SPEEDX AND QUANTUMDX AIM FOR FIRST-IN-KIND DIAGNOSTIC TO RAPIDLY IDENTIFY BACTERIAL INFECTIONS AND PROVIDE A PHENOTYPIC RESULT IN REMOTE SETTINGS
The portable battery-operated device could detect Chlamydia trachomatis and Neisseria gonorrhoeae and guide treatment in under one hour
By Robin Berghaus
As the SARS-CoV-2 virus swept across the globe and caused the COVID-19 pandemic, SpeeDx pivoted to create diagnostics and products that hospitals and communities needed to contain the virus and minimize deaths. To meet global demand, SpeeDx doubled its staff and scaled up its manufacturing capabilities by more than 500 percent. “The planet was in a big mess, and we worked hard to get new COVID tests out quickly,” says Dr. Alison Todd, SpeeDx Co-founder and Chief Scientific Officer. “It was a challenge to ramp up production, and it slowed down other clinical research. But every time there has been a challenge, we’ve risen to it.”
Honored by AusBiotech and Johnson & Johnson as 2021 Australian Company of the Year, SpeeDx has returned to its roots, pioneering tests for sexually transmitted infections (STIs). Dr. Todd’s innovation group is developing a proprietary technology, InSignia™, which has the potential to detect two of the world’s most common STIs–Chlamydia trachomatis and Neisseria gonorrhoeae–and guide appropriate treatment in under one hour. STIs are rampant with 1 million new cases occurring daily around the world. They can cause devastating health effects, including pelvic inflammatory disease, chronic pain, infertility, and increased risk of contracting HIV. Children are not spared, as infections can be passed from mothers to newborns, causing sepsis, blindness, deformities, and death.
SpeeDx has joined forces with UK-based QuantuMDx to shrink SpeeDx’s bench assay into QuantuMDx’s battery-operated device to deliver rapid results in a range of settings, including low- and middle- income countries (LMICs). The ability to be tested and treated in under one hour would be a game changer for patients. Traditional testing methods, which involve growing bacteria in culture, can take days to deliver results. While waiting, doctors often prescribe an antibiotic as a best guess in the hope it will cure the infection. Yet many patients cannot return for a follow up appointment if their antibiotics must be changed. Rapid and accurate test results–and the ability to use older drugs that are still effective–are particularly important for patients infected with Neisseria gonorrhoeae. It has become resistant to every antibiotic class used to treat it–only one antibiotic, ceftriaxone, remains effective.
“You only have one shot to select an effective treatment for a disease where drug resistance has eroded confidence in the use of almost all antibiotics,” says Erin Duffy, Ph.D., R&D Chief of CARB-X. “This type of diagnostic is critical, which is why CARB-X is enthusiastic about its potential.”
Matthew Marini, Quality Control Manager, sets up a Polymerase Chain Reaction (PCR) experiment. Photo courtesy of SpeeDx
HOW THE TEST WORKS AND WHY IT MEASURES THE RATIO OF RNA TO DNA
SpeeDx’s InSignia™ technology is a PCR-based phenotypic assay that provides pathogen identification and antibiotic susceptibility results. For the test to work in clinics without expensive lab equipment, Dr. Todd’s team needed a small, rapid instrument that could perform the entire process. “QuantuMDx developed an all-in-one box that could prepare and amplify the nucleic acid sample,” says Dr. Todd. “We’re taking it a step further, developing cartridges for the antibiotic testing right on the same instrument.”
Q-POC™ system and InSignia™ cartridge. Photo courtesy of QuantuMDx
When a patient’s urine or a vaginal, penial or throat swab is loaded onto QuantuMDx’s Q-POC™ instrument, it will briefly expose the bacteria in the sample to an antibiotic, and then extract and amplify RNA and DNA using PCR. The instrument’s built-in software will calculate the ratio of RNA to DNA. Changes in the ratio of specific RNA transcripts in the presence of the antibiotic will indicate the bacteria is sensitive to the drug and could be an effective treatment. In contrast, if the ratio is unchanged this may indicate resistance. The approach could enable clinicians to switch antibiotics when resistance is detected, or use older drugs to treat sensitive cases.
While gonorrhea resistance rates are high in some parts of the world, Dr. Todd notes that 70% of cases in Australia can still be treated by ciprofloxacin, an older, inexpensive and broad-spectrum oral antibiotic that patients can take at home. In contrast, the one remaining antibiotic routinely used to treat this STI is injectable and must be administered by trained personnel. “Ciprofloxacin works well when there isn’t resistance, and it is still in our arsenal,” says Dr. Todd. “These tests are enabling us to use what we have, but appropriately.”
Additionally, InSignia™ differentiates viable from non-viable infections. This is a departure from rapid molecular diagnostics currently available, which simply detect either DNA or RNA. “If the DNA or RNA is present, the physicians will treat,” says Dr. Todd. “But these standard molecular tests don’t tell you if you have a viable infection, because DNA and RNA can hang around in the body after the organism has died.”
Dr. Todd worries that patients are routinely given antibiotics when they do not have active infections. “I was asked one day, ‘How do you tell if the bacterium is alive?’ And I said, ‘The DNA is still transcribing RNA, so you have more of it,’” says Dr. Todd. “That’s why our test measures the ratio of RNA to DNA.” The idea inspired Dr. Todd’s team to engineer InSignia™ to help curb overtreatment.
While SpeeDx has engineered InSignia™ to identify two of the most common STIs–Chlamydia trachomatis and Neisseria gonorrhoeae–future iterations could be adapted to detect other bacteria and be used with a comprehensive panel of antibiotics. “So, we’ll have one test that we can challenge with a range of antibiotics to determine which is the most effective and convenient to use,” says Dr. Todd.
Photo by Michael Amendolia
A FIRST-IN-KIND DIAGNOSTIC WITH SURVEILLANCE CAPABILITIES
While the technology is still in the early feasibility stage, if successful, the companies would achieve a first-in-kind product: a rapid molecular pathogen ID test that measures a phenotypic result requiring neither bacterial culture nor expensive laboratory equipment. Currently there are a small number of PCR-based molecular tests which can provide rapid results for antibiotic susceptibility for STIs, but these require prior knowledge of the precise genetic mutations that cause antibiotic resistance. In practice, they can only be developed when there are few underlying mutations. Furthermore, those tests are blind to new mutations that are not already included in the test, so they cannot detect new emerging resistance mechanisms. In contrast, InSignia™ provides molecular phenotypic results independent of the causative mechanism. As new resistant strains evolve, SpeeDx’s InSignia™ test would continue to provide definitive results without having to be re-engineered.
Beyond its clinical applications, Dr. Todd envisions InSignia™ as a tool for detecting emerging health threats. She suggests the CDC’s surveillance program could consider using rapid molecular phenotypic tests such as InSignia™ as an alternative to culturing organisms. “For surveillance, these may be useful to screen for resistance organisms, which could then be sequenced to reveal emerging mechanisms causing resistance,” says Dr. Todd. “There are a number of opportunities–both at the level of the individual patient and at a population level–where this kind of technology could be useful.”
While Dr. Todd identifies scientific obstacles–such as finding ways to preserve samples so the bacterial cells remain viable for antibiotic testing–she posits a greater challenge might be altering mindsets. “We’re changing the dogma about how things are done, and big companies are making large profits on their tests that measure either DNA or RNA,” says Dr. Todd. “The more data we can generate, the more people’s minds we might be able to change and move away from what is standard testing now.”
ACADEMIC AND STRATEGIC PARTNERSHIPS SPUR INNOVATION
Since 2009, SpeeDx has pioneered the field of molecular diagnostics and a personalized medicine approach for STIs and cancer. Dr. Todd credits her company’s success in research and innovation in large part to its academic feeder system. For more than 25 years, Dr. Todd has served as an adjunct professor at the University of New South Wales, supervising postgraduate students who are wholly embedded within industry. While Dr. Todd led the diagnostics group at Johnson and Johnson (J&J) Research Australia, she mentored PhD student Dr. Elisa Mokany. When J&J closed its research during the global financial crisis, Drs. Todd and Mokany co-founded SpeeDx. “We developed some great technology at J&J that we believed could make a difference, and we didn’t want it to languish in a filing cabinet somewhere,” says Dr. Todd. “Since then, we’ve continued to invent and greatly expand what we had in the early days.”
From left to right: Bhavin Raval (Chief Financial Officer), Elisa Mokany (Co-founder and Chief Technology Officer), Alison Todd (Co-founder and Chief Scientific Officer), and Colin Denver (Chief Executive Officer). Photo by Michael Amendolia
While companies must deliver products to generate revenue, basic research often takes a backseat since funding is hard to attract for early-stage technology development. Dr. Todd views the PhD students as the lifeblood of her innovation group. While the students learn invaluable scientific and business skills under Dr. Todd’s mentorship, they have contributed a pipeline of new ideas for SpeeDx, including InSignia™. That technology was co-invented by Dr. Nicole Lima, who was Dr. Todd’s PhD student and currently serves as a Research Manager at SpeeDx. Dr. Lima took the InSignia™ technology far enough in her PhD program to attract a $1.8M award from CARB-X. The company is using that award to develop the test through the feasibility stage in a project led by Dr. Tina Lonergan. “That funding enables you to get over the next hump, to start to get it out to people who can do the litmus test to make sure it works in the real world,” says Dr. Todd.
Being a part of CARB-X has opened doors for SpeeDx’s innovation group by connecting them with key leaders around the world. “The value CARB-X brings is enormous, because they can help facilitate connections with investigators with a range of capabilities, from identifying informative genetic sequences through to serving as the early adopters who push the technology into clinical practice,” says Dr. Todd. “Collaboration is key to getting these technologies out. You need to work with those clinicians who are not just treating patients, but who are working on ways to better treat their patients.”
As SpeeDx continues to grow from a company that began with four employees, it launched a new facility in December that will enable the now 117-person company to expand and support production of over 4 million tests per week. The increased scale is integral to its mission in providing diagnostics that address an array of global health needs from STIs to COVID-19 testing and other respiratory diseases.
Alison Todd
Co-founder and Chief Scientific Officer
Dr. Alison Todd co-founded SpeeDx in 2009, and serves as Chief Scientific Officer. She is an elected Fellow of the Australian Academy of Technology and Engineering. Along with Dr. Elisa Mokany, she was the recipient of the Academy’s Clunies Ross Innovation Award in 2020 for “discovery, development, and adoption of a technology that has significantly improved societal or industry capabilities.”
Photo by Michael Amendolia
Dr. Todd is a serial inventor with a portfolio of 18 patent families that comprises over 90 granted patents which protect SpeeDx’s intellectual property including PlexZyme®, PlexPrime® and InSignia™. She is a pioneer in the field of personalized medicine, having pursued a career which has focused on developing and commercializing diagnostic tests to tailor and monitor therapies for patients with cancer or infectious diseases.
Prior to founding SpeeDx, Dr. Todd was a Senior Research Director at Johnson & Johnson Research Pty Limited, Sydney. She spent nearly 20 years within the pharmaceutical industry and was internationally recognized with the Johnson & Johnson Philip B. Hofmann Research Scientist Award for outstanding achievement in R&D.
Dr. Todd studied at the University of Sydney, obtaining a BSc (Hons 1st Class) before completing a PhD through the Faculty of Medicine in conjunction with Royal Prince Alfred Hospital. She maintains an active involvement within the academic community and is an Adjunct Professor at the University of New South Wales.
For more information, plexpcr.com
Published on June 13, 2022