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Ontera Developing Single-Pore Sensor for Sepsis, TB, and Zika Diagnostic Testing


NEW YORK – Ontera is preparing to launch a single-pore sensor technology as part of an early access program for academic researchers, its CEO said last week on the sidelines of the 38th annual JP Morgan Healthcare Conference in San Francisco.

Formerly named Two Pore Guys, the Santa Cruz, California-based company has been advancing its silicon nanopore technology for diagnostic applications. Based on that technology, it is developing a single-pore sensor for detecting sepsis, tuberculosis, and Zika at the point of care, said Ontera CEO Murielle Thinard-McLane, who was appointed to the post in conjunction with the company's rebranding last May.

Ontera anticipates eventually applying to the US Food and Drug Administration for marketing clearance for an integrated sample-to-answer system currently called the NanoDetector. 

It expects to integrate its proof-of-concept single-pore sensor into a prototype multiplexed testing platform this year.  

The silicon sensor with a pore size between 25 and 35 nanometers — large enough for biological molecules of interest to slide through and be counted — is the core component of the platform. Biological molecules flowing through the pores are tagged and identified using the firm's proprietary chemistry. 

For clinical diagnostic applications, the firm is taking a two-path approach to implementing the silicon nanopore sensor technology.  

"The first way is to be able to detect a molecule one at a time, which means we tag the molecule of interest and have it go through the pore so that you can see whether it's present or not and count the number of times it is present. That's the single-pore technology," Thinard-McLane said. The two-pore technology, by contrast, involves placing  two pores side by side. "You can use one for detection and the other one for actuation," Thinard-McLane said. "You can hold the DNA in place in order to look at tags of interest, and that type of tool can be deployed for genome mapping." The dual-pore technology is most suitable for epigenetic biomarker research, according to Ontera.

"Research into cancer is evolving and, obviously, NGS is a big piece of that but people are also looking at methylation, for example, including hypomethylation and hypermethylation," Thinard-McLane said. "That's where epigenetics comes into play, and again with this we have a very early proof of concept and believe that there are applications for a tool that could be easier to use than current predicates, such as ATAC-seq and ChIP-seq." 

A research tool that the firm anticipates launching for early access at the end of this month consists of the single-pore sensor. It is not the integrated point-of-care system, which would require further development before a diagnostic prototype can be completed.   

In practice, the single-pore system extracts DNA through a membrane and sends it to a PCR chamber within a cartridge. There, the DNA is eluted and amplified through rapid heating and cooling, producing billions of copies of the target, the firm said. Independent single nanopore sensors then identify and count the number of target molecules. 

For future clinical diagnostic purposes and as one of its primary areas of focus, Ontera is taking aim at a triage test for sepsis.  

Thinard-McLane noted that the company's sepsis diagnostic development work is part of a collaboration announced last month with Newcastle upon Tyne, UK-based QuantuMDx. The firms anticipate eventually marketing the sepsis test to urgent care facilities and, longer term, to retail pharmacy clinics. 

The sepsis point-of-care diagnostic platform will use QuantuMDx’s sample preparation technology, Capture-XT, along with Ontera's single-pore sensor technology.  

"It is rare that a new biosensor emerges that combines ease of use, an attractive price point, single molecular analysis, and more," said QuantuMDx CSO Jonathan O’Halloran. "Ontera’s nanopore checks every box." The speed at which the pore works and the system's ability to perform fractional abundance analysis in seconds are particularly noteworthy, he added. 

O’Halloran said that the companies "came together with a shared vision of creating a next-generation platform that would combine the speed and sensitivity of QuantuMDx’s cell capture technology with the immense power of Ontera’s nanopore technology."  

Over a few months, the firms ran experiments to ascertain the compatibility and performance of their technologies working together. "In that short timeframe, we achieved the sensitivity required for the identification of bloodstream infections that could lead to sepsis — with a test turnaround time that could significantly impact patient outcomes," O'Halloran said. 

In less than one hour, the combined technologies may enable not only the detection of sepsis but also resistance to most common antibiotics, in line with the quick turnaround time required for a triage test for sepsis, Thinard-McLane said. 

The firms are working on a product development plan, and they are in discussions with partners to take the platform toward commercialization, she added. 

Clinicians frequently use point-of-care tests that employ lactate as a biomarker in diagnosing sepsis. But lactate is a single biomarker and can be elevated in conditions other than sepsis. "Right now, you don't have anything that works well in under an hour, and our goal is to fill that gap," Thinard-McLane said. 

Achieving a fast turnaround is important not only for diagnosing sepsis but also for guiding decision-making associated with whether to prescribe antibiotics and with determining the type of antibiotics to prescribe to the patient. 

Because of the shortcomings of single biomarker tests, such as those that use lactate, procalcitonin, or C-reactive protein as markers of sepsis, a number of companies are looking to develop multimarker instruments and assays for the condition. Mologic, for example, is developing a multimarker lateral flow technology that includes six undisclosed host-response biomarkers to detect sepsis at the point of care. Stanford University spinout Inflammatix and Duke University spinout Predigen Diagnostics are separately developing sepsis tests that leverage gene expression associated with the immune system's response to infection. 

Ontera also is developing applications in addition to sepsis detection that leverage its single-pore technology.

Last June, Ontera landed a $983,000 contract with the US government's Intelligence Advanced Research Projects Activity to develop a molecular test for Zika at the point of care. Its first Zika test is being developed to identify patients infected with a Zika gene variant that has been associated with microcephaly, a capability not possible with current protein-based tests for the condition. 

In November 2018, the firm received a $2.8 million grant from the Bill & Melinda Gates Foundation to develop a sensitive, low-cost molecular diagnostic assay for tuberculosis. The grant is being used to develop sensitive and low-cost point-of-care device that it said would be compatible with automated, wireless reporting for resource-poor areas. The dominant testing technology for active TB disease used in resource-poor areas uses sputum samples, but companies are developing alternate sampling methods to broaden access to such testing.   

Thinard-McLane said last week that Ontera's developers are investigating use of mouth swabs and urine as sample sources for TB testing. "Obviously, [new sampling methods] would change significantly how you can deploy that test in low- and middle-income countries," she added. 

Further, Ontera has an ongoing collaboration with oncologists at the University of California, San Francisco to develop a liquid biopsy assay. The collaborators are evaluating a handheld nanopore platform for detecting circulating tumor DNA, and specifically, for detecting a KRAS mutation from blood and urine samples. 

The group has thus far demonstrated a prototype that is as sensitive and specific as liquid biopsy droplet digital PCR testing for the same application, Thinard-McLane said.  

Outside of the human diagnostics space, Ontera is collaborating with BASF in the ag-bio space. In late 2017, it also reached a deal with Bayer's Monsanto business to develop technologies targeting that market.

In 2017, Ontera — then Two Pore Guys — had closed a $24.5 million Series A financing round led by Khosla Ventures. When asked whether the firm is planning to raise additional funds, Thinard-McLane said that as a startup, the firm is continuously in fundraising mode.