Parkinson’s disease (PD) is a progressive neurodegenerative disorder affecting millions worldwide. Current treatments primarily manage symptoms but do not halt disease progression. PD is the second most common neurodegenerative disease after Alzheimer’s disease. The incidence of PD increases with age, but it is estimated that approximately 4% of people with PD are diagnosed before age 50. Worldwide, more than 10 million people have been diagnosed with PD. With an increasing number of diagnosed patients and the high societal burden of PD, there is a pressing need for novel therapeutic approaches.[1]
Herantis Pharma has developed HER-096, a small synthetic peptidomimetic molecule designed to cross the blood-brain barrier efficiently and offer disease-modifying potential. Quinta-Analytica played a crucial role in the analytical validation necessary for its development, contributing to its journey from preclinical research to human clinical trials.
HER-096 is a promising candidate for Parkinson’s disease treatment. It is based on the active site of the Cerebral Dopamine Neurotrophic Factor (CDNF) protein, combining its mechanism of action with the convenience of subcutaneous administration.
To advance HER-096 into clinical trials, Herantis Pharma needed an analytical partner capable of developing a GLP-compliant method within a reasonable timeline while addressing complex analytical challenges. Quinta-Analytica was selected due to its deep scientific expertise, proactive problem-solving approach, and transparent, client-focused collaboration.
According to Natalia Kulesskaya, Head of Nonclinical Pharmacology of Herantis Pharma:
The communication with the analytical team was highly effective, with a strong focus on understanding the compound’s specifics and the project’s needs. Their deep expertise in analytical techniques and GLP requirements enabled the development of reliable methods and ensured high-quality analytical support. Moreover, it was very useful to have a chance to communicate directly with scientific team during method development. It allowed us to effectively combine our knowledge about the compound and Quinta’s expertise in analytical approaches for overcoming practical challenges related to method development
Establishing Robust ADA Detection Methods
Herantis had conducted a 30-day GLP toxicology study with daily subcutaneous dosing of HER-096 with several doses. The goal of this study was to develop and validate a method for detecting anti-drug antibodies (ADA) in rat plasma using ELISA and MSD to analyze these GLP-tox samples.
The development of the methods required a customized approach due to the small molecular weight of HER-096 (approx. 1000 Da), which limited the applicability of conventional assay coating strategies. One of the early solutions involved conjugating the molecule to bovine serum albumin (BSA, approx. 66 kDa) to increase its size and improve assay performance. Although this approach initially showed promise, batch-to-batch variability of BSA led the team to pursue alternative strategies. Ultimately, a biotin-labelled HER-096 format was adopted, enabling successful method validation under GLP conditions.
The validation process was supported by intensive laboratory work to ensure robustness and timely delivery within the project’s ambitious timeline.
In summary, the development phase of the assay lasted six months, followed by a one-and-a-half-month validation period. The study lasted approximately two weeks, during which 160 rat samples were analyzed in the screening test, 121 of which were potentially positive for the presence of anti-drug antibodies against HER-096. These were subsequently analyzed in the confirmatory test, which revealed that all samples were negative. As a result, the study concluded that no anti-HER-096 antibodies were detected. This outcome demonstrated a very low immunogenicity of the HER peptide in the respective animal model, further indicating low immunogenicity in humans.
Translating Insights to Canine Plasma Analysis
Following the successful adaptation of ADA detection methods in rat plasma, a similar validation process under GLP conditions was planned for canine plasma to further support preclinical data. However, even with leveraging prior findings, some optimization needs remained, particularly regarding background signal levels and sensitivity in negative control canine plasma samples.
Various strategies were tested, including different blocking agents, alternative detection techniques, multiple batches of Biot-HER, different plate types, and specialized purification methods (e.g. active carbon purification or Zeba columns). Ultimately, the method showed optimal performance in assay buffer, while signal variability in the native matrix indicated that further refinement would be needed for full GLP compliance. Therefore, a non-GLP verification study was strategically conducted to generate reliable immunogenicity data within the given timeline, achieving all necessary acceptance criteria including Screening Cut Point, Critical Control Points, and System Suitability Test.
The assay development took five months, and the non-GLP study lasted two weeks, including measurement of samples in the screening assay followed by confirmatory testing of positive samples. Out of 64 analyzed samples, 4 were confirmed positive, suggesting low immunogenicity in the canine model. Accordingly, a low immunogenicity of the HER-096 peptide can be expected in humans.
Mária Dujčíková, ADA specialist reponsible for the HER-096 project
The Impact of This Research on Parkinson’s Disease Treatment
The analytical work conducted by Quinta-Analytica is part of Herantis’ preclinical safety data package for HER-096 used for applying clinical trial authorizations within EU for HER-096:
- Phase 1a clinical trial, completed in 2023 demonstrating that single subcutaneous doses of HER-096 are safe and well-tolerated in healthy volunteers. In addition, the study demonstrated efficacious brain penetration of HER-096.
- The ongoing Phase 1b trial aims at establishing the safety of repeated dosing of HER-096 and identifying novel treatment-response biomarkers in Parkinson’s patients.
Currently, additional PK measurements are underway at Quinta-Analytica, focusing on rat plasma and cerebrospinal fluid. These ongoing investigations will further support the understanding of HER-096’s pharmacokinetics and its potential clinical applications. Herantis and Quinta-Analytica are also discussing about potential future collaboration with patient samples.
Natalia Kulesskaya, Head of Nonclinical Pharmacology of Herantis Pharma, affirms:
We would recommend Quinta-Analytica for their high level of scientific and technical expertise in analytical methods, transparent and client-oriented communication, and deep understanding of regulatory and GLP requirements.
A Partnership Driving Innovation in Neuroscience
The collaboration between Herantis Pharma and Quinta-Analytica exemplifies the critical role of expert analytical support in advancing groundbreaking therapeutics. By addressing complex analytical challenges and ensuring high-quality data generation, Quinta-Analytica has been proud to contribute to the progression of HER-096 toward clinical application.
Milan Maděra, Head of the Biologics Department at Quinta-Analytica, sums it up perfectly:
Working with Herantis Pharma has been an absolute pleasure. From the first meeting, we had open and constructive communication, and whole Herantis team were always there to support our biologics team. It was true teamwork, despite the distance of 1400 km between us. To work with such a professional and engaged team is simply enjoyable.
This collaboration has been instrumental in advancing the development of HER-096 and its potential to reshape Parkinson’s disease treatment. As research progresses, the partnership between Herantis Pharma and Quinta-Analytica continues to play a significant role in driving innovation and moving closer to a potential breakthrough in Parkinson’s disease therapy.
Roman Grunt, CEO Quinta-Analytica (left) and Antti Vuolanto, CEO, Herantis Pharma (right)
Herantis Pharma Plc is a clinical-stage biotechnology company focused on developing disease-modifying therapies for Parkinson’s disease. The company has a strong scientific foundation, supported by a representative collection of publications related to the research behind its drug candidates. Their lead product, HER-096, is an advanced small synthetic peptidomimetic molecule based on the active site of the CDNF protein.
Herantis has been publicly traded on the Nasdaq First North Growth Market Finland under the ticker symbol HRTIS since 2014 and receives financial support from The Michael J. Fox Foundation for Parkinson’s Research (MJFF) and Parkinson’s UK.
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