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Navignostics Using Single-Cell Spatial Proteomics to Guide Oncology Treatment, Drug Development

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NEW YORK – Swiss startup Navignostics is looking to use single-cell spatial proteomics data to support oncology drug development efforts and guide cancer treatments.

The company, a spinout from the lab of Bernd Bodenmiller, a professor at the University of Zurich and ETH Zurich, announced earlier this month that it had raised CHF 7.5 million ($7.6 million) in seed funding to support these efforts.

Launched in April, Navignostics uses Standard BioTools' (formerly Fluidigm) Hyperion imaging mass cytometry system for its work. The system enables simultaneous imaging of up to 40 protein markers at single-cell resolution, allowing researchers to collect protein expression data and spatial information on a sample at the same time.

Bodenmiller, who is a cofounder of Navignostics, has published research that was key to the development of the Hyperion platform, including a 2014 study in Nature Methods in which he and his ETH Zurich colleague Detlef Günther coupled a laser ablation cell to a CyTOF instrument and used it to simultaneously image 32 different proteins in breast cancer cells at subcellular resolution.

Bodenmiller's lab also developed the histoCAT cytometry imaging software package that Standard BioTools sells for analysis of Hyperion data.

Jana Fischer, Navignostics' cofounder and CEO, described the company as emerging from ongoing developments in Bodenmiller's lab that had pushed its proteomic imaging work closer to clinical applications.

"We have been wanting to bring our approaches closer to the clinic, closer to the actual benefit of patients," she said. "And step by step, these ideas started to solidify."

In September, Navignostics received a CHF 1 million convertible loan from the UZH Life Sciences Fund. The recent seed funding round was led by mass spectrometry firm Bruker, which was joined by Think.Health Ventures, Ventura Biomed Investors, and Zürcher Kantonalbank.

Fischer said the company is currently pursuing a two-track strategy. On the one hand, it is focused on establishing collaborations with pharma companies to aid in clinical trial work and drug development; on the other hand, it is developing its own in-house diagnostic products, for example for guiding cancer immunotherapy.

With regard to its pharma work, Fischer said Navignostics believes its platform could be useful for applications like exploring the modes of action of drug candidates as well as identifying likely responders to therapy for clinical trials. Ultimately, she said, the company aims to develop companion diagnostics based on its single-cell data.

Fischer said Navignostics has not yet signed any pharma collaboration deals but that it is currently involved in pilot projects with three potential, unnamed collaborators.

Navignostics' internal diagnostics work is focused primarily on developing tests for helping guide immunotherapy treatment in patients with solid tumors, Fischer said.

"This is where we see that we can add the most value, because there are very limited diagnostics available to help identify the specific immunotherapy approach that will be best for a patient," she said.

Fischer said the company envisions offering these tests as a service out of its laboratory, analogizing the process to that for laboratory-developed tests in the US. She acknowledged that the relative novelty of spatial proteomics as a clinical tool presented challenges from a regulatory perspective.

"There is a lot of work in front of us in terms of developing [a] product with respect to the required regulatory standards because it’s a bit of a new territory," she said. "There are no fixed guidelines on how exactly to develop a highly multiplexed imaging technology into a [clinical] test."

Spatial proteomics has become a highly active market in recent years, with a number of companies entering both the tools and data analysis sides of the space. On the tools side, companies including Ionpath, Lunaphore, NanoString Technologies, and NeoGenomics all compete with Standard BioTools in offering platforms for highly multiplexed spatial proteomics. The data analysis and diagnostics development side is somewhat less crowded, with much of this activity still taking place in academia, though firms like Ozette, a spinout from the Fred Hutchinson Cancer Research Center and the Allen Institute for Artificial Intelligence (AI2), as well as Immunai, have announced intentions to pursue such applications.

Fischer said she expects the Navignostics team's experience running Hyperion workflows as well as its expertise analyzing data produced on the instrument to help set it apart from others in the field. She said the company would also benefit from relationships the Bodenmiller lab has established with clinicians throughout Switzerland as part of its research.

"We have already had the opportunity to demonstrate some of these approaches to clinicians and have them evaluate which are most useful or what type of data would be most useful to inform their treatment decisions," she said.

In 2020, Bodenmiller's lab published a study in Nature (on which Fischer was a lead author) in which the researchers used the Hyperion platform to measure 35 markers in tumor tissue samples from roughly 350 breast cancer patients, identifying 18 pathological subgroups and associating them with clinical outcomes. His lab has also published recent papers using imaging mass cytometry to study immunotherapy response in melanoma and for three-dimensional mapping of tumor tissue and the tumor microenvironment.

Fischer said Navignostics plans to use the Hyperion system for the time being but that it might in the future consider using data from other spatial proteomic and omics platforms. The last year has seen several advances in spatial proteomics technologies, with Marlborough, Massachusetts-based Akoya presenting data in April showing that its PhenoCycler-Fusion System can now analyze panels as large as 100 proteins at single-cell resolution, up from a previous capacity of around 40 proteins. Also in April, Bruker, the lead investor in Navignostics' seed round, presented a new workflow using MALDI mass spectrometry to measure peptide-linked antibodies in tissue samples. The company said this workflow would allow researchers to measure more than 100 proteins per sample and more quickly than existing technologies, though not at subcellular resolution.

Additionally, this year, Standard BioTools launched a new version of the Hyperion, the Hyperion+, which the company said offers a 1.6-fold lower limit of detection than the previous system, along with the ability to process 100-plus samples per week — double the throughput of the original Hyperion system.