Pre-clinical validation and demonstration of PeptiCHIP: an immunopurification microfluidic device and software for (neo)antigen identification and prioritization

Project Information

PeptiCHIP

Grant agreement ID: 101112948

DOI

10.3030/101112948

Project closed

EC signature date 13 March 2023

Start date 1 April 2023

End date 30 September 2025

Funded under

• The European Innovation Council (EIC)

Total cost

€ 2 226 280,00

EU contribution

€ 2 226 280,00

Coordinated by

VALO THERAPEUTICS OY
Finland

Periodic Reporting for period 2 - PeptiCHIP (Pre-clinical validation and demonstration of PeptiCHIP: an immunopurification microfluidic device and software for (neo)antigen identification and prioritization)

Reporting period: 2024-04-01 to 2025-09-30

Summary of the context and overall objectives of the project

Clinical translation of cancer immunotherapies remains very challenging since 60-80% of patients fail to respond. The core of immunotherapy stands in identifying tumour-specific fingerprints – the neoantigens – that are peptides expressed uniquely by cancer cells, capable of triggering an efficient immune response against cancer. Currently, there is no standard method to identify neoantigens and the few methods available have significant limitations by being quite long, complicated and resource demanding in terms of knowledge, expertise, laboratory equipment and consumables. This limits their availability to a few well-equipped laboratories, hindering the broader application of personalized cancer immunotherapies that require efficient, sample-conserving, and cost-effective antigen identification technologies.

Valo Therapeutics (ValoTx) addresses this critical gap with PeptiCHIP, an innovative platform integrating a microfluidic pre-analytical immunoaffinity purification device with mass spectrometry analysis and antigen prioritization software. This technology revolutionizes antigen profiling by allowing the identification of relevant antigens without prior knowledge of their sequences, applicable to cancer, autoimmune, inflammatory, and infectious diseases. PeptiCHIP simplifies the process significantly, delivering rapid, accurate results with minimal sample usage and reduced costs.

PeptiCHIP is set to transform the clinical development of immunotherapies by offering a more precise and efficient method for neoantigen identification. This is crucial for developing therapies that precisely target the unique aspects of each patient’s tumour, enhancing the success rates of immunotherapy treatments. By addressing these technological limitations, PeptiCHIP will empower immunotherapy companies, clinicians, and researchers with more meaningful and cost-effective neoantigen identification, supporting the personalized medical treatment landscape in oncology, as well as infectious, inflammatory, and autoimmune diseases. This innovation stands to enhance the application of immunotherapies by ensuring more patients can benefit from tailored, effective treatment protocols, potentially improving outcomes in the challenging field of cancer treatment and beyond.

PeptiCHIP has the potential to overcome these hurdles in the clinical translation of personalized cancer immunotherapies and further facilitate development of novel neoantigen-based immunotherapies. During the project, the device and software were developed to provide valuable tools for basic and pre-clinical research on the immunopeptidome, which is a critical component for understanding the immune system as a whole. The EIC Transition project PeptiCHIP (4/2023-9/2025) focused on further technology development, testing, pre-clinical validation, and demonstration activities, maturing PeptiCHIP to TRL 6 together with an extensive business plan for efficient scale-up manufacturing and market entry.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

During the the Transition project, the PeptiCHIP microchip designs and protocols were optimized to confer very high sensitivity and robustness, introducing advancing elements of automation to further speed up and simplify sample processing for mass spectrometry analysis. Manufacturing was set up to supply validation and demonstration needs, and novel versions of the device were developed to cover immunopeptidomics user needs (e.g. human HLA-I and HLA-II). The complete in-house workflow was extensively validated and demonstrated using numerous cell lines and human samples, providing evidence of market-leading sensitivity with optimal peptide length distribution profiles. High-performance computing elements were introduced to allow near real-time analysis together with ultrasensitive LC-MS/MS. The PeptiCHIP software’s proprietary antigen prioritisation algorithms were improved with additional features, recoded and benchmarked against several other tools, ranking #1 for antigen prioritisation for in vitro immunogenicity assays. User needs were mapped using Design Thinking methods and the product-market fit was evaluated as part of the business planning, demonstrating that PeptiCHIP effectively addresses significant unmet needs and validating many of its unique selling points foreseen in the proposal through demo showcases and “stress-testing” with top academic groups and several large biopharma. PeptiCHIP was featured at key events. Academic and industrial collaborations were started to support PeptiCHIP’s further development and advance cancer research. The technology was granted several patents in main markets. Regulatory path-to-market analysis was conducted to outline the roadmap to market launch.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

Traditional methods, such as ligandome analysis, require large tissue samples and are often unsuitable for clinical samples, while predictive models based on genomic data fall short in accuracy. PeptiCHIP overcomes these obstacles, providing a valuable tool for both discovery and validation of target antigens, facilitating the advancement of new treatments for a range of diseases. PeptiCHIP already outperforms both the academic proof-of-concept (PoC) and state-of-the-art (SotA); validation of the new design has evidenced very high sensitivity, robustness, and significantly lower cost-of-goods-sold and hands-on time than any other published method for direct antigen identification using immunopeptidomics. PeptiCHIP is currently laboratory validated for 1000 cells, which represents a 1000-fold sensitivity improvement to PoC and >50 000-fold to traditional SotA, providing consistently more antigen identifications per run and higher numbers of unique antigens identified. The ultrasensitive workflow is operational, demonstrated in relevant environments (TRL6) and can be completed in less than 7 hours from sample to result. Additional automation has been introduced to further increase throughput and robustness.

PeptiCHIP workflow simplified