CogniPD+: Advancing a First-in-Class Therapy for Parkinson’s Disease Dementia
CogniPD+ is a pre-clinical project developing N1(4)inh-IL, a selective Nox1/4 inhibitor for intranasal brain delivery targeting cognitive decline in Parkinson’s Disease.
Unmet Clinical Need
Parkinson’s Disease Dementia (PDD) is a severe and progressive neurodegenerative condition affecting approximately 30% of Parkinson’s patients, which significantly impairs memory, executive function, and patient autonomy. Despite its enormous burden on patients and caregivers, there are currently no approved therapies capable of modifying disease progression.
Oxidative Stress & Nox1/Nox4
Neurodegeneration in PDD is driven by oxidative stress linked to the NADPH oxidases Nox1 and Nox4, which are overexpressed in patients’ brains. Nox4, in particular, accumulates in the hippocampus and correlates with the build-up of α-synuclein, β-amyloid, and tau, which are key proteins associated with cognitive decline.
Failed Existing Approaches
The existing NOx inhibitors have failed to demonstrate efficacy in clinical practice due to their poor selectivity, low bioavailability, and significant toxicity. No compound targeting this pathway is currently in an advanced stage of clinical development for neurodegenerative diseases. This is the gap CogniPD+ addresses.
N1(4)inh-IL: A First-in-Class Nox1/Nox4 Inhibitor in Ionic Liquid Form
Ionic Liquid Formulation · Intranasal Brain Delivery
N1(4)inh-IL was developed at the University of Beira Interior (UBI – RISE Health) and is exclusively licensed to NeuroSoV (Fastprinciple, Lda). It selectively inhibits the Nox1 and Nox4 oxidase isoforms by blocking the oxidative cascade that drives dopaminergic neurodegeneration, neuroinflammation, mitochondrial dysfunction, and pathological protein aggregation.
The compound is formulated as an ionic liquid optimized for intranasal delivery, enabling efficient brain targeting and enhanced bioavailability.
This combination of molecular precision, innovative formulation, and targeted delivery route creates a profile with no direct equivalent in the current drug development landscape.
Differentiators in N1(4)inh-IL
First-in-Class Nox1/4 Inhibition
Novel mechanism for neurodegeneration with no current clinical competitors.
Intranasal Delivery to the Brain
Direct central nervous system (CNS) targeting, validated in preclinical studies.
Ionic Liquid Formulation
Enhanced stability, bioavailability, and translational potential.
Translational Preclinical Model
Development of new animal models for Parkinson’s Disease Dementia (PDD).
Regulatory Alignment
Strong scientific foundation aligned with EMA/FDA pathways.
Intellectual Property
Protected by international patent WO2023144742A1.
This integrated approach positions N1(4)inh-IL as a disruptive solution in the treatment of neurodegenerative diseases.
From Proof of Concept to Regulatory Readiness
CogniPD+ is currently at the preclinical stage (TRL 4–5) and aims to reach regulatory-ready (TRL 6–7) by the end of the project. The project builds on robust proof-of-concept data from the predecessor project PDSolve (PT2020), including in vivo prevention of motor dysfunction in rodent models of PD, preliminary pharmacokinetics, safety, and blood–brain barrier validation.
The next milestone is regulatory preparation for IND/CTA submission and entry into clinical trials, closing the critical gap towards translation.
Five Interconnected Activities Over 36 Months
CogniPD+ is a 36-month R&D structured around five interconnected activities:
Activity 1 — DMPK and Regulatory Studies (ADME, Toxicology, GMP Production)
We will generate a complete ADME/toxicology package of tests (in vitro and in vivo) aligned with EMA and FDA requirements. In parallel, we will establish a GMP manufacturing process for N1(4)inh-IL in partnership with a certified international CRO (WuXi AppTec or Eurofins). The outputs of this activity form the core regulatory dossier for future IND/CTA submission.
Activity 2 — Evaluation of the Cognitive Effectiveness of N1(4)inh-IL in the PFF Model of Dementia
Using a PFF model, we will evaluate whether N1(4)inh-IL can prevent cognitive decline when delivered via the intranasal route. Animals will be assessed at 2, 3, and 6 months using established behavioural tests (novel object recognition, Barnes maze, elevated plus maze and beam walk balance) and comprehensive neuropathological analyses (α-synuclein, tau, amyloid-beta, tyrosine hydroxylase, dopamine).
Activity 3 — Development of a New Paraquat-Induced Translational PDD Model
We will develop and validate a novel animal model of PDD based on chronic paraquat exposure, a herbicide with known links to Parkinson’s disease in humans. The model will be characterized longitudinally through the evaluation of behavioral, neurochemical, and histopathological markers, enabling its future use as a research tool or specialized service for pharmaceutical companies and CROs.
Activity 4 — Dissemination, Communication, and Result’s Valorization
This activity covers scientific communication, dissemination, valorization, and industry engagement, promoting project results within the health innovation ecosystem through digital visibility, publications, conferences, and outreach materials. It also includes stakeholder mapping, market value assessment, and intellectual and industrial property support, with value creation activities supported by Ambiom, a company specialised in technology scouting and economic evaluation of biomedical assets.
Activity 5 — Project Management (Scientific, Technical and Administrative)
Led by NeuroSoV (Fastprinciple, Lda) in collaboration with UBI, the project ensures efficient coordination through an integrated management system covering governance, timeline, reporting, and FAIR-aligned data management, supported by regular project management meetings, intellectual property and risk oversight, and involvement of a research fellow in science, entrepreneurship, and innovation management.
Complementary Competencies Across All Dimensions of Drug Development
CogniPD+ is led by NeuroSoV (Fastprinciple, Lda), in co-promotion with the University of Beira Interior (UBI – RISE-Health). The project team integrates complementary competencies across all dimensions of drug development — from basic science to clinical strategy and market access.
Fastprinciple
Ana Clara Cristóvão
CSO & PINeurodegenerative disease researcher with deep expertise in Parkinson’s disease, NADPH oxidase biology and preclinical model development. Leads the company’s scientific vision, ensuring coordination between academic and industry partners. Coordinates teams, supervises doctoral students, and maintains active international collaborations.
Dina Pereira
CEOInnovation project management specialist and executive director of UBImedical. Leads business development, international partnerships and operational management.
Ricardo Pacheco
CMOPhysician with an MBA who has held positions at multinational companies such as Novartis, Roche, and AstraZeneca. Leads the company’s clinical and regulatory strategy and ensures alignment with market requirements and industry stakeholders.
João Leitão
CFOProfessor of Economy and specialist in finance, sustainability, and entrepreneurship. Ensures the project’s economic and financial viability, as well as its value-creation strategy.
UBI (RISE-Health)
Gilberto Alves
Pharmaceutical SciencesProfessor of Pharmaceutical Sciences, specialist in pharmacokinetics and metabolism (ADME), with extensive experience in regulatory preclinical studies.
Samuel Silvestre
Pharmaceutical SciencesProfessor of Pharmaceutical Sciences, responsible for providing support in medicinal chemistry and for the analysis and validation of the stability and reactivity of the N1(4)inh-IL formulation.
Luís Passarinha
BiomedicineProfessor of Biomedicine, specialist in biochemistry and chromatographic techniques, with experience in quantifying neurotransmitters in animal models, will be responsible for assisting with the quantification of dopamine and its metabolites using HPLC.
External Consultants & Partners
Mara Freire
CICECO, University of AveiroInternational expert in ionic liquid chemistry. Advises on formulation design and optimisation.
Marcelo Mendonça
Champalimaud FoundationClinical neurologist. Ensures clinical relevance of endpoints and supports regulatory and clinical translation strategy.
Yoon-Seong Kim
Rutgers University, USAProfessor of Neurology and specialist in Parkinson’s molecular mechanisms. Supports translational model validation.
Ambiom
Life Science Commercial AdvisoryAssist in stakeholder mapping, market positioning and economic valorization of the N1(4)inh-IL by supporting the development of a robust strategy for clinical transition and fundraising.
Doctoral Researchers
Mariana Fiadeiro
Senior PhD ResearcherSenior PhD researcher with experience in Parkinson’s models. Active across Activities 2 and 3.
Ana Alexandra Silva
PhD ResearcherPhD researcher contributing to in vivo testing and biochemical analysis.
Rita Curto
PhD ResearcherPhD researcher leading experimental execution in Activity 2, under supervision of Dr. Ana Clara Cristóvão.
Building the Path to Clinical Translation
By the end of CogniPD+ (September 2028), NeuroSoV (Fastprinciple, Lda) will hold a complete preclinical regulatory dossier—including DMPK, GMP batch production, and cognitive and neuropathological efficacy data—positioning N1(4)inh-IL for IND/CTA submission and Phase I entry (estimated 2029–2030).
With this solid preclinical foundation, we are actively engaging pharmaceutical and biotech companies, as well as institutional investors, to explore co-development, licensing, and out-licensing opportunities. Initial discussions with pharmas have already begun, strengthening the path towards strategic partnerships and clinical translation.
Licensing Opportunity — N1(4)inh-IL
- First-in-class mechanism (selective Nox1/Nox4 inhibition)
- Innovative pharmaceutical ionic liquid formulation
- Intranasal CNS delivery (proven blood–brain barrier penetration)
- Patent protected internationally (PCT WO2023144742A1)
- TRL 6–7 by end of 2028
- Phase I entry estimated 2029–2030
Secondary Opportunity — PDD Animal Model
- Novel paraquat-induced PDD animal model
- Offered as a specialised preclinical service from 2028/29
- Designed for evaluating cognitive therapies
- Target users: pharmaceutical companies and CROs
We Welcome Engagement With
We welcome engagement with pharmaceutical companies in neuroscience, biotech companies in CNS and neurodegeneration, venture capital and corporate VC, innovation funding bodies (e.g. EIC Accelerator), and strategic co-development partners.
For scientific collaboration enquiries, partnership and licensing discussions, or media and press requests, please contact the CogniPD+ project team.