NEW YORK – Neurology testing firm C2N Diagnostics is developing a fully automated mass spectrometry platform to facilitate decentralized use of assays including its Precivity blood tests for Alzheimer's disease.
C2N CEO Joel Braunstein said the decision to produce its own mass spec system was driven by factors including the US Food and Drug Administration's increased oversight of laboratory-developed tests and the company's desire to provide itself and its lab partners with standardized, streamlined tools for running its tests.
Last week, the company announced it has received an investment of up to $7.0 million from the Alzheimer's Drug Discovery Foundation's Diagnostics Accelerator initiative to support its mass spec development efforts. Braunstein said the system will be a C2N-branded instrument produced by a third-party original equipment manufacturer (OEM), though he declined to name the manufacturer. He added that it will be a true sample-to-answer instrument, with all steps of the sample prep, mass spec, and data reporting processes fully automated. The company expects to have a first-generation system in hand in the first half of 2025.
For a small diagnostics firm like C2N, producing this sort of mass spec platform is an ambitious undertaking. Mass spectrometry is widely used in clinical laboratories, but clinical assay development and implementation are typically complex and require highly trained personnel. This has led some large mass spec vendors to develop simpler, more automated clinical platforms, but these systems have struggled commercially. Danaher’s Sciex discontinued its clinical platform, the Topaz, in 2020 due to poor sales. Thermo Fisher Scientific discontinued its sample-to-answer instrument, the Cascadion, in 2022 for the same reason.
Diagnostics giant Roche has its own clinical mass spec program and plans to launch a fully automated mass spec analyzer, the Cobas i601, this year in markets that accept the CE mark and in the US in 2025.
While C2N is significantly smaller than these firms, its mass spec development plans are, in some ways, even more challenging. The efforts from Sciex, Thermo Fisher, and Roche have focused on triple quadrupole-based devices — which are well established as clinical tools. C2N, on the other hand, plans to develop a high-resolution mass spec system, a technology that is far less common in clinical settings.
Adding to the challenge is the fact that C2N is targeting proteins with its tests (primarily forms of tau and amyloid beta). While mass spec is used for certain clinical protein measurements, it is more commonly used for small molecule-based tests. The Sciex, Thermo Fisher, and Roche systems all focused or plan to focus on small molecule assays. Additionally, the proteins targeted by C2N's tests are present in blood at low concentrations, requiring highly sensitive assays to detect and quantify them reliably. C2N uses upfront immunoenrichment of target analytes to boost the sensitivity of its assays, which adds a layer of complexity to the process.
Leigh Anderson, CEO of clinical proteomics firm SISCAPA Assay Technologies, which similarly develops immunoenrichment mass spec assays to protein targets, said that an instrument like that proposed by C2N would be "a step forward," but he raised questions about its development and commercial viability.
A key question for Anderson is the experience and expertise of the OEM C2N is using to produce the device.
"Are they OEMing this from a recognized mass spec instrument company or from somebody who is newer to the game?" he asked.
Another issue Anderson raised — one that confounded Thermo Fisher's Cascadion effort — is the fact that labs are often reluctant to purchase instruments with limited test menus.
"A limited-menu instrument is a tough sell," he said.
C2N's Braunstein acknowledged these challenges, but said the company is well along in its development process.
"C2N has been working on elements of this plan for years now," he said. "This is not an overnight 'Eureka!' concept."
"From our experience developing the Precivity tests and offering testing through our [CLIA] lab, we understand these assays extremely well and understand the essential components that should become part of the kit … and we know the specifications for a mass spectrometer that will allow us to get the kind of reliability that we are currently experiencing."
Braunstein did not provide detail on the system's planned specifications, but in a recent validation study of the company's PrecivityAD2 test, C2N researchers used Thermo Fisher's Fusion Lumos Tribrid instrument. This instrument was released almost a decade ago, indicating that the company will not necessarily need cutting-edge mass spec technology for its system and assays to work.
Braunstein said C2N chose to develop its own automated mass spec system to streamline its own internal testing workflows and to better enable decentralized, distributed testing both in the US and globally.
"As demand for what we do grows and the clinical testing volumes increase, we see value in standardization, in having this end-to-end platform," he said. "We see this standardization as a way for [outside] labs to get quickly trained and also for us to have a clear window into what is happening inside that lab."
Regulatory concerns, particularly around the FDA’s final rule on laboratory-developed tests, also played into C2N's decision to develop the platform.
"At least within the US, there is an intensifying focus on regulation of LDTs," Braunstein said. "And so you can begin to see the advantages of having a regulatory-compliant LC-MS system. Because once you register an instrument as a Class I device, you can now start adding Class II IVDs on that platform with markedly improved efficiency and greater ease."
Blood-based Alzheimer's testing is still in its early stages, but the market for blood-based assays is potentially a large one, especially if such tests become commonly used for diagnosing the disease and qualifying patients for treatments with anti-amyloid therapies. C2N currently offers its PrecivityAD and PrecivityAD2 tests through its CLIA lab. It has received FDA breakthrough device designation for the PrecivityAD test. C2N also recently inked a deal with Unilabs to offer the tests in Europe and other geographies as well as a deal with Mediford Corporation to offer them in Japan. Additionally, it has a nonexclusive agreement with Mayo Clinic Laboratories to include the Precivity tests in its test menus.
But while blood-based Alzheimer's testing is a rapidly growing space, it is also becoming a crowded one. In addition to C2N, Quest Diagnostics, Laboratory Corporation of America, and Quanterix have blood-based tests for the disease on the market. Roche and Beckman Coulter have announced plans to develop blood-based Alzheimer's test, while, in September, Fujirebio Diagnostics filed its Lumipulse G pTau 217/β-Amyloid 1-42 Plasma Ratio in vitro diagnostic test for Alzheimer's with the FDA.
C2N's Precivity tests have shown across a number of studies to be among the highest-performing Alzheimer's blood tests as measured by their concordance with established measures for assessing brain amyloid pathology such as cerebrospinal fluid testing and PET imaging. However, the need to purchase a mass spec system for running the test could cause some potential customers to balk, especially as competing tests offered by large IVD firms with extensive installed bases come to market.
"Big upfront capital spending is never easy for clinical labs," Braunstein acknowledged. He suggested, though, that the potentially large market for blood-based Alzheimer's testing could justify the investment.
"If you have a market that is primed for the testing demand, then you can make an economic argument for bringing this instrumentation in-house," he said, noting that while the system might not make sense for a small community hospital, larger health systems could prove a good fit.
Braunstein added that C2N is considering a variety of sales models for the system, including leasing and reagent rental models.
"There are a variety of different models," he said. "We don't have full visibility on that yet, but it is in the works."