 40 thousand....At the end of 2022, the company decided that CDNF will no longer to be developed. Based on this decision, the company applied for the waiving of the capital of CDNF-related loans from Business Finland."

Commercial • Discontinued • Alzheimer's Disease • Amyotrophic Lateral Sclerosis • CNS Disorders • Parkinson's Disease • Proteinopathy • Tauopathies And Synucleinopathies

Intraputamenal Cerebral Dopamine Neurotrophic Factor in Parkinson's Disease: A Randomized, Double-Blind, Multicenter Phase 1 Trial. (PubMed, Mov Disord) - "Intraputamenally administered CDNF was safe and well tolerated, and possible signs of biological response to the drug were observed in individual patients."

Clinical • Journal • P1 data • CNS Disorders • Movement Disorders • Parkinson's Disease

Augmenting hematoma-scavenging capacity of innate immune cells by CDNF reduces brain injury and promotes functional recovery after intracerebral hemorrhage. (PubMed, Cell Death Dis) - "Administration of rhCDNF results in upregulation of the Nrf2-HO-1 pathway, but alleviation of oxidative stress and unfolded protein responses in the perihematomal area. Finally, we demonstrate that intravenous delivery of rhCDNF has beneficial effects in an animal model of ICH and that systemic application promotes scavenging by the brain's myeloid cells for the treatment of ICH."

Immune cell • Journal • Cerebral Hemorrhage • CNS Disorders • Hematological Disorders • Immunology • Inflammation • Vascular Neurology • AVEN

HER-096 IS A NOVEL BRAIN-PENETRATING PEPTIDOMIMETIC THAT PROMOTES PROTEOSTASIS AND REDUCES NEUROINFLAMMATION IN AGED MOUSE MODEL OF SYNUCLEINOPATHY (ADPD 2023) - "Aims: To develop a next generat ion, brain -penetrating compound based on unconventional neurotrophic factor CDNF. Intraputamenal CDNF infusion has previously been tested in a Phase 1 study in moderately advanced Parkinson's disease (PD). A more patient -friendl y route of administration will support further development of a disease - modifying therapy for PD and allow access to earlier stage patients. We conclude that HER -096, a CDNF -derived peptidomimetic, is a novel candidate for disease -modification in Parkinson 's disease."

Preclinical • CNS Disorders • Developmental Disorders • Immunology • Inflammation • Movement Disorders • Parkinson's Disease • Targeted Protein Degradation

Herantis Marks A Successful 2021; An Ambitious and Promising 2022 Ahead to Advance Robust CNS Pipeline (Market Screener) - "Herantis Pharma Plc...gives a 2021 year end summary of the progress of the company and the plans for 2022....Successful completion of HER-096 non-clinical program to support the first-in-human study...Filing for regulatory approval to start a first-in-human study with HER-096...Defining the patient population for further clinical development...Confirmation of feasibility of rhCDNF brain distribution following intranasal spray administration"

New trial • Preclinical • CNS Disorders • Parkinson's Disease

Nanoform Interim Report January - September 2021 (PRNewswire) - "In February, Nanoform and Herantis Pharma Plc signed a Biologics Proof of Concept Agreement aiming to enhance nasal drug delivery to the brain of Herantis' CDNF therapies for Parkinson's disease using Nanoform's proprietary biological nanoparticle technology. As a result, Nanoform achieved its near-term business target of 'First Biologics PoC project signed in 2021'."

Commercial • CNS Disorders • Parkinson's Disease

Nanoform technology delivers successful results for Herantis CDNF drug candidate (PRNewswire) - "Nanoform Finland Plc...and Herantis Pharma Plc...announced that results from the Nanoform Proof of Concept (PoC) project show that the nanoforming process has been successfully applied to Herantis' rhCDNF drug candidate....The project includes nanoforming PoC studies to combine Herantis' intranasally administered CDNF therapy for Parkinson's disease with Nanoform's nanoparticle technology. The PoC project shows that the nanoforming process can be successfully applied to rhCDNF. Most importantly, during the nanoparticle formation process, rhCDNF protein remains stable, retaining its structure, function, efficacy and neuroprotective effects in line with CDNF controls...The project will move on to the next phase - a Proof of Process (PoP) study to further refine the size and shape of the nanoformed rhCDNF nanoparticles and evaluate biodistribution following intranasal delivery."

PK/PD data • Preclinical • CNS Disorders • Parkinson's Disease

"Nanoform technology delivers successful results for Herantis CDNF drug candidate https://t.co/ohlpHwbR0d" (@CisionNews)

"Herantis Pharma Announces xCDNF Preclinical Candidate Selection https://t.co/IvnTdi5pXF" (@CisionNews)

Preclinical

Cerebral Dopamine Neurotrophic Factor Reduces α-Synuclein Aggregation and Propagation and Alleviates Behavioural Alterations in vivo. (PubMed, Mol Ther) - "CDNF's beneficial effects on rodent behaviour appear not to be related to amount of inclusions formed in the current context and further study of its effects on the aggregation mechanism in vivo are needed. Nonetheless, the interaction of CDNF with α-synuclein, modifying its aggregation, spreading, and associated behavioural alterations, provide novel insights into the potential of CDNF as a therapeutic strategy in PD and other synucleinopathies."

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

"#HerantisPharma to focus on #CDNF and #xCDNF programs https://t.co/jPJn37kDRR" (@1stOncology)

"Herantis Pharma to focus on CDNF and xCDNF programs https://t.co/bPqLImSTFk" (@CisionNews)

Long-Term Follow-up Safety After DDS Implantation With/Without CDNF Infusions (clinicaltrials.gov) - P1/2; N=15; Active, not recruiting; Sponsor: Renishaw; Enrolling by invitation ➔ Active, not recruiting

Clinical • Enrollment closed • CNS Disorders • Movement Disorders • Parkinson's Disease

[VIRTUAL] PHASE I-II FIRST-IN-MAN CLINICAL TRIAL OF INTRAPUTAMENAL CDNF IN PARKINSON’S DISEASE: EXPLORATORY FLUID-BASED BIOMARKER ENDPOINTS OF THE 12-MONTH TREATMENT PERIOD (ADPD 2021) - "The results from these exploratory CSF analyses are expected to provide further insight into the biological responses to intraputamenal CDNF infusions in PD patients."

Biomarker • Clinical • P1/2 data • CNS Disorders • Movement Disorders • Parkinson's Disease • CCL2 • IL10 • IL1B • IL6 • TNFA

Nanoform and Herantis partner to look for opportunities to enhance BBB penetration of CDNF and xCDNF molecules (PRNewswire) - "Nanoform Finland Plc...and Herantis Pharma Plc...today announced that they have signed a letter of intent to collaborate to seek to enhance nasal drug delivery to the brain of Herantis' CDNF and xCDNF therapies (Parkinson's disease) using Nanoform's proprietary biological nanoparticle technology. The planned and non-exclusive collaboration is intended to assess the utility of Nanoform's latest platform technology for biologic drugs....Nanoform will in this partnership carry out, for compensation on standard commercial terms, two Proof of Concept studies on Herantis' CDNF and xCDNF molecules...Nanoform is committed to supporting Herantis in the development of these programs and has undertaken to invest...1,600,000 euros in a planned immediate directed share issue by Herantis."

Licensing / partnership • CNS Disorders • Parkinson's Disease

"Nanoform and Herantis partner to look for opportunities to enhance BBB penetration of CDNF and xCDNF molecules https://t.co/rc36wpGW7E" (@CisionNews)

Herantis Pharma Announces R&D Update (Herantis Pharma Press Release) - "Herantis has decided to evaluate...using alternative administration methods....Herantis will build on the current research data and knowledge attained from the Phase I/II study and purpose the drug for alternative available administration options such as via subcutaneous injection or intranasal application....The company continues to progress on track for final xCDNF lead selection early in 2021."

Preclinical • CNS Disorders • Parkinson's Disease

Herantis Pharma to Host a Webinar on the Cerebral Dopamine Neurotrophic Factor (CDNF) Phase I-II Data Readout (Herantis Pharma Press Release) - "Herantis Pharma Plc...will be hosting a webinar to share more details on CDNF Phase I-II Study Met Primary Endpoints of Safety and Tolerability at 12 months..."

P1/2 data • Alzheimer's Disease • CNS Disorders • Parkinson's Disease