NEW YORK – Against a backdrop of increased drug resistance that has made treating patients with gonorrhea more challenging, Prompt Diagnostics aims to deliver portable PCR-based tests to quickly give clinicians drug susceptibility information that could expand treatment options.
The Baltimore-based Johns Hopkins University spinout also intends to minimize the cost of its platform and cartridge-based tests so they could be used to improve access to testing through sexually transmitted disease-focused clinics in the US and providers in low-resource areas of developing countries.
The company recently secured a $1 million grant from the Combating Antibiotic-Resistant Bacteria Biopharmaceutical Accelerator (CARB-X), which said that it had provided the funding for the development of Prompt's first test to detect gonorrhea and characterize the pathogen's susceptibility to ceftriaxone and other antibiotics. In an interview, Prompt's CEO Alex Trick said that the funding will support the development of the company's tests for markers of resistance to ciprofloxacin and ceftriaxone and noted that the firm is also developing tests to diagnose Chlamydia trachomatis and Trichomonas vaginalis and to characterize drug resistances in those pathogens.
Trick cofounded the firm in 2020 with Johns Hopkins professor Tza-Huei Wang, and currently, Prompt operates out of the LifeBridge Health BioIncubator at Sinai Hospital of Baltimore. The company name comes from the portable, rapid, on-cartridge magnetofluidic purification and testing (PROMPT) testing platform that was developed at Johns Hopkins and licensed to Prompt.
The technologies underlying Prompt's tests were developed out of Trick's Ph.D. work in the BioMEMS lab at Johns Hopkins University focused on the use of microfluidics for developing infectious disease diagnostic tests. In collaboration with experts on sexually transmitted infections and epidemiology, Trick set out to develop faster, more accessible, and more affordable tests that could be used to respond to growing infection rates in the US and globally.
"This turned into a project where we packaged PCR into a portable box and brought it to STI clinics in Baltimore as well as collaborated with the Infectious Diseases Institute in Uganda to demonstrate this 15-minute PCR where we're detecting gonorrhea and also showing ciprofloxacin resistance," he said.
Ciprofloxacin was one of several recommended treatments for gonorrhea until resistance to it emerged and spread in the late 1990s and early 2000s, according to the US Centers for Disease Control and Prevention. By 2006, about 14 percent of gonorrhea isolates from patient samples were resistant to ciprofloxacin, and in April 2007, the agency stopped recommending its use and other fluoroquinolone drugs for gonorrhea treatment. Instead, since 2010 the agency has recommended ceftriaxone as the only first-line antibiotic treatment.
Trick noted, however, that many Neisseria gonorrhoeae infections could still be treated with ciprofloxacin if a susceptibility test was available. With that in mind, Prompt has developed a prototype test to identify the S91F mutation in the N. gonorrhoeae gyrA gene that is associated with ciprofloxacin resistance.
Further, the spread of multidrug-resistant gonorrhea has been a global concern that has limited treatment options and led to treatment failures in many countries. Earlier this month, the World Health Organization reported that an estimated 82 million new N. gonorrhoeae infections occurred in 2020, with the majority occurring in the African and Western Pacific regions. While drug resistance emerged soon after antimicrobial treatments became available, it has continued to expand through unrestricted access to antimicrobials, inappropriate drug selection and overuse, and poor-quality antibiotics, according to Trick.
In 2022, the WHO established a goal of reducing N. gonorrhoeae infections by 90 percent by 2030, compared to the case volumes in 2020. That plan includes improving surveillance for infections, establishing same-day testing and treatment, and supporting R&D for low-cost tests, among other actions.
Prompt is one of four firms that have received funding through CARB-X's 2022-2023 funding call for tests for STDs. The nonprofit awarded $1.8 million in February to Visby Medical for the development of an instrument-free PCR-based test for N. gonorrhoeae and susceptibility to ciprofloxacin, as well as $1 million in April to Scout for the development of a point-of-care test to differentiate N. gonorrhoeae and C. trachomatis using its proprietary Loop-de-Loop isothermal molecular diagnostic chemistries, and $1 million to Fuse Diagnostics for proof-of-concept and feasibility testing of a proprietary instrument-free test that uses multi-analytic amplification chemistries for the detection of N. gonorrhoeae and C. trachomatis.
Those firms are poised to enter an increasingly crowded market for point-of-care STI testing with entries from a mix of startups and industry giants.
Trick was the lead author of a 2021 article in Science Translational Medicine that describes the development of an automated point-of-care PCR assay for the simultaneous detection of N. gonorrhoeae and determination of ciprofloxacin resistance in 217 urethral swab samples from patients at sexual health clinics in Baltimore and Kampala, Uganda. The authors wrote that the cartridge-based test performed with 97.7 percent sensitivity and 97.6 percent specificity for the detection of infections and 100 percent concordance with culture results for ciprofloxacin resistance, with results in less than 15 minutes.
The testing platform prototype had a footprint about the size of a mobile phone, and a portable mobile phone charger provided sufficient power for more than 20 tests. Trick said that the company has set a target of producing a commercial testing platform that can run at least 20 tests on battery power over the course of a nine-hour day.
Prompt's PCR instrument will be used with simple, low-cost cartridges to perform the sample processing, heating, and fluorescence-based detection steps of the PCR, and it will deliver the results through texts on a built-in touchscreen. The firm aims to keep the cost per cartridge between $2 and $3 each and sell the instrument at a price that is competitive with other point-of-care testing devices, although Trick declined to provide an estimated price for the instrument.
Trick said that Prompt is focusing on delivering traditional PCR methods and giving users access to well-established, accurate testing methods that allow for multiplexing and melt analysis. The platform provides the flexibility to design tests for DNA and RNA targets in various sample types including urine, blood, plasma, and vaginal swab samples. His team also intends to give users access to more in-depth information such as quantitative results and PCR cycle threshold values.
The CARB-X grant supports work on transitioning from a prototype device to a manufacturable instrument and ensuring that the cartridges are shelf stable and fit for scalable, low-cost production, Trick said. The team aims to begin manufacturing in 2025 for clinical studies in 2026, and he hopes that the tests will be available in 2026 or 2027. He said that the firm is seeking additional external funding for that transition.
He said that demonstrating the sensitivity and specificity of the device through clinical trials will be crucial to offering Prompt's platform as a viable substitute for lab-based tests. As a result, publishing the company's data and presenting it to stakeholders are key priorities. Officials at Johns Hopkins clinics and Baltimore-area STI clinics have expressed interest in becoming early adopters of the technology, and Trick plans to reach out to public health departments and other stakeholders through conferences and meetings that are attended by clinicians who are on the frontlines of combating the spread of STIs.
While securing US Food and Drug Administration clearance is a high hurdle, Prompt intends to bring its tests onto the market in the US first as that would make it easier to pass regulatory muster elsewhere, Trick said. After FDA clearance, Prompt plans to turn its attention to developing countries.
"We're very interested in pursuing the developing markets and being a solution for those places where the infectious disease burden is highest," he said.