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BforCure Preparing Multiple Infectious Disease Panels for Point-of-Care qPCR Platform

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NEW YORK — Emboldened by the CE-IVD marking of its rapid SARS-CoV-2 test and accompanying point-of-care quantitative PCR instrument, France's BforCure is looking to expand its test menu for the in vitro diagnostics market.

Christophe Pannetier, chief scientific officer and cofounder of the Montreuil-based company, said that the firm is developing panels for respiratory diseases, gastrointestinal ailments, women's health, urinary tract infections, sexually transmitted diseases, and meningitis.

The primary market for the tests will be the EU, he said. Timelines for delivering the assays to market are somewhat incumbent on changes in the European regulatory environment, as the EU's more stringent In Vitro Diagnostic Regulation, or IVDR, is slated to come into effect next May.

"As a result, there is some uncertainty as to when we will be able to launch these panels," underscored Pannetier. "We aim at launching some of them in 2022 though," he said. Pannetier added that BforCure is contemplating selling its tests in other markets, like the US or in some African countries, with the help of partners.

BforCure in May obtained a CE-IVD mark for Chronos, its portable quantitative PCR thermocycler and an accompanying assay for SARS-CoV-2. The instrument relies on a microfluidic thermal heating and cooling engine, trademarked as Fastgene, to rapidly cycle samples and enable multiplex qPCR testing in less than 15 minutes.

The system is currently able to analyze samples that are compatible with direct qPCR or have been processed manually or with a third-party preanalytical device. A component to the system that the firm is already using is its PCR design software called Ortholigo that involves proprietary algorithms and design strategies.

The company's SARS-CoV-2 test relies on a nasopharyngeal swab as a sample input. The launch of the assay has served as a vehicle for building a group of first adopters that might later use the other IVDs BforCure has in development.

"COVID-19 has presented an unanticipated opportunity to gain initial customers in France who are interested in on-site rapid screening of patients," said Pannetier. "After having operated its first Chronos device for a couple of months, our first customer has already ordered additional devices."

Pannetier did not name the customer, but the firm has acknowledged placements at Marseille-Provence Airport via Inovie, a group of medical biology laboratories in France. Indeed, the firm sees its tests and Chronos platform as a good fit for rapid testing at airports and nursing homes, as well as for epidemiological surveillance.

The current list price for the Chronos system is €25,000 ($30,000), and €8 for its single-chamber consumable chips. A four chamber cartridge will be commercialized this summer and a 10-chamber cartridge is in development. The current iteration of the Chronos can already support four-plex assays, and devices on the market can be upgraded to support 10-plex assays once they are available, Pannetier said.

High-content PCR

Pannetier cofounded BforCure in 2018 with CEO Maël Le Berre to commercialize technology developed in-house at Elvesys, a Parisian microfluidics firm. Le Berre said that the company sought to deliver a platform that could perform better than PCR machines on the market. One aspect was to offer a system that measured fluorescence in real time, versus conventional systems that measure fluorescence once per cycle.

"This allows us to extract more information from the PCR compared to traditional machines," said Le Berre. "It's what we call high-content PCR; it will eventually allow us to make large panels that expand the number of colors in the machine."

This multicolor capability will also support the company's new IVD panels when they roll out.

"A very nice aspect of this machine is to be very fast, to allow large panels, and to have a good throughput, because it can currently process four samples in parallel with only 15 minutes of PCR," he said.

Since its inception, BforCure has sought to serve three distinct markets: defense and security, industry and environment, and then medical and veterinary diagnosis. A French military grant received in 2017 supported a focus on security and defense applications, but the COVID-19 pandemic led the company, like many others, to reorient toward handling the public health threat.

BforCure had intended to have its first IVD on the market by 2023, said Le Berre, but the crisis had other plans. "As you can see, we did it three years earlier," he said.

This was achieved thanks to the French Ministry of the Armed Forces' Nomorecov project, the aim of which was to support the development of new screening technologies. BforCure in April 2020 received €1.5 million through the project via the French Defense Innovation Agency, plus an additional €635,000 from the Ile-de-France regional government.

"We answered a call for French companies to help with the crisis," said Le Berre. "This figured prominently in us coming onto the IVD market."

The grant was transformative for BforCure. It grew from 25 to 40 employees in the course of a year and marked its entry into the molecular diagnostics market. According to Le Berre, the firm will continue its growth trajectory and aims to employ 100 people by 2022.

BforCure obtained its CE-IVD mark under the current In Vitro Diagnostic Directive regulation, the IVDD, enacted in 1998, which will remain in effect until May 2022, when most IVDs in Europe will require certification by designated standards organizations, called notified bodies, under the new IVD Regulation or IVDR. Le Berre noted that BforCure has worked with an NB for years, and that the company is preparing to have its products cleared under the IVDR.

Some uncertainty remains around the implementation of the IVDR, as there is a shortage of capacity at NBs for reviewing applications, but Le Berre said the company is preparing its IVDR application for next year. "We know the IVDR is a long process and NBs are not really ready," he said, "so we have prepared for both the IVDD and IVDR in parallel."

Noramid

BforCure continues to innovate on its platform. The EU recently awarded it €197,000 to support a project called Noramid. The full name of the effort is, "A novel rapid nucleic acid isolation microchip integrated in the Fastgene PCR microfluidics device for point of care diagnosis of infectious diseases."

The project will commence in December and run through November 2023. Its aim is to develop a nucleic acid isolation microchip that can be integrated into Fastgene for future use in infectious disease testing. The objective is to develop a highly sensitive testing platform capable of detecting the presence of target bacteria or viruses from difficult samples, such as saliva or water. The device should be able to detect pathogens in less than 20 minutes. BforCure will also file patent applications around any IP created during the Noramid project.

"Sometimes we are able to perform direct PCR on a sample without any treatment, but sometimes we need to extract RNA or DNA from the sample," said Veronica Negro, BforCure's collaborative product manager.

This is the case with saliva tests for SARS-CoV-2, as sometimes the RNase present in the saliva sample can attack the RNA of the virus, necessitating a pretreatment for PCR. "We want to miniaturize this technology and make it faster," said Negro of the company's ambitions. "We want to develop a technology that can be used outside of the lab, more at bedside or the point of care."

Such a chip could also be used to test water samples, as part of environmental monitoring for Legionella, for instance. "A water sample can be very high volume but have a very low concentration of target," Negro said.

While BforCure's current interest is infectious disease testing, it could find applications for its technology in other settings, such as food testing, Negro said.

Le Berre confirmed that the company has also not lost sight of its original goals. "We will return to our activities to develop solutions for the defense markets," said Le Berre. Some envisioned assays will be able to quickly identify biothreats from bioterrorists, he added.